Beruflich Dokumente
Kultur Dokumente
Otorhinolaryngology
Head and Neck
Surgery
Sixteenth Edition
James B. Snow Jr, MD
Professor Emeritus
University of Pennsylvania
Philadelphia, Pennsylvania
Former Director National Institute on Deafness and
Other Communication Disorders
National Institutes of Health
Bethesda, Maryland
Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs and
drug dosages, is in accord with the accepted standard and practice at the time of publication. However, since research and regulation constantly
change clinical standards, the reader is urged to check the product information sheet included in the package of each drug, which includes rec-
ommended doses, warnings, and contraindications. This is particularly important with new or infrequently used drugs. Any treatment regi-
men, particularly one involving medication, involves inherent risk that must be weighed on a case-by-case basis against the benefits anticipated.
The reader is cautioned that the purpose of this book is to inform and enlighten; the information contained herein is not intended as, and should
not be employed as, a substitute for individual diagnosis and treatment.
Contents
11 Cranial and Intracranial Complications of Acute and Chronic Otitis Media 294
Lee A. Harker, MD
12 Otosclerosis 317
Herman A. Jenkins, MD, Omid Abbassi, MD, PhD
14 Trauma to the Middle Ear, Inner Ear, and Temporal Bone 345
Mitchell K. Schwaber, MD
16 Ototoxicity 374
Leonard P. Rybak, MD, PhD, John Touliatos, MD
21 Presbyacusis 443
John H. Mills, PhD, Paul R. Lambert, MD
59 Imaging of the Oral Cavity, Pharynx, Larynx, Trachea, Salivary Glands, and Neck 1353
Mahmood F. Mafee, MD
66 Laryngoscopy 1537
Ellen S. Deutsch, MD, Jane Y. Yang, MD, James S. Reilly, MD
67 Bronchoesophagology 1549
Jane Y. Yang, MD, Ellen S. Deutsch, MD, James S. Reilly, MD
INDEX 1578
Foreword
This edition of Ballenger’s Otorhinolaryngology Head and Neck Surgery continues in the tra-
dition of being a comprehensive compendium of current knowledge in the fields of otol-
ogy/neurotology, rhinology, facial plastic and reconstructive surgery, pediatric
otorhinolaryngology, laryngology, head and neck surgery, and bronchoesophagology. The
informational content for the 16th edition has been reorganized into 67 chapters with new
sections on facial plastic and reconstructive surgery and pediatric otorhinolaryngology.
More than half of the authors are new to the book, and another third of the chapters have
been redesigned to address major developments in the topical areas. The content reflects the
central responsibility of the otorhinolaryngologist in treating patients with diseases affect-
ing the senses of smell, taste, and balance and with disorders of human communication
affecting hearing, voice, speech, and language. The presentation of basic science underlying
clinical otorhinolaryngology head and neck surgery has been expanded, and chapters on
clinical topics have been structured to provide comprehensive coverage to meet the needs of
practitioners in the twenty-first century.
The 64 senior authors have been chosen not only for their contribution to new knowl-
edge to their topics through highly regarded research but also for their intellectual leadership
of the specialty and, thereby, are truly authoritative in the subject matter of their chapters.
Both the basic science and clinical chapters stress the important role of molecular biol-
ogy in understanding the pathogenesis of disease. Throughout the book, the genetic basis
of disease is emphasized. This book provides students, residents, fellows, and practitioners
with the understanding necessary to participate fully in the coming role of molecular biol-
ogy in therapy.
Ballenger’s Otorhinolaryngology Head and Neck Surgery is in its 94th year in this sixteenth
edition. It has been in continuous use since 1908, when my great-uncle, William Lincoln
Ballenger, brought out the first edition. My father, Howard Charles Ballenger, succeeded my
great-uncle as editor, and in 1957, I succeeded my father. I am greatly pleased to have James
B. Snow Jr. as coeditor. This reorganized and revitalized version is much to the credit of his
leadership and forward-looking enthusiasm. We are delighted to have BC Decker Inc as the
book’s new publisher.
This new edition, as in the past, is enriched by the outstanding contributions of 118 dis-
tinguished scholars and practitioners, all of whom have written on their special interests. I
extend my gratitude to each of them as well as their medical artists and illustrators, whose
work clarifies the text. The contributors are drawn mainly from the United States but from
several other countries as well.
The general format is to present an accurate picture of normal anatomy and physiol-
ogy as a basis for the understanding of altered conditions that underlie diseases and their
symptoms and signs. I believe that this book will be of great value to all studying this spe-
cialty and to other specialists seeking an authoritative reference.
Fabiola Müller, Dr. habil rer nat David Reiter, MD, DMD
School of Medicine Department of Otolaryngology
University of California Thomas Jefferson University
Davis, California Philadelphia, Pennsylvania
The temporal bone is a complex portion of the skull nomastoid suture. Failure in development of this
base that contains the labyrinth with its nerve sup- part of the TB is responsible for congenital aural
ply (cranial nerve VIII) but also other cranial nerves atresia, a form of conductive hearing loss correctable
such as the facial, trigeminal, vagus, glossopharyn- by surgery.
geal, spinal accessory, and hypoglossal nerves. A The major portion of the TB formed by the
thorough knowledge of the gross and microscopic mastoid portion attributes its large size to extensive
anatomy1,2 of the temporal bone (TB) and the phys- pneumatization. The mastoid process projects pos-
iology of the labyrinthine sense organs is essential teriorly and inferiorly behind the external auditory
for the specialist who strives for accuracy in diagno- meatus and serves as the attachment for the ster-
sis and precision in surgery of the TB. This knowl- nocleidomastoid muscle. A deep groove in its inferior
edge is gained first from dissection of cadaveric aspect houses the posterior belly of the digastric
whole TB specimens but is greatly enhanced by muscle, which is innervated by the facial nerve. The
study of prepared histologic sections from normal superior surface of the mastoid compartment is
and pathologic TB. formed by a thin plate of bone known as the tegmen
mastoidea. Posteriorly, it forms the anterior plate
of the posterior cranial fossa and is indented by a
OSTEOLOGY groove for the sigmoid sinus. The superior and infe-
Four major components of the temporal bone (TB) rior petrosal sinuses travel medially along the supe-
contribute to the skull base: the squamous, mastoid, rior and inferior aspects of this part of the TB.
tympanic, and petrous. The petrous portion of the TB forms its medial
The squamous portion of the TB provides part inferior to the middle cranial fossa; posteriorly,
attachment for the temporalis muscle, which is
bounded inferiorly by the temporal line (Figure
1–1). The temporal line provides an external land-
mark for the floor of the middle cranial fossa. The
zygomatic process projects forward from the lower
portion of this bone, and together they form the
anterior border of the mandibular fossa, which
receives the condyle of the mandible.
The tympanic portion of the TB is an incom-
plete cylindrical portion of the TB that, together
with the squamosal portion, forms the medial part
of the external auditory canal. This portion of the
external auditory canal is 2 cm in length by 1 cm in
diameter. Its anterior boundary is the posterior limit
of the mandibular fossa; medially, its border is the
tympanic membrane. The posterior part fuses with FIGURE 1–1. Right temporal bone, lateral view. Repro-
the mastoid component of the TB at the tympa- duced with permission from Anson BJ and Donaldson JA.2
1
2 Ballenger’s Otorhinolaryngology
AUDITORY SYSTEM
EXTERNAL EAR
The external or outer ear is that portion of the ear
that is lateral to the tympanic membrane (Figure
FIGURE 1–2. Left temporal bone, posterolateral view.
1–3). It consists of the external auditory canal as well
Reproduced with permission from Anson BJ and Don-
as the auricle and cartilaginous portion of the ear.
aldson JA.2
The auricle is a semicircular plate of elastic cartilage
characterized by a number of ridges or grooves. The
it forms the anterior surface of the posterior cranial major ridges of the auricle are the helix and antihe-
fossa (Figure 1–2). The superior surface of the lix, the tragus and antitragus, which surround the
petrous bone is highlighted by the prominence of concha, which is the scaphoid depression posterior
the superior semicircular canal, a landmark in sur- to the external auditory meatus. The cartilage of the
gery within the middle cranial fossa. Anterior to this external auditory meatus is continuous with that of
portion of the petrous bone is the hiatus for the the outer portion of the ear canal and auricle.
greater superficial petrosal nerve, which joins with The external auditory canal is made up of a
the geniculate ganglion of the facial nerve. In some cartilaginous extension of the auricle in its outer half
temporal bones, this hiatus is enlarged, and the and the mastoid and tympanic portion of the TB in
geniculate ganglion may be exposed in the middle its medial half. It is bounded medially by the tym-
cranial fossa. Anterior and medial to this region is a panic membrane and is lined with skin that is thin
concave area for the semilunar ganglion of the with little subcutaneous tissue medially but laterally
trigeminal nerve. On the posterior surface of the contains numerous hair follicles and ceruminous
petrous bone are several important landmarks. The and sebaceous glands. The bony external auditory
most obvious aperture is the internal auditory mea- canal averages 31⁄2 cm in length, with a diameter of 1
tus (canal) that transmits the seventh and eighth cm. The tympanic membrane is composed of three
cranial nerves as well as the labyrinthine artery or layers: the outer squamous cell epithelial layer, the
loop of the anterior inferior cerebellar artery. The medial mucosal layer facing the middle ear, and the
lateral end (fundus) of the internal auditory canal fibrous layer or tunica propria, forming the sub-
(IAC) is divided horizontally by the falciform stance of the tympanic membrane.3 The fibrous
crest.1–3 The superior compartment contains the layer gives the tympanic membrane its shape and
facial nerve anteriorly and the superior division of consistency. Radial fibers of the tunica propria insert
the vestibular nerve posteriorly. The inferior com- into the manubrium, circumferential fibers provid-
partment transmits the cochlear nerve anteriorly ing strength without interfering with vibration,
and the inferior division of the vestibular nerve pos- whereas tangential fibers reinforce the architecture
teriorly. The endolymphatic sac may be found in a of the tympanic membrane. These physical charac-
depression covered by a bony shelf (operculum) teristics are important for the vibratory characteris-
anterior to the sigmoid groove. It narrows down tics necessary for sound transmission.
into the vestibular aqueduct as the endolymphatic The tympanic membrane is identified by
duct. The depression for the semilunar ganglion and a prominent landmark, the manubrium of the
the fifth cranial nerve on the anterior surface of the malleus, which is limited superiorly by its lateral or
petrous bone also carries the sixth cranial nerve short process and inferiorly by a rounded end
Anatomy of the Auditory and Vestibular Systems 3
referred to as the umbo. The umbo forms the deep bone, the stapedius muscle posteriorly, and the canal
apex of the conical shape formed by the tympanic for the tensor tympani muscle anteriorly. The oval
membrane. The tympanic membrane is incomplete window is kidney bean shaped with a convex supe-
superiorly, where it lacks a fibrous layer in the por- rior rim and a concave inferior rim. In the oval win-
tion superior to the short process of the manub- dow, the footplate of the stapes bone is held in place
rium.4 Since it lacks a fibrous layer, this portion is by the annular ligament. The RWN forms a deep
called the pars flaccida (Shrapnell’s membrane). The recess often covered with various mucous mem-
major or inferior portion of the tympanic mem- brane configurations that obscure the round win-
brane is referred to as the pars tensa. dow membrane (RWM). The RWM is a fibrous
membrane covered with a layer of mucosa that is
roughly kidney bean shaped, with a major compo-
MIDDLE EAR nent anterior and inferior and a minor component
The space between the tympanic membrane and the located posteriorly and horizontally in the RWN.
bony capsule of the labyrinth in the petrous portion Posteriorly in the mesotympanum there are two
of the TB contains the ossicular chain with its asso- bony recesses of clinical importance. The recess lat-
ciated muscles, the aperture of the eustachian tube, eral to the vertical segment of the facial canal is
and the vascular system. The tympanic cavity is called the facial recess. The space medial to the facial
divided into the epitympanic, mesotympanic, and canal is called the sinus tympani (Figure 1–4). These
hypotympanic regions. The hypotympanic portion is two recesses are important clinically as they fre-
that portion of the middle ear that lies inferior to quently harbor chronic middle ear infection and
the aperture of the eustachian tube and the round must be controlled in surgery. The facial recess also
window niche (RWN). This portion of the middle provides access to the middle ear space and RWN in
ear contains various bony trabeculae and the bony those procedures in which the ear canal wall is pre-
covering of the jugular bulb. This bony surface may served (ie, intact canal wall mastoidectomy, cochlear
be dehiscent, exposing the jugular bulb in the hypo- implantation). A bony projection from the facial
tympanic region. Inferiorly, a small channel (the canal (pyramidal eminence) contains the tendon of
inferior tympanic canaliculus) transmits Jacobson’s the stapedius muscle before its insertion into the
nerve (a branch of cranial nerve IX). neck of the stapes bone. The most anterior portion
The mesotympanic portion of the middle ear is of the middle ear space is called the protympanum
limited superiorly by the horizontal portion of the and is bordered superiorly by the orifice of the
facial canal and inferiorly by the RWN. This region eustachian tube and anteriorly by the canal for the
contains the oval and round windows, the stapes internal carotid artery (see Figure 1–4).
4 Ballenger’s Otorhinolaryngology
LIGAMENTS AND MUSCLES nucleus and the lateral superior olivary nucleus.
LIG. MALLEI SUPERIUS
to head of malleus
LIG. INCUDIS SUPERIUS
to body of incus
Contraction of the stapedius muscle displaces the
stapes posteriorly and attenuates sound transmitted
LIG. MALLEI LATERALE
to neck of malleus by the ossicular chain. Since reflex contraction of the
LIG. INCUDIS POSTERIUS
LIG. MALLEI ANTERIUS
to short limb
of incus
stapedius muscle is activated by sound, it is regarded
to anterior process
of malleus as a protective mechanism for the cochlea.
M. TENSOR TYMPANI
to manubrium
M. STAPEDIUS
to head of stapes
Eustachian Tube The eustachian tube is an essen-
of malleus
Attachment of tial communication between the nasopharynx and
membrana tympani
to manubrium the middle ear (Figure 1–8). It is responsible for
LIG. ANNULARE (BASEOS) STAPEDIS pneumatization of the middle ear and the mastoid
to margin of vestibular fenestra
and for maintaining normal pressure between the
FIGURE 1–6. Auditory ossicles: their adult form and middle ear and the atmosphere. It represents the pha-
muscles and ligaments. Reproduced with permission ryngeal extension of the first branchial arch and
from Anson BJ, editor. Morris’ human anatomy. 12th ed. extends from the lateral wall of the nasopharynx.
New York: McGraw-Hill; 1966. The skeleton of the medial three-fourths of the
eustachian tube is cartilage that is surrounded by soft
tissue, adipose tissue, and respiratory epithelium. The
cartilage of the eustachian tube, which is hook
an important principle in middle ear surgery. The shaped on cross-section, is stabilized and displaced
stapes therefore acts in a piston-like fashion in the
oval window. The stapes bone is shaped like a stirrup
with a head, neck, and footplate or base. The crura
are bowed, the posterior one more so than the ante-
rior, and fused with the footplate, which is formed
from both otic capsule and periosteal bone. These
auditory ossicles are controlled to some degree by
two middle ear muscles, the tensor tympani and the
stapedius. The tensor tympani muscle is housed in a
bony semicanal in the anterior mesotympanum just
superior to the orifice of the eustachian tube (Figure
1–7). The muscle converges posteriorly into a tendi-
nous segment that is anchored at the cochleariform
process and turns abruptly lateralward to insert on
the neck of the malleus. The tensor tympani is
innervated by a branch of the fifth cranial nerve. Its
motoneurons are located centrally in the parvocel-
lular division of the trigeminal motor nucleus, and FIGURE 1–7. A more inferior cut through the same
its action causes the drumhead to be pulled medially, temporal bone as in Figure 1–5 demonstrates the cochlea
thus raising the resonant frequency of the sound (C), the utricular macula and its nerve (U), the cochlear
conduction system. nerve (CN), the facial nerve (FN), and vestibular nerves
The stapedius muscle arises within either its (VN) in the internal auditory canal. The muscle and ten-
own or the fallopian canal and is accompanied by don of the tensor tympani muscle (TT) overlie the
the motor portion of the facial nerve. It converges cochlea as it turns laterally in the cochleariform process
superiorly and anteriorly to form the stapedius ten- (CP) to attach near the neck of the malleus (M). The
don, which emerges through the pyramidal emi- articulation of the long process (L) of the incus with the
nence to insert at the neck of the stapes. The stapes head (S) can be seen in the mesotympanum. The
stapedius muscle is innervated by a branch of the chorda tympani nerve (CT) passes between the malleus
seventh nerve, and its motoneurons are located in and incus. TM = tympanic membrane; EAC = external
the brainstem in the interface between the facial auditory canal; TMJ = temporomandibular joint space.
6 Ballenger’s Otorhinolaryngology
guide in tracing infection into deep recesses of the superior or the vestibular labyrinth with the excep-
mastoid compartment, particularly the PA. tion of the saccule, the pars inferior (cochlea and the
Cell tracts arising from the middle ear space saccule), and the endolymphatic duct and sac. All of
also are important for the surgeon. These cell tracts, the sense organs of the labyrinth have in common
particularly those that may lead to air cell develop- that they contain hair cells with rigid cilia and are
ment in the PA, are those that course inferior to the innervated by afferent and efferent neurons.7,8 Dis-
labyrinth or those that extend around the canal of placement of the cilia of the hair cells is responsible
the internal carotid artery (see Figure 1–8). Exten- for opening potassium and calcium channels that
sive pneumatization in the development of the PA initiate the electrical potential within the hair cell
may create air cells that can become isolated when that is then leaked into the afferent neuron and car-
the cell tract is obliterated by bone or fibrous tissue ried to the brainstem.
leading to the formation of cholesterol cysts over a
Cochlea The cochlear duct, the auditory portion
period of many years. Over time, these cysts erode
of the labyrinth, extends approximately 35 mm.9 The
the surrounding bone and may reach considerable
cochlear duct and associated sensory and supportive
size in early or late adulthood. Compression of the
structures assume the form of a spiral similar to a
trigeminal nerve and the sixth nerve near the PA
snail shell of 21⁄2 to 23⁄4 turns (Figure 1–9). This allows
may present a clinical picture similar to Gradenigo’s
the long cochlear duct to be contained in a small
syndrome, which is the clinical manifestation of
space. A cross-section of a cochlear turn (Figure
petrous apicitis.
1–10) demonstrates the essential structures in this
The PA is of special interest because of a vari-
sense organ. The scala media or cochlear duct con-
ety of lesions that may involve this region. The clin-
ical manifestation may be subtle and requires a high
index of suspicion to pursue the diagnosis.6 Imag-
ing (both computed tomography and magnetic res-
onance imaging) is especially sensitive to the
identification of pathology in the PA. Since the com-
position of the PA can include air cells (see Figure
1–8), bone marrow (Figure 1–4), the internal carotid
artery (Figure 1–4), and the cartilage of the foramen
lacerum, the list of lesions that occur here is lengthy.
Cholesterol cysts and congenital cholesteatomas are
the most common; however, infection, bone marrow
neoplasms, cartilage tumors, metastatic malignan-
cies, neurogenic tumors, and aneurysms of the inter-
nal carotid artery have been reported. Clinical signs
of a progressive lesion in the PA relate to nearby
structures: eustachian tube obstruction, facial pain
or anesthesia, and lateral rectus muscle palsy.
and a basal body representing a rudimentary also sends a trifurcating branch to the dorsal
kinocilium is located on the spiral ligament side of cochlear nucleus in an orderly fashion according to
the ciliary tuft. The inner hair cells are supported by frequency.9 Apical turn neurons terminate in the
interphalangeal cells, whereas the outer hair cells are most medial portion of the nuclear complex,
supported by Deiters’ cells inferiorly and laterally by whereas the basal turn neurons terminate laterally.
Hensen’s cells. The tectorial membrane is anchored Remaining frequency projections are ordered be-
medially at the limbus and attached to the Hensen’s tween these two regions of the cochlear nucleus. The
cells laterally by a fibrous net. The basilar membrane central termination of the type II ganglion cells is
and tectorial membrane are displaced vertically by not known largely because the small caliber axons
the traveling wave created by sound energy delivered are difficult to trace for long distances.
to the oval window. Since the fulcrum of these two This frequency organization of the auditory
structures is separate, they will slide horizontally pathway characterizes the remainder of the afferent
when stimulated, resulting in a shearing action pathway from end-organ to cortex. Another feature
between the tectorial membrane and the cuticular of the afferent auditory pathway is that the numbers
plate. The resultant displacement of stereocilia initi- of neurons involved at the various nuclear way sta-
ates an electrical event in the hair cell. The organ of tions undergo a progressive increase from cochlear
Corti contains approximately 15,500 hair cells, with nucleus to the cortex.11 Although there are 30,000
about 3,500 of them being inner hair cells and spiral ganglion cells in the monkey auditory nerve,
12,000 being outer hair cells. These hair cells are 88,000 neurons are found in one cochlear nucleus in
innervated by afferent and efferent neurons in a the primate. One superior olivary complex contains
complex but orderly manner. The afferent neurons 34,000 neurons, whereas the nucleus of the lateral
to the auditory sense organ are bipolar neurons lemniscus has 38,000 neurons, and at the inferior
referred to as spiral ganglion cells that are located in colliculus level there are almost 400,000 neurons on
Rosenthal’s canal of the bony modiolus. Approxi- each side and at the medial geniculate body 500,000.
mately 30,000 spiral ganglion cells innervate the The auditory cortex has approximately 10 million
human organ of Corti (see Figure 1–11). The spiral neurons.
ganglion takes the form of clusters of ganglion cells A brief description of the afferent auditory
throughout the extent of the length of the cochlea. pathway follows (Figure 1–12). The cells of the dor-
Ninety to 95% of the spiral ganglion neurons are sal cochlear nucleus project axons to the dorsal
type I neurons, which are large and myelinated and acoustic striae, which crosses the midline and
project a single dendrite directly to an inner hair ascends in the contralateral lateral lemniscus to ter-
cell.10 Approximately 10 to 20 type I spiral ganglion minate in the dorsal nucleus of the lateral lemniscus
cells innervate one inner hair cell. These form the and the inferior colliculus, particularly its inferior
major afferent input from stimulation of the organ half. The cell bodies of the ventral cochlear nucleus
of Corti. Type I ganglion cells degenerate readily fol- project axons to the ipsilateral accessory and main
lowing injury to the dendrite. The remaining 5% of superior olivary nuclei and to the medial dendrites
afferent neurons in the spiral ganglion are type II of the contralateral accessory olive. The neurons of
ganglion cells, which are smaller and unmyelinated the accessory olive have bipolar dendrites arranged
and have very thin distal processes. The dendrites of horizontally. This arrangement is favorable to receive
these type II neurons cross the tunnel space along its input from projections of both cochlear nuclei. As
floor enveloped by pillar cell processes and form spi- such, it is an important nuclear way station for
ral bundles between Deiters’ cells. These dendrites determining sound localizaton. Some fibers of the
then course apically between Deiters’ cells to inner- intermediate and ventral cochlear striae travel
vate several to many outer hair cells per type II den- beyond the superior olivary complex and enter the
drite.9 A type II ganglion survives following injury to contralateral lateral lemniscus to terminate in the
its dendrite. The axons of the spiral ganglion cells inferior colliculus. The superior olive is thought to
project to the cochlear nucleus complex, which has function as both a relay station for the auditory
anteroventral and posteroventral divisions of the pathway and as a reflex center. The best-known
ventral cochlear nucleus and the dorsal cochlear reflex mediated through the superior olive is the
nucleus. Each type I afferent neuron bifurcates and stapedius reflex. Stapedius muscle motoneurons are
10 Ballenger’s Otorhinolaryngology
Inf. colliculi
located in the interface between the superior olivary
and the facial nerve nuclei. The accessory superior
Dorsal nuclei
olive projects bilaterally in the lateral lemnisci to ter- Lat. lemniscus
minate in the dorsal nuclei of the lateral lemnisci Ventral nuclei
and the inferior colliculi. The lateral superior olive
projects homolaterally in the lateral lemniscus to ter-
minate in the dorsal nucleus of the lateral lemniscus DCN
Thoracic Cord
MR
III
III
ATD IV
BC BC
MLF
MLF
L
NPH IFC
M
D
NPH
and caudal portions of the lateral vestibular nucleus. ond-order neurons in the superior, medial, lateral,
Truncal and limb musculature of the intervening seg- and descending nuclei relay input from the utricular
ments are organized in orderly fashion between these and saccular maculae to the same areas. There is also
extremes. This pathway provides excitatory tone to some relay of canal input to the vestibular nuclei on
extensor muscles of the limbs. The medial vestibu- to the cerebellum. The importance of such direct as
lospinal tracts (MVSTs) travel down the MLF and are well as relayed labyrinthine input to the cerebellum is
largely inhibitory, although some facilitatory connec- not known but may have some bearing on different
tions are made from the descending vestibular information coming in for modification of cerebellar
nucleus.21 The projections through the MLF arise output. For example, the relayed canal input may be
from the caudal portions of the medial and descend- modified by commissural inhibition before entering
ing vestibular nuclei. Since they are largely inhibitory, the cerebellum. Furthermore, other afferent input
they act synergistically with the innervation of neck (spinal) may alter the labyrinthine (macular) input
and upper truncal muscles excited by the LVST. The before relay to the cerebellum.
MVSTs extend down to the upper cord levels but do Input from the labyrinth and spinal cord,
not reach the thoracic, lumbar, and sacral region lev- although important, is not the only source of in-
els reached by the LVST. putting information to this important part of the
Other pathways exist in the vestibular nuclei vestibular system.21 The visual system also has sig-
that are of importance. One such pathway is the com- nificant input to the flocculus and nodulus, where
missural pathway that interconnects the vestibular overlap with labyrinth input occurs. Therefore,
nuclei (see Figure 1–19). The major intervestibular interaction between vestibular and visual signals in
or commissural projections are between the supe- the VC has firm anatomic and physiologic support.
rior, medial, and descending vestibular nuclei.21 A These various inputs to the VC probably determine
minor projection may exist between the lateral the pattern of output from these regions, which will
vestibular nuclei. As mentioned earlier, the group Y then impact on neurons in the vestibular nuclei.
nucleus also forms a significant commissural projec- In a reciprocal fashion, there are extensive pro-
tion to the contralateral group Y nucleus as well as jections to the vestibular nuclei from the cerebellar
the superior nucleus. The commissural pathways cortex and nuclei.21 The anterior and posterior parts
are largely inhibitory on second-order neurons acti- of the vermis provide extensive projections to the
vated by canal input. It is possible that they serve to lateral vestibular nucleus, particularly the dorsal half.
potentiate the differential response arising from The output of the VC is distributed throughout the
stimulation of coplanar canals. The commissural vestibular nuclei, especially to those areas related to
projections are important in the recovery of balance the cerebellar input. These cerebellar projections are
following ablation of one set of vestibular sense entirely inhibitory since Purkinje cells are inhibitory
organs (labyrinthectomy). It has been demonstrated neurons.
that the commissural pathways are largely responsi- However, not all cerebellar output is inhibitory.
ble for providing the reactivation of input to the The fastigial nucleus (FN), which receives labyrinth-
denervated side of the brainstem to approximate ine input, exerts an excitatory effect on the vestibu-
that in the intact half.27 lar nuclei. The caudal part of the FN projects to parts
The interaction of vestibular pathways with the of all of the contralateral vestibular nuclei, whereas
cerebellum is emphasized by reference to certain the rostral region projects to the ipsilateral nuclei.
areas of the cerebellum as the vestibulocerebellum The FN can be a link between the cerebellar cortex
(VC). These are the nodulus, uvula, flocculus, and and the vestibular nuclei that provides an excitatory
ventral paraflocculus (see Figure 1–19). Other areas input on vestibular neurons.
of the anterior and posterior lobes of the vermis are
also included to a lesser extent. This association is
based on the projection of the first- and second-
EFFERENT VESTIBULAR PATHWAY
order vestibular afferents to the cerebellar cortex by An efferent vestibular pathway has also been demon-
way of mossy fibers.21 All canal afferents continue strated in lower and higher mammalian forms.14,28,29
through the superior nucleus after termination there, This pathway originates bilaterally from small neu-
to converge and terminate on neurons in the VC. Sec- rons located lateral to the abducens nucleus near the
18 Ballenger’s Otorhinolaryngology
medial vestibular nucleus30 and projects in a sym- that the imbalance in number is similar to that in
metric fashion to each vestibular labyrinth (Figure lower forms. The function of the efferent system to
1–24). The axons, which are fine axons, converge the vestibular sense organs is not known. Most
with the olivocochlear bundle as the vestibular root experimental studies indicate an inhibitory effect on
is reached in the brainstem. They travel with the afferent vestibular activity.31 However, an excitatory
olivocochlear bundle efferents through the vestibu- effect has also been demonstrated in primates.29 It is
lar nerve to the point where the vestibular ganglia possible that the efferent effect is to raise or lower
are reached. At this point, the vestibular efferents the resting activity level in vestibular afferents,
diverge from the parent efferent bundle to break thereby modifying their operating range. Unlike the
up into fascicles and individual axons that then dis- efferent auditory pathway, the vestibular efferent
perse throughout the ampullary and macular nerve pathway is represented by small neurons located
branches. They branch and ramify richly along their near the medial vestibular nucleus, where they can
course within the nerve trunks and after penetra- be contacted by first-order afferents. Thus, a two-
tion of the basement membrane in the neuroepithe- neuron reflex arc exists to type I hair cell afferent ter-
lium of the vestibular sense organs. Here they minals and type II hair cell soma.
represent fine fibers that form many bouton-like
vesiculated endings in termination on type II hair
cells and the calyces encapsulating type I hair cells
FLUIDS OF THE INNER EAR
(see Figure 1–16). These fibers are cholinergic, as are As mentioned earlier, there are two fluid compart-
the olivocochlear efferents, and can be demonstrated ments of the inner ear, the endolymph and the per-
selectively with acetylcholinesterase localization ilymph. Endolymph is a fluid that has a similar
techniques.15 The number of efferent neurons is rel- ionic composition to intracellular fluid and fills the
atively small compared with the number of afferent membranous auditory and vestibular labyrinth.
neurons in the vestibular nerve. In the cat, for the Endolymph is formed by secretory cells in the stria
8,000 afferent neurons, there are 200 to 300 efferent vascularis and by dark cells near the ampullary ends
neurons that supply through their branching an of the semicircular ducts and the walls of the utricle.
almost equal number of efferent terminals to the The endolymph is thought to be absorbed in the
afferent terminals in the sense organs. Although endolymphatic sac. Endolymph composition is
the number of vestibular efferents in the human characterized by a high potassium level and a low
labyrinth has not been determined, it is presumed sodium level.32
Anatomy of the Auditory and Vestibular Systems 19
CSF = cerebrospinal fluid; MDH = malate dehydrogenase; LDH = lactate dehydrogenase. Adapted from Smith CA et al.32
The membranous labyrinth is suspended temporal bone before taking an abrupt redundant
within the bony labyrinth by a fine trabecular net- turn on itself (jugular bulb) to exit through the
work in a space that is filled with perilymph. Peri- jugular foramen accompanied by cranial nerves IX,
lymph, in contradistinction to endolymph, has an X, and XI (see Figure 1–4). This structure is impor-
ionic composition similar to extracellular fluid, with tant as it may represent a lethal complication of bac-
low potassium and high sodium levels.32 A compar- terial mastoiditis (thrombophlebitis) when erosion
ison of the composition of the two fluids with that of its bony covering occurs. The anatomy of the
of serum and cerebrospinal fluid is found in Table jugular bulb is particularly crucial to the diagnosis
1–1. This differential chemical makeup in the two and surgical management of neoplasms, which orig-
fluid compartments is important to the establish- inate in the bulb such as glomus jugulare tumors or
ment of a standing voltage surrounding the sense schwannomas.
organs, which permits the generation of nerve The internal carotid artery enters the temporal
impulse in the hair cell afferent neuron unit. Peri- bone just anterior to the jugular foramen and trav-
lymph is secreted largely as the result of diffusion els in a bony canal anterior to the middle ear space,
from the capillary network in the spiral ligament first in a vertical direction and then in a horizontal
adjacent to the scala tympani with a smaller portion anteromedial direction medial to the eustachian
derived from cerebrospinal fluid by way of the tube (see Figure 1–4). Its main clinical significance is
cochlear aqueduct. as an important landmark in surgery of the petrous
apex and skull base. Rarely, an anomalous internal
carotid artery may appear clinically to be a vascular
BLOOD VESSELS OF THE EAR neoplasm in the middle ear.
Two major vessels have little or nothing to do with The circulatory networks of the external and
the vascular supply of the ear itself but are impor- middle ears and the inner ear are completely sepa-
tant in disorders and surgery of the temporal bone. rate, with the one being supplied by the carotid sys-
These are the sigmoid sinus and the internal carotid tem, whereas that of the labyrinth is derived from
artery. The sigmoid sinus is a continuation of the lat- the vertebrobasilar system.9 The external ear is sup-
eral (transverse) sinus, which is formed by the supe- plied by the auriculotemporal branch of the super-
rior sagittal sinus. It makes an indentation into the ficial temporal artery and branches of the posterior
posterior fossa plate of the mastoid portion of the auricular branches of the external carotid artery. The
20 Ballenger’s Otorhinolaryngology
middle ear and mastoid are supplied by a different The external radiating arteriole courses through the
set of arterial branches from the external carotid sys- interscalar septum to supply the vascular arcades
tem. The arterial branches to the middle ear space and capillaries of the stria vascularis. This arteriole
are the anterior tympanic branch from the internal anastomoses with the venous supply near the spiral
maxillary artery, which enters through the petro- prominence, with the venous return being along the
tympanic fissure and travels along the eustachian floor of the scala tympani, where the veins merge
tube and the semicanal for the tensor tympani. The with the collecting venules from the spiral vein to
middle meningeal artery gives off the superior tym- form the posterior spiral vein. This posterior spiral
panic branch that enters the middle ear through the vein, or inferior cochlear vein, then travels along the
petrosquamous fissure. The middle meningeal artery scala tympani to exit at the cochlear aqueduct
also gives off the superificial petrosal artery that trav- through a separate channel and enter the inferior
els with the greater superficial petrosal nerve and petrosal sinus. The remainder of the labyrinth is
enters the facial canal at the hiatus. This vessel anas- drained by a venous system, which parallels to some
tomoses with a branch of the posterior auricular degree the arterial system. Therefore, an anterior
artery, the stylomastoid artery, which enters the facial vestibular vein and the posterior vestibular vein
canal inferiorly through the stylomastoid foramen. A drain the posterior duct ampulla as well as the sac-
branch of the stylomastoid artery leaves the fallopian cule and a portion of the utricle and superior duct
canal to travel through the canaliculus with the ampulla. These merge to join the vein at the cochlear
chorda tympani nerve to enter the middle ear. aqueduct. The venous return from the semicircular
Finally, the inferior tympanic artery, a branch of the ducts and the body of the utricle converge to form
ascending pharyngeal artery, enters the middle ear the vein at the vestibular aqueduct, which travels as
through the tympanic canaliculus in the hypotym- the vein of the paravestibular aqueduct. This vein
panum with the tympanic branch of the ninth nerve. travels along with the endolymphatic duct toward
The vascular supply to the ossicles is derived the endolymphatic sac. This venous system drains
from the anterior tympanic artery, the posterior into the sigmoid sinus.
tympanic artery, and branches from the plexus of
vessels on the promontory. The most tenuous link in
the ossicular chain as regards blood supply is the tip
FACIAL NERVE
of the long process of the incus, which commonly The anatomy of the facial nerve and its branches are
undergoes necrosis secondary to conditions that important in clinical practice, not only because of the
compromise its blood supply.33 cosmetic effects of facial paralysis, whether it be by
disease or by surgical injury, but because the various
Blood Supply to the Inner Ear The blood supply components of facial nerve are important for the
to the inner ear is derived from the labyrinthine diagnosis and localization of lesions in the temporal
branch of the anterior inferior cerebellar artery off bone. The facial nerve has sensory function and auto-
the basilar artery.9 Occasionally, the internal audi- nomic afferent and efferent function, together with
tory artery has a direct origin from the basilar artery. the motor function for the facial musculature. The
This vessel represents an end artery as it receives no neuronal pathway from the motor cortex to the facial
known anastomosing arterial vessels. The internal nucleus is either two or three neurons in a mono- or
auditory artery as it enters the IAC divides into three disynaptic pathway. The motor control of the facial
branches. The first branch, the anterior vestibular muscles is located at the inferior end of the presylvian
artery, supplies the semicircular ducts, utricle, and gyrus. The area for facial musculature innervation is
saccule. The second branch, the vestibulocochlear located near the area of innervation of laryngeal
artery, supplies the saccule, utricle, posterior duct, muscles. Although a modest corticonuclear projec-
and basal turn of the cochlea. Its third and terminal tion exists, it is not the only higher pathway inputting
branch is the cochlear artery, which enters the modi- the facial nucleus. Various extrapyramidal neurons
alus, where it gives off the spiral vessels that form located in the red nucleus as well as the periaque-
external and internal radiating arterioles. The inter- ductal gray nucleus also project to the facial nucleus.
nal radiating arterioles descend to supply the limbus The projection to the facial nucleus is largely con-
as well as the basilar membrane and organ of Corti. tralateral, as are most corticobulbar projections, but
Anatomy of the Auditory and Vestibular Systems 21
there is bilateral innervation to the facial neurons form the vidian nerve in the vidian canal. The tym-
supplying the frontalis muscle. panic portion of the facial nerve travels superior to
The facial nerve consists of four major compo- the oval window in a posterolateral direction to the
nents: the motor component to the facial muscula- level of the horizontal or lateral semicircular canal,
ture, a sensory component to receptors in facial where it makes a 90-degree turn in a ventral direction
muscles as well as to the face, autonomic secretomo- to continue as the mastoid portion of the facial nerve
tor and special sensory pathways. The motor compo- (Figure 1–25). After traveling the length of the verti-
nent of the facial nerve is the largest component and cal canal, the facial nerve emerges from the stylo-
arises from the facial nerve nucleus, which is located mastoid foramen to enter the parotid gland anterior
just caudal to the lateral superior olivary nucleus of to the mastoid tip. Before emerging from the stylo-
the auditory system.34 Immediately caudal to the mastoid foramen, the chorda tympani nerve is given
facial nerve nucleus is the rostral limit of the nucleus off through a bony canal in a retrograde direction
ambiguus, which provides the motor innervation to toward the middle ear, where it passes between the
the laryngeal musculature. It has been demonstrated neck of the malleus and long process of the incus to
in the cat with retrograde neuronal tracers that the enter the epitympanum and leave the middle ear
regional facial muscle groups are supplied by groups space before joining the lingual nerve. The facial
of neurons within the facial nerve nucleus in a medial nerve provides innervation to the posterior belly of
and lateral arrangement.34 The number of facial the digastric muscle just external to the stylomastoid
motoneurons has been estimated at approximately foramen and then emerges into the parotid gland,
10,000 to 20,000. As axons leave the facial nucleus, where it gives rise to four to five branches providing
they travel in a dorsal direction to loop around the innervation to the facial musculature. Although the
abducens nucleus under the floor of the fourth ven- motoneurons in the facial nerve are spatially organ-
tricle and then curve in a ventrolateral direction pass- ized within the nucleus, the fibers to the peripheral
ing between the lateral superior olivary nucleus and facial muscle groups are interspersed throughout the
the descending trigeminal root to emerge from the course of the facial nerve but gather together again
brainstem ventral to the eighth nerve. The nerve is on exiting the temporal bone to provide the four to
joined by the nervus intermedius and travels in the five distal branches supplying the regional facial
IAC in its anterior and superior compartment. In this musculature.34
portion of the IAC, it has an intimate anatomic rela-
tionship with the superior division of the vestibular
nerve, and indeed the nervus intermedius may travel
within the vestibular nerve for a part of its intra-
canalicular course. At the distal end of the IAC, the
facial nerve diverges in an anterolateral direction to
enter the labyrinthine segment of the fallopian canal
(see Figure 1–5). At the geniculate ganglion, it makes
an acute bend near the floor of the middle cranial
fossa to continue within the bony canal in its tym-
panic segment. The course within the labyrinthine
segment of the fallopian canal is associated with an
extension of the subarachnoid space. This extension
of the subarachnoid space is usually limited by the
location of the geniculate ganglion but in a small
portion of temporal bones may extend into the tym-
panic portion of the fallopian canal. The greater
superficial petrosal nerve emerges from the genicu-
late ganglion at the facial hiatus (see Figure 1–9) and
courses along the floor of the middle cranial fossa
between layers of dura to reach the foramen lacerum, FIGURE 1–25. The facial nerve and its relationships
where it joins with the carotid sympathetic nerves to (diagrammatic). Sp.pal.g. = sphenopalatine ganglion.
22 Ballenger’s Otorhinolaryngology
Lacrimal
Gland Trigeminal G.
Motor
Sublingual & Facial
Submandibular Nerve
A B Glands
FIGURE 1–26. A, Diagram of the autonomic secretomotor pathways associated with the facial nerve. B, Diagram of
the special sensory pathways in the facial nerve.
GENERAL SENSORY COMPONENT mandibular gland. The sensory bundle is located lat-
eral to the motor component throughout the
An unknown number of sensory afferent neurons are
intratemporal course of the facial nerve.9
intermixed with the motor axons in the facial nerve
trunk. In an animal model (cat), approximately 15 to
20% of the nerve fibers in the medium to large fiber SPECIAL SENSORY FUNCTION
size persist even after total facial nerve transection in Special sensory function for taste receptors in the
the cerebellopontine angle. It is not clear what anterior two-thirds of the tongue as well as the soft
peripheral receptors these afferents innervate. The palate and nasopharyngeal mucosa are carried by
possibilities are either spindles within the facial mus- unipolar ganglion cell masses in the facial nerve
culature or some sensory receptors in the skin, par- (Figure 1–26, B). Taste receptors in the anterior two-
ticularly the dermis. thirds of the tongue are innervated by dendrites of
the geniculate ganglion and travel by way of the lin-
AUTONOMIC SECRETOMOTOR NEURONS gual and the facial nerve trunk, where they are con-
tained in the sensory bundle of the facial nerve to
Secretomotor or motor preganglionic neurons of the ganglion cells in the geniculate ganglion.35 Axons of
facial nerve are located in the superior salivatory these ganglion cells pass into the brainstem in the
nucleus in the brainstem (Figure 1–26, A). They nervus intermedius to reach the tractus and nucleus
travel in the nervus intermedius, with some traveling solitarius, where they terminate. Taste receptors in
within the vestibular nerve trunk. Those traveling the oral cavity, primarily the soft palate and the
within the vestibular nerve leave in the vestibulofacial nasopharynx, are supplied by afferent dendrites,
anastomosis in the distal part of the IAC to join the which travel in the vidian nerve and the greater
nervous intermedius as it travels with the facial nerve superficial petrosal nerve. They pass through the
trunk in the meatal canal.9 Some efferent pregan- facial hiatus to join the nervus intermedius, which
glionic neurons pass through the geniculate ganglion brings them to their ganglion cells in the meatal
to the foramen lacerum and the vidian canal. After ganglion of the facial nerve within the IAC.35,36
leaving the vidian canal, they synapse with postgan- Axons of these neurons also enter the brainstem in
glionic neurons in the sphenopalatine ganglion that the nervus intermedius to terminate in the tractus
innervate the lacrimal gland and secretory glands of and nucleus solitarius. The meatal ganglion located
the nose. Other preganglionic neurons travel within within the IAC has special significance in harboring
the sensory bundle of the facial nerve and leave with neurotropic viruses (herpes virinae), which gain
the chorda tympani nerve to join the lingual nerve, entry through nerve endings in the oral cavity.36,37
which carries them to the submandibular ganglion, After long latent periods, the viruses can be reacti-
where they synapse with postganglionic neurons, vated later in life to manifest as viral neuropathies
providing secretomotor function to the sub- (Bell’s palsy, recurrent vertigo).
Anatomy of the Auditory and Vestibular Systems 23
oxidase. Acta Otolaryngol (Stockh) 1974;77: 34. Gacek RR, Radpour S. Fiber orientation of the facial
92–101. nerve: an experimental study in the cat. Laryngo-
31. Klinke R, Schmidt CL. Efferent influence on the scope 1982;92:547–56.
vestibular organ during active movements of the 35. Gacek RR. On the duality of the facial nerve gan-
body. Pflugers Arch 1970;318:352–3. glion. Laryngoscope 1998;108:1077–86.
32. Smith CA, Lowry OH, Wu ML. The electrolytes of 36. Gacek RR. Pathology of facial and vestibular neu-
the labyrinthine fluids. Laryngoscope 1954;64:141–53. ronitis. Am J Otolaryngol 1999;20:202–10.
33. Alberti PW. The blood supply to the incudostapedial 37. Gacek RR, Gacek MR. Meatal ganglionitis: clinical
joint and the lenticular process. Laryngoscope 1963; pathologic correlation in idiopathic facial paralysis.
73:605–15. Otorhinolaryngol Nova 1999;9:229–38.
CHAPTER 2
25
26 Ballenger’s Otorhinolaryngology
Middle
Ear Cleft
MIDDLE EAR
EAC
The middle ear cavity forms as a lateral extension of
the first pharyngeal pouch known as the tubotym-
panic recess (see Figure 2–3). The proximal end of
Tympanic the extension remains as the eustachian tube. The
Membrane Eustachian
Tube lateral endoderm of the tubotympanic recess inter-
C faces with the ectoderm of the meatal plug to form
the tympanic membrane. The tympanic membrane
FIGURE 2–3. Drawing showing the development of
is a three-layered structure consisting of a medial
the external auditory canal and middle ear. Development
mucosal epithelium, a fibrous middle layer of mes-
of the external meatus, ear canal, and middle ear space
enchymal origin, and an outermost layer of squa-
involves a complex process of ectodermal proliferation,
mous cell epithelium contiguous with the skin lining
cellular resorption, and coordinated maturation with the
the external auditory canal and originating from
tubotympanic recess forming the tympanic membrane
ectoderm. The malleus and incus appear to develop
and middle ear cleft. The ectodermal cells at the dorsal
from a common ossicular mass around the sixth
end of the first branchial groove proliferate and expand
week of development. Both the malleus and the
medially (A, B). This solid core of ectodermal cells is
incus are thought to be derived from the neural crest
referred to as the meatal plug. By the twenty-first week,
in the first and second arch mesoderm, Meckel’s car-
this meatal plug begins to hollow out, leaving the ear
tilage and Reichert’s cartilage, respectively (Figure
canal lumen. Formation of the ear canal is typically com-
2–4). By the sixteenth week, the ossicles attain adult
plete by the twenty-eighth week of gestation (C). Note
size, and ossification begins at discrete ossification
that the medial-most ectoderm and endoderm of the
centers (eg, medial surface of the neck of the
tubotympanic recess interface in such a way that these
malleus). Stapes development involves a complex
two layers combine to form the tympanic membrane (C).
morphogenesis starting as a blastema at 41⁄2 weeks
(derived from the neural crest in the second arch
mesenchyme). The facial nerve divides the blastema
into stapes, interhyale, and laterohyale. By the sev-
Proliferation of these ectodermal cells generates enth week, a stapes “ring” forms around the stape-
a meatal “plug” that expands medially. Resorption dial artery. The interhyale becomes the stapedial
of cells in the center of this meatal plug leaves a hol- muscle and tendon, whereas the laterohyale becomes
low tube-like structure representing the external the posterior wall of the middle ear and also a por-
meatus and ear canal. Failure of this canalization tion of the fallopian (facial nerve) canal. By the tenth
process results in aural atresia. The medial-most week, the stapes assumes its more typical shape.
ectoderm forms the outer squamous cell epithelial Notably, the footplate seems to develop in conjunc-
layer of the tympanic membrane. It is noteworthy tion with the otic capsule, with ossification begin-
that external auditory canal development occurs ning around the nineteenth week. The mastoid
subsequent to external ear morphogenesis. Accord- antrum expands late in fetal development and con-
ingly, it is possible to see a developmental malfor- tinues to expand significantly after birth.
mation resulting in isolated aural atresia without The two middle ear muscles (the tensor tym-
any auricular malformations, suggesting abnormal pani and stapedius muscles) are first and second
development around the twenty-eighth week. How- arch derivatives, respectively. Accordingly, each mus-
Development of the Ear 27
9 wk (40 mm)
INCUS MALLEUS
MALLEUS
15 wk (100 mm) head
12 wk (84 mm) lateral process
STAPES anterior process
INCUS MALLEUS manubrium
INCUS
body
STAPES
short crus
base
crura BONE long crus
head CARTILAGE MECKEL’S
CARTILAGE
STAPES
(bronchial arch I)
FIGURE 2–4. Ossicular development. A, By the ninth week of gestation, the incus and malleus are still fused but begin
to differentiate into individual structures. The stapes at this stage has developed beyond the stapes ring stage and more
closely resembles the mature stirrup configuration. B and C, By 12 to 15 weeks, the ossicles are more clearly differen-
tiated and approximate adult size. Shortly following this stage, ossification begins at discrete centers of ossification.
Reproduced with permission from Anson BJ, Davies J, Duckert LG. Embryology of the ear. In: Paparella MM, Shum-
rick DA, editors. Otolaryngology. 3rd ed. Philadelphia (PA): WB Saunders; 1991.
cle obtains its innervation from the respective nerve organs within the inner ear. Concurrent with the
associated with each branchial arch: trigeminal development of the ganglion, the otocyst proper
innervation for the tensor tympani muscle and facial undergoes a complex morphogenesis, and the gross
nerve innervation for the stapedius muscle. anatomy of the membranous labyrinth is nearly
mature by the end of the eighth week of gestation
(Figure 2–6).
INTERNAL EAR
The first morphologic change in the otocyst is
The internal ear consists of two components, a the appearance of a diverticulum that first grows out
membranous and a bony labyrinth. The membra- dorsally and then moves medially and elongates to
nous labyrinth is derived from the ectoderm, form the endolymphatic duct and sac. The rest of
whereas the bony labyrinth/otic capsule is derived the otocyst enlarges and lengthens and can be
from the mesoderm and neural crest surrounding roughly divided into a dorsal vestibular and a ventral
the primordial membranous labyrinth. saccular and cochlear region. The dorsal region
develops into the utricle and three semicircular
DEVELOPMENT OF THE MEMBRANOUS ducts and their respective ampullae. The ventral
region develops into the saccule and the auditory
LABYRINTH component of the inner ear, the cochlear duct (see
The membranous portion of the inner ear orignates Figure 2–6, A).
from a thickening of the ectoderm adjacent to the The three semicircular ducts, superior, poste-
hindbrain known as the otic placode (Figure 2–5). In rior, and lateral, develop sequentially during the fifth
humans, the otic placode is evident at the third week week, with the superior duct forming first, followed
of embryonic development. The otic placode soon by the posterior and lateral ducts. The superior and
invaginates from the surface ectoderm to form an posterior ducts form from a vertical outgrowth in
otic cup. By the end of the fourth week, the edges of the dorsal region of the otocyst. The lateral duct
the otic cup come together and fuse to form the otic forms from a horizontal outgrowth in the lateral
vesicle/otocyst. Some cells of the otic epithelium at portion of the otocyst. In the central region of each
the otic cup and otocyst stage delaminate from the presumptive duct, the opposing epithelia of each
epithelium and coalesce to form neurons of the sta- outgrowth fuse together and reabsorb, leaving
toacoustic (eighth cranial) ganglion just anterior behind a tube-shaped duct (see Figure 2–6, B to D;
and medial to the otocyst. These neurons subse- upper panel). One end of each duct opens into the
quently send afferent fibers to innervate sensory utricle, and the other end forms a bulge-like struc-
28 Ballenger’s Otorhinolaryngology
ture known as the ampulla that houses one of the mature inner ear, two additional ducts are evident
vestibular sensory organs, the crista ampullaris. The medially: the utricular and saccular ducts that con-
superior and lateral ampullae form at the anterior nect the endolymphatic duct and sac to the utricle
end of their respective ducts, whereas the posterior and saccule, respectively (see Figure 2–7).
ampulla forms at the posterior end of the posterior
duct (see Figures 2–6, E, and 2–7).
The primordium of the cochlear duct evaginates
DEVELOPMENT OF THE SENSORY ORGANS
from the ventral portion of the otocyst starting at the Six major sensory organs are present in the human
fifth week. This evagination extends anteromedially inner ear. Only the organ of Corti is responsible for
and gradually begins to coil. By the eighth week, the auditory function. The remaining five sensory organs
cochlea has formed 11⁄2 turns (see Figure 2–6, E) and are vestibular in function and include three cristae
at the tenth week, two turns; at the twenty-fifth week, ampullaris and the maculae of the utricle and sac-
the cochlear duct has acquired the mature 21⁄2 turns. cule. In addition, a small vestibular organ, the mac-
The utricle and saccule start to form during the sixth ula neglecta, is thought to be present in only 1% of
week. As the cochlear duct extends, the opening humans. The origin and lineage relationships among
between the saccule and cochlea becomes constricted these sensory organs during development are not
and forms the narrow cochleosaccular duct. In the clear. Based on morphologic studies in the chicken, it
FIGURE 2–6. Diagram showing the development of the membranous labyrinth of the internal ear. A to E, Lateral
views of the left inner ear from the fifth to eighth weeks. The dotted lines represent the level of section for the diagrams
shown in the upper panel, illustrating the development of the superior and posterior semicircular ducts. Orientations:
D = dorsal; P = posterior. Reproduced with permission from Moore KL. The developing human. Philadelphia (PA):
WB Saunders; 1977.
Development of the Ear 29
has been proposed that all sensory organs in the Notch signaling pathway is used in a variety of tis-
inner ear originate in the ventromedial wall of the sues for generating cell type diversity and regulating
otic cup, and each sensory organ is derived from this differentiation during development.4,5 Genes in the
common region as morphogenesis continues.1 Thus Notch signaling pathway have also been implicated
far, there are no early fate-mapping studies in chicken in the determination of hair cells and supporting
or other animal models that lend direct support to cells in the inner ear. Mutation or deletion of genes
this hypothesis. However, early gene expression stud- in this pathway resulted in the absence or aberrant
ies of the inner ear at stages before the onset of his- number of sensory hair cells in zebra fish and
tologic differentiation suggest that the sensory organs mice.6–8
might be defined differently molecularly. For exam-
ple, in mice, BMP-4 (bone morphogenetic protein 4) Cristae Ampullaris The sensory epithelium for the
and Msx1 (muscle segment homeobox gene) are crista elevates into a ridge-like fold where hair cells
expressed only in the three presumptive cristae and and supporting cells develop. Cells surrounding the
not other sensory organs.2 Whether these molecular sensory epithelium are secretory in function and are
differences represent differences in the origin and/or thought to generate the gelatinous cupula in which
mechanisms of specification for these sensory organs the stereocilia of the sensory hair cells are embedded.
remains to be verified. The mound-like elevation of the crista is evident by
Once the position and type of a sensory organ the eighth week, and the sensory structure is mature
have been specified, morphologic differentiation fol- by the twenty-third week (see Figure 2–7).
lows, and the sensory epithelium can be identified by
an increase in the thickness of the otic epithelium Maculae The maculae develop in a similar fashion
into a pseudostratified layer that later differentiates as the cristae except the sensory epithelium is flat,
into sensory hair cells and supporting cells. The and it is covered by an otolithic membrane that con-
30 Ballenger’s Otorhinolaryngology
tains superficial calcareous deposits, the otoconia. vestibular portion that innervates the macula of the
The maculae appear to be fully differentiated saccule and posterior crista and the spiral ganglion
between 14 and 16 weeks (see Figure 2–7). that innervates the organ of Corti.
Helix loop helix transcription factors, such as
Organ of Corti The organ of Corti develops from Neurogenin1, have been implicated in the formation
the posterior wall of the cochlear duct. As the of the statoacoustic ganglion. In mice with a deletion
cochlear duct increases in length, the cross-sectional in Neurogenin1, the statoacoustic ganglion fails to
shape of the duct changes from round to oval to tri- form.11 Growth factors such as fibroblast growth fac-
angular (see Figures 2–7 and 2–8). The posterior tor 3 are also important for the formation of the
wall develops into the sensory tissue, the organ of vestibular ganglion in the mouse.12 Once the neurons
Corti; the anterior wall forms part of Reissner’s of the ganglion reach their final position and finish
membrane; and the lateral wall forms the stria vas- proliferation, they express high-affinity neurotrophin
cularis. The organ of Corti starts to differentiate at receptors and become dependent on neurotrophins
the basal region of the cochlear duct around the secreted by the presumptive sensory organs in the
seventh week, whereas the epithelium in the apical membranous labyrinth. Mice with targeted deletion
turn is undifferentiated and pseudostratified at this (knockout) of genes encoding brain-derived nerve
age. By the twenty-fifth week, the organ of Corti is growth factor or neurotrophin 3 or their respective
fully differentiated. receptors had a loss of ganglionic neurons and inner-
vations to the sensory organs.13 However, this trophic
DEVELOPMENT OF THE STATOACOUSTIC dependency of ganglionic neurons on their target tis-
sues is not reciprocal. In the absence of afferent
GANGLION innervation, the differentiation of sensory hair cells
Based on studies in animal models, neurons of the appears unaffected, at least until birth.14,15
statoacoustic ganglion are thought to originate from
the otic epithelium, whereas glial cells in the ganglion
DEVELOPMENT OF THE BONY LABYRINTH
are derived from the neural crest.9 Morphologic stud-
ies suggest that cells in the anteroventral lateral Concurrent with the development of the otocyst, the
region of the otic cup/otocyst delaminate from the mesenchymal cells surrounding the otic vesicle differ-
epithelium, migrate away from the otocyst, and entiate into a cartilaginous otic capsule by the eighth
undergo proliferation before aggregating to form the week. As the membranous labyrinth enlarges, vac-
ganglion.10 In parallel with the growth of the otocyst, uoles appear in areas surrounding the otic epithelium
the statoacoustic ganglion forms a pars superior and as a result of programmed cell death. These vacuoles
a pars inferior at about the time when the membra- soon coalesce to form the perilymphatic space that is
nous labyrinth is divided into a dorsal vestibular and filled with perilymph. In the cochlea, the perilym-
a ventral cochlear region. The pars superior of the phatic space develops in two divisions; the scala tym-
ganglion provides the peripheral neural connections pani forms before the scala vestibuli (see Figure 2–8).
to the superior and lateral cristae and the macula of Ossification of the cartilaginous capsule to form
the utricle. The pars inferior gives rise to a distinct the bony labyrinth does not occur until the membra-
nous labyrinth has acquired its adult size. Bone for- middle, or inner ear or a combination of more than
mation starts at the fifteenth week and ends by the one of these components (Table 2–1). Examples of
twenty-first week, with a total of 14 ossification cen- some of these syndromes are described below. For
ters. The first ossification center appears at the base of syndromes that are associated with the lack of proper
the cochlea, and ossification advances more rapidly in differentiation and functioning of sensory hair cells,
the cochlea than in the canal region, where membra- see Chapter 13 on hereditary hearing impairment, as
nous growth continues to about the twenty-first week. well as a review by Steel and Bussoli.16
By the twenty-third week, all ossification centers have
fused with no “suture lines,” thus limiting further
growth in the membranous or bony labyrinth.
BRANCHIO-OTO-RENAL AND BRANCHIO-
OTO SYNDROMES
HUMAN EAR MALFORMATIONS Branchio-oto-renal (BOR) syndrome is an autoso-
AND MODELS OF MOLECULAR mal dominant disorder characterized by branchial
arch anomalies (branchial cleft cysts and sinuses),
DEVELOPMENT ear malformations (affecting the external, middle,
Many genes causing human deafness have been iden- and inner ear regions), and various renal anomalies
tified recently. In some cases, the functional deficit is ranging from undetected in the branchio-oto (BO)
the result of gross malformations of the external, syndrome to bilateral aplasia.17 Hearing loss is the
most common presenting symptom and occurs in The presence of goiter is usually variable in severity;
88% of patients with BOR syndrome.18,19 however, most patients have a positive perchlorate
The most common external ear anomalies are discharge test indicative of a defective organification
preauricular pits and skins tags, but microtia and of iodine in the thyroid gland. The onset of deafness
aural atresia are also noted in patients with BOR is typically congenital, profound, and sensorineural
syndrome. The middle ear cleft is commonly in nature. Cochlear malformation with missing api-
hypoplastic in BOR syndrome, as can be the middle cal turns, known as Mondini’s phenotype, and
ear ossicles. In the inner ear, aplasia or hypoplasia of widened vestibular aqueducts are often described in
the cochlea has been reported as a BOR phenotype these patients.35,36
(Figure 2–9). The vestibular portions of the inner The gene responsible for causing Pendred’s syn-
ear similarly show absent or malformed semicircular drome was identified using a positional cloning
canals. Depending on the ear phenotype, hearing approach and was named PENDRIN.25 Functional
loss can be sensorineural, conductive, or mixed, as studies in Xenopus oocytes show that the encoded
seen in approximately one half of the patients with protein functions as a chloride/iodide transporter.37
BOR syndrome.17 The clinical significance of this gene broadened when
The gene responsible for causing BOR and BO mutations in PENDRIN (PDS) were also shown to
syndromes has been identified to be the human cause autosomal, recessive deafness locus 4 (DFNB4),
homologue of the Drosophila eyes absent (Eya) a recessive nonsyndromic form of deafness.27 Expres-
gene.16,19 The spectrum of malformations seen in sion and gene-targeting studies in mice have provided
BOR syndrome suggests a defect in the EYA1 molec- insights into the etiology of this disorder. In mice, Pds
ular pathway occurring sometime between the is activated during embryonic development. Its
fourth and the tenth week of gestation. The types of expression is restricted to nonsensory regions of the
DNA mutations identified in patients with BOR syn- inner ear including the endolymphatic duct and sac,
drome suggest that the developmental malforma- nonsensory regions of the utricle and saccule, and the
tions result from reduced gene dosage.19 external sulcus region in the cochlea.38 Pendrin knock-
Mice with a targeted deletion of Eya1 also dis- out mice are deaf and display variable vestibular
played similar severe external, middle, and inner ear defects.39 However, the cause of inner ear dysfunction
defects, suggesting that the function(s) of this protein in these mice most likely is not attributable to struc-
in ear development is evolutionary conserved.32 In tural malformations as implied by the human disor-
mice, Eya1 is specifically expressed in the early oto- der. The membranous labyrinth of the Pds knockout
cyst along the ventromedial wall and the adjacent mice swells during late embryonic development
statoacoustic ganglion.33 At later embryonic time indicative of an ionic imbalance presumably owing to
points, Eya1 is expressed along the neuroepithelium a lack of the transporter function of Pds. The sensory
that eventually gives rise to key cochlear structures, hair cells develop and appear normal at birth but
including the inner and outer hair cells. In addition, degenerate later in life, most likely as a consequence of
Eya1 is also expressed in the external and middle ear disrupted fluid homeostasis. It is likely that the etiol-
primordia. These results suggest that the encoded ogy of human Pendred’s syndrome is similar to that of
protein of Eya1 plays a direct role in the formation the Pds knockout mouse model, where the deficit lies
of all three components of the ear in mice as well as in ionic imbalance of the endolymph rather than
in humans. structural malformations during development. The
Studies in Drosophila eye imaginal disks show widened vestibular aqueduct associated with Pen-
that the Eya gene product is a transcriptional coac- dred’s syndrome supports this hypothesis. Mutant
tivator that acts as part of a complex with other tran- mice containing mutations similar to those found in
scription factors during eye morphogenesis.34 Its patients with Pendred’s syndrome will help to clarify
mode of action in ear development remains to be this issue.
established.
SYMPHALANGISM AND MULTIPLE
PENDRED’S SYNDROME SYNOSTOSES SYNDROMES
Pendred’s syndrome is an autosomal recessive disor- Symphalangism syndrome (SYM1), an autosomal
der classically characterized by deafness and goiter. dominant disorder with aberrant bone fusion at
Development of the Ear 33
with bilateral conductive hearing loss, and occasion- reporter gene assays have demonstrated the endoge-
ally malformations of the inner ear have also been nous production of RA by the organ of Corti.49 In
reported.3 This syndrome is caused by mutations in addition, several of the key RA receptors, both at the
the TCOF1 gene that encodes for a nucleolar pro- cytoplasmic and nuclear levels, have been demon-
tein.31,46 TCOF1 is widely expressed in fetal and adult strated in the developing ear region.50 Gain of func-
tissues and is thought to function as a trafficking tion studies have revealed in both chicken and mouse
protein between the nucleolus and cytoplasm. that exogenous RA, administered at low levels during
early embryogenesis, induces a spectrum of inner ear
malformations that are similar to the variety of ear
CROUZON’S DISEASE AND CRANIOSYNOSTOSIS malformations observed with human retinoid
Crouzon’s disease is characterized by craniofacial embryopathy.51,52 Intriguingly, delivery of exogenous
abnormalities and hearing loss. The hearing loss is RA to cultures of the organ of Corti has also been
usually conductive owing to anomalies of the middle shown to cause development of supernumerary hair
ear and atresia of the external auditory canal. Muta- cells.49 Most recently, loss of function studies have
tions in both fibroblast growth factor receptor probed the role of individual and multiple RA recep-
(FGFR) 2 and 3 have been shown to cause Crouzon’s tors in ear development.53–55 Generation of null
disease.21–23 A unique mutation in FGFR3 has also mutant mice carrying targeted deletions of nuclear
been shown to cause craniosynostosis that is associ- retinoic acid receptor and retinoid X receptor iso-
ated with deafness and abnormalities on radi- forms and cytoplasmic retinoic acid binding proteins
ographs of hands and feet.24 In mice, knockout of isoforms has demonstrated the complexity of the
Fgfr3 affected the development of the cochlea in molecular signaling system existing for RA during
which the pillar cells were missing and the tunnel of development.56–58 In several examples, loss of indi-
Corti failed to form.47 vidual RA receptor isoforms fails to yield a signifi-
cant or informative phenotype, possibly owing to
redundancy in the molecular pathways.59 Accord-
TOWNES-BROCKS SYNDROME ingly, investigators have been forced to recognize the
Townes-Brocks syndrome is an autosomal dominant importance of normal RA signaling during develop-
syndrome associated with anal, renal, limb, and ear ment and the compensatory mechanisms in place so
anomalies. External ear malformations and sen- that perturbation of normal signaling does not
sorineural hearing loss are frequently found in this occur, despite interruption of any single signal trans-
syndrome. Malformations of the malleus and incus duction pathway. Also interesting to note is the inter-
have also been reported.29 This syndrome is caused action of RA receptors with other members of the
by mutations in the SALL1 gene, a putative C2H2 steroid hormone superfamily of nuclear receptors.
zinc-fingered transcription factor gene.30 For example, data suggest that thyroid hormone
nuclear receptors may heterodimerize with activated
RA receptors and regulate transcription.60,61 Such
RETINOIDS AND EAR DEVELOPMENT mechanisms would provide a plausible explanation
Since the early 1950s, it was evident to clinicians that for the widespread developmental effects of retinoids
retinoids (vitamin A, retinoic acid [RA], etc) had that seemingly affect various organ systems.
potent teratogenic effects when administered early in Specific to the developing inner ear, RA has
pregnancy.48 Either excess or inadequate maternal been shown to have significant effects on cell
retinoid intake could result in a spectrum of congen- growth and differentiation as early as the otocyst
ital anomalies affecting the central nervous system, stage. Using in vitro62 and in vivo51 animal models
eye, and heart or result in craniofacial defects such as of inner ear development, exogenous RA has been
midface hypoplasia and cleft lip and palate as well as shown to down-regulate cellular proliferation in the
ear and limb malformations. Retinoic acid is one of otocyst in association with altered levels of c-fos
the better-studied retinoids whose role in molecular expression. Furthermore, RA has been shown to
development of the ear has been extensively studied down-regulate the expression of critical genes such
in animal models. Several lines of evidence suggest as Bmp4 that in the chicken and mouse appear to be
an essential role for RA in ear development. First, involved in sensory organ generation. However, a
Development of the Ear 35
key consideration in trying to dissect the molecular 12. Mansour SL, Goddard JM, Capecchi MR. Mice
effects of RA rests in the likelihood that RA impacts homozygous for a targeted disruption of the proto-
multiple signaling pathways; therefore, isolating oncogene int-2 have developmental defects in the
individual effects and their sequelae will be tail and inner ear. Development 1993;117:13–28.
extremely difficult. However, the extensive work 13. Fritzsch B, Pirvola U, Ylikoski J. Making and break-
with RA receptor isoform-specific knockouts com- ing the innervation of the ear: neurotrophic support
bined with work on the various (endogenous and during ear development and its clinical implications.
synthetic) retinoid metabolites may provide the Cell Tissue Res 1999;295:369–82.
means with which to start dissecting this complex 14. Fritzsch B, Farinas I, Reichardt LF. Lack of NT-3
system and thereby determine the role of RA in ear causes losses of both classes of spiral ganglion neu-
development. rons in the cochlea in a region specific fashion. J
Neurosci 1997;17:6213–25.
15. Silos-Santiago I, Fagan AM, Garber M, et al. Severe
REFERENCES sensory deficits but normal CNS development in
1. Knowlton VY. Correlation of the development of newborn mice lacking trkB and trkC tyrosine
membranous and bony labyrinths, acoustics ganglia, protein kinase receptors. Eur J Neurosci 1997;9:
nerves, and brain centers of the chick embryos. J 2045–56.
Morphol 1967;121:179–208. 16. Steel KP, Bussoli TJ. Deafness genes: expressions of
2. Morsli H, Choo D, Ryan A, et al. Development of the surprise. Trends Genet 1999;15:207–11.
mouse inner ear and origin of its sensory organs. J 17. Vincent C, Kalatzis V, Abdelhak S, et al. BOR and BO
Neurosci 1998;18:3327–35. syndromes are allelic defects of EYA1. Eur J Hum
3. Schuknecht HF. Developmental defects. In: Pathol- Genet 1997;5:245–6.
ogy of the ear. 2nd ed. Philadelphia (PA): Lea & 18. Fraser FC, Sproule JR, Halal F. Frequency of the
Febiger; 1993. p. 115–89. branchio-oto-renal (BOR) syndrome in children
4. Artavanis-Tsakonas S, Rand M, Lake R. Notch sig- with profound hearing loss. Am J Med Genet 1980;7:
naling: cell fate control and signal integration in 341–9.
development. Science 1999;284:770–6. 19. Millman B, Gibson WS, Foster WP. Branchio-oto-
5. Bray S. Notch signaling in Drosophila: three ways to renal syndrome. Arch Otolaryngol Head Neck Surg
use a pathway. Semin Cell Dev Biol 1998;9:591–7. 1995;121:922–5.
6. Haddon C, Jiang Y, Smithers L, Lewis J. Delta-notch 20. Abdelhak S, Kalatzis V, Heilig R, et al. A human
signalling and the patterning of sensory cell homologue of the Drosophila eyes absent gene under-
differentiation in the zebrafish ear: evidence from lies branchio-oto-renal (BOR) syndrome and identi-
the mind bomb mutant. Development 1998;125: fies a novel gene family. Nat Genet 1997;15:157–64.
4637–44. 21. Wilkes D, Rutland P, Pulleyn LJ, et al. A recurrent
7. Lanford PJ, Lan Y, Jiang R, et al. Notch signalling mutation, ala391glu, in the transmembrane region
pathway mediates hair cell development in mam- of FGFR3 causes Crouzon syndrome and acanthosis
malian cochlea. Nat Genet 1999;21:289–92. nigricans. J Med Genet 1996;33:744–8.
8. Bermingham NA, Hassan BA, Price SD, et al. Math1: 22. Reardon W, Winter RM, Rutland P, et al. Mutations
an essential gene for the generation of inner ear hair in the fibroblast growth factor receptor 2 gene cause
cells. Science 1999;284:1837–41. Crouzon syndrome. Nat Genet 1994;8:98–103.
9. D’Amico-Martel A, Noden D. Contribution of pla- 23. Meyers GA, Orlow SJ, Munro IR, et al. Fibroblast
code and neural crest cells to avian cranial peripheral growth factor receptor 3 (FGFR3) transmembrane
ganglia. Am J Anat 1983;163:351–72. mutation in Crouzon syndrome with acanthosis
10. Carney PR, Couve E. Cell polarity changes and migra- nigricans. Nat Genet 1995;11:462–4.
tion during early development of the avian periph- 24. Muenke M, Gripp KW, McDonald-McGinn DM, et al.
eral auditory system. Anat Rec 1989;225:156–64. A unique point mutation in the fibroblast growth fac-
11. Ma Q, Anderson DJ, Fritzsch B. Neurogenin 1 null tor receptor 3 gene (FGFR3) defines a new craniosyn-
mutant ears develop fewer, morphologically normal ostosis syndrome. Am J Hum Genet 1997;60:555–64.
hair cells in smaller sensory epithelia devoid of 25. de Kok YJ, van der Maarel SM, Bitner-Glindzicz M,
innervation. I J Assoc Res Otokiryn 2000;1:129–43. et al. Association between X-linked mixed deafness
36 Ballenger’s Otorhinolaryngology
and mutations in the POU domain gene POU3F4. 40. Holley SA, Neul JL, Attisano L, et al. The Xenopus
Science 1995;267:685–8. dorsalizing factor noggin ventralizes Drosophila
26. Everett LA, Glaser B, Beck JC, et al. Pendred syn- embryos by preventing DPP from activating its
drome is caused by mutations in a putative sulphate receptor. Cell 1996;86:607–17.
transporter gene (PDS). Nat Genet 1997;17:411–22. 41. Brunet LJ, McMahon JA, McMahon AP, Harland
27. Li XC, Everett LA, Lalwani AK, et al. A mutation in RM. Noggin, cartilage morphogenesis, and joint for-
PDS causes non-syndromic recessive deafness. Nat mation in the mammalian skeleton. Science 1998;
Genet 1998;18:215–7. 280:1455–7.
28. Gong Y, Krakow D, Marcelino J, et al. Heterozygous 42. McMahon JA, Takada S, Zimmerman LB, et al. Nog-
mutations in the gene encoding noggin affect human gin-mediated antagonism of BMP signaling is
joint morphogenesis. Nat Genet 1999;21:302–4. required for growth and patterning of the neural
29. Ferraz FG, Nunes L, Ferraz ME, et al. Townes-Brocks tube and somite. Genes Dev 1998;12:1438–52.
syndrome. Report of a case and review of the litera- 43. Phippard D, Heydemann A, Lechner M, et al. Changes
ture. Ann Genet 1989;32:120–3. in the subcellular localization of the Brn4 gene prod-
30. Kohlhase J, Wischermann A, Reichenbach H, et al. uct precede mesenchymal remodeling of the otic
Mutations in the SALL1 putative transcription factor capsule. Hear Res 1998;120:77–85.
gene cause Townes-Brocks syndrome. Nat Genet 44. Phippard D, Lu L, Lee D, et al. Targeted mutagenesis
1998;18:81–3. of the POU-domain gene Brn4/Pou3f4 causes devel-
31. The Treacher Collins Collaborative Group. Posi- opmental defects in the inner ear. J Neurosci 1999;
tional cloning of a gene involved in the pathogenesis 19:5980–9.
of Treacher Collins syndrome. Nat Genet 1996;12: 45. Minowa O, Ikeda K, Sugitani Y, et al. Altered cochlear
130–6. fibrocytes in a mouse model of DFN3 nonsyndromic
32. Xu PX, Adams J, Peters H, et al. Eya1-deficient mice deafness. Science 1999;285:1408–11.
lack ears and kidneys and show abnormal apoptosis 46. Isaac C, Marsh KL, Pazekas WA, et al. Characteriza-
of organ primordia. Nat Genet 1999;23:113–7. tion of the nucleolar gene product, treacle, in
33. Kalatzis V, Sahly I, El-Amraoui A, Petit C. Eya1 expres- treacher collins syndrome. Mol Biol Cell 2000;11:
sion in the developing ear and kidney: towards the 3061–71.
understanding of the pathogenesis of branchio-oto- 47. Colvin JS, Bohne BA, Harding GW, et al. Skeletal
renal (BOR) syndrome. Dev Dyn 1998;213:486–99. overgrowth and deafness in mice lacking fibroblast
34. Pignoni F, Hu B, Zavitz KH, et al. The eye-specifica- growth factor receptor 3. Nat Genet 1996;12:
tion proteins So and Eya form a complex and regu- 390–7.
late multiple steps in Drosophila eye development. 48. Wilson J, Roth C, Warkany J. An analysis of the syn-
Cell 1997;91:881–91. drome of malformations induced by maternal vita-
35. Phelps PD, Coffey RA, Trembath RC, et al. Radio- min A deficiency. Effects of restoration of vitamin A
logical malformations of the ear in Pendred syn- at various times during gestation. Am J Anat 1953;
drome. Clin Radiol 1998;53:268-273. 92:189–217.
36. Johnsen T, Jorgensen MB, Johnsen S. Mondini 49. Kelley MW, Xu XM, Wagner MA, et al. The develop-
cochlea in Pendred’s syndrome. A histological study. ing organ of Corti contains retinoic acid and forms
Acta Otolaryngol (Stockh) 1986;102:239–47. supernumerary hair cells in response to exogenous
37. Scott DA, Wang R, Kreman TM, et al. The Pendred retinoic acid in culture. Development 1993;119:
syndrome gene encodes a chloride-iodide transport 1041–53.
protein. Nat Genet 1999;21:440–3. 50. Smith SM, Eichele G. Temporal and regional differ-
38. Everett LA, Morsli H, Wu DK, et al. Expression pat- ences in the expression pattern of distinct retinoic
tern of the mouse ortholog of the Pendred’s syn- acid receptor–beta transcripts in the chick embryo.
drome gene (Pds) suggests a key role for pendrin Development 1991;111:245–52.
in the inner ear. Proc Natl Acad Sci U S A 1999;96: 51. Choo D, Sanne JL, Wu DK. The differential sensitiv-
9727–32. ities of inner ear structures to retinoic acid during
39. Everett LA, Belyanseva IA, Noben-Trauth K, et al. development. Dev Biol 1998;204:136–50.
Targeted disruption of mouse Pds provides insight 52. Frenz DA, Liu W, Galinovic-Schwartz V, Van De
about the inner-ear defects encountered in Pendred Water TR. Retinoic acid-induced embryopathy of
syndrome. Hum Mol Genet 2001;10:153–61. the mouse inner ear. Teratology 1996;53:292–303.
Development of the Ear 37
53. Lohnes D, Mark M, Mendelsohn C, et al. Function of 62. Represa J, Sanchez A, Miner C, et al. Retinoic acid
the retinoic acid receptors (RARs) during develop- modulation of the early development of the inner
ment (I). Craniofacial and skeletal abnormalities ear is associated with the control of c-fos expression.
in RAR double mutants. Development 1994;120: Development 1990;110:1081–90.
2723–48.
54. Lohnes D, Mark M, Medelsohn C, et al. Develop-
mental roles of the retinoic acid receptors. J Steroid
SUGGESTED READING
Biochem Mol Biol 1995;53:475–86. Anson JA, Davies J, Duckert LG. Embryology. In: Papar-
55. Mark M, Ghyselinck NB, Wendling O, et al. A genetic ella MM, Shumrick DA, editors. Otolaryngology. Vol
dissection of the retinoid signalling pathway in the 1. Philadelphia (PA): WB Saunders; 1991. p. 3–22.
mouse. Proc Nutr Soc 1999;58:609–13. Donaldson JA, Miller JM. Anatomy of the ear. In: Papar-
56. Morriss-Kay GM, Ward SJ. Retinoids and mam- ella MM, Shumrick DA, editors. Otolaryngology. Vol
malian development. Int Rev Cytol 1999;188: 73–131. 1. Philadelphia (PA): WB Saunders; 1973. p. 75–110.
57. Collins MD, Mao GE. Teratology of retinoids. Annu Donaldson JA, Lambert PM, Duckert LG, Rubel EW. The
Rev Pharmacol Toxicol 1999;39:399–430. ear: developmental anatomy. In: Donaldson JA,
Lambert PM, Duckert LG, Rubel EW, editors. Surgi-
58. Ross SA, McCaffrey PJ, Drager UC, DeLuca LM.
cal anatomy of the temporal bone. New York: Raven
Retinoids in embryonal development. Physiol Rev
Press; 1992. p. 19–108.
2000;80:1021–54.
Krsti’c RV. Human microscopic anatomy. New York:
59. Mendelsohn C, Mark M, Dolle P, et al. Retinoic acid
Springer-Verlag; 1997.
receptor beta 2 (RAR beta 2) null mutant mice Moore KL. The developing human. Philadelphia (PA):
appear normal. Dev Biol 1994;166:246–58. WB Saunders; 1977.
60. Brown NS, Smart A, Sharma V, et al. Thyroid hormone Schuknecht HF. Anatomy. In: Schuknecht HF. Pathology
resistance and increased metabolic rate in the RXR- of the ear. Philadelphia (PA): Lea & Febiger; 1993.
gamma-deficient mouse. J Clin Invest 2000;106:73–9. p. 31–75.
61. Lee SK, Lee B, Lee JW. Mutations in retinoid X Sulik KK. Embryology of the ear. In: Gorlin RJ, Toriello
receptor that impair heterodimerization with spe- HV, Cohen MM, editors. Hereditary hearing loss and
cific nuclear hormone receptor. J Biol Chem 2000; its syndromes. New York: Oxford University Press;
275:33522–6. 1995. p. 22–42.
CHAPTER 3
Molecular biology is a branch of modern biology in has led to the isolation of many families, some quite
which biologic processes are studied using physical, extensive, of genes encoding related proteins. Other
biochemical, cellular, and genetic principles at the widely used methods in molecular biology include
molecular level. The techniques of molecular biol- the polymerase chain reaction (PCR) for amplifica-
ogy use deoxyribonucleic acid (DNA) sequences that tion of DNA sequences present in low copy num-
encode proteins or that regulate protein expression. bers1 and in situ mRNA hybridization for the
This emerging science has contributed to localization of gene expression to individual cells.2
major advances in our understanding of cellular (Terms that are frequently used in molecular biology
function, in health as well as in disease. It also has are listed in Table 3–1, and a number of important
resulted in a deeper understanding of the pathogen- concepts and methods are illustrated in Figures 3–1
esis of many diseases and the revolutionary develop- through 3–5).
ment of new approaches in diagnosis, prevention,
and treatment of diseases, including gene therapy.
This chapter reviews the rapidly developing molec-
GENE EXPRESSION SYSTEMS
ular methodologies that have made contributions to The expression of cloned genes in biologic systems
advance our understanding of the cellular functions ranging from bacteria and Xenopus oocytes3 (Figure
and dysfunctions of the auditory and vestibular sys- 3–6) to eukaryotic cell lines and intact mammals has
tems, in molecular terms. It reviews recent advances become a major tool in biologic research. The
achieved with these techniques in both the basic and expression of functional proteins in cells has added
clinical arenas. to our knowledge of numerous molecules such as
neuronal receptors, ion channels, and transcription
factors. Targeted mutations in the translated
MOLECULAR METHODOLOGY sequences of genes have made fundamental contri-
The rapid expansion of molecular research has been butions to the molecular determinants of protein
the result of the introduction of several powerful function, as in studies that identify the functional
methodologies for isolating gene sequences and domains of potassium channels and provide evi-
characterizing their expression. At the center of these dence to support a “ball-and-chain” model of their
methodologies are gene-cloning techniques, which action4,5 and amino acid sequences governing inter-
rely on the replication of DNA sequences in bacte- action between subunits of ion transport adenosine
riophages and plasmids, generating large amounts of triphosphatases (ATPases).6 The use of different pro-
DNA that can be screened, characterized, and moter elements and mutations within promoters has
sequenced. Another crucial method is reverse tran- dramatically increased our understanding of the
scription of messenger RNA (mRNA), in which viral control of gene expression.7
enzymes capable of copying RNA into DNA are used
to generate complementary DNA (cDNA) copies of
mRNAs isolated from tissue. Reverse transcription
TRANSGENIC ANIMALS
and cloning have allowed the rapid discovery of new The influence of genes in the organism has been
genes, usually based on homology with known DNA studied by placing the gene sequences of interest
sequences or on assay of functional characteristics under control of tissue-specific promoter sequences
when cDNAs are cloned in expression vectors. This that target expression to given tissue and inserting
38
Molecular Biology of Hearing and Balance 39
FIGURE 3–2. Basic structure of a developmentally regulated gene is illustrated. The promoters of most genes encod-
ing proteins are found at the 5´ (upstream) end of the gene. Enhancers are often even farther upstream, but they can
also occur within an intron of the gene or at the 3´ end. Proteins that bind to promoters and enhancers interact to reg-
ulate transcription of the gene. Adapted from Gilbert SF.8
Molecular Biology of Hearing and Balance 41
Hybrid
phage
Add to lawn
of E. coli cells
Reverse Transcriptase
cDNA Transfer some phage
onto nitrocellulose
mRNA
filter
RNase H, DNA polymerase I
cDNA Nitrocellulose
filters
mRNA
FIGURE 3–5. Schematic illustration of protocol to make complementary deoxyribonucleic acid (cDNA) libraries. Step
A: Messenger ribonucleic acid (mRNA) is isolated from a tissue of interest and reverse transcribed into cDNA. This
cDNA represents all of the genes being expressed in the tissue. It is made double-stranded in a nick translation reac-
tion, in which ribonuclease H nicks the mRNA strand, creating a primer for second-strand DNA synthesis by DNA
polymerase I. Sequences (adapters) that allow ligation into a cloning vector are added to double-stranded cDNA. Step
B: The cDNA can then be inserted into specially modified vectors, in this case bacteriophages. Step C: Phages con-
taining the recombinant DNA will infect Escherichia coli and reproduce, making many copies and eventually lysing the
bacteria forming plaques. Step D: The plaques are transferred to nitrocellulose paper and treated with alkali to lyse the
phages and denature the DNA in place. These filters are then incubated in a radioactive probe. This can be a short DNA
sequence (oligonucleotide), a cDNA, or other DNA fragment. In the case of differential cDNA library screening, the
same phage library is screened with radioactive cDNA probes reverse transcribed from mRNA isolated from two dif-
ferent tissues. This allows the identification of a relatively abundant mRNA that would be found in one type of tissue
but not in the other. Adapted from Gilbert SF.8
Molecular Biology of Hearing and Balance 43
same neurotransmitter. In addition, mRNA tran- increased exponentially after the introduction of
scribed from a single gene can often be assembled molecular methodology, from a few dozen in the
into mRNAs encoding functionally different forms early 1980s to nearly 10,000 in 1991,28 and the num-
of the protein product from different combinations ber continues to increase. This increase was the
of exons by the process of alternative splicing, lead- result of several critical technical developments. The
ing to even greater variation.23 Increased under- isolation of large numbers of restriction enzymes to
standing of the molecular basis for functional cut DNA at specific locations has led to the discov-
diversity of proteins may be one of the most signifi-
cant contributions of molecular biology.
32p-labeled
size markers Electrophoresis
Gel Nitrocellulose
Salt
solution
Probe hybridized
to complementary Remove Gel filter
sequence unbound probe
DNA transferred
Expose to Hybridize with to filter
x-ray film unique nucleic acid
Filter in
probe
“Seal-a-Meal”
bag
Autoradiogram
FIGURE 3–9. Schematic illustration of Southern blotting. Deoxyribonucleic acid (DNA) digested with restriction
enzymes is loaded onto a gel and electrophoretically separated by molecular size. After the fragments of DNA are sep-
arated, the DNA is denatured into single strands. The gel is then placed on a support on top of filter paper saturated
with buffer. A nitrocellulose or nylon filter is placed on top of the gel, and absorbent towels are placed on top of the
filter. The transfer buffer makes its way through the gel, nitrocellulose paper, and towels by capillary action, taking the
DNA with it. The single-stranded DNA sticks to the filter. The filter is then removed, the DNA is immobilized on to
the filter, and the filter is hybridized with a radioactively labeled probe. The position of the DNA fragment comple-
mentary to the probe appears as a band on x-ray film, which reflects the position of the DNA fragment in the gel.
Adapted from Watson JD et al.29
methods. The limited amount of tissue that is avail- becoming available for genotyping individuals with
able from the middle ear, labyrinth, and many cen- potential genetic disorders affecting hearing or for
tral auditory structures, coupled with the diversity identifying disease pathogens as in otitis media
of cell types present, has contributed to the dispar- (OM). However, molecular therapy has yet to be
ity. This has slowed the generation of cDNA applied to the ear. However, many otologists recog-
libraries, especially those for specific cell types. It has nize the potential of molecular medicine to improve
also made the application of other methods for cat- diagnosis and treatment in the future.
aloguing gene expression, such as gene array tech- As noted above, molecular biologic studies of
nology, difficult. A second impediment to progress is the ear have increased greatly in the past several years,
a relative paucity of in vitro models of many aspects to the point where it is no longer possible to provide
of auditory development and function that are a comprehensive review in the space available. How-
appropriate for molecular manipulation. Thus, ever, some recent highlights are presented below.
molecular methods often need to be applied to the
intact organism as opposed to culture systems or
cell lines.
DEAFNESS GENES
Molecular biology has been minimally applied Molecular Basis of Deafness A notable exception
in the clinic. Molecular diagnostic techniques are to the generally slower rate of molecular progress in
46 Ballenger’s Otorhinolaryngology
our field is the molecular genetics of deafness, per- family of genes in which defects in another member,
haps because this field is less dependent on extract- EYA1, cause a separate hereditary hearing impair-
ing molecular information from the auditory tissues ment disorder, branchio-oto-renal syndrome.51,52
themselves. We now know the identity of more than In addition, around 50 new hearing- and/or
16 genes of the 60+ loci known to be involved in balance-defective mouse mutants have been created
nonsyndromic deafness in humans, and many new by two large European ethylnitrosourea (ENU)
syndromic deafness genes have also been identified.32 mutagenesis programs,53,54 with more becoming
For example, Alport’s syndrome has been associated available from other, similar programs in the United
with a mutation in the gene encoding the basement States. A number of the genes involved in deafness in
membrane collagen (COL4A5).33,34 Waardenburg’s these new mouse mutants and other older mouse
syndrome types I and III have been identified with mutations have been identified. An example is the
mutations in the transcription factor gene PAX3.35 novel unconventional myosin, myosin 15, which is
Myosin VIIA (MyoIIIA) has been identified as the mutated in the Shaker 2 mouse. This example is par-
gene responsible for Usher’s syndrome type IB.36 ticularly notable for the use of bacterial artificial
Linkage of neurofibromatosis 2 (NF2) to chromo- chromosome (BAC) transgenic mice to identify the
some 22q37,38 led to fine-scale mapping39 and then to mutated gene.55 With the completion of draft
identification of a mutated gene, which encodes a sequences of the human genome and progress
new member of the family of 4.1 cytoskeletal associ- toward completion of mouse genome sequencing,
ated proteins known as merlin.40,41 Neurofibromato- the transition from linkage to gene identification has
sis 2 is an autosomal dominant inherited disease and will become increasingly more rapid. Many gene
characterized by bilateral vestibular schwannomas knockouts also have effects on the development or
and other central nervous system tumors and is function of the ear, which has allowed us to build up
often associated with hearing impairment caused by rapidly our knowledge of the molecular basis of
cochlear nerve compression. Similarly, testing of auditory function and development.56 Examples
candidate genes near the linkage site for X-linked include genes encoding PMCA2,57 Brn-4,58 and oto-
deafness with stapes fixation (DFN3 = nonsyn- gelin.59
dromic deafness X-linked gene third to be discov- There is an important trend emerging toward
ered) led to the identification of the mutated gene as using the information obtained from genetic screen-
Brn-4, which encodes a transcription factor with a ing to study the functional biology of the inner ear,
POU domain (POU3F4).42 A mutation in the related for example, the work of Karen Steel and others
gene, Brn-3.1, causes nonsyndromic deafness in showing changes in susceptibility to ototoxicity in
DFNA15 (nonsyndromic deafness autosomal domi- myosin VIIA–deficient animals.60 Another example
nant gene fifteenth to be discovered). These tran- is pendrin, which is giving insights into cochlear ion
scription factors are members of a gene family that transport processes.61 Microarray analysis is also
is expressed in the cochlea during development.43 beginning to be used to investigate changes in pat-
The indentification of mutations in the connexin 26 terns of gene expression resulting from single-gene
gene, encoding a gap junction protein,44 as the basis mutations, giving clues to the pathways affected by
for DFNA1 is particularly significant. Mutations in the mutations.
this gene are particularly common, and it is esti- Molecular genetics is an arena in which there is
mated that up to 50% of all nonsyndromic heredi- extensive interaction between clinicians and basic
tary deafness in the United States is caused by scientists. In particular, several genes involved in
mutations in this gene.45 A defect in mitochondrial inherited deafness have been first cloned in basic sci-
DNA that increases susceptibility to aminoglycoside ence laboratories or identified with the aid of mouse
ototoxicity and that, in combination with an auto- models.49,62,63
somal mutation, leads to maternally inherited non- Linkage and identification of mutations caus-
syndromic deafness has also been characterized.46–48 ing deafness and vestibular disorders have immedi-
The gene responsible for Usher’s syndrome ate clinical significance since they allow genetic
type 1C has been identified and reveals a unique testing and counseling and may eventually provide a
pathologic mutation.49 Also of note is the finding in basis for gene therapy. They are also proving to be an
DFNA10 of mutations in EYA4,50 a member of a important means of identifying genes whose expres-
Molecular Biology of Hearing and Balance 47
sion is important for normal cochlear development tory system. However, deletion of both a and g iso-
and function. types results in absence of the stapes, an abnormal
incus, a small and incomplete cartilaginous otic cap-
sule, and absence of the organ of Corti and spiral
INNER EAR DEVELOPMENT ganglion.71
Many genes involved in auditory ontogeny have Bone morphogenetic proteins (BMPs) are
been identified by screening for gene expression in members of the transforming growth factor-alpha
developing auditory tissues. Polymerase chain reac- (TGF-) superfamily. Oh and Wu investigated BMP
tion and in situ hybridization have provided a wealth (BMP-4, -5, -7) expression during development of
of information regarding which genes are expressed the chick otocyst.72 In situ hybridization analysis
and in which tissues. Whereas expression of a gene showed that BMP-4 mRNA was present in the future
in a cell or tissue suggests a functional role, mutation ampullae of the three semicircular ducts on embry-
of the gene leading to a phenotype provides much onic day 2.5 to 3. Bone morphogenetic protein 5
more convincing evidence that the molecule func- mRNA, however, was only found transiently in the
tions within the context of the intact tissue and future ampulla of the posterior semicircular duct.
organism. Many genes involved in syndromic and Bone morphogenetic protein 7 mRNA, on the other
nonsyndromic deafness appear to be critical devel- hand, was initially expressed in most parts of the
opmental regulators, such as the unconventional otocyst and became restricted to specific regions by
myosins that are involved in stereociliary morpho- embryonic day 3. These investigators suggested that
genesis.64 Similarly, despite the risks of redundancy, BMPs may play an important role in the differentia-
the targeted deletion of an increasing number of tion of inner ear sensory organs. Inactivation of
genes has illuminated their role in auditory develop- BMP-4 results in embryonic lethality73; however,
ment and/or function. This includes a variety of mice heterozygous for BMP-4 deletion exhibit
developmental genes that influence organogenesis of abnormal vestibular behavior and malformations of
the labyrinth or the development of inner ear cell the lateral semicircular canal,74 suggesting a role in
types.56 Many such genes involved in inner ear mor- labyrinthine patterning.
phogenesis are known to play roles in the morpho- In the sensory epithelia of the inner ear, several
genesis of other developing structures.65–67 genes involved in hair cell fate selection and differ-
Several genes have been shown using molecu- entiation have recently been identified with this
lar techniques to affect the basic morphogenesis of approach. For example, deletion of the Math1 gene
the labyrinth, beginning at the stage of the otocyst. in mice results in failure of cells in the organ of Corti
For example, retinoids68,69 affect ear development. to adopt the hair cell phenotype.75 In addition, exit
The retinoic acid receptor (RAR) family of nuclear of committed hair cells from the cell cycle appears to
receptors for retinoic acid (RA) is one of two groups be dependent on expression of p27Kip1 since dele-
of DNA binding proteins that are activated by inter- tion of this gene leads to formation of supernumer-
action with this ligand. They serve as ligand- ary hair cells.76,77 The related factor p19Ink4d may
inducible regulators of transcription by activating play a similar role (Chen P and Segil N, unpublished
RA responsive promoters. There are three RAR gene observations). Hair cell differentiation requires
isotypes, RARa, RARb, and RARg, each with their expression of the POU domain transcription factor
own isoforms, and they have widespread expression Brn-3.1. In mice null for Brn-3.1, hair cells never
patterns in the developing inner ear. Retinoic acid develop cuticular plates or stereocilia, and many
receptor a expression is ubiquitous in cochlear eventually die.78,79 The differentiation of hair cells
sensory and nonsensory structures. Retinoic acid from supporting cells appears to be regulated in
receptor b is expressed mainly in structures of mes- addition by Notch/Delta signaling since deletion of
enchyme origin and in vestibular sensory epithelia. the gene encoding the Delta family protein Jagged 2
Retinoic acid receptor g is located in the cochlear results in increased numbers of hair cells, perhaps
and vestibular compartments in the epithelium of via down-regulation of Notch in supporting cells.80
the inner ear.70 Because of functional redundancy, Understanding the lineage relationships
deletion of individual receptor isoforms has rela- between hair and supporting cells and the molecules
tively little effect on the development of the audi- involved in a cell’s decision to become either a hair
48 Ballenger’s Otorhinolaryngology
or a supporting cell provides insights into mecha- dle on each sensory cell surface. Deflection of the cil-
nisms of hair cell regeneration. Delta appears to be iary bundle by mechanical force toward the kinocil-
involved in hair cell regeneration in the avian basilar ium (or basal body in the case of the cochlea) is
papilla. The underlying supporting cells begin excitatory and toward the opposite direction is
expressing Delta upon hair cell loss.81 In perhaps the inhibitory for neural discharges. Deflection of the
most intriguing recent observation, Zheng and Gao stereociliary bundle toward the excitatory direction
have shown that transfection of the developing is now known to open transduction channels located
organ of Corti with the Math1 coding sequence on the upper part of the stereocilia.88–90 The opening
results in the adoption of the hair cell phenotype of the transduction channels is believed to be medi-
by cells far outside the normal location of hair ated by filamentous structures connecting the tip of
cells.82 Math1 thus appears to be both necessary and the lower stereocilium to the neighboring taller
sufficient for promoting hair cell fate selection and stereociliary surface known as tip links.91,92 Most of
differentiation. the molecules responsible for the hair cell transduc-
Neurotrophic growth factors such as basic tion process have yet to be identified. However, some
fibroblast growth factor (bFGF), TGF-α, and neu- progress has been made in the transduction chan-
rotrophins, such as neurotrophin 3 (NT-3) and nel93,94 and the adaptation motor in vestibular sen-
brain-derived neurotrophic factor (BDNF), are sory hairs.95 The precise location of the transduction
necessary for survival and neurite extension in channels is not yet established. It is believed to be
auditory and vestibular neurons during both early associated with tip links because a calcium chelator
and late stages of ear development.83 Messenger eliminates both transduction current and tip links.91
RNAs encoding both BDNF and NT-3 are expressed Hackney et al used an antibody to the amiloride-
in the inner ear during development.84,85 Cochlear sensitive sodium channel to label the side of the
and vestibular neurons both respond to BDNF and stereocilia just below the tip-link attachment site.93 A
NT-3 in vitro. 16 Inhibition of BDNF and NT-3 recent advance is the identification of a mechanically
expression using antisense oligonucleotides pre- sensitive ion channel of the TRP superfamily that is
vents neurite extension in vitro. 86 Finally, using required for mechanotransduction in the bristle
mutant mice with knockout of the BDNF gene or organ of Drosophila.96 A mammalian homologue
NT-3 gene or both genes, Ernfors et al demon- would be an excellent candidate for the transduction
strated that BDNF is critical for survival of the channel of hair cells.
vestibular ganglion and maintenance of both affer- To retain sustained sensitivity during transient
ent and efferent innervation.87 These data are displacement, the vestibular sensory cell must adapt
consistent with observations in mice lacking a func- to sustained stimuli. Adaptation of vestibular sen-
tional NT-3 gene reported by Farinas et al.17 In the sory cell is thought to be mediated by a “slipping” of
cochlea, BDNF gene–deleted mice showed loss of tip-link attachment and by an active “tensioning.” 97
presumptive type II ganglion cells and afferent Readjusting tension of the tip link is necessary for
innervation to outer hair cells, whereas NT-3 gene– the adaptation of the vestibular sensory cells.95,98
deleted mice showed loss of presumptive type I gan- This tensioning is suggested to be mediated by 120
glion cells and the majority of afferent innervation. kDa myosin motors, which are presumably located
The double mutants lose all vestibular and cochlear in the insertional plaque and run on the surface of
ganglion cells.16 the stereociliary actin filaments as guides.94,95,98
The discoveries of the acoustic emission99 and
MOLECULAR SUBSTRATES OF AUDITORY the electromotor activity of the dissociated outer
hair cells in mammals 100,101 led to the concept of
FUNCTION active hearing. According to this concept, amplifica-
Hair Cell Transduction The major function of tion of auditory sensitivity and sharp tuning of the
the sensory hair cells in the inner ear is to transduce basilar membrane frequency response are the result
mechanical energy into neural information. The of motor activity by the outer hair cell. There is
sensory cells of both the cochlea and the vestibular strong evidence that this motor activity is driven by
sensory organs are mechanoreceptors equipped with multiple molecular motors, which are an integral
a geometrically arranged sensory stereociliary bun- part of the cell membrane.102,103
Molecular Biology of Hearing and Balance 49
An exciting development is the identification be strongly expressed in cochlear hair cells and to
of prestin as a candidate for the outer hair cell motor match exactly the pharmacology of the outer hair
protein. This molecule, related to the anion trans- cell response to this transmitter.116 In general, the
porter pendrid, was one of several identified in a dif- diversity of receptor and transmitter expression
ferential screen of cDNAs performed by subtractive associated with the efferent system matches the com-
PCR between cDNAs derived from outer versus plex pharmacology of the inner ear.
inner hair cells. A full-length cDNA produced mem-
brane motility when transfected into an unrelated Inner Ear Fluid Regulation Differences in the
cell type, identifying this molecule as a strong can- ionic composition between endolymph and peri-
didate for the outer hair cell membrane motor pro- lymph have been shown to play a critical role in
tein.104 Supporting the evolutionary relationship inner ear function. It is, therefore, not surprising
between prestin and an anion transporter is the that the expression of genes encoding a number of
observations that the intracellular anions chloride ion transport enzymes117,118 and ion channels119 has
and bicarbonate are required for prestin’s voltage been found in the inner ear. Of particular interest
sensitivity.105,106 are the Na, K-ATPase genes since this enzyme
appears to be the most important determinant of the
Neurotransmitters Afferent and efferent (medial composition of perilymph and endolymph. In the
and lateral) systems and the innervation patterns of stria vascularis, the α1 and β2 isoforms are the only
the auditory organ are relatively well established. ones expressed. 117 This combination is not found in
Although remarkable progress has been made in isolation in any other tissue in the body. However,
recent years, our knowledge concerning inner ear the β2 subunit is associated with transporting
neurochemistry is yet to be completed. Afferent neu- sodium against a high electrochemical gradient. In
rotransmission between the cochlear hair cells and order for the stria vascularis to transport sodium
spiral ganglion neurons is mediated by an as yet against the highest gradient in the body, perhaps this
unidentified neurotransmitter. Based on molecular unique composition of the enzyme is required. Sev-
analysis evidence, the strongest candidate for this eral additional proteins that appear to be involved in
transmitter is glutamate or a related amino acid.107 circulation of K+ ions from the organ of Corti to the
The expression of mRNAs encoding glutamate stria vascularis have been identified via natural or
receptors has been detected in spiral ganglion neu- induced mutations.120 These include connexin 26
rons. These include members of the AMPA (α- expressed in cells of the organ of Corti,44 a Na-K-Cl
amino-3-hydroxy-5-methyl-4-isoxazolepropionate),108 cotransporter expressed in basal cells of the stria vas-
NMDA, and kainate108,109 glutamate receptor fami- cularis,121 and an ISK potassium channel expressed
lies. These observations strongly support the by marginal cells.122
hypothesis that an excitatory amino acid like gluta-
mate is one of the cochlear afferent neurotrans-
mitters. The primary efferent neurotransmitter be- INNER EAR PROTEINS
tween the brainstem and cochlea is thought to Genes important for inner ear function have often
be acetylcholine, with other transmitters, including been highlighted by mutational analysis. An addi-
γ-aminobutyric acid (GABA), opioid and other pep- tional paradigm for identifying functionally impor-
tides, and possibly adenosine triphosphate (ATP), tant proteins is to look for genes whose pattern of
also being involved. Members of several neuronal expression is limited to the inner ear and to test if
receptor gene families have been shown to be these genes are important for inner ear function,
expressed in the cochlea. Expression of genes encod- creating animal models with nonfunctional mutant
ing nicotinic,110 muscarinic,111 and metabotropic112 versions of these genes. To date, very few genes
acetylcholine receptors; GABA receptors113; and ATP showing a pattern of expression limited to the inner
receptors114 has been documented in the cochlea, ear have been reported. The organ of Corti–specific
whereas preproenkephalin mRNA has been found in proteins OCP I and OCP II have been identified,123
cochlear and vestibular efferent cell bodies in the and the OCP II gene has been cloned.124 Tectorial
brainstem.115 In particular, the α9 member of the membrane proteins (tectorins) with little homology
nicotinic acetylcholine receptor has been shown to to known proteins have also been cloned.125
50 Ballenger’s Otorhinolaryngology
An inner ear–specific novel structural protein of other proteins, or antisense RNA for suppression
in the sunfish saccule has been cloned and charac- of targeted proteins, as well as cell-specific gene dele-
terized.126 A cDNA, obtained by differential screen- tions using CRE-LOX recombinant and similar
ing of a saccular cDNA library, that encodes an methodologies, in auditory cells.
inner ear–specific collagen molecule was identified.
The predicted amino acid sequence of this protein
showed 40% identity and 56% overall homology
GENE THERAPY IN ANIMAL MODELS
with collagen types VIII and X.127 In situ hybridiza- The use of gene therapy for disorders of the ear
tion with an antisense saccular collagen cRNA remains a prospect for the future. However, research
showed that transcripts encoding this protein are on this topic gives promise to the idea that at least
localized only to the edge of the saccular epithe- some inner ear conditions might be treated using
lium, indicating that these specialized epithelial molecular biologic methodologies.
(supporting) cells may secrete this protein, which For example, mutations that delete a critical
is believed to be a component of the otolithic gene can, in some instances, be corrected by supply-
membrane.126 ing the missing gene. Yoo et al studied the shiverer
Much of the molecular data generated to date mouse, which has a neurologic disorder caused by a
has involved identification of novel gene sequences mutation in the gene encoding myelin basic protein
for structural proteins and has not been well inte- and characterized by defects in the myelination of
grated into the functions of the inner ear. Future nerve tracts.130 These mice show deficits in both the
studies will be needed to test the importance of these amplitude and latency of auditory brainstem
genes and others for normal inner ear function. responses (ABRs) owing to abnormal conduction in
auditory nerve fibers. When a transgene encoding
normal myelin basic protein was integrated into the
GENE EXPRESSION IN AUDITORY TISSUES genome of shiverer mice, the ABR deficits were par-
Several laboratories have generated cDNA libraries tially corrected. A similar approach, combined with
from specific tissues or cell types of the inner ear, in vitro fertilization, might someday be used to
such as outer hair cells,127 and the National Institute prevent certain devastating genetic disorders in
on Deafness and Other Communication Disorders humans. Transgenic mice carrying a bacterial antibi-
(NIDCD) is currently sponsoring the generation of otic resistance gene were found to be resistant to
cDNA libraries from auditory tissues such as the ototoxicity.131 Molecular studies of otologic disease
otocyst. Differential screening techniques, such as and gene therapy research are both areas in which
subtraction, differential display, and suppressive there is considerable interaction between basic sci-
subtractive hybridization (SSH), are currently being entists and clinicians.
employed by a number of laboratories in an attempt A more practical form of therapy is one that
to identify genes specifically expressed in different can be used in the adult organism. Several laborato-
inner ear cell types.104 Efforts to use gene arrays to ries are studying methods for gene delivery into the
provide broad profiles of gene expression in audi- tissues of the inner ear, either for investigative pur-
tory tissues are under way, including efforts spon- poses or as the basis for eventual gene therapy. Sev-
sored by the NIDCD. A hair cell–specific promoter eral viral vectors carrying reporter genes under the
has been isolated and used to direct expression of control of constitutive promoters have been shown
green fluorescent protein (GFP) limited to hair to mediate the transduction of inner ear cells, both
cells.128 Using homologous recombination, Zuo et al in vivo132,133 and in vitro.134 These studies have gen-
introduced GFP into the α9 acetylcholine receptor erally found that transduction of hair cells is less
locus in a BAC, which was used to create a trans- effective than that of other cell types, such as
genic mouse that showed hair cell–specific expres- Schwann cells or cells lining the perilymphatic
sion.129 Analysis of these and other tissue-specific spaces. Vectors have also been used to deliver growth
promoters will help to define the nuclear signals that factors, resulting in the rescue of damaged inner ear
direct expression to auditory cell types and allow the ganglion neurons135 and hair cells.136 Ryan et al
development of tissue-specific viral vectors for the explored different molecular biologic methods to
auditory system. It will also permit the production deliver a factor into the inner ear.137 They injected
Molecular Biology of Hearing and Balance 51
into the adult mouse inner ear fibroblasts that had genic and gene knockout animals are being devel-
been genetically engineered to secrete high levels of oped for the study of host defense mechanisms
acidic FGF. To suppress proliferation, the fibroblasts against infection.
were irradiated, and the researchers found that the
irradiated cells were well tolerated in the cochlea,
with few side effects, and continued to produce the
BACTERIAL ADHERENCE
growth factor for several weeks. Because the gan- To be successful pathogens on a mucous membrane,
glion cells are bathed with fluid freely communicat- bacteria must be able to colonize, evade host defense,
ing with perilymph, growth factors secreted by the and express toxins that damage host cells and tissues.
fibroblast in the spiral ligament will be available to To accomplish these goals, the bacteria must be able to
the ganglion cells. Staecker et al also found that adapt to the new environment by altering their phe-
inner ear injections of fibroblasts engineered to pro- notypic expression through transcriptional regula-
duce BDNF promoted survival of spiral ganglion tion. Although the exact mechanisms by which
neurons after hair cell destruction in guinea pigs.138 bacteria attach to the mucosal surface are poorly
However, the use of nonirradiated cells in this study understood, it is generally believed that receptor lig-
led to destructive overproliferation. Although pre- and–mediated bacterial binding plays a major role,
liminary, these studies demonstrate theoretical pos- even though nonreceptor ligand binding may also
sibilities of molecular genetically based therapy for play a role in the adherence. The host receptor for
diseases in the human inner ear. Streptococcus pneumoniae is now known to be Glc
Nac1-3Gal,144 whereas the host receptor for nonty-
MOLECULAR PATHOGENESIS OF pable Haemophilus influenzae (NTHi) is not yet fully
characterized. However, several of the bacterial lig-
OTITIS MEDIA ands of NTHi have been described. The suggested lig-
In the middle ear, molecular methods are being ands include 22 kDa pilin,145 27.5 kDa LKP1 (a single
applied in diagnosis, research, and experimental serotype) pilin,146 36.4 kDa fimbrin,147,148 and 120 kDa
treatments for disease. Polymerase chain reaction has high-molecular-weight OMPs (HMW-1, HMW-2),149
proven to be extremely useful in the identification of which may mediate bacterial binding to the host
microbes in OM,139 and quantitative PCR has been epithelial cell surface. Pilin is a subunit of the rigid,
used to measure cytokine production.140 Genetics has tubular surface appendage pilus and mediates hemag-
been shown to be an important factor in OM sus- glutination. Fimbrin is a subunit of the surface
ceptibility.141 Mechanisms of mucosal proliferation appendage fimbria, which is a nontubular filament,
and immunoregulation have been probed using a thinner than pilus and nonhemagglutinating.146,148
variety of molecular techniques, including in situ The gene encoding LKP1 pilus (27.5 kDa)
hybridization142 and the implantation of genetically from an NTHi strain obtained from a middle ear
modified cells.137 Extraction of RNA from human effusion has been cloned and expressed in
archival temporal bones may also prove to be useful Escherichia coli, and the recombinant pili were capa-
for the analysis of such samples for the expression of ble of mediating both the binding of bacteria to the
genes involved in the inflammatory process.143 buccal mucosa and hemagglutination.146 Coleman et
Purification and sequencing of gene products al cloned and sequenced the gene encoding the 22
are important in understanding the pathogenesis of kDa hemagglutinating pilin from another strain of
OM. Cloning bacterial genes has allowed investiga- NTHi, found the DNA sequence to be 77% identical
tors to produce a number of mutant or genetically to that of the H. influenzae type b pilin gene, and
engineered bacteria, in which a gene is either deleted showed it to be 68% homologous via the derived
or altered. These mutants or genetically engineered amino acid sequence.145 Because only less than 5% of
bacteria can be used to probe the molecular mecha- middle ear isolates and 35% nasopharyngeal isolates
nisms of bacteria–host interaction, virulence factors, expressed pili,150 the precise role of the pili in the
and immunogenicity. The genetically engineered pathogenesis of OM is unclear.
bacteria can also be used to mass-produce recombi- Although it has not yet been established that
nant outer membrane proteins (OMPs) for vaccine fimbrial expression is mandatory for the establish-
candidates. Although not yet fully explored, trans- ment of infection, there is good evidence indicating
52 Ballenger’s Otorhinolaryngology
that 100% of NTHi isolates from the middle ear of Pneumococcal proteins pneumolysin and
patients with chronic OM with effusion are fimbri- autolysin contribute significantly to the virulence of
ated.151 Sirakova et al sequenced and cloned a 36.4 pneumococci.157 Streptococcus pneumoniae type 3
kDa fimbrial protein from another strain of NTHi mutants deficient in the production of either pneu-
recovered from middle ear effusion.148 The trans- molysin or autolysin were constructed by transfor-
lated amino acid sequence of fimbrin was found to mation of DNA from derivatives of a rough strain, in
be homologous with various members of the outer which the respective genes had been interrupted by
membrane protein A (OMP A) family of proteins of insertion-duplication mutagenesis using internal
other gram-negative bacteria152 and with type b H. fragments of the cloned genes in the vector.157 Both
influenzae OMP P5, with which it showed 92% iden- the pneumolysin-negative and the autolysin-nega-
tity. Disruption of fimbrin gene resulted in a mutant tive strains had significantly reduced virulence in
lacking fimbrial expression and loss of immunore- mice, as judged by survival time after intraperitoneal
activity to the antisera directed against isolated fim- challenge. When pneumolysin and autolysin pro-
brial proteins.148 Importantly, this isogenic mutant ductions are restored by back-transformation of the
showed reduced adherence to human oropharyngeal mutants with an intact copy of the respective cloned
cells in vitro and significantly reduced induction of gene, the mean survival time was indistinguishable
OM through intranasal inoculation of NTHi in the from that of mice challenged with the wild-type
chinchilla animal model. Thus, fimbrin not only strain. Thus, pneumolysin and autolysin are impor-
causes adhesin-mediating bacterial adherence but is tant virulence factors in type 3 pneumococci.157 Mice
also a virulence factor for NTHi.148 were challenged with a genetically modified mutant
Although the exact mechanism or role of the strain of pneumococcus, which was unable to
fimbria in the pathogenesis of OM is not clear, one express active pneumolysin. Preimmunization of
possibility is that when fimbrin is expressed, it may such mice with autolysin failed to provide any sig-
help to establish an intimate association between the nificant protection against the challenge. 158 The
bacteria and host cell.151 It is possible that through authors suggested that the most important contri-
such an interaction, bacterial toxins can be delivered bution made by autolysin to the virulence of S.
to the host cell, causing cell injury and mediating pneumoniae may be its role in mediating the release
inflammatory cell responses. of pneumolysin from the pneumococcal cytoplasm
during infection.
VIRULENCE FACTORS
Endotoxin plays an important role in the pathogen- MOLECULAR BIOLOGIC APPROACHES
esis of OM.153 Evidence indicates that phase varia- IN THE DEVELOPMENT OF VACCINES
tion of the endotoxin lipo-oligosaccharide (LOS) is AGAINST OTITIS MEDIA
a virulence factor in type b H. influenzae.154 Phase
variation is a reversible switch between two stable The intention of this section is not meant to be a
genotypes. Phase variation provides bacteria with an review on current OM vaccines; rather, it is intended
advantage in evading host immune response and to focus on the molecular biologic aspects of vaccine
becoming successful pathogens. The genes responsi- development. Excellent reviews on the OM vaccine
ble for phase variation have been identified, and development are available elsewhere.159,160
three lic genes (LIC1, LIC2, and LIC3) are known to
be responsible for variable translation of the lic loci, NONTYPABLE HAEMOPHILUS INFLUENZAE
which enables a number of different LOS structures
to be produced from a limited set of genes.154,155
VACCINES
Although the loss of phase variation did not affect Several lines of evidence suggest that a number of
bacterial colonization, it has affected the ability to OMPs of NTHi are potential candidates for vaccines
invade the bloodstream from the respiratory epithe- against this microorganism. The genes encoding sev-
lium when the genes are inactivated.156 It is possible eral of these OMPs have been cloned, sequenced,
that similar phase variation of LOS may also exist and expressed.161–163 This nucleotide sequence infor-
in NTHi. mation, together with mapping of bactericidal epi-
Molecular Biology of Hearing and Balance 53
tope molecules, enabled investigators to define the Pneumococcal proteins autolysin and pneu-
structure and function of these OMPs and identify molysin contribute significantly to the virulence of
domains that are conserved across the strains.164,165 this microorganism. Autolysin and a defined toxoid
Such information is critical in selecting antigens as derivative of pneumolysin were tested for efficacy in
vaccine candidates. Among those identified as a mouse model as antigens protecting against chal-
potential vaccine candidates, NTHi OMP P6 (pepti- lenge with virulent, wild-type S. pneumoniae, and
doglycan-associated lipoprotein), which is common the result showed that each antigen alone provided
to both nontypable and type b Haemophilus, is the significant protection.158 When mice were challenged
most promising because P6 is a target of bactericidal with a genetically modified mutant strain of pneu-
antibodies in convalescent sera. A truncated P6 gene mococcus unable to express active pneumolysin,
without the signal peptide has been constructed by preimmunization of mice with autolysin failed to
Green and his associates,166 and the recombinant provide any significant protection against the chal-
protein encoded by this construct is capable of elic- lenge.158 When mice were immunized with a geneti-
iting bactericidal antibody in vitro. Using a mono- cally engineered toxoid version of pneumolysin
clonal antibody, Murphy and Kirkham identified a derived from serotype 2 pneumococcus and chal-
region of P6 encoding an epitope recognized by bac- lenged with 12 strains of pneumococci covering cap-
tericidal antibody.167 Another OMP, P26, also shows sular types 1 to 6, 7F, 8, and 18c, pneumolysin toxoid
conservation across strains of NTHi and a recombi- conferred protection against all nine pneumococcal
nant preprotein-induced protection in animals.168 serotypes.172 Thus, these investigators suggested that
Another Haemophilus OMP known as P6 pneumolysin toxoids warrant consideration for
cross-reactive protein (PCP) is also considered to be inclusion in pneumococcal vaccines. Molecular
an excellent vaccine candidate because polyclonal analysis of pneumococcal surface protein A also
antisera against PCP are bactericidal. The PCP is reveals several relatively conserved domains,173 sug-
antigenically conserved and present in both type b gesting that this molecule may also be a vaccine can-
and NTHi. Deich et al recently cloned and se- didate.
quenced this protein.169
Other Haemophilus OMPs, believed to medi-
ate bacterial adherence and also considered as
DNA VACCINES AGAINST RESPIRATORY VIRUSES
potential vaccine candidates, include pilin and Acute OM is frequently preceded by a viral upper
fimbrin. Antibody response to such proteins by respiratory infection. Recent data using PCR
immunization can block the bacterial adherence demonstrated that a high number of middle ear
mediated by these proteins, thus reducing coloniza- effusions contained evidence of upper respiratory
tion and infection.148,150 Another vaccine candidate viruses,174 and upper respiratory viral infection is
is a group of high-molecular-weight surface- causally related to the bacterial OM. It has been
exposed proteins of NTHi, which are related to the shown that attenuated influenza viral vaccine con-
filamentous hemagglutinin protein of Bordetella per- ferred protection against pneumococcal OM in the
tussis. The high-molecular-weight proteins are chinchilla.175 Thus, preventing upper respiratory
known to be critical adhesion molecules but also are viral infection will reduce the incidence of acute
major targets of human serum antibody.170 To fur- OM. In recent years, clinical trials have been initiated
ther characterize these proteins, Barenkamp and with live attenuated vaccines for respiratory syncy-
Leninger cloned and sequenced genes encoding two tial virus, influenza, and parainfluenza viruses and
related high-molecular-weight proteins (120 kDa adenovirus.159 Such trials can provide an excellent
and 125 kDa).171 opportunity to test the above hypothesis. In a clini-
cal trial in Finland, attenuated influenza virus was
administered to children under 4 years old. During
STREPTOCOCCUS PNEUMONIAE VACCINES a 6-week epidemic, 83% of the children were pro-
Many new vaccines including multivalent polysac- tected from confirmed influenza A–associated acute
charide vaccines and polyvalent pneumococcal con- OM and 36% from acute OM in general.176 However,
jugate vaccines are under development and being efficacies of viral vaccines against disease in suscep-
field-tested, and they will not be covered here. tible populations are modest at best owing to rapid
54 Ballenger’s Otorhinolaryngology
changes of viral surface antigens and heterogeneity also located within a transposon.184 Molecular
of surface antigens among different strains, as well as cloning and mechanisms of trimethoprim resistance
incomplete knowledge of the characteristics of pro- in H. influenzae were elucidated by cloning the gene
tective immunity of different upper respiratory for trimethoprim resistance into a cosmid vector
viruses.159 and transducing recombinant plasmids into E.
Most of the current viral and bacterial vaccines coli.185 The results indicated that the acquisition of
are largely using surface antigens. However, such an trimethoprim resistance involved a chromosomally
approach poses a serious problem because a mediated rearrangement or change of nucleotide
microbe’s surface structures frequently change at a sequences. The mechanism of trimethoprim resist-
rapid rate, rendering vaccines useless. For example, ance is overproduction of dihydrofolate reductase.185
evolution of the genes for surface proteins of
influenza virus occurs so fast that a new vaccine
ANTIBIOTIC RESISTANCE IN STREPTOCOCCUS
must be made every year to be effective. However,
proteins in the interior of viruses are more highly PNEUMONIAE
conserved (stable) than those of the surface. The dis- Penicillin resistance to S. pneumoniae is believed to
covery that naked DNA from a virus injected into be mediated by changes in the production of altered
the body could function as a vaccine may provide PBPs.186 The PBPs la, 2b, and 2x have been cloned
a new opportunity to develop an effective viral and sequenced.186–188 No β-lactamase-mediated
vaccine.177 Futhermore, investigators described penicillin resistance was reported in pneumococci.
the results of experiments on mice using DNA Dowson and his associates investigated PBP 2b
from influenza virus.178 The opponents of viral from several sensitive and resistant pneumococci
DNA vaccines caution a theoretical possibility of and demonstrated a major change in the carboxyl-
activation of an oncogene, which may induce cancer terminal sequence.187 It is postulated that this change
in the host. is responsible for the development of penicillin
resistance.
MOLECULAR MECHANISMS OF
MOLECULAR EPIDEMIOLOGY
ANTIBIOTIC RESISTANCE AMONG
AND DIAGNOSIS
OTITIS MEDIA PATHOGENS
Molecular biologic techniques have been used to
ANTIBIOTIC RESISTANCE IN HAEMOPHILUS diagnose bacterial and viral diseases and fingerprint
specific microorganisms in epidemiologic surveys.189
INFLUENZAE
Using a sensitive total genomic DNA restriction fin-
The genetic basis of ampicillin and chloramphenicol gerprinting method, different isolates of H. influen-
resistance in H. influenzae has been well character- zae have been identified.190 Restriction endonuclease
ized, and the principal mechanism of the resistance analysis of bacterial chromosomal DNA was used to
is largely enzymatic.179 The gene that encodes the compare NTHi obtained from middle ear effusions
β-lactamase enzyme is located within a large gene with that from nasopharynges of patients with OM.
segment, transposon A.180 Mendelman et al reported The restriction digest profiles of strains isolated
a small number of strains that demonstrate ampicillin simultaneously from the middle ear effusion and
resistance in the absence of β-lactamase production, nasopharynx of an individual child were identical,
which is believed to be mediated by alterations in whereas the restriction profiles of strains isolated
one or more penicillin-binding proteins (PBPs).181 from different children were different from one
The PBPs 3a and 3b showed a decrease in affinity for another.191 In this study, the isolates from recurring
β-lactams in antibiotic-resistant strains.182 The gene episodes of NTHi in six children were different from
for the altered PBPs has been cloned.183 The genetic those that caused the initial episode.
basis for resistance of H. influenzae type b to chlo- Like in the NTHi, another gram-negative bac-
ramphenicol has been elucidated, and it is believed teria, Branhamella catarrhalis, was subject to restric-
to be caused largely by the enzyme acetyltransferase. tion fragment mapping for epidemiologic study for
The genetic sequence that codes for this enzyme is this newly emerging pathogen for OM. Dickinson et
Molecular Biology of Hearing and Balance 55
al were able to fingerprint and compare B. catarrhalis cular endothelial growth factors (VEGFs) and their
isolates obtained from middle ear effusions and receptors (VEGF-Rs), important receptor tyrosine
those from nasopharynges of the same patients kinases involved in normal and pathologic angio-
using restriction fragment mapping following diges- genesis, and found that VEGF, VEGF-C, VEGF-D,
tion of genomic DNA with restriction endonuclease and VEGFR-2 (flk-1) were up-regulated in the
such as Pst1 and Cla1.192 This microorganism was mucosa of rat middle ears inoculated with bacte-
considered as a normal flora of the nasopharynges of ria.194 DeFoire-Hyrmer and Bakaletz provided evi-
healthy children as well as adults. However, it has dence to link phosphorylation of tyrosine with
become increasingly associated with acute purulent NTHi adherence and actin nucleation.195 Sudhoff et
OM and OM with effusion in recent years. There- al documented the presence of angiogenic growth
fore, it is important to learn about strains that are factors and receptors in cholesteatoma.196 Using
pathogens versus nonpathogens, and the restriction immunocytochemisry, Huang et al found epidermal
fragment mapping technique allows investigation of growth factor, FGF, and platelet-derived growth fac-
the epidemiology of this microorganism reliably. tor in cholesteatoma keratinocytes,197 whereas
Polymerase chain reaction assay based on the Ishibashi et al detected keratinocyte growth factor
amplification of pneumolysin gene fragments in sera and receptor mRNA.198 Huang and colleagues found
was developed to diagnose acute pneumococcal evidence that ras, c-jun, and p53 may be involved in
pneumonia.193 Analysis of DNA restriction patterns signaling from these receptors.197,199 Schilling et al
of genomic DNA provided a sensitive measure of observed high levels of tenascin in proliferating
genetic similarity between strains and a convenient cholesteatoma keratinocytes, suggesting a role for
method for use in epidemiologic studies. integrin signaling.200 In addition, the role of the sig-
naling molecule phospholipase C (PLC)-γ-1 was
RESPONSE OF THE MIDDLE EAR MUCOSA explored by Park et al.201 Their studies suggested a
possible involvement of PLC-γ-1 in cholesteatoma
TO OTITIS MEDIA
pathogenesis.
The middle ear mucosa exhibits dramatic responses Expression of interleukins has been docu-
to OM. It is unique among mucosae in that it has the mented by several investigators. In general, genes
capacity for extreme hyperplasia when stimulated by encoding proinflammatory cytokines are expressed
inflammatory events. The simple squamous cell very rapidly, within 6 hours of middle ear inocula-
epithelium that lines much of the normal middle ear tion with bacteria, and decline by 24 hours.140,202
can rapidly proliferate and differentiate into a respi- Anti-inflammatory and immunoregulatory cytokines
ratory mucosa with a well-organized and vascular- are expressed over a much longer time course, with
ized stroma and a pseudocolumnar epithelium with some lasting for weeks.203,204
ciliated and goblet cells. John and Nam reported that the concentration
of nitric oxide (NO), an important intracellular sec-
Growth Factors and Signal Transduction Extra- ond messenger, is higher in middle ear effusion.205
cellular stimuli induce both physiologic and patho- In experimental chronic OM, endothelial nitric
logic cellular responses via activation of signal oxide synthase (eNOS) mRNA is increased and
transduction pathways extending from receptors on inducible nitric oxide synthase (iNOS) gene expres-
the cell surface to the transcription factors in the sion is dramatically up-regulated.142 In addition to
nucleus. Therefore, investigating these signal trans- the role of NO in the pathogenesis of OM, Juhn et al
duction mechanisms not only provides new insights provided evidence indicating that NO may be
into molecular mechanisms of physiologic re- involved in the cochlear transduction process.206
sponses, development, and pathogenesis but may The role of mitogen-activated protein (MAP)
also open up novel therapeutic targets for the treat- kinases in the pathogenesis of OM has been
ment of ear diseases such as OM. explored. Li et al investigated the signal transduction
Progress has been made recently in the studies mechanisms involved in H. influenzae–induced
of signal transduction mechanisms involved in the mucin up-regulation and found that H. influenzae
pathogenesis of OM. Oehl and Ryan used reverse up-regulates mucin gene transcription via activation
transcriptase PCR to examine the expression of vas- of a Rac-dependent MEKK-SEK-p38 MAP kinase
56 Ballenger’s Otorhinolaryngology
pathway, suggesting that H. influenzae up-regulates In consistence with this study, Jung et al reported
mucin transcription via activation of an intracellu- that human MUC5AC, MUC5B, MUC7, and MUC8
lar signaling pathway different from Pseudomonas are all expressed in the middle ear mucosa of
aeruginosa.207,208 In addition to the involvement of patients with chronic OM.214 In the study reported
p38, Xu et al reported that oxygen radical species by Severn et al, human MUC1 and MUC2, in addi-
(ROS) may be involved in activation of p38 MAP tion to MUC5AC and MUC5B, were also found to be
kinase, which, in turn, led to the activation of mucin expressed in middle ear mucosa.215
transcription.209 Chun et al also showed that MAP Efforts have also been made toward under-
kinase ERK (extracellular signal regulated) is standing the molecular mechanisms controlling
involved in IL-1-induced down-regulation of sur- mucin overproduction. Wang et al investigated the
factant protein B in the middle ear.210 role of H. influenzae in mucin up-regulation and
Transcription factor nuclear factor kappa B found that H. influenzae up-regulates mucin
(NF-κB) has been shown to play an important role MUC5AC gene transcription via activation of a p38
in inflammatory responses. One possible involve- MAP kinase pathway, suggesting that H. influenzae
ment of NF-κB is to regulate the transcription of up-regulates mucin transcription via activation of
proinflammatory cytokines. It has been shown that intracellular signaling pathway different from
activation of NF-κB is involved in IL-8 gene expres- P. aeruginosa.207,216 Interestingly, in addition to the
sion in human adenoidal fibroblasts. involvement of p38 in mucin up-regulation, Shuto
et al showed that activation of p38 also plays an
Mucin Gene Expression in the Middle Ear and Up- important role in inflammatory responses.217 The
regulation of Mucin in Otitis Media Mucins are role of proinflammatory cytokines in mucin regu-
high-molecular-weight glycoproteins that constitute lation has also been studied by Lin et al.212 Their
the major component of mucus in the middle ear, studies showed that tumor necrosis factor-alpha
trachea, and digestive and reproductive tracts. They (TNF-α) up-regulates mucin MUC2 gene expres-
protect epithelia and trap particulates, including sion in the middle ear of rats. All of these studies
bacteria, for mucociliary clearance. In diseases such suggest the complexity of regulatory mechanisms
as OM, chronic bronchitis, and cystic fibrosis, mucin underlying mucin up-regulation in OM.
production is up-regulated, which, in turn, con-
tributes to the pathogenesis of diseases. In OM with Epithelial Antimicrobial Peptides and Proteins in
effusion, overproduced mucin is believed to play an the Pathogenesis of Otitis Media It is now
important role in causing conductive hearing loss as believed that in addition to the components of the
well as defective mucociliary clearance and recurrent adaptive immune system, the homeostasis of the
infection. nasopharyngeal tract, eustachian tube, and middle
Progress has been made in the study of mucin ear is also maintained by epithelial antimicrobial
gene expression in the middle ear and eustachian proteins and peptides that function to defend these
tube. Chun et al examined human mucin gene tissues against microbial invasion. The larger
expression and found that mucin MUC2, MUC5AC, antimicrobial proteins are often lytic enzymes,
and MUC5B genes are expressed in human middle nutrient-binding proteins, or proteins containing
ear epithelial cells.210 A similar result was found in sites that target specific microbial macromolecules.
human primary cultures of middle ear epithelial The smaller antimicrobial peptides (defined as pep-
cells by Moon et al.211 In addition to mucin gene tides containing fewer than 100 amino acids) act, at
expression in the middle ear, Lin et al also reported least in part, by disrupting the structure or function
the expression of glycoconjugates in human of microbial cell membranes. Included in the mol-
eustachian tubes.212 ecules of the innate immune system are the
More attention has been given to determining defensins, lysozyme, lactoferrin, and members of
mucin expression in OM middle ear mucosa and the collectin family, including the surfactant pro-
effusions. Hutton et al isolated and purified high- teins A and D.218
molecular-weight mucins from effusions of children The defensins are cationic (polar) molecules
with OM with effusion and provided direct evidence with spatially separated hydrophobic and charged
for expression of different mucin gene products.213 regions. In vitro, the defensins (at micromolar con-
Molecular Biology of Hearing and Balance 57
centrations) have a broad spectrum of antimicro- The collectins are proteins that are related
bial activity against bacteria, fungi, and even some structurally and functionally to the first component
enveloped viruses.219 In humans and other verte- of the classic complement pathway C1q and are
brates, the defensins can be divided into the α- and known to play significant roles in innate immunity
β-defensin subfamilies. The α-defensins are pro- through opsonization and complement activa-
duced by neutrophils and intestinal Paneth’s tion.231,232 The collectin family of proteins includes
cells. 220 The β-defensins, on the other hand, are the mannose binding protein, conglutinin, CL-43,
mainly produced by epithelial cells of the skin, kid- and surfactant proteins A and D. Surfactant proteins
neys, and tracheabronchial lining of nearly all A and D are expressed in the middle ear and
vertebrates. 221 The β-defensins are released on eustachian tube and are likely to be involved in the
microbial invasion and are located at the host– protection of the tubotympanum against OM
environment interface, such as mucosal surfaces pathogens.218
and skin. Two types of human β-defensins,
β-defensins 1 (HBD-1) and 2 (HBD-2), have been Gene Transfer to the Middle Ear Mucosa Ryan et
identified. Human β-defensin 2 is produced by al successfully implanted cells that had been stably
epithelial cells and exhibits potent antimicrobial transformed to secrete FGF-1 into the subepithelial
activity against gram-negative bacteria and Can- compartment.137 Mondain et al demonstrated that
dida. But it is not as effective against gram-positive an adenovirus vector can be used to transduce cells
Staphylococcus aureus.222,223 Human β-defensin rep- of the adult guinea pig middle ear mucosa.233 Simi-
resents the first human defensin that is produced larly, Dazert et al demonstrated adenovirus trans-
following stimulation of epithelial cells by contact duction of mucosal cells in the neonatal rat.133 These
with microorganisms or cytokines such as TNF-α studies demonstrate the feasibility of gene therapy
and IL-1α. Human β-defensin 2 functions as a NF- in the middle ear cavity for the treatment of OM.
κB target gene in the intestinal epithelium, but
HBD-1 is not affected by IL-1α and other proin-
flammatory stimuli.221 The presence of HBD-1 has
FUTURE DIRECTIONS
been reported in the pars tensa and pars flaccida of The explosive pace of development of molecular
the tympanic membrane and in the meatal skin.224 techniques does not allow us to do justice in this
Recently, Lim et al demonstrated that both HBD-1 chapter to all aspects of molecular biology that are
and HBD-2 are expressed in human middle ear relevant to otology. We have just begun to scratch
epithelial cells and that both molecules have bacte- the surface of many important areas of biology of
ricidal/bacteriostatic activity against NTHi.218 the ear with these new tools. The availability of such
Lysozyme is an important component of powerful techniques is already beginning to impact
innate immunity against pathogens at mucosal sur- our understanding of cellular functions and mal-
faces. Human chronic middle effusions contain high functions on a molecular level. Identification of
levels of this molecule, which is produced by secre- genes important for the formation of the ear and the
tory cells of the middle ear mucosal epithelia, as well maintenance and normal function of the sensory
as by polymorphonuclear leukocytes and macro- and nonsensory cells of the inner ear are now possi-
phages.218,226 Lim and coworkers have shown that ble, and discovery of many new genes of importance
human milk–derived lysozyme, in combination with will be accelerated. Many more transgenic animals
other innate immune molecules, exhibits antibacter- and gene knockout animals of interest will be made
ial activity against NTHi.218 available, and these animals will propel our knowl-
Lactoferrin is an iron-binding glycoprotein edge concerning specific gene functions important
found in the milk and exocrine secretions of mam- for the ear.
mals that is released from neutrophilic granules dur- Although only limited attempts have been
ing inflammation.227,228 Lactoferrin has also been made, many innovations for gene or gene-based
detected in middle ear effusion and has been local- therapy will allow scientists to develop new
ized to the serous cells of eustachian tube glands, as approaches (eg, antisense oligonucleotide therapy)
well as the cuboidal epithelium of the transition to prevent or cure human diseases, which currently
zone of the middle ear.229,230 cannot be ameliorated.
58 Ballenger’s Otorhinolaryngology
For OM, molecular biologic techniques already 6. Fambrough DM, Lemas MV, Hamrick M, et al.
have made a major impact on our understanding of Analysis of subunit assembly of Na, K-ATPase. Am J
bacterial pathogenesis at the molecular level. We are Physiol 1994;6:579–89.
beginning to understand the molecular mechanisms 7. Siddique M, Goswami S, Qasba P, et al. Regulation of
involved in bacteria–host interaction. A number of muscle tissue specific transcription: analysis of
OM-causing bacterial surface antigens important for chicken cardiac myosin light chain 2 gene promoter.
the protective host immune response have now been Proceedings of the 1st World Congress of Cellular
identified, and their genes are cloned. Molecular Molecular Biology 1991. p. 345.
methods will allow us to incorporate this new 8. Gilbert SF. Genes and development: introduction
knowledge in developing strategies to prevent and and techniques; development biology. 4th ed.
treat OM. The molecular biology of host responses, Sunderland (MA): Sinauer Associates, Inc; 1994.
including the innate and acquired immune p. 34–76.
responses, cytokine and β-defensin regulation, 9. Rosenfeld M, Crenshaw E, Lira S, Swanson L. Trans-
inflammatory cell mobilization, B and T cell activa- genic mice: applications to the study of the nervous
tion, tissue proliferation, and mucin regulation, con- system. Ann Rev Neurosci 1988;17:353–72.
stitutes a large body of knowledge that is relevant for 10. Gridley T, Soriano P, Jaenish R. Insertional mutage-
understanding the pathogenesis and progression of nesis in mice. Trends Genet 1987;3:162–6.
OM. Rapid progress is being made in these areas, 11. Naori H, Kumura M, Otami H, et al. Transgenic
including identification of genes regulating various mouse model of hemifacial microsomia: cloning and
aspects of host responses, which will impact the way characterization of insertional mutation region on
we manage OM in the future. chromosome 10. Genomics 1994;23:515–9.
In summary, molecular biologic techniques are 12. Xiang X, Benson KF, Chada K. Mini-mouse: disrup-
no longer an esoteric scientific curiosity; rather, they tion of the pygmy locus in a transgenic insertional
are beginning to be used in diagnosis, new vaccine mutant. Science 1990;247:967–9.
development, and even gene therapy. Many more 13. Gordon J, Uehlinger J, Dayani N, et al. Analysis of
molecular biology–based innovative approaches will the hotfoot (ho) locus by creation of an insertional
become available in the future, which will ultimately mutation in a transgenic mouse. Dev Biol 1990;137:
change our understanding and treatment of these 349–58.
diseases. 14. Crenshaw EB, Ryan AF, Dillon SR, et al. Wocko, a
neurological mutant generated by insertional muta-
REFERENCES genesis in a transgenic mouse pedigree. J Neurosci
1991;11:1524–30.
1. Saiki RK, Gelrand DH, Stoffel S, et al. Primer-directed
15. Friedman RA, Adir Y, Crenshaw EB, et al. A trans-
enzymatic amplification of DNA with a thermostable
genic insertional inner ear mutation on mouse chro-
DNA polymerase. Science 1988;239:487–91.
2. Simmons DM, Arriza JL, Swanson LW. A complete mosome 1. Laryngoscope 2000;110:489–96.
protocol for in situ hybridization of messenger 16. Ernfors P, Lee K-F, Jaenisch R. Mice lacking brain-
RNAs in brain and other tissues with radiolabeled derived neurotrophic factor develop with sensory
single-stranded RNA probes. J Histotechnol 1989;12: deficits. Nature 1994;368:147–50.
169–81. 17. Farinas I, Jones KR, Backus C, et al. Severe sensory
3. Battey JF, Fathi S, Wada E, et al. Molecular genetic and sympathetic deficits in mice lacking neu-
approaches to the analysis of neuropeptide recep- rotrophin-3. Nature 1994;369:658–61.
tors. Cell Physiol Biochem 1993;3:3–230. 18. Gu W, Schneider JW, Condorelli G, et al. Interaction
4. Hoshi T, Zagotta WN, Aldrich RW. Biophysical and of myogenic factors and the retinoblastoma protein
molecular mechanisms of Shaker potassium channel mediates muscle cell commitment and differentia-
inactivation. Science 1990;250:533–8. tion. Cell 1993;72:309–24.
5. Zagotta WN, Hoshi T, Aldrich RW. Restoration of 19. Boulter J, Connoly J, Deneris E, et al. Functional
inactivation of mutants of Shaker potassium chan- expression of two neural nicotinic acetylcholine
nels by a peptide derived from ShB. Science 1990; receptors from cDNA clones identifies a gene family.
250:568–71. Proc Natl Acad Sci U S A 1987;84:7763–7.
Molecular Biology of Hearing and Balance 59
20. Wada K, Ballivet M, Boulter J, et al. Functional 34. Tryggvason K, Zhou J, Hostikka SL, Shows TB. Mol-
expression of a new pharmacological subtype of ecular genetics of Alport syndrome. Kidney Int 1993;
brain nicotinic acetylcholine receptor. Science 1988; 43:38–44.
240:330–4. 35. Tassabehji M, Read AP, Newton VE, et al. Waarden-
21. Boulter J, Hollmann M, O’Shea-Greenfield A, et al. burg’s syndrome patients have mutations in the
Molecular cloning and functional expression of gluta- human homologue of the Pax-3 paired box gene.
mate receptor subunit genes. Science 1990;249:1033–7. Nature 1992;355:635–6.
22. Young RM, Shull GE, Lingrel JB. Multiple mRNAs 36. Weil D, Blanchard S, Kaplan J, et al. Defective myosin
from rat kidney and brain encode a single Na+, K+- VIIA gene responsible for Usher syndrome type 1B.
ATPase beta subunit protein. J Biol Chem 1987;262: Nature 1995;374:60–1.
4905–10. 37. Seizinager BR, Martuza RL, Gusella JF. Loss of genes
23. Hammes A, Oberdorf S, Strehler EE, et al. Differen- on chromosome 22 in tumorigenesis of human
tiation-specific isoform mRNA expression of the acoustic neuroma. Nature 1986;322:644–7.
calmodulin-dependent plasma membrane Ca(2+)- 38. Rouleau GA, Wertelecki W, Haines JA, et al. Genetic
ATPase. FASEB J 1994;8:428–35. linkage of bilateral acoustic neurofibromatosis to a
24. Johnson DE, Williams LT. Structural and functional DNA marker on chromosome 22. Nature 1987;
diversity in the FGF receptor multigene family. Adv 329:246–8.
Cancer Res 1993;60:1–41. 39. Frazer KA, Boehnke M, Budarf ML, et al. A radiation
25. Heinemann S, Bettler B, Boulter J, et al. The gluta- hybrid map of the region on human chromosome
mate receptor gene family: evidence that the GluRl, 22 containing the neurofibromatosis type 2 location.
GIuR2, GluR3 subunits form multiple glutamate Genomics 1992;34:574–84.
receptors. In: Sidia Research Foundation transmitter 40. Trofatter JA, MacCollin MM, Rutter JL, et al. A novel
amino acid receptors: structures, transduction and moesin-, radixin-like gene is a candidate for the neu-
models for drug development. London: Royal Soci- rofibromatosis 2 tumor suppressor. Cell 1993;72:
ety; 1990. 791–800.
26. Wenthold RJ. Structure and distribution of gluta- 41. McCollin M, Ramesh V, Jacoby LB, et al. Mutational
mate receptors: subunit-specific antibody studies. analysis of patients with neurofibromatosis 2. Am J
Neurosci Facts 1992;3:2–3. Hum Genet 1994;55:314–20.
27. Brown TA. Gene cloning: an introduction. 2nd ed. 42. de Kok YJM, van der Maarel SM, Bitner-Glindzicz
Norwell (MA): Chapman & Hall; 1990. M, et al. Association between X-linked mixed deafness
28. Farrer LA. Gene localization by linkage analysis. and mutations in the POU domain gene POU3F4.
Otolaryngol Clin North Am 1992;25:907–22. Science 1995;267:685–8.
29. Watson JD, Gilman M, Witkowski J, Zoller M. 43. Ryan AF, Simmons DM, Crenshaw EB. Gene expres-
Recombinant DNA. 2nd ed. New York: Scientific sion in normal and abnormal inner ears. Ann N Y
American Books; 1992. Acad Sci 1991;630:129–32.
30. Lee WH, Bookstein R, Hong F, et al. Human 44. Carrasquillo MM, Zlotogora J, Barges S, Chakravarti
retinoblastoma gene: cloning, identification and A. Two different connexin 26 mutations in an inbred
sequencing. Science 1987;235:1394–9. kindred segregating non-syndromic recessive deaf-
31. Koenig M, Hoffman EP, Bertelson CJ, et al. Complete ness: implications for genetic studies in isolated pop-
cloning of the Duchenne muscular dystrophy ulations. Hum Mol Genet 1997;6:2163–72.
(DMD) cDNA and preliminary genomic organiza- 45. Denoyelle F, Weil D, Maw MA, et al. Prelingual deaf-
tion of the DMD gene in normal and affected indi- ness: high prevalence of a 30delG mutation in the
viduals. Cell 1987;50:509–17. connexin 26 gene. Hum Mol Genet 1997;6:2173–7.
32. Tseng CJ, Lalwani AK. Cracking the auditory genetic 46. Jaber L, Shohat M, Bu X, et al. Sensorineural deaf-
code: part II. Syndromic hereditary hearing impair- ness inherited as a tissue specific mitochondrial dis-
ment. Am J Otol 2000;21:437–51. order. J Med Genet 1992;29:86–90.
33. Barker DF, Hostikka SL, Zhou J, et al. Identification 47. Prezant TR, Shohat M, Jaber L, et al. Biochemical
of mutations in the COL4A5 collagen gene in Alport characterization of a pedigree with mitochondrially
syndrome. Science 1990;248S:1224–7. inherited deafness. Am J Med Genet 1992;44:465–72.
60 Ballenger’s Otorhinolaryngology
48. Fischel-Ghodsian N, Prezant TR, Bu X, Oztas S. 61. Everett LA, Morsli H, Wu DK, Green ED. Expression
Mitochondrial ribosomal RNA gene mutation in a pattern of the mouse ortholog of the Pendred’s syn-
patient with sporadic aminoglycoside ototoxicity. drome gene (Pds) suggests a key role for pendrin in the
Am J Otolaryngol 1993;74:399–403. inner ear. Proc Natl Acad Sci U S A 1999;96:9727–32.
49. Verpy E, Leibovici M, Zwaenepoel I, et al. A defect 62. Vahava O, Morell R, Lynch ED, et al. Mutation in
in harmonin, a PDZ domain-containing protein transcription factor POU4F3 associated with inher-
expressed in the inner ear sensory hair cells, under- ited progressive hearing loss in humans. Science
lies Usher syndrome type 1C. Nat Genet 2000;26: 1998;279:1950–4.
6–7. 63. Verhoeven K, Van Laer L, Kirschhofer K, et al.
50. Wayne S, Robertson NG, DeClau F, et al. Mutations Mutations in the human alpha-tectorin gene cause
in the transciptional activator Eya4 cause late-onset autosomal dominant non-syndromic hearing impair-
deafness at the DFNA10 locus. Hum Mol Genet ment. Nat Genet 1998;19:60–2.
2001;10:195–200. 64. Friedman TB, Sellers JR, Avraham KB. Unconven-
51. Abdelhak S, Kalatzis V, Heilig R, et al. A human tional myosins and the genetics of hearing loss. Am
homologue of the Drosophila eyes absent gene under- J Med Genet 1999;89:147–57.
lies branchio-oto renal (BOR) syndrome and identi- 65. Acampora D, Merlo GR, Paleari L, et al. Craniofa-
fies a novel gene family. Nat Genet 1997;15:157–64. cial, vestibular and bone defects in mice lacking the
52. Xu PX, Adams J, Peters H, et al. Eya1-deficient mice Distal-less-related gene Dlx5. Development 1999;
lack ears and kidneys and show abnormal apoptosis 126:3795–809.
of organ primordia. Nat Genet 1999;23:113–7. 66. Morsli H, Tuorto H, Wu DK, et al. Otx1 and Otx2
53. Hardisty RE, Mburu P, Brown SD. ENU mutagene- activities are required for the normal development of
sis and the search for deafness genes. Br J Audiol the mouse inner ear. Development 1999;26:2335–43.
1999;33:279–83. 67. Salminen M, Meyer BI, Bober E, Gruss P. Netrin 1 is
54. Nolan PM, Peters J, Strivens M, et al. A systematic, required for semicircular canal formation in the
genome-wide, phenotype-driven mutagenesis pro- mouse inner ear. Development 2000;127:13–22.
gramme for gene function studies in the mouse. Nat 68. Granstrom G. Retinoid-induced ear malformations.
Genet 2000;25:440–3. Otolaryngol Head Neck Surg 1990;103:702–9.
55. Probst FJ, Fridell RA, Raphael Y, et al. Correction of 69. Jarvis BL, Johnston MC, Sulik KK. Congenital mal-
deafness in shaker-2 mice by an unconventional formations of the external, middle, and inner ear
myosin in a BAC transgene. Science 1998;280: produced by isotretinoin exposure in mouse
1444–7. embryos. Otolaryngol Head Neck Surg 1990;
56. Mullen LM, Ryan AF. Transgenic mice: genome 102:391–401.
manipulation and induced mutations. In: Willott J, 70. Romand R, Sapin V, Dollé P. Spatial distributions of
editor. Handbook of mouse auditory research: from retinoic acid receptor gene transcripts in the prenatal
molecular biology to behavior. Boca Raton (FL): mouse inner ear. J Comp Neurol 1998;393:298–308.
CRC Press; 2001. p. 457–74. 71. Lohnes D, Mark M, Mendelsohn C, et al. Function of
57. Kozel PJ, Friedmann RA, Erway L, et al. Balance and the retinoic acid receptors (RARs) during develop-
hearing deficits in mice with a null mutation in the ment (I). Craniofacial and skeletal abnormalities in
gene encoding plasma membrane Ca2+-ATPase iso- RAR double mutants. Development 1994;120:
form 2. J Biol Chem 1998;273:18693–6. 2723–48.
58. Minowa O, Ikeda K, Sugitani Y, et al. Altered 72. Oh SH, Wu D. Expression of bone morphogenetic
cochlear fibrocytes in a mouse model of DFN3 non- protein 4, 5 and 7 in the developing chick inner ear
syndromic deafness. Science 1999;285:1408–11. [abstract 422]. Assoc Res Otolaryngol Mid-Winter
59. Simmler MC, Cohen-Salmon M, El-Amraoui A, et Meeting; 1995. p. 6.
al. Targeted disruption of otog results in deafness 73. Winnier G, Blessing M, Labosky PA, Hogan BL. Bone
and severe imbalance. Nat Genet 2000;24:139–43. morphogenetic protein-4 is required for mesoderm
60. Richardson G, Forge A, Kros C, et al. A missense formation and patterning in the mouse. Genes Dev
mutation in myosin VIIA prevents aminoglycoside 1995;9:2105–16.
accumulation in early postnatal cochlear hair cells. 74. Teng X, Ahn K, Bove M, et al. Malformations of the
Ann N Y Acad Sci 1999;884:110–24. lateral semicircular canal occur in heterozygous
Molecular Biology of Hearing and Balance 61
Bmp4 knockout mice [abstract]. In: Assoc Res Oto- 89. Corey DP, Hudspeth AJ. Kinetics of the receptor cur-
laryngol Mid-Winter Meeting; 2000 Feb 20–24. rent in bullfrog saccular hair cells. J Neurosci 1983;
p. 51. 3:962–76.
75. Bermingham NA, Hassan BA, Price SD, et al. Math1: 90. Hudspeth AJ. Extracellular current flow and the site
an essential gene for the generation of inner ear hair of transduction by vertebrate hair cells. J Neurosci
cells. Science 1999;284:1837–41. 1982;2:1–10.
76. Chen P, Segil N. p27(Kip1) links cell proliferation to 91. Pickles JO, Comis SD, Osborne MP. Cross-links
morphogenesis in the developing organ of Corti. between stereocilia in the guinea pig organ of Corti,
Development 1999;126:1581–90. and their possible relation to sensory transduction.
77. Lowenheim H, Furness DN, Kil J, et al. Gene disrup- Hear Res 1984;15:103–12.
tion of p27(Kip1) allows cell proliferation in the 92. Assad JA, Shepherd CMC, Corey DP. Tip-link
postnatal and adult organ of Corti. Proc Natl Acad integrity and mechanical transduction vertebrate
Sci U S A 1999;96:4084–8. hair cells. Neuron 1991;7:985–94.
78. Erkman L, McEvilly RJ, Luo L, et al. Role of tran- 93. Hackney CM, Furness DN, Benos DJ, et al. Putative
scription factors Brn-3.1 and Brn-3.2 in auditory and immunolocalization of the mechanoelectrical trans-
visual system development. Nature 1996;381:603–6. duction channels in mammalian cochlear hair cells.
79. Xiang M, Gao WQ, Hasson T, Shin JJ. Requirement Proc R Soc Lond B Bio Sci 1992;8:5–2.
for Brn-3c in maturation and survival, but not in 94. Hudspeth AJ, Gillespie PG. Pulling springs to tune
fate determination of inner ear hair cells. Develop- transduction: adaption by hair cells. Neuron 1994;
ment 1998;125:3935–46. 12:1–9.
80. Lanford PJ, Lan Y, Jiang R. Notch signalling pathway 95. Gillespie PG, Wagner MC, Hudspeth AJ. Identifica-
mediates hair cell development in mammalian tion of a 120 kd hair-bundle myosin located near
cochlea. Nat Genet 1999;21:289–92. stereociliary tips. Neuron 1993;11:581–94.
81. Stone JS, Rubel EW. Delta1 expression during avian 96. Walker RG, Willingham AT, Zuker CS. A Drosophila
hair cell regeneration. Development 1999;126:961–73. mechanosensory transduction channel. Science 2000;
82. Zheng JL, Gao WQ. Overexpression of Math1 induces 287:2229–34.
robust production of extra hair cells in postnatal rat 97. Howard J, Hudspeth AJ. Mechanical reaction of the
inner ear cultures. Nat Neurosci 2000;3:580–6. hair bundle mediated adaptation in mechanoelec-
83. Lefebvre PP, Van De Water TR, Weber T, et al. trical transduction by the bullfrog’s saccular hair
Growth factor interactions in cultures of dissociated cell. Proc Natl Acad Sci U S A 1987;84:3064–8.
adult acoustic ganglia: neuronotrophic effects. Brain 98. Sole CK, Derfler BH, Duyks GM, Corey DP. Mole-
Res 1991;567:306–12. cular cloning of myosins from the bullfrog saccular
84. Pirvola U, Ylikoski J, Palgi J, et al. Brain-derived neu- macula: a candidate for the hair cell adaptation
rotrophic factor and neurotrophin 3 mRNAs in the motor. Auditory Neurol 1994;3:63–75.
peripheral target fields of developing inner ear gan- 99. Kemp DT. Stimulated acoustic emissions from
glia. Proc Natl Acad Sci U S A 1992;89:9915–9. within the human auditory system. J Acoust Soc
85. Ylikoski J, Privola U, Moshnyakow M, et al. Expres- Am 1978;64:1386–91.
sion patterns of neurotrophin and their receptor 100. Brownell WE, Bader CR, Bertrand D, de Rib-
mRNAs in the rat inner ear. Hear Res 1993;65:69–78. aupierre Y. Evoked mechanical responses of isolated
86. Staecker H, Lefebvre P, Liu W, et al. Brain derived cochlear outer hair cells. Science 1985;227:194–6.
neurotrophic factor and its influence on the otocyst 101. Kachar B, Brownell WE, Altschuler R, Fex J. Elec-
[abstract]. In: Assoc Res Otolaryngol Mid-Winter trokinetic shape changes of cochlear outer hair
Meeting; 1993 Feb 7–11. cells. Nature 1986;322:365–7.
87. Ernfors P, Van De Water T, Loring J, Jaenisch R. 102. Dallos P, Evans BN, Hallworth R. Nature of the
Complementary roles of BDNF and NT-3 in motor element in electrokinetic shape changes of
vestibular and auditory development. Neuron 1995; cochlear outer hair cells. Nature 1991;350:155–7.
14:1153–64. 103. Kalinec F, Holley MC, Iwasa K, et al. A membrane-
88. Corey DP, Hudspeth AJ. Ionic basis of the receptor based force generation mechanism in auditory
potential in a vertebrate hair cell. Nature 1979;281: sensory cells. Proc Natl Acad Sci U S A 1992;89:
675–7. 8671–5.
62 Ballenger’s Otorhinolaryngology
104. Zheng J, Shen W, He DZ, et al. Prestin is the motor 117. Ryan AF, Watts AC. Expression of genes coding for
protein of cochlear outer hair cells. Nature 2000; α and β isoforms of Na/K-ATPase in the cochlea of
405:149–55. the rat. Cell Mol Neurosci 1991;2:179–87.
105. Ludwig J, Oliver D, Frank G, et al. Reciprocal 118. Fina M, Ryan AF. Expression of mRNAs encoding
electromechanical properties of rat prestin: the subunit isoforms of the Na, K-ATPase in the
motor molecule from rat outer hair cells. Proc Natl vestibular labyrinth of the rat. Cell Mol Neurosci
Acad Sci U S A 2001;98:4178–83. 1994;5:604–13.
106. Oliver D, He D, Klöcker N, et al. Intracellular 119. Killick R, Richardson G. Isolation of clones for the
anions as the voltage sensor of prestin, the outer α-subunit of the epithelial Na channel from chick
hair cell motor protein. Science 2001;292:2340–3. cochlear cDNA library. Presented at the Inner Ear
107. Niedzielski AS, Safieddine S, Wenthold RJ. Molec- Neuropharmacology Symposium, Montpellier,
ular analysis of excitatory amino acid receptor France, 1994.
expression in the cochlea [published erratum 120. Steel KP. The benefits of recycling. Science 1999;
appears in Audiol Neurootol 1997;2:231]. Audiol 285:1363–4.
Neurootol 1997;2:79–91. 121. Delpire E, Lu J, England R, et al. Deafness and
108. Ryan AF, Brumm D, Kraft M. Occurrence and dis- imbalance associated with inactivation of the
tribution of non-NMDA glutamate receptor secretory Na-K-2Cl co-transporter. Nat Genet
mRNAs in the cochlea. Neuroreport 1991;2:643–46. 1999;22:192–5.
109. Niedzielski AS, Wenthold RJ. Expression of AMPA, 122. Vetter D, Mann J, Wangemann P, et al. Inner ear
kainate, and NMDA receptor subunits in cochlear defects induced by null mutation of the isk gene.
and vestibular ganglia. J Neurosci 1995;15:2338–53. Neuron 1996;17:1251–64.
110. Housley CD, Batcher S, Kraft M, Ryan AF. Nico- 123. Thalmann I, Suzuki H, McCourt D, et al. Partial
tinic acetylcholine receptor subunits expressed in amino acid sequences of organ of Corti proteins
rat cochlea detected by polymerase chain reaction. OCP1 and OCP2: a progress report. Hear Res 1993;
Hear Res 1994;75:47–53. 64:191–8.
111. Drescher DC, Upadhyay S, Wilcox E, Fex J. Analysis of 124. Chen H, Thalmann I, Adams J, et al. Cloning,
muscarinic receptor subtypes in the mouse cochlea molecular analysis and tissue distribution of Ocp2,
by means of PCR. J Neurochem 1992;59:765–7. a gene encoding a putative transcription-associated
112. Eybalin M, Safieddine S. Neurotransmitters and factor predominantly expressed in the auditory
neuro-modulators in the cochlea. Presented at the organs. Genomics 1995;27:389–98.
Inner Ear Neuropharmacology Symposium, Mont- 125. Legan K, Killick R, Goodyear R, Richardson G.
pellier, France, 1994. Expression of the 41 Kda chick tectorin MRNA is
113. Drescher DC, Green GE, Khan KM, et al. Analysis restricted to the striolar region within the lagenar
of gamma-aminobutyric acid A receptor subunits macula [abstract]. Abstracts Inner Ear Biology
in the mouse cochlea by means of polymerase 1994;31:48.
chain reaction. J Neurochem 1993;61:1167–70. 126. Davis JG, Oberholtzer JC, Burns FR, Greene MI.
114. Housley GD, Raybould NP, Taylor L. Variation in Molecular cloning and characterization of an inner
conductances activated in response to extracellular ear-specific structural protein. Science 1995;267:
ATP and tonotopic-dependent expression of P2 1031–4.
purinoceptors in the sensory hair cells of the inner 127. Harter C, Ripoll C, Lenoir M, et al. Expression pat-
ear. Presented at the Inner Ear Neuropharmacol- tern of mammalian cochlea outer hair cell (OHC)
ogy Symposium Montpellier, France, 1994. mRNA: screening of a rat OHC cDNA library. DNA
115. Ryan AF, Simmons DM, Watts A, Swanson LW. Cell Biol 1999;18:1–10.
Enkephalin mRNA production by cochlear and 128. Ryan AF, Dulon D, Keithley EM, Erkman L. A
vestibular efferents in the gerbil brainstem. Exp Brn-3.1 promoter element directs gene expression
Brain Res 1991;87:259–67. limited to hair cells in postnatal transgenic mice
116. Elgoyhen A, Johnson D, Boulter J, et al. Alpha 9: [abstract]. Abstr Conf Mol Biol Hear Deafness
acetylcholine receptor with novel pharmacological 1998;3:166.
properties expressed in rat cochlear hair cells. Cell 129. Zuo J, Treadaway J, Buckner TW, Fritzsch B. Visu-
1994;18:705–15. alization of alpha9 acetylcholine receptor expres-
Molecular Biology of Hearing and Balance 63
sion in hair cells of transgenic mice containing a 142. Ryan AF, Luo L. Expression of nitric oxide synthase
modified bacterial artificial chromosome. Proc in the mouse middle ear mucosa during immune-
Natl Acad Sci U S A 1999;96:14100–5. mediated chronic otitis media. In: Tos M, Thomsen
130. Yoo TJ, Fujiyoshi T, Readhead C, Hood L. Restora- J, Balle V, editors. Recent advances in otitis media.
tion of auditory evoked potential by myelin basic Amsterdam: Kugler; 2000. p. 112–6.
protein (MBP) gene therapy in shiverer mice. In: 143. Ohtani F, Furuta Y, Iino Y, et al. Amplification of
Assoc Res Otolaryngol Mid-Winter Meeting; 1993 RNA from archival human temporal bone sections.
Feb 7–11 p. 147. Laryngoscope 1999;109:617–20.
131. Dulon D, Ryan AF. The bacterial neo gene confers 144. Andersson B, Svanborg-Eden C. Attachment of
neomycin resistance to mammalian cochlear hair Streptococcus pneumoniae to human pharyngeal
cells. Neuroreport 1999;10:1189–93. epithelial cells. Respiration 1989;55 Suppl 1:49–52.
132. Han JJ, Mahtre AN, Wareing M, et al. Transgene 145. Coleman T, Grass S, Munson R. Molecular cloning,
expression in the guinea pig cochlea mediated by a expression, and sequence of the pilin gene from
lentivirus-derived gene transfer vector. Hum Gene nontypeable Haemophilus influenzae M37. Infect
Ther 1999;10:1867–73. Immun 1991;59:1716–22.
133. Dazert S, Aletsee C, Brors D, et al. In vivo adenovi- 146. Kar S, To SC, Brinton CC. Cloning and expression
ral transduction of the neonatal rat cochlea and in Escherichia coli of LKP pilus genes from a non-
middle ear. Hear Res. 2001;151:30–40. typeable Haemophilus influenzae strain. Infect
134. Holt JR, Johns DC, Wang S, et al. Functional Immun 1990;58:903–8.
expression of exogenous proteins in mammalian 147. Bakaletz LO, Ahmed MA, Kolattukudy PE, et al.
sensory hair cells infected with adenoviral vectors. Cloning and sequence analysis of a pilin-like gene
J Neurophysiol 1999;81:1881–8. from an otitis media isolate of nontypeable
135. Staecker H, Gabaizadeh R, Federoff H, Van De Haemophilus influenzae. J Infect Dis 1992;165
Water TR. Brain-derived neurotrophic factor gene Suppl 1:S201–3.
therapy prevents spiral ganglion degeneration after 148. Sirakova T, Kolattukudy PE, Murwin D, et al. Role
hair cell loss. Otolaryngol Head Neck Surg 1998; of fimbriae expressed by nontypeable Haemophilus
119:7–13. influenzae (NTHi) in the pathogenesis of and pro-
136. Suzuki M, Yagi M, Brown JN, et al. Effect of trans- tection against otitis media and relatedness of the
genic GDNF expression on gentamicin-induced fimbrin subunit to outer membrane protein A.
cochlear and vestibular toxicity. Gene Ther 2000; Infect Immun 1994;62:2002–20.
7:1046–54. 149. St. Geme JW, Falkow S, Barenkamp SJ. High-
137. Ryan AF, Luo L, Baird A. Implantation of cells molecular-weight proteins of nontypeable
transfected with the FGF-1 gene induces middle Haemophilus influenzae mediate attachment to
ear mucosal proliferation. In: Lim DL, editor. human epithelial cells. Proc Natl Acad Sci U S A
Recent advances in otitis media with effusion. 1993;90:75–9.
Amsterdam: Kugler; 1997. p. 248–50. 150. Brinton CC, Carter M, Derber DB, et al. Design
138. Staecker H, Kopke R, Lefebvre P, et al. The effects of and development of pilus vaccines for Haemo-
neurotrophins on adult auditory neurons in vitro philus influenzae diseases. Pediatr Infect Dis J
and in vivo [abstract]. In: Assoc Res Otolarynol 1989;Suppl 8:54–61.
Mid-Winter Meeting; 1995 Feb 5–9. p. 177. 151. Bakaletz LO, Tallan BM, Hoepf TM, et al. Fre-
139. Post JC, Ehrlich GD. The impact of the polymerase quency of fimbriation of nontypeable Haemophilus
chain reaction in clinical medicine. JAMA 2000; influenzae and its ability to adhere to chinchilla and
283:1544–6. human respiratory epithelium. Infect Immun 1988;
140. Melhus A, Ryan AF. Expression of cytokine genes 56:331–5.
during pneumococcal and nontypeable Haemo- 152. Spinola SM, Griffiths GE, Shanks KL, Blake MS.
philus influenzae acute otitis media in the rat. Infect The major outer membrane protein of Haemo-
Immun 2000;68:4024–31. philus ducreyi is a member of the OmpA family of
141. Ehrlich GD, Post JC. Susceptibility to otitis media: proteins. Infect Immun 1993;61:1346–51.
strong evidence that genetics plays a role. JAMA 153. DeMaria TF, Yamaguchi T, Lim DJ. Quantitative
1999;282:2167–9. cytologic and histologic changes in the middle ear
64 Ballenger’s Otorhinolaryngology
after the injection of non-typeable Haemophilus tein Haemophilus influenzae by using recombinant
influenzae endotoxin. Am J Otolaryngol 1989; proteins and synthetic peptides. Infect Immun
10:261–6. 1991;59:1457–64.
154. Weiser JN, Lindberg AA, Manning EJ, et al. Identi- 165. Haasse EM, Yi K, Morse GD, Murphy TF. Mapping
fication of chromosomal locus for expression of of bactericidal epitopes on the P2 porin protein of
lipopolysaccharide epitopes in Haemophilus in- nontypeable Haemophilus influenzae. Infect
fluenzae. Infect Immun 1989;57:3045–52. Immun 1994;62:3712–22.
155. Weiser JN, Williams A, Moxon ER. Phase-variable 166. Green BA, Metcalf BJ, Quinn-Dey T, et al. A recom-
lipopolysaccharide structures enhance the invasive binant non-fatty acylated form of the Hi-PAL (P6)
capacity of Haemophilus influenzae. Infect Immun protein of Haemophilus influenzae elicits biologi-
1990;58:3455–7. cally active antibody against both nontypeable and
156. Weiser JN, Maskell DJ, Butler PD, et al. Character- type b H. influenzae. Infect Immun 1990;58:3272–8.
ization of repetitive sequences controlling phase 167. Murphy TF, Kirkham C. Amino acid sequence of a
variation of Haemophilus influenzae lipopolysac- surface-exposed epitope of the P6 outer membrane
charide. J Bacteriol 1990;172:3304–9. protein of nontypable Haemophilus influenzae
157. Berry AM, Paton JC, Hansman D. Effect of inser- [abstract]. In: Lim DJ, editor. Abstracts of the Fifth
tional inactivation of the genes encoding pneu- International Symposium on Recent Advances in
molysin and autolysin on the virulence of Otitis Media. Ft. Lauderdale (FL): 1993. p. 120–l.
Streptococcus pneumoniae type 3. Microb Pathog 168. El-Adhami W, Kyd JM, Bastin DA, Cripps AW.
1992;12:87–93. Characterization of the gene encoding a 26-kilo-
158. Lock RA, Hansman D, Paton JC. Comparative effi- dalton protein (OMP26) from nontypeable
cacy of autolysin and pneumolysin as immunogens Haemophilus influenzae and immune responses to
protecting mice against infection by Streptococcus the recombinant protein. Infect Immun 1999;
pneumoniae. Microb Pathog 1992;12:137–43. 67:1935–42.
159. Ogra PL, Barenkamp SJ, Mogi G, et al. Microbiol- 169. Deich RA, Anilionis A, Fulginiti J, et al. Antigenic
ogy, immunology, biochemistry and vaccination; conservation of the 15,000-dalton outer membrane
Recent Advances in Otitis Media. Report of the lipoprotein PCP of Haemophilus influenzae and
Fifth Research Conference. Ann Otol Rhinol biologic activity of anti-PCP antisera. Infect
Laryngol 1994; Suppl 164 103:8:27–43. Immun 1990;58:3388–93.
160. Karma PH, Bakaletz LO, Giebink GS, et al. Present 170. Barenkamp SJ, Bodor FF. Development of serum
views on possibilities of immunoprophylaxis of bactericidal activity following nontypeable
acute otitis media in infants and children. In: Haemophilus influenzae acute otitis media. Pediatr
Immunological aspects of otitis media. Int J Fed Infect Dis J 1990;9:333–9.
Otolaryngol 1995;32:127–34. 171. Barenkamp SJ, Leininger E. Cloning, expression,
161. Nelson MB, Munson RS, Apicella MA, et al. Mole- and DNA sequence analysis of genes encoding
cular conservation of the P6 outer membrane pro- nontypeable Haemophilus influenzae high-molec-
tein among strains of Haemophilus influenzae: ular-weight surface-exposed proteins related to fil-
analysis of antigenic determinants, gene sequences, amentous hemagglutinin of Bordetella pertussis.
and restriction fragment length polymorphisms. Infect Immun 1992;60:1302–13.
Infect Immun 1991;59:58–63. 172. Alexander JE, Lock RA, Peeters CC, et al. Immu-
162. Deich RA, Metcalf BJ, Finn CW, et al. Cloning of nization of mice with pneumolysin toxoid confers
genes encoding a 15,000-dalton peptidoglycan- a significant degree of protection against at least
associated outer membrane lipoprotein and an nine serotypes of Streptococcus pneumoniae. Infect
antigenically related 15,000-dalton protein from Immun 1994;62:5683–8.
Haemophilus influenzae. J Bacteriol 1988;170:489–98. 173. Swiatlo E, Brooks-Walter A, Briles DE, McDaniel LS.
163. Sikkema DJ, Murphy TF. Molecular analysis of the Oligonucleotides identify conserved and variable
P2 porin protein of nontypeable Haemophilus regions of pspA and pspA-like sequences of Strepto-
influenzae. Infect Immun 1992;60:5204–11. coccus pneumoniae. Gene 1997;188:279–84.
164. Martin D, Munson R, Grass S, et al. Mapping of B- 174. Okamoto Y, Kudo K, Ishikawa K, et al. Presence of
cell epitopes on the outer membrane P2 porin pro- respiratory syncytial virus genomic sequences in
Molecular Biology of Hearing and Balance 65
middle ear fluid and its relationship to expression South African isolate of Streptococcus pneumoniae.
of cytokines and cell adhesion molecules. J Infect Mol Microbiol 1989;3:95–102.
Dis 1993;168:1277–81. 188. Klugman KP, Coffey TJ, Smith A, et al. Cluster of
175. Giebink GS. Studies of Streptococcus pneumoniae an erythromycin-resistant variant of the Spanish
and influenzae virus vaccines in the chinchilla multiply resistant 23F clone of Streptococcus pneu-
otitis media model. Pediatr Infect Dis J 1989;8(1 moniae in South Africa. Eur J Clin Microbiol Infect
Suppl):S42–4. Dis 1994;13:171–4.
176. Heikkinen T, Ruuskanenn 0, Waris M, et al. 189. Soares S, Kristinsson KG, Musser JM, Tomasz A.
Influenza vaccination in the prevention of acute Evidence for the introduction of a multiresistant
otitis media in children. Am J Dis Child 1991;145: clone of serotype 6B Streptococcus pneumoniae
445–8. from Spain to Iceland in the late 1980s. J Infect Dis
177. Robinson HL, Hunt LA, Webster RG. Protection 1993;168:158–63.
against a lethal influenza virus challenge by immu- 190. Owen RJ. Chromosomal DNA fingerprinting — a
nization with hemoagglutinin-expressing plasmid new method of species and strain identification
DNA. Vaccine 1993;11:957–60. applicable to microbial pathogens. J Med Micro-
178. Montgomery DL, Shiver JW, Leander KR, et al. biol 1989;30:89–99.
Heterologous and homologous protection against 191. Loos BG, Bernstein JM, Dryja DM, et al. Determi-
influenza A by DNA vaccination: optimization of nation of the epidemiology and transmission of
DNA vectors. DNA Cell Biol 1993;12:777–83. non-typeable Haemophilus influenzae in children
179. Needham CA. Haemophilus influenzae: antibiotic with otitis media by comparison of total genomic
susceptibility. Clin Microbiol Rev 1988;1:218–27. DNA restriction fingerprints. Infect Immun 1989;
180. DeGraff J, Elwell OP, Falkow S. Molecular nature of 57:2751–7.
two beta-lactamase-specifying plasmids isolated 192. Dickinson DP, Loos GB, Dryja DM, Bernstein JM.
from Haemophilus influenzae type b. J Bacteriol Restriction fragment mapping of Branhamella
1976;126:439–46. catarrhalis: a new tool for studying the epidemiol-
181. Mendelman PM, Chaffin DO, Stull TL, et al. Char- ogy of this middle ear pathogen. J Infect Dis 1988;
acterization of non-beta-lactamase-mediated ampi- 158:205–8.
cillin resistance in Haemophilus influenzae. Antimi- 193. Salo P, Ortqvist A, Leinonen M. Diagnosis of bac-
crob Agents Chemother 1984;26:235–44. teremic pneumococcal pneumonia by amplifica-
182. Clairoux N, Picard M, Brochu A, et al. Molecular tion of pneumolysin gene fragment in serum. J
basis of the non-beta-lactamase-mediated resist- Infect Dis 1995;171:479–82.
ance to beta-lactam antibiotics in strains of 194. Oehl H, Ryan A. Expression of genes encoding
Haemophilus influenzae isolated in Canada. Anti- growth factor receptors in middle ear mucosa
microb Agents Chemother 1992;36:1504–13. [abstract]. In: Lim DJ, editor. Abstracts of the 7th
183. Malouin F, Bryan LE. DNA probe technology for International Symposium on Recent Advances in
detection of Haemophilus influenzae. Mol Cell Otitis Media. Ft. Lauderdale (FL): 1999. p. 70.
Probes 1987;1:221–32. 195. DeFoire-Hyrmer J, Bakaletz LO. Evidence obtained
184. Roberts MC, Swenson CD, Owens LM, Smith by confocal microscopy that links phosphorylation
AL. Characterization of chloramphenicol-resistant of tyrosine with nontypeable Haemophilus influen-
Haemophilus influenzae. Antimicrob Agents zae adherence and actin nucleation [abstract]. In:
Chemother 1980;18:610–5. Lim DJ, editor. Abstracts of the 7th International
185. de Groot R, Campos J, Moseley SL, Smith AL. Mol- Symposium on Recent Advances in Otitis Media.
ecular cloning and mechanism of trimethoprim Ft. Lauderdale (FL): 1999. p. 175.
resistance in Haemophilus influenzae. Antimicrob 196. Sudhoff H, Dazert S, Gonzales AM, et al. Angio-
Agents Chemother 1988;32:477–84. genesis and angiogenic growth factors in middle
186. Klugman KP. Pneumococcal resistance to antibi- ear cholesteatoma. Am J Otol 2000;21:793–8.
otics. Clin Microbiol Rev 1990;3:171–96. 197. Huang CC, Chen CT, Huang TS, Shinoda H. Medi-
187. Dowson CG, Hutchinson A, Spratt BG. Extensive ation of signal transduction in keratinocytes of
remodeling of the transpeptidase domain of peni- human middle ear cholesteatoma by ras protein.
cillin-binding protein 2B of a penicillin-resistant Eur Arch Otorhinolaryngol 1996;253:385–9.
66 Ballenger’s Otorhinolaryngology
198. Ishibashi T, Shinogami M, Kaga K, Fukaya T. Ker- pathway is required for Pseudomonas aeruginosa-
atinocyte growth factor and receptor mRNA induced mucin overproduction in epithelial cells.
expression in cholesteatoma of the middle ear. Acta Proc Natl Acad Sci U S A 1998;95:5718–23.
Otolaryngol (Stockh) 1997;117:714–8. 209. Xu H, Wang B, Kim JH, et al. Oxygen radicals as
199. Shinoda H, Huang CC. Expressions of c-jun and second messengers for bacteria-induced up-regu-
p53 proteins in human middle ear cholesteatoma: lation of mucin gene transcription [abstract]. In:
relationship to keratinocyte proliferation, differen- Lim DJ, editor. Abstracts of the 7th International
tiation, and programmed cell death. Laryngoscope Symposium on Recent Advances in Otitis Media.
1995;105:1232–7. Ft. Lauderdale (FL): 1999. p. 255.
200. Schilling V, Lang S, Rasp G, et al. Overexpression of 210. Chun YM, Li JD, Lim DJ. MEK1/2-MAPK pathway
tenascin in cholesteatoma and external auditory is involved in IL-1-induced down-regulation of
meatal skin compared to retroauricular epidermis. surfactant B [abstract]. In: Lim DJ, editor. Abstracts
Acta Otolaryngol (Stockh) 1996;116:741–6. of the 7th International Symposium on Recent
201. Park K, Park HJ, Chun YM, Lee DH. Expression of Advances in Otitis Media. Ft. Lauderdale (FL):
PLC-gamma 1 in experimental cholesteatoma 1999. p. 256.
[abstract]. In: Lim DJ, editor. Abstracts of the 7th 211. Moon SK, Yoon JH, Lee HK, et al. Effects of
International Symposium on Recent Advances in retinoic acid, triiodothyronine and hydrocortisone
Otitis Media. Ft. Lauderdale (FL): 1999. p. 80. on mucin and lysozyme expression in passage-2
202. Hebda PA, Alper CM, Doyle WJ, et al. Up- normal human middle ear epithelial cells
regulation of messenger RNA for inflammatory [abstract]. In: Lim DJ, editor. Abstracts of the 7th
cytokines in middle ear mucosa in a rat model of International Symposium on Recent Advances in
acute otitis media. Ann Otol Rhinol Laryngol 1998; Otitis Media. Ft Lauderdale (FL): 1999. p. 257.
107:501–8. 212. Lin J, Kawano H, Tsuboi Y, et al. Alterations of mucin
203. Melhus Å, Forseni M, Ryan AF. Molecular markers gene expression in the transition of acute to mucoid
for bone formation during bacterial otitis media in otitis media. In: Lim DJ, editor. Abstracts of the 7th
the rat. In: Lim DJ, et al, editors. Recent advances in International Symposium on Recent Advances in
otitis media with effusion. Amsterdam: Kugler; Otitis Media. Ft. Lauderdale (FL): 1999. p. 72.
2000. 213. Hutton DA, Fogg FJ, Kubba H, et al. Heterogeneity
204. Bikhazi P, Luo L, Ryan AF. Expression of in the protein cores of mucins isolated from
immunoregulatory cytokines during acute and human middle ear effusions: evidence for expres-
chronic middle ear immune response. Laryngo- sion of different mucin gene products. Glycocon-
scope 1995;105:629–34. jugate J 1998;15:283–91.
205. John EO, Nam TTK. Concentration of nitric oxide 214. Jung HH, Lee JH, Lim HH, Chung C. Expression of
in middle ear effusion [abstract]. In: Lim DJ, edi- mucin genes in otitis media [abstract]. In: Lim DJ,
tor. Abstracts of the 7th International Symposium editor. Abstracts of the 7th International Sympo-
on Recent Advances in Otitis Media. Ft. Lauderdale sium on Recent Advances in Otitis Media. Ft.
(FL): 1999. p. 83. Lauderdale (FL): 1999. p. 251.
206. Juhn S, Li W, Flaagan J, Javel E. Inflammatory NO 215. Severn TL, Hutton DA, Birchall JP, Pearson JP.
involvement in auditory function [abstract]. In: Mucin gene expression in human middle ear
Lim DJ, editor. Abstracts of the 7th International [abstract]. In: Lim DJ, editor. Abstracts of the 7th
Symposium on Recent Advances in Otitis Media. International Symposium on Recent Advances in
Ft. Lauderdale (FL): 1999. p. 88. Otitis Media. Ft. Lauderdale (FL): 1999. p. 253.
207. Li JD, Xu H, Wang B, et al. Signal transduction 216. Wang B, Lim DJ, Han J, et al. Novel cytoplasmic
mechanisms involved in bacteria-induced mucin proteins of nontypeable Haemophilus influenzae
overproduction [abstract]. In: Lim DJ, editor. up-regulate human MUC5AC mucin transcription
Abstracts of the 7th International Symposium on via a positive p38 MAP kinase pathway and a neg-
Recent Advances in Otitis Media. Ft. Lauderdale ative PI 3-kinase-Akt pathway. J Biol Chem 2002;
(FL): 1999. p. 77. 277:949–57.
208. Li JD, Feng WJ, Gallup M, et al. Activation of NF- 217. Shuto T, Xu H, Wang B, et al. Activation of NF-
kappaB via a Src-dependent Ras-MAPK-pp90rsk kappa B by nontypeable Hemophilus influenzae is
Molecular Biology of Hearing and Balance 67
mediated by toll-like receptor 2-TAK1-dependent ferricins of human, murine and caprine origin.
NIK-IKK alpha/beta-I kappa B alpha and Scand J Infect Dis 1998;30:513–7.
MKK3/6-p38 MAP kinase signaling pathways in 228. Qiu J, Hendrixson DR, Baker EN, et al. Human
epithelial cells. Proc Natl Acad Sci U S A 2001;98: milk lactoferrin inactivates two putative coloniza-
8774–9. tion factors expressed by Haemophilus influenzae.
218. Lim DJ, Chun YM, Lee HY, et al. Cell biology of Proc Natl Acad Sci U S A 1998;95:12641–6.
tubotympanum in relation to pathogenesis of otitis 229. Hanamure Y, Lim DJ. Normal distribution of
media — a review. Vaccine 2000;19 Suppl 1:S17–25. lysozyme- and lactoferrin-secreting cells in the
219. Lehrer RI, Ganz T. Antimicrobial peptides in chinchilla tubotympanum. Am J Otolaryngol 1986;
mammalian and insect host defense. Curr Opin 7:410–25.
Immunol 1999;11:23–7. 230. Park K, Lim DJ. Development of secretory ele-
220. Ganz T, Lehrer RI. Defensins. Pharmacol Ther ments in murine tubotympanum: lysozyme and
1995;66:191–205. lactoferrin immunohistochemistry. Ann Otol Rhi-
221. McNamara N, Van R, Tuchin OS, Fleiszig SM. Ocu- nol Laryngol 1993;102:385–95.
lar surface epithelia express mRNA for human beta 231. Lu J. Collectins: collectors of microorganisms for the
defensin-2. Exp Eye Res 1999;69:483–90. innate immune system. Bioessays 1997;19:509–18.
222. Schroder JM, Harder J. Human beta-defensin-2. Int 232. Malhotra R, Lu J, Holmskov U, Sim RB. Collectins,
J Biochem Cell Biol 1999;31:645–51. collectin receptors and the lectin pathway of com-
223. Takemura H, Kaku M, Kohno S, et al. Evaluation of plement activation. Clin Exp Immunol 1994;97
susceptibility of gram-positive and -negative bacteria Suppl 2:4–9.
to human defensins by using radial diffusion assay. 233. Mondain M, Restituito S, Vincenti V, et al. Aden-
Antimicrob Agents Chemother 1996;40:2280–4. ovirus-mediated in vivo gene transfer in guinea pig
224. O’Neil DA, Porter EM, Elewaut D, et al. Expression middle ear mucosa. Hum Gene Ther 1998;9:1217–21.
and regulation of the human beta-defensins hBD-
1 and hBD-2 in intestinal epithelium. J Immunol
1999;163:6718–24.
SUGGESTED READING
225. Boe R, Silvola J, Yang J, et al. Human beta-defensin- Bockaert J. G proteins and G-protein coupled receptors:
1 mRNA is transcribed in tympanic membrane and structure, function and interactions. Curr Opin
adjacent auditory canal epithelium. Infect Immun Neurobiol 1991;1:32–42.
1999;67:4843–6. Click RB, Pasternak JJ. Molecular biotechnology: princi-
226. Lim DJ, Liu YS, Birck H. Secretory lysozyme of the ples & applications of recombinant DNA. Washing-
human middle ear mucosa: immunocytochemical ton (DC): ASM Press; 1994.
localization. Ann Otol Rhinol Laryngol 1976;85(1 Darnell J, Lodish H, Baltimore D. Molecular cell biology.
Pt 1):50–60. 2nd ed. New York: Scientific American Books; 1990.
227. Vorland LH, Ulvatne H, Andersen J, et al. Lacto- Davis L, Kuehl M, Battey J. Basic methods in molecular
ferricin of bovine origin is more active than lacto- biology. 2nd ed. New York: Appleton & Lange; 1994.
CHAPTER 4
68
Physiology of the Auditory and Vestibular Systems 69
T Total: 45 T
20 1 Spherical head
Acoustic Gain Components (dB)
sic analysis, shown in Figure 4–1, most of the indi- fluids (perilymph and endolymph) of the cochlea
vidual components of the external ear provide com- and (2) the acoustic reflex of the middle ear muscle
plementary gains, resulting in a significant increase system.
in sound pressure from approximately 2 to 7 kHz. The widespread use of surgical modification of
When the overall additive effect is appreciated (“T” middle ear structures to improve hearing and the
in Figure 4–1), it can be seen that at certain fre- usefulness of immittance audiometry make the con-
quencies this gain is substantial, resulting in sound cept of acoustic impedance and its relationship to
pressure increases on the order of 20 dB. middle ear function important to the clinician.
Studies of models of the human external ear Accordingly, the discussion of the middle ear begins
suggest that the pinna extracts information about by reviewing some basic principles of acoustic
sound location by altering the transmission proper- impedance.
ties of different frequencies according to the location
of the sound source relative to the pinna. For exam- Transmission of Acoustic Energy Through the
ple, when the sound source is behind the ear, inter- Middle Ear Figure 4–3, A, diagrams the route for
ference of directly transmitted sound with sound the transmission of sound energy through the mid-
waves scattered off the pinna flange or helix alters dle ear into the cochlear portion of the inner ear.
the response in the 3 to 6 kHz range. Thus, the exter- The ossicular chain (see Figure 4–2), consisting of
nal ear modifies the spectrum of the incoming the malleus, incus, and stapes, can be thought of as
sound, allowing an individual to make judgments a lever system. The tympanic membrane moves the
about the location of unknown sound sources. This manubrium or handle of the malleus. In turn, the
localization ability suggests that the central part of long process of the incus and manubrium move
the auditory system can use very subtle spectral cues together because the malleoincudal joint is essen-
in the analysis of environmental sounds.3 tially fixed. In contrast, the joint between the incus
and the stapes is flexible. Therefore, because the
stapes is fixed at its posteroinferior border, move-
MIDDLE EAR ment of the tympanic membrane causes it to rock in
Figure 4–2 outlines the anatomy of the middle and and out of the oval window. The changes in acoustic
inner ears. The middle ear ossicles form a transmis- pressure caused by the stapes moving in and out of
sion pathway that conducts sound energy from the the oval window are transmitted instantaneously by
tympanic membrane, at the interface of the external the perilymph through the cochlear partition and
and middle ear, to the oval window of the cochlea. then to the round window. This pressure transmis-
The discussion of middle ear function is separated sion through the cochlear partition causes it to move
into two categories: (1) “impedance matching” either upward or downward, depending on the
between the air of the external environment and the direction of the pressure change. The pressure
70 Ballenger’s Otorhinolaryngology
FIGURE 4–2. Schematic drawing of the inner ear (labyrinth), which consists of a series of tunnels within the petrous
portion of the temporal bone. The osseous labyrinth (outer tunnel) is clear, and the membranous labyrinth (inner tun-
nel) is stippled. SV = scala vestibuli; ST = scala tympani; SM = scala media; SG = spiral ganglion, containing the cell
bodies of the auditory nerve; VG = vestibular ganglia, containing the cell bodies of the vestibular nerve; VIII (A) = audi-
tory part of the eighth cranial nerve; VIII (V) = vestibular part of the eighth cranial nerve; VII = facial nerve; Ma =
macula; CU = cupula; CR = crista; Sa = sacculus; U = utriculus. Semicircular canals are labeled AV (anterior vertical),
PV (posterior vertical), and H (horizontal). EAM = external auditory meatus; RW = round window; M = malleus; I =
incus; S = stapes; MA = mastoid air cells in temporal bone.
change initiates a mechanical traveling wave, shown gesting that the somatic sensation caused by exces-
in Figure 4–3, B, that reaches a maximum at some sive sounds may be caused by the detection of the
point on the basilar membrane depending on the altered ossicular vibration by middle ear bone and
frequency of the stimulating sound. The mechanical tendon receptors.
traveling wave moves from the base to the apex of
the cochlea largely owing to a reduced stiffness of Impedance Matching by the Middle Ear Hearing
the basilar membrane in the apical direction. As dis- by terrestrial animals requires transmission of sound
cussed below, this traveling wave disturbance causes from an air to a fluid environment. A useful way to
the hair cells in the organ of Corti to stimulate the appreciate the problem in conducting sound effec-
dendritic endings of the cochlear nerve, thus signal- tively between two distinct media is to recall how
ing to the central auditory system that a sound stim- difficult it is to listen to sounds produced even a few
ulus has occurred. inches above the surface while swimming underwa-
At high sound levels of ~100 to 110 dB SPL ter. Thus, direct transmission of sound across an
(sound pressure level), the mode of vibration of the air/water boundary is extremely inefficient because
ossicular chain changes. Thus, instead of rotating the specific acoustic impedances of air and water dif-
about its short axis, as shown in Figure 4–3, A, the fer greatly. Moreover, whenever energy is transmit-
stapes footplate turns about its long axis.4 Because ted between media with different specific
this change results in less efficient sound transmis- impedances, much of the energy is reflected back
sion through the middle ear, it likely serves a protec- from the boundary between the two media. To help
tive function. Interestingly, the change in vibration solve this problem, the middle ear matches reason-
mode occurs at the threshold of feeling, thus sug- ably well the impedances of the air with those of the
Physiology of the Auditory and Vestibular Systems 71
A
Stiffness (S)
Force (F)
Mass
Driving (M) Velocity (V)
Freq. (f)
Fluid
Frictional
Resistance (R)
Force 2
Impedance 2 S
R 2 fM
Velocity 2 f
B Semicircular Canal
FIGURE 4–4. Principles of mechanical impedance. Fric-
Vestibule tional resistance is represented by a “dashpot”—a perfo-
rated piston operating inside a fluid-filled cylinder. The
Stapes diagram could be converted to a representation of
Basilar Membrane
Round Window
Scala Vestibuli acoustic impedance by interposing a cylinder, or
Scala Tympani
diaphragm, between the driving force (F) and the driven
Cochlea mass (M) and expressing the displacing input as pressure
(ie, force per unit area).
Heliocotrema
FIGURE 4–3. A, Transmission of tympanic membrane mechanical impedance of the middle ear system.
movement to the cochlea via the ossicles. The system at Friction, the resistive component of impedance,
rest is unstippled. The stippled ossicles and dashed consumes energy and is independent of the driving
cochlear partition illustrate the system when the tym- frequency. Stiffness and mass store energy; thus, they
panic membrane is pushed inward by a sound wave. B, comprise the reactive component of impedance. For
Inward pressure (arrows) initiates a traveling wave that example, once the “fluid”-filled cylinder in Figure
migrates toward the apex of the cochlea (toward the heli- 4–4 is set in motion, it tends to continue because of
cotrema). This propagation depends largely on fluid cou- inertia, and if the spring representing stiffness is
pling and the fact that the basilar membrane changes in compressed, it tends to push backward.
stiffness, with the traveling wave moving from a region of Acoustic impedance represents a special type
highest stiffness (base) to a point of lower stiffness of mechanical impedance in which force is replaced
(apex). Reproduced with permission from Zweig G, Lipes by pressure (ie, force per unit area) and the system is
R, Pierce JR. The cochlear compromise. J Acoust Soc Am driven by sound. Thus, Figure 4–4 could be con-
1976;59:975–82. verted into a diagram of an acoustic system by inter-
posing a piston, or membrane, between the force
and the mass.
cochlea and thereby greatly increases the efficiency When air conducts sound, the stiffness com-
of transmitting acoustic energy from the ambient ponent of its acoustic impedance is determined by
environment into the cochlea. the elastic coupling between air molecules, the mass
The term impedance describes the opposition component is determined by the mass of the air
of a system to movement. Thus, the more force molecules, and the frictional component is deter-
required to move a mechanical system at a given mined by frictional resistance between the mole-
speed, the greater its impedance. Figure 4–4 illus- cules. Because water is much denser and less
trates the principles of mechanical impedance. The compressible than air, it might seem at first that
impedance of a mechanical system involves a com- mass and stiffness create the principal difference
plex relationship between the three physical param- between the acoustic impedance of the cochlea and
eters illustrated in Figure 4–4. Together, mass, that of air. However, Figure 4–4 demonstrates that
stiffness, and resistance (ie, friction) determine the transmission of energy into the cochlea does not
72 Ballenger’s Otorhinolaryngology
involve compression of the cochlear fluid itself. In greatly. In the human, the area ratio of the tympanic
addition, the elastic restorative forces of the membrane to the oval window is about 20 to 1.
cochlear partition and round window tend to can- However, the tympanic membrane does not vibrate
cel out the effect of the fluid’s mass. Thus, the effec- as a whole.6 Thus, the effective area ratio is only
tive acoustic impedance of the cochlea is primarily about 14 to 1. The ossicular chain also contributes to
resistive.5 the transformer role of the middle ear by a levering
As noted earlier, a primary function of the action that increases the vibration amplitude (Figure
middle ear is to provide a means of “matching” the 4–5, B). The ossicular chain lever ratio is around 1.3
low impedance of air with the high cochlear imped- to 1. A final factor influencing the efficiency of
ance resulting from fluid flow and the distensibility energy transfer depends on the conical shape of the
of the cochlear membranes that separate the tympanic membrane that allows a buckling action
endolymph from the perilymph. Impedance match- to occur (Figure 4–5, C). The buckling motion of the
ing by the middle ear is achieved by three factors: (1) tympanic membrane results in an increased force
the area of the tympanic membrane relative to the and decreased velocity to produce approximately a
oval window, (2) the lever action of the middle ear fourfold increase in the effectiveness of energy trans-
ossicles, and (3) the shape of the tympanic mem- fer.7 Together, these actions of the middle ear system
brane. The principles behind these factors are result in an estimated overall transformer ratio of
depicted in the three diagrams of Figure 4–5. By 73 to 1.
focusing the incident sound pressure from the large
area of the tympanic membrane onto the small area Middle Ear Muscles Mammals have two small
of the oval window (Figure 4–5, A), the effectiveness skeletal muscles, the tensor tympani and the
of energy transfer between the air of the external ear stapedius, which are attached to the ossicular chain.
canal and the fluids of the cochlea is increased In primates, the stapedius muscle, which attaches to
L1 L2
F2 V2
F1, V1
L1 = F2 = V1
L2 = F1 = V2
Physiology of the Auditory and Vestibular Systems 73
the stapes and is innervated by the stapedial branch Contraction of the middle ear muscles can also
of the facial nerve, contracts reflexively in response be caused by nonauditory factors, including (1)
to intense sound stimuli. However, the tensor tym- spontaneous contractions, (2) body movements,8 (3)
pani muscle, which attaches to the malleus and is vocalizations in which contractions begin prior to
innervated by the trigeminal nerve, probably does vocalization8 (ie, prevocalization contractions), (4)
not.8 In laboratory animals such as the cat, rabbit, movements of facial muscles involving only the ten-
and guinea pig, both muscles contract in response sor tympani,8 (5) stimulation of the external ear
to loud sound. However, the threshold of the tensor canal,14 and (6) voluntary contractions.15
tympani is often higher than that of the stapedius As diagrammed in Figure 4–8, the stapedius
muscle. A four-neuron reflex arc consisting of the muscle moves the stapes footplate backward and
afferent fibers of the auditory nerve, neurons of the into the oval window, whereas the tensor tympani
ventral cochlear nucleus, neurons of the medial muscle pulls the manubrium inward. The effects of
superior olive, and facial motoneurons comprises these contractions on the transmission of pure tones
the stapedius reflex pathway illustrated in Figure 4–6 through the middle ear are illustrated in Figure
for the rabbit. The reflex arc for the tensor tympani 4–9.15,16 In summary, the transmission of low-fre-
muscle is slightly different in that neurons of the quency sounds is attenuated by contraction of either
ventral nucleus of the lateral lemniscus are also muscle,11 but the stapedius is probably a somewhat
involved.9 From the neural pathway depicted in Fig- better attenuator than the tensor tympani.
ure 4–6, it is clear that clinical abnormalities of the The function of the human acoustic reflex has
acoustic reflex primarily implicate pathology at the been studied by recording (1) gross muscle poten-
level of the lower brainstem. tials via the electromyogram,8 (2) pressure changes
In Figure 4–7, the sensitivity of the stapedius in the external auditory canal,17 and (3) acoustic
reflex in humans is plotted as a function of sound immittance changes.11,13 The clinical application of
frequency. The reflex threshold curve evoked by pure acoustic impedance measurements is known as
tones parallels the audibility threshold curve but is immittance audiometry, with the terms “imped-
about 80 dB above it.10 Not surprisingly, because of ance” and “immittance” being interchangeable. In
their greater overall energy levels, broadband stimuli Figure 4–10, the time course is shown for the human
(eg, white noise) elicit the reflex more effectively stapedius reflex as recorded by the immittance
than do pure tones.11 Experimental evidence indi- change method. The latency or time to the first
cates that the stapedius reflex threshold decreases detectable change generally varies from 10 to 30 ms,
with increasing stimulus duration, with a time con- whereas the reflex decays over about 500 ms after the
stant of about 200 ms.12 This value approximates the onset of the stimulus. The initial reduction in
time constant of temporal summation for the per- impedance is frequency dependent.
cepts of loudness and sensitivity. These findings, To date, acoustics-based clinical evaluations of
along with the clinical observation that the stapedius middle ear function using immittance audiometry
reflex exhibits “recruitment” in patients with are an important part of the audiologic diagnostic
cochlear hearing loss,13 suggest that the acoustic test battery. However, they are not specific enough to
reflex threshold correlates more with subjective represent independent diagnostic tests mainly
loudness than with absolute stimulus intensity. because of limitations in the frequency range over
VCN SO SO VCN
N. VIII N. VIII
m. Stapedius
FIGURE 4–6. Neural pathway for the acoustic middle ear reflex in the rabbit. Reflex is mainly a chain of four neurons
with a small ipsilateral three-neuron link. N. VIII = auditory nerve; N. VII = facial nerve; VCN = ventral cochlear
nucleus; SO = superior olive; n. VII = facial nerve motoneuron. Reproduced with permission from Møller AR. Audi-
tory physiology. New York: Academic Press; 1983.
74 Ballenger’s Otorhinolaryngology
110
105
100
95
90
85
80
75
200 300 500 1,000 2,000 4,000
Frequency (Hz)
–10
0
Hearing Level (dB)
10
20
30
40
Uncontracted Contracted
Smith
Reger
Scala Vestibuli
Reissner’s Membrane
Perilymph
Stria Vascularis
Endolymph Scala Media
Spiral Ligament
Organ of Corti
Scala Tympani
Perilymph
Scala Vestibuli
(Perilymph)
Bone ran
e
e mb Stria Vascularis
er’s M
ssn
Rei Scala Media
(Endolymph)
Limbus
Hair Cells FIGURE 4–12. The perilymph/endolymph barriers
Internal External Tactorial Membrane
Reticular around the scala media and stria vascularis. The dotted
Lamina
Hansen’s
Claudius’ Cells
line represents “intermediate-to-tight” tight junctions,
whereas the solid line represents “very tight” tight junc-
Nerve Fibers
Basilar Membrane
Deiters’ Cells tions. The circles represent blood vessels, which all have
Intraganglionic Rods and Tunnel
Spiral Bundle
Cochlear Neurons
or Corti Spiral Ligament
tight junctions that separate them from the intracochlear
Scala Tympani
(Perilymph) spaces. SV = scala vestibuli; ST = scala tympani; CD =
FIGURE 4–11. A, Simplified drawing depicting a cross- cochlear duct; OC = organ of Corti; S = stria vascularis;
section through one turn of the cochlea showing the SL = spiral ligament. Reproduced with permission from
three compartments (scalae). The middle compartment Jahnke K.24
(scala media) is filled with K+-rich endolymph. The other
two compartments (scala tympani and scala vestibuli)
are enclosed in the osseous labyrinth. These compart- of scala tympani via relatively large channels
ments are filled with Na+-rich perilymph. B, Semidia- through the basilar membrane.26 Thus, cortilymph
grammatic representation of a cross-section of the is probably identical to perilymph with respect to
guinea pig cochlear duct. A reproduced with permission its electrolyte content. The tectorial membrane
from Salt AN, Konishi T. The cochlear fluids: perilymph resembles a rather stiff, oval, gelatinous tube. It is
and endolymph. In: Altschuler RA, Hoffman DW, Bobbin attached to the limbus by a flexible membranous
RP, editors. Neurobiology of hearing: the cochlea. New band that allows it to move up and down like the
York: Raven Press; 1986. B reproduced with permission cover of a book.27
from Davis H. Advances in the neurophysiology and neu- Mammals have three rows of OHCs. A fourth
roanatomy of the cochlea. J Acoust Soc Am 1962;34:1377. row of OHCs is seen in an occasional cross-section,
especially in primates, but there is no well-defined
fourth row.28 There is only one row of IHCs. The fine
finger-like projections present on the apical surface
lium (eg, the cells of Hensen and Claudius, the cells of the hair cells are called stereocilia. The detailed
lining the spaces of Nuel, and the cells of Reissner’s arrangements of the stereocilia on the hair cell apices
membrane) are not as “tight” (dotted line) as the are unique to each class of receptor and are illus-
junctions between the sensory cells and the basal trated in the SEM of Figure 4–13. The IHC stere-
cells (solid line) of the stria vascularis.24 The fluid ocilia form a longitudinally oriented, relatively
within the organ of Corti (ie, between the basilar shallow curve, whereas the OHC cilia make a radially
membrane and the reticular lamina) has been oriented “V,” with a notch at the apex marking the
termed cortilymph.25 However, the fluid in this site of the missing kinocilium that degenerates
space is in free communication with the perilymph embryonically during development of cochlear hair
Physiology of the Auditory and Vestibular Systems 77
Stimulus
FIGURE 4–15. Generator sites of
Sensory Input cochlear potentials (upper left
TM
Structures Mechanical
C Deformation from top to bottom: sound stimu-
lus, cochlear microphonic, and
BB Receptive summating potential) and func-
Region
tional diagram of the cochlear
M
OHC transducer mechanism (right).
Receptor
Potentials TM = tectorial membrane; C =
N cilia; OHC = outer hair cell body;
Presynaptic N = cell nucleus; M = mitochon-
Region
PSS
dria; PSS = presynaptic structures;
Synapse Chemical NE = afferent nerve endings;
NE Transmission NMNF = nonmyelinated segment
Dendritic of nerve fiber; MNF = myelinated
Region Generator
Potential
segment of nerve fiber; BB = basal
body. Reproduced with permis-
NMNF sion from DaIlos P. The auditory
Axon Spikes periphery. New York: Academic
MNF Press; 1973.
mechanical coupling of the free-floating IHC cilia in CM53 led to the hypothesis that auditory nerve fiber
such a way as to produce the mechanical rectifica- endings are stimulated electrically.54 However, stud-
tion. Thus, the concept that the IHCs generate the ies with the transmission electron microscope
SP fits well with what is known about the morphol- (TEM) revealed that the morphology of the inter-
ogy of this class of hair cell. Other evidence, how- faces between the afferent nerve endings and the hair
ever, derived from recording in the fluid spaces of cell bases was unmistakably that of a chemical
the cochlea with OHCs selectively damaged by synapse. The chemical synapse-like structures found
kanamycin,50 suggests that both the IHCs and OHCs there include (1) a synaptic cleft (ie, a uniform space
contribute to the volume-recorded SP and CM. between the hair cell and nerve-fiber membranes),
Indeed, this latter notion represents the current con- (2) synaptic vesicles, and (3) a synaptic bar in the
sensus of the field.51 form of an electron-dense disk surrounded by vesi-
Generation of the CM can be understood by cles that resembles the synaptic ribbon of the
examination of the resistance battery model of retina.55
Davis52 depicted in Figure 4–16. In this conceptual- The presence of subcellular organelles consis-
ization, the EP serves as the “battery” that provides tent with a chemical synapse at the hair cell/auditory
the driving force to move current through the high nerve junction supports the current view that a
resistance of the reticular lamina in which the apical chemical transmitter released by the hair cell stimu-
ends of the hair cells are embedded. The traveling lates the auditory nerve endings.55 Thus, cochlear
wave displaces the basilar membrane, resulting in receptor potentials are probably either directly
the deflection of the stereocilia and changes in hair involved in the cause-and-effect chain leading to
cell resistance. Thus, hair cells acting as variable chemical stimulation of the auditory nerve or are
resistors modulate current flow across the reticular intimately related to a process that is directly
lamina to produce a time-varying potential, the CM, involved but does not stimulate the auditory nerve
which follows the waveform of the input stimulus.3 fibers electrically.52
Current thinking about cochlear transduc-
ROLE OF THE COCHLEAR POTENTIALS IN STIMULUS tion, which originates primarily from the studies of
TRANSDUCTION. Wever and Bray’s discovery of the Hudspeth and colleagues,56 is illustrated in Figure
80 Ballenger’s Otorhinolaryngology
Scala Stria
Vestibuli Vascularis
+ 80 mV
Scala
FIGURE 4–16. Diagram of Media
Davis’ battery model of trans-
duction in which the positive
endocochlear potential and neg-
ative intracellular potential pro- – 40
mV
vide the force to drive current
through the variable resistances
at the top of the hair cells. Hair Scala
Reprinted with permission from Cell Tympani
Pickles J.3
4–17. In this formulation, displacement of the hair transmitter substance, other chemicals, called neu-
cell bundle opens the transduction channels romodulators,57 that influence the action of the
located at the tips of the stereocilia to allow K+ to transmitter are also believed to be released into the
flow into the cell. This influx of K+ depolarizes the synaptic cleft.58
cell, causing calcium (Ca2+) channels at the base of In the search for neurotransmitters, several cri-
the hair cell to open, thus admitting Ca2+ into the teria have been established that are requisite for the
cell. The Ca2+ ions, in turn, stimulate the transmit- identification of transmitter substances.59 These cri-
ter vesicles to fuse with the hair cell membrane and teria require that (1) the transmitter must produce
release transmitter into the synaptic cleft. Trans- the same response when applied to the synapse as
mitter substance then diffuses across the synaptic the natural stimulation of presynaptic elements, (2)
space to initiate action potentials in the adjacent extraneous substances that alter natural synaptic
auditory nerve fibers. transmission such as blocking agents should pro-
Cochlear Transmitters One area of intense duce the same effect on the transmitter candidate,
research interest in the study of cochlear transduc- (3) stimulation of presynaptic elements should
tion leading to intercellular communication has release the transmitter substance, (4) the transmitter
been the identification of the afferent transmitter substance must be shown to exist presynaptically, (5)
substance that is released onto the primary afferent enzymes responsible for the synthesis of the trans-
neurons at the bases of the IHCs and OHCs. In com- mitter candidate must be present, and (6) a mecha-
bination with these studies, other efforts have nism must be demonstrated that can deactivate the
attempted to characterize the efferent neurotrans- transmitter once it has been released into the synap-
mitter released on the hair cells, and on afferent end- tic cleft. To date, concrete evidence for the auditory
ings terminating on hair cells, by efferent neurons transmitter in the mammalian cochlea is scanty
originating in the brainstem. Recent evidence indi- when compared with the findings of other studies of
cates that the afferent neurotransmitter is probably a the central nervous system. That is to say, all of the
single excitatory amino acid, or a structurally related criteria have yet to be met for any candidate afferent
compound, which is responsible for initiating audi- transmitter substance. However, based on our pres-
tory nerve action potentials. Besides this chemical ent ability to satisfy the above criteria, one of the
Physiology of the Auditory and Vestibular Systems 81
1 Displacement of 2 3 4
Hair Bundle
K+
+
K+
K
Kinocilium
Stereocilia
Depolarization
Nucleus
CA++ CA++
Vesicles
Transmitter
Synapse
Afferent To
Nerve Brain
FIGURE 4–17. Schematic representation of the major steps involved in stimulus transduction in hair cells. Deflection
of the hair bundle (1) opens the transduction channels to allow K+ to flow into the hair cell. This results in a reduc-
tion of potential difference or depolarization. Depolarization spreads instantly to the lower part of the cell (2), caus-
ing Ca2+ channels to open. Ca2+ ions (3) cause transmitter vesicles to fuse with the basal part of the cell membrane.
Fusing vesicles release transmitter substance into the synaptic cleft. (4) Transmitter diffuses across the synaptic cleft to
initiate an action potential in the adjacent auditory nerve fiber. Reproduced with permission from Hudspeth AJ.56
most likely afferent transmitter substances is transmitters, readers are encouraged to consult an
believed to be the excitatory amino acid glutamate,60 excellent review.67
and aspartate, too, represents a more recently docu-
mented potential candidate.61 Coding in the Cochlea The cochlea must encode
Documentation regarding the efferent trans- acoustic features into properties of neural activity.
mitter in the mammalian cochlea is considerably The principal acoustic parameters to be encoded are
stronger with the most persuasive evidence favoring frequency, intensity, and temporal pattern, whereas
acetylcholine (ACh). The strongest support for ACh the basic biologic variables available for neural
comes from a set of experiments demonstrating that encoding are place (ie, the location of the activated
anticholinergic compounds block the effects of cell), amount of neural firing, and temporal pattern
efferent stimulation but do not influence afferent of firing. Because they are the percepts most studied,
cochlear activity.62 From other histochemical and the cochlear encoding of frequency and intensity is
immunostaining studies of the mammalian cochlea, addressed below. For a recent discussion of tempo-
there is considerable evidence for a GABAergic (ie, ral processing, see Frisina.68
γ-aminobutyric acid) efferent innervation of the
OHCs, as well as the IHC afferents, including (1) FREQUENCY CODING. In the late nineteenth century,
measurements of the uptake of tritiated GABA,63 (2) two opposing theories of frequency coding in the
immunostaining for glutamic acid decarboxylase,64 auditory periphery were proposed. These classic
and (3) immunostaining for GABA.64 Interestingly, “place” and “frequency” theories have influenced
evidence that isolated OHCs stain for GABA65 and subsequent thinking about cochlear frequency cod-
that GABA application to isolated OHCs induces ing.3 The place theory of Helmholtz held that the
membrane hyperpolarization and membrane elon- basilar membrane acts as if it were a series of tuned
gation66 infers that the functional consequences of resonators, analogous to a set of piano strings. Each
this candidate transmitter substance is inhibition of tuned resonator vibrates sympathetically to a differ-
the electromechanical transduction process. For a ent frequency and thus selectively stimulates a par-
more in-depth treatment of studies of cochlear ticular nerve fiber. Rutherford’s frequency theory,
82 Ballenger’s Otorhinolaryngology
later termed “telephone” theory, proposed that all firmed the general nature of von Békésy’s results but,
frequencies activate the entire length of the basilar as discussed below, modified his conclusions with
membrane, which transmits, essentially unchanged, respect to several important details.69
the temporal pattern of the auditory stimulus. The principal features of the mechanical
According to the telephone theory, it remains for responses that von Békésy observed are illustrated in
more central neural structures to “decode” these Figure 4–18. Each pure-tone cycle elicits a traveling
temporal patterns to educe the features of the wave that moves along the cochlear partition from
acoustic stimulus. base to apex.4 As it travels, the wave’s amplitude
increases slowly, passes through a maximum, and
EVIDENCE FOR PLACE CODING: MECHANICAL AND then declines rapidly (Figure 4–18, A). As the fre-
NEURAL TUNING CURVES. Von Békésy used optical quency of the stimulating tone is increased, the max-
methods to make the first direct observations of the imum of the traveling wave moves basally toward
mechanical place analysis of stimulus frequency in the oval window.
the cochlea.4 Subsequent observations using more The inset at the bottom of Figure 4–18, B, illus-
sensitive techniques (eg, Mössbauer radioactive trates the tuned behavior of the vibration of a spe-
source, capacitive probe, laser interferometry) con- cific locus on the cochlear partition that results from
ulation of the crossed olivocochlear bundle (OCB), malian hair cells that OHCs display electromotil-
which preferentially provides efferent innervation to ity.85,86 Using mechanical trituration to dissociate
the OHCs, modulates the magnitude of OAEs82,83; and single OHCs from other organ of Corti tissues and
(3) the emission is extremely sensitive to the detri- video-enhanced imaging to visualize the isolated
mental effects of cochlear pathology, acoustic trauma, OHC directly, these investigators used both intracel-
and ototoxic drugs.83,84 The most parsimonious inter- lular and transcellular electrical stimulation85 or
pretation of the existence of the various OAE types, pharmacologic (K+, cholinergic chemicals) agents86
their duration, bandwidth, and delayed-onset charac- to elongate and shorten OHCs from their resting
teristics and their relationship to the activity of the lengths. Because it has been demonstrated that hair
cochlear efferent system is that they originate in the cells possess both actin and myosin,87 it was origi-
OHCs, which possess a mechanical energy that gener- nally presumed that some aspect of the active motile
ates the frequency-selective output of the cochlea. mechanism is mediated, as in muscle, by interactions
Brownell and Zenner and their colleagues were between these molecules. However, as more details
the first to show in in vitro preparations of mam- developed about OHC electromotility, including the
Physiology of the Auditory and Vestibular Systems 87
FIGURE 4–23. Distortion-product otoacoustic emissions (DPOAEs). A, DPOAE at 2f1-f2 is shown in the spectrum of
the ear canal sound. Note the position of the geometric mean frequency (5) with respect to the primary tones (f1, f2)
and the frequency range over which the noise floor (NF) is measured relative to that of the emission (dotted region sur-
rounding the DPOAE frequency). B, A typical DPOAE frequency/level function or “DP-gram” elicited by 75 dB SPL
primaries is shown for the right (open circles) and left (solid circles) ears of a normal-hearing individual. The pairs of
long (above) and short (below) dotted lines represent the ranges of average activity and their related NF levels, respec-
tively, associated with normal function. C, A typical response/growth or input/output curve depicts the growth of the
DPOAE (DPE) with progressive increases in the levels of the primary tones. The pair of dotted lines above depicts the
normal range of emission levels, whereas the striped lines below represent the average NF. Reproduced with permis-
sion from Lonsbury-Martin BL, Whitehead ML, Martin GK. Clinical applications of otoacoustic emissions. J Speech
Hear Res 1991;34:964–81.
knowledge that they mechanically vibrate at fre- terms of their morphology, biochemistry, physiology,
quencies up to at least 30 kHz, it became clear that a and afferent and efferent innervation patterns. Phylo-
very fast-acting motor molecule,88 or some instanta- genetically, OHCs are much younger than IHCs,
neous physical phenomenon induced by an electro- being present only in the mammalian cochlea. In
kinetic process,89 formed the basis of the ability of keeping with their relative phylogenetic youth, OHCs
the OHC to vibrate in response to changes in the develop later embryologically,92 are more easily com-
receptor potential. Most recently, Zheng and col- promised by various damaging agents, and have many
leagues tentatively identified a protein they called unique characteristics that distinguish them from hair
prestin as the motor protein of the OHC.90 The cells in other mechanoreceptor systems.
detailed follow-up studies of these investigators fur- It seems clear that the OHCs and IHCs are
ther support the proposition that this membrane functionally different, but our concept of the nature
protein is the motor molecule responsible for the of this difference is changing. The classic view that
electromotility of OHCs.91 the relatively insensitive IHC system carries the fre-
quency place code, whereas the OHCs comprise a
INNER VERSUS OUTER HAIR CELL FUNCTION. Figure 4–24 sensitive low-level detector system that has poor
illustrates the salient characteristics of IHC and OHC place-coding ability, has been abandoned in favor of
anatomy, and Figures 4–25 and 4–26 illustrate their more recent notions based on the active biomechan-
afferent and efferent innervation, respectively. There ical functioning of the organ of Corti. That the
are many differences between IHCs and OHCs in OHCs possess effector abilities supports the pro-
88 Ballenger’s Otorhinolaryngology
A B Microvilli C
Stereocilia Stereocilia
Stereocilia Basal Body
Basal Body
Nucleus
Cuticular
Plate Afferent
Efferent Nerves
Mitochondria Terminals (OCB)
Afferent
Nerves
FIGURE 4–24. Schematic drawing of cochlear hair cells. A, The common structures on the apical portion of acousti-
colateral hair cells include rows of stereocilia that are graded in height and joined by cross-links. The tip links may be
involved in transduction by opening the transducer channels. The kinocilium is not present in the mature cochlea,
although it is present in vestibular hair cells. B and C, Inner hair cells are shaped like a flask (B), and outer hair cells
are shaped like a cylinder (C). OCB = olivocochlear bundle. Reproduced with permission from Pickles JO. An intro-
duction to the physiology of hearing. 2nd ed. New York: Academic Press; 1988.
posal of Kim that these receptors are bidirectional rated on this notion by postulating the existence of
transducers that are capable of converting acoustic two distinct but parallel cochlear subsystems that
energy into neural energy (ie, mechanoelectrical use OHCs as the modulators and IHCs as the carri-
transduction) and electrical into mechanical energy ers of auditory information.93 Table 4–1 presents a
(ie, electromechanical transduction).93 Kim elabo- summary of a comparison of the two subsystems.
FIGURE 4–25. Diagram of the cochlea’s afferent innervation pattern. The view is through Reissner’s membrane, look-
ing down on the organ of Corti. Principal fiber bundles are 1 and 2, intraganglionic spiral bundles (fibers labeled “1”
are efferent olivocochlear fibers); 2a and 3a = internal spiral fibers; 4 = external spiral fibers, traveling in radial bun-
dle to innervate outer hair cells (OHCs); 5 and 6 = radial fibers, innervating inner hair cells (IHCs). The “V” shape of
cilia pattern on the OHCs and the shallower “U” pattern on the IHCs are shown in the upper corners of the diagram.
Reproduced with permission from Wever EG.94
Physiology of the Auditory and Vestibular Systems 89
FIGURE 4–26. The descending auditory system. A, Origination in the brainstem, distribution, and termination within
the cochlea of the olivocochlear bundle efferent fibers of the cat. B, Organization of the lateral and medial olivo-
cochlear (OC) systems. Lateral OC neurons project to the region beneath the inner hair cells, where they form axo-
dendritic contacts on the dendrites of type I spiral ganglion cells. Medial OC neurons project to the region beneath
the outer hair cells and synapse directly with them. A reproduced with permission from Warr WB et al.95 B reproduced
with permission from Spangler KM and Warr WB.96
There is good evidence that the vulnerable filter trapezoid acoustic stimulus elicits from a auditory
sharpening described previously involves some kind nerve fiber a spike train with a complex time course,
of interaction between the IHCs and OHCs includ- suggesting combined IHC and OHC influences,
ing the following: (1) selective damage to OHCs whereas selective damage to OHCs by kanamycin
causes detuning of neural tuning curves (Figure treatment simplifies the trapezoidal response pattern
4–27),97 which presumably are from IHC fibers; (2) in a way compatible with isolated IHC influence.38
crossed OCB stimulation, which presumably affects The precise mechanism by which OHCs influ-
only OHCs (see below), strongly depresses the audi- ence the response of IHCs is unknown at this time.
tory nerve’s click-evoked, whole-nerve, or compound However, because the physiologically vulnerable
action potential (CAP), which apparently originates cochlear filter-sharpening process appears to involve
entirely from IHC fibers; (3) crossed OCB stimula- basilar membrane vibrations, the mechanism
tion also reduces the amplitude of the receptor requires that the OHCs directly influence the
potential recorded intracellularly from IHCs98; (4) mechanical vibration of the basilar membrane. A
crossed OCB stimulation as well reduces the firing corollary to this conclusion is that the OAEs
rate and synchronization index99 and shifts the recorded from the human ear canal reflect OHC
dynamic range of auditory nerve fibers100; and (5) a function. Indeed, one intensely studied subfield of
90 Ballenger’s Otorhinolaryngology
IHCs = inner hair cells; OHCs = outer hair cells; LSO = lateral superior olive; MSO = medial superior olive.
OAE research is focused on using emitted responses emission that can be recorded noninvasively have
to evaluate the normality of central auditory pro- some important implications for our understanding
cessing based on the influence of the descending of pathophysiologic processes in the cochlea. First,
efferent system on OHC-generated activity.101,102 although it is unlikely that the majority of cases
exhibiting severe tinnitus are related to spontaneous
CLINICAL CONSEQUENCES. The existence of a vulnera- OAEs, emissions may elucidate the mechanism of at
ble cochlear filtering process and a related cochlear least some kinds of tinnitus.103 Moreover, by separat-
ing the sensory from the neural aspects of ear dys-
function, OAEs may reveal the critical underlying
causes of some common but puzzling otologic dis-
eases such as Meniere’s disease104 and sudden idio-
pathic sensorineural hearing loss.105 Second, as
shown in Figure 4–28, detuning of the neural
response in cochlear pathologic conditions may also
explain recruitment.106 As previously described,
detuning caused by cochlear pathology eliminates the
low-threshold, sharply tuned tip region of the tuning
curve but preserves the high-threshold tail region.
Elimination of the tip region raises threshold, but
preservation of the tail region preserves neural
responsiveness at high intensities. Thus, the loudness
function (bottom right plot) is made abnormally
steep because threshold is elevated. However, at high
intensities, loudness is normal because a normal
number of neurons are responding.
FIGURE 4–28. Possible explanation of recruitment (elevated threshold and abnormal growth of loudness) based on
detuning with pathology. Solid diagrams at bottom depict increase in number of active auditory nerve fibers as tone
level is increased in normal (left) and abnormal (right) ears. The tone’s frequency (T) is indicated by the dashed line
in the upper diagram. Because the effect of disease is to remove the sharply tuned “tips” but leave the broadly tuned
“tails” relatively unaffected, the threshold of the pathologic cochlea is increased. However, as tone level is increased into
the normal tail regions, the number of active fibers responding becomes normal; hence, loudness grows abnormally
rapidly from the elevated threshold. Reproduced with permission from Evans EF.107
progressively better as frequency is lowered. Analyz- studies of Sachs and Young on the representation of
ing the spike discharges of single auditory nerve speech sounds in hundreds of auditory nerve fibers
fibers to low-frequency stimulation demonstrated have demonstrated that the temporal pattern of fiber
“phase-locking” to the individual cycles of the elicit- discharges in the form of phase-locking provides
ing tone that preserves the temporal firing pattern.108 considerable information about the frequency con-
Compiling large numbers of single-unit spikes into tent of the stimulus at all levels of stimulation.111
spike discharge histograms showed an impressive These population measures of temporal synchrony
ability of single auditory unit discharges to repro- were based on Fourier transforms of period his-
duce the waveform of the stimulating sound. The tograms from fibers with CFs near each frequency
upper limit of this phenomenon is generally esti- component of the sound. Such measures were com-
mated at about 4 kHz, but critical inspection of bined to provide discharge rate profiles for groups of
quantitative single-unit data suggests that phase- active nerve fibers. Because information concerning
locking becomes poor at around 2.5 kHz.109 rate, timing, and place is represented in these meas-
Another line of evidence supporting the ures, these spectra provide details concerning tem-
importance of the encoding of phase or timing poral fine structure from a localized cochlear region
information comes from the outcome of studies of and thus represent a type of temporal place code.
the responses of auditory nerve fibers to speech
sounds. The work of Kiang addressed the limitations “TELEPHONE PLACE” THEORY OF FREQUENCY CODING.
of fiber discharge rate place encoding in neurally One shortcoming of the telephone theory became
representing the frequency components in speech apparent when neural refractoriness was discovered.
signals, especially those of moderate to high intensi- This process imposed a physical limitation on nerve
ties.110 More recently, the single-unit population fiber firing at the very short time intervals associated
Physiology of the Auditory and Vestibular Systems 93
with high-frequency stimuli. Thus, to reconcile in part INTENSITY CODING Loudness is the approximate
the effects of neural refractoriness on the telephone subjective correlate of the physical dimension of
theory, Wever published an auditory frequency cod- sound intensity. It is generally assumed that the neu-
ing theory, which he termed the volley theory, but ral correlate of loudness is the amount of nervous
which has since become known as the “telephone activity, with the amount factor meaning the total
place” or “frequency place” theory.94 Wever advanced number of action potentials delivered by a popula-
an interesting evolutionary argument in support of tion of nerve fibers over a given time period. Thus,
the telephone place code theory. Primitive ears (as loudness is encoded as a combination of the number
found in fish, amphibians, and lower reptiles) are tele- of fibers firing and the rate at which they are firing.
phone coders that cannot analyze high frequencies Figure 4–29 compares plots of stimulus level
because of the inherent limitation of the rate at which versus single auditory nerve fiber firing rates (left)
nerve fibers can respond. Therefore, as evolution pro- and stimulus level versus subjective loudness
gressed, place coding had to be added to allow analy- (right). The agreement in the general shapes of the
sis of high frequencies, which are important in sound curves supports the view that the amount of audi-
localization and directionality. tory nerve firing encodes loudness. On closer
Our use of sounds in communication is greatly scrutiny, however, it is apparent that firing rate
aided by our keen sensitivity to the frequency region changes only over a 20 dB sound intensity range,
between 1 to 4 kHz, and although our sensitivity whereas loudness varies over a 100 dB range. This
falls off beyond 4 kHz, we still depend on the higher limited dynamic range is a general property of all
frequencies for many of our discriminations of con- primary auditory neurons.112
sonants and sharp transients. The appearance and The obvious way to solve this loudness encod-
elaboration of the place principle for frequency rep- ing problem is to assume that additional nerve fibers
resentation, therefore, was a major event in the evo- are “recruited” as stimulus level is increased. This
lution of the ear.94 process would increase the total number of dis-
FIGURE 4–29. Effects of sound intensity on subjective loudness (right) and auditory nerve fiber firing rate (left). The
shapes of the curves are similar, but the dynamic range of the single auditory nerve fiber is much narrower than that
of the auditory system as a whole. Above the auditory nerve firing rate curve (B) are single-fiber responses to sounds
of progressively increasing levels (A). Subjective loudness curve from Gulick (1971) noted in the legend for Figure 4–21.
Auditory nerve curve reprinted with permission from Katsuki Y, Sumi T, Uchiyama H, Watanabe T. Electric responses
of auditory neurons in cat to sound stimulation. J Neurophysiol 1958;21:569.
94 Ballenger’s Otorhinolaryngology
charges per unit time by increasing the number of tem include the middle ear reflex and the olivo-
fibers firing rather than the firing rate for an indi- cochlear efferent system.
vidual fiber. However, most studies of auditory nerve Finally, Liberman classified auditory nerve
single units agree that the thresholds of the nerve fibers into three functional subclasses according to
fiber population fall within a relatively restricted spontaneous discharge rate as low-, medium-, and
stimulus range, that is, within 20 to 30 dB of behav- high-firing units.118 Whereas high spontaneous rate
ioral threshold.113 Thus, there is no possibility of (SR) fibers exhibited low thresholds and restricted
recruiting additional fibers as sound level is dynamic ranges of about 20 dB, the medium and
increased more than 60 dB above threshold. The low SR units displayed higher thresholds and
fiber recruitment hypothesis also creates problems dynamic ranges as great as 60 dB. Thus, it is possible
for frequency place coding because adding new that although fewer in number than the high SR
responding fibers as stimulus level is increased fibers, the low and medium SR fibers are available to
would quickly require the spread of activity to fibers encode the higher-intensity sounds.119
of adjacent CFs. This tradeoff between the ability to Viemeister concluded from his review of the
recruit new fibers and the ability to place code is psychophysical and physiologic literature relevant to
especially bothersome for explaining the perception intensity encoding in auditory nerve fibers that a
of complex sounds for which multiple frequencies localized rate code “seems theoretically possible and,
must be distinguished simultaneously. Thus, the at present, appears to be the best candidate for a gen-
dynamic range problem becomes apparent.114 The eral intensity code.”120 The conclusion that rate
dynamic range of auditory nerve fibers, that is, the information from a frequency-specific population of
range over which the spike rate changes as stimulus active nerve fibers provides the neural basis for a
level is altered, is too narrow to account for (at least code of stimulus intensity is consistent with the find-
in simple terms) the extent over which the human ings discussed above concerning the encoding of
ear discriminates sound levels. high-level speech sounds by a population of audi-
Several subsequent observations shed light on tory nerve fibers that possibly exhibit low to inter-
the dynamic range problem. Evans and Palmer dis- mediate spontaneous firing rates.
covered that approximately two-thirds of the cells in
the dorsal cochlear nucleus (DCN) had dynamic Efferent Auditory System ANATOMY. Rasmussen
ranges that extend to well over 100 dB and thus established the existence of a chain of descending
could easily “code” loudness over the necessary auditory neurons that links auditory cortex to hair
sound intensity range.115 However, the problem of cells and that parallels the classic afferent projection
the input pathway to these DCN cells remains to be pathway (discussed below).121 The OCB, the final
resolved. In addition, some auditory nerve units link in the descending chain, originates in the supe-
have been found that do, after all, have wide rior olivary complex (SOC).
dynamic ranges, but these are only a minority of the Figure 4–26, A, summarizes schematically the
total auditory nerve fiber population.116 Other stud- origins, course, and distribution of the OCB to one
ies have also demonstrated that relative degrees of cochlea, whereas Figure 4–26, B, analyzes the princi-
phase-locking117 of different frequency components pal relationships between the two afferent and the
in complex sounds could code the relative intensity two efferent innervations of the organ of Corti.95
levels of the frequency components. However, The OCB is divided into crossed and uncrossed
because phase-locking does not occur above 3 to 4 components. The crossed component is composed
kHz, this mechanism could not account for the primarily of relatively large myelinated fibers that
loudness coding of high frequencies. originate in large globular neurons surrounding the
Another approach to the dynamic range prob- medial region of the SOC.122 Most of the uncrossed
lem is the concept of an automatic gain control component is composed of small fibers,123 a large
operating at the input of the auditory system.114 percentage of which may be unmyelinated and
Such a control mechanism would feed back a which originate in the small fusiform neurons in the
decreased gain command signal to the input to lateral region of the SOC.122 The majority of the
maintain the cochlear output within an acceptable large crossed fibers innervate OHCs, whereas most
operating range. Possibilities for such a control sys- of the small uncrossed fibers innervate IHCs.122
Physiology of the Auditory and Vestibular Systems 95
The crossed olivocochlear fibers decussate just addition, unlike the crossed bundle, the termina-
beneath the floor of the fourth ventricle and then tions of the uncrossed bundle do not show high con-
enter the vestibular nerve. At this point, they are centrations of acetylcholinesterase,132 and curare
joined by the uncrossed fibers. The combined crossed does not block the effect of stimulating the
and uncrossed fibers travel in the vestibular nerve uncrossed bundle (although strychnine does).127
and cross into the cochlear nerve via the vestibulo- Thus, the uncrossed system may not be cholinergic.
cochlear anastomosis. Within the cochlea, efferent
fibers have been identified among the external spiral FUNCTIONAL SIGNIFICANCE The function of the
fibers (3b in Figure 4–25), the tunnel spiral fibers, olivocochlear efferent system is, at present, largely
and the internal spiral fibers.124 unknown. Several attempts to demonstrate func-
tional deficits after sectioning the crossed OCB have
PHYSIOLOGY. In cases in which olivocochlear axons failed.133 A series of more recent studies has system-
have been labeled histochemically and traced follow- atically examined the effects of electrically stimu-
ing single nerve fiber recordings, the labeled fibers lating the crossed OCB on auditory nerve fiber
terminate beneath OHCs in cochlear regions with dynamic ranges that have been compressed by
best frequencies corresponding to the CFs of the broadband noise stimulation.100 The restoration of
fiber.125 Such direct recordings from efferent axons dynamic range in the presence of background noise
within the periphery have demonstrated that these supports the notion that the cochlear efferent sys-
units possess thresholds and tuning curve properties tem may function to improve the ability to discrim-
that are essentially identical to those of primary affer- inate complex signals (ie, the signal-to-noise ratio).
ents with similar CFs.125 Although the proportion of However, the hypothesis that the olivocochlear sys-
olivocochlear neurons that can be excited by ipsilat- tem primarily provides some sort of input gating
eral and contralateral stimuli is consistent with the mechanism may not be completely correct.
predominant efferent innervation to a given cochlea, The most recent and unexpected effect of stim-
many units are binaurally responsive.126 ulating the crossed OCB is a decrease in the levels of
The effects of stimulating the crossed OCB are OAEs that are generated mechanically by the cochlea
almost certainly mediated by the release of ACh as the and recorded in the ear canal. Mountain was first to
major neurotransmitter at the OHCs,127 as noted report that electrical stimulation of the olivocochlear
above. In turn, ACh acts on ACh receptors (AChRs) efferent system directly affected the active nonlinear-
located on the OHC postsynaptic membrane to mod- ities in OHC mechanics inferred from decreases in
ulate the electrical properties of the OHCs. Elgoyhen DPOAEs.82 A number of other studies evaluating the
and associates established that ACh acts on nicotinic influence of contralateral acoustic stimulation with
AChRs (nAChRs) containing the α9 subunit, which wideband noise on OAEs recorded ipsilaterally
mediates synaptic transmission between the cholin- reported small reductions in TEOAEs101 and in 2f1-f2
ergic olivocochlear fibers and the OHCs.128 It has long DPOAEs.134 The influence of contralateral stimulation
been known that stimulating the crossed OCB in the on OAEs also supports the notion that the cochlear
floor of the fourth ventricle causes depression of the efferent system is involved in the modulation of OHC
auditory nerve’s response to sound stimulation (ie, micromechanics. These effects, along with the reduc-
the CAP) and a simultaneous increase in the ampli- tions in neural discharge rate and tuning, suggest that
tude of the CM.129 It is likely that the α9 nAChR sub- the function of the crossed OCB is to allow the cen-
unit mediates such efferent inhibition because an α9 tral auditory system to govern the mechanical prop-
knockout mouse model showed no suppression of erties of the basilar membrane by controlling the
either CAPs or DPOAEs by electrically stimulating the vulnerable cochlear tuning mechanism previously
OCB at the floor of the fourth ventricle.130 It was fur- discussed. Because detuning a frequency bandpass
ther shown that the α9 nAChR protein opens its ion system increases damping, the detuning effect of the
channel via associated Ca2+-activated K+ channels.131 crossed OCB could be useful as a method of improv-
Much less is known about the uncrossed OCB. ing auditory temporal resolution (eg, to improve
Stimulation of the uncrossed bundle decreases the speech perception). The consensus view at present is
click-evoked action potential amplitude, but the that the active transduction process135 is regulated in
effect is much less than for the crossed bundle.99 In some way through efferent innervation of the
96 Ballenger’s Otorhinolaryngology
OHCs.89 Also, as noted above, the olivocochlear effer- Anatomy Figure 4–30 diagrams the direct audi-
ent system may also contribute toward extending the tory projection pathway. The numbers in each
dynamic range of the auditory system.136 nucleus indicate neuronal order (determined by the
In addition, other experimental results suggest number of synapses). The auditory projection path-
that the olivocochlear system may help protect way is more complex than the pathways of other
against acoustic trauma.136 In this work, it was dis- sensory systems, possibly because it developed rela-
covered that the amount of threshold shift induced tively late on the phylogenetic scale and had to
by overstimulation of one ear could be reduced by incorporate pieces of other already developed neu-
the presentation of a simultaneous tone to the con- ronal systems. Although the basic wiring diagram
tralateral ear, thus inferring that activating the effer- depicted in Figure 4–30 has remained relatively
ent system reduced the effects of overexposure. One unchanged for many years, it should be emphasized
intriguing line of current research on the traumatic that within the last 25 years, a number of advances
effects of noise exposure is the notion of “training” have been made in the development of methods for
the cochlea to become less susceptible to damaging describing neuronal connectivity.144 These break-
sounds.138,139 One common protocol to induce the throughs have relied on the discovery that, when
training (or conditioning or toughening) effect is to certain amino acids, conjugated enzymes (eg, horse-
apply daily, moderate-level sound exposures to radish peroxidase–conjugated lectin from soy bean),
reduce injury from a subsequent high-level noise sugars, or immunocytochemicals (eg, polyclonal or
exposure.140 Although the underlying mechanism(s) monoclonal antibodies) are injected into a neuronal
responsible for the trained protective effect is, at or fluid (eg, cochlear duct) region of interest, they will
present, unknown, the most likely site is the crossed be taken up by the cells or nerve fiber endings in this
cochlear efferent system.141,142 Indeed, LePage region and transported by the normal cellular process
demonstrated that loud sound induces a mechanical of axonal transport in both retrograde and antero-
baseline shift in the position of the cochlear parti- grade directions. Other techniques make use of such
tion.143 It is highly probable that such a gain control
system is effected by cochlear efferents.
Superior Temporal
(Heschl’s) Gyrus
CENTRAL AUDITORY PATHWAY CORTEX
labels as lipophilic dyes (eg, dilinoleyl-tetramethylin- sion of best frequencies. Thus, as in the direct pro-
docarbocyanine or Dil), which can be retrogradely jection pathways of all sensory systems, multiple
transported in fixed tissue by diffusion. representation of the receptor surface occurs. It is
Visualization of the location of cellular projec- likely that nerve fiber branching in the various
tions or the cellular/subcellular location of labeled nuclei, as described for the CN, is the anatomic basis
substances at the light and electron microscope lev- of this multiple-frequency representation.147
els is achieved either by autoradiography, in the case All auditory nerve fibers display relatively uni-
of radioactive compounds, or by catalyzation of his- form response characteristics to pure-tone stimuli
tochemical reactions, which are typically viewed compared to the activity of CN cells when catego-
under epifluorescence or darkfield optics. With rized by the use of a poststimulus time histogram
recent refinement of these tract-tracing and cell (PSTH).113 The PSTH plots the number of nerve dis-
component–labeling techniques using immunohis- charges that occur in small time bins within the
tochemical markers, virtually all projection path- period that begins slightly before and extends
ways and cell types of the auditory system have been throughout the duration of the stimulus. Poststimu-
described. Lagging far behind our description of the lus time histograms are shown for an auditory nerve
connections of the neural pathway for hearing is our fiber and various CN cells in Figure 4–31. The CN
understanding of how this network of interconnec- consists of at least nine different cell types described
tions interacts to produce our complex auditory sen- for their anatomic characteristics revealed by various
sations. Presented below is a brief description of the staining techniques.148 It can be seen from the unit
major projections of the auditory pathway sufficient activity patterns of Figure 4–31 that the uniform
for the clinician to understand the transfer of infor- response characteristics of auditory nerve fibers are
mation within the auditory system, without consid- soon elaborated on by the various cells of the CN to
eration of the many lesser connections revealed by produce a variety of response types named after the
modern immunocytochemical staining techniques. patterns seen in the PSTH.149 When examined in the
The reader is referred to several comprehensive frequency intensity domain, some CN cells exhibit
reviews that provide more details of the intricate complex response patterns that describe regions of
interconnections of the central auditory system.96,145 excitation and inhibition produced by a pure-tone
stimulus. An example of such complex response pat-
COCHLEAR NUCLEUS. Central processing of the infor- terns by cells in the CN is shown in Figure 4–32.149
mation carried in the auditory nerve begins in the Three fiber pathways project information
cochlear nucleus (CN), the first obligatory synapse from the CN to higher brainstem centers. These
for all nerve fibers. On entering the CN, the auditory fiber tracts include the ventral (trapezoid body),
portion of the eighth nerve bifurcates into two intermediate, and dorsal acoustic striae. The ventral
branches, one that sends fibers to synapse in the acoustic stria, originating from AVCN and PVCN
anteroventral cochlear nucleus (AVCN) and one that regions, projects ventrally and medially to send fibers
synapses in the posteroventral cochlear nucleus ipsilaterally to the lateral superior olive (LSO) and
(PVCN) and DCN. The distribution of fibers within the medial superior olive (MSO) and then to the
the CN is not random but follows an orderly pattern medial nucleus of the trapezoid body (MTB). The
of tonotopic projection throughout the nucleus, fibers then cross the midline to terminate on the con-
with low-frequency fibers projecting ventrally and tralateral MSO and MTB but do not innervate the
high-frequency fibers distributed dorsally. Thus, LSO on the opposite side. Thus, for any one ear, con-
both neurophysiologic and anatomic observations nections are bilateral only to the MSO and MTB.150
show that cochlear place is represented in an orderly The intermediate acoustic stria, the primary
manner throughout the projection pathways of the output of the PVCN, sends some fibers ipsilaterally
central auditory system.146 The security of tonotopic to a group of cells around the SOC called the perio-
organization is also apparent in the multiple repre- livary nucleus (PON), whereas other fibers ascend in
sentation of the stimulus frequency domain. For the lateral lemniscus (LL). This pathway also crosses
example, typically, along any one penetration of a the midline to innervate the same structures on the
microelectrode trajectory within a principal nucleus, contralateral side. Fibers of the intermediate acoustic
there are two or more breaks in the orderly progres- stria that enter the LL synapse within the nucleus.
98 Ballenger’s Otorhinolaryngology
Frequency
Physiology of the Auditory and Vestibular Systems 99
level in the auditory system at which binaural pro- sive only to specific parameters of complex speech
cessing takes place.151 However, at all levels in the sounds. In general, it has been extremely difficult to
auditory projection pathway above the trapezoid attribute specific feature extraction capabilities to
body, there are units that are sensitive to binaural neurons in the higher auditory nuclei that cannot
time and level differences.152,153 be explained by complex responses already present
at the level of the CN.
LATERAL LEMNISCUS. The LL is the major ascending
projection from the CN and SOC to the IC and con- AUDITORY CORTEX. The auditory cortex has been
tains both contralateral and ipsilateral fibers from most extensively studied in the cat and can be
lower auditory brainstem structures. Although there divided into three areas based on similarity of Nissl-
are three distinct nuclei within the LL, historical stained cytoarchitectural details.158 These include a
emphasis has been simply on its function as a con- primary area AI, a secondary area AII, and a remote
nection between the SOC and IC. Recently, these projection region Ep. In human and nonhuman pri-
nuclei have received more attention in attempts to mates, the primary auditory projection area is
define their role in auditory processing.154 located in the temporal lobe but hidden by the syl-
vian fissure. The ventral division of the MG projects
INFERIOR COLLICULUS. The IC receives synapses from almost entirely to AI,159 which can be considered the
the majority, if not all, of the fibers projecting from primary auditory cortex. Surrounding auditory areas
the lower auditory nuclei. The three neuronal areas receive projections from all divisions of the MG. Like
that make up the IC are the central, external, and the auditory relay nuclei, the auditory cortex is also
pericentral nuclei. The predominant termination tonotopically organized. As might be expected by the
zone for the ascending auditory projections is in the many intricate interconnections of the auditory sys-
ventrolateral region of the central nucleus. This tem prior to input arriving at the cortex, the under-
region receives inputs from the SOC and a heavy standing of cortical processing has been a complex
contralateral input from the DCN. Other major pro- and difficult task. One approach to solving the prob-
jections come ipsilaterally from the MSO and bilat- lem of cortical function has been the use of ablation
erally from the LSO. The function of the IC is far studies in which the auditory cortex is removed after
from completely understood, with many neurons training an animal to perform a specific auditory
exhibiting complex excitatory/inhibitory interac- task. These studies have demonstrated that cortical
tions. A simple view is that the IC integrates the ablation does not result in a complete loss of func-
frequency analysis features of the DCN with the tion as do similar lesions in the visual system. In fact,
localization abilities of the SOC.150 for many simple tasks, no long-term deficits can be
detected.157 Based on these results, it is reasonable to
MEDIAL GENICULATE. The medial geniculate (MG) is assume that the auditory cortex is involved in
the thalamic relay nucleus for auditory informa- numerous details of more complex auditory pro-
tion. All auditory projections from the IC to the cessing. Consequently, it is unlikely that one simple
auditory cortex pass through the MG. This nucleus unifying concept will be uncovered that describes
is also composed of three divisions, the ventral, the functional role of the auditory cortex.
dorsal, and medial nuclei.155 The ventral nucleus
receives heavy ipsilateral projections from the ven- Summary Although there have been many studies
trolateral portion of the central nucleus of the IC. of single-unit activity in the auditory nuclei over the
This portion of the MG projects to the AI, AII, and past 50 years, they have thus far yielded few unifying
Ep regions of the auditory cortex (see below). principles about the data-processing mechanisms of
Again, a wide variety of single-unit response types the auditory nervous system. However, a number of
have been recorded in the MG. In attempting to recent studies suggest that, in many instances, the
understand the MG’s role in auditory processing, brain makes use of patterns of activity distributed
special efforts have been made to examine MG sin- over many cells to extract relevant information.147
gle-unit responses to complex sounds. Thus, David Consequently, if future studies focus on describing
and associates156 and Keidel157 demonstrated that the responses of individual cells without viewing
MG neurons in the unanesthetized cat were respon- their participation, as a whole, in some functional
100 Ballenger’s Otorhinolaryngology
unit, they may be doomed to result in failure as a potentials have been termed electrocochleography
means of understanding central auditory processing. (ECochG). The second class of auditory evoked
potentials is recorded between one electrode located
AUDITORY-EVOKED ELECTROPHYSIOLOGIC on the vertex and another near the external ear (eg,
either on the mastoid or earlobe). This latter class of
RESPONSES evoked potentials has been subdivided convention-
Modern averaging techniques have made it possible ally according to their onset latency range into early,
to record from humans, with surface electrodes, middle, and late responses.
electrical responses reflecting the entire auditory
pathway, from cochlea to cortex.160,161 Clinical appli- Electrocochleographic Responses: Whole-Nerve
cations of this technique have expanded rapidly and Compound Action Potential, Cochlear Micro-
are routine in most otolaryngology clinics today. In phonic, Summating Potential DESCRIPTION OF
this section, some basic physiologic principles are THE RESPONSES. Figure 4–33 shows a typical example
discussed on which the clinical applications of audi- of cochlear and auditory nerve click-evoked poten-
tory evoked potentials are based. tials recorded from the ear canal. Evoked responses
Two major classes of human auditory evoked to clicks of opposite polarity are shown in Figure
potentials generated by acoustic transients (clicks) 4–33, A. The whole-nerve CAP has two or more ear
are used clinically. One class is recorded with an elec- canal negative peaks designated N1, N2, N3 (N2 and
trode located as close to the cochlea as possible, that N3 not labeled here), and so forth. Each peak lasts
is, either extratympanic (eg, located on the external about 1 ms and, in normal ears, N1 is always the
ear canal skin) or transtympanic (eg, penetrating the larger peak. In Figure 4–33, B, the CM appears as a
eardrum to rest on the medial wall of the middle series of sinusoidal oscillations, typically about 3
ear).162 Tests based on this class of auditory evoked kHz, on the leading edge of the N1 peak. The SP in
N1
A
R and C
0.5 µV
0 MSec 5
AP
B C
R–C R+C
CM 0.25 µV SP 0.5 µV
0 Ms 5 0 Ms 5
FIGURE 4–33. Examples of cochlear and auditory nerve electrical responses to clicks recorded from the human outer
ear canal. The cochlear potentials are the cochlear microphonic (CM) and summating potential (SP). A, The whole-
nerve compound action potential typically has a large negative peak (N1). R and C are shown as separate condensa-
tion (dashed line) and rarefaction (solid line) rectangular-pulse click responses recorded from the outer ear canal with
a nasion “reference” electrode. B, R – C is the waveform produced by subtracting C from R responses. C, R + C is the
waveform produced by adding C and R responses. Upward deflections represent negativity at the ear canal, and time
scale zeroes are set at the leading edge of the rectangular pulse driving the earspeaker. Click rate was 8/s; click level was
115 dB peak equivalent SPL. Each C and R response was the average of 1,000 single sweeps.
Physiology of the Auditory and Vestibular Systems 101
Figure 4–33, C, appears as an ear canal negative quency (basal) fibers contribute more effectively to
hump on the leading edge of the N1 peak, with the the whole-nerve CAP and also to the evoked audi-
CM oscillations superimposed. tory brainstem response (ABR) than do low-fre-
The auditory nerve CAP (see Figure 4–33, A) is quency fibers.
the sum of the synchronous firing of single-fiber This principle leads to several important con-
auditory nerve fibers as seen by the distant recording clusions for clinical applications: (1) broadband-
electrode as illustrated in Figure 4–34.163 The single- click evoked CAPs preferentially reflect high-
unit spikes are triggered by the passage of the frequency fiber activity, and, as a corollary, high-fre-
cochlear traveling wave. Thus, spikes from basal quency clicks are more effective generators of audi-
(high-frequency) fibers appear at the recording elec- tory evoked potentials than low-frequency clicks164;
trode earlier than spikes from apical (low-frequency) (2) high-frequency hearing loss caused by selective
fibers. Because the degree to which single neural unit removal of basal units tends to bias the broadband
responses contribute to the evoked potential is click-evoked CAP and ABR toward more apical
determined largely by their synchrony, high-fre- units. Therefore, high-frequency cochlear deficits
prolong N1 peak latencies164; and (3) a low-frequency
deficit does not cause a corresponding basalward
Cochlea Auditory shift because of the already existing heavy bias
Nerve
Apex toward basal units in the normal response. There-
fore, low-frequency cochlear deficits have no appar-
ent effect on CAP and ABR latencies. Because the
CM response follows the waveform of basilar mem-
brane vibration, it reverses polarity when click
polarity is reversed, whereas the envelope-following
SP does not. The neural response also maintains the
same polarity. Thus, adding together responses to
Base opposite-polarity clicks cancels out the polarity-
Velocity
reversing CM and allows a better view of the SP (see
ECochG Time Figure 4–33, C). In contrast, subtracting the con-
Electrode densation and rarefaction responses preserves the
CM, while canceling the SP and most of the CAP
Unit APs as “seen” by (see Figure 4–33, B).
ECochG Electrode The cochlear receptor potentials (CM, SP) can
(amplitude greatly
exaggerated) also be separated from the CAP because receptor
potentials are nonrefractory and do not adapt,
whereas neural responses do. Thus, masking and
increasing click rate are often used in clinical testing
Whole-Nerve AP to depress selectively the neural response while pre-
(sum of unit APs) serving the CM and SP.
Reliable methods for separation of the SP from
the other cochlear potentials have made this
FIGURE 4–34. Summation of the single-unit spikes response useful in the diagnosis of Meniere’s dis-
(amplitude exaggerated) picked up by a distant electro- ease.165 A number of studies have demonstrated that
cochleographic (ECochG) electrode to form the whole- the SP is enlarged in a certain percentage of patients
nerve compound action potential (CAP). Note that the with Meniere’s disease.166 Evidence supporting the
highly synchronized spikes from the basal end of the notion that SP enlargement is specifically related to
cochlea sum more effectively than the poorly synchronized endolymphatic hydrops is provided by observations
spikes from the apical end of the cochlea. The records of that manipulations expected to reduce fluid accu-
unit action potentials (APs) and the whole-nerve CAP at mulation within the endolymphatic space (eg,
the bottom are from a simplified computer experiment. administration of hyperosmotic agents such as glyc-
Reproduced with permission from Elberling C.163 erol) often shrink abnormally enlarged SPs.167
102 Ballenger’s Otorhinolaryngology
Vertex-Recorded Auditory Evoked Potentials to an electrode on the mastoid). Note the differences
Description of the Responses Figure 4–35 shows in the time and voltage scales. The early response,
examples of early (A), middle (B), and late (C) ver- commonly termed the ABR, is the smallest and also
tex-recorded auditory evoked potentials generated is the most recently discovered.
by broadband clicks. Commonly used peak designa-
tions are also shown. In all traces, upward deflection AUDITORY BRAINSTEM RESPONSE. An example of an
represents negative voltage at the vertex (“referred” ABR is shown in Figure 4–35, A, in which the peaks
of this response are labeled with Roman numerals I
to VII. It can be seen that the ABR occurs approxi-
mately between 1 and 8 ms after stimulus onset.
A
Wave V is typically the largest and most robust of
VII the potentials, and waves beyond V are seldom used
I II clinically. Studies in humans168 and animals169 sug-
VI
gest that wave V is generated at the LL. Thus, the
0.2 µV ABR is probably not useful in detecting abnormali-
III
ties at or above the level of the IC.170 However, for
IV V
12.5 ms the lower brainstem, the ABR is one of the best audi-
B ologic tests for detecting dysfunction.
Nb The ABR is one of the most frequently used
Na auditory evoked potential procedures because the
No variables that affect this response have been well
described and it provides a good measure of
cochlear sensitivity and retrocochlear status. Clini-
Po
0.4 µV cally, the response can be interpreted by quantitative
Pa measures of peak latencies, interpeak intervals, and
50 ms interpeak latency differences. In addition, the pres-
C ence or absence of the various waves is noted as well
N1
N2 as waveform morphology.171
frequencies including low frequencies below 1,000 highly similar to those used to obtain the traditional
Hz and, consequently, offers a complementary index evoked responses already described. The primary
of high- and low-frequency hearing.175 The MLR can difference is that brain mapping simultaneously
also be useful in assessment of central auditory sys- records the electrical activity from an array of scalp
tem disorders, neurologic evaluation, and, most electrodes. Although this mass of data could be
recently, as a tool for cochlear implant assessment.176 viewed as many evoked potentials, the human
The most significant disadvantage of MLR is that observer cannot readily interpret such a massive
subject variables such as sleep state or sedation can amount of data. Therefore, brain mapping was
severely reduce the amplitude of this potential. Thus, developed using computer-processing techniques to
behavioral state must be controlled for to obtain provide a visual display of the potential fields among
meaningful results. all of the electrodes simultaneously. This method
reduces the data into a multicolored or shaded plot
LATE AUDITORY EVOKED RESPONSE. The relatively in which intense activity is usually given the most
high-amplitude late auditory evoked response brilliant color or the darkest shading. An example of
(LAER), labeled P1, N1, and so forth (also called the the typical electrode placements and the derivation
vertex potential), occurs between 50 and 250 ms of a simple brain map are shown in Figure 4–36.
after the stimulus (Figure 4–35, C). It is a cortical With this type of visual output, patterns of activity
response, but its long latency suggests that the LAER in normal patients can be established and abnor-
is not generated within the primary auditory cortex malities easily visualized in pathologic cases. Com-
but rather that it originates in the associative cor- puter techniques also allow the clinician to view the
tex.161 These potentials are often very dependent on patterns of activity throughout the duration of the
the subject’s state of alertness and consequently have stimulus to produce a motion picture of the evoked
received little use in clinical situations. electrical activity that occurred over time. This
method allows for the visualization of the spa-
Auditory Brain Mapping One technique that is tiotemporal patterns of brain activity. Because the
receiving considerable attention as a new and poten- data are stored in the computer, a number of
tially powerful diagnostic tool is the use of auditory advanced mathematical processing methods, which
brain mapping. Methods for this procedure are permit further refinement of the data, can be applied
Magnetoencephalography Magnetoencephalog-
raphy (MEG) involves the completely noninvasive
recording of weak cerebral magnetic fields, which
represent about one part in 109 of the earth’s geo-
magnetic field, outside the head.179 The neuromag-
netic technique was made possible by the invention
of SQUID (superconducting quantum inter-
A B
FIGURE 4–38. Averaged magnetic
responses from the auditory cortex.
A, Averaged magnetic response (n =
120) to “hei” words (solid lines) and
noise bursts (dashed lines) from the
right hemisphere in one subject; the
upper curves are from an anterior
and the lower ones from a posterior
measurement location near the ends
of the sylvian fissure. The passband
was 0.05 to 70 Hz. B, Effect of
increasing the duration of “h” in
another subject. Reproduced with
permission from Hari R et al.180
Physiology of the Auditory and Vestibular Systems 105
the right hemisphere (ie, along the superior surface diagnostic indicator of various ear diseases including
of the temporal lobe) are shown for one subject for a Meniere’s disease104 and acoustic neurinoma.185 In
spoken word (solid line) and noise bursts (dashed addition, Kemp and Ryan have also established the
lines) on the left side of Figure 4–38. The right side of use of the click-evoked OAE as a method of screen-
Figure 4–38 illustrates the effects of increasing the ing for hearing dysfunction in newborns.186
duration of the onset of the word in another subject. Because of the frequency specificity of the elic-
It is clear that sound evokes a complex magnetic iting pure tones, DPOAEs (see Figure 4–23) also
waveform, which lasts several hundred milliseconds have a beneficial clinical applicability. This stimulus-
after stimulus onset. Interesting and clinically useful related frequency specificity permits DPOAEs to be
data have been obtained about the perception of measured after averaging the responses to only a few
speech of deaf patients with cochlear prostheses by stimuli. Thus, under computer control, the fine res-
examining the activity of their auditory cortices with olution of DPOAEs in both the stimulus frequency
MEG.180 Information of this real-time sort implies and level domains permits the precise determination
that neuromagnetic recording may be used to assess of the boundary between normal and abnormal
functional disorders in more detail than what is pos- OHC function. Data from our laboratory illustrate
sible by other clinical evidence; thus, it is likely to this feature of DPOAEs in the plots of Figure 4–39,
become an important diagnostic tool of the future. A,187 which show the development of ototoxicity
during a course of antineoplasm therapy with cis-
Neuroimaging The beginning of in vivo imaging platin. Comparing the OAE findings with behavioral
in awake and behaving subjects has revolutionized hearing (top), note the abrupt change in hearing and
the ability to relate structure to function, particularly emission activity between 2 and 3 kHz (open cir-
in the human brain. For example, three-dimensional cles), which accurately followed the 40 dB loss in
magnetic resonance imaging (MRI) provides detailed hearing sensitivity produced by the ototoxic agent.
static images of the in vivo brain, with spatial resolu- Based on their ability to distinguish between
tion on the order of cubic millimeters. Other func- the relative contribution that sensory and neural
tionally related techniques in neuroimaging such as components of the cochlea make to a hearing loss,
positron emission tomography and functional MRI OAEs promise to facilitate identification of the
provide excellent spatial and temporal resolutions for anatomic substrate of complex ear diseases. For
recording changes in regional blood flow and cellular example, the records shown in Figure 4–39, B, repre-
metabolism during auditory stimulation. These tech- sent a typical pattern of audiometric loss in early
niques have been used to study a number of central Meniere’s disease, which is accompanied by thresh-
auditory processes, including speech perception,181,182 olds that are > 40 dB HL and, not unexpectedly, no
revealing tinnitus-related abnormalities in brain TEOAEs (bottom left) and abnormally low-level
function.183,184 Although these individual functional DPOAEs (solid circles). Together, these results imply
imaging approaches still have some limitations, the that the OHC system is involved in this patient’s dis-
results are converging to improve our understanding ease. However, other patients with Meniere’s disease,
of the neural processes underlying both normal and who show a similar hearing loss, can demonstrate
pathologic auditory function. rather robust DPOAEs, even for test frequencies for
which behavioral thresholds are > 50 dB HL.188 Such
Evoked Otoacoustic Emissions One of the princi- differential findings for patients with Meniere’s dis-
pal benefits of OAEs with respect to clinical testing is ease suggest that OAEs can distinguish between dis-
that they provide an objective and noninvasive meas- ease states that involve either OHCs (see Figure 4–39,
ure of cochlear activity, which is completely inde- B) or other cochlear processes that are probably neu-
pendent of retrocochlear activity. In particular, OAEs ral in origin (eg, degeneration of the unmyelinated
measure the functional responses of OHCs that are dendritic endings of the cochlear nerve). A compara-
uniquely sensitive to agents that damage hearing. ble example of this feature of OAE testing to con-
Kemp,80 the pioneer investigator into the basic fea- tribute toward differentiating between cochlear
tures of OAEs, has also been instrumental in estab- versus noncochlear involvement in hearing disease is
lishing one class of evoked emissions, the click-based illustrated in Figure 4–40 for two patients diagnosed
TEOAE (see Figure 4–22, C), as a potentially useful with acoustic neurinomas. The patient in Figure
106 Ballenger’s Otorhinolaryngology
FIGURE 4–39. Conventional audiograms (top), distortion-product otoacoustic emission (DPOAE) frequency/level or
DP-gram functions (middle) relating emission magnitude to stimulus frequency, in 0.1 octave steps from 0.8 to 8 kHz,
for primary tone levels of 75 dB SPL, and click-evoked transient evoked otoacoustic emissions (OAEs) (bottom) elicited
by the “default” mode of the ILO88 Otodynamic Analyser. A, Behavioral hearing and evoked OAE findings for the right
ear of an 8-year-old girl comparing pre- (solid circles) versus post-treatment (open circles) responses following a course
of antineoplasm therapy with cisplatin. Immittance and speech testing results were normal for the baseline session and
were not tested during the post-treatment examination. B, Audiometric and OAE results for the left ear of a 49-year-
old woman for two test sessions separated by about 2 weeks. The patient complained of a fluctuating hearing loss, tin-
nitus, aural fullness, and episodic dizziness of several months duration. Immittance findings were normal, whereas the
speech discrimination score and speech reception threshold improved from 72 to 96% and 55 to 25 dB HL, respec-
tively, at the last evaluation period (open circles). Reproduced with permission from Balkany TJ et al.187
4–40, A, displays the expected outcome for OAE test- as tumors of the cerebellopontine angle, cochlear
ing in the presence of a retrocochlear disease. That is, function can be adversely affected, probably owing to
in the presence of a moderate hearing loss on the compromise of the vascular supply to the inner ear.
tumor side (solid circles), both TEOAEs and One benefit of OAE testing illustrated in Fig-
DPOAEs are measurable. However, it is clear for the ure 4–39, B, is its sensitivity to changes in hearing
patient in Figure 4–40, B, diagnosed with a right- status, which are mediated by the OHC system. In
sided (open circles) acoustic neurinoma, that the this instance, at the time the patient returned for
tumor has modified cochlear function in a manner follow-up testing (open circles), her hearing had
that mimics the frequency configuration of the hear- improved, particularly over the low-frequency test
ing loss. Thus, in certain retrocochlear disorders such range. The 20 to 30 dB improvement in low-fre-
Physiology of the Auditory and Vestibular Systems 107
FIGURE 4–40. Audiometric and otoacoustic emission findings for two patients with acoustic neurinomas confirmed
by magnetic resonance imaging. A, A 39-year-old man with an acoustic neurinoma on the left side who had normal
tympanograms but absent reflexes bilaterally. Although speech testing was normal for the right ear (open circles), the
speech discrimination score and speech reception threshold were 0% and 70 dB HL, respectively, for the involved left
ear (solid circles). B, A 47-year-old woman with a right-sided acoustic neurinoma. Whereas her tympanograms were
normal, the only measurable acoustic reflex threshold was for ipsilateral stimuli at 1 kHz. Speech testing was normal
for the left ear, whereas the right ear was associated with a speech discrimination score of 60% and a speech reception
threshold of 35 dB HL. Reproduced with permission from Balkany TJ et al.187
quency hearing was mirrored by a similar increase TEOAEs and DPOAEs. The interested reader is
in DPOAEs and by the ability to now measure encouraged to refer to these comprehensive reviews
TEOAEs. concerning the strengths and limitations of the clini-
In addition to the clinical applications noted cal application of OAEs.194,195
above for OAEs, a number of studies have also
demonstrated the utility of using emitted responses
to understand the fundamental basis of a number of VESTIBULAR SYSTEM
cochlear lesions, including the effects of noise-
GENERAL PRINCIPLES
induced hearing loss,189 hereditary hearing impair-
ment,190 congenital hearing disorders,188 ototoxicity,191 The nonauditory part of the inner ear (termed the
bacterial meningitis,192 and presbycusis193 on both vestibular apparatus) consists of two functional sub-
108 Ballenger’s Otorhinolaryngology
divisions: (1) the semicircular ducts consisting of two tion, as in the cochlea, the receptor cells of the
vertical and one horizontal and (2) the otolithic vestibular apparatus are ciliated, and these cilia
organs consisting of the saccule and the utricle. The extend into a gelatinous matrix.
semicircular ducts respond to head rotation (ie, angu- The three semicircular canals are oriented
lar acceleration), whereas the otolithic organs are orthogonally or at right angles to each other. They
stimulated by the effects of gravity and linear acceler- can be thought of as lying in a bottom corner of a
ation of the head. The primary function of the utri- box. The horizontal (or lateral or external) canal is in
cle is to signal head position relative to gravity. the plane of the bottom of the box, and the anterior-
Ablation of the saccule produces a less significant vertical (or superior) and posterior-vertical (or pos-
deficit than ablation of the utricle; hence, the function terior) canals are in the planes of the two sides of the
of the saccule is less well defined than that of the utri- box. In humans, the entire canal complex is tilted
cle. In fact, it has been proposed that the saccule is a upward about 30 degrees. In the physiologic posi-
low-frequency auditory receptor.196 However, a series tion, the head is bent forward about 30 degrees from
of systematic studies using single-unit recordings the earth’s horizontal plane; therefore, the 30-degree
have revealed that saccular nerve fibers respond only upward tilt puts the horizontal canal in the horizon-
to linear acceleration.197–199 These findings suggest tal position under everyday conditions.202 The
that the saccular system provides the high-level verti- superior and posterior canals are oriented in vertical
cal acceleration signals required to elicit the motor planes that form an angle of approximately 45
response necessary to land optimally from a fall.200 degrees with the sagittal head plane. Each semicir-
Conventionally, the vestibular system is cular canal lies parallel to one of the canals in the
regarded as one of three sensory systems that func- opposite vestibular labyrinth. Thus, the right hori-
tion to maintain body balance and equilibrium. The zontal canal is coplanar with the left horizontal
other two are the somatosensory (chiefly proprio- canal, whereas the right superior and posterior
ceptive) and visual systems. Loss of proprioception canals are coplanar with the left posterior and supe-
(eg, as in tabes dorsalis) or vision causes more sig- rior canals, respectively.
nificant balance and equilibrium difficulty than does The sensory epithelia or cristae of the semicir-
loss of vestibular function. With bilateral vestibular cular ducts are located in enlarged areas, referred to
function loss, difficulties occur only when one of the as ampullae, at one end of each duct. The nonam-
other systems is disrupted (eg, when walking in the pullated ends of the vertically oriented superior and
dark or on a soft surface) or when balance must be posterior ducts connect to form the common crus.
maintained under particularly difficult conditions The bony vestibular aqueduct originates in the
(eg, walking on a narrow beam).201 Thus, in humans, vestibule (ie, the entrance to the inner ear) and con-
under physiologic conditions, the vestibular system nects to the cerebrospinal fluid space medially.
is probably the least important of the three balance Within the vestibular aqueduct is the fibrous
and equilibrium sensory systems. The most signifi- endolymphatic duct that establishes a route
cant functional deficits occur when the vestibular between the membranous vestibule and the cranial
system suffers acute, asymmetric damage and gener- meninges, where the duct ends in the endolym-
ates “false” head position or head rotation signals. phatic sac. The utriculosaccular duct, connecting
the utricle and saccule, permits communication
between the saccule and endolymphatic duct.
VESTIBULAR APPARATUS Although there is no agreement concerning the site
The top portion of Figure 4–2 illustrates the general of endolymph absorption, it is likely that the K+-
anatomic plan of the vestibular apparatus. There are rich fluid is absorbed in the endolymphatic sac.203
many similarities with cochlear anatomy. For exam- The ductus reuniens connects the saccule with the
ple, both end-organs are located in a tunnel that is cochlear duct.
hollowed out of the petrous portion of the temporal Figure 4–41, A, shows the anatomy of the
bone (embryologically, both organs come from the crista. It is a saddle-shaped mound of tissue,
same tunnel). The tunnel is divided into an outer attached to the ampullar wall at right angles to the
perilymph-filled bony labyrinth and an inner long axis of the ampulla. The hair cells are on the
endolymph-filled membranous labyrinth. In addi- surface of the crista. The ampullar nerve fibers travel
Physiology of the Auditory and Vestibular Systems 109
actin.32 The membrane enveloping the stereocilia is of vertical cristae, they point away from the utricle.
a thickened continuation of the hair cell cuticular Thus, vertical and horizontal cristae are morpholog-
membrane.212 The stereocilia are constricted at their ically polarized in opposite directions.207
base and, when deflected, move like stiff rods pivot-
ing around the basal constricted area.36 Interconnec- TRANSDUCTION AND CODING
tions between stereocilia via fibrils or tip links have
been demonstrated.213 Mechanical Events As in the cochlea, the final
Kinocilia end in basal bodies, located just mechanical event in vestibular transduction is the
beneath the hair cell membrane. Within each bending of the hair cell cilia. Figure 4–44 illustrates
kinocilium, there are nine peripherally arranged transduction by the macula. When the macular
double-tubular filaments, positioned regularly surface is tilted, the heavy otoliths tend to slide
around two centrally located tubular filaments. This downward, carrying the gelatinous membrane and
9-plus-2 tubule pattern is found in many motile cilia attached cilia with them.
(eg, respiration epithelia, oviduct epithelium, uni- The six semicircular ducts consist of a circular,
cellular flagellates).214 Stereocilia are coupled to the narrow-bore tube in the temporal bone filled with
kinocilium and to each other so that during deflec- fluid called endolymph. The tube originates from
tion, all cilia are stimulated as one bundle.49 and returns to a reservoir (the utricle), but each
On each hair cell, the single kinocilium is duct may be treated, for practical purposes, like a
located to one side of the bundle of stereocilia. In fluid ring. When the head undergoes an angular
both maculae and cristae, hair cells in the same area acceleration, the fluid is left behind because of its
tend to have kinocilia on the same side of the stere- inertia. This causes the endolymph to flow relative
ocilia bundle. Thus, the vestibular sensory epithelium to the duct and to push on the cupula, which lies
has a morphologic directional polarization210 that is across the duct blocking it. The cupula is attached
determined by the direction of the cilia alignment. to the ampulla wall around its entire periphery and
Figure 4–43, C, illustrates the directional polarization billows, like a sail, under endolymph pressure.215,216
of the utricular macula. The kinocilia all tend to Normal deflections are tiny, in the range of 0.01 to
point toward a line of demarcation called the striola, 0.3 mm.217 The subsequent strain on the hair cells
or linea alba, running across the approximate center by the bending of their cilia embedded in the
of the macula. In the saccule, the kinocilia point away cupula creates a generator potential that modulates
from the striola. In the horizontal duct crista, the discharge rate of primary vestibular afferent
kinocilia point toward the utricle, whereas in the pair fibers.
Physiology of the Auditory and Vestibular Systems 111
FIGURE 4–43. Microanatomy of the vestibular hair cells. A, Schematic drawing of the two vestibular hair cell types. B,
Diagram showing morphologic polarization of the hair cells. Arrow shows the direction of cilia bending that produces
excitation. At right is a cross-section through the hair-bearing end of the hair cell showing many stereocilia (open circles)
and one kinocilium (filled circle). C, A diagrammatic surface view of the human utricular macula. Arrows indicate direc-
tion of polarization. Dashed line is the linea alba. A reproduced with permission from Brodal A.223 B and C reproduced
with permission from Lindeman HH, Ades HW, Bredberg G, Engstrom H. The sensory hairs and the tectorial membrane
in the development of the cat’s organ of Corti. Acta Otolaryngol (Stockh)1971;72:229–42 and Wersall J et al, respectively.206
Inferior Saccular n.
Post. canal n.
Prepositus
Hypoglossi
Vestibulospinal
Tract
Descending
MLF
nucleus prepositus hypoglossi, which is classically prepositus is included in the diagram of the vestibu-
thought to relate to taste sensation, has strong effer- lar nuclear complex in Figure 4–47.
ent and afferent vestibulo-oculomotor, through the As indicated in Figure 4–47, each subnucleus
medial longitudinal fasciculus (MLF), and cerebellar has a unique set of connections with the periphery
projections. In addition, microelectrode recordings and with specific regions of the central nervous sys-
from awake monkeys have demonstrated that tem including the spinal cord, cerebellum, and
prepositus neurons fire in relation to both vestibu- brainstem oculomotor nuclei (III, IV, VI). Most of
larly and visually induced eye movements.224 Studies the semicircular duct afferents terminate in the
on the activity of ocular motoneurons in alert mon- superior nucleus and rostral portion of the medial-
keys have shown that the neural commands for all vestibular nucleus. Both of these nuclei, in turn,
conjugate eye movements (vestibular, optokinetic, project to the oculomotor nuclei of the extraocular
saccadic, and pursuit) have both velocity and posi- muscles via the ascending MLF. The superior
tion commands.225 nucleus projects only to the ipsilateral MLF, whereas
The vestibular input to prepositus is disynaptic the medial nucleus projects bilaterally. The medial
and reciprocally organized (ie, ipsilateral input is exci- nucleus, via the medial vestibulospinal tracts in the
tatory, whereas contralateral input is inhibitory). In descending MLF, also sends bilateral descending
addition, if cells in the monkey’s nucleus prepositus projections to spinal anterior horn cells that control
hypoglossi are lesioned with kainic acid, the monkey’s the cervical musculature.227 Thus, the input and out-
eye movements only reflect the velocity command.226 put of the superior and medial vestibular nuclei pro-
A great amount of neurophysiologic evidence indi- vide a possible anatomic basis for the nystagmus and
cates that the position command is obtained from the head-turning-reflex responses to semicircular duct
velocity command by the mathematical process of stimulation (see below).
integration. That is, a neural network located in the The otolith organs, particularly the utriculus,
nucleus prepositus hypoglossi integrates, in the math- project primarily to the inferior nucleus and caudal
ematical sense, velocity-coded signals; thus, the part of the lateral nucleus. Outputs from these
Physiology of the Auditory and Vestibular Systems 115
nuclei, in turn, project downward to the ventral lum. As discussed below, the primary vestibular
horn region throughout the length of the spinal cord input to the vestibulocerebellum appears to be
via the lateral vestibulospinal tract. Thus, the affer- important in controlling the vestibulo-oculomotor
ent and efferent connections of the lateral vestibular reflex (VOR). Moreover, the primary vestibular
nucleus provide a possible anatomic basis for anti- input to the vestibulocerebellum and the climbing
gravity muscle responses in the limbs (extensors of fiber input from the inferior olive appear to be
the legs and flexors of the arms) to postural change. important in controlling the VOR.
The otolith organs have relatively sparse connections
to the extraocular muscles. These may be the con- SECONDARY VESTIBULAR FIBERS. The vestibulocerebel-
nections that produce the ocular counter-rolling lum receives secondary fibers primarily from the
response to head tilt.228 medial and inferior vestibular nuclei but also from
the other divisions. In addition, the fastigial nucleus
Efferent Innervation of the Vestibular System and the cortex of the vermis receive a strong, soma-
The vestibular organs in all vertebrates receive effer- totopically organized projection from the lateral
ent innervation originating in brainstem nuclei. vestibular nucleus. Since this nucleus is the primary
Although there are relatively few parent efferent neu- origin of the vestibulospinal tract, connections to it
rons, their axons branch to innervate more than one from the cerebellum are probably important in reg-
end-organ and also ramify extensively in the neu- ulating antigravity reflexes that help to maintain an
roepithelium of the individual organs. By means of upright body posture.231
this divergent innervation pattern, efferent fibers
provide a major source of synaptic input to type II Projections to Cerebral Cortex Whether the
hair cells, afferent calyces, and other unmyelinated vestibular system has a direct cortical projection has
afferent processes. In nonvestibular organs, efferent long been a controversial question. The functional
activation typically reduces afferent activity by hyper- corollary to this question is whether we can con-
polarizing the hair cell receptor. In contrast, efferent sciously appreciate a sensation owing to vestibular
responses in vestibular organs are more heteroge- stimulation. This question also has generated debate
neous. For example, in fish and mammals, there is an because most of the subjective sensations produced
excitation of afferents, whereas in frogs and turtles, by vestibular stimulation (eg, vertigo) are secondary
both excitation and inhibition are observed. In addi- to motor reflex or to autonomic responses, and it is
tion, there are variations in the efferent responses of difficult or impossible to separate a primary vestibu-
vestibular afferents innervating different parts of the lar sensation from the secondary sensations.200
neuroepithelium, which differ in their responses to
Experiments employing electrical stimulation of
natural stimulation. Moreover, efferent neurons
the vestibular nerve have demonstrated relatively
receive convergent inputs from several vestibular and
short-latency localized cortical responses in both the
nonvestibular receptors and also respond in associa-
cat and the monkey.232 The cat’s vestibular area is adja-
tion with active head movements. On the basis of the
cent to both the auditory and somatosensory fields,
discharge properties of efferent neurons, one of their
but in the monkey, and possibly in the human, it is
proposed functions is that they switch the vestibular
located near the face area of the somatosensory field
organs from a postural to a volitional mode. For a
on the postcentral gyrus. Deecke et al demonstrated
more detailed review of the vestibular efferent sys-
that the ventroposteroinferior (VPI) nucleus is the
tem, see a recent summary by Goldberg.229
thalamic relay for the vestibulocortical projection.233
The VPI nucleus lies adjacent to the thalamoso-
Vestibulocerebellar Connections PRIMARY VESTI- matosensory representation of the face. Prior to this
BULAR FIBERS. Primary vestibular neurons project not study, the function of the VPI nucleus was unknown.
only to the vestibular nuclei but also to the cerebel-
lum. Most of these fibers are distributed to the ipsi- Vestibular Influence on Postural Control The
lateral flocculus and nodulus and the medially main unit for the control of tone in the trunk and
located uvula.230 Because of this innervation by pri- extremity muscles is the myotactic reflex. These
mary vestibular fibers, these three cerebellar areas reflexes of the antigravity muscles are under the com-
have been termed collectively the vestibulocerebel- bined excitatory and inhibitory influence of multiple
116 Ballenger’s Otorhinolaryngology
supraspinal centers. Two of these supraspinal centers izontal rotation or to stimulation of a horizontal
are facilitory, that is, the lateral vestibular nucleus and ampullary nerve and vice versa.
rostral reticular formation, and four are inhibitory
centers including the pericruciate cortex, basal gan- CLASSIFICATION OF NEURONAL RESPONSE TYPES. Both
glia, cerebellum, and caudal reticular formation. The duct and otolithic vestibular nucleus units preserve
balance of input from these different centers deter- the basic properties of the primary afferent input,
mines the degree of tone in the antigravity muscles. but some respond in the same direction (eg, ipsilat-
eral horizontal rotation increases firing rate); others
Physiology of Vestibular Nuclei GENERAL CHAR- respond in the opposite direction. A few of the
ACTERISTICS OF N EURONAL R ESPONSES . Microelec- vestibular nucleus neurons respond with either inhi-
trode studies of responses of vestibular nucleus bition or facilitation in both directions. Table 4–2
neurons to electrical stimulation of individual outlines the characteristics of the duct units. The
ampullary nerves and to “natural” stimuli, such as type I units, exhibiting a primary response pattern,
those involving rotation and tilt, have established are innervated by the ipsilateral labyrinth, whereas
the following general characteristics: (1) neurons the type II units, showing response patterns that are
can be classified as tilt responders (otolith units) opposite to those of the primary units, are inner-
or rotation responders (duct units); (2) the loca- vated by the contralateral labyrinth.
tions of these two types correspond with that The analogous classification for otolith respon-
expected from the anatomic projections of ders subdivides all types into (1) “a” units, which
otolithic and semicircular duct afferents to the increase firing on ipsilateral tilt; (2) “b” units,
vestibular nuclear complex. Thus, the tilt respon- which decrease firing on ipsilateral tilt; (3) “y” units,
ders are found primarily in the areas innervated by which increase firing in response to tilt in both
the sacculus and utriculus, that is, the inferior directions; and (4) “o” units, which decrease firing
nucleus and caudal part of lateral nucleus, whereas by tilt in both directions. Analogous to the duct
the rotation responders are found mainly in the units, the relative populations of these units are a >
areas innervated by the semicircular ducts, that is, b > y > o.234
the superior nucleus and the rostral part of medial
nucleus; and (3) among the rotation responders, COMMISSURAL INHIBITION AND VESTIBULAR COMPEN-
pathways from individual ducts seem to be pre- SATION Many of the contralateral (type II) semicir-
served. Thus, for example, a neuron that responds cular duct responses listed in Table 4–2 are abolished
to vertical rotation or to electrical stimulation of a when a midline dorsal brainstem incision is made
vertical ampullary nerve does not respond to hor- that interrupts the vestibular crossing fibers. Thus,
the “opposite-primary” type II responses are likely mal again develops signs of acute unilateral vestibular
elicited by inhibitory input from type I neurons of loss with nystagmus directed toward the previously
the opposite labyrinth. Figure 4–48 summarizes the operated ear, that is, a condition referred to as
simplest of the probable neuronal interconnections Bechterew’s compensatory nystagmus.239 That is, the
responsible for this contralateral inhibition. overall effect is as if the first labyrinthectomy had not
The commissural inhibitory system is also occurred. Compensation after the second labyrinthec-
important in the mechanism of compensation fol- tomy is slightly faster than the first but still requires
lowing labyrinthectomy. Thus, immediately after several days. For a recent review on the molecular
labyrinthectomy, the type I units on the mechanisms underlying vestibular compensation, see
labyrinthectomized side show no spontaneous the summary by Darlington and Smith.240
activity and do not respond to rotation. However,
within a few days, the deafferented type I units Vestibulo-oculomotor Reflex Although there are
regain their spontaneous activity and, via inhibi- neural connections between the maculae and the
tion from the contralateral pathway, also regain extraocular muscles, they are less important in
their normal response to rotation. The mechanisms humans, both functionally and clinically, than are
by which this recovery process occurs are un- the semicircular duct connections. This discussion
known, but a contributing factor is the lowered of the VOR will therefore focus on the reflex con-
threshold of the deafferented type I neuron for nection between the semicircular ducts and the
contralateral input.235 In animal studies, the course extraocular muscles.
of compensation is affected by exercise,236 visual An important function of the semicircular
experience,237 and drugs.238 Thus, as a rule, stimu- ducts is to provide afferent input to the VOR that
lants accelerate and sedatives slow compensation.237 generates eye movements that compensate for head
Fetter and Zee showed further that visual experi- movements by maintaining a stabilized visual image
ence was not necessary for the acquisition or for on the retina during rotation. Such eye adjustments
the maintenance of this recovery process.237 are called compensatory eye movements. Figure
If a second labyrinthectomy is performed after 4–49 diagrams the neural connections that stabilize
compensation for the first labyrinthectomy, the ani- gaze during head movement.
118 Ballenger’s Otorhinolaryngology
ANATOMIC CONNECTIONS. The VOR is subserved by a put that is synergistic to the conjugate right-eye
three-neuron pathway. That is, motions detected by deviation, generated by the output of the opposite
the end-organ are transduced into neural impulses duct. Figure 4–49, upper right, depicts this sequence
that are sent via the vestibular nerve to the vestibu- of events.
lar nuclei and rostrally through the ascending MLF Functionally, the VOR provides more than
to the oculomotor nuclei of the extraocular muscles. a simple one-to-one transfer of information from
Secondary vestibulo-ocular connections via the the semicircular duct to the extraocular muscles. It
reticular formation have been described, but func- should be recalled that the response of the ampullary
tionally these are less important than the “direct” nerves reflects head velocity, yet the ocular rotation,
three-neuron MLF vestibulo-ocular pathway. at the vestibular reflex output, reflects head position.
Inhibitory crossed connections at the levels of Therefore, at some point in the transfer from
both vestibular and oculomotor nuclei, which were vestibular input to ocular output, some form of neu-
described above, probably also participate in the ral integration must occur that converts the velocity
VOR. The crossed inhibitory oculomotor connec- signal at the input into the displacement signal at the
tions subserve antagonistic extraocular muscles.241 output. The location of this integrator, as noted
These inhibitory interconnections are important in above, is the nucleus prepositus hypoglossi.226
the formation of conjugate eye movements.
CONTROL OF THE GAIN OF THE VESTIBULO-OCULOMO-
FUNCTIONAL CONNECTIONS. A number of investiga- TOR REFLEX. In studies of the VOR, the concept of
tions have uncovered many details of the facilitatory gain is important. Gain of the VOR is simply the
and inhibitory interactions between neurons of the amplitude of eye rotation divided by amplitude of
vestibular nuclear complex and motoneurons of the the head rotation. Generally, amplitudes of eye and
extraocular eye muscles. For a review, the reader is head rotation are expressed as angles.
referred to Wilson and Melvill-Jones.234 However, in Because eye rotation is supposed to be equal
older experiments, the effect of mass stimulation of and opposite to head rotation (ie, to compensate
individual ampullary nerves on eye movements pro- fully and leave gaze steady), it might seem at first
vided the clinician with the most useful integrative that the ideal VOR gain would be –1. However, there
concepts of the functional organization of the VOR. are many real-life situations for which the ideal VOR
The results of all of these ampullary nerve-stimulating gain is not –1. Functionally, such situations can be
experiments agree on the principle, illustrated by Fig- divided into long-term (ie, slow) and short-term (ie,
ure 4–49, that stimulation of an ampullary nerve gen- fast) adjustments. The short-term or fast VOR gain
erates conjugate eye movements away from the side adjustments occur in the course of visual tracking
stimulated and in the plane of the duct stimulated. tasks, in which both the head and the eyes follow the
This principle allows a straightforward descrip- fixation target at varying relative velocities. For
tion of the events leading from endolymph move- example, in a tracking task in which the head and
ment in the horizontal duct to the compensatory eye eyes must move in the same direction, the VOR must
movement depicted in Figure 4–50: (1) head move- be completely suppressed. In the clinical test situa-
ment to the left generates endolymph movement to tion, this visual suppression of the VOR is observed
the right in the left duct. This is toward the ampulla as suppression of caloric or rotational nystagmus
and therefore increases the ampullary nerve dis- during visual fixation.
charge rate; (2) the increased ampullary nerve out- An example of functionally beneficial long-
put, according to the aforementioned rule, causes term VOR gain control is the situation in which a
conjugate eye deviation away from the side stimu- prescription for new glasses has been received. The
lated (ie, to the right, which is opposite to the direc- change in magnification of the visual image changes
tion of head movement); (3) similarly, head the speed with which the visual image moves across
movement to the left generates ampullofugal move- the retina (eg, increasing magnification would
ment in the right duct, which decreases neural out- increase the speed of movement of retinal images).
put; and (4) decreased neural output inhibits the Therefore, to maintain a stable retinal image after
extraocular muscles, thus causing the eyes to deviate new glasses have been obtained, the VOR gain must
conjugately to the left, which provides a neural out- be adjusted for the new magnification levels. Such
Physiology of the Auditory and Vestibular Systems 119
and long-term248 control of the VOR gain. The strong Purkinje cells.253 Finally, Luebke and Robinson
primary vestibular afferent projection to the vestibu- reversibly silenced the flocculus of alert cats adapted
locerebellum and equally strong projection from the to either high- or low-gain VOR.254 This reversible
vestibulocerebellum to the oculomotor portion of floccular shutdown did not alter the adapted VOR
the vestibular nuclear complex have already been gain, yet the animals were subsequently unable to
described. There is also a strong input to the vestibu- modify their VOR gain, while the flocculus was
locerebellum from the retina by way of the inferior silenced.
olivary climbing fibers. Most of these visual units
detected in the vestibulocerebellum are “movement Clinical Considerations of Vestibular Reflexes
detectors.”249 They are thus ideally suited to provide GENERAL PATTERN. It has been stated that the vestibu-
information on “retinal slip” of the visual image, lar system functions primarily as an afferent input
which is needed to modify VOR gain control. The for motor reflexes and that, at rest, most primary
visual and vestibular inputs to the cerebellum con- vestibular neurons have high and remarkably regu-
verge on the Purkinje cells of the flocculus cortex. lar spontaneous discharge rates. For the purposes of
Furthermore, experiments on alert monkeys, in the following clinically oriented discussion, the
which rotation of the animal’s visual environment spontaneous vestibular neuronal activity will be
and its head were controlled independently, showed referred to as the resting discharge.
that visual and vestibular inputs modulate Purkinje Normally, with the head at rest in the neutral
cell outputs in ways exactly appropriate for the func- position, the resting discharges in the two vestibular
tionally useful control of the VOR gain. nerves are equal. Vestibulomotor reflexes are elicited
Ablation experiments further support the role when inputs from the two vestibular end-organs or
of the flocculonodular lobes in control of VOR gain. their central projections are made unequal (ie, they
It has been demonstrated, for example, that removal are unbalanced). Such unbalancing can occur by an
of the vestibulocerebellum eliminates suppression abnormality involving one side to a greater degree
of caloric nystagmus by visual fixation.250 An analo- than the other. In this case, we term the resultant
gous failure of fixation suppression (FFS) of nys- vestibular reflex spontaneous. Vestibular input from
tagmus is also observed in humans with cerebellar the two sides can also be unbalanced by stimulating
lesions.251 However, clinical data suggest that FFS one or both of the vestibular end-organs. In this case,
can be produced by lesions in the brainstem and, the resultant vestibular reflex is termed “induced.”
less frequently, cerebral hemispheres, as well as the When a vestibular input imbalance is unusu-
cerebellum.252 ally large or prolonged, a constellation of stereo-
Robinson reported the results of a notable typed responses occurs.255 These responses are head
ablation experiment that demonstrates the role of turning, falling (or swaying), past pointing, vertigo
the flocculus in causing long-term or plastic changes representing a sensation of rotation, and nystagmus
in VOR gain.244,248 Specifically, cats wore reversing involving a rhythmic back-and-forth eye movement,
prisms for several days, and VOR gain was measured with alternate slow phases in one direction and fast
each day by rotating the cats in the dark. After sev- phases in the opposite direction. These slow and fast
eral days, as expected, VOR gain dropped from 0.9 to eye movements are termed the slow and fast phases
0.1. When the vestibulocerebellum was removed, the of vestibular nystagmus. The head turning, falling,
VOR gain promptly increased to about 1.2. Further- past pointing, and nystagmus slow phase are all in
more, it proved impossible to reinstate the VOR gain the same direction, that is, away from the ear with
decrease by continued wearing of prisms after the greater output. In this discussion, the reference is
removal of the vestibulocerebellum. In addition, to the nystagmus slow or vestibular phase. The clin-
Miles et al uncovered results in the monkey that ical convention is to designate nystagmus direction
implicated synaptic changes at other sites, especially by the fast of central phase, presumably because
in the brainstem.252 More recently, Lisberger pro- these movements can be easily observed. Thus, the
vided further evidence that the modifiable synapses indicated reflex directions may be the opposite of
were located between vestibular primary afferents those to which the reader is accustomed. Fast-phase
and those second-order and/or possibly third-order nystagmus is in the direction of the angular acceler-
vestibular neurons that also received synapses from ation. The rotation sensation, or vertigo, may be
Physiology of the Auditory and Vestibular Systems 121
referred either to the subject’s body (ie, subjective In the clinical laboratory, this temperature change is
vertigo) or to the environment (ie, objective ver- usually produced by running cool or warm water
tigo). If the body rotates, it is in the same direction into the external auditory canal. The temperature
as the nystagmus slow phase; if the environment change is conducted through bone to the semicircu-
rotates, it is in the opposite direction. lar canals. Since the horizontal semicircular canal is
closest to the irrigating water, it is the most affected;
METHODS OF ELICITING. Vestibular responses can be hence, caloric nystagmus is almost entirely in the
generated by rotational, caloric, or galvanic stimula- horizontal plane.
tion of the vestibular periphery. The caloric and Figure 4–51 illustrates the generation of caloric
rotational responses are discussed in the following nystagmus. The subject is in the supine position,
section. The galvanic vestibular response occurs with his head elevated 30 degrees to bring the hori-
when an electrical current is applied to the head in zontal canal into the vertical position. The cold
the vicinity of the ear.251 Electrical current applied in caloric irrigation cools the endolymph in part of the
this manner elicits the entire constellation of horizontal duct. This cooled endolymph becomes
vestibular responses except vertigo. Interestingly, slightly denser than the surrounding endolymph
however, some subjects may report a slight sense of and thus falls, causing the eyes to rotate toward the
disorientation. If the current is positive, the nystag- irrigated ear. This vestibular eye movement is repeat-
mus slow-phase, past-pointing, and body-sway edly interrupted by a compensatory rapid central eye
responses are toward the stimulated ear; in contrast, movement in the opposite direction. A cold caloric
if the current is negative, these responses are away nystagmus is thus created, with its slow phase toward
from the stimulated ear. and its fast phase away from the irrigated ear.
Because the galvanic stimulus probably acts at a Although the slow phase is the vestibular phase
retrolabyrinthine location (ie, either vestibular nerve, of vestibular nystagmus, it is the clinical convention
Scarpa’s ganglia, or a more central location), it has to designate the direction of the vestibular nystag-
been suggested as a means of differentiating vestibu- mus by the direction of the fast phase. This conven-
lar end-organ from vestibular nerve lesions. However, tion, as noted above, originated because the fast
this procedure has not found widespread clinical phase is easier to observe than the slow phase.
acceptance, possibly because of uncertainty over the
exact locus of action. For example, patients with their NEURAL MECHANISMS OF NYSTAGMUS. Figure 4–49
vestibular nerves sectioned intracranially still have a diagrams the neural mechanisms of different kinds
recognizable body-sway galvanic response,256 suggest-
ing that at least part of the action of the galvanic stim-
ulus is central to the vestibular nerve (ie, at the level
of the brainstem or possibly cerebellum).
of vestibular nystagmus.257 This figure shows the cursors or progenitors of the regenerated cochlear269
physiologic rather than the anatomic form of the and vestibular270 hair cells.
horizontal VOR system. It is drawn to reflect the fact The knowledge that noise- or drug-damaged
that increased neural activity from a horizontal hair cells of birds, reptiles, and even guinea pigs271
semicircular duct rotates the eyes horizontally away can regenerate has motivated researchers to learn
from the duct.258 how to stimulate the regrowth of the sensory cells of
At rest, both ducts generate equal neural activ- the human inner ear. In fact, recently it has been
ity, which represents the resting discharge described shown that brief treatments with forskolin enhance
above. Unbalancing the vestibular inputs from the proliferation and regeneration by increasing the
two ears generates vestibular nystagmus if the imbal- amounts of growth factor receptors at the mem-
ance is prolonged. Caloric and rotational stimuli brane.272 It is quite likely that, in the future, it will be
unbalance the vestibular input via the normal trans- possible to correct hearing and balance impairments
ducer action of the semicircular ducts. Lesioning one by stimulating the growth of new hair cells.
labyrinth by surgery or disease causes a pathologic
imbalance by eliminating or reducing the resting Molecular Basis of Hearing and Balance and Clin-
discharge on the involved side. ical Implications A current view is that many of
the 60% of cases of hearing impairment that have
no obvious environmental origins, that is those
THE FUTURE other than conditions associated with meningitis,
REGENERATION OF HAIR CELLS perinatal complications, maternal-fetal infections,
A great amount of study has focused over the past 15 acoustic trauma, and ototoxic drugs, have a genetic
years on the ability of vertebrate hair cells to regen- basis.273 Moreover, it has been estimated that 30% of
erate. One popular model has been the bird, in prelingual deafness causes are syndromic. Several
which it has been shown that the sound- or drug- hundred such syndromes, consisting of hearing loss
damaged sensory epithelium, that is, the basilar in association with a variety of anatomic anomalies
papilla, is capable of undergoing significant struc- involving, for example, eye, musculoskeletal, renal,
tural repair.258–260 Detailed morphologic examination nervous system, and pigmentary disorders, have
of damaged cochleae showed that immediately after been described.274 Syndromic hearing loss can have
damage, there is a substantial loss of hair cells, an many modes of transmission including maternal
expansion of the surrounding supporting-cell sur- inheritance, owing to a mitochondrial mutation.
face area,261 and a degeneration of the tectorial The forms may be conductive, sensorineural, or
membrane overlying the region of the lost hair mixed defects.
cells.262 In the days following acoustic overstimula- The nonsyndromic forms of hearing loss are
tion, the regenerative processes repair many of the collectively referred to as DFN for the X-linked
damaged structures so that the hair cells are almost forms (1 to 3% incidence), DFNA for the autosomal
completely replaced by regenerated hair cells,263 dominant forms (15% incidence), and DFNB for the
cochlear ganglion cells appear to form new synapses autosomal recessive forms (85% incidence). The
with the regenerated hair cells,264 and a new tector- autosomal recessive forms of hearing loss are often
ial membrane is partially regenerated over the the most severe and account for the vast majority of
lesioned area.262 In parallel to the structural repair is cases of congenital profound deafness. To date, 20
a considerable recovery of auditory function as DFNB, 14 DFNA, and four DFN loci have been
measured with physiologic techniques.265 mapped to specific chromosomal positions.275 In
Other investigators have documented the addition, within the past 10 years, 10 genes have
capacity of the avian cochlear and vestibular sensory been cloned and shown to underlie certain nonsyn-
epithelia to repair following aminoglycoside toxic- dromic hearing losses. Two of these genes frequently
ity266 and even to restore function.267,268 Using are the cause of nonsyndromic forms of deafness.
cell proliferation marker procedures (ie, tritiated- First, the connexin 26 gene, which contains a single
thymidine autoradiography or proliferating cell coding exon, was shown to account for up to 50% of
nuclear-antigen immunochemistry), it has been well all causes of prelingual, autosomal, and recessive
documented that the supporting cells are the pre- hearing loss.276 Second, a mutation in the mitochon-
Physiology of the Auditory and Vestibular Systems 123
drial 12s ribosomal ribonucleic acid gene was shown 9. Borg E. On the neuronal organization of the acoustic
to underlie an isolated form of sensorineural deaf- middle ear reflex. A physiological and anatomical
ness and deafness induced by aminoglycoside treat- study. Brain Res 1973;49:101–23.
ment.277 In addition, the sequencing of the human 10. Møller AR. The sensitivity of contraction of the tym-
genome is expected to be complete in 2003, which panic muscles in man. Ann Otol Rhinol Laryngol
will allow more deafness-related genes to be discov- 1962;71:86–95.
ered. For certain, new technologies, such as the 11. Møller A: Acoustic reflex in man. J Acoust Soc Am
deoxyribonucleic acid microarrays used to study dif- 1962;34:1524.
ferential gene expression under various normal and 12. Djupesland G, Zwislocki JJ. Effect of temporal sum-
pathologic conditions, promise to rapidly advance mation on the human stapedius reflex. Acta Oto-
our knowledge of the diseases of the ear.278 For a laryngol (Stockh) 1971;71:262–5.
recent review of this active field of research, see 13. Jerger J. Clinical experience with impedance audiom-
Kalatzis and Petit.275 etry. Arch Otolaryngol 1970;92:311–24.
So far, however, this research has yet to result 14. Klockhoff IH. Middle ear muscle reflexes in man.
in the development of new treatments for deafness. Acta Otolaryngol Suppl (Stockh) 1961;164:1.
Currently, the treatments available are the amplifi- 15. Reger SN. Effect of middle ear muscle action on cer-
cation of sound, using analog or digital hearing tain psychophysical measurements. Ann Otol Rhinol
aids, or the artificial, electrical stimulation of the Laryngol 1960;69:1179–98.
cochlear nerve via a cochlear implant. Efforts to 16. Smith HD. Audiometric effects of voluntary con-
induce regeneration of inner ear sensory cells and traction of the tensor tympani muscles. Arch Oto-
methods to introduce replacement genes via viral laryngol 1943;38:369–72.
vectors279 will soon become the most exciting treat- 17. Holst HE, et al. Ear drum movements following
ment options leading to a possible reversal of hear- stimulation of the middle ear muscles. Acta Oto-
ing impairment. laryngol Suppl (Stockh) 1963;182:73–84.
18. Keefe DH, Bulen JC, Arehart KH, Burns EM. Ear-canal
impedance and reflection coefficient in human infants
REFERENCES and adults. J Acoust Soc Am 1993;94:2617–38.
1. Shaw EA, Teranishi R. Sound pressure generated in 19. Goode RL, Ball G, Nishihara S, Nakamura K. Laser
an external-ear replica and real human ears by a Doppler vibrometer (LDV)—a new clinical tool for
nearby point source. J Acoust Soc Am 1968;44:240–9. the otologist. Am J Otol 1996;17:813–22.
2. Shaw EAG. The external ear. In: Keidel WD, Neff 20. Zakrisson JE, Borg E, Diamant H, Miller AR. Audi-
WD, editors. Handbook of sensory physiology. Vol tory fatigue in patients with stapedius muscle paral-
V/1: auditory system, anatomy physiology (ear). ysis. Acta Otolaryngol (Stockh) 1975;79:228–32.
New York: Springer-Verlag; 1974. p. 455–90. 21. Simmons FB. Perceptual theories of middle ear
3. Pickles JO. An introduction to the physiology of muscle function. Ann Otol Rhinol Laryngol 1964;
hearing. New York: Academic Press; 1982. 73:724–40.
4. von Békésy G. Experiments in hearing. Translated and 22. Harford ER, Jerger JF. Effect of loudness recruitment
edited by EG Wever. New York: McGraw-Hill; 1960. on delayed speech feedback. J Speech Hear Res 1959;
5. Møller AR. An experimental study of the acoustic 2:361–8.
impedance of the middle ear and its transmisssion 23. Borg E, Zakrisson JE. The activity of the stapedius
properties. Acta Otolaryngol (Stockh) 1965;60:129–49. muscle in man during vocalization. Acta Otolaryn-
6. Tonndorf J, Khanna SM. The role of the tympanic gol (Stockh) 1973;79:325–33.
membrane in middle ear transmission. Ann Otol 24. Jahnke K. The fine structure of freeze-fractured
Rhinol Laryngol 1970;79:743–53. intercellular junctions in the guinea pig inner ear.
7. Khanna SM, Tonndorf J. Tympanic membrane Acta Otolaryngol Suppl (Stockh) 1975;336:1–40.
vibration in cats studied by time-averaged hologra- 25. Engstrom H. The cortilymph, the third lymph of the
phy. J Acoust Soc Am 1972;51:1904–20. inner ear. Acta Morphol Neer Scand 1960;3:195–204.
8. Salomon G, Starr A. Electromyography of middle ear 26. Nadol JB. Intercellular fluid pathways in the organ of
muscles in man during motor activities. Acta Neurol Corti of cat and man. Ann Otol Rhinol Laryngol
Scand 1963;Suppl (39):161–8. 1979;88:2–11.
124 Ballenger’s Otorhinolaryngology
27. Steele KP. Tectorial membrane. In: Altschuler RA, 41. Tasaki I, Davis H, Eldredge DH. Exploration of
Hoffman DW, Bobbin RP, editors. Neurobiology of cochlear potentials in guinea pig with a microelec-
hearing: the cochlea. New York: Raven Press; 1986. trode. J Acoust Soc Am 1954;26:765–73.
28. Smith CA. Structure of the cochlear duct. In: Naun- 42. Tasaki I, Spyropoulos CS. Stria vascularis as source
ton RF, Fernandez C, editors. Evoked electrical activ- of endocochlear potential. J Neurophysiol 1959;22:
ity in the auditory nervous system. New York: 149–55.
Academic Press; 1978. p. 3–19. 43. Konishi T, Kelsey E. Effect of cyanide on cochlear
29. Lim DJ. Fine morphology of the tectorial mem- potentials. Acta Otolaryngol (Stockh) 1968;65:381–90.
brane: its relationship to the organ. Corti Arch Oto- 44. Tasaki I, Fernandez C. Modification of cochlear
laryngol 1972;96:199–215. microphonics and action potentials by KCl solution
30. Flock A. Physiological properties of sensory hairs in and by direct currents. J Neurophysiol 1952;15:
the ear. In: Evans EF, Wilson JP, editors. Psycho- 497–512.
physics and physiology of hearing. New York: Acad- 45. Davis H, Derbyshire AJ, Lurie JH, Saul LJ. The electric
emic Press; 1977. p. 15–25 response of the cochlea. Am J Physiol 1934;107:311–32.
31. Nielsen DW, Slepecky N. Stereocilia. In: Altschuler 46. Tasaki I, Davis H, Legouix JP. The space-time pat-
RA, Hoffman DW, Bobbin RP, editors. Neurobiology tern of the cochlear microphonic (guinea pig) as
of hearing: the cochlea. New York: Raven Press; 1986. recorded by differential electrodes. J Acoust Soc Am
p. 23–46. 1952;24:502–19.
32. Flock A, Cheung HC. Actin filaments in sensory 47. Davis H, Deatheridge BH, Eldredge DH, Smith CA.
hairs of inner ear receptor cells. J Cell Biol 1977;75: Summating potentials of the cochlea. Am J Physiol
339–43. 1958;195:251–61.
33. Flock A, Bretscher A, Weber K. Immunohistochemi- 48. Konishi T, Yasuno T. Summating potential of the
cal localization of several cytoskeletal proteins in cochlea in the guinea pig. J Acoust Soc Am 1963;
inner ear sensory and supporting cells. Hear Res 35:1448–52.
1982;7:75–89. 49. Hudspeth AJ. Extracellular current flow and the site
34. Hudspeth AJ, Choe Y, Mehta AD, Martin P. Putting of transduction by vertebrate hair cells. J Neurosci
ion channels to work: mechanoelectrical transduc- 1982;2:1–10.
tion, adaptation, and amplification by hair cells. Proc 50. Dallos P, Cheatham MA. Production of cochlear
Natl Acad Sci U S A 2000;97:11765–72. potentials by inner and outer hair cells. J Acoust Soc
35. Slepecky N, Chamberlain SC. Distribution and Am 1976;60:510–2.
polarity of actin in the sensory hair cells of the chin- 51. Durrant JD, Wang J, Ding DL, Salvi RJ. Are inner or
chilla cochlea. Cell Tissue Res 1982;224:15–24. outer hair cells the source of summating potentials
36. Flock A, Flock B, Murray E. Studies on the sensory recorded from the round window? J Acoust Soc Am
hairs of receptor cells in the inner ear. Acta Oto- 1998;104:370–7.
laryngol (Stockh) 1977;83:85–91. 52. Davis H. A model for transducer action in the
37. Steele CR. A possibility for sub-tectorial membrane cochlea. Cold Spring Harb Symp Quant Biol 1965;
fluid motion. In: Møller AR, editor. Basic mecha- 30:181–90.
nisms in hearing. New York: Academic Press; 1973. 53. Wever EG, Bray CW. Action currents in the auditory
38. Dallos P, Billone MC, Durrant JD, et al. Cochlear nerve in response to acoustical stimulation. Proc
inner and outer hair cells: functional differences. Sci- Natl Acad Sci U S A 1930;16:344–500.
ence 1972;177:356–8. 54. Davis H, Tasaki I, Goldstein R. The peripheral origin
39. Russell IJ, Sellick PM. The responses of hair cells to of activity with reference to the ear. Cold Spring
low frequency tones and their relationship to the Harb Symp Quant Biol 1952;17:143–54.
extracellular receptor potentials and sound pressure 55. Brownell WE. Cochlear transduction: an integrative
level in the guinea pig cochlea. In: Syka J, Aitkin L, model and review. Hear Res 1982;6:335–60.
editors. Neuronal mechanisms of hearing. New York: 56. Hudspeth AJ. The hair cells of the inner ear. Sci Am
Plenum Press; 1981. 1983;248:54–64.
40. von Békésy G. Shearing microphonics produced by 57. LeBlanc CS, Fallon M, Parker MS, et al. Phosphoroth-
vibrations near the inner and outer hair cells. J ioate oligodeoxynucleotides can selectively alter neu-
Acoust Soc Am 1953;25:786. ronal activity in the cochlea. Hear Res 1999;135:105–12.
Physiology of the Auditory and Vestibular Systems 125
58. Puel J-L. Chemical synaptic transmission in the 73. Evans EF. Auditory frequency selectivity and the
cochlea. Prog Neurobiol 1995;47:449–76. cochlear nerve. In: Zwicker E, Terbardt E, editors.
59. Werman R. Criteria for identification of a central Facts and models in hearing. New York: Springer-
nervous system transmitter. Comp Biochem Physiol Verlag; 1974. p. 118–29.
1966;18:745–66. 74. Kiang NYS, Moxon EC, Levine RA. Auditory nerve
60. Kuriyama H, Jenkins O, Altschuler RA. Immunocy- activity in cats with normal and abnormal cochleas.
tochemical localization of AMPA selective glutamate In: Wolstenhome GEW, Knight J, editors. Ciba Sym-
receptor subunits in the rat cochlea. Hear Res 1994; posium on Sensorineural Hearing Loss. London:
80:233–40. Churchill Press; 1970. p. 241–68.
61. Jager W, Goiny M, Herrera-Marschitz M, et al. 75. Robertson D. Cochlear neurons: frequency selectiv-
Sound-evoked efflux of excitatory amino acids in the ity altered by perilymph removal. Science 1974;186:
guinea-pig cochlear in vitro. Exp Brain Res 1998; 153–5.
121:425–32. 76. Cody AR, Johnstone BM. Single auditory neuron
62. Bobbin RP, Bledsoe SC, Jenison GL. Neurotransmit- response during acute acoustic trauma. Hear Res
ters of the cochlea and lateral line organ. In: Berlin 1980;3:3–16.
CI, editor. Hearing science: recent advances. San 77. Johnstone BM, Boyle AJ. Basilar membrane vibra-
Diego: College-Hill Press; 1984. tion examined with the Mössbauer technique. Sci-
63. Schwartz IR, Ryan AF. Uptake of amino acids in the ence 1967;158:389–90.
gerbil cochlea. In: Altschuler RA, Hoffman DW, Bob- 78. Rhode WS. Measurement of vibration of the basilar
bin RP, editors. Neurobiology of hearing: the membrane in the squirrel monkey. Ann Otol Rhinol
cochlea. New York: Raven Press; 1986. Laryngol 1974;83:619–25.
64. Fex J, Altschuler RA. Neurotransmitter-related 79. Kim DO, Neely ST, Molnar CE, Matthews JW. An
immunocytochemistry of the organ of Corti. Hear active cochlear model with negative damping in the
Res 1986;22:249–63. partition: comparison with Rhode’s ante- and post-
65. Plinkert PK, Mohler H, Zenner HP. A subpopulation mortem observations. In: van den Brink G, Bilsen
of outer hair cells possessing GABA receptors with FA, editors. Psychophysical, physiological, and be-
tonotopic organization. Arch Otorhinolaryngol 1989; havioral studies in hearing. Delft, Netherlands: Delft
246:417–22. University Press; 1980. p. 7–14.
66. Gitter AH, Zenner HP. Gamma-aminobutyric acid 80. Kemp DT. Stimulated acoustic emissions from
receptor activation of outer hair cells in the guinea pig within the human auditory system. J Acoust Soc Am
cochlea. Eur Arch Otorhinolaryngol 1992;249:62–5. 1978;64:1386–91.
67. Eybalin M. Neurotransmitters and neuromodulators 81. Wit HP, Ritsma RJ. Evoked acoustical responses from
of the mammalian cochlea. Physiol Rev 1993;73: the human ear: some experimental results. Hear Res
309–73. 1980;2:253–61.
68. Frisina RD. Subcortical neural coding mechanisms 82. Mountain DC. Changes in endolymphatic potential
for auditory temporal processing. Hear Res 2001; and crossed olivocochlear bundle stimulation alter
158:1–27. cochlear mechanics. Science 1980;210:71–2.
69. LePage EL, Johnstone BM. Nonlinear mechanical 83. Engdahl B, Kemp DT. The effect of noise exposure on
behaviour of the basilar membrane in the basal turn the details of the distortion-product otoacoustic emis-
of the guinea pig cochlea. Hear Res 1980;2:183–9. sions in humans. J Acoust Soc Am 1996;99:1573–87.
70. Liberman MC, Kiang NYS. Acoustic trauma in cats. 84. Allen GC, Tiu C, Koike K, et al. Transient-evoked
Cochlear pathology and auditory-nerve activity. otoacoustic emissions in children after cisplatin
Acta Otolaryngol Suppl (Stockh) 1978;358:1–63. chemotherapy. Otolaryngol Head Neck Surg 1998;
71. Ruggero MA, Rich NC. Application of a commer- 118:584–8.
cially manufactured Doppler-shift laser velocimeter 85. Brownell WE, Bader CR, Bertrand D, de Ribaupierre
to the measurement of basilar-membrane vibration. Y. Evoked mechanical responses of isolated cochlear
Hear Res 1991;51:215–30. outer hair cells. Science 1985;227:194–6.
72. Møller AR. Studies of the damped oscillatory re- 86. Zenner HP, Zimmermann U, Schmitt U. Reversible
sponse of the auditory frequency analyzer. Acta contraction of isolated mammalian cochlear hair
Physiol Scand 1970;78:299–314. cells. Hear Res 1985;18:127–33.
126 Ballenger’s Otorhinolaryngology
87. Flock A. Hair cells, receptors with a motor capac- tory nerve response to tones in noise. J Neurophys-
ity? In: Klinke R, Hartman R, editors. Hearing, iol 1987;57:1002–21.
physiological bases and psychophysics. New York: 101. Collet L. Use of otoacoustic emissions to explore
Springer-Verlag; 1983. p. 2–7. the medial olivocochlear system in humans. Br J
88. Dallos P, Evans BN, Hallworth R. Nature of the Audiol 1993;27:155–9.
motor element in electrokinetic shape changes of 102. Berlin CI, Hood LJ, Hurley A, Wen H. Contralateral
cochlear outer hair cells. Nature 1991;350:155–7. suppression of otoacoustic emissions: an index of
89. Brownell WE. Outer hair cell electromotility and the function of the medial olivocochlear system.
otoacoustic emissions. Ear Hear 1990;11:82–92. Otolaryngol Head Neck Surg 1994;110:3–21.
90. Zheng J, Shen W, He DZ, et al. Prestin is the motor 103. Penner MJ. An estimate of the prevalence of tinnitus
protein of cochlear outer hair cells. Nature 2000; caused by spontaneous otoacoustic emissions. Arch
405:149–55. Otolaryngol Head Neck Surg 1990;116:418–23.
91. Oliver D, He DZ, Klocker N, et al. Intracellular 104. Fetterman BL. Distortion-product otoacoustic
anions as the voltage sensor of prestin, the outer emissions and cochlear microphonics: relation-
hair cell motor protein. Science 2001;292:2340–3. ships in patients with and without endolymphatic
92. Rubel EW. Ontogeny of structures and function in hydrops. Laryngoscope 2001;111:946–54.
the vertebrate auditory system. In: Jacobson M, 105. Schweinfurth JM, Cacace AT, Parnes SM. Clinical
editor. Handbook of sensory physiology. Vol applications of otoacoustic emissions in sudden
IX: development of sensory systems. New York: hearing loss. Laryngoscope 1997;107:1457–63.
Springer-Verlag; 1978. p. 135–237. 106. Evans EF. The sharpening of cochlear frequency
93. Kim DO. Functional roles of the inner- and outer- selectivity in the normal and abnormal cochlea.
hair-cell subsystems in the cochlea and brainstem. In: Audiology 1975;14:419–42.
Berlin CI, editor. Hearing science: recent advances. 107. Evans EF. The frequency response and other prop-
San Diego: College-Hill Press; 1984. p. 241–62. erties of single fibers in the guinea-pig cochlear
94. Wever EG. Theory of hearing. New York: John nerve. J Physiol 1972;226:263–87.
Wiley & Sons Press; 1949. 108. Brugge JF, Anderson DJ, Hind JE, Rose JE. Time
95. Warr WB, Guinan JJ, White JS. Organization of the structure of discharges in single auditory nerve fibers
efferent fibers: the lateral and medial olivocochlear of the squirrel monkey in response to complex peri-
systems. In: Altschuler RA, Hoffman DW, Bobbin odic sounds. J Neurophysiol 1969;32:386–401.
RP, editors. Neurobiology of hearing: the cochlea. 109. Rose JE, Brugge JF, Anderson DJ, Hind JE. Phase-
New York: Raven Press; 1986. p. 333–48. locked response to low-frequency tones in single
96. Spangler KM, Warr WB. The descending auditory auditory nerve fibers of the squirrel monkey. J
system. In: Altschuler RA, Bobbin RP, Clopton BM, Neurophysiol 1967;30:769–93.
Hoffman DW, editors. Neurobiology of hearing: 110. Kiang NY. Processing of speech by the auditory
the central auditory system. New York: Raven Press; nervous system. J Acoust Soc Am 1980;68:830–5.
1991. 111. Sachs MB, Young ED. Encoding of steady state
97. Evans EF, Harrison RV. Correlation between vowels in the auditory nerve: representation in
cochlear outer hair cell damage and deterioration terms of discharge rate. J Acoust Soc Am 1979;66:
of cochlear nerve tuning properties in the guinea 470–9.
pig. J Physiol 1976;256:43–4. 112. Kiang NYS, Watanabe T, Thomas EC, Clark LF.
98. Brown MC, Nuttal AL, Masta RI. Intracellular Discharge patterns of single fibers in the cat’s audi-
recordings from cochlear inner hair cells: effects of tory nerve. Cambridge (MA): Massachusetts Insti-
stimulation of the crossed olivocochlear efferents. tute of Technology Press; 1965. MIT research
Science 1983;222:69–72. monograph no. 35.
99. Gifford ML, Guinan JJ. Effects of crossed-olivo- 113. Kiang NYS. A survey of recent developments in the
cochlear-bundle stimulation on cat auditory nerve fi- study of auditory physiology. Ann Otol Rhinol
ber responses to tones. J Acoust Soc Am 1983; Laryngol 1968;77:656–75.
74:115–23. 114. Evans EF. The dynamic range problem: place and
100. Winslow RL, Sachs MB. Effect of electrical stimu- time coding at the level of the cochlear nerve and
lation of the crossed olivocochlear bundle on audi- nucleus. In: Syka J, Aitkin L, editors. Neuronal
Physiology of the Auditory and Vestibular Systems 127
mechanisms of hearing. New York: Plenum Press; San Diego: Singular/Thompson Learning Press;
1981. p. 69–85. 2001. p. 575–611.
115. Evans EF, Palmer AR. Responses of units in the 128. Elgoyhen AB, Johson DS, Boulter J, et al. Alpha 9:
cochlear nerve and nucleus of the cat to signals in an acetylcholine receptor with novel pharmacolog-
the presence of bandstop noise. J Physiol 1975; ical properties expressed in rat cochlear hair cells.
252:60P–62P. Cell 1994;79:705–15.
116. Palmer AR, Evans EF. On the peripheral coding of 129. Desmedt JE. Physiological studies of the efferent
the level of individual frequency components of recurrent auditory system. In: Keidel WD, Neff
complex sound levels. Exp Brain Res 1979; Suppl WD, editors. Handbook of sensory physiology. Vol
2:19–20. V/2: physiological (CNS), behavioral studies, psy-
117. Young ED, Sachs MB. Representation of steady- choacoustics. New York: Springer-Verlag; 1974.
state vowels in the temporal aspects of the dis- p. 219–46.
charge patterns of populations of auditory-nerve 130. Vetter DE, Liberman MC, Mann J, et al. Role of
fibers. J Acoust Soc Am 1979;66:1381–403. alpha 9 nicotinic ACh receptor subunits in the
118. Liberman MC. Auditory-nerve response from cats development and function of cochlear efferent
raised in low-noise chamber. J Acoust Soc Am innervation. Neuron 1999;23:93–103.
1978;63:442–55. 131. Fuchs PA. Synaptic transmission at vertebrate hair
119. Kawase T, Liberman MC. Spatial organization of cells. Curr Opin Neurobiol 1996;6:514–9.
the auditory nerve according to spontaneous dis- 132. Ishii D, Balogh K. Distribution of efferent nerve
charge rate. J Comp Neurol 1992;319:312–8. endings in the organ of Corti. Their graphic recon-
120. Viemeister NF. Intensity coding and the dynamic struction in cochleae by localization of acetyl-
range problem. Hear Res 1988;34:267–74. cholinesterase activity. Acta Otolaryngol (Stockh)
121. Rasmussen GL. Anatomic relationships of the 1968;66:282–8.
ascending and descending auditory systems. In: 133. Igarashi M, Cranford JL, Nakai Y, Alford BR.
Fields WS, Alford BR, editors. Neurological aspects Behavioral auditory function after transection of
of auditory and vestibular disorders. Springfield crossed olivo-cochlear bundle in the cat. IV. Study
(MA): Charles C. Thomas Press; 1964. p. 1–19. of pure-tone frequency discrimination. Acta Oto-
122. Warr WB. The olivocochlear bundle: its origins and laryngol (Stockh) 1979;87:79–83.
terminations in the cat. In: Naunton RF, Fernandez 134. Moulin A, Collet L, Duclaux R. Contralateral audi-
C, editors. Evoked electrical activity in the auditory tory stimulation alters acoustic distortion products
nervous system. New York: Academic Press; 1978. in humans. Hear Res 1993;65:193–210.
p. 43–63. 135. Davis H. An active process in cochlear mechanics.
123. Iurato S, Smith CA, Eldredge DH, et al. Distribution Hear Res 1983;9:79–90.
of the crossed olivocochlear bundle in the chin- 136. Geisler CD. Hypothesis on the function of the
chilla’s cochlea. J Comp Neurol 1978;182:57–76. crossed olivocochlear bundle. J Acoust Soc Am
124. Spoendlin HH, Gacek RR. Electronmicroscopic 1974;56:1908–9.
study of the efferent and afferent innervation of the 137. Cody AR, Johnstone BM. Temporary threshold
organ of Corti in the cat. Ann Otol Rhinol Laryn- shift modified by binaural acoustic stimulation.
gol 1963;72:660. Hear Res 1982;6:199–205.
125. Liberman MC, Brown MC. Physiology and 138. Canlon B. The effect of acoustic trauma on the tec-
anatomy of single olivocochlear neurons in the cat. torial membrane, stereocilia, and hearing sensitivity:
Hear Res 1986;24:17–36. possible mechanisms underlying damage, recovery,
126. Liberman MC. Response properties of cochlear and protection. Scand Audiol Suppl 1988;27:1–45.
efferent neurons: monaural vs. binaural stimula- 139. Franklin DJ, Lonsbury-Martin BL, Stagner BB,
tion and the effects of noise. J Neurophysiol 1988; Martin GK. Altered susceptibility of 2f1-f2 acoustic-
60:1779–98. distortion products to the effects of repeated noise
127. Le Prell CG, Bledsoe SC, Bobbin RP, Puel J-L. exposure in rabbits. Hear Res 1991;53:185–208.
Neurotransmission in the inner ear: functional 140. Dagli S, Canlon B. The effect of repeated daily
and molecular analyses. In: Jahn AF, Santos- noise exposure on sound-conditioned and uncon-
Sacchi J, editors. Physiology of the ear. 2nd ed. ditioned guinea pigs. Hear Res 1997;104:39–46.
128 Ballenger’s Otorhinolaryngology
141. Brown MC, Kujawa SG, Liberman MC. Single 155. Morest DK. The neuronal architecture of the
olivocochlear neurons in the guinea pig. II. medial geniculate body of the cat. J Anat 1964;
Response plasticity due to noise conditioning. J 98:611–30.
Neurophysiol 1998;79:3088–97. 156. David E, et al. Decoding processes in the auditory
142. Canlon B, Fransson A, Viberg A. Medial olivo- system and human speech analysis. In: Evans EF,
cochlear efferent terminals are protected by sound Wilson JP, editors. Psychophysics and physiology of
conditioning. Brain Res 1999;850:253–60. hearing. New York: Academic Press; 1977. p. 509–16.
143. LePage EL. Frequency-dependent self-induced bias 157. Keidel WD. Information processing in the higher
of the basilar membrane and its potential for con- parts of the auditory pathway. In: Zwicker E, Ter-
trolling sensitivity and tuning in the mammalian hardt E, editors. Facts and models in hearing. New
cochlea. J Acoust Soc Am 1987;82:139–54. York: Springer-Verlag; 1974. p. 216–26.
144. Heimer L, Robards MJ. Neuroanatomical tract- 158. Rose JE. The cellular structure of the auditory
tracing methods. New York: Plenum Press; 1981. region of the cat. J Comp Neurol 1949;91:409–39.
145. Helfert RH, Snead CR, Alschuler RA. The ascend- 159. Winer JA, Diamond IT, Raczkowski D. Subdivi-
ing auditory pathways. In: Altschuler RA, Bobbin sions of the auditory cortex of the cat: the retro-
RP, Clopton BM, Hoffman DW, editors. Neurobi- grade transport of horseradish peroxidase to the
ology of hearing: the central auditory system. New medial geniculate body and posterior thalamic
York: Raven Press; 1991. p. 1–25. nuclei. J Comp Neurol 1977;176:387–417.
146. Moore JK. Cochlear nuclei: relationship to the 160. Coats AC. On electrocochleographic electrode
auditory nerve. In: Altschuler RA, Hoffman DW, design. J Acoust Soc Am 1974;56:708–11.
Bobbin RP, editors. Neurobiology of hearing: the 161. Picton TW, Hillyard SA, Krausz HI, Galabos R.
cochlea. New York: Raven Press; 1986. p. 283–301. Human auditory evoked potentials. I. Evaluation of
147. Phillips DP. Introduction to the central auditory components. Electroencephalogr Clin Neurophys-
nervous system. In: Jahn AF, Santos-Sacchi J, edi- iol 1974;36:179–90.
tors. Physiology of the ear. 2nd ed. San Diego: Sin- 162. Haapaniemi J, Laurikainen E, Johansson R, Karja-
gular/Thompson Learning Press; 2001. p. 613–38. lainen S. Transtympanic versus tympanic membrane
148. Lorenté de No R. Anatomy of the eighth nerve: I. electrocochleography in examining cochleovesti-
The central projection of the nerve endings of the bular disorders. Acta Otolaryngol Suppl (Stockh)
internal ear. Laryngoscope 1933;43:1–38. 2000;543:127–9.
149. Brawer JR, Morest DK, Kane EC. The neuronal 163. Elberling C. Simulation of cochlear action poten-
architecture of the cochlear nucleus of the cat. J tials recorded from the ear canal in man. In:
Comp Neurol 1974;155:251–300. Ruben RJ, Elberling C, Salomon G, editors.
150. Young ED. Response characteristics of neurons of Electrocochleography. Baltimore: University Park
the cochlear nucleus of the cat. In: Berlin CI, edi- Press; 1976.
tor. Hearing science: recent advances. San Diego: 164. Coats AC. Electrocochleography: recording tech-
College-Hill Press; 1984. p. 423–60. niques and clinical applications. Semin Hear 1986;
151. Goldberg JM, Brown PB. Response of binaural neu- 7:247.
rons of dog superior olivary complex to dichotic 165. Ferraro JA, Tibbils RP. SP/AP area ratio in the diag-
tonal stimuli: some physiological mechanisms of nosis of Meniere’s disease. Am J Audiol 1999;8:21–8.
sound localization. J Neurophysiol 1969;32:613–36. 166. Wuyts FL, Van de Heyning PH, Van Spaendonck M,
152. Thompson GC. Structure and function of the cen- et al. Rate influences on tone burst summating poten-
tral auditory system. Semin Hear 1983;4:81. tial amplitude in electrocochleography: clinical (a)
153. Brugge JF, Anderson DJ, Aitkin LM. Responses of and experimental (b) data. Hear Res 2001;152:1–9.
neurons in the dorsal nucleus of the lateral lemnis- 167. Moffat DA, Gibson WP, Ramsden RT, et al.
cus of cat to binaural tonal stimulation. J Neuro- Transtympanic electrocochleography during glyc-
physiol 1970;33:441–58. erol dehydration. Acta Otolaryngol (Stockh) 1978;
154. Schofield BR, Cant NB. Ventral nucleus of the lat- 85:158–66.
eral lemniscus in guinea pigs: cytoarchitecture and 168. Møller AR. Physiology of the ascending auditory
inputs from the cochlear nucleus. J Comp Neurol pathway with special reference to the auditory
1997;379:363–85. brainstem response (ABR). In: Pinheiro ML,
Physiology of the Auditory and Vestibular Systems 129
Musiek FE, editors. Assessment of central auditory 182. Shaywitz BA, Shaywitz SE, Pugh KR, et al. Sex dif-
dysfunction: foundations and clinical correlates. ferences in the functional organization of the brain
Baltimore: Williams and Wilkins; 1985. for language. Nature 1995;373:607–9.
169. Wada S, Starr A. Generation of auditory brainstem 183. Melcher JR, Sigalovsky IS, Guinan JJ, Levine RA.
responses. III. Effects of lesions of the superior Lateralized tinnitus studied with functional mag-
olive, lateral lemniscus, and inferior colliculus on netic resonance imaging: abnormal inferior col-
the ABR in guinea pig. Electroencephalogr Clin liculus activation. J Neurophysiol 2000;83:1058–72.
Neurophysiol 1983;56:352–66. 184. Cacace AT, Tasciyan T, Cousins JP. Principles of
170. Musiek FE, Gollegly KM, Kibbe KS, Verkest SB. functional magnetic resonance imaging: applica-
Current concepts on the use of ABR and auditory tion to auditory neuroscience. J Am Acad Audiol
psychophysical tests in the evaluation of brain stem 2000;11:239–72.
lesions. Am J Otol 1988;Suppl 9:25–35. 185. Filipo R, Delfini R, Fabiani M, et al. Role of tran-
171. Hosford-Dunn H. Auditory function tests. In: sient-evoked otoacoustic emissions for hearing
Cummings CW, et al, editors. Otolaryngology— preservation in acoustic neuroma surgery. Am J
head and neck surgery. St. Louis: CV Mosby; 1986. Audiol 1997;18:746–9.
172. Kaga K, Hink RF, Shimada Y, Suzuki J. Evidence for 186. Kemp DT, Ryan S. The use of transient evoked
a primary cortical origin of a middle latency audi- otoacoustic emissions in neonatal hearing screen-
tory evoked potential in cats. Electroencephalogr ing programs. Semin Hear 1993;14:30–45.
Clin Neurophysiol 1980;50:254–66. 187. Balkany TJ, Telischi FF, Lonsbury-Martin BL, Mar-
173. McGee TJ, Özdamar Ö, Kraus N. Auditory middle tin GK. Otoacoustic emissions in clinical practice.
latency responses in the guinea pig. Am J Oto- Am J Otol 1994;Suppl 15:29–38.
laryngol 1983;4:116–22. 188. Martin GK, Ohlms LA, Franklin DJ, et al. Distor-
174. Scherg M, Von Cramer D. Topographical analysis of tion-product otoacoustic emissions in humans: III.
auditory evoked potentials: derivation of compo- Influence of sensorineural hearing loss. Ann Otol
nents. In: Nodar R, Barber C, editors. Evoked poten- Rhinol Laryngol 1990;Suppl 147:30–42.
tials. Stoneham (MA): Butterworth Press; 1984. 189. Hotz MA, Probst R, Harris FP, Hauser R. Monitor-
175. Fifer RC, Sierra-Irizzary B. Clinical applications of ing the effects of noise exposure using transiently
the auditory middle latency response. Am J Otol evoked otoacoustic emissions. Acta Otolaryngol
1988;Suppl 9:47–56. (Stockh) 1993;113:478–82.
176. Kileny PR, Kemink JL. Electrically evoked middle- 190. Fiore C, Cagini C, Menduno P, et al. Evoked otoa-
latency auditory potentials in cochlear implant coustic emissions behaviour in retinitis pigmen-
candidates. Arch Otolaryngol Head Neck Surg 1987; tosa. Doc Ophthalmol 1994;87:167–76.
113:1072–7. 191. Zorowka PG, Schmitt HJ, Gutjahr P. Evoked otoa-
177. Duffy FH. Auditory brain mapping. In: Jahn AF, coustic emissions and pure tone threshold audiom-
Santos-Sacchi J, editors. Physiology of the ear. New etry in patients receiving cisplatinum therapy. Int J
York: Raven Press; 1988. Pediatr Otorhinolaryngol 1993;25:73–80.
178. Baran JA, Long RR, Musiek FE, Ommaya A. Topo- 192. Fortnum H, Farnsworth A, Davis A. The feasibility
graphic mapping of brain electrical activity in the of evoked otoacoustic emissions as an in-patient
assessment of central auditory nervous system hearing check after meningitis. Br J Audiol 1993;
pathology. Am J Otol 1988;Suppl 9:72–6. 27:227–31.
179. Hari R, Lounasmaa OV. Recording and interpre- 193. Stover L, Norton SJ. The effects of aging on otoa-
tation of cerebral magnetic fields. Science 1989;244: coustic emissions. J Acoust Soc Am 1993;94:
432–6. 2670–81.
180. Hari R, Pelizzone M, Makela JP, et al. Neuromag- 194. Hall JW, Baer JE, Chase PA, Schwaber MK. Clinical
netic responses from a deaf subject to stimuli pre- application of otoacoustic emissions: what do we
sented through a multi-channel cochlear prosthesis. know about factors influencing measurement and
Ear Hear 1988;9:148–52. analysis? Otolaryngol Head Neck Surg 1994;110:
181. Zatorre RJ, Belin P. Spectral and temporal process- 22–38.
ing in human auditory cortex. Cereb Cortex 2001; 195. Lonsbury-Martin BL, Martin GK, Balkany T. Clinical
11:946–53. applications of otoacoustic emissions. In: Lucente
130 Ballenger’s Otorhinolaryngology
FE, editor. Highlights of the instructional courses. chemical stimuli. Acta Otolaryngol (Stockh) 1991;
Alexandria (VA): American Academy of Otolaryn- 111:291–7.
gology—Head and Neck Surgery; 1994. p. 343–55. 210. Wersall J, Flock A, Lundquist PG. Structural basis
196. Igarashi M, Miyata L, Alford BR. Utricular ablation for directional sensitivity in cochlear and vestibu-
and dysequilibrium in squirrel monkeys. Acta Oto- lar sensory receptors. Cold Spring Harb Symp
laryngol (Stockh)1972;74:66–72. Quant Biol 1965;30:115–32.
197. Fernandez C, Goldberg JM. Physiology of periph- 211. Engstrom H, Bergstrom B, Ades HW. Macula utri-
eral neurons innervating otolith organs of the culi and macula saculi in the squirrel monkey. Acta
squirrel monkey. I. Response to static tilts and to Otolaryngol Suppl (Stockh) 1972;301:75–126.
long-duration centrifugal force. J Neurophysiol 212. Tilney LG, DeRosier DJ, Mulroy MJ. The organiza-
1976;39:970–84. tion of actin filaments in the stereocilia of cochlear
198. Fernandez C, Goldberg JM. Physiology of peripheral hair cells. J Cell Biol 1980;86:244–59.
neurons innervating otolith organs of the squirrel 213. Assad JA, Shepherd GM, Corey DP. Tip link
monkey. II. Directional selectivity and force- integrity and mechanical transduction in verte-
response relations. J Neurophysiol 1976;39:985–95. brate hair cells. Neuron 1991;7:985–94.
199. Fernandez C, Goldberg JM. Physiology of periph- 214. Spoendlin H. Receptor ultrastructure. In: De Reuck
eral neurons innervating otolith organs of the AVS, Knight J, editors. Symposium on hearing
squirrel monkey. III. Response dynamics. J Neuro- mechanisms in vertebrates. Boston (MA): Little
physiol 1976;39:996–1008. Brown Press; 1968. p. 89–119.
200. Wendt GR. Vestibular functions. In: Stevens SS, 215. Hillman DE, McLaren JW. Displacement configu-
editor. Handbook of experimental psychology. ration of semiciruclar canal cupulae. Neuroscience
New York: John Wiley & Sons; 1951. 1979;4:1989–2000.
201. Cogan DG. Some objective and subjective observa- 216. McLaren JW, Hillman DE. Displacement of semi-
tions on the vestibulo-ocular system. Am J Oph- circular canal cupula during sinusoidal rotation.
thalmol 1958;45:74. Neuroscience 1979;4:2001-8.
202. de Beer GR. Presidential address: how animals hold 217. Oman CM, Young LR. Physiological range of pres-
their heads. Proc Linn Soc Lond 1947;159:125. sure difference and cupula deflections in the
203. Juhn SK. Biochemistry of the labyrinth: a manual. human semicircular canal: theoretical considera-
Rochester (MN): American Academy of Ophthal- tions. Prog Brain Res 1972;37:529–39.
mology and Otolaryngology; 1973. 218. Steinhausen W. The cupula. Z Hals Nas Ohrenh
204. Dohlman GF. Critical review of the concept of 1931;29:211.
cupula function. Acta Otolaryngol Suppl (Stockh) 219. Goldberg JM, Ferenadez C. Physiology of periph-
1980;376:1–30. eral neurons innervating semicircular canal of the
205. Carlstrom D, et al. Electron microscopic and x-ray squirrel monkey. I. Resting discharge and response
diffraction studies of statoconia. Laryngoscope to constant angular accelerations. J Neurophysiol
1953;63:1052–7. 1971;34:635–60.
206. Wersall J, et al. Ultrastructure of the vestibular end 220. Goldberg JM, Fernandez C. Vestibular mecha-
organs. In: De Reuck AVS, Knight J, editors. nisms. Ann Rev Physiol 1975;37:129–62.
Myotatic, kinesthetic and vestibular mechanisms. 221. Keller EL. Behavior of horizontal semicircular
Boston (MA): Little, Brown Press; 1968. p. 105–16. canal afferents in alert monkey during vestibular
207. Spoendlin H. Ultrastructure of the vestibular sense and optokinetic stimulation. Exp Brain Res 1976;
organ. In: Wolfson RJ, editor. The vestibular system 24:459–71.
and its diseases. Philadelphia (PA): University of 222. Fernandez C, Goldberg JM. Physiology of periph-
Pennsylvania Press; 1966. eral neurons in innervating semicircular canals of
208. Anniko M, Thornell LE, Virtanen I. Cytoskeletal the squirrel monkey. II. Response to sinusoidal
organization of the human inner ear. IV. Expres- stimulation and dynamics of peripheral vestibular
sion of actin in vestibular organs. Acta Otolaryngol system. J Neurophysiol 1971;34:661–75.
Suppl (Stockh) 1987;437:5–76. 223. Brodal A. Neurological anatomy in relation to
209. Zenner HP, Zimmermann U. Motile responses of clinical medicine. New York: Oxford University
vestibular hair cells following caloric, electrical or Press; 1969.
Physiology of the Auditory and Vestibular Systems 131
224. Baker R. The nucleus prepositus hypoglossi. In: 239. Bechterew W. Ergebnisse der Durchschneidung des N.
Brooks BA, Bajandas FJ, editors. Eye movements. acusticus, nebst Eroerterung der Bedeutung der semi-
New York: Plenum Press; 1977. circulaeren Canaele fuer das Koerpergleichgewicht.
225. Keller EL. The behavior of eye movement motoneu- Pfluegers Arch Ges Physiol 1883;30:312–47.
rons in the alert monkey. Bibl Ophthalmol 1972;82: 240. Darlington CL, Smith PF. Molecular mechanisms
7–16. of recovery from vestibular damage in mammals:
226. Cannon SC, Robinson DA. Loss of the neural recent advances. Prog Neurobiol 2000;62:313–25.
integrator of the oculomotor system from brainstem 241. Highstein SM. Abducens to medical rectus pathway
lesions in monkey. J Neurophysiol 1987;57:1383–409. in the MLF: a possible cellular basis for the syn-
227. Wilson VJ, Wylie RM, Marco LA. Organization of drome of internuclear ophthalmoplegia. In: Brooks
the medial vestibular nucleus. J Neurophysiol 1968; BA, Bajandas FJ, editors. Eye movements. New
31:166–75. York: Plenum Press; 1977.
228. Miller EF, Graybiel A. A comparison of ocular 242. Gauthier GM, Robinson DA. Adaptation of the
counter rolling movements between normal per- human vestibulo-ocular reflex to magnifying
sons and deaf subjects with bilateral labyrinthine lenses. Brain Res 1975;92:331–5.
defects. Ann Otol Rhinol Laryngol 1963;72:885–93. 243. Miles FA, Fuller JH. Adaptive plasticity in the
229. Goldberg JM. Afferent diversity and the organiza- vestibulo-ocular responses of the rhesus monkey.
tion of central vestibular pathways. Exp Brain Res Brain Res 1974;80:512–6.
2000;130:277–97. 244. Robinson DA. Adaptive gain control of the
230. Kotchabhakdi N, Walberg F. Primary vestibular vestibulo-ocular reflex by the cerebellum. J Neuro-
afferent projections to the cerebellum as demon- physiol 1976;39:954–69.
strated by retrograde axonal transport of horserad- 245. Kohler I. Experiments with goggles. Sci Am 1962;
ish peroxidase. Brain Res 1978;142:142–6. 206:62–84.
231. Kotchabhakdi N, Walberg F. Cerebellar afferent 246. Melvill-Jones G, et al. Long-term effects of main-
projections from the vestibular nuclei in the cat: an tained vision reversal: is vestibulo-ocular adaptation
experimental study with the method of retrograde either necessary or sufficient? In: Baker R, Berthoz A,
axonal transport of horseradish peroxidase. editors. Control of gaze by brainstem neurons. Vol 1:
Exp Brain Res 1978;31:591–604. developments in neuroscience. Amsterdam: Else-
232. Fredrickson JM, Frigge U, Scheid P, Kornhuber HH. vier/North-Holland Biomedical; 1977.
Vestibular nerve projection to the cerebral cortex of 247. Miles FA. The primate flocculus and eye-head
the rhesus monkey. Exp Brain Res 1966;2:318–27. coordination. In: Brooks BA, Bajandas FJ, editors.
233. Deecke L, Schwartz DW, Fredrickson JM. The Eye movements. New York: Plenum Press; 1977.
vestibular thalamus in the rhesus monkey. Adv 248. Robinson DA. Is the cerebellum too old to learn?
Otorhinolaryngol 1973;19:210–9. In: Brooks BA, Bajandas FJ, editors. Eye move-
234. Wilson VJ, Melvill-Jones G. Mammalian vestibular ments. New York: Plenum Press; 1977.
physiology. New York: Plenum Press; 1979. 249. Simpson J, Alley KE. Visual climbing fiber input to
235. Precht W, Shimazu H, Markham CH. A mechanism rabbit vestibulo-cerebellum: a source of direction-
of central compensation of vestibular function fol- specific information. Brain Res 1974;82:301–8.
lowing hemilabyrinthectomy. J Neurophysiol 1966; 250. Honrubia V, Koehn WW, Jenkins HA, Fenton WH.
29:996–1010. Effect of bilateral ablation of the vestibular cere-
236. Igarashi M, Levy JK, O-Uchi T, Reschke MF. bellum on visual-vestibular interaction. Exp Neu-
Further study of physical exercise and locomotor rol 1982;75:616–26.
balance compensation after unilateral labyrinthec- 251. Sato Y, Kato I, Kawasaki T, et al. Failure of fixation
tomy in squirrel monkeys. Acta Otolaryngol suppression of caloric nystagmus and ocular motor
(Stockh) 1981;92:101–5. abnormalities. Arch Neurol 1980;37:35–8.
237. Fetter M, Zee DS. Recovery from unilateral 252. Miles FA, Braitman DJ, Dow BM. Long-term
labyrinthectomy in rhesus monkey. J Neurophysiol adaptive changes in primate vestibuloocular reflex.
1988;59:370–93. IV. Electrophysiological observations in flocculus
238. Brandt T. Management of vestibular disorders. J of adapted monkeys. J Neurophysiol 1980;43:
Neurol 2000;247:491–9. 1477–93.
132 Ballenger’s Otorhinolaryngology
253. Lisberger SG. The neural basis for learning of sim- ototoxicity in domestic chickens. J Neurophysiol
ple motor skills. Science 1988;242:728–35. 1999;81:1025–35.
254. Luebke AE, Robinson DA. Gain changes of the cat’s 268. Woolley SM, Wissman AM, Rubel EW. Hair cell
vestibulo-ocular reflex after flocculus deactivation. regeneration and recovery of auditory thresholds
Exp Brain Res 1994;98:379–90. following aminoglycoside ototoxicity in Bengalese
255. McNally WJ, Stuart WA. Physiology of the finches. Hear Res 2001;153:181–95.
labyrinth. Chicago: American Academy of Oph- 269. Girod DA, Duckert LG, Rubel EW. Possible precur-
thalmology and Otolaryngology; 1967. sors of regenerated hair cells in the avian cochlea fol-
256. Benson AJ, Jobson PH. Body sway induced by a low lowing acoustic trauma. Hear Res 1989;42:175–94.
frequency alternating current. Int J Equilib Res 270. Tsue TT, Watling DL, Weisleder P, et al. Identifica-
1973;3:55–61. tion of hair cell progenitors and intermitotic
257. Cohen B. Vestibulo-ocular relations. In: Bach-y- migration of their nuclei in the normal and regen-
Rita P, Collins CC, Hyde JE, editors. The control of erating avian inner ear. J Neurosci 1994;14:140–52.
eye movements. New York: Academic Press; 1971. 271. Forge A, Li L, Nevill G. Hair cell recovery in the
p. 105–48. vestibular sensory epithelia of mature guinea pigs.
258. Corwin JT, Jones JE, Katayama A, et al. Hair cell J Comp Neurol 1998;397:69–88.
regeneration: the identities of progenitor cells, 272. Montcouquiol M, Corwin JT. Brief treatments with
potential triggers, and instructive cues. In: Regen- forskolin enhance s-phase entry in balance epithe-
lia from the ears of rats. J Neurosci 2001;21:974–82.
eration of vertebrate sensory receptor cells (Ciba
273. Marazita ML, Ploughman LM, Rawlings B, et al.
Foundation Symposium 160). Chichester (Eng-
Genetic epidemiological studies of early-onset
land): Wiley Press; 1991. p. 103–19.
deafness in the U.S. school-age population. Am J
259. Rubel EW. Regeneration of hair cells in the avian
Med Genet 1993;46:486–91.
inner ear. In: Dancer AL, Henderson D, Salvi RJ,
274. Tseng CJ, Lalwani AK. Cracking the auditory
Hamernik RP, editors. Noise-induced hearing loss.
genetic code: Part II. Syndromic hereditary hear-
St. Louis: Mosby Yearbook; 1992.
ing impairment. Am J Otol 2000;21:437–51.
260. Cotanche DA, Lee KH, Stone JS, Picard DA. Hair
275. Kalatzis V, Petit C. The fundamental and medical
cell regeneration in the bird cochlea following
impacts of recent progress in research on heredi-
noise damage or ototoxic drug damage. Anat
tary hearing loss. Hum Mol Genet 1998;7:1589–97.
Embryol (Berl) 1994;189:1–18. 276. Smith RJ, Van Camp G. Cloning genes for non-syn-
261. Cotanche DA. Regeneration of hair cell stereocil- dromal hearing impairment. Br J Audiol 1999;
iary bundles in the chick cochlea following severe 33:271–8.
acoustic trauma. Hear Res 1987;30:181–95. 277. Fischel-Ghodsian N. Genetic factors in aminogly-
262. Cotanche DA. Video-enhanced DIC images of the coside toxicity. Ann N Y Acad Sci 1999;84:99–109.
noise-damaged and regenerated chick tectorial 278. Lomax MI, Huang L, Cho Y, et al. Differential dis-
membrane. Exp Neurol 1992;115:23–6. play and gene arrays to examine auditory plasticity.
263. Ryals BM, Rubel EW. Hair cell regeneration after Hear Res 2000;147:293–302.
acoustic trauma in adult Coturnix quail. Science 279. Luebke AE, Steiger JD, Hodges BL, Amalfitano A. A
1988;240:1774–6. modified adenovirus can transfect cochlear hair
264. Ryals BM, Westbrook EW. TEM analysis of neural cells in vivo wthout compromising cochlear func-
terminals on autoradiographically identified regen- tion. Gene Ther 2001;8:789–94.
erated hair cells. Hear Res 1994;72:81–8.
265. Cohen YE, Saunders JC. The effects of sound over- USEFUL WEBSITES
exposure on the spectral response patterns of www.bme.jhu.edu/labs/chb/oto.wustl.edu/cochleafluids
nucleus magnocellularis in the neonatal chick. Exp www.medschool.lsumc.edu/otor/kresge.htm
Brain Res 1993;95:202–12. www.parmly.luc.edu/parmly/
266. Weisleder P, Rubel EW. Hair cell regeneration after www.khri.med.umich.edu/index.htm-depts.washington
streptomycin toxicity in the avian vestibular .edu/hearing
epithelium. J Comp Neurol 1993;331:97–110. www.oae.it
267. Goode CT, Carey JP, Fuchs AF, Rubel EW. Recovery www.neurophys.wisc.edu/www/aud/ctl.augie.edu/perry/
of the vestibulocolic reflex after aminoglycoside ear/tours.htm
Physiology of the Auditory and Vestibular Systems 133
Within the past 25 years, dramatic advances in tech- strategies for hearing assessment of adults, with an
nology and techniques have contributed to more emphasis on the application of a test battery
powerful audiologic test batteries and more effective approach that maximizes diagnostic accuracy and
management options for pediatric and adult popu- efficiency while minimizing test time and costs. The
lations. With auditory brainstem response (ABR) chapter includes a review of current hearing aid
and otoacoustic emissions (OAEs), newborn infants technology for nonmedical management of hearing
can be screened for hearing impairment within days impairment. Following the review is a summary of
after birth and managed audiologically within the pediatric audiologic habilitation approaches. At the
next critical 6 months. New techniques and strate- end of the chapter, we define in a glossary common
gies for the assessment of auditory function in adults audiologic terms and abbreviations.
have also been introduced in recent years. Pure-tone
audiometry, immittance measurements (tympa-
nometry and acoustic reflexes), and calculation of BASIC AUDIOLOGIC TEST BATTERY
word recognition scores continue to be important
for hearing assessment, and the traditional audio-
PURE-TONE AUDIOMETRY
gram remains very useful in summarizing the results Pure-tone audiometry, the most common hearing
of basic audiologic assessment. Clinical audiology, test, is a measure of hearing sensitivity using sinu-
however, now also includes other behavioral and soid stimuli at octave frequencies from 250 Hz up to
electrophysiologic test procedures. For example, 8,000 Hz and usually at two interoctave frequencies
electrocochleography (ECochG) can contribute to (3,000 and 6,000 Hz). The normal-hearing young
the diagnosis of Meniere’s disease. Auditory brain- (under 20 years) ear responds to frequencies from
stem response offers a readily accessible and rela- 20 to 20,000 Hz. Test results are graphed on an
tively inexpensive means for identification of audiogram. Two common audiogram versions are
retrocochlear auditory dysfunction. A variety of illustrated in Figure 5–1, A and B. All audiograms
speech and nonspeech behavioral measures and sev- include, minimally, a graph for plotting hearing
eral cortical auditory evoked responses are available threshold levels (HTLs) as a function of the fre-
for clinical assessment of central auditory nervous quency of pure-tone signals, although the exact for-
system dysfunction and associated auditory process- mat and symbols may vary.
ing disorders. Finally, OAEs, because of their unique The unit of stimulus intensity is the decibel
sensitivity and specificity to cochlear dysfunction, (dB), a logarithmic unit. The intensity of any sound
have become the latest addition to the clinical audi- is defined by a ratio of its sound pressure (or sound
ologic test battery. intensity) compared to a reference sound pressure
The otolaryngologist is in a pivotal position to (or sound intensity). The reference sound pressure is
identify children and adults at risk for hearing loss, the amount of pressure against the eardrum, caused
to work closely with audiologists in diagnostic hear- by air molecules when a sound is present, that
ing assessment, and to contribute to timely and vibrates the eardrum and can just be detected by a
appropriate medical or surgical intervention. In this normal human ear. Briefly, the relationship for
chapter, we summarize current techniques and sound intensity is described as dB = 10 log 10 (sound
134
Diagnostic Audiology, Hearing Aids, and Habilitation Options 135
FIGURE 5–1. Two examples of audiogram formats. A includes sections for graphically and numerically reporting
results for pure-tone audiometry (top portion), speech audiometry (middle portion), and aural immittance measure-
ment (bottom portion). Masking is indicated by filled symbols. Findings for the right ear represent a typical sensorineural
hearing loss audiometric pattern, whereas left ear findings typify a conductive hearing loss. continued
136 Ballenger’s Otorhinolaryngology
FIGURE 5–1 Continued. With B, the results for both ears are plotted on the same graph, requiring a separate symbol
system for each ear. The same audiometric findings shown in A are also plotted in B, producing less clear analysis.
(see Figure 5–1), the dB scale has as its reference ment. They offer distinct advantages over the tradi-
0 dB, which is described as “audiometric 0 (zero).” tional supra-aural earphones, including increased
This is the standard for the intensity level that cor- comfort, reduced likelihood of ear canal collapse,
responds to the average normal HTL, the minimal greater interaural attenuation, disposability (aural
detectable intensity for each test frequency for nor- hygiene), and greater acceptance by young children.1
mal hearers. Another common unit for expressing Pure-tone audiometry can also be performed with
sound intensity is dB sensation level (SL) which is the stimuli presented by a bone-conduction oscillator or
intensity of the stimulus in dB above an individual’s vibrator placed on the mastoid bone. During pure-
hearing threshold. For example, a word recognition tone audiometry, all equipment meets ANSI (Amer-
test may be administered at an intensity level of 40 dB ican National Standards Institute) specifications,
SL (40 dB above the patient’s pure-tone average). and testing is carried out according to clinical adap-
In adult audiologic assessment, hearing thresh- tations of psychoacoustic methods.2 Patients are
olds for tonal or speech signals are measured sepa- instructed to listen carefully for the tones and to
rately for each ear with earphones (air-conduction respond (usually by pushing a button that activates
stimulation). Insert earphones (ER-3A) are now the a response light on the audiometer or raising their
transducer of choice for routine audiologic assess- hand) every time they think they hear a tone. To
Diagnostic Audiology, Hearing Aids, and Habilitation Options 137
minimize interference by ambient background vibrator may be transmitted through the skull to
acoustic noise, pure-tone audiometry should always either or both inner ears. Actual perception of this
be carried out with the patient in a double-walled, bone-conducted signal will, of course, depend on the
sound-treated room meeting ANSI specifications.1,3 patient’s sensorineural hearing sensitivity in each ear.
For adults, the clinically normal region on the Masking is the audiometric technique used to
audiogram is from 0 to 20 dB HL. The normal region eliminate participation of the nontest ear whenever
for children is more limited because even very mild air- and bone-conduction stimulation exceeds inter-
hearing loss can interfere with speech and language aural attenuation. An appropriate noise (narrow-
acquisition. Pediatric hearing threshold levels exceed- band noise for pure-tone signals and speech noise
ing 15 dB may be considered abnormal. Thresholds for speech signals) is presented to the nontest ear
in the 20 to 40 dB HL region constitute a mild hear- when the stimulus is presented to the test ear. With
ing loss, 40 to 60 dB HL thresholds define a moder- adequate masking, any signal crossing over to the
ate loss, and threshold levels greater than 60 dB HL nontest ear is masked by the noise. Selection of
are considered a severe hearing loss.1 As a reference, appropriate masking is sometimes difficult, espe-
the intensity level of whispered speech close to the cially when there is bilateral hearing impairment.
ear is less than 25 dB HL, conversational speech is One should always attempt to verify that appropri-
in the 40 to 50 dB HL region, and a shouted ate masking was used in interpreting audiologic
voice within a foot of the ear is at a level of about results when the tester is not known and, particu-
80 dB HL. The essential frequencies for understand- larly, if testing was not performed by an audiologist.
ing speech are in the 500 through 4,000 Hz region, Comparison of the hearing thresholds for air-
although higher frequencies also contribute to dis- versus bone-conduction signals is useful in classify-
crimination between certain speech sounds. Hearing ing type of hearing loss, that is, whether a hearing loss
sensitivity within the “speech frequency” region is is sensorineural (no air–bone gap), conductive (nor-
traditionally summarized by calculating the pure- mal bone conduction and a loss by air conduction),
tone average (PTA) (hearing thresholds for 500, 1,000, or mixed (loss by bone conduction with a superim-
and 2,000 Hz divided by three and reported in dB). posed air- versus bone-conduction gap). Configura-
The validity of audiometric results depends tion refers to hearing loss as a function of the test
on whether the patient’s responses result from stim- frequency. With the sloping configuration, hearing
ulation of the test ear. If a sound of greater than is better for low frequencies and then becomes
40 dB HL is presented to one ear via standard ear- poorer for higher frequencies. High-frequency
phones with supra-aural (resting on the outer ear) deficit hearing loss is the most common pattern
cushions, it is possible that the acoustic energy will associated with a sensorineural hearing impairment.
cross over from one side of the head to the other and A rising configuration is typified by relatively poor
stimulate the nontest ear. The mechanism for the hearing for lower-frequency stimuli and better hear-
crossover is presumably bone-conduction stimula- ing for the high frequencies. The rising configura-
tion caused by vibration of the earphone cushion tion can result from varied types of middle ear
against the skull at high stimulus intensity levels. pathology. One exception to the typical association
The amount of sound intensity needed before the of conductive hearing loss with rising configuration
crossover occurs is a reflection of interaural attenu- is Meniere’s disease (see Chapter 20). Meniere’s dis-
ation, that is, the sound insulation between the two ease is a manifestation of a cochlear lesion that pro-
ears provided by the head. Interaural attenuation is duces a rising configuration. A flat audiometric
usually about 50 dB for lower test frequencies and configuration is often recorded from patients with
60 dB for higher test frequencies (such as those con- mixed hearing loss, that is, when both sensorineural
tributing to the ABR). Interaural attenuation is con- and conductive components are present.
siderably higher for insert earphones.1 With
bone-conduction stimulation, interaural attenuation
is very limited (at most 10 dB). Clinically, one must
SPEECH AUDIOMETRY
assume that interaural attenuation for bone-con- Speech audiometry measures how well a person hears
ducted signals is 0 dB. That is, any sound presented and understands speech signals. Speech audiometry
to the mastoid bone of one ear by a bone-conduction procedures are used routinely to measure hearing
138 Ballenger’s Otorhinolaryngology
sensitivity (thresholds in dB) for words or to esti- materials presented via a compact disc player and an
mate word recognition (ie, speech discrimination) audiometer.1 Diagnostic speech audiometry using
ability. Spondee reception threshold (SRT), also more sophisticated materials (eg, spectrally
referred to as the speech reception threshold (SRT) degraded or temporally distorted speech, or speech
or speech threshold (ST), is the softest intensity level in noise materials) is feasible for assessment of the
at which a patient can correctly repeat words central auditory system.1,4
approximately 50% of the time. Spondee words,
two-syllable words with equal stress on each syllable
(eg, airplane, baseball, cowboy), are presented to the IMMITTANCE MEASUREMENT
patient monaurally via earphones. The technique is Aural immittance (impedance) measures are an
equivalent to the method for determining pure-tone important part of the basic audiometry test battery.
thresholds described previously. Immittance is a term derived from the terms for two
Because the PTA indicates HTLs in the speech related techniques for assessing middle ear function
frequency region and ST or SRT is measured with a (impedance and admittance), techniques that have
speech signal, close agreement between the PTA and been applied clinically since 1970.5 Briefly, the exter-
the ST is expected. If the difference between PTA and nal ear canal is sealed with a soft rubber probe tip.1
ST exceeds ±7 dB, there is reason to suspect that one Connected to the probe tip is a device producing a
or both of the measures is invalid. An unusually good tone that is delivered toward the eardrum. Middle
ST relative to PTA (eg, ST of 5 dB and PTA of 45 dB) ear impedance or admittance is calculated from the
should immediately alert the tester to the possibility intensity and other physical properties (eg, phase) of
of a nonorganic hearing loss, as in malingering. With the tone in the ear canal. A middle ear (tympanic
cooperative adult patients, particularly if pure-tone membrane and ossicles) system with low impedance
hearing thresholds are within the normal region (high admittance) more readily accepts the acoustic
from 500 to 4,000 Hz, there is probably little or no energy of the probe tone, whereas a middle ear with
clinical benefit in measuring speech thresholds. Test abnormally high impedance (low admittance)
time can be saved, with no loss of diagnostic infor- caused, for example, by fluid within the middle ear
mation, by excluding speech threshold measurement space tends to reject energy flow. Thus, impedance
from the test battery for such patients. (admittance) characteristics of the middle ear sys-
The common clinical approach for estimating tem can be inferred objectively with this quick and
a person’s ability to hear and understand speech is noninvasive technique and then related to well-
speech recognition for phonetically balanced (PB) known patterns of findings for various types of mid-
words.1 Usually, a list of 25 or 50 single-syllable dle ear lesions.
words is presented to the patient via earphones at
one or more fixed intensity levels, and the percent- Tympanometry Tympanometry is the continuous
age of words correctly repeated by the patient is cal- recording of middle ear impedance as air pressure in
culated by the tester. One ear is tested at a time. the ear canal is systematically increased or decreased.
Within the list of words, specific speech sounds The technique is a sensitive measure of tympanic
(phonemes) occur approximately as often as they membrane integrity and middle ear function (Figure
would in everyday conversation (they are “phoneti- 5–2). Compliance (the reciprocal of stiffness) of the
cally balanced”). Traditionally, these words were middle ear, the dominant component of immittance,
spoken into a microphone by the tester, while the is the vertical dimension of a tympanogram. Tympa-
level was monitored with a VU (volume unit) meter. nometry is popular clinically because it requires min-
Then the words were routed to the patient through imal technical skill and less than a minute to
the audiometer after selection of the test ear and perform. Because immittance measurement is an
desired intensity level. This is, however, an outdated electrophysiologic (versus behavioral) method, it
and poor clinical practice since it lacks standardiza- does not depend on cooperation of the patient.
tion and consistency and increases the variability of Importantly, it is a sensitive measure of middle ear
test outcome. With adult patients, it is almost always function. Tympanometric patterns, in combination
possible and always preferable to use professionally with audiogram patterns, permit differentiation
produced (and commercially available) speech among and classification of middle ear disorders.
Diagnostic Audiology, Hearing Aids, and Habilitation Options 139
In 1970, James Jerger described what has from patients with fixation of the ossicular chain,
become the most clinically widespread approach for including those with the diagnosis of otosclerosis. In
describing tympanograms. There are three general contrast, with an usually steep and high-compliance
tympanogram types: A, B, and C. The normal, or tympanogram (type Ad for deep), the peak may
type A, tympanogram has a distinct peak in compli- actually exceed the upper compliance limits of the
ance within 0 to –100 mm of water pressure (deca- equipment. The Ad tympanogram type is recorded
pascals) in the ear canal (see Figure 5–2). To be from patients with disruption of the ossicular chain,
classified as normal, the location of the compliance which leaves the middle ear extremely mobile and
peak on the pressure dimension and the height of the hypercompliant (ie, very little impedance). In the
peak must be within the normal range, indicated in absence of serious hearing loss, however, this tym-
the figure by the stippled area. With a type B tym- panogram pattern is usually associated with minor
panogram, there is no peak in compliance but, tympanic membrane abnormality, such as scarring.
rather, a flat pattern with little or even no apparent During the initial portion of the tympanometry pro-
change in compliance as a function of pressure in the cedure, high positive or negative pressure is intro-
ear canal. This pattern is most often associated with duced into the ear canal. This essentially decouples
fluid within the middle ear space (eg, otitis media), the middle ear system from the measurement. If the
although other middle ear lesions may give rise to a immittance device records an abnormally large
type B tympanogram as well. Type C tympanograms equivalent volume of air (eg, 2 cm3 or more in an
also have a distinct peak in compliance (as with the adult or twice the volume that was recorded for the
type A), but the peak is within the negative pressure other ear) between the probe tip and presumably the
region beyond –150 mm H2O (or dkPa). This pat- eardrum at this stage in the procedure, the integrity
tern is usually found in patients with eustachian tube of the eardrum should be questioned. That is, the
dysfunction and inadequate ventilation of the middle immittance device is recording not just ear canal vol-
ear space and often precedes the type B tym- ume but also volume of the middle ear space. This
panogram in the development of otitis media. test finding is consistent with either a perforation of
The type As (see Figure 5–2) is a variation of the tympanic membrane or an open (patent) middle
the type A tympanogram. The “s”stands for shallow. ear ventilation tube.
Peak compliance is below the lower normal limits of
compliance. That is, middle ear impedance is abnor- Acoustic Stapedial Reflex Measurement Measure-
mally high. The type As pattern is typically recorded ment of contractions of the middle ear stapedial mus-
140 Ballenger’s Otorhinolaryngology
cle to high sound intensity levels (usually 80 dB or auditory late response (ALR), the P300 response, and
greater) is the basis of the acoustic reflex test. The the mismatch negativity (MMN) response.1,6 In fact,
stapedial muscle within the middle ear is the smallest cortical auditory evoked responses were reported as
muscle in the body. Acoustic reflex measurement is early as the 1930s, and, with the exception of the
clinically useful for estimating hearing sensitivity and MMN, all of the above responses were well described
for differentiating among sites of auditory disorders, before the ABR was even discovered. Cortical audi-
including the middle ear, inner ear, eighth cranial tory evoked responses are characterized by longer
nerve, and auditory brainstem. The afferent portion latencies (100 to 300 ms) than ECochG and ABR
of the acoustic reflex arc is the eighth cranial nerve. because they arise from more rostral regions of the
There are complex brainstem pathways leading from auditory central nervous system and are dependent
the cochlear nucleus on the stimulated side to the on multisynaptic pathways. Amplitudes of the corti-
region of the motor nucleus of the seventh (facial) cal responses are considerably larger (2 to 20 times
nerve on both sides (ipsilateral and contralateral to larger) than those of the earlier responses because
the stimulus) of the brainstem. The efferent portion they reflect activity evoked from a greater number of
of the arc is the seventh nerve innervating the neurons. Measurement parameters are distinctly dif-
stapedius muscle. When the muscle contracts, the ferent for the cortical versus cochlear or brainstem
result is increased stiffness (decreased compliance) of responses. For example, stimulus rate must be slower
the middle ear system. This small change in compli- and physiologic filter settings lower. As a rule, stimu-
ance following stapedius muscle contraction (within lus intensities are moderate rather than high. Corti-
10 ms) is detected by the probe and immittance cal evoked responses are best elicited with
device. longer-duration, and therefore frequency-specific,
Measurement of the acoustic reflex is useful tonal stimuli rather than the click stimuli that are
clinically because it can quickly provide objective optimal for evoking ECochG and ABR. The analysis
information on the status of the auditory system time must, of course, extend beyond the expected
from the middle ear to the brainstem. Distinctive latency of the response (> 300 ms) for the cortical
acoustic reflex patterns for ipsilateral and contralat- responses. Recording electrode sites also are different
eral stimulation and measurement conditions for the cortical responses, with more emphasis on
characterize middle ear, cochlear, eighth nerve, scalp sites over the hemispheres and less concern
brainstem, and even facial nerve dysfunction (see about electrode sites near the ears.
“faces” in lower portion of Figure 5–1, A). Compar-
ison of acoustic reflex threshold levels, the lowest AUDITORY BRAINSTEM RESPONSE
stimulus intensity level that activates the reflex, for
tonal versus noise signals permits estimation of the Among the many auditory evoked responses, the
degree of cochlear hearing impairment.1 This tech- ABR (often referred to by neurologists as the brain-
nique is especially valuable in children and difficult- stem auditory evoked response or BAER) and
to-test patients. ECochG are applied most often clinically. An ABR
recording is shown schematically in Figure 5–3. The
ABR is generated with transient acoustic stimuli
AUDITORY EVOKED RESPONSES (clicks or tone bursts) and detected with surface
Auditory evoked responses are electrophysiologic electrodes (disks) placed on the forehead and near
recordings of responses to sounds. With proper test the ears (earlobe or within the external ear canal).
protocols, the responses can be recorded clinically Using a computer-based device, it is possible to pres-
from activation of all levels of the auditory system, ent rapidly (eg, at rates of 20 to 30 per second) thou-
from the cochlea to the cortex. More than a dozen sands of sound stimuli and to average reliable ABR
subtypes of auditory evoked responses can be waveforms in a matter of minutes. Automated
recorded beyond the brainstem from auditory devices are now available for special clinical applica-
regions of the thalamus, hippocampus, internal cap- tions, for example, newborn hearing screening. The
sule, and cortex. Prominant among the cortical anatomic generators of the ABR components have
evoked responses measured for clinical purposes are been studied extensively.6 Waves I through V arise
the auditory middle latency response (AMLR), the from the eighth cranial nerve and auditory regions
Diagnostic Audiology, Hearing Aids, and Habilitation Options 141
in the caudal and rostral brainstem (see Figure 5–3). If the response is not highly replicable, modifications
Wave I clearly represents the synchronously stimu- in the test protocol should be made, and then poten-
lated compound action potentials from the distal tial technical problems must be considered and sys-
(cochlear) end of the eighth cranial nerve. Wave II tematically ruled out. When a replicable response is
may also arise from the eighth nerve, but near the confirmed, absolute latencies for each replicable wave
brainstem (the proximal end). Waves I and II are component and relative (interwave) latencies
generated by structures ipsilateral to the ear stimu- between components are calculated in milliseconds.
lated. All later ABR waves have multiple generators These latency data for each ear are assessed for sym-
within the auditory brainstem. Wave III, which is metry (wave V should be within 0.4 ms between ears)
usually prominent, is generated within the caudal and also compared with appropriate normative data.
pons, with likely contributions from the cochlear Common ABR waveform patterns are illustrated in
nuclei, the trapezoid body, and the superior olivary Figure 5–3. A well-formed and clear wave I at a
complex. The largest and most rostral component of delayed latency value for the maximum stimulus
the ABR, wave V, is generated in the region of the intensity level is characteristic of a conductive or
lateral lemniscus as it approaches the inferior col- mixed hearing loss. When wave I is small and poorly
liculus, presumably mostly on the side contralateral formed but interwave latency values are within nor-
to the ear stimulated. mal limits (the wave I to V latency value is less than
The first objective in ABR waveform analysis is 4.60 ms), a high-frequency sensory (cochlear) hear-
to be sure that the response is reliably recorded. Min- ing loss is suspected. Delayed interwave latency val-
imally, two replicated waveforms should be averaged. ues are the signature of retrocochlear auditory
142 Ballenger’s Otorhinolaryngology
dysfunction. Abnormal delays between the early wave rently, ECochG is performed most often for intraop-
components (eg, I to III) are consistent with poste- erative monitoring of cochlear and eighth nerve sta-
rior fossa lesions involving the eighth nerve and/or tus and in the diagnosis of Meniere’s disease. Optimal
lower brainstem, whereas a prolonged III to V latency ECochG waveforms are recorded from a small needle
suggests intra-axial auditory brainstem dysfunction. electrode placed through the tympanic membrane to
A primary goal in any neurodiagnostic ABR is the promontory, although tympanic membrane and,
to record a clear and reliable wave I component. to a lesser extent, ear canal electrode locations are
Wave I serves as the benchmark for peripheral audi- also clinically useful. Stimulus and acquisition
tory function. Subsequent interwave latencies offer parameters for recording ECochG have been well
indices of retrocochlear (eighth nerve and brainstem) defined for decades.6 The three major components of
function that are relatively unaffected by conductive the ECochG are the cochlear microphonic (CM), the
or sensory hearing loss. The likelihood that a wave I summating potential (SP), and the action potential
will be recorded is enhanced by the use of either ear (AP). The CM and SP reflect cochlear bioelectric
canal (TIPtrodeTM) or tympanic membrane electrode activity, whereas the AP is generated by synchronous
designs, along with alterations of the test protocol, firing of distal afferent eighth nerve fibers and is
such as a slower stimulus rate, rarefaction stimulus equivalent to ABR wave I (Figure 5–4). The typical
polarity, and maximum stimulus intensity level. ECochG analysis technique in neurotology requires
Reports on ABR dating back to the late 1970s con- determination of the amplitude of the SP and the AP
firmed that waveforms evoked by high intensity from a common baseline. Then the ratio of the SP to
yielded neurodiagnostic information on cochlear and the AP is calculated and reported in percent. Normal
retrocochlear auditory function and could be applied SP to AP ratio ranges and cutoffs in percent have
in the identification of retrocochlear disorders (eg, been reported for each electrode type. Abnormal
acoustic neuromas), with a hit rate exceeding 95%. SP to AP ratio values are defined as > 50% for the
With the development of sophisticated neuroradio- ear canal electrode type (the TIPtrode), > 40% for the
logic techniques, such as computed tomography tympanic membrane electrode, and > 30% for
(CT) or magnetic resonance imaging (MRI) with the transtympanic needle electrode type.1,6
enhancement, reports of normal ABR findings The characteristic ECochG finding for patients
among patients with very small posterior fossa with Meniere’s disease is an abnormal enlargement
tumors have appeared in the literature. These are of the SP amplitude relative to the AP amplitude.
clearly false-negative ABR outcomes in patients at With the tympanic membrane electrode technique,
risk for retrocochlear auditory dysfunction usually sensitivity of ECochG in the diagnosis of endolym-
caused by very small intracanalicular vestibular phatic hydrops is reported as 57%, whereas speci-
schwannomas. On the other hand, false-positive out- ficity is 94% in a series of 100 patients.7 Only 3 of 30
comes for CT and MRI have also been reported for patients yielded false-positive findings. Thus, an
patients with normal ABRs and no surgical evidence abnormally high SP to AP ratio is highly suggestive
of tumor.1 Auditory brainstem response continues to of endolymphatic hydrops according to these data.
be a readily available, relatively inexpensive, and rea- In this study, the likelihood of an abnormal ECochG
sonably sensitive procedure for initial diagnostic SP to AP ratio was statistically higher as hearing loss
assessment of eighth nerve and auditory brainstem increased and when the hearing loss fluctuated.
status in patients with retrocochlear signs and symp-
toms. Auditory brainstem response is also valuable in
electrophysiologic monitoring of the eighth nerve
OTOACOUSTIC EMISSIONS
and auditory brainstem function during certain neu- Otoacoustic emissions are low-intensity sounds pro-
rotologic surgeries (eg, vestibular nerve section, pos- duced by the cochlea in response to an acoustic
terior fossa tumor removal). stimulus.8 A moderate-intensity click, or an appro-
priate combination of two tones, can evoke outer
hair cell movement or motility. Outer hair cell motil-
ELECTROCOCHLEOGRAPHY ity affects basilar membrane biomechanics, resulting
For over 30 years, ECochG has been applied in the in a form of intracochlear energy amplification, as
assessment of peripheral auditory function. Cur- well as cochlear tuning for more precise frequency
Diagnostic Audiology, Hearing Aids, and Habilitation Options 143
AP
SP = 0.30 µV Normal ECochG
AP = 1.00 µV
SP/AP = 30%
SP
resolution. The outer hair cell motility generates are presented to the ear simultaneously (Figure 5–5).
mechanical energy within the cochlea that is propa- The most robust DPOAE occurs at the frequency
gated outward via the middle ear system and the determined by the equation 2f1-f2, whereas the actual
tympanic membrane to the ear canal. Vibration of cochlear frequency region that is assessed with
the tympanic membrane then produces an acoustic DPOAE is between these two frequencies and prob-
signal (the OAE), which can be measured by a sen- ably close to the f2 stimulus for recommended test
sitive microphone. There are two broad classes of protocols. With all of the five US Food and Drug
OAEs: spontaneous and evoked. Spontaneous otoa- Administration (FDA)-approved instruments that
coustic emissions (SOAEs), present in only about are commercially available for recording DPOAE,
70% of persons with normal hearing, are measured amplitude as detected in the ear canal and described
in the external ear canal when there is no external in dB SPL is plotted as a function of the frequencies
sound stimulation. A significant gender effect for of the stimuli in a DPOAEgram (see Figure 5–5).
SOAE has been confirmed, with females demon- Transient evoked otoacoustic emissions (TEOAEs)
strating SOAEs at twice the rate of males. are elicited by brief acoustic stimuli such as clicks or
Evoked OAEs, elicited by moderate levels (50 to tone bursts. Although there are distinct differences
80 dB SPL) of acoustic stimulation in the external in the methodology for recording DPOAEs versus
ear canal, are generally classified according to char- TEOAEs, and the exact cochlear mechanisms
acteristics of the stimuli used to elicit them or char- responsible for their generation are also different,
acteristics of the cochlear events that generate them. each type of evoked OAE is now being incorporated
Stimulus-frequency otoacoustic emissions (SFOAEs), into routine auditory assessment of children and
which are technically difficult to record, are the least adults.8 Clinical applications of OAEs, along with
studied of the evoked OAEs. Distortion-product their rationale, are summarized in Table 5–1.
otoacoustic emissions (DPOAEs) are produced When outer hair cells are structurally damaged
when two pure-tone stimuli at frequencies f1 and f2 or at least nonfunctional, OAEs cannot be evoked by
144 Ballenger’s Otorhinolaryngology
dB SPL
0
–10
f2 f1 2f1-f2
Probe
OHCs –20
Probe Tip 500 1,000 2,000 4,000 8,000
F2 (Hz)
FIGURE 5–5. A, Schematic illustration of the generation of distortion-product otoacoustic emissions (DPOAEs) from
outer hair cells (OHCs) within the cochlea showing the two stimulus-frequency generators, the probe for delivery of
the stimuli and housing of a microphone (Mic) for detection of the OAE in the canal, and the inward propagation of
the stimuli to the cochlea and the outward propagation of the DPOAEs from the cochlea. B, DPgram recorded from
the left ear of a 5-year-old girl with a ventilation tube in the tympanic membrane, yet hearing sensitivity is within nor-
mal limits. Replicated plots of DPOAE amplitudes in dB SPL (the X symbols) are shown as a function of the f2 stimuli
in a “DPgram” format. Noise levels as a function of frequency are indicated in the lower portion of the DPgram by the
square symbols. The faint solid line represents the upper limits (95th percentile) for normal noise levels. Distortion-
product amplitudes are reduced in the low-frequency region (500 to 1,000 Hz), consistent with a slight air–bone gap
in pure-tone hearing thresholds. Distortion-product amplitudes for higher frequencies are generally within normal
limits (the two solid lines representing the 5th to 95th percentile region for normal adult subjects). NF = noise floor.
acoustic stimuli. Among patients with mild cochlear potential clinical applications, ranging from audi-
dysfunction, OAEs may be recorded, but amplitudes tory screening to sensorineural diagnosis.
are below normal limits for some or all stimulus fre-
quencies. Importantly, some patients with abnormal
OAEs, consistent with cochlear dysfunction, will INDICATIONS FOR DIAGNOSTIC
have normal pure-tone audiograms. An example is a AUDIOLOGIC ASSESSMENT
patient with the symptom of tinnitus yet a normal
audiogram. Abnormal OAEs are expected in the fre-
CHILDREN
quency region represented by the tinnitus. Up to Hearing loss influences speech and language devel-
30% of a population of outer hair cells may be dam- opment of infants and young children, and these
aged without substantially affecting the simple effects begin within the first 6 months of life.9,10
audiogram. In such cases, however, abnormal OAE Even mild peripheral hearing deficits among pre-
findings are invariably recorded. The noninvasive school- and school-age children interfere with
nature of OAE recording, coupled with their accu- educational development. Therefore, early identifi-
racy and objectivity in assessing cochlear, in partic- cation of hearing loss, coupled with timely and
ular outer hair cell, function suggests diverse appropriate intervention and management, is nec-
Diagnostic Audiology, Hearing Aids, and Habilitation Options 145
TABLE 5–1. Clinical Applications of Otoacoustic Emissions (OAEs) and Their Rationale
Application Rationale
Newborn hearing screening OAEs can be recorded reliably from newborn infants
OAE recording can be performed in nursery setting (test performance may be
affected by noise)
Normal OAEs are recorded in persons with normal sensory (cochlear) function
OAEs are abnormal in persons with even mild degrees of sensory hearing loss; the
main objective of screening is to detect sensory hearing impairment
OAE recording may require a relatively brief test time
OAE measurement may be performed by nonaudiologic personnel (ie, at reduced
cost)
Pediatric audiometry OAE recording is electrophysiologic and not dependent on patient behavioral
response
OAEs assess cochlear function specifically (behavioral audiometry and ABR are
dependent also on the status of the central auditory nervous system)
OAEs can be recorded from sleeping or sedated children
OAE recording requires a relatively short test time
OAEs provide ear-specific audiologic information
OAEs provide frequency-specific audiologic information
OAEs are a valuable contribution to the “crosscheck principle”*
Diagnosis of central auditory OAE recording is electrophysiologic and not dependent on patient behavioral response
processing disorders OAEs are a sensitive means of ruling out cochlear (outer hair cell) dysfunction
Assessment in suspected OAE recording is electrophysiologic and not dependent on patient behavioral
functional hearing loss response
Normal OAEs invariably imply normal sensory function
OAEs provide frequency-specific audiologic information
Differentiation of cochlear OAEs are site specific for cochlear (sensory) auditory dysfunction
versus retrocochlear In combination with ABR, OAEs can clearly distinguish sensory versus neural
auditory dysfunction auditory disorders
Monitoring ototoxicity OAEs are site specific for cochlear (sensory) auditory dysfunction
Ototoxic drugs exert their effect on outer hair cell function; OAEs are dependent on
outer hair cell integrity
OAE recording is electrophysiologic and not dependent on patient behavioral
response; can be recorded from patients who, owing to their medical condition, are
unable to perform behavioral audiometry tasks or from infants and young children
OAEs can detect cochlear dysfunction before it is evident by pure-tone audiometry
OAEs provide frequency-specific audiologic information
Tinnitus OAEs are site specific for cochlear (sensory) auditory dysfunction
OAEs can provide objective confirmation of cochlear dysfunction in patients with
tinnitus and normal audiograms
Continued
146 Ballenger’s Otorhinolaryngology
TABLE 5–1 Continued. Clinical Applications of Otoacoustic Emissions (OAEs) and Their Rationale
Application Rationale
OAEs provide frequency-specific audiologic information that may be associated
with the frequency region of tinnitus
Noise/music exposure OAEs are site specific for cochlear (sensory) auditory dysfunction
Excessive noise/music intensity levels affect outer hair cell function; OAEs are
dependent on outer hair cell integrity
OAEs can provide objective confirmation of cochlear dysfunction in patients with
normal audiograms
OAE findings are associated with cochlear frequency specificity, ie, “tuning”;
musician complaints of auditory dysfunction can be confirmed by OAE findings,
even with a normal audiogram
OAEs can provide an early and reliable “warning sign” of cochlear dysfunction
owing to noise/music exposure before any problem is evident in the audiogram
*The crosscheck principle in pediatric audiology is that the results of any single audiologic test should not be relied on without
independent corroboration or crosscheck from another audiologic test.
Adapted from Hall JW.8 ABR = auditory brainstem response.
essary for children to reach their full communica- • attention-deficit disorder (ADD) with or without
tive and educational potential.11 A number of fac- hyperactivity
tors put children at risk for hearing impairment. • reading delay or disorder
Table 5–2 summarizes risk factors for hearing • learning disabilities
impairment identified by the 2000 Joint Committee • history of central nervous system insult (eg, head
on Infant Hearing.12 Otolaryngologists and audiol- injury, neonatal asphyxia)
ogists must coordinate efforts in properly and
There are now a variety of behavioral and elec-
promptly assessing and managing pediatric hearing
trophysiologic measures for diagnosis of APDs. Elec-
impairment.
trophysiologic procedures were outlined above.
In addition to peripheral hearing impairment
Among them, cortical evoked responses are especially
secondary to common causes, such as conductive
appropriate for evaluation of APD. The behavioral
hearing loss with otitis media or sensorineural hear-
procedures include measures of detection (eg, audi-
ing loss in ototoxicity, one must also consider the
tory integration tasks), suprathreshold discrimina-
possibility of auditory processing disorders (APDs)
tion (eg, temporal ordering tasks), and identification
in children. According to a recent consensus confer-
(eg, recognition of speech signals from phonemes to
ence report, 4 auditory processing disorders are
sentences), presented monotically, diotically, and
defined as “deficits in the processing of information
dichotically.4 Speech and nonspeech materials for
that is specific to the auditory modality.” Often
assessment of APDs are available in compact disc for-
APDs are related to central auditory nervous system
mat from multiple commercial sources.1,13
dysfunction. Common risk factors for APDs in
school-age children include the following:
• teacher concern about hearing despite a normal
ADULTS
audiogram In adults, risk factors for central auditory nervous
• academic underachievement system dysfunction include, but are not limited to,
• recurrent middle ear disease advanced age and history or clinical evidence of
• suggestion of APD on language evaluation stroke, head injury, brain neoplasms, Alzheimer’s dis-
• poor response to language treatment ease, and other disorders affecting the central nerv-
Diagnostic Audiology, Hearing Aids, and Habilitation Options 147
TABLE 5–2. Joint Committee on Infant Hearing Screening 2000 Indicators Associated with Sensorineural
Hearing Loss
Birth through age 28 d (neonate)
Family history of congenital or delayed-onset childhood hereditary sensorineural hearing loss
Congenital infection, such as toxoplasmosis, syphilis, rubella, cytomegalovirus, and herpes
Craniofacial anomalies including abnormalities of the pinna and ear canal, absent philtrum, and low hairline.
Birth weight less than 1,500 g (3.3 lb); hyperbilirubinemia at level requiring exchange transfusion
Ototoxic medications including but not limited to the aminoglycosides (eg, gentamicin, tobramycin, kanamycin,
streptomycin) used in multiple courses or in combination with loop diuretics
Bacterial meningitis
Apgar scores of 0 to 4 at 1 min or 0 to 6 at 5 min
Mechanical ventilation lasting 5 days or longer
Stigmata or other findings associated with a syndrome known to include sensorineural and/or conductive hearing
loss (eg, Waardenburg’s or Usher’s syndrome).
Age 29 d through 2 y (infant)
Parent caregiver concern regarding hearing, speech, language, and/or developmental delay
Bacterial meningitis and other infections associated with sensorineural hearing loss
Ototoxic medications including but not limited to chemotherapeutic agents or aminoglycosides used in multiple
courses or in combination with loop diuretics
Recurrent or persistent otitis media with effusion for at least 3 mo
For use with infants (age 29 d through 3 y) requiring monitoring of hearing
Indicators associated with delayed-onset sensorineural hearing loss
Family history of hereditary childhood hearing loss
In utero infections (eg, cytomegalovirus, rubella, syphilis, herpes, or toxoplasmosis)
Neurofibromatosis 2 and neurodegenerative disorders
Indicators associated with conductive hearing loss
Recurrent or persistent otitis media with effusion
Anatomic deformities and other disorders that affect eustachian tube function
Neurodegenerative disorders
ous system. In general, it is a good clinical policy to one’s hand behind the ear. This technique is effec-
always consider the possibility of central auditory tive because it helps channel the acoustic signal into
dysfunction when a patient’s hearing complaints the ear canal. Another simple means for improving
exceed expectations based on the audiogram. the reception of an acoustic signal is to move closer
to the sound source. When the distance between the
listener and the sound source is doubled, the
HEARING AIDS acoustic intensity is reduced by 6 dB at the listener.
A hearing aid is a medical device that delivers an Similarly, a reduction in the distance by one half
amplified acoustic signal into the ear canal. The use increases the intensity by 6 dB. When the acoustic
of some form of amplification to overcome the signal is from an electronic device, such as a televi-
deleterious effects of a hearing impairment on com- sion or radio, reception can easily be enhanced by
munication has been used for centuries. The most adjusting the volume control to make a more
simplistic “hearing aid” is easily made by cupping intense signal. All of these methods enhance the
148 Ballenger’s Otorhinolaryngology
completely fills the concha and contains most of the of the tympanic membrane.17 They have a nylon
electronic components, the battery, and a volume cord attached to its lateral surface to aid in retrieval
control. The anterosuperior arm of the ITE hearing of the instruments from the ear canal. Because of
aid fits into the helix of the auricle inferior to the tri- its size and microphone location, these devices have
angular fossa and functions primarily to keep the a number of advantages. 17,18 These advantages
instrument in place. The microphone is sometimes include a reduction in the occlusion effect, ease of
located within this portion of the instrument. The use on the telephone, no problems with wind noise
medial portion fits partially in the ear canal and con- on the microphone, an increase in gain by as much
tains the receiver. In-the-ear hearing aids are com- as 15 dB, and an enhancement of the acoustic effects
pletely self-contained. There is no tubing or earmold of the auricle and ear canal. Unfortunately, these
assembly. The hearing aid is essentially built into the devices also have a number of disadvantages. These
earmold. Properly fitted ITE hearing aids are appro- disadvantages include problems getting a good
priate for mild to severe losses of hearing. The loca- acoustic seal, which may lead to feedback problems,
tion of the microphone, which is close to the level of increased repair problems owing to cerumen, diffi-
the ear canal, is an advantage of the ITE style. How- culty inserting and removing the device from the
ever, the size of the instrument within the auricle ear canal, increased expense, reduction in the num-
minimizes the use of its natural resonance. Despite ber of advanced features, and an inability to appro-
these advantages and its cosmetic appeal, it does have priately fit more severe hearing losses.
a few disadvantages. First, when the instrument must
be repaired or replaced, the patient is usually without
a hearing aid for a number of days. A BTE loaner may
HEARING AID TECHNOLOGY
be provided when coupled with a temporary ear- In the past few years, hearing aid technology has
mold, but this is usually not an acceptable alterna- grown by leaps and bounds. Hearing aids today have
tive. Additionally, ITE hearing aids may be difficult many advanced components and features. We will
for some patients to insert and remove, especially for now review briefly some of the more important
individuals with manual dexterity problems. developments in hearing aid technology. Unfortu-
In-the-canal hearing aids fit primarily into the nately, a detailed review of all of the available fea-
ear canal. Only the faceplate of the hearing aid is vis- tures is not appropriate here. The reader is referred
ible in the concha area. A properly fitted ITC hear- to a text by Sandlin for a more in-depth review.19
ing aid may accommodate up to a moderately severe Disposable and instant fit hearing aids are the
hearing loss. The location of the microphone is at newest development to emerge on the hearing aid
the opening of the ear canal, taking advantage of the market. These devices are receiving increased atten-
acoustic properties of most of the auricle.16 Also, tion because of their ability to be fit immediately.
these devices are inserted deeper than ITE hearing The products are available in a wide range of sizes
aids, which creates an increase in gain of about 5 dB. and technology, from BTE to CIC instruments.20 An
Although the size of the ITC instrument is an advantage of these devices is their significantly
acoustic advantage, there are a few disadvantages. reduced price in comparison with custom-made
First, there is less structure holding the hearing aid products. Disposable hearing aids have an added
in place, making it easier to become dislodged and benefit in that there is never a need to replace the
lost. Second, their small size makes them more diffi- battery since the entire hearing aid is replaced after
cult to insert and remove, hindering use by those 40 days. However, these devices may only be fit on
with manual dexterity limitations. individuals with milder degrees of hearing impair-
Completely-in-the-canal hearing aids are the ment, rendering those with severe and profound
smallest of the hearing aid styles and therefore the hearing losses ineligible for this technology.
most cosmetically appealing and most popular. Conventional hearing aids are the least techno-
These hearing aids are inserted deeply into the ear logically sophisticated of the custom-made hearing
canal by the patient and are essentially invisible to aids. These devices are analog hearing aids. An ana-
the casual observer. These instruments are designed log hearing aid receives the acoustic signal from the
to be placed past the second bend of the ear canal, microphone, converts it into an electrical signal,
with the medial end of the hearing aid within 5 mm amplifies and filters it according to the individual’s
150 Ballenger’s Otorhinolaryngology
hearing loss, and reconverts it into an acoustic signal tortion of the signal. The signal is then amplified and
that is delivered to the ear canal.19 In this type of converted back to an acoustic signal that is delivered
technology, the audiologist selects a matrix for the to the ear canal through the receiver. These devices
hearing aid, which determines its overall gain, slope, offer a number of advantages, which include
and maximum output. Relatively few adjustments increased flexibility of shaping the frequency
can be made directly by the hearing aid dispenser or response of the instrument, feedback suppression
audiologist. These minor changes may be made by capabilities, improved sound quality, decreased bat-
screwdriver controls. Typically, these devices provide tery drain, and less internal circuit noise. As was
linear amplification, although some do provide noted in programmable hearing instruments, these
some forms of compression. Linear amplification devices may have multiple memories and may be
refers to the types of hearing aids that provide the adjusted via a computer or handheld programmer.
same amount of gain regardless of the input signal. The memories may also be accessed via a remote
As the input signal increases in loudness, so will the control or a switch on the device. Recently, one hear-
resulting output of the hearing aid until the hearing ing aid company produced an instrument that
aid’s maximum output limit is reached. At this changes the program automatically based on the
point, signal distortion occurs. Compression, on the noise levels in the environment.
other hand, helps eliminate the problem of distor- The major complaint of individuals with sen-
tion created by linear hearing aids. In this type of sorineural hearing loss is the inability to hear in
hearing aid, the amount of gain provided by the background noise. Currently, directional microphones
hearing aid depends on the intensity of the incom- provide the individual with hearing impairment the
ing signal. Signals with greater intensity receive less best opportunity for understanding in noise. Simply
amplification than those with lower intensities. This put, this microphone arrangement allows the wearer
reduction in gain helps decrease distortion as the to hear the sound originating from the front, which
signal becomes closer to the maximum output pro- is where the sound source is usually located, and
vided by the hearing aid. Typically, these instru- reduces sounds from the rear, which is usually where
ments have a volume control that may be adjusted noise is located.19 Recent studies have noted 5 to 8 dB
by the user. of improvement when listening in noise in compari-
Programmable hearing aids provide increased son with standard, omnidirectional microphones.19,22
flexibility and options for the wearer. Just as in con- This improvement may result in improvement in
ventional hearing aids, these instruments have ana- speech recognition by as much as 60%. Currently,
log amplifiers. However, unlike the conventional this microphone technology is available in conven-
hearing instruments, these devices can be modified tional, programmable, and digital hearing aids. How-
in the audiologist’s office via a computer or hand- ever, the performance of the directional microphone
held programmer. This programming allows for is better in the advanced devices. Additionally, this
increased flexibility in shaping the frequency microphone technology is available in BTE instru-
response, output limitations, compression charac- ments through half-shell ITE instruments.
teristics, and enhanced features provided by the
hearing aid. Additionally, many of these devices offer INDICATIONS FOR AMPLIFICATION
multiple memories or programs. The use of these
Hearing aids are indicated whenever it can be
multiple programs allows the patient access to dif-
demonstrated that the patient’s ability to communi-
ferent settings that may be designed for various lis-
cate will be significantly improved through the use
tening environments. These multiple programs may
of amplification. A hearing aid is not recommended
be accessed via a remote control or a switch on the
under the following conditions:
hearing instrument.
Digital hearing aids are the most popular hear- • effective medical treatment can be implemented to
ing aid technology available in today’s market.19,21 A restore normal hearing
digital hearing aid processes the acoustic signal dif- • hearing aid use would exacerbate the disease or
ferently than an analog instrument. In this arrange- interfere with treatment
ment, the acoustic signal is converted to a digital or • a hearing aid fails to improve the ability of the
binary code, which minimizes the possibility for dis- patient to communicate
Diagnostic Audiology, Hearing Aids, and Habilitation Options 151
A common myth is that amplification is of no physical health status. Hence, the use of ampli-
benefit in the case of sensorineural hearing loss. fication has the potential to improve significantly
Although there is no evidence correlating the use of the quality of life of an individual with hearing
a hearing aid with restoration or treatment of the impairment.
impaired auditory system, hearing aids are routinely
used to offset the effects of sensory hearing impair-
ment. Sensory hearing loss accounts for 90% of all MONAURAL VERSUS BINAURAL AMPLIFICATION
types of hearing loss. In excess of 95% of all hearing
A great deal of research has been devoted to the fol-
aids are purchased by patients with sensorineural
lowing question: if hearing loss is bilateral, are two
hearing loss. Amplification is an effective means of
hearing aids better than one? The intuitive answer
improving the communicative abilities of individu-
is, of course, that two hearing aids would best offset
als with sensory hearing impairment, as attested by
the effects of a hearing loss in both ears. The ques-
hundreds of research articles published in the last 50
tion persists, however, because many patients choose
years.
monaural fittings. This decision is usually based on
Amplification is an extremely effective means
cosmetic or financial reasons, although some
of improving the hearing of patients with conduc-
patients claim to hear just as well with one hearing
tive hearing loss. A hearing aid is clearly not an
aid as with two, whereas others appear to hear bet-
acceptable alternative to effective medical treatment
ter with a single instrument.
of a pathologic condition, but it may be used after
The benefits of binaural amplification have
the course of treatment to offset residual hearing
been well documented in the audiologic literature.9,16
impairment. Residual conductive hearing loss is
The most commonly cited benefits are as follows:
commonly present following placement of an ossic-
ular prosthesis, for example. In this case, a hearing • improved word identification, particularly in
aid is often an effective means for further improving adverse listening conditions
hearing sensitivity. In contrast, a hearing aid may be • improved localization of the sound source
of little benefit for patients with retrocochlear (neu- • a sense of “balanced hearing”
ral or central) auditory disorders. In some cases, • the need for less gain
amplification may actually exacerbate the effects of • elimination of the head shadow effect
the disorder. The use of amplification must be care- • increased perception of high-frequency consonants
fully evaluated in all cases of central impairment.
In addition to these advantages, a number of
However, there are alternatives for these patients.
recent studies have appeared that document the
Perhaps the most common approach is the recom-
effects of auditory deprivation in unaided ears. The
mendation of an assistive listening device, like an
research indicates that word identification scores in
FM system, for improvement of speech under-
the unaided ear decrease over time relative to the
standing by significantly enhancing the speech sig-
scores in the aided ear in a monaural fitting. In con-
nal in relation to background noise.
trast, this decrement is not observed in either ear in
a binaural fitting. Further, limited recovery in word
BENEFITS OF AMPLIFICATION identification is observed following the subsequent
provision of amplification to the deprived ear.
It is readily apparent that the use of amplification
With regard to this evidence, binaural amplifi-
significantly improves the communicative ability of
cation should be recommended unless specifically
an individual with hearing impairment. However,
contraindicated. Valid contraindications to binaural
recent research has revealed additional benefits in
amplification are as follows:
psychosocial and functional health measures. 23
These studies have shown that individuals using • unilateral hearing loss
amplification reported less depressive feelings, • medical complication in one ear
richer social relationships, and less anxiety and • one ear cannot be aided owing to insufficient
paranoia. Additionally, and perhaps as a result of residual hearing
improved communicative psychosocial function- • binaural amplification results in diminished word
ing, these individuals noted improvements in their identification
152 Ballenger’s Otorhinolaryngology
HEARING AID SELECTION box that analyzes the sound pressure present within
this cavity. This analysis provides information
The selection of an appropriate hearing aid requires
regarding the gain characteristics of the hearing aid
a combination of factors. First, it is essential that the
at each frequency, frequency response, maximum
practitioner thoroughly assess the patient’s motiva-
output, battery drain, and distortion of the hearing
tion, concerns, communicative goals, and listening
aid. These results can be compared to the specifica-
needs before selecting a hearing instrument.24 Issues
tions of the hearing instrument provided by the
such as cosmetics, dexterity, and financial con-
manufacturer. If discrepancies occur, the hearing
straints may significantly limit the style and techno-
instruments should be returned to the manufacturer
logical options. Additionally, one’s communicative
for repair or replacement.
goals or typical listening environment may dictate
the need for a directional microphone or other Additionally, a listening check of the instru-
advanced features. To aid in this endeavor, the use of ments should be performed. This check will provide
self-assessment inventories, which will be discussed information regarding the sound quality, circuit
in the following section, may be of benefit. noise, and any intermittent function of the devices.
To aid in the selection of a hearing aid, multi- Once again, if problems are noted, the devices
ple researchers have developed prescriptive formulae should be returned to the manufacturer.
that are based on audiometric thresholds or
Functional Gain Measures Functional gain meas-
suprathreshold information.25 The goal of these for-
ures are designed to assess the realistic benefit
mulae is to provide the listener with the optimum
patients derive from their hearing instrument by
aided speech intelligibility possible. However, these
determining behaviorally the amount the hearing
formulae are not expected to be a panacea but are
aid improves the patient’s thresholds of audibility.9,25
merely intended to provide the dispenser with a
This procedure is conducted in the sound field,
valid approximation, a logical starting point. From
using a speech signal and/or warble tones, to deter-
here, minimal modifications should be required.
mine the difference in the patient’s aided and
Currently, there are a number of prescriptive for-
unaided hearing thresholds. Although this test pro-
mulae available, but no standard has been adopted.
cedure is designed to assess the patient’s “real-world”
benefit, it is plagued by a number of limitations.
ASSESSMENT OF HEARING AID OUTCOMES These limitations include poor test–retest reliability,
Any time treatment is rendered, some measure of limited frequency response information, lack of
efficacy of the service should be performed. In the maximum output information, and a dependence
age of managed care, it is exceedingly important to on the patient’s behavioral responses.
document the success (or failure) of rehabilitation
services. Currently, there are a number of means to Real-Ear Measures Owing to the number of limi-
assess the efficacy of amplification, which include tations presented by functional gain measures, real-
electroacoustic analysis, functional gain measures, ear measures are currently the most accepted means
real-ear measures, and self-assessment inventories. of verifying hearing aid performance.3,25,27,28 Real-ear
Each of these procedures will be discussed briefly in measurement systems use a specially designed probe
the following sections. microphone to measure the sound pressure in the ear
canal at the eardrum. This probe microphone is
Electroacoustic Analysis On arrival of the hear- inserted along the side of the patient’s ear canal into
ing instruments from the manufacturer and before a position located within 6 to 8 mm of the tympanic
dispensing the devices to the patient, it is essential membrane. A broadband noise, speech composite
that the devices be evaluated to determine if they are noise, an International Collegium of Rehabilitative
functioning appropriately.3 According to the Ameri- Audiology (ICRA) noise, or tonal series is presented
can Speech-Language Hearing Association, these via a loudspeaker that is located approximately 1
devices should be assessed via an electroacoustic meter away from the patient. Measurements are
analysis according to the ANSI S3.22 standard and a made and graphically displayed with and without the
listening check.26 In this first test, the hearing aid is hearing aid in place. Aided test results are usually
attached to a 2 cm3 coupler and evaluated in a test compared to and adjusted to match the prescribed
Diagnostic Audiology, Hearing Aids, and Habilitation Options 153
target. At a minimum, this testing should be con- ule that gradually extends the length of time that the
ducted at an input level of 60 to 70 dB SPL, which is hearing aids are worn each day. Some programs also
typical of average conversational speech. Addition- restrict hearing aid use to quiet listening environ-
ally, testing of the saturation level of the hearing aid ments during the initial period of accommodation
should be conducted to ensure that the maximum with systematic exposure to more demanding condi-
output of the hearing aid is set below the patient’s tions as accommodation progresses.
threshold of uncomfortable loudness. For nonlinear A common problem arises when a patient is ini-
hearing aids, testing at a high input level (80 to 85 dB tially unhappy with the performance of the hearing
SPL) and a low input level (50 dB SPL) should also be aid. According to federal law, a customer may return
included. At each of these input levels, patient feed- a hearing aid to the dispenser within 30 days for a
back regarding the volume of the input signal should refund. Unfortunately, 30 days is often an insufficient
be solicited. For a comprehensive discussion regard- period of time to allow for complete accommodation
ing real-ear technology and a variety of clinical pro- and/or modification of the instruments. Therefore,
cedures based on this technique, the reader is referred prospective hearing aid patients should receive proper
to a text by Mueller and colleagues25 and a text by counseling before, during, and after the initial fitting
Valente.27 to avoid making a premature decision.
Self-Assessment Inventories Perhaps the most Pediatric Issues in Amplification Children present
compelling evidence of the success of a hearing aid a unique set of issues in the selection and fitting of
fitting comes directly from the patient. After a brief amplification. These issues primarily exist because of
period of hearing aid use, most patients are quite the small size of children’s ears in comparison with
capable of determining whether the prescribed adult ears, the noncompliance of some children, the
amplification has improved their ability to hear. This increased demands in their communication needs,
is understandable considering that the vast majority and a lack of complete audiometric data on which to
of individuals who purchase hearing aids cope with base these decisions. To address these matters, audiol-
the hearing impairment before deciding to pursue ogists have developed a set of standards for selecting
amplification. After very little experience wearing the and fitting hearing aids for young children. As men-
new hearing aids, most patients are able to precisely tioned previously, BTE instruments are the most pop-
describe the listening situations in which their hear- ular hearing aid style for children. This style allows
ing aids are effective or ineffective. To quantify this for maximum flexibility.16 First, this design allows for
valuable patient report, a number of self-assessment an inexpensive means for accommodating changes in
inventories have been developed for use by audiolo- the size of the auricle and ear canal as the child grows.
gists and hearing aid dispensers.3 These inventories While these changes are being made, the child is still
are widely used to evaluate the initial fitting and the able to use the hearing instrument. Second, these
effectiveness of subsequent modifications. devices are more resistant to feedback problems
owing to the increased distance between the micro-
Patient Accommodation to Amplification An phone and the receiver. Furthermore, using an ear-
individual with hearing impairment requires a mold with superthick tubing may also decrease the
period of adjustment to become accustomed to likelihood of feedback. Third, this style offers options
wearing hearing aids. The average patient has devel- that aid in the retention of the hearing aid in the ear
oped a hearing loss over a period of years before canal, such as wire retention attachments, kiddie tone
deciding to pursue amplification. During this time, hooks, and Huggie-Aids. Finally, a BTE hearing
considerable adaptation has occurred in the central instrument offers many additional features that may
auditory system.29 The sudden introduction to not be available on smaller styles.
amplified sound initiates compensatory neurophysi- In addition to the style of hearing aid, a number
ologic changes that may take 5 to 6 weeks to develop. of other hearing aid options should be considered.16
In this time period, adjustments to the hearing Every hearing aid dispensed to a child should have
instruments are often needed to assist the patient in direct audio input, telecoil, and microphone/telecoil
the process of accommodation. Many hearing aid options available. These features will provide maxi-
programs encourage patients to use a wearing sched- mum adaptability with assistive listening devices, such
154 Ballenger’s Otorhinolaryngology
as FM systems. Additionally, tamper-resistant volume mode and training has raged since the fourteenth
controls and battery doors should be considered. For century. Unfortunately, there is no one communica-
maximum flexibility, digital hearing aids with feed- tion modality that is right for every child.9,15,31,32 This
back suppression, programmable features, and multi- decision must be made on an individual basis, and
ple memories that offer both omnidirectional and consideration should be given to issues such as the
directional microphone technology are added assets. characteristics of the child (ie, age of diagnosis and
Finally, owing to the likelihood of the hearing instru- accompanying learning disabilities), available com-
ments becoming lost or damaged in young hands, a munity resources, and the commitment of the fam-
loss and damage warranty for the hearing instru- ily to the child and the chosen communication
ments is highly encouraged. modality. A basic review of the various communica-
Noting the difficulties in fitting and the com- tion options will be covered in the following para-
munication needs of young children, a prescriptive graphs. Major methods are summarized in Table
formula called the Desired Sensation Level (DSL) was 5–3. It is important to keep in mind that variations
developed.3,30 This formula calculates a prescriptive on these methodologies also exist. (See also Chapter
target for average conversational speech and maxi- 23, “Cochlear Implants.”)
mum output of the hearing instrument from a vari-
ety of sources, whether it is pure-tone thresholds Oral Approaches Two major forms of oral Eng-
obtained under telephonic dynamic headphones lish in practice today are the auditory-verbal
(standard earphones for audiometric testing) or ABR approach and the auditory-oral approach.31,32 These
thresholds. Additionally, if hearing aid verification two approaches are based on the idea that all chil-
and adjustments cannot be made using real-ear meas- dren with hearing impairment can realistically attain
ures, these adjustments may be made using a 2 cm3 receptive and expressive language competence
coupler in the hearing aid test box by using real-ear to regardless of the degree of hearing loss. The audi-
coupler differences (RECDs). Real-ear to coupler dif- tory-verbal philosophy places an emphasis on the
ference is the dB difference between the level of sound child’s residual hearing through the use of amplifi-
in the ear canal versus the level that is measured in the cation with the goal of developing listening skills
2 cm3 coupler. This measurement is obtained by tak- through natural communication. In this approach,
ing an unaided measurement in the child’s ear canal. the child is placed in mainstreamed education
If this measurement cannot be obtained, the formula beginning in preschool. The auditory-oral approach,
provides average RECDs for children of various ages. on the other hand, emphasizes the development of
Hence, with this prescriptive formula, appropriate amplified residual hearing and spoken language,
amplification can be provided with little dependence using speechreading cues as a supplement to the
on the cooperation of the child. auditory signal. In this approach, the child is usually
enrolled in an oral program until he or she can be
ADVISING THE PARENTS OF YOUNG appropriately mainstreamed.
CHILDREN WITH HEARING Both of these approaches have their advantages
and disadvantages. The biggest benefit of these pro-
IMPAIRMENT
grams is that they provide the child with the greatest
Although the otolaryngologist is principally con- access to the hearing world. Geers and Moog
cerned with the medical or surgical management of reported that children who attended oral education
aural disease and disorders, it is important that one programs attained better speech production, speech
has an understanding and an appreciation for the perception, and overall spoken language skills than
various educational options and communication those students who attended total communication
modalities available to the families of children with programs.33 Additionally, evidence suggests that these
hearing impairments.31,32 Since otolaryngologists are students attain literacy scores twice the national aver-
one of the professionals responsible for the identifi- age for children with hearing impairments. Unfortu-
cation and diagnosis of hearing impairments, they nately, the success of these programs is dependent on
are often the first, if not only, resource that the par- early identification of the hearing loss and amplifica-
ent has for information regarding these difficult tion use, as well as consistent, quality aural habilita-
choices. The debate over the best communication tion training. Another major drawback to these
Diagnostic Audiology, Hearing Aids, and Habilitation Options 155
TABLE 5–3. Summary of Strengths and Limitations of Various Approaches for Auditory Habilitation of
Children with Hearing Impairment and Deafness
Educational Option Benefits Limitations
Auditory-verbal Greatest access to hearing world Dependent on early identification and
Better speech production, speech intervention
perception, and spoken language Isolation from the Deaf community
Higher literacy rates
Early mainstream education
Auditory-oral Greatest access to hearing world Dependent on early identification and
Better speech production, speech intervention
perception, and spoken language Isolation from the Deaf community
Higher literacy rates
Cued speech Reading and writing skills on par with Few educational programs available
hearing peers Few transliterators
Access to hearing world Isolation from the Deaf community
Total communication Allows the child access to all means Few programs put this into practice
of communication May overstimulate the child
Bilingual-bicultural Designed to teach language and culture Little information available regarding
of the Deaf and hearing communities its success
Promotes increased literacy and
academic skills
Signing Exact English Uses English syntax and grammatical Denial of Deaf culture
features
American Sign Language Natural mode of communication for Syntax not conducive to the
the Deaf child development of English language
Allows membership in the Deaf
community and may improve
self-confidence
approaches is isolation from the Deaf community which has the capability of improving the child’s
owing to a lack of training in sign language. self-esteem and confidence. A major limitation of
ASL is that its syntax is not conducive to develop-
Manual Approaches In stark contrast to the ment of the English language, which may hinder
aforementioned oral approaches are the manual spoken language and literacy skill acquisition.
approaches. American Sign Language (ASL) is the
common language of the Deaf community in the In an attempt to alleviate the difficulties in
United States. It is a vast lexicon of hand shapes and learning English language through manual commu-
motions, or signs, and has its own syntax and gram- nication, educators developed English-based sign sys-
mar.9,31,32 Additionally, this mode of communication tems.9,34 The most popular form of the English-based
places a heavy emphasis on the facial expressions sign systems is Signing Exact English (SEE2). Signing
and body language of the signer. It is a unique lan- Exact English uses much of the same vocabulary as
guage, having no simple translation to the oral Eng- ASL but adds grammatical features and follows Eng-
lish language. Proponents of ASL believe that it is an lish syntax. This system is primarily geared toward
easier, more natural mode of communication for the preschool and lower elementary schoolchildren to
child with hearing loss. Additionally, this system provide them with access to English during the lan-
allows for membership into the Deaf community, guage-learning years. Opponents of this system
156 Ballenger’s Otorhinolaryngology
believe that it is a denial of Deaf culture by inflicting ally, these individuals are unable to communicate with
the standards of the hearing world on the Deaf child. the Deaf community unless ASL is also learned.
A variety of educational methods are available
Bilingual-Bicultural Approach Recently, momen- to the individual with hearing impairment. For the
tum has been growing for the development of vast majority of families, this important educational
bilingual-bicultural education for children who are decision is often made during a period of emotional
Deaf.35 This approach is designed to educate the child turmoil. These parents view the identification of a
on the mores, customs, and practices, as well as the hearing loss as a loss of their dreams of a normal
languages, of the hearing world and the Deaf culture. child and may grieve accordingly. Unfortunately, a
In these programs, children are taught ASL as their lack of understanding of the hearing loss, its impli-
first language, which provides a foundation for which cations, and remedial interventions can only exacer-
English is later taught. This early access to language is bate this emotional reaction. Although most parents
designed to promote increased literacy and academic would have liked to receive this information, they
skills. However, since these programs are relatively report that few professionals offer the supportive
new, little information is available regarding its counseling and information they need.39
success. The concept of critical period of development
during which the central nervous system exhibits
Combination Approaches A combination of the maximal plasticity is central to any discussion about
oral and manual approaches is referred to as a com- the education of the individual with hearing
bination approach. The most popular combination impairment. Should one maximize language devel-
approach is total communication. Total communi- opment or the use of residual hearing within a given
cation involves the use of one or more modes of time period? With the recent implementation of
communication at any given time in the child’s edu- universal newborn hearing screening, it is logical to
cational program, whether it be manual, oral, audi- ask if early identification and management causes a
tory only, or written.9,31,32,36 The design of this significant improvement in the acquisition of com-
approach is to use whatever communication modal- munication skills. Yoshinago-Itano et al provided
ity is most appropriate for the child at that stage of evidence that children with hearing loss who are
development or for that given situation, allowing the identified prior to 6 months of age and receive
child access to all means of communication. Despite immediate intervention have greater language
its promise, this approach has a number of limita- development, better receptive and expressive vocab-
tions. First, few programs actually put this philoso- ularies, and higher social-emotional aspects of
phy in practice owing to the biases of the instructor development than infants who are identified later,
and the difficulty of combining all of these methods regardless of the degree of hearing loss or mode of
at the same time. Additionally, the use of all of these communication.10,40 Additionally, no significant dif-
modalities may overstimulate the child and be a ferences in language development were noted in
detriment to the development of communication. terms of time of identification for those children
A less popular combination approach is cued identified after 6 months. This finding suggests that
speech. Cued speech is a visual communication sys- language stimulation within the first 6 months of
tem that employs eight hand shapes placed at four dif- life is critical for neural development.
ferent locations near the mouth.9,37 These hand shapes In summary, each of the currently available
are designed to supplement spoken language and educational methods has its proponents and oppo-
speechreading cues since many sounds may be indis- nents. Whenever appropriate, and with the support
tinguishable on the lips. The purpose of this approach of parents and other caregivers, otolaryngologists
is to allow the child to see and hear the English lan- should encourage and facilitate maximal use of
guage as it is spoken. Wandel found that children who residual hearing and language development in an
used this system developed reading and writing skills attempt to help these children reach their full com-
on par with their hearing peers.38 The limitations of municative potential. It is essential that the oto-
this approach are that few programs provide this type laryngologist provide the parent with supportive,
of education and few transliterators (individuals who unbiased information regarding the benefits and
cue what an instructor says) are available. Addition- limitations of the aforementioned modalities. No
Diagnostic Audiology, Hearing Aids, and Habilitation Options 157
matter what the family’s educational decision, early cochlear versus retrocochlear auditory dysfunction.
intervention services should be highly encouraged. Békésy audiometry is based on the comparison of
responses to pulsed versus continuous tones varied
across a wide frequency range. Four patterns of
GLOSSARY Békésy responses were classified by Jerger.
ABLB: Alternate binaural loudness balance. A tradi- BOA: Behavioral observation audiometry. A pedi-
tional diagnostic auditory procedure for detecting atric behavioral audiometry procedure in which
“loudness recruitment” used in differentiating motor responses to sounds (eg, eye opening, head
cochlear versus retrocochlear auditory dysfunction turning) are detected by a trained observer.
in unilateral hearing loss. The task is to balance the BTE: Behind-the-ear hearing aid design.
sensation of loudness for the better versus the CIC: Completely-in-the-canal hearing aid design.
poorer hearing ear. Loudness recruitment is a configuration: Term used to describe the shape or
cochlear auditory sign. pattern of an audiogram, that is, how hearing loss
ABR (BAER): Auditory brainstem response. Electri- varies as a function of the audiometric test frequency.
cal activity, evoked (stimulated) by brief-duration There are three main configurations: rising (low-fre-
sounds, arises from the eighth cranial nerve and quency loss), sloping (high-frequency loss), and flat.
auditory portions of the brainstem. The ABR is usu- CROS: Contralateral routing of signals. A hearing
ally recorded from the surface of the scalp and exter- aid configuration in which a microphone is located
nal ear with disk-type electrodes and processed with on the poorer ear and the sounds are transduced and
a fast signal-averaging computer. Auditory brainstem delivered electrically to the normal or mildly
response wave components are labeled with Roman impaired ear.
numerals (eg, I, III, V) and described by the latency crossover: Sound stimulus presented to one ear (the
after the stimulus (in ms) and the amplitude from test ear) travels around the head (by air conduction)
one peak to the following trough (in microvolts). or across the head (by bone conduction) to stimulate
AC: Air conduction. Audiometric signals presented the other (nontest) ear. See interaural attenuation.
via earphones to the ear canal. dB HL: A decibel scale referenced to accepted stan-
air–bone gap: The difference in pure-tone thresh- dards for normal hearing (0 dB is average normal
olds for air- versus bone-conducted signals. With hearing for each audiometric test frequency).
calibrated audiometers, the normal ear and the sen- dB nHL: A decibel scale used in auditory brainstem
sorineurally impaired ear show no air–bone gap, response measurement referenced to average behav-
whereas conductive hearing losses are characterized ioral threshold for the click stimulus of a small
by an air–bone gap. group of normal-hearing subjects.
ASL: American Sign Language. A manual mode of dB SL: Sound level or intensity described in refer-
communication that is commonly used by the Deaf ence to an individual patient’s behavioral threshold
community. for an audiometric frequency or some other meas-
audiologist: A hearing care professional who is edu- ure of hearing threshold (eg, the speech reception
cated and trained clinically to measure auditory sys- threshold).
tem function and to manage nonmedically persons dB SPL: A decibel scale referenced to a physical stan-
with auditory and communicative impairments. dard for intensity (eg, 0.0002 dynes/cm2).
Minimal educational requirements for audiologists dichotic: Simultaneous presentation of a different
are a master’s degree and certification and/or state sound to each ear.
licensure. DPOAE: Distortion-product otoacoustic emission.
BC: Bone conduction. Audiometric signals pre- DPgram (DPOAEgram): A graph of distortion-
sented via an oscillator to the skull (eg, mastoid bone product otoacoustic emission amplitude in the ear
or forehead). canal (in dB SPL) as a function of the frequencies of
BCL: Békésy Comfortable Level. A Békésy audiome- the stimulus tones (in Hz).
try procedure conducted at a comfortable loudness ECochG: Electrocochleography. Evoked responses
level versus a threshold level. originating from the cochlea (the summating poten-
Békésy audiometry: An audiometric procedure per- tial or SP and the cochlear microphonic or CM) and
formed with a Békésy audiometer for differentiating the eighth cranial nerve (the action potential or AP).
158 Ballenger’s Otorhinolaryngology
electrical event and background acoustic or electro- 3. Mueller HG, Hall JW. Audiologists’ desk reference.
physiologic energy. Vol II. San Diego: Singular Publishing Group; 1998.
SRT: Speech reception level. The lowest intensity level 4. Jerger J, Musiek F. Report of the Consensus Confer-
at which a person can accurately identify a speech sig- ence on the Diagnosis of Auditory Processing Disor-
nal (eg, two-syllable spondee words). See PTA. ders in School-Aged Children. J Am Acad Audiol
SSI: Synthetic sentence identification. A measure of 2000;11:467–74.
central auditory function that involves identification 5. Jerger JF. Clinical experience with impedance
of syntactically incomplete sentences (a closed set of audiometry. Arch Otolaryngol 1970;92:311–24.
10 sentences) presented simultaneously with a com- 6. Hall JW. Handbook of auditory evoked responses.
peting message (an ongoing story about Davy Needham (MA): Allyn & Bacon; 1992.
Crockett). 7. Pou AM, Hirsch BE, Durrant JD, et al. The efficacy of
SSPL: Saturation sound pressure level. A measure of tympanic electrocochleography in the diagnosis of
the maximum power output (MPO) of the hearing endolymphatic hydrops. Am J Otol 1996;17:607–11.
aid. 8. Hall JW. Handbook of otoacoustic emissions. San
SSW: Staggered spondaic word test. A measure of Diego: Singular Publishing Group; 2000.
central auditory function developed by Katz that 9. Northern JL, Downs M. Hearing disorders in chil-
uses spondee words presented dichotically. dren. 4th ed. Baltimore: Williams & Wilkins; 1991.
Telecoil: An option on a hearing aid that enables it 10. Yoshinaga-Itano C, Sedley Al, Coulter DK, Mehl AL.
to receive the electromagnetic signals directly from Language of early- and later-identified children with
the telephone. This option may be used to reduce hearing loss. Pediatrics 1998;102:1161–71.
the presence of feedback while the wearer is on the 11. Hall JW. Screening for and assessment of infant
telephone. hearing impairment. J Perinatol 2000;20:12–20.
TEOAEs: Transient evoked otoacoustic emissions. 12. Joint Committee on Infant Hearing. Year 2000 posi-
Otoacoustics emissions elicited by brief (click or tion statement: principles and guidelines for early
tone burst) stimuli. hearing detection and intervention. Am J Audiol
tone decay test: A clinical measure of auditory adap- 2000;9:9–29.
tion in which a tone is presented continuously to a 13. Hall JW. Central auditory processing disorder
hearing-impaired ear until it becomes inaudible. (CAPD) in Y2K. Hear J 1999;52:35–42.
There are numerous versions of tone decay tests. 14. Staab WJ, Lybarger SF. Characteristics and use of
Excessive tone decay is a sign of retrocochlear audi- hearing aids. In: Katz J, editor. Handbook of clinical
tory dysfunction.
audiology. 4th ed. Baltimore: Williams & Wilkins;
TROCA: Tangible reinforcement operant condition-
1994. p. 657–722.
ing audiometry. A pediatric behavioral audiometry
15. Maxon AB, Brackett D. The hearing impaired child:
technique that reinforces a response to auditory sig-
infancy through high-school years. Boston: Andover
nals with food. TROCA is used mainly with men-
Medical Publishers; 1992.
tally retarded or developmentally delayed children.
16. Beauchaine KL, Donaghy KF. Amplification selec-
UCL/LDL: Uncomfortable level or loudness dis-
tion considerations in the pediatric population. In:
comfort level. The intensity level of a sound that is
Bess FH, Gravel JS, Tharpe AM, editors. Amplifica-
perceived as too loud.
tion for children with auditory deficits. Nashville:
VRA: Visual reinforcement audiometry. A pediatric
Bill Wilkerson Speech and Hearing Center; 1996.
behavioral audiometry procedure that reinforces
localization responses to acoustic signals with a p. 145–60.
visual event (eg, an animal playing). 17. Chasin M. The acoustic advantages of CIC hearing
aids. Hear J 1994;47:13–7.
18. Knowles Electronics. Optimizing the emerging market
REFERENCES for completely-in-the-canal instruments. Available at:
1. Hall JW, Mueller HG. Audiologists’ desk reference. http://www.knowles-electronics.com/Knelec/html/
Vol I. San Diego: Singular Publishing Group; 1997. f6_3.htm (accessed December 17, 2000).
2. Carhart R, Jerger JF. Preferred method for clinical 19. Sandlin R. Hearing aid amplification: technical and
determination of pure-tone thresholds. J Speech clinical considerations. San Diego: Singular Publish-
Hear Disord 1959;24:330–45. ing Group; 2000.
160 Ballenger’s Otorhinolaryngology
20. Bray V. Instant fit hearing aids. Available at: http:// 32. Reamy CE, Brackett D. Communication methodolo-
AudiologyOnline.com/newroot/resources/chat.hom gies: options for families. Otolaryngol Clin North
e/cfm?tid=2/ (accessed December 17, 2000). Am 1999;32:1103–16.
21. Schweitzer C. Development of digital hearing aids. 33. Geers A, Moog J. Speech perception and production
Trends Amplific 1997;2:41–78. skills of students with impaired hearing from oral
22. Valente M, Fabry DA, Potts LG. Recognition of and total communication education settings. J
speech in noise with hearing aids using dual micro- Speech Hear Res 1992;35:1384–93.
phones. J Am Acad Audiol 1995;6:440–9. 34. Gustason G. Educating children who are deaf or
23. Crandell CC. Hearing aids: their effects on func- hard of hearing: English-based sign systems. Reston
tional health status. Hear J 1998;51:2–6. (VA): The Council for Exceptional Children; 1997.
24. Dempsey JJ. Hearing aid fitting and evaluation. In: No. EDO-EC-97-3.
Katz J, editor. Handbook of clinical audiology. 4th 35. Baker S, Baker K. Educating children who are deaf or
ed. Baltimore: Williams & Wilkins; 1994. p. 723–35. hard of hearing: bilingual-bicultural education.
25. Mueller G, Hawkins D, Northern J. Probe microphone Reston (VA): The Council for Exceptional Children;
measurements: hearing aid selection and assessment. 1997. No. EDO-EC-96-8.
San Diego: Singular Publishing Group; 1992. 36. Hawkins L, Brawner J. Educating children who are
26. ASHA Ad Hoc Committee on Hearing Aid Selection deaf or hard of hearing: total communication.
and Fitting: guidelines for hearing aid fitting for Reston (VA): The Council for Exceptional Children;
adults. ASHA 1997;40 Suppl 18:123–30. 1997. No. EDO-EC-97-6.
27. Valente M. Strategies for selecting and verifying hear- 37. Caldwell B. Educating children who are deaf or hard
ing aid fittings. 2nd ed. New York: Thieme; 2002. of hearing: cued speech. Reston (VA): The Council
28. Valente M, Van Vliet MA. The Independent Hearing for Exceptional Children; 1997. No. EDO-EC-97-2.
Aid Fitting Forum (IHAFF) protocol. Trends Amplific 38. Wandel J. Use of internal speech in reading by hearing
1997;2:6–35. and hearing impaired students in oral, total communi-
29. Hurley RM. Onset of auditory deprivation. J Am cation, and cued speech programs [dissertation]. New
Acad Audiol 1999;10:529–34. York: Teacher’s College, Columbia Univ.; 1989.
30. Seewald R. The desired sensation level (DSL) 39. Kricos P. The counseling process: children and par-
method for hearing aid fitting in infants and chil- ents. In: Alpiner J, McCarthy P, editors. Rehabilita-
dren. Phonak Focus 1995;20:3–19. tive audiology: children and adults. Baltimore:
31. Oticon, Inc, and the Academy of Dispensing Audiol- Williams & Wilkins; 1993. p. 211–33.
ogists. Open doors: options in communication and 40. Yoshinago-Itano C. Benefits of early intervention for
education for children who are deaf or hard of hear- children with hearing loss. Otolaryngol Clin North
ing [booklet]. Somerset (NJ): Oticon Inc; 1998. Am 1999;32:1089–102.
CHAPTER 6
In considering the evaluation of the patient with tions. Add to the testing specific or general health
complaints of vertigo, light-headedness, imbalance, inventories such as the Dizziness Handicap Inven-
or combinations of these descriptors, one must look tory12 and predictive assessment of disability is
beyond just the peripheral and central parts of the improved but remains significantly limited. It is
vestibular system with its oculomotor connections. hypothesized that the reason for this dichotomy in
The various pathways involved in postural control, test results versus functional disability and symptom
only part of which have direct or indirect vestibular complaints is the inability of the tests to character-
input, should be kept in mind during an evaluation. ize adequately the status of the central vestibular
Additionally, significant variations in symptoms and compensation process.13–15 It is the exception, not the
test findings can be generated by migraine disor- rule, that vestibular and balance laboratory tests
ders1,2 and/or anxiety disorders,3–5 yet these are diag- return results that would drive management of the
nosed primarily by history, requiring a specific line dizzy patient. It would be extremely rare that these
of questioning. These issues, as well as the tradi- studies return a diagnosis. Therefore, the routine use
tional investigation avenues, will be integrated to of these tools to determine how to proceed with the
present an overall view of the evaluation of the management of a dizzy patient is a false line of rea-
“dizzy” patient. Although the focus of this chapter is soning and not productive in the majority of the
the laboratory investigations, it is important to be patients. What, then, is the role of the laboratory
reminded that the principles and techniques behind studies of ENG, rotational chair, and CDP? It is the
the laboratory investigations can be applied in determination of the extent and site of lesion within
detailed direct office examinations of these patients.6 the peripheral and central parts of the vestibular sys-
The evaluation of the dizzy patient should be tem and the functional limitations in static and
guided by what information is needed to make ini- dynamic postural control (this may relate directly to
tial and subsequent management decisions. When gait abnormalities). The use of this information is in
various tests are reviewed and correlated with high- the confirmation of the suspected site of lesion and
level activities of daily living, virtually no significant diagnosis derived from the patient history and direct
relationships exist for the chronic dizzy patient. Tests physical examination, including aspects of the direct
considered extent- and site-of-lesion studies, office vestibular evaluation. This does not imply a
electronystagmography (ENG),7 rotational chair,8 prioritized order to the testing versus the office visit
and specific protocols in postural control assess- as with chronic dizzy patients it can be very useful to
ment9 give results that are unable to be used to pre- triage them to at least core laboratory evaluations (to
dict symptom type, magnitude, or the level of be discussed below) prior to the office visit.
disability of an individual patient. Conversely, To summarize the above discussion, the fol-
patient complaints cannot be used to predict the lowing are required elements to management deci-
outcomes of these tests. In a limited manner, more sions for the chronic dizzy patient: detailed
functionally oriented evaluation tools, computerized neurotologic history, office vestibular and physical
dynamic posturography (CDP)10 and dynamic visual examination, and formal audiometric testing given
acuity testing,11 provide for some correlation among the inescapable anatomic relationship between the
results, patient symptoms, and functional limita- peripheral parts of the auditory and vestibular
161
162 Ballenger’s Otorhinolaryngology
systems. The following are considered important; time of the office visit, to initiate treatment with
however, they are less likely to drive directly the vestibular and balance rehabilitation therapy
management in the typical case: laboratory vestibu- (VBRT) and to discontinue vestibular suppressive
lar and balance function studies, neuroradiographic medication, were not in any manner altered with
evaluations, and serologic tests. It is important to the obtaining of the laboratory findings. The
realize that there will be patients for whom unex- vestibular function and balance tests were well jus-
pected findings on any one of these latter studies will tified given the length of symptoms and the fact
either alter the complete course of the management that the testing has better sensitivity for some ocu-
or add dimensions to the management not originally lomotor findings than the direct examination,
considered. But for the majority of patients, the specifically saccade velocity testing and quantifi-
vestibular and balance tests will be confirmatory in cation of smooth pursuit. Although it was not
nature. Consider the following contrasting examples needed in this case, sensitivity to mild peripheral
to illustrate this discussion: vestibular function asymmetry is also better with
the laboratory testing. In this case, the magnitude
• Case 1 — Testing is confirmatory. A man, 35 years of the peripheral asymmetry made it detectable by
of age, was seen for complaints of sudden onset, 6 both the direct examination and the caloric irriga-
months previously, of vertigo, nausea, and vomit- tion studies.
ing in a crisis event with continuous symptoms • Case 2 — Testing drives management. A 31-year-
lasting 3 days, steadily showing slow improvement old man presented with the onset of head
and no accompanying auditory symptoms. The motion–provoked vertigo with more or less con-
continuous vertigo resolved into head move- stant imbalance with standing and walking. He
ment–provoked spells of light-headedness with denied any vestibular crisis event or auditory com-
imbalance and occasional vertigo lasting seconds plaints. His symptoms were more concentrated in
to a minute after a movement. All planes of sagittal plane movement and when rolling left or
motion would provoke symptoms. Symptoms had right from a supine position. These symptoms had
continued to improve but still occurred on an been ongoing for several years with intervals when
infrequent daily basis. He presented with no neu- the vertigo was resolved and the imbalance was
rologic focal complaints, and past medical history reduced but not absent. He reported an MRI from
was noncontributory. Audiometric evaluation was several years prior to this evaluation that was nor-
completely normal bilaterally, as was his contrast mal, with a cervical MRI positive for mild disk
magnetic resonance imaging (MRI) study of the abnormalities. Audiologic examination was nor-
head. His detailed vestibular examination both mal. Other than the development of mild pares-
with and without visual fixation was remarkable thesia of the right hand and arm over the last year,
for a positive head thrust test to the left, right- he had no other neurologic complaints, and his
beating post–head shake nystagmus, and sponta- past medical history was noncontributory. His
neous right-beating nystagmus with visual direct office examination was remarkable for ante-
fixation removed. The full neurologic and oculo- rior semicircular canal benign paroxysmal posi-
motor components of the examination together tional vertigo (BPPV). The remainder of the
with the Hallpike maneuver were normal. The his- examination was normal. He was treated in the
tory with the examination was strongly sugges- office with a canalith repositioning procedure and
tive of uncompensated left peripheral vestibular referred on for a formal VBRT program. Secondary
hypofunction secondary to vestibular neuritis. to the length of time of the symptoms and the
Laboratory vestibular function testing revealed complaints of persistent imbalance (although this
spontaneous right-beating nystagmus with visual is a common report with BPPV), vestibular and
fixation removed, a 76% left reduced vestibular balance function testing was requested. The labo-
response with normal oculomotor testing, and ratory studies showed anterior canal BPPV with no
postural control assessment. In this case, the test other indications of peripheral vestibular system
was, as is typical in most cases, confirmatory of the involvement. Pursuit tracking tests were normal,
clinical suspicions from the history and direct but saccade testing (these will be discussed below)
examination. Management decisions made at the was positive for mild right internuclear ophthal-
Evaluation of the Vestibular (Balance) System 163
moplegia. Postural control abnormalities were col- initial comments. Sometimes patients will volunteer
lectively consistent with those seen in demyelinat- that their symptoms are trivial or have resolved
ing disorders. Secondary to these findings and his completely, but they simply want to make sure that
report on a return visit of paresthesia starting in they have not suffered a stroke or developed a brain
the left foot, a new MRI was obtained that showed tumor. If the patient is not permitted to share this
multiple hyperintense spots throughout the brain- information freely, important aspects of the individ-
stem region. He was referred to neurology and is ual’s care may be overlooked.
being followed with a diagnosis of probable multi- Once the patient has shared the main concerns
ple sclerosis with BPPV. Unlike case 1, this case was raised by his or her condition, the first specific ques-
driven strongly by the results of the vestibular and tions should be phrased to gain information regard-
balance function tests. The test results were able to ing the initial onset of symptoms. The characteristics
reveal abnormalities too subtle to be detected in a and intensity of the balance disturbance at that time
direct examination. This is clearly the exception to provide useful insight for the differential diagnosis. If
the impact that the testing has on a more routine the patient can recount specifics surrounding the
basis in the decisions regarding management of the symptom onset such as date and time of day, along
dizzy patient. with the activity interrupted by intense vertigo, the
probability is high that the patient has suffered a sig-
nificant peripheral labyrinthine insult. Surprisingly, if
HISTORY the professional does not specifically inquire, patients
Before consideration of the actual laboratory tests, who are preoccupied with recent symptoms and dis-
some discussion of the neurotologic history is ability may neglect to report a very profound vestibu-
needed. Given the various tools for assessment, the lar crisis that occurred initially. If the onset was more
history is the single most important factor in deter- insidious and the patient is unable to provide any
mining the course of management and therefore account of an initial event, an acute peripheral disor-
requires discussion.14,16–22 The differentiation among der is less likely. Other important issues to discuss at
the various peripheral vestibular disorders is partic- this stage of the interview include the association of
ularly dependent on historical information and the physical trauma, barotrauma, or an intercurrent ill-
conclusions that the physician draws from the inter- ness prior to the onset of vertigo. Patients should also
view. Most vestibular disorders cannot be distin- be asked about previous remote episodes of vertigo.
guished from one another simply by vestibular It is very important to question the patient
testing or other diagnostic interventions. Failure to regarding the association of a hearing loss or other
discriminate properly among these disorders on his- auditory symptoms with the onset of vertigo. A
torical grounds may be the source of considerable complete audiometric assessment should be per-
ongoing distress for the patient and may lead to formed early in the evaluation. The presence of an
improper management by the physician. Since sub- associated sensorineural hearing loss, whether sta-
sequent treatment decisions will be based on the ble, progressive, or fluctuating, is the single strongest
clinical diagnosis, it is particularly appropriate to incriminating factor in identifying a pathologic
spend additional time during the history to clarify labyrinth.23 The presence of other otologic symp-
important features. In addition, balance function toms such as aural fullness and tinnitus may also be
study results are best interpreted in light of a proper helpful in lateralization. Head trauma associated
clinical history. The main reason that the patient is with dysequilibrium and fluctuating sensorineural
seeking medical attention for his or her balance dis- hearing loss or a history of previous otologic surgery
turbance should be identified. Although little spe- or familial hearing loss is also important.
cific diagnostic information may be gained, it is Most patients with acute vertigo will improve
often helpful to hear an account of the patient’s per- with supportive, expectant management. When this
ception of his or her illness prior to pursuing more is not the case, they may present for evaluation after
specific questions. One can often gain a sense of the several months or years of dizziness. The patient
degree of functional disability that the vestibular should be asked to describe the progression of symp-
symptoms have produced. The psychosocial impact toms over time, along with the nature and duration
of the illness may also become clear in the patient’s of typical spells. Specifically, one wishes to know if
164 Ballenger’s Otorhinolaryngology
the spells are continuous or occur in discrete ticular symptoms that specifically interfere with the
episodes. If the symptoms are episodic, it is extremely patient’s recovery process.
important to distinguish whether they are sponta- Other psychosocial aspects can be important
neous or motion provoked. If the symptoms are brief in understanding the patient’s situation. Complicat-
and predictably produced by head movements or ing features of anxiety, depression, or excessive
body position changes, the patient most likely has a dependence on psychotropic medications should be
stable lesion but has not yet completed central nerv- identified. It is desirable to understand the degree of
ous system compensation. Those who describe these functional disability produced by the patients’
symptoms sometimes also note a chronic underlying vestibular complaints, especially with respect to their
sense of dysequilibrium or light-headedness. The professional and favorite social activities. The stabil-
chronic symptoms may be quite troublesome, but ity and commitment of their psychological support
any intense vertigo should be primarily motion pro- system should also be evaluated.
voked. These patients are suitable candidates for
vestibular rehabilitation. It is important to point out LABORATORY TESTS OF VESTIBULAR
that historical information is essential in deciding
who might benefit from rehabilitation therapy. AND BALANCE FUNCTION
If the episodic spells described by the patient The principal tests that are found in most dedicated
are longer periods of intense vertigo that occur balance centers are ENG, rotational chair, and CDP.
spontaneously and without warning, this is probably Other evaluation tools are available for specific tasks.
progressive or unstable peripheral dysfunction. One These include head on body studies (autorotation
must also suspect a progressive lesion if the vertigo tests),24 special protocols that use eye movement
is accompanied by fluctuating or progressive sen- recordings that can quantify linear horizontal and
sorineural hearing loss. Such patients are managed vertical as well as torsional activity,25 dynamic visual
with medical therapy, and if this fails, they constitute acuity,11 and protocols to assess the otolith organs
the best candidates for surgical intervention. Such specifically.26 Although these additional studies can
patients are not candidates for vestibular rehabilita- be useful, the primary discussion will be confined to
tion, except as an adjunctive modality. the principal tools of ENG, rotary chair, and CDP.
As discussed above in generalities, two of the Assuming that all of the studies are available, it
critical elements in developing a differential diagnosis is not necessary for each patient to have all aspects of
involve the determination of spontaneity versus visual the major evaluative tools as a selection of the tests
or head-movement provocation together with the may be adequate. One suggested strategy for deter-
temporal characteristics of the symptoms. These two mining what tests are needed is based on a core set of
features play such a major role in the development of studies that would be appropriate for all patients, and
the working diagnosis that a more detailed discussion the use of those studies together with the neurotologic
is appropriate. Table 6–1, which is not intended to be history determines when the other tests are needed.
exhaustive, suggests the use of these two aspects of the This means that the selection of the tests occurs as the
patient history and the possible sources to consider in testing is being performed and is not predetermined
the diagnosis. To differentiate among the diagnostic at the time of referral. When consideration is given to
options further, the other historical information and the discussion above regarding the utility for the test-
auditory function can be immediately useful. ing in the management decision process, the better
Additional history regarding current or prior approach is to let the testing determine the studies
use of medications should be elicited. Many patients needed given the strengths of the individual tools that
are under the mistaken impression that vestibular will be discussed below. A suggested core would be the
suppressants will prevent spells of vertigo and take ENG with full oculomotor studies (by computerized
them habitually. Because oversedation from these system), full history, and screening evaluation of pos-
centrally acting drugs may retard central nervous tural control. The basic site-of-lesion investigation
system compensation for vestibular lesions, one and first approximation of the functional assessment
should consider tapering or discontinuing these of balance can be obtained in this manner.14 The
medications whenever possible. Medications that rationales for proceeding with total-body rotational
must be continued should be directed toward par- chair testing are as follows:
Evaluation of the Vestibular (Balance) System 165
TABLE 6–1. Suggested Differential Diagnostic Entries Based on Temporal Course and Symptom Characteristics
Temporal Course “Dizziness” Auditory Differential
of Symptoms Characteristics Characteristics to Consider
Episodic (s) HM-HP provoked Normal Benign paroxysmal
positional vertigo,
uncompensated stable
peripheral lesion
Episodic (s–min < 60) Spontaneous Normal or mild Migraine, transient
fluctuations ischemic attacks, anxiety
disorders
Meniere’s disease (spells
over 20 min)
Episodic (min–h < 24) HM-HP provoked Normal Uncompensated stable
peripheral lesion, migraine
Episodic (min–h < 24) Spontaneous Fluctuant + progressive Labyrinthine disorders, eg,
Meniere’s disease;
autoimmune disorders
Episodic (min–h < 24) Spontaneous Normal or mild Migraine, anxiety disorders,
fluctuations cardiovascular disorders
Days Spontaneous Normal Vestibular neuritis, vascular
resolving in 1 to 3 d events
to HM-HP
provoked
Days Spontaneous resolving Sudden loss at time of Labyrinthitis,
in 1 to 3 d to vertigo onset posteroinferior cerebellar
HM-HP provoked artery or anteroinferior
cerebellar artery
distribution strokes
Days typically < 7 Spontaneous or Normal or mild Migraine
HM-HP provoked fluctuation
relatively constant
overall
Continuous May or may not be Normal Central vestibular
exacerbated by disorders, anxiety disorders,
HM-HP nonvestibular disorders
such as sensory or motor
neuropathy of lower limbs
• When the ENG is normal, and oculomotor results • When the ENG suggests a well-compensated sta-
are either normal or observed abnormalities would tus (no spontaneous or positional nystagmus),
not invalidate rotational chair results. Chair testing despite the presence of a clinically significant uni-
is used here to expand the investigation of periph- lateral caloric weakness and ongoing symptom
eral system involvement and compensation status. complaints. Chair testing is used here to expand
166 Ballenger’s Otorhinolaryngology
the investigation of compensation in a patient influence the patient’s overall performance, even
with a known lesion site and complaints suggest- though unsteadiness is not a major complaint.
ing poor compensation.
• When the caloric irrigations produce nystagmus
below 10 degrees/second bilaterally, when caloric
ELECTRONYSTAMOGRAPHY
irrigations cannot be performed, or when results Traditional ENG, using electro-oculography for eye
in the two ears may not be compared reliably movement recordings, is a process that estimates the
owing to anatomic variability. Chair testing is used position of the eye as a function of time indirectly.
in these cases to verify and define the extent of a The estimates are reliable whether recorded with eyes
bilateral weakness or to investigate further the rel- open or closed and in a darkened or well-lit environ-
ative responsiveness of the peripheral vestibular ment. Changes in eye position are indicated by the
apparatus bilaterally when caloric studies are polarity of the corneal-retinal potential (dipole) rela-
unreliable or unavailable. tive to each electrode placed near the eyes (Figure 6–1,
• When a baseline is needed to follow the natural A). These electrodes are typically placed at each lateral
history of the patient’s disorder (such as possible canthus and above and below at least one eye with a
early Meniere’s disease) or for assessing the effec- common electrode on the forehead (Figure 6–1, B).
tiveness of a particular treatment, such as that of Since the primary purpose of the vestibular apparatus
chemical ablation of one or both vestibular end- is to control eye movements, the movements of the
organs. eyes may be used to examine the activity of the
vestibular end-organs and their central vestibulo-ocu-
In a like manner, decisions for use of full pos-
lar pathways. More recently, the technique of infrared
tural control studies can be made based on the his-
video-oculography has begun to replace the standard
tory and the screening tools for postural control
electro-oculography. This technique has the advan-
assessment. Therefore, based on the results of the
tages of direct estimate of the eye position as a func-
Clinical Test of Sensory Integration and Balance
tion of time and reduction in electrical artifacts. A
(CTSIB)27,28 and the patient’s full neurotologic his-
typical horizontal ENG trace of right-beating nystag-
tory, CDP would be called for under the following
mus (could be from either electrodes or video tech-
conditions:
niques) is shown in Figure 6–2. In this figure, a rapid
• If the CTSIB was abnormal with a fall reaction, upward deflection of the trace (fast or saccade com-
significantly increased sway, or sudden change of ponent of the nystagmus) is seen followed in each
strategy for maintaining stance during a trial. case by a slower downward drift of the trace (slow
Based on the comparison between CTSIB and component of the nystagmus). The convention in the
CDP, we know that the patient who can perform recordings is that the upward trace deflections repre-
CTSIB in the normal range is very unlikely to fail sent rightward (horizontal trace) or upward (vertical
the sensory organization portion of CDP. On the trace) eye movements. Conversely, downward deflec-
other hand, CDP is needed to delineate further tions of the trace represent leftward and downward
postural control difficulties when abnormal per- eye movements. Calculation of the principal parame-
formance is noted on the CTSIB. ter used in the analysis of nystagmus, slow-compo-
• If the patient has a major complaint involving nent eye velocity, is illustrated in Figure 6–3. The ENG
unsteadiness when standing or walking, inde- evaluation is a series of subtests performed to assess
pendent of the CTSIB results. Dynamic posturog- peripheral and central portions of the vestibular sys-
raphy, especially motor control testing (MCT), is tem. It is important to understand that assessment of
used in this case to investigate further postural the peripheral part of the vestibular system with ENG
control. This patient would also be a candidate for is significantly limited, typically reflecting function of
postural evoked response testing, a third special the horizontal semicircular canal with restricted
protocol that can be used with CDP in conjunc- information from vertical canals and otolith organs.
tion with lower limb electromyography (EMG) With the use of computerized ENG systems, which
recording, described below. afford significant visual stimulus control and quanti-
• If the patient had a history of known pathology tative analysis, evaluation of the central vestibulo-
involving the postural control pathways that may ocular pathways can be quite thorough.
Evaluation of the Vestibular (Balance) System 167
FIGURE 6–1. A, Shown schematically is the corneal-retinal potential that forms the basis for electro-oculography as
an indirect recording technique for eye movement position as a function of time. B, Typical electrode montage
(arrangement) for monitoring eye position as a function of time in both the lateral and vertical dimensions.
The ENG consists of the following groups of the ENG, the Hallpike maneuver should be analyzed
subtests: oculomotor evaluation, typically with by direct examination, not requiring quantification
smooth pursuit tracking, saccade analysis, gaze fixa- with recording, and should not be analyzed by the
tion, and optokinetic stimulation; spontaneous nys- typical two-dimensional (horizontal and vertical)
tagmus; rapid positioning (Hallpike-Dix maneuver); recorded eye movements from an ENG. The oculo-
positional nystagmus; and caloric irrigations. The motor tests are quantified according to the eye
slow-component eye velocity of the nystagmus (see movements generated during the task and analyzed
Figure 6–3) is the measurement of interest as it by comparison to normative data when a computer-
reflects the portion of the nystagmus that is gener- ized system is used.
ated by the vestibulo-oculomotor reflex (VOR)
(with the fast component generated from the pons Oculomotor Tests Just as the eyes serve as the
area of the brainstem in response to the position of window for investigating the function of the periph-
the eye in the orbit). Although traditionally part of eral part of the vestibular system, they provide a
R10
Degrees
L10
L20
0:07
FIGURE 6–2. Right-beating horizontal nystagmus is demonstrated from a patient’s eye movement recording with the
patient’s eyes closed in the head turned left from a supine position. The vertical axis is in degrees of movement, with
the horizontal axis in time going from left to right, showing a total of 14 seconds.
168 Ballenger’s Otorhinolaryngology
means to investigate the oculomotor pathways in the indicative of specific cerebellar degenerative disor-
brainstem and cerebellum that are required for the ders (saccade intrusions). Optokinetic stimulation
function of the VOR. measures jerk nystagmus eye movements created by
A variety of testing paradigms can assist in repeated objects moving across the subject’s visual
identifying abnormalities in the central oculomotor field and filling at least 80% of the visual field. Opto-
control systems that may produce the patient’s com- kinetic stimulation is the least sensitive, probably
plaints. The smooth pursuit test evaluates the ability owing to the combination of both smooth pursuit
to track a moving object with smooth eye move- and saccade systems, allowing the optokinetic nys-
ments and head still. Smooth pursuit is the most tagmus to be generated by a combination of foveal
sensitive of the oculomotor tests but provides poor and peripheral retinal stimulation. At present, it
lesion site localization within the multiple pathways serves best as a cross-check with significant abnor-
involved in pursuit generation. Abnormalities with malities seen during pursuit or saccade testing. Illus-
pursuit are typically taken as an indication of possi- trated in Figures 6–4 and 6–5 are typical recordings
ble vestibulo-cerebellar region involvement, the final and analysis of smooth pursuit and reactionary sac-
common portion of the multiple pathways for pur- cade testing.
suit production.18 Saccade testing evaluates rapid Compared with gaze fixation and saccade test-
movement of the eye used to place an object of ing, smooth pursuit is significantly more sensitive to
interest on the most sensitive portion of the retina, the presence of pathology. Sensitivity performance of
the fovea. Saccade testing is not as sensitive as pur- these tests was evaluated in a group of 134 patients
suit but when tested with different paradigms can diagnosed with multisystem atrophy, olivoponto-
provide for differentiating information concerning cerebellar atrophy, Friedreich’s ataxia, or multiple
brainstem versus posterior cerebellar vermis involve- sclerosis.14 All had clearly defined brainstem/cerebel-
ment. Suggestions for possible frontal or parietal lar lesions on MRI. Eighty-seven percent had
lobe involvement can also be obtained from saccade evidence for central vestibulo-ocular pathway dys-
testing. Gaze fixation evaluates the ability to hold the function on oculomotor testing, as indicated by
eyes in a fixed direction of gaze without drifting off abnormal performance on any single or combined
the target, typically straight ahead and to the right, test of gaze fixation, saccades, and smooth pursuit
left, up, and down. Gaze fixation provides general measures. Smooth pursuit measures alone identified
suggestions of brainstem/cerebellar involvement in central system involvement in 73% of these cases,
most instances of abnormal results. There are spe- independent of results on saccade and fixation test-
cific abnormalities of fixation of gaze that can be ing, compared with only 40% identified by saccade
Evaluation of the Vestibular (Balance) System 169
Horizontal Tracking
Horizontal Eye Position
R20
R10
Degrees
L10
L20
0:04 500 ms
Frequency = 0.20 Hz R Gain = 0.65 L Gain = 0.71 Phase Shift = 2.2°
Tracking Gain
1.25
Velocity Gain
1.00
0.75
FIGURE 6–4. An example of
0.50
smooth pursuit eye movement
0.25 recording with the target at two of
0.7 0.6 0.5 0.4 0.3 0.2 0.2 0.3 0.4 0.5 0.6 0.7 the multiple frequencies tested.
Target Frequency (Hz) Accepted Cycles: 18 Shown in both top and bottom
Horizontal Tracking
panel sets is a plot of horizontal
Horizontal Eye Position
eye position as a function of time
R20
(500 ms time mark shown) for
R10 sinusoidal tracking (dotted trace).
Degrees
1.00
performance. The top panel set is
0.75
for a target frequency of 0.2 Hz,
0.50 and the bottom panel set is for
0.25 0.71 Hz. Reproduced with permis-
0.7 0.6 0.5 0.4 0.3 0.2 0.2 0.3 0.4 0.5 0.6 0.7
sion from Shepard NT and Telian
Target Frequency (Hz) Accepted Cycles: 18 SA.14
testing alone and 47% for fixation testing. These tools derived from a group of patients suspected of having
also can suggest central nervous system involvement pure peripheral lesions.14 Given the advanced nature
in patients without obvious structural abnormalities of the disease states of the groups of patients used for
identified by MRI. As it is possible to have abnormal the sensitivity and specificity figures, it is highly likely
central nervous system function without structural that both figures are overestimates of performance
changes on neuroradiographic studies, it is difficult with actual sensitivity and specificity figures in the 75
to provide overall true sensitivity figures. Statistically, to 80% range.
as normal values are typically based on two standard In a review conducted by Shepard and Telian14
deviations from the mean performance, a small per- of 2,266 patients seen over a 32-month period, 14%
centage of those with suspected central involvement had abnormalities suggesting brainstem and/or cere-
will be false positives. An estimate of 86% specificity bellar involvement without any indications of
(14% false positives) for the oculomotor studies is involvement of the peripheral part of the system.
170 Ballenger’s Otorhinolaryngology
The percentage of those suspected of involvement of horizontal head movements at about 2 to 3 Hz for 10
the central part of the system increased to 21% when seconds are presented with fixation removed. When
combinations of peripheral and central abnormali- the head is brought to a stop, recording of eye move-
ties were included. Therefore, since exact sensitivity ments is continued long enough to capture nystag-
and specificity performance figures cannot be deter- mus that had been provoked or no nystagmus if the
mined, it seems best to employ test protocols that test is negative. The presence of three or more hori-
may reduce the false-positive rate (increase speci- zontal nystagmus beats is suggestive of a peripheral
ficity) without decreasing test sensitivity. The three asymmetry. In most cases, the direction of the fast
crucial principles to assist in these goals are (1) the component of the nystagmus is away from a paretic
use of computerized, quantitative analysis; (2) appli- lesion; however, this is not always the case, and the
cation of age-appropriate normative data compar- nystagmus may beat toward the side with a lesion.
isons; and (3) repetition of initially abnormal test Vertical nystagmus resulting from the horizontal
measures to obtain optimal performance. head shake is a positive sign for brainstem and/or
cerebellar involvement and is referred to as cross-
Spontaneous Nystagmus This test is performed coupling nystagmus. Although the sensitivity for
with the patient sitting, head straight and eyes closed. identification of peripheral involvement is reported
The purpose is to record eye movements when visual to be only fair, the ease of the test and its short time
fixation is removed, without any provocative head for execution make it reasonable to add to the ENG
movements or positions. Jerk nystagmus is the prin- battery.29
cipal abnormality of interest in most situations.
Other forms of abnormal eye movements, such as Hyperventilation Nystagmus This is another of
pendular nystagmus (sinusoidal horizontal repeating the office examination tools that can be easily and
eye movements with no distinguishable slow and fast effectively used during an ENG protocol. The use of
components), may be seen. Clinically significant, hyperventilation testing has a dual purpose. The first
direction-fixed nystagmus is interpreted to indicate is identification of nystagmus suggestive of eighth
possible pathology within the peripheral part of the cranial nerve involvement on the side to which the
vestibular system if the oculomotor evaluation is fast component of the nystagmus is directed. The
normal (Figure 6–6, A). nystagmus results from myelin being absent from a
section of the nerve secondary to a demyelination
Head-Shake Nystagmus The head-shake protocol process from disease or a mass lesion.30 The second
is commonly associated with the direct office exam- use is to identify an individual more likely to be
ination yet can be usefully incorporated as part of experiencing an anxiety disorder. This is recognized
the ENG.6 As with the office examination, reciprocal by the production of symptoms of light-headed-
Evaluation of the Vestibular (Balance) System 171
FIGURE 6–6. A through D plot horizontal eye position in degrees as a function of time, each showing right-beating
nystagmus. The time in the lower right corner of each panel is the total elapsed time in seconds for that recording, not
the total time shown. Each panel represents 7 seconds of tracing. A, ECHS = eyes closed head straight, spontaneous.
B, HTR = eyes closed head turned right, sitting position. C, Eyes closed, lying on the right side (right decubitus posi-
tion). D, Eyes closed, extension of the neck (by approximately 30 degrees) with the head turned to the right. These are
4 of a total of 11 positions tested on this patient. Reproduced with permission from Shepard NT and Telian SA.14
ness/imbalance within 30 seconds of starting the therefore cannot be recorded with standard electro-
hyperventilation, with no nystagmus visualized. oculography techniques or typical standard video
Hyperventilation is more likely to provoke dizziness, systems as both are two-dimensional in the printed
light-headedness, autonomic symptoms, and acute output.
anxiety attacks in patients with certain anxiety dis- The Hallpike maneuver is also typically part of
orders than in the general population.31 It also may the standard ENG protocol (Figure 6–7). Classically,
provoke light-headedness and autonomic arousal positive Hallpike responses produce a torsional nys-
without significant anxiety in patients with auto- tagmus (pure rotational movement of the eye about
nomic dysfunction (eg, hyperventilation syn- an axis through the center of the globe going from
drome).32 Anxiety disorders or dysautonomia should anterior to posterior when that axis is oriented par-
be suspected in patients who experience a marked allel to the axis perpendicular to the plane of the
reproduction of their symptoms, without nystag- canal involved). The fast component is directed
mus, during hyperventilation. toward the involved ear (left torsional for left ear and
right torsional for right ear, from the patient’s per-
Hallpike Maneuver The Hallpike maneuver is a spective, relative to the superior pole of the eye). To
well-known office procedure used primarily to elicit detect this action adequately, the movements must
evidence for BPPV. Since this is typically a problem be viewed by the examiner (directly or with video
with a single semicircular canal at a time, the equipment), not reviewed after the fact by two-
description of the nystagmus is critical to identifi- dimensional recordings from standard surface elec-
cation of the canal involved. Each canal has an indi- trode or standard video recording techniques.
vidual and unique eye movement signature that can
be used to recognize which canal is causing this dis- Positional Nystagmus Positional nystagmus is the
order.33 In the variants of BPPV, only the horizontal most common abnormality noted with ENG evalu-
canal variant does not have torsional eye move- ation. In this study, the patient is moved slowly into
ment; all others involve torsional movements and stationary positions. The eye movements are moni-
172 Ballenger’s Otorhinolaryngology
studies of the presence of positional nystagmus in a Caloric Irrigations The caloric test is the study
normal population is as follows: slow-component eye that is most likely to indicate the side of a peripheral
velocity > 5 degrees/second, slow-component eye lesion with objective, repeatable eye movement data.
velocity < 6 degrees/second with persistent nystag- The stimulus employed is nonphysiologic compared
mus in 4 or more of the 8 to 11 positions, and slow- to the normal function of the system during head
component eye velocity < 6 degrees/second with motion, when one side is stimulated and the other is
sporadic nystagmus in all positions tested and direc- simultaneously inhibited. Nevertheless, the caloric
tion changing within a given head position.34 test is the only portion of the test battery that pro-
Two other conditions that can produce posi- vides a measure of unilateral labyrinthine function.
tional nystagmus without oculomotor abnormalities There are three primary delivery methods for caloric
must be considered before involvement of the irrigations: closed-loop water (circulates in a thin
peripheral part of the system is suggested. Migraine latex balloon that expands in the external auditory
headache conditions can produce these findings, in canal), open-loop water (runs into the external audi-
addition to mild caloric asymmetries.35,36 No partic- tory canal and drains out), and air irrigation (Figure
ular patterns of positional nystagmus are indicative 6–8). During any of the methods, the fluid or air is
of migraine. Since migraines and dizziness related to set at temperatures above or below that of the body;
migraine are diagnoses of exclusion, it is important typically, 44°C for the warm and 30°C for the cool
to keep this in mind if the total presentation of the are used for the open-loop water systems. All are rea-
patient is not convincing for involvement of the sonably reliable when the tympanic membrane is
peripheral part of the system. Somewhat less well intact. When a tympanic membrane perforation or
documented in producing positional eye movement short ventilation tube is present, the closed-loop
abnormalities are anxiety disorders. The most com- water irrigation method is preferable.
monly recognized eye movements associated with In both terrestrial and weightless environ-
anxiety, especially related to the testing process, ments, there appears to be at least two mechanisms
causing symptoms are macrosquare wave jerks operating to produce the caloric VOR response to
(square waves of a 5- to 15-degree subtended arc the temperature changes. The one that seems to pre-
with normal intersaccade intervals).18 This type of dominate in routine testing involves gravity and the
intrusion saccade is noted only with fixation density changes that occur in the endolymph of the
removed. Classic positional jerk nystagmus of a horizontal canal when it is heated or cooled (density
direction-fixed or direction-changing nature can decreased or increased, respectively). The head is
also be provoked by anxiety disorders.31 positioned so that the horizontal canal is oriented
FIGURE 6–8. Three techniques for caloric irrigations are shown. Reproduced with permission from Shepard NT and
Telian SA.14
174 Ballenger’s Otorhinolaryngology
parallel to the gravitational vector, with the nose of ment (directional preponderance) (Figure 6–9). Tra-
the patient upward and the head tilted 20 to 30 ditionally, the four maximum values are combined
degrees upward from the horizontal plane. During a to produce the two outcomes through the use of
warm irrigation, the less dense fluid attempts to rise Jongkee’s formulas.37
upward. This produces a deviation of the cupula Although four irrigations are typical, there are
toward the utricle owing to the pressure differential situations in which use of “ice water” (4°C) is
across the cupula, causing stimulation of the eighth needed and other situations in which only two irri-
nerve. The reverse action occurs for the more dense gations of either warm or cool are sufficient.14,38
area of cooled fluid, causing inhibition. This results Directional preponderance is interpreted as a bias in
in the well-known mnemonic “COWS,” which refers the central part of the system, making it easier to
to the direction of the fast component of the nystag- produce nystagmus in one direction than another.
mus: Cold Opposite, Warm Same (relative to the This bias is most often a result of asymmetric
side of irrigation). peripheral function, for which the central compen-
The traditional interpretation of caloric stimu- sation process is incomplete, and is less likely to be a
lation uses a relative comparison of maximum, aver- result of a lesion of the central part of the system.
age slow-component eye velocity on the right versus It is critical in the interpretation of the caloric
the left. These values are used to provide a percent- test to recognize its limitations. The most dominant
age comparison of response magnitude (reduced of these is that the test is one of the horizontal semi-
vestibular response) and direction bias of eye move- circular canal function. Participation by either of the
FIGURE 6–9. Plots of slow-component eye velocity (SCV) from nystagmus provoked by open-loop water irrigations
as a function of time. Each triangle represents one SCV movement of the eye from the nystagmus trace. Responses for
the right ear are shown on the left; those for the left ear are on the right. The orientation of the triangles represents
either cool (30°C) or warm (44°C) irrigations. The plots are arranged so that right-beating nystagmus SCVs are on
the bottom (right warm, left cool) and left-beating nystagmus SCVs are on the top (right cool, left warm). The veloc-
ity values given in the top or bottom of each plot represent the average maximum SCV calculated for the nystagmus
beats within the rectangle shown on each plot. These maximum, average SCV values were used to calculate the caloric
weakness and directional preponderance values shown at the bottom of the figure. Nine percent in the right ear means
a 9% weaker response on the right compared with the left. Nine percent to the right means a 9% greater response for
right-beating nystagmus compared with left-beating nystagmus. For purposes of calculations, SCVs from right-beat-
ing nystagmus are assigned a negative number and those for left-beating nystagmus are assigned a positive number.
Reproduced with permission from Shepard NT and Telian SA.14
Evaluation of the Vestibular (Balance) System 175
Spikes/s Spikes/s
c
a
Time Time
(a + b) – (c + d)
RVR = ⫻ 100% Left Reduced Vestibular Response
a+b+c+d
(a + d) – (b + c)
DP = ⫻ 100% Left Directional Preponderance
a+b+c+d
FIGURE 6–10. A schematic representation of a caloric irrigation test giving a left-side reduced vestibular response
(RVR) with left directional preponderance (DP). The two plots at the top show in graphic form the estimated firing
rate activity in spikes per second on the right and left eighth cranial nerves during the caloric test. The three intervals
shown during the test are preirrigation (spontaneous) then the result from warm or cool open-loop water irrigations
performed in an alternating bithermal protocol (right warm, followed by left warm, followed by left cool, and finally
right cool). The amplitudes of the responses to the irrigations are given with the variables a, b, c, d. The spontaneous
preirrigation neural activity on the eighth nerve is greater on the left than the right; however, the responses to irriga-
tions are significantly less on the left than the right. For the caloric response traces, an upward deflection indicates an
excitatory response on the nerve with the downward deflection indicating an inhibitory (reduction in firing rate)
response. Given the relative values of the responses shown in the figure, the corresponding calculations of RVR and
DP would produce the indicated result.
vertical canals is minimal at best. The test is also lim- which the directional preponderance is oriented. Yet
ited in its frequency response for the peripheral sys- nystagmus always beats toward (fast component of
tem (discussed in more detail below). Finally, the test the nystagmus toward) the side of greater neural
is one of relative responsiveness of the peripheral activity. This presents as a dichotomy in that the side
system (horizontal canal) to an attempt at driving with the reduced vestibular response must have the
the system with an exogenous stimulus. It is not a greater neural activity ongoing to have the sponta-
test that is intented to reveal in a direct manner the neous and positional nystagmus, as well as the direc-
ongoing strength of the neural activity of the right tional preponderance oriented toward that same
versus the left peripheral part of the system. As a side. This is illustrated in the simple model pre-
result of this, it is possible to have a reduced vestibu- sented in Figure 6–10. Figure 6–11 shows the actual
lar response on the same side as that to which spon- results in a patient with classic Meniere’s syndrome.
taneous and positional nystagmus beats and to The hearing loss and all auditory complaints for the
176 Ballenger’s Otorhinolaryngology
FIGURE 6–11. Plots of slow-component eye velocity (SCV) from nystagmus provoked by open-loop water irrigations
as a function of time. Each triangle represents one SCV movement of the eye from the nystagmus trace. Responses for
the right ear are shown on the left and those for the left ear on the right. The orientation of the triangles shown on the
figure represents either ice water (4°C) or warm water (44°C) irrigations. The plots are arranged so that right-beating
nystagmus SCVs are on the bottom (right warm, left ice water) and left-beating nystagmus SCVs are on the top (right
water ice, left warm). The velocity values given in the top or bottom of each plot represent the average maximum SCV
calculated for the nystagmus beats within the rectangle shown on each plot. These average maximum SCV values were
used to calculate the caloric weakness and directional preponderance values shown at the bottom of the figure. For pur-
poses of calculations, SCVs from right-beating nystagmus are assigned a negative number and those from left-beating
nystagmus are assigned a positive number (note that left ice water gave a left-beating nystagmus, not a right, as would
be expected—hence a positive averaged value). Reproduced with permission from Shepard NT and Telian SA.14
patient in this example were on the left. During the formed on both sides, the use of warm and ice water
ENG, spontaneous left-beating nystagmus was noted is not a problem. The purpose is to increase the
and persisted in all positions with fixation removed. absolute value of the caloric response (as shown for
This indicates that the neural activity on the left the right irrigations in Figure 6–11) to avoid per-
must be greater than that on the right. Yet the caloric centage calculations with numbers at or less than 10
results shown in Figure 6–11 demonstrate a signifi- degrees/second. However, as in this example, if both
cant left reduced vestibular response. Not surpris- sides are not equivalent in their response to the irri-
ingly, given the spontaneous nystagmus, a left gation, the increased response to ice on one side
directional preponderance is shown. This result is alone can lead to an artificially increased or falsely
referred to as a left paretic lesion with an irritative produced directional preponderance. In Figure
status. This suggests that although the pathologic 6–11, the actual directional preponderance, when
process is destructive, it is causing an irritative focus. estimated with the added effect of ice taken into
The two most common disorders to result in an irri- account, is about 36%, not 73%.14
tative lesion, with or without a paretic component, The use of the formulas provided in Table 6–2
are early mass lesions of the cerebellopontine angle requires the following assumptions to be met. First,
and Meniere’s disease. anatomic symmetry between the external auditory
An additional feature of the example given in canals, middle ears, and lateral aspects of the tempo-
Figure 6–11 is the consequence of using a combina- ral bones must be present. Once the first assumption
tion of unequal temperatures, warm and ice water is fulfilled, then the second is that, technically, the
irrigations. As long as the same protocol is per- same temperature of fluid or air must be delivered to
Evaluation of the Vestibular (Balance) System 177
TABLE 6–2. Formulas for the Calculation of Reduced Vestibular Response and Directional Preponderance
Reduced vestibular response (RVR) [(RW + RC) – (LW + LC)] × 100%
=
(values –100% to +100%) RW + RC + LW + LC
Directional preponderance [(RW + LC) – (LW + RC)] × 100%
=
(values unlimited) RW + RC + LW + LC
the plane of the tympanic membrane on each side. not likely to alter or impact significantly the course
These both deal with the establishment of equivalent of patient management, excepting the patient with
temperature gradients for stimulating the horizontal bilateral peripheral weakness.
semicircular canals. If the first assumption is violated The review of 2,266 patients was used to inves-
secondary to congenital or acquired processes, the tigate the clinical utility of rotary chair testing in the
test can still be performed, but the responses, right evaluation of the peripheral part of the vestibular
versus left, cannot be compared. The results can be system. Among this group of patients, 16% had
used to indicate the presence or absence of a completely normal ENG studies. Among those with
response. There are other protocols for calorics that normal ENG results, rotational chair testing indi-
will not be covered in this chapter; however, one in cated abnormalities suggesting possible pathology in
particular, the Torok Monothermal Caloric test, was the peripheral part of the system in 80% of the cases.
developed to use data from only one ear irrigation at In all cases of bilateral caloric weakness, the chair
a time and not via a comparison.39 findings help confirm the bilateral reduction in
Since the peripheral part of the vestibular sys- function of the peripheral part of the system. The
tem functions across a frequency range, it is reason- test further defines the extent of the bilateral lesions.
able to question what portion of that range a caloric This additional information plays an important role
response occupies. The equivalent angular accelera- in designing a vestibular rehabilitation program for
tion response falls in the lower-frequency range of these patients. It is the patient with bilateral lesions
response of the system (0.002 to 0.004 Hz). There- for whom rotational chair testing can make a direct
fore, absence of a caloric response to warm, cool, or impact on the management course in a rehabilita-
ice water irrigations cannot be taken as an indica- tion program. There are also patients who for rea-
tion of complete lack of function. Testing by rota- sons other than vestibular dysfunction have mildly
tional chair is the tool needed to help define the true reduced caloric responses. Of these patients, the
extent of bilateral lesions of the peripheral part of majority have normal rotational chair responses,
the vestibular system. In addition to the bilateral suggesting that indication of bilateral paresis was a
issue, the frequency response effect for the caloric false-positive finding or that the extent of the bilat-
test allows for a peripheral lesion to be present, yet eral lesions is mild and restricted to only the low-
not affect the caloric, but result in abnormalities on frequency range of function. Rotational chair testing
other tests such as the rotational chair (see below) or is the only tool currently available for defining the
head on body rotation testing.24 extent of suspected bilateral peripheral lesions.
Patients diagnosed by clinical presentation and
hearing test results, independent of balance function
ROTATIONAL CHAIR TESTING test results, with Meniere’s disease, labyrinthitis, or
Rotational chair testing has been used to expand the vestibular neuritis numbered 311 during the period
evaluation of the peripheral part of the vestibular of this study.14 Of this group, ENG was abnormal in
system. As with the ENG findings, the rotational 90%, suggesting a test sensitivity of this value.
chair evaluation can assist in site-of-lesion determi- Rotary chair testing had a sensitivity suggesting
nation, counseling the patient, and confirmation of involvement of the peripheral part of the system of
clinical suspicion of diagnosis and lesion site but is only 66%. However, it is important to note that the
178 Ballenger’s Otorhinolaryngology
Rotating to Right
given frequency are delivered, producing repetitive Slow-component eye velocity
to-and-fro movement of the chair in a sinusoidal
Rotating to Left
response for the test frequency. The frequency is
then changed, and the process is repeated. Ideally,
p = phase (in time or degree)
the more cycles that can be averaged, the more reli- Gain = b1/a
able the signal. Pragmatically, the number of cycles asymmetry = b2 – b1/b2 + b1 ⫻ 100 (in %)
needs to be considered in light of the period (length
of time for a single cycle) of the stimulus. As the FIGURE 6–13. Averaged head and eye velocity plotted as
period at 0.01 Hz is 100 seconds, to do more than a function of time or degrees is shown with indications
three cycles becomes prohibitive. Unfortunately, the for the development of the three parameters used to char-
very low frequencies (less than 0.08 Hz) produce the acterize performance with chair stimulation by sinusoids.
weakest response from the VOR system and there- b1 = the maximum excursion of the slow-component eye
fore have the poorest signal-to-noise ratio. In gen- velocity trace for rotating to the right; a = the maximum
eral, the very low frequencies are also most likely to excursion of the head velocity trace for rotating to the
produce unpleasant neurovegetative symptoms such right; b2 = the maximum excursion of the slow-compo-
as nausea and vomiting. The frequencies from nent eye velocity trace for rotating to the left. Reproduced
0.16 Hz and above can be completed quickly, allow- with permission from Shepard NT and Telian SA.14
ing responses from as many as 10 cycles to be aver-
aged. For all frequencies tested, the peak chair
velocity is typically fixed at 50 to 60 degrees/second. 0.08 Hz. Under these circumstances, the compensa-
Therefore, as the frequency is increased, the subject tory eye movements can lead the head movement, as
experiences increasing acceleration with decreasing shown in Figure 6–13. The amount of this phase
excursion of the chair. lead is called the phase angle and is typically meas-
Three parameters are measured during rota- ured in degrees. The center panel of Figure 6–14
tional chair testing to characterize the function of the shows a plot of phase angle versus frequency of rota-
VOR and thereby evaluate the function of the tion in a patient with normal rotary chair findings.
peripheral part of the vestibular system. These The phase results can be used to calculate the system
parameters are phase, gain, and asymmetry. Figure time constant from any frequency tested; however,
6–13 shows a schematized version of an averaged assumptions can be applied that significantly sim-
slow-component velocity response from multiple plify the calculations if the frequencies are restricted
cycles of stimulation at a single frequency. The chair to 0.04 Hz and below.17 In general, in this restricted
velocity is also shown, which correlates to head veloc- frequency range, the relationship between phase
ity, assuming that the head is properly stabilized. The angle and time constant is an inverse proportion. As
parameters that characterize VOR function are devel- phase angle increases, time constant decreases. In
oped by comparing the slow-component eye velocity general, phase angle and its complement time con-
profile to the head velocity profile. stant should be thought of as a measure of the tim-
ing relationship of head and eye movement and are
PHASE. This parameter of the VOR is the least intu- parameters that have specific values indicating nor-
itive of the three but has the greatest clinical signifi- mal VOR functioning.17,40
cance owing to its ability to document dysfunction As seen in the center panel of Figure 6–14, the
of the peripheral part of the system. Phase measure- normal range for phase (based on two standard
ments objectify the timing relationship between deviations above and below the mean) is indicated
head movement and reflex eye movement. Figure by the clear area. An increase in the phase lead out-
6–13 illustrates findings expected from a normally side this range implies an abnormally low time con-
functioning VOR system at test frequencies below stant. From experimental studies of the velocity
180 Ballenger’s Otorhinolaryngology
FIGURE 6–14. Normal rotary chair results from a patient. The plot on the left shows gain (eye velocity divided by head
velocity) as a function of frequency of chair sinusoidal stimulation. The center plot shows phase angle in degrees as a
function of frequency, and the plot to the right gives symmetry data in percent as a function of frequency. The shaded
areas represent abnormality, and the individual values for gain, phase, and symmetry are given in the table at the
bottom of the figure. Normal ranges are two standard deviations above the mean. Reproduced with permission from
Shepard NT and Telian SA.14
storage integrator (vestibular nucleus region) that measures is to define the extent of a bilateral reduc-
regulates the VOR system time constant, we know tion in responsiveness of the peripheral part of the
that damage to the labyrinth or the vestibular por- system when using the sinusoidal protocol. The gain
tion of the eighth cranial nerve causes a decrease in value helps verify that severely reduced or absent
the time constant. Hence, increased phase lead, responses to caloric irrigations accurately reflect a
implying an abnormally low time constant, strongly bilateral weakness and did not result from an artifact
suggests pathology in the peripheral part of the sys- of alertness or some other test pitfall. Figure 6–14
tem. Caution in this interpretation must be used as (left panel) shows normal results for gain as a func-
other sources for the increased phase lead can result tion of the sinusoidal frequency of the stimulation.
from damage in the vestibular nuclei within the
brainstem and possible influence of migraine Asymmetry In Figure 6–13, the schematic represen-
headache conditions. Therefore, other clinical infor- tation of asymmetry involves a comparison between
mation is needed to help localize the lesion to the the slow-component eye velocity to the right (posi-
labyrinth or eighth nerve. The significance of an tive values) compared with the left (negative values).
abnormally low phase lead (abnormally high time It is important to recognize that these values are cal-
constant) can suggest a lesion in the nodulus region culated and named by the direction of the eye move-
of the cerebellum, an area that influences the veloc- ment that is produced by the VOR, that is, the slow
ity storage integrator in the brainstem.41 component of the nystagmus. The situation is
reversed when discussing directional preponderance
Gain The second parameter of the VOR measured from caloric irrigations. Directional preponderance
in rotary chair testing is gain (eye velocity divided by values are calculated by slow-component velocity
head velocity) (see Figure 6–13). Gain measures give but, by convention, are named by the direction of the
an indication of the overall responsiveness of the fast component of the nystagmus. Therefore, a
system. Unilateral peripheral weaknesses can cause a patient who exhibits a right-beating directional pre-
mild reduction in gain, especially at the lowest fre- ponderance (left slow-component velocity greater
quencies. However, the principal clinical use of gain than right slow-component velocity) may show a left
Evaluation of the Vestibular (Balance) System 181
greater than right asymmetry on rotational chair eration step, usually of equal magnitude to the initial
testing, indicating that during chair testing, left slow- acceleration, bringing the chair to a rapid stop.
component velocity was greater than right slow- Although the chair is now stationary, the subject will
component velocity, consistent with the directional perceive motion in the opposite direction. The VOR
preponderance. Directional preponderance and response will produce nystagmus beating in the
asymmetry from chair testing will not always both be direction opposite to that produced by the initial
abnormal. Both directional preponderance (caloric acceleration, known as postrotary nystagmus. The
testing) and asymmetry (rotary chair testing) give an decay of the slow-component eye velocity over time
indication of bias within the system, favoring larger should be similar to that seen after the acceleration
slow-component velocities in one direction versus impulse, and, ideally, both should give similar esti-
the other. A bias usually results from a peripheral mates of the system’s time constant. The entire pro-
lesion with incomplete dynamic compensation in the cedure is then repeated with the initial rotation in the
central nervous system. Less commonly, it may indi- opposite direction. If a constant velocity of 180 to
cate the presence of an uncompensated lesion in the 240 degrees/second is used, the time constant calcu-
central pathways. Whenever a VOR asymmetry is lation is not as accurate; however, differences in gain
noted on rotary chair testing, the finding may be for acceleration to the right versus the left are made
attributed to abnormalities in either peripheral part apparent in this manner, helping to identify a periph-
of the system: either a peripheral weakness on the ery with a weaker response.
side of the stronger slow-component velocity The results are heavily influenced by the noise
response or an irritative lesion on the opposite side. in both the recording and physiologic systems and
For example, a patient with an uncompensated right the arousal of the patient prior to the acceleration as
peripheral weakness will generally demonstrate a averaging is not used in this paradigm. As a result,
right greater than left slow-component velocity there will be patients for whom the estimates of time
asymmetry. This is owing to an ability to produce a constant from this protocol may not agree with esti-
greater rightward compensatory eye movement mates from the sinusoidal protocol. Given that both
when rotated toward the intact left side and a less the step test and the sinusoidal acceleration tests are
intense leftward compensatory eye movement influenced by the noise issue, the two can be
response produced after rotation toward the weaker employed in parallel to increase the accuracy of esti-
right side. Figure 6–14 (right panel) shows a normal mates of the system time constant and identification
result for the asymmetry measurement. of which periphery, if any, is functioning in an
abnormal manner.8,17,40,42,43
Step Test This protocol is performed, as in the
sinusoidal case, with the test booth in total darkness. POSTURAL CONTROL ASSESSMENT
A fixed chair velocity between 60 and 40 degrees/
second is achieved by applying an acceleration Just as all patients who are being evaluated in the lab-
impulse with a magnitude near 100 degrees/second2. oratory need tests for peripheral and central
Once the desired velocity is reached, the acceleration vestibulo-ocular pathway involvement, they also
is returned to 0 degrees/second2, and the patient con- require some assessment of postural control ability.
tinues at the desired velocity. The VOR response to However, just as in the use of ENG and rotational
the initial acceleration stimulus is known as per- chair testing, not all patients would need high-tech-
rotary nystagmus. The slow-component velocity nology, formal postural control assessment. There are
intensity decays over time if the chair velocity is con- several different general approaches to formal pos-
stant, and the subject falsely perceives that the chair tural control testing, each with specific technical
is slowing down. The decay in slow-component eye equipment requirements and goals for the test-
velocity over time can be used to estimate the sys- ing.10,14,44 To reduce the scope of this discussion, com-
tem’s time constant, as discussed above. Use of a con- ments will be restricted to the most common formal
stant-velocity step protocol of 60 to 100 degrees/ assessment tool used in the United States, CDP as
second works best to calculate the time constant. formulated in the EquiTest® equipment (NeuroCom
After 45 to 60 seconds of fixed-velocity rotation, a International, Inc., Clackamus, OR).45–48 Briefly, the
second impulse is applied to the chair. This is a decel- equipment detects vertical and horizontal forces
182 Ballenger’s Otorhinolaryngology
from the feet by two independent force plates on during a series of six specific conditions (Figure
which the subject stands. The force plates can be 6–15). The first three provide for uninterrupted, accu-
made to translate forward or backward and rotate rate foot support surface information on a surface
toes up or down to provoke movement of the sub- with adequate friction that is larger than the foot size.
ject’s center of mass. The rotation movements can In condition 1, the eyes are open, whereas in condi-
also be stimulated by the subject’s own movements tion 2, the eyes are closed. Under condition 3, the
to create information from the ankle that is inaccu- visual surround moves in a pattern that is stimulated
rate. The visual surround can also be made to move by the anterior/posterior sway movements of the
stimulated by the subject’s movements or independ- patient. Conditions 1 and 2 are a modified Romberg’s
ent of subject activity. Two principal testing proto- test (a qualitative clinical test of patient stability when
cols (discussed below) are used in patient evaluation: standing with feet together, arms folded, and eyes
the Sensory Organization Test (SOT), using patient- opened or closed) as the feet are at their normal sep-
stimulated floor and visual surround movements, aration rather than close together. Condition 3 pres-
and MCT using the translation and rotations of the ents a situation of visual conflict, for which visually
support surface to cause subject movements. As with accurate information is provided but of no significant
rotational chair testing, not all patients need to have help in maintaining quiet stance. Condition 3 pres-
full formal CDP. Suggested criteria as to when the ents misleading optokinetic and foveal visual cues
use of full CDP would be most clinically revealing about the position of the body in space. Conditions 4,
were presented in the introductory discussion above. 5, and 6 use the same sequence of the three visual
The survey of 2,266 patients with consecutive conditions but with the foot support surface giving
balance disorder, introduced in the ENG and rota- misleading information. As with the movement of the
tional chair discussions, can again be used to assess visual surround in condition 3, when testing under
the percentage of patients with abnormalities on conditions 4, 5, and 6, sway movements of the patient
CDP (EquiTest) and to study the types of patients in the sagittal (anterior/ posterior) plane drive the
most likely to have abnormal posturography results. movement of the support surface in a rotational man-
In general, when all patients with indications of ner about an axis parallel to the ankle joint. In this
involvement of the peripheral part of the system are way, somatosensory and proprioceptive information
considered, only 30 to 35% show abnormalities on is not removed in conditions 4, 5, and 6 but is of lim-
formal CDP. However, there was a group of 4 to 5% ited use in maintaining upright stance. These condi-
of this total population of 2,266 patients for whom tions provide a disrupted relationship between body
CDP was the only abnormal finding across all of the position and the ankle angle (that angle made
ENG and rotational chair tests. This group was pri- between the upper surface of the foot and the anterior
marily over 65 years of age, with the chief complaint portion of the lower leg). Typically, after the simpler
of unsteadiness with standing and walking. These conditions 1 and 2, three trials are given for each of
patients had no complaints when sitting or lying and the more challenging conditions. The average per-
no perceptions of vertigo or other abnormal move- formance is taken as representative of the patient’s
ments. These statistics played a principal role in the postural control ability under that sensory condition.
development of the above discussed criteria for when The equilibrium score is a percentage repre-
to proceed for full CDP. The protocols for EquiTest senting the magnitude of sway in the sagittal (pitch)
assess various aspects of quiet and dynamic postural plane for each trial of each condition. Details of how
control abilities. Although certain aspects of postural this score is obtained will not be repeated here.48
control are prerequisites for gait activities and certain However, it is important to realize that this score is
abnormalities of postural control may cause prob- based on a normal value of 12.5 degrees of ante-
lems in ambulation, posturography cannot be used rior/posterior sway about the ankle joint, typically 8
in isolation to evaluate gait deficits. Gait evaluation degrees forward and 4.5 degrees backward. It is
has its own complete set of parameters that must be assumed that this range of sway is available to
tested under a completely different set of conditions. patients during the test. Some patients may not have
this normal range because of physical restrictions at
Sensory Organization Test Briefly, the SOT meas- the ankle, or, because of limits of sway, patients have
ures the ability to perform volitional, quiet stance adopted secondary strategies owing to their sense of
Evaluation of the Vestibular (Balance) System 183
FIGURE 6–15. The six sensory organization test conditions, showing which sensory input cues are available or accu-
rate for each condition. Reproduced with permission from NeuroCom International, Inc., Clackamus, OR.
imbalance and fear of a potential fall. It is important As with the overall balance system evaluation,
to recognize the patient who has a reduction in lim- this study is also interpreted using pattern recogni-
its of sway. If the limits of sway are reduced more tion. The combinations of the six conditions that are
than 50%, the interpretation of the patient’s results abnormal are used to define a pattern of abnormal-
may be inaccurate.14 Figure 6–16 (top panel) is an ity that can then be functionally interpreted. Table
example of the graphic representation of these 6–3 presents the most common patterns and the
results in a patient with normal CDP findings. related nomenclature.
184 Ballenger’s Otorhinolaryngology
FIGURE 6–16. Results of dynamic posturography testing in a patient with all results interpreted as normal. The bar
graph at the top plots a percentage equilibrium score for each of the six sensory organization test conditions (see Fig-
ure 6–15). A score of 100 indicates no sway in the sagittal plane, with “Fall” indicating that sway reached a magnitude
equal to the theoretical limits of sway for the patient in the sagittal plane. The composite graph is the numeric aver-
age of the scores from the six conditions. The left panel of the center three shows a ratio analysis of the six conditions
relative to four of the most frequent abnormal patterns. SOM = somatosensory dysfunction; VIS = visual dysfunction
(typically combined with vestibular dysfunction); VEST = vestibular dysfunction; PREF = visual preference pattern.
See the text for a discussion of these and other patterns. The middle panel in the center row plots a measure of hori-
zontal shear force (an indication of body segment movement strategy) on the abscissa against the equilibrium scores
on the ordinate for each of the six test conditions. The right panel of the center row shows a measure of alignment of
the center of gravity (COG) in the sagittal and lateral planes for each of the six conditions tested. The bar graphs in
the bottom row (from movement coordination portion of the testing) plot latency to onset of active recovery to
induced forward sway (left graph) and induced backward sway (right graph). The latencies are given in milliseconds
for left and right leg for two sizes of platform translations. See the text for interpretation of these results. Reproduced
with permission from NeuroCom International, Inc. Reproduced with permission from Shepard N, Telian SA. Evalu-
ation and management of balance system disorders. In: Katz J, editor. Handbook of audiology. 4th ed. Baltimore: Lip-
pincott Williams & Wilkins; 1994.
Evaluation of the Vestibular (Balance) System 185
TABLE 6–3. Common Patterns of Abnormal Performance on the Sensory Organization Test
• Vestibular dysfunction pattern: abnormal on conditions 5 and 6 (alternatively condition 5 alone).
Vestibular dysfunction pattern indicates the patient’s difficulty in using vestibular information alone for
maintenance of stance. When provided with accurate visual and/or foot somatosensory information, stance is
within a normal range.
• Visual and vestibular dysfunction pattern: abnormal on conditions 4, 5, and 6.
Visual and vestibular dysfunction pattern indicates the patient’s difficulty in using accurate visual information
with vestibular information or vestibular information alone for maintenance of stance. When provided with
accurate foot support surface cues, stance is within a normal range.
• Visual preference pattern: abnormal on conditions 3 and 6 (alternatively condition 6 alone).
Visual preference pattern indicates the patient’s abnormal reliance on visual information, even when inaccurate.
When provided with accurate foot support surface information together with accurate or absent visual cues, or
absent vision and vestibular information alone, stance is within a normal range.
• Visual preference and vestibular dysfunction pattern: abnormal on conditions 3, 5, and 6.
Visual preference and vestibular dysfunction pattern indicates the patient’s difficulty in using vestibular information
alone and the patient’s abnormal reliance on visual information, even when inaccurate. When provided with accurate
foot support surface information together with accurate or absent visual cues, stance is within a normal range.
• Somatosensory and vestibular dysfunction pattern: abnormal on conditions 2, 3, 5, and 6.
Somatosensory and vestibular dysfunction pattern indicates the patient’s difficulty in using foot support surface
information with vestibular information or vestibular information alone for maintenance of stance. When
provided with accurate visual information, stance is within a normal range.
• Severe dysfunction pattern: abnormal on four or more conditions not covered in the above descriptions, for
example, 3, 4, 5, and 6; 2, 3, 4, 5, and 6; or 1, 2, 3, 4, 5, and 6.
Severe dysfunction pattern indicates the patient’s difficulty with stance independent of the sensory information
(vestibular, visual, and/or somatosensory) provided. Note that these situations often involve a dominant feature
such as significantly abnormal conditions 5 and 6, or they may involve equally distributed difficulties on all
conditions affected.
• Inconsistent pattern: abnormal on conditions 1, 2, 3, 4, or any combination and normal on conditions 5 and 6.
Inconsistent pattern indicates that performance of the patient is difficult to explain with normal or typical
pathophysiologic conditions and could imply volitional or nonvolitional exaggerated results.
By far the most common pattern is the vestibu- abnormalities. Therefore, the SOT of CDP provides
lar dysfunction pattern, comprising approximately no site-of-lesion information; it is strictly a test of
45% of all abnormalities on this test in our facility. functional ability. The test in no way implies that
The most important aspect of interpretation for the there is a central or peripheral vestibular system
SOT is that it provides information as to which lesion, nor does it imply central or peripheral path-
input system cues the patient is unable to use for way lesions in the visual or somatosensory/proprio-
performing the task of maintaining postural control. ceptive systems. The information should be
In other words, it provides a relative measure of the interpreted only to reflect which input information
patient’s ability to use the sensory input cues of the patient is able (or, conversely, unable) to use for
vision, vestibular, and proprioceptive/somatosensory the task at hand.
to maintain quiet upright stance. The test does not Dynamic posturography is useful for identifi-
provide relative information as to which of the sen- cation of patients who may be, for whatever reason,
sory systems has lesions, causing postural control exaggerating their condition. Recent work by several
186 Ballenger’s Otorhinolaryngology
investigators (not all with EquiTest) has attempted fore, abnormalities of the movement coordination
to quantify the use of this tool to identify these test, related to latency, are nonspecific indicators of
patients and list qualitative factors that would raise potential problems in the long tracts or the muscu-
questions in this dimension.49–51 loskeletal system needed to coordinate recovery
from unexpectedly induced sway in the sagittal
Motor Control Test Information about the ability plane. Other abnormalities from this portion of the
to react to unexpected perturbations in the subject’s testing include inappropriate weight bearing or an
center of mass position is obtained with the MCT. inability to scale properly the strength of the
The center of mass perturbations is created response to the increasing size of the perturbations.
by abrupt anterior or posterior horizontal transla- Such findings may provide information that helps
tions of the support surface. Typically, three increas- explain the patient’s complaints of dysequilibrium.
ingly large translations in both directions are These abnormalities are unlikely to directly impli-
administered. The increasing size of the translation cate involvement of the neural pathways if the
creates a stimulus intensity series. The profile of the latency findings are normal. In many cases, the
surface movement is varied for each patient based weight shift or scaling problems may be maladaptive
on height so that all translations are normalized to a behaviors developed in response to the initial symp-
6-foot-tall person.48 This allows for direct compari- toms of the vestibular disorder.9
son of results across patients. After the three poste-
rior and the three anterior translations, unexpected Postural Evoked Responses Postural evoked
rotations about the ankle are used. Contrary to the responses are used to define patterns of muscle
horizontal translations, the typical muscle response response that have been associated with specific
that is mapped to the stimulus provoked by rotary lesion sites and dieases. Muscle activity from the dis-
stimuli is destabilizing. The patient must then be tal lower extremities is stimulated by sudden toe-up
able to adapt to the new stimulus on repeated trials. rotations of the support surface (the force plate plat-
Five randomly timed toes-up or toes-down rotations form of EquiTest). The muscle activity stimulated by
provide relative information about the patient’s abil- this dorsiflexion movement at the ankle is recorded
ity to adapt to this familiar but destabilizing stimu- with surface EMG electrodes.47,52 The responses from
lus. For this protocol, as with the SOT, floor reaction the medial gastrocnemius and the anterior tibialis
force detected by the force plates in the support sur- are recorded. To improve the signal-to-noise ratio of
face is measured. The principal output parameter is the evoked EMG activity, the rotation is repeated,
the latency to onset of active recovery from the with random, interstimulus intervals, and the EMG
unexpected translations (see Figure 6–16, bottom responses are rectified and averaged over 15 to 20
panels). Other information obtained from the pro- responses. This allows for clearer identification of
tocol includes weight distribution onto right or left onset and offset times of muscle contraction follow-
leg and a relative measure of strength as a function ing the stimulus. There are three specific responses
of the size of the perturbation.48 obtained, as illustrated in Figure 6–17. The short and
This study is used less as a functional evalua- medium latency responses from the contraction of
tion than the SOT and more to evaluate the long- the gastrocnemius are shown in traces from chan-
loop neural pathway. This pathway begins with nels 1 and 3 of Figure 6–17. The third response is
inputs from the ankle, knee, and hip regions (tendon the long latency obtained from the contraction of
and muscle stretch receptors) and projects to the the anterior tibialis, shown in channels 2 and 4 of
motor cortex and back to the various muscles of Figure 6–17.
postural control, including upper and lower body. The EMG patterns for contraction from the
When an abnormal latency to onset of active recov- gastrocnemius and the anterior tibialis muscles are
ery from induced sway is noted, then problems in compared with those that have been associated with
the long-loop pathway should be considered. The specific pathologies, such as multiple sclerosis,
explanation may be as simple as ongoing joint or Parkinson’s disease, or other neurologic lesions. Pat-
back pain, a congenital condition of the back or terns have been described for lesions in the anterior
lower limbs, or an acquired lesion involving the neu- cerebellum and the basal ganglia, as well as for spinal
ral pathways of the afferent or efferent tracts. There- cord compression. When the contraction pattern is
Evaluation of the Vestibular (Balance) System 187
FIGURE 6–17. Postural evoked response results for a normal subject. The plot at the top shows the position profile of
the rotation of the surface the subject is standing on as a function of time. Deflection upward indicates toe-up rota-
tion. The four plots on the left give the averaged, rectified surface electromyographic responses in amplitude of con-
traction (in microvolts) as a function of time. Channels 1 and 3 (CH1 and 3) are results from the left and right
gastrocnemius muscles, respectively. Channels 2 and 4 (CH2 and 4) are the results from the left and right anterior tib-
ialis muscles, respectively. The short (SL), medium (ML), and long latency (LL) responses are indicated at onset with
a number 1 and offset with a 2. The tables at the right give the numeric values for each response, indicating onset and
offset times and amplitudes, peak amplitude contraction, and integrated amplitude (IEMG). Reproduced with per-
mission from Shepard NT and Telian SA.14
unrecognized, the interpretation is based on knowl- sites and disease classifications.53 Normative results
edge of the underlying neural pathways considered for the paradigm have been developed across age
responsible for the specific muscle activity. In gen- and have been shown to have sensitivity and speci-
eral, these involve mediation of the short latency ficity of 68% and 87%, respectively, for identifying
response via the spinal cord (H-reflex). The medium the specific disease entities reflected by the defined
latency response is primarily controlled via the patterns of abnormal responses.9,52 As with the MCT,
spinal cord, with amplitude size determined by the the EMG evaluation does not distinguish afferent
brainstem and basal ganglia. The functional stretch from efferent disruptions that may underlie the
reflex, the long latency response, involves brainstem abnormal muscle responses. With additional clinical
and cortical activity. Defined patterns of muscle investigations of sensitivity in the lower limbs
response have been associated with specific lesion and/or the use of lower limb somatosensory evoked
188 Ballenger’s Otorhinolaryngology
central indicator is that of pure vertical nystagmus Patients with a history of brainstem or cerebellar
(especially when noted with fixation present) or a symptoms mentioned above lasting from typically 5
pure torsional nystagmus with fixation removed. to 60 minutes may be having posterior circulation
Additional signs are as follows: (vertebrobasilar) transient ischemic attacks. This is
an indication for the use of MRA to rule out steno-
• direction-changing nystagmus in a given head sis of the vertebral or basilar arteries. Magnetic res-
position onance angiography can evaluate both intracranial
• sustained or nonfatiguing positional nystagmus and cervical vessels. Transcranial Doppler studies
• dissociated (disconjugate) eye movements most can be performed on the intracranial circulation and
easily noted with saccade testing provide evidence of stenosis by showing increased
• saccadic disruptions to smooth pursuit flow velocity. The direction of blood flow can also be
• direction-changing gaze-evoked nystagmus determined: with proximal vertebral artery occlu-
• abnormal posture when seated, inability to stand sion there can be retrograde blood flow from the
• focal motor deficit basilar into a vertebral artery.
• dysarthria, dysphagia, diplopia, dysmetria (limb Computed tomography without contrast is the
ataxia) examination of choice for delineating the bony
• Horner’s syndrome (sympathetic paresis of the anatomy of the temporal bone. There are several indi-
pupil, with unilateral failure to dilate in darkness cations for this study in patients with the primary
and ptosis) complaint of dizziness. This type of scan may detect a
• loss of pinprick or temperature sensation on one perilabyrinthine fistula secondary to cholesteatoma.
side of the face and/or on the other side of the body In primary lesions of the petrous apex that invade the
• intractable hiccups labyrinth or internal auditory canal, this scan can be
• hyperventilation-induced nystagmus used both to aid in the diagnosis and to determine the
• hemifacial or hemibody sensory or motor deficit extent of involvement of the temporal bone. Choles-
• visual inversion (90- to 180-degree reversals of the terol granulomas and cholesteatomas of the petrous
visual scene, “floor on the ceiling”), drop attacks, apex will appear as homogeneous lesions that gradu-
visual loss, and/or confusion ally expand the margins of the bone.57–60 Fibrous dys-
plasia will manifest as an osseous lesion with a
There are signs with acute-onset vertigo that heterogeneous, “ground glass” appearance on scan.
should trigger an emergent imaging study. A diffu- Sarcomas, such as chondrosarcomas, will manifest as
sion-weighted MRI is the preferred technique over bulky, irregular, and destructive lesions that display a
CT if it can be obtained within hours of the onset of “popcorn” pattern of calcification. Metastases to the
symptoms. Cerebellar infarcts may mimic peripheral temporal bone will appear as irregular, destructive
vestibular paresis. These may become hemorrhagic, lesions.60 The degree of bony invasion and destruc-
and swelling during the first few days after the stroke tion of glomus jugulare tumors can also be assessed
can cause brainstem herniation and death. The signs by this scan. A suggestion of the presence of an
that necessitate a scan are the following: acoustic neuroma may be made by the observation of
asymmetric widening of the internal auditory canal.
• unilateral or asymmetric hearing loss In younger patients, congenital osseous dysplasias of
• brainstem or cerebellar symptoms other than ver- the inner ear can be detected by CT scan.61 A further
tigo, most commonly vertical nystagmus, nystag- use of CT, but with very fine (0.1 to 0.5 mm) cuts, is
mus not suppressed with fixation, and/or inability in the detection of superior semicircular canal dehis-
to stand unassisted (cerebellar infarctions are usu- cence that has been shown to result in a sound-
ally cardioembolic) and/or pressure-provoked vertigo. As with other uses
• stroke risk factors (diabetes, hypertension, tobacco of CT and MRI, there are clues in the history and pre-
use, history of myocardial infarct) senting signs that would lead to a request for this spe-
• acute onset associated with neck pain (suggestive cialized study.62
of a vertebral artery dissection) Computed tomography of the temporal bone
• direction-changing spontaneous nystagmus with contrast is rarely indicated for the evaluation of
• new-onset severe headache dizziness. The addition of contrast does not improve
190 Ballenger’s Otorhinolaryngology
the visualization of cholesteatomas, cholesterol gran- overdose, metronidazole, or cisplatinum. Distal sen-
ulomas, or other cystic lesions of the temporal bone. sory loss may also be on the basis of lumbar or cer-
In contrast, chondrosarcomas and metastatic lesions vical spine disease.
will enhance. This examination remains the evalua- In patients with hearing loss associated with
tion of choice to rule out the presence of an acoustic true vertigo, serologic testing is usually indicated once
neuroma in patients who cannot undergo MRI. a retrocochlear lesion has been ruled out. In these
Of all of the radiologic evaluations available, cases, it is mandatory to rule out late secondary or ter-
MRI remains the most useful in evaluating the tiary syphilis using the FTA-ABS (fluorescent tre-
patient complaining of dizziness. It is the undis- ponemal antibody-absorbed) or equivalent test. The
puted evaluation of choice to rule out the presence VDRL (Venereal Disease Research Laboratory) or
of acoustic neuromas or other neoplasms of the RPR test lacks sufficient sensitivity to be used as a
cerebellopontine angle.63,64 When evaluating the screen in this population. Autoimmune testing is
petrous apex, it provides invaluable assistance in reserved for patients with rapidly progressive hearing
determining the specific type of cystic lesion pres- loss, evolving over a period of weeks to months.
ent.57–60 Cholesterol granulomas are bright on both Approximately 30% of these patients will manifest
T1-weighted and T2-weighted images and do not vestibular complaints.67 There is no standardized test-
enhance. In contrast, epidermoids (cholesteatomas) ing protocol for the workup of these patients. A com-
are bright only on T2-weighted scans. They are also plete blood count with differential, ESR, electrolytes,
the imaging study of choice for evaluation of tumors blood urea nitrogen, creatinine, and urinalysis should
of the jugular foramen region. be part of the general screen. The ANA assay has been
The fast spin echo, T2-weighted MRI scan has the most revealing. The role of antiphospholipid anti-
been suggested as a useful and economical examina- bodies in neurotologic disease has yet to be clarified,
tion to screen for the presence of acoustic neuro- but they may prove to be significant mediators of
mas.65,66 Although its accuracy has been validated, it labyrinthine pathology.68 A Western blot test to detect
has not found universal acceptance. This form of antibodies directed against the inducible form of heat
scan is also a useful complement to the CT scan in shock protein 70 is commercially available and may
patients with suspected inner ear dysplasias. be predictive of the presence of corticosteroid-respon-
sive hearing loss.69,70 Other tests that may compose
part of an autoimmune screen include assays for
SEROLOGIC STUDIES rheumatoid factor, complement levels, anti-Sjögren’s
Serologic studies can be used for investigation of antibodies, and c-ANCA, although the cost effective-
central disorders and peripheral neuropathy. A list- ness of these tests has yet to be established. Authori-
ing of the more common of these is given below: ties often advocate the performance of Lyme titers in
patients with neurovestibular complaints, although
• Vasculitic disorders: erythrocyte sedimentation there is little literature to support the association
rate (ESR), complement levels, rheumatoid factor, between Lyme disease and peripheral auditory and
antineutrophil cytoplasmic antibodies (ANCA) especially vestibular disorders.71,72 Similarly, metabolic
(Wegener’s granulomatosis, polyarteritis nodosa), diseases (diabetes mellitus, hypothyroidism, hyperc-
cryoglobulinemia, hepatitis B antigenemia, holesterolemia) have not been established as media-
eosinophilia, systemic lupus erythematosus (anti- tors of neurovestibular disease.
nuclear antibody [ANA] and anti–disease-specific
DNA), Sjögren’s (autoantibodies SSA and SSB)
• Peripheral neuropathy owing to infectious, meta- VESTIBULAR AND BALANCE
bolic, or neoplastic conditions: rapid plasma REHABILITATION THERAPY
reagin (RPR), human immunodeficiency virus,
Although this chapter is dedicated to the evaluative
glucose, hemoglobin A1c (diabetes), SPEP, vitamin
process for the patient with complaints of imbal-
B12 deficiency
ance, vertigo, or general dysequilibrium, it is during
When evaluating patients with peripheral neu- this process that the first suggestions for use of
ropathy, one should consider in the history factors VBRT should be developed. Therefore, closing the
known to be toxic to peripheral nerves, such as B6 chapter with a brief discussion on this topic and the
Evaluation of the Vestibular (Balance) System 191
relationship between the evaluation tools and the • No provocative activity or balance dysfunction can
use of VBRT is appropriate. be realized during the therapy evaluation; there-
Vestibular and balance rehabilitation therapy is fore, nothing is found on which to base exercise
a symptom-driven program for determination of who activities.
is an appropriate candidate. Therefore, it is during the • Progressive central lesions involving gait and bal-
history that the first possible indications for the use of ance have not been shown to respond to therapy
this management technique would be developed. For for balance and gait. These patients may benefit
the most part, other than the SOT of posturography, from exercises to reduce eye and head movement
the laboratory tests described above do not provide sensitivity and improve safety with ambulation-
indications for the use of this treatment option. There oriented goals.
are situations in which the symptom complaints are
The general principles of designing vestibular
questionable for use of the program, yet findings on
rehabilitation programs involve exposing the patient
postural control studies suggest functional deficits
to the stimuli that provoke vertigo and cause slip-
that can be addressed with the VBRT techniques, and
page of the visual signal on the retina and challeng-
its use would be appropriate. In the case of bilateral
ing areas of deficiency in postural control and
vestibular paresis, the rotary chair is the only test that
ambulation. First, the therapist must identify those
can provide information about the extent of the bilat-
activities or environmental situations that provoke
eral weakness. With those chair results, VBRT pro-
symptoms. Second, the patient’s functional deficits
grams can be altered for more realistic goals. Lastly,
regarding balance and gait must be identified. These
indications from ENG or rotary chair of a unilateral
may be caused by the vestibular symptoms, lesions
reduced vestibular response to caloric irrigation or
in nonvestibular regions, or maladaptive behavior
abnormal timing relationship between eye and head
that has developed in response to the symptoms.
movement from rotary chair support the use of adap-
Lastly, it is desirable to challenge the sedentary
tation exercises to improve VOR gain. It is unlikely
lifestyle that the patient with vestibular disorder
that repeat use of ENG or rotary chair following
often adopts. An active lifestyle including regular
VBRT would be called for since the utility of these
exercise that accounts for age and other health con-
tools in determining compensation status is very lim-
straints will serve as a maintenance program once
ited, and the primary focus in a VBRT program is to
active therapy is completed. Extensive literature is
enhance the compensation process in many dimen-
available to discuss the protocols, techniques, and
sions. However, repeated use of various postural con-
efficacy of this form of management.33,73–76
trol and dynamic visual acuity assessments11 would be
useful as a monitor and/or final outcome measure of
the effectiveness of a VBRT program since these stud- REFERENCES
ies are primarily functional in nature. The patients
1. Tusa RJ. Diagnosis and management of neuro-oto-
who are the most appropriate for VBRT on first
logical disorders due to migraine. In: Herdman SJ,
review are suggested from any one of the following:
editor. Vestibular rehabilitation. Philadelphia: FA
• Patients with symptoms provoked by head or Davis; 2000. p. 298–315.
visual motion 2. Neuhauser H, Leopold M, von Brevern M, et al. The
• Symptoms that are continuous with motion exac- interrelations of migraine, vertigo and migrainous
erbation vertigo. Neurology 2001;56:436–41.
• Evaluations revealing balance or gait dysfunction 3. Staab JP. Diagnosis and treatment of psychologic
with or without either of the traits listed above symptoms and psychiatric disorders in patients with
dizziness and imbalance. Otolaryngol Clin North
The patients who are most probably not appropriate
Am 2000;33:617–36.
for use of VBRT as the initial management tech-
4. Tusa RJ. Psychological problems and the dizzy
nique have the following characteristics to their
patient. In: Herdman SJ, editor. Vestibular rehabili-
symptoms:
tation. Philadelphia: FA Davis; 2000. p. 316–30.
• Symptoms of only spontaneous events that are 5. Yardley L. Overview of psychologic effects of chronic
more frequent than one time every 6 to 8 weeks dizziness and balance disorders. Otolaryngol Clin
and last longer than 15 minutes at a time. North Am 2000;33:603–16.
192 Ballenger’s Otorhinolaryngology
6. Walker MF, Zee DS. Bedside vestibular examination. surgical treatment of vertigo. J Laryngol Otol 1991;
Otolaryngol Clin North Am 2000;33:495–506. 105:18–20.
7. Shepard NT. Electronystagmography (ENG) testing. 24. O’Leary DP, Davis LL. High-frequency autorota-
In: Goebel JA, editor. Practical management of the tional testing of the vestibulo-ocular reflex. Neurol
dizzy patient. Philadelphia: Lippincott Williams & Clin 1990;8:297–312.
Wilkins; 2000. 25. Henn V, Straumann D. Three-dimensional eye
8. Shepard NT. Rotational chair testing. In: Goebel JA, movement recording for clinical application. J Vestib
editor. Practical management of the dizzy patient. Res 1999;9:157–62.
Philadelphia: Lippincott Williams & Wilkins; 2000. 26. Halmagyi GM, Curthoys IS. A clinical sign of canal
9. Shepard NT. Clinical utility of the motor control test paresis. Arch Neurol 1988;45:737–9.
(MCT) and postural evoked responses (PER). Clack- 27. Whitney SL, Herdman SJ. Physical therapy assess-
amus (OR): A NeuroCom Publication; 2000. p. 3–19. ment of vestibular hypofunction. In: Herdman SJ,
10. Monsell EM, Furman JM, Herdman SJ, et al. Technol- editor. Vestibular rehabilitation. Philadelphia: FA
ogy assessment: computerized dynamic platform pos- Davis; 2000. p. 333–72.
turography. Otolaryngol Head Neck Surg 1997;117: 28. El-Kashlan HK, Shepard NT, Asher A, et al. Evalua-
394–8. tion of clinical measures of equilibrium. Laryngo-
11. Herdman SJ, Tusa RJ, Blatt P, et al. Computerized scope 1998;108:311–9.
dynamic visual acuity test in the assessment of 29. Jacobson GP, Newman CW, Safadi I. Sensitivity and
vestibular deficits. Am J Otol 1998;19:790–6. specificity of the head-shaking test for detecting
12. Jacobson GP, Newman CW. The development of the vestibular system abnormalities. Ann Otol Rhinol
Dizziness Handicap Inventory. Arch Otolaryngol Laryngol 1990;99:539–42.
Head Neck Surg 1990;116:424–7. 30. Minor LB, Haslwanter T, Straumann D, Zee DS.
13. Jacobson GP, Newman CW, Hunter L, Balzer G. Bal- Hyperventilation-induced nystagmus in patients
ance function test correlates of the Dizziness Hand- with vestibular schwannoma. Neurology 1999;53:
icap Inventory. J Am Acad Audiol 1991;2:253–60. 2158–67.
14. Shepard NT, Telian SA. Practical management of the 31. Papp LA, Klein DF, Gorman JM. Carbon dioxide
balance disorder patient. San Diego: Singular Pub- hypersensitivity, hyperventilation, and panic disor-
lishing Group; 1996. der. Am J Psychiatry 1993;150:1149–57.
15. Zee DS. Vestibular adaptation. In: Herdman SJ, edi- 32. Han JN, Stegen K, Schepers R, et al. Subjective symp-
tor. Vestibular rehabilitation. Philadelphia: FA Davis; toms and breathing pattern at rest and following
2000. p. 77–90. hyperventilation in anxiety and somatoform disor-
16. Jacobson GP, Newman CW, Kartush JM, editors. ders. J Psychosom Res 1998;45:519–32.
Handbook of balance function testing. St. Louis: 33. Herdman SJ, Tusa RJ. Assessment and treatment of
Mosby-Year Book; 1993. patients with benign paroxysmal positional vertigo.
17. Baloh R, Honrubia V. Clinical neurophysiology of the In: Herdman SJ, editor. Vestibular rehabilitation.
vestibular system. 2nd ed. Philadelphia: FA Davis; 1990. Philadelphia: FA Davis; 2000. p. 451–75.
18. Leigh RJ, Zee DS. The neurology of eye movements. 34. Barber HO, Stockwell CW. Manual of electronystag-
3rd ed. Philadelphia: FA Davis; 1999. mography. 2nd ed. St. Louis: CV Mosby; 1980.
19. Baloh RW, Halmagyi GM, editors. Disorders of the 35. Cutrer FM, Baloh RW. Migraine-associated dizzi-
vestibular system. New York: Oxford University ness. Headache 1992;32:300–4.
Press; 1996. 36. Johnson GD. Medical management of migraine-
20. Furman JM, Cass SP. Balance disorders: a case-study related dizziness and vertigo. Laryngoscope 1998;108
approach. Philadelphia: FA Davis; 1996. Suppl 85:1–30.
21. Bronstein AM, Brandt T, Woollacott M, editors. 37. Fitzgerald G, Hallpike CS. Studies in human vestibu-
Clinical disorders of balance, posture and gait. Lon- lar function: I. Observations of the directional pre-
don: Arnold; 1996. ponderance of caloric nystagmus resulting from
22. Rosenberg ML, Gizzi M. Neuro-otologic history. cerebral lesions. Brain 1942;65:115.
Otolaryngol Clin North Am 2000;33:471–82. 38. Jacobson GP, Calder JA, Shepherd VA, et al. Reap-
23. Shonel G, Kemink JL, Telian SA. Prognostic signifi- praisal of the monothermal warm caloric screening
cance of hearing loss as a lateralising indicator in the test. Ann Otol Rhinol Laryngol 1995;104:942–5.
Evaluation of the Vestibular (Balance) System 193
39. Torok N. Differential diagnosis of the caloric nystag- normal subjects, patients and suspected malingerers.
mus. Equilibrium Res 1973;3:70–9. Otolaryngol Head Neck Surg 1997;117:293–302.
40. Wall C. The sinusoidal harmonic acceleration rotary 52. Lawson GD, Shepard NT, Oviatt DL, Wang Y. Elec-
chair test. Theoretical and clinical basis. Neurol Clin tromyographic responses of lower leg muscles to
1990;8:269–85. upward toe tilts as a function of age. J Vestib Res
41. Waespe W, Cohen B, Raphan T. Dynamic modifica- 1994;4:203–14.
tion of the vestibulo-ocular reflex by the nodulus 53. Dichgans J, Diener HC. The use of short- and long-
and uvula. Science 1985;228:199–202. latency reflex testing in leg muscles of neurological
42. Stockwell CW, Bojrab DI. Background and tech- patients. In: Struppler A, Weindl A, editors. Clinical
nique of rotational testing. In: Jacobson GP, New- aspects of sensory-motor integration: implications
man CW, Kartush JM, editors. Handbook of balance for neurological patients. New York: Springer-Ver-
function testing. St. Louis: Mosby Year Book; 1993. lag; 1987. p. 165–75.
p. 237–48. 54. Shumway-Cook A, Horak FB. Assessing the influ-
43. Stockwell CW, Bojrab DI. Interpretation and useful- ence of sensory interaction on balance. Suggestion
ness of rotational testing. In: Jacobson GP, Newman from the field. Phys Ther 1986;66:1548–50.
CW, Kartush JM, editors. Handbook of balance 55. Beynon GJ, Jani P, Baguley DM. A clinical evaluation
function testing. St. Louis: Mosby Year Book; 1993. of head impulse testing. Clin Otolaryngol 1998;23:
p. 249–60. 117–22.
44. Allum JH, Shepard NT. An overview of the clinical 56. Ruckenstein MJ, Staab JP, Solomon D, Shepard NT.
use of dynamic posturography in the differential The BSI-53: its use in identifying patients with psy-
diagnosis of balance disorders. J Vestib Res chogenic dizziness. Annual Meeting of the American
1999;9:223–52. Academy of Otolaryngology-Head and Neck Surgery
45. Nashner LM. Practical biomechanics and physiology Foundation, Washington, DC, September 27, 2000.
of balance. In: Jacobson GP, Newman CW, Kartush 57. Arriaga MA, Brackmann DE. Differential diagnosis
JM, editors. Handbook of balance function testing. of primary petrous apex lesions [published erratum
St. Louis: Mosby-Year Book; 1993. p. 261–79. appears in Am J Otol 1992;13:297]. Am J Otol
46. Nashner LM. Computerized dynamic posturogra- 1991;12:470–4.
phy. In: Jacobson GP, Newman CW, Kartush JM, edi- 58. Jackler RK, Parker DA. Radiographic differential
tors. Handbook of balance function testing. St. diagnosis of petrous apex lesions. Am J Otol 1992;
Louis: Mosby-Year Book; 1993. p. 280–307. 13:561–74.
47. Nashner LM. Computerized dynamic posturogra- 59. Curtin HD, Som PM. The petrous apex. Otolaryngol
phy: clinical applications. In: Jacobson GP, Newman Clin North Am 1995;28:473–96.
CW, Kartush JM, editors. Handbook of balance 60. Muckle RP, De la Cruz A, Lo WM. Petrous apex
function testing. St. Louis: Mosby-Year Book; 1993. lesions. Am J Otol 1998;19:219–25.
p. 308–34. 61. Jackler RK, Dillon WP. Computed tomography and
48. Shepard NT, Schultz A, Alexander NB, et al. Postural magnetic resonance imaging of the inner ear. Oto-
control in young and elderly adults when stance is laryngol Head Neck Surg 1988;99:494–504.
challenged: clinical versus laboratory measurements. 62. Minor LB, Solomon D, Zinreich JS, Zee DS. Sound-
Ann Otol Rhinol Laryngol 1993;102:508–17. and/or pressure-induced vertigo due to bone dehis-
49. Allum JHJ, Huwiler M, Honegger F. Objective meas- cence of the superior semicircular canal. Arch Oto-
ures of non-organic vertigo using dynamic postur- laryngol Head Neck Surg 1998;124:249–58.
ography. In: Taguchi K, Igarashi M, Mori S, editors. 63. Doyle KJ. Is there still a role for auditory brainstem
Vestibular and neural front: proceedings of the 12th response audiometry in the diagnosis of acoustic
International Symposium on Posture and Gait. Ams- neuroma? Arch Otolaryngol Head Neck Surg 1999;
terdam: Elsevier; 1994. p. 51–5. 125:232–4.
50. Cevette MJ, Puetz B, Marion MS, et al. Aphysiologic 64. Ruckenstein MJ, Cueva RA, Morrison DH, Press G. A
performance on dynamic posturography. Otolaryn- prospective study of ABR and MRI in the screening for
gol Head Neck Surg 1995;112:676–88. vestibular schwannomas. Am J Otol 1996;17:317–20.
51. Goebel JA, Sataloff RT, Hanson JM, et al. Posturo- 65. Shelton C, Harnsberger HR, Allen R, King B. Fast
graphic evidence of nonorganic sway patterns in spin echo magnetic resonance imaging: clinical
194 Ballenger’s Otorhinolaryngology
application in screening for acoustic neuroma. Oto- hearing loss. Arch Otolaryngol Head Neck Surg
laryngol Head Neck Surg 1996;114:71–6. 1995;121:1167–71.
66. Linker SP, Ruckenstein MJ, Acker J, Gardner G. An 71. Peltomaa M, Pyykkö I, Seppälä I, Viljanen M. Lyme
accurate, cost-effective approach for diagnosing borreliosis — an unusual cause of vertigo. Auris
retrocochlear lesions utilizing the T2-weighted, fast- Nasus Larynx 1998;25:233–42.
spin echo magnetic resonance imaging scan. Laryn- 72. Peltomaa M, Pyykkö I, Seppälä I, Viljanen M. Lyme
goscope 1997;107:1525–9. borreliosis, an etiologic factor of sensorineural hear-
67. McCabe BF. Autoimmune sensorineural hearing ing loss? Eur Arch Otorhinolaryngol. [In press]
loss. Ann Otol Rhinol Laryngol 1979;88:585–9. 73. Whitney SL, Maureen MR. Efficacy of vestibular
68. Lake GM, Sismanis A, Ariga T, et al. Antibodies to rehabilitation. Otolaryngol Clin North Am 2000;33:
glycosphingolipid antigens in patients with immune- 659–73.
mediated cochleovestibular disorders. Am J Otol 74. Clendaniel RA. Outcome measures for assessment of
1997;18:175–8. treatment of the dizzy and balance disorder patient.
69. Gottschlich S, Billings PB, Keithley EM, et al. Otolaryngol Clin North Am 2000;33:519–34.
Assessment of serum antibodies in patients with 75. Shepard NT, Telian SA. Programmatic vestibular
rapidly progressive sensorineural hearing loss rehabilitation. Otolaryngol Head Neck Surg 1995;
and Meniere’s disease. Laryngoscope 1995;105: 112:173–82.
1347–52. 76. Smith-Wheelock M, Shepard NT, Telian SA. Physical
70. Bloch DB, San Martin JE, Rauch SD, et al. Serum therapy program for vestibular rehabilitation. Am J
antibodies to heat shock protein 70 in sensorineural Otol 1991;12:218–25.
CHAPTER 7
The temporal bone is unique in the human body obtained by placing the external auditory meatus of
because it contains, in the small volume of a cubic the side to be examined 1 cm above the center of the
inch, a concentration of vital osseous and membra- film or of the tabletop.
nous structures surrounded by a more or less exten- The extent of the pneumatization of the mas-
sive system of pneumatic cells. Because of the toid, distribution of the air cells, degree of aeration,
different densities of its bony components and of the and status of the trabecular pattern are the main fea-
air- and fluid-filled spaces around and within them, tures of this projection (Figure 7–1). The anterior
the temporal bone lends itself to accurate visualiza- plate of the vertical portion of the sigmoid sinus
tion and assessment by various imaging procedures. groove (corresponding to the most lateral part of the
Conventional radiography, computed tomog- posterior aspect of the petrous pyramid) casts an
raphy (CT), magnetic resonance imaging (MRI), almost vertical line, slightly concave posteriorly in its
and arteriography are the techniques currently used upper portion, superimposed on the air cells. At its
to study the temporal bone and auditory-vestibular upper extremity, this line joins another line that
pathways. The otolaryngologist should know how to slopes gently forward and downward to form the sin-
select the proper procedure for the anatomic area odural angle of Citelli. The latter line is produced by
and the clinical problem under investigation. the superior aspect of the lateral portion of the
petrous pyramid. The more medial portion of the
superior petrous ridge, from the arcuate eminence to
CONVENTIONAL RADIOGRAPHY the apex, has been displaced downward by the angu-
Today, the use of conventional radiography is limited lation of the x-ray beam and casts a line that extends
to evaluation of the mastoid pneumatization and forward and downward, crossing the epitympanic
assessment of the position and integrity of cochlear area and, more anteriorly, the neck of the mandibu-
implant electrodes. The latter cannot be established lar condyle. Above this line, the upper portion of the
by tomographic techniques because the wires often attic with the head of the malleus is usually visible.
are visualized in several contiguous sections; there- Finally, the temporomandibular joint is outlined.
fore, their continuity cannot be demonstrated. Only
three projections are of practical interest: the lateral
or Schüller’s, the frontal or transorbital, and the
TRANSORBITAL PROJECTION
oblique or Stenvers’. The other special projections This view can be obtained with the patient’s face
have historical significance but no useful clinical either to or away from the film. The patient’s head is
application. flexed on the chin until the orbitomeatal line is per-
pendicular to the tabletop. For better details, each
side should be obtained separately, and the central x-
SCHÜLLER’S OR RUNGSTROM’S PROJECTION ray beam should be directed at the center of the
The Schüller’s projection is a lateral view of the mas- orbit of the side under examination and perpendi-
toid obtained with a cephalocaudad angulation of cular to the film.
the x-ray beam of 25 to 30 degrees. The patient’s The petrous apex is outlined clearly but fore-
head is turned so that the sagittal plane of the skull shortened because of its obliquity to the plane of the
becomes parallel to the tabletop and the side under films. The internal auditory canal is visualized in its
examination is closer to the film. Proper centering is full length as a horizontal band of radiolucency
195
196 Ballenger’s Otorhinolaryngology
FIGURE 7–1. Schüller’s projection: (1) root of the zygoma, (2) condyle of the mandible, (3) temporomandibular joint,
(7) malleus, (8) incus, (12) air cells, (14) anterior plate of the sigmoid sinus, (15) dural plate, (25) petrous apex.
extending through the petrous pyramid (Figure 7–2). vestibule and of the superior and horizontal semicir-
At the medial end of the canal, the free margin of the cular canals are usually detectable. The apical and
posterior wall casts a well-defined and smooth mar- middle coils of the cochlea are superimposed on the
gin, concave medially. Often the radiolucent band of lateral portion of the internal auditory canal,
the internal auditory canal seems to extend medially whereas the basal turn is visible underneath the canal
to the lip of the posterior wall into the petrous apex. and the vestibule.
This band is not caused by the internal auditory
canal but is produced by the medial extension of the
upper and lower lips of the porus (opening) of the
STENVERS’ PROJECTION
canal and by the interposed groove. Lateral to the The patient is positioned facing the film, with the
internal auditory canal, the radiolucencies of the head slightly flexed and rotated 45 degrees toward
FIGURE 7–2. Transorbital projection: (4) external auditory canal, (12) air cells, (13) mastoid process, (19) cochlea, (20)
internal auditory canal, (21) orbital rim, (28) medial lip of the posterior wall of the internal auditory canal, (29)
vestibule, (30) base of the skull.
Imaging of the Temporal Bone 197
the side opposite the one under examination. The 360 by 360 picture element (pixel) matrix, where the
lateral rim of the orbit of the side under investiga- brightness of each point is proportional to the atten-
tion should lie in close contact with the tabletop. uation coefficient.
The x-ray beam is angulated 14 degrees caudad. The study is often performed after intravenous
The entire petrous apex is visualized in its full injection of iodinated contrast agents that produce
length lateral to the orbital rim (Figure 7–3). The an increase in density value or enhancement of sev-
porus of the internal auditory canal seen on face eral anatomic structures and pathologic tissues.
appears as an oval-shaped radiolucency open medi- Recently, conventional CT has been replaced
ally and limited laterally by the free margin of the by helical or spiral CT, which allows rapid acquisi-
posterior canal wall. Lateral to the porus, the inter- tion of volumetric data of the part of the body under
nal auditory canal appears foreshortened. The examination. Images are acquired at an angled plane
vestibule and semicircular canals, especially the pos- of section and then reconstructed by interpolating
terior, which lies in this projection in a plane paral- the volumetric data set as two-dimensional or high-
lel to the film, are usually recognizable. On the quality three-dimensional reformations. The contin-
outside, the entire mastoid is outlined, with the mas- uous acquisition of images is made possible by
toid process free from superimpositions. replacing the former electric cabling of the gantry
with slip-ring design that allows continuous rotation
of the source detector assembly and by the use of
COMPUTED TOMOGRAPHY high heat capacity x-ray tubes. The advantage of spi-
Computed tomography is a radiographic technique ral CT includes the elimination of respiratory mis-
that allows measurement of small absorption coeffi- registration, a decrease of motion artifact, and an
cients and differentials not recognizable by previ- obvious improvement in patient comfort owing to
ously available recording or displaying systems. the shortening of the examination time. This is par-
The scan is initiated at a chosen level, and the ticularly important in children, whether they have
x-ray tube, collimated to a thin or pencil beam, been administered anesthesia or sedation, and in
rotates around the patient. The transmitted x-rays older patients who have difficulty in extending the
are picked up by detectors arrayed along the cir- head. Reconstruction of axial data in other planes
cumference of the tube trajectory, converted into produces satisfactory images provided that a colli-
electronic current, amplified, and transmitted to the mation as small as 1 or 0.5 mm is used. A scanning
computer for storing and processing. The computer time of less than 1 minute is sufficient to cover the
analyzes these data and develops an image on a mastoid and petrous portions of the temporal bone.
FIGURE 7–3. Stenvers’ projection: (2) condyle of the mandible, (12) air cells, (16) arcuate eminence, (17) superior
semicircular canal, (18) horizontal semicircular canal, (20) internal auditory canal, (22) basilar turn of the cochlea, (25)
petrous apex, (29) vestibule.
198 Ballenger’s Otorhinolaryngology
New multidetector scanners will further decrease the toward the side under examination so that the
scanning time. The CT images provide exquisite medial wall becomes perpendicular to the plane of
bony details and excellent demonstration of soft tis- section. For this projection, we position the patient
sue density within the air space of the mastoids, prone with the head extended. This projection is
external auditory canal, and middle ear but very lim- particularly useful for the study of the oval window,
ited identification of the type of substance produc- promontory, and tympanic segment of the facial
ing the abnormal density. For instance, the density of canal. It should be used in all patients with otoscle-
cholesteatoma is identical to that of a tumor or gran- rosis (Figure 7–6).
ulation tissue and even of fluid.
The densitometric readings obtained with a Sagittal or Lateral Projection It is impossible or
cursor of variable size are often unreliable because of extremely difficult to obtain direct sagittal sections.
partial volume averaging within the small cavities of However, computer reconstructed sagittal images
the ear. Time-density curves obtained by rapid can be obtained from the raw data collected for the
sequential images of a preselected section after injec- horizontal sections. This is particularly true if fast or
tion of a bolus of contrast are useful for the identifi- spiral CT is used, and thin sections at 0.5 or 1 mm
cation of vascular masses. At present, MRI provides increments are obtained. These images are satisfac-
a far more precise identification of the type of tissue tory for the demonstration of the mastoid segment
within the air spaces and abnormal cavities in the of the facial canal and of the vestibular aqueduct
temporal bone. Three-dimensional reconstruction (Figure 7–7).
of the temporal bone has not added diagnostic
information but is of great value in surgical plan-
ning in large lesions of the base of the skull. MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging is an imaging modality
COMPUTED TOMOGRAPHIC PROJECTIONS capable of producing cross-sections of the human
body in any plane without exposing the patient to
OF THE TEMPORAL BONE
ionizing radiation. Magnetic resonance images are
Horizontal or Axial Projection This is the basic obtained by the interaction of hydrogen nuclei or
projection of the CT study.1 It is comfortable for the protons of the human body, high magnetic fields,
patient, who lies supine on the table, and is easy to and radiofrequency pulses. The strength of the MRI
obtain and reproduce. It allows a good demonstra- signal to be converted into imaging data depends on
tion of the external, middle, and inner ears except the concentration of the free hydrogen nuclei or pro-
for the structures parallel to the plane of section, tons and on two magnetic relaxation times, T1 and
such as the tegmen (Figure 7–4). T2, which are tissue specific. One of the characteris-
tics of MRI is the possibility of changing appearance
Coronal or Frontal Projection The patient lies on and therefore information of the images by changing
the table, either prone or supine, with the head the contribution of the T1 and T2 relaxation times.
extended. The gantry of the scanner is often tilted to This is accomplished by varying the time between
compensate for an incomplete extension of the head. successive pulses (TR or by repetition time) and the
This projection is indispensable to complement the time that the emitted signal or echo is measured
axial sections but is often difficult to obtain, particu- after the pulse (TE or echo time).
larly in young children and older people (Figure 7–5). Magnetic resonance imaging has undergone
multiple changes and refinements to increase defini-
Twenty-Degree Coronal Oblique Projection tion of the images and to decrease the acquisition
This projection is a modification of the coronal pro- time of the image.2 First, the use of surface coils
jecton for the study of the medial wall of the tym- placed adjacent to the area of interest has increased
panic cavity. The medial or labyrinthine wall of the the signal-to-noise ratio and consequently improved
middle ear forms an angle, open posteriorly, of 15 to the image. Shorter acquisitions have been obtained
25 degrees with the midsagittal plane of the skull. by shortening the TR, using pulses with flip angles
The patient is first positioned as for the coronal pro- smaller than 90 degrees (gradient echo imaging),
jection, and the head is then rotated 20 degrees reducing the number of phase-encoded steps, and
Imaging of the Temporal Bone 199
FIGURE 7–4. Horizontal computed tomographic sections of a normal right temporal bone, in sequence from top to
bottom: A, M = mastoid; S = superior semicircular canal; PA = petrous apex. B, MA = mastoid antrum; O = ossicles;
V = vestibule; F = facial nerve canal; IAC = internal auditory canal; PSC = posterior semicircular canal. C, C = cochlea;
RW = round window. D, E = external auditory canal; CA = cochlear aqueduct; LS = lateral sinus plate.
200 Ballenger’s Otorhinolaryngology
A B
C D
FIGURE 7–5. Coronal computed tomographic sections of a normal right temporal bone in sequence from front to
back. A, OS = ossicles; C = cochlea; fnc = facial nerve canal; CC = carotid canal. B, eac = external auditory canal; a =
attic; mt = mesotympanum; i = incus. C, OW = oval window; V = vestibule; SC = semicircular canals; iac = internal
auditory canal. D, rw = round window; st = sinus tympani.
A B
C D
FIGURE 7–7. Reformatted sagittal computed tomographic sections of the right ear showing A, the external auditory
canal, attic, and vertical segment of the facial canal (arrow); B, the ossicles (arrow) and the horizontal semicircular
canal; C, the common crus, vestibular aqueduct (arrow), and the jugular fossa; D, the internal auditory canal.
as dark areas of no signal. Fat and body fluid are rich ear appear in the MRI as dark areas without pattern
in free protons and produce signals of high inten- or structures within them. The petrous pyramid is
sity, fat in the T1- and fluid in the T2-weighted equally dark except for a gray or white cast of the
images. Blood vessels usually appear as areas of sig- inner ear structures and internal auditory canal pro-
nal void because the stimulated protons of the cir- duced by the fluid within their lumens (Figure 7–8).
culating blood have moved out of the section before Pathologic processes are demonstrated by MRI
their emitted signals can be detected. Because corti- whenever the hydrogen density and relaxation times
cal or nondiploic bone and air emit no signal, the of the pathologic tissues are different from the nor-
normal mastoid, external auditory canal, and middle mal. The intravenous injection of ferromagnetic
202 Ballenger’s Otorhinolaryngology
ANGIOGRAPHY
Gradient echo techniques and flow-encoding gradi-
ents have enabled the development of magnetic
resonance angiography (MRA). Time of flight an-
giography is a gradient echo technique in which the
stationary tissues within the imaging plane are satu-
rated with the magnetic field so that they will not
produce a signal. Blood flowing within the same
B plane is unsaturated and will be the only tissue to
produce a signal.
FIGURE 7–8. Magnetic resonance imaging sections of
Phase-contrast angiography is acquired differ-
the normal temporal bone. A, Coronal T1. B, Axial T2 fast
ently. Instead of saturating the stationary tissues
spin echo. The normal mastoid, external auditory canal,
with radiofrequency pulses, a bipolar gradient of
and middle ear cavity appear as dark areas of signal void.
magnetization is applied to the entire slice, first with
The internal auditory canals and inner ear structures are
a positive value and then with a negative value. In
recognizable because of the signal produced by the fluid
the stationary tissues, the two opposite gradients
and the neural structures within their lumens. The cere-
cancel each other out. In the flowing blood, however,
brospinal fluid has a low signal in T1 but a high signal in
the two opposite gradients cannot cancel each other
T2. AN = acoustic nerve; C = cochlea; FL = fluid in the
out because the blood will have moved to a different
mastoid and middle ear; H = horizontal semicircular
plane in the region before the inverse gradient is
canal; iac = internal auditory canal; V = vestibule.
applied.
The obtained slices are reconstructed into pro-
jection images, which can be rotated in different
contrast agents (gadolinium DTPA [diethylenetri- planes to separate vessels and eliminate superimpo-
amine pentaacetic acid] and gadolinium chelate) has sition. Magnetic resonance angiography of the
improved the recognition and differentiation of intracranial vasculature has been particularly useful
pathologic processes. Because the contrast material in the demonstration of aneurysms (Figure 7–9) in
does not penetrate the intact blood barrier, normal the region of the circle of Willis, arteriovenous mal-
brain does not enhance except for structures such as formation (AVM) (particularly a small dural AVM
Imaging of the Temporal Bone 203
tion, the otologist could enter the sinus with conse- superior semicircular canal. A depression of the
quent severe bleeding and possible complications tegmental plate is not unusual, particularly in patients
from sinus thrombosis. with congenital atresia. As seen in the coronal sec-
tions, the floor of the middle cranial fossa deepens to
Tegmen The tegmen of the mastoid and attic usu- form a groove lateral to the attic and to the labyrinth
ally passes in a horizontal plane slightly lower than (Figure 7–11). The low-lying dura may cover the roof
the arcuate eminence produced by the top of the of the external auditory canal and, when the canal is
not developed, extend lateral to the mesotympanum. destroyed, with formation of coalescent areas of sup-
Unless aware of this feature, the otologist may pene- puration.3 Erosion of the cortex of the mastoid
trate the cranial cavity during surgery. results in subperiosteal abscesses (Figure 7–12, B).
Involvement of the posterior sinus plate often leads
Acute Mastoiditis The early findings of acute to thrombophlebitis of the lateral sinus and to pos-
mastoiditis are diffuse and homogeneous clouding terior fossa abscesses (Figure 7–13), whereas erosion
of the middle ear cavity and mastoid air cells and of the tegmen may lead to extension of the infection
often air-fluid levels within the air cells (Figure 7–12, into the middle canal fossa with formation of
A). With the progression of the process, the mastoid extradural (epidural) or temporal lobe abscesses.
trabeculae first become demineralized and then
B B
FIGURE 7–12. A, Acute mastoiditis. This axial computed FIGURE 7–13. Acute mastoiditis with perisinus and
tomographic (CT) section of the left mastoid shows epidural abscess. A, Axial computed tomographic (CT)
clouding and air-fluid levels within the air cells. The tra- section. There is a coalescent cavity in the posterior
becular pattern is intact. B, Coalescent mastoiditis, axial aspect of the mastoid with erosion of the sinus plate. B,
CT section of the left mastoid. A large coalescent cavity Axial CT section after injection of contrast. A ring of
is noticed in the mastoid with erosion of the outer cortex enhancement surrounds an area of low density produced
and formation of a subperiosteal abscess. by the cerebellar abscess.
206 Ballenger’s Otorhinolaryngology
with consequent accumulation of epithelial debris Carcinoma Carcinoma of the temporal bone usu-
(keratosis obliterans), or by dyskeratosis with local- ally arises in the external auditory canal. The CT
ized accumulation of debris on the floor of the canal findings vary with the extent of the lesion. In an
(invasive keratitis). In the first type, a soft tissue mass early lesion, portions of the bony wall of the exter-
fills and expands the canal medial to the site of nal auditory canal are eroded (Figure 7–20). When
stenosis or obstruction (Figure 7–19). In the second further destruction occurs, the tumor may spread
type, the lumen of the canal is patent, but areas of anteriorly into the temporomandibular fossa; poste-
bony erosion are demonstrated in the involved por- riorly into the mastoid, where it often reaches the
tion of the canal. When the cholesteatoma is large facial canal; and medially into the middle ear, jugu-
and erodes the annulus, it may extend into the mid- lar fossa, petrous pyramid, and labyrinth. Extension
dle ear cavity. into the mastoid and petrous pyramid causes a typ-
208 Ballenger’s Otorhinolaryngology
complete agenesis. In the majority of cases with an within the lumen of the bulb, usually paralleling its
atretic external auditory canal, the middle ear cavity wall, owing to variations in flow velocity. In ques-
is normal in size and aerated. The head of the tionable cases, an MR venogram should be per-
malleus and body of the incus are often fused and formed using a two-dimensional (2–D) time of flight
fixed to the atretic plate at the level of the malleus technique sensitive to slow flow or a two-dimen-
neck (see Figure 7–16). If the middle ear cavity is sional phase contrast using short velocity encoding.
grossly hypoplastic, the malleus and incus form a The intratemporal segment of the carotid
rudimentary amalgam that is often in an ectopic artery may take an ectopic course through the mid-
position (Figure 7–21). A congenital anomaly may dle ear. In these cases, the CT examination shows a
be confined to the ossicular chain, which may be soft tissue mass extending throughout the entire
malformed or fixed. length of the middle ear cavity to regain its normal
Malformation of the stapes superstructure and position in the petrous apex (Figure 7–22). The
fixation of the stapes footplate are not uncommon, proximal portion of the carotid artery, rather than
isolated defects. Computed tomographic sections in being located underneath the cochlea, enters the
20-degree coronal oblique projection are useful for temporal bone through a canal or defect in the floor
the study of the stapes and oval window. of the posterior part of the hypotympanum. A
The jugular bulb sometimes projects into the carotid arteriogram, or MRA, may be used to con-
hypo- or mesotympanum. The bulb may be covered firm the anomalous course of the artery.
by a thin bony shell or may be exposed in the mid-
dle ear, often in contact with the medial surface of Trauma The middle ear cavity is usually involved
the tympanic membrane, thus mimicking a glomus in longitudinal fractures of the temporal bone.
tumor. The MRI appearance of a high jugular bulb Computed tomography permits precise evaluation
may be misread as showing a glomus tumor because of the course of the fracture and status of the ossic-
of the mixed signal within the bulb produced by tur- ular chain. A fracture line may disappear at a certain
bulent flow. However, whereas a glomus tumor con- level only to reappear a few millimeters distant. This
tains multiple punctate areas of signal void within a apparent gap is not caused by interruption of the
mass of medium or high signal, in a high jugular fracture line but rather by a change in its course so
bulb, linear streaks of high and low signal are seen that the fracture becomes invisible in some of the
FIGURE 7–21. Congenital malformation of the right external and middle ears, coronal computed tomographic sec-
tions. A, Agenesis of the external auditory canal with hypoplasia of the attic and rudimentary ossicular mass. B, Notice
the lack of development of the mastoid pneumatization and the outward rotation of the vertical segment of the facial
canal (arrow).
210 Ballenger’s Otorhinolaryngology
A A
B B
FIGURE 7–24. Longitudinal fracture of the right tempo- FIGURE 7–25. Meningoencephalocele, after modified
ral bone. A, Axial; B, coronal computed tomographic sec- radical mastoidectomy. A, Coronal computed tomo-
tions. A fracture extends from the mastoid cortex to the graphic section showing a large defect in the tegmen of
region of the aditus (black arrows). The head of the malleus the cavity with a soft tissue mass underneath it. B, T1
and the body of the incus are in normal relationship, but coronal magnetic resonance image clearly identifying the
the incudostapedial joint is disrupted (white arrows). soft tissue mass (arrow) as a brain herniation.
encephaloceles have the same characteristics of the media, a partial, nonhomogeneous clouding of the
adjacent brain, which are quite different from a middle ear cavity is caused by granulation tissue,
cholesteatoma (Figure 7–25, B). polyps, and fluid or pus. Because the tympanic mem-
bane is perforated, some aeration of the middle ear
Acute Otitis Media The CT sections demonstrate space is present. Erosion of the long process of the
a nonspecific and diffuse clouding of the middle ear incus is a common finding, whereas erosion of the
cavity. The tympanic membrane is often swollen and body of the incus and the head of the malleus is rare
bulges externally. unless a cholesteatoma is present. In chronic adhesive
otitis media, the middle ear space is contracted
Chronic Otitis Media There are two types of because of retraction of the tympanic membrane
chronic otitis media. In chronic suppurative otitis onto the promontory (Figure 7–26). The handle of
212 Ballenger’s Otorhinolaryngology
the malleus is foreshortened, and the long process of eral attic wall, posterosuperior canal wall, and ossi-
the incus is often thinned out or eroded. In these cles. If the middle ear cavity is aerated, the soft tissue
cases, the retracted tympanic membrane may be mass is well outlined. When fluid or inflammatory
attached to the head of the stapes with formation of tissue surrounds the cholesteatoma, the margin of
a natural myringostapediopexy. Tympanosclerotic the mass is obscured because the x-ray densities of
deposits are recognizable by CT whenever they are cholesteatoma, inflammatory tissue, and fluid are
sufficiently large and calcified. The deposits appear similar. Magnetic resonance imaging with contrast
as punctate or linear densities within the tympanic may be useful in these cases to differentiate the
membrane or the mucosa covering the promontory. enhancing granulation tissue from fluid and cho-
Large deposits of tympanosclerosis in the attic may lesteatoma. Different patterns of x-ray findings are
surround and fix the ossicles. observed. Cholesteatomas that arise from the pars
Active and vascular granulation tissue undergoes flaccida of the tympanic membrane produce erosion
a nonhomogeneous enhancement in the T1 MRIs of the anterior portion of the lateral wall of the attic
obtained after injection of contrast. This approach and tympanic spine (Figure 7–28). The lesion
may occasionally be useful to differentiate granulation extends into the attic lateral to the ossicles, which
tissue from cholesteatoma, cholesterol granuloma, or may become medially displaced. Cholesteatomas
other masses occurring in the middle ear. arising from the pars tensa, usually from the pos-
terosuperior margin of the tympanic membrane,
Cholesteatomas Congenital cholesteatomas appear as a soft tissue mass in the middle ear, erod-
appear as well-defined soft tissue masses often pro- ing the long process of the incus and extending into
ducing an outward bulge of the intact tympanic the attic medial to the ossicles that may be displaced
membrane (Figure 7–27). If there is accompanying laterally (Figure 7–29). The lateral wall of the attic is
serous otitis media, the fluid may obscure the mass usually intact, but the posterosuperior canal wall is
as the entire tympanic cavity becomes cloudy. If the often eroded. Sometimes a cholesteatoma may
lesion extends into the attic, the medial aspect of the involve both the pars flaccida and tensa, producing a
lateral wall of the attic is eroded from within. mixed x-ray pattern. In advanced cholesteatoma of
Acquired cholesteatoma produces a soft tissue all types, extensive bony destruction occurs, and no
mass in the middle ear and typical erosion of the lat- distinct pattern remains. The ossicles in the attic,
Imaging of the Temporal Bone 213
contour of the horizontal semicircular canal and of a preselected section showing the tumor mass,
erosion of the bony capsule covering the lumen of obtained after injection of a bolus of contrast mate-
the canal. Further complications of cholesteatoma rial, generate a curve with a high quasiarterial peak
are extension into the petrous pyramid, which usu- rather than the high but delayed venous peak of a
ally occurs in well-pneumatized bones, and erosion high jugular bulb5 (Figure 7–31, B). Selective arteri-
of the facial nerve canal, which may lead to facial ography with subtraction is indicated to identify
paralysis. feeding vessels before embolization. Carcinomas
extend into the middle ear from the external audi-
Tumors Osteomas are frequent in the external tory canal. Adenocarcinoma is rare and produces a
auditory canal but also occur in the middle ear, nonspecific soft tissue mass, often eroding the walls
where they may cause conductive hearing loss by of the middle ear.
impinging on the ossicular chain. Glomus tumors,
also called chemodectomas or nonchromaffin para- Otosclerosis Otosclerosis that involves the oval
gangliomas, arise in the middle ear or jugular fossa window causes fixation of the stapes and consequent
from minute glomus bodies. Glomus tympanicum conductive hearing loss. A 20-degree coronal oblique
tumors arise from glomus bodies along Jacobson’s is far superior to the other projections for the study
nerve on the promontory. The CT sections reveal a of the oval window. In active otosclerosis or oto-
soft tissue mass of variable size, usually in the lower spongiosis, the margin of the oval window becomes
portion of the middle ear cavity (Figure 7–31, A). As decalcified so that the window seems larger than
the lesion enlarges, it may cause a lateral bulge of the normal. In mature otosclerosis, the oval window
tympanic membrane, smooth erosion of the becomes narrowed or closed (Figure 7–32), and in
promontory, and involvement of the mastoid and severe cases, the entire oval window niche is obliter-
hypotympanic air cells. If the lesion erodes into the ated by calcified otosclerotic foci. The x-ray assess-
jugular fossa, it becomes indistinguishable from a ment is useful before surgery to confirm the clinical
glomus jugulare tumor. Rapid sequential CT images diagnosis and in some bilateral cases for selection of
FIGURE 7–31. Right glomus tympanicum. A, Coronal computed tomographic (CT) section showing a small soft tis-
sue mass in the lower portion of the middle ear cavity (arrow). B, Dynamic CT study of the preselected section show-
ing the mass. Graphic display of the circulation in the tumor (1) and internal carotid artery (2). Notice the high peak
of the tumor at quasiarterial time.
Imaging of the Temporal Bone 215
INNER EAR
Both CT and MRI are used for the study of the inner
ear structures. Computed tomography is best for the
study of the labyrinthine capsule; MRI is best for the
assessment of the membranous labyrinth.
FIGURE 7–33. Michel malformation of the right inner ear structures. Axial (A) and coronal (B) computed tomo-
graphic sections. The middle ear cavity is normal, but the petrous pyramid is hypoplastic. The cochlea is absent or
markedly hypoplastic. Notice the cavity in the region of the vestibule with rudimentary semicircular canals.
216 Ballenger’s Otorhinolaryngology
during a stapedectomy for congenital footplate fixa- extend from the dome of the jugular fossa to the
tion or otosclerosis. superior petrous ridge. Laterally placed fractures
involve the promontory, vestibule, horizontal and
Trauma Bleeding within the lumen of the inner posterior semicircular canals, and occasionally the
ear structures may occur after trauma. If bleeding tympanic segment of the facial nerve (Figure 7–36).
occurs by concussion without actual fracture, MRI Medially situated fractures involve the vestibule,
may be indicated to confirm the diagnosis. The cochlea, fundus of the internal auditory canal, and
study should be performed at 36 hours after the common crus.
injury to allow the transformation of deoxyhemo-
globin into methemoglobin, which has a bright sig- Labyrinthitis Enhancement within the lumen
nal in both T1 and T2 images (Figure 7–35). of the bony labyrinth is often observed in MRI
The inner ear structures are seldom crossed by obtained after injection of contrast material in
longitudinal fractures of the temporal bone but are patients with acute bacterial or viral labyrinthitis
usually involved in transverse fractures. These frac- and sudden deafness8–10 (Figure 7–37).
tures typically cross the petrous pyramid at a right Chronic labyrinthitis varies from a localized
angle to the longitudinal axis of the pyramid and reaction caused by a fistula of the bony labyrinth to
Imaging of the Temporal Bone 217
a diffuse process. The lumen of the inner ear is par- Labyrinthine Schwannomas In the past, small
tially or totally filled with granulation and fibrous schwannomas have been found within the vestibule
tissues. Osteitis of the bony labyrinth occurs, which and cochlea during postmortem dissection of the
may lead to a partial or complete bony obliteration temporal bone. These lesions are usually not recog-
of its lumen (Figure 7–38). Whereas bony oblitera- nizable by CT but are well demonstrated as small,
tion of the inner ear is readily identified by CT, enhanced masses in MRI examinations performed
fibrous obliteration is recognizable only by MRI. In after injection of contrast material (Figure 7–39).
the T2 images, the high signal seen within the normal
inner ear structures is absent, therefore making Endolymphatic Sac Tumors Endolymphatic sac
involved structures no longer recognizable. tumors are locally aggressive papillary adenomatous
FIGURE 7–36. Transverse fracture of the left petrous pyramid. A and B, Axial computed tomographic sections. The
fracture extends from the superior part of the petrous ridge to the undersurface of the temporal bone crossing the
superior semicircular canal, vestibule, and promontory of the cochlea.
218 Ballenger’s Otorhinolaryngology
tumors.11 They are often associated with von Hip- toid and petrous pyramid by tumor. Axial CT images
pel-Lindau disease, a genetic multisystem neoplastic initially show a localized area of erosion of the pos-
disorder. An early finding in endolymphatic sac terior aspect of the petrous pyramid in the region of
tumors is a sensorineural hearing loss. At first, the endolymphatic sac (Figure 7–40, A). As the
endolymphatic sac tumors involve the adjacent dura lesion enlarges, destruction of the petrous pyramid
and endolymphatic duct. From there the lesion is observed with involvement of the inner ear struc-
extends to the vestibule, semicircular canals, mas- tures. In the T1 MRI, the tumor has a heterogeneous
toid, and middle ear cavity, where it appears through appearance with areas of high signal owing to cysts
an intact tympanic membrane as a bluish mass, filled with blood or high proteinaceous fluid and
often confused with a glomus tumor. Continuous multiple small areas of signal void owing to calcifi-
growth leads to complete replacement of the mas- cations and blood vessels. Following administration
of contrast, the solid portion of the mass undergoes
a nonhomogeneous enhancement (Figure 7–40, B).
A B
FIGURE 7–42. A, Densitometric profile of the normal cochlear capsule with standard deviations. B, Densitometric pro-
file of the patient shown in Figure 7–41 (interrupted line). Comparison with the densitometric profile of the normal
capsule (solid line) shows a diffuse demineralization of the cochlear capsule that is more severe in the region of the mid-
dle and apical coils. RW = round window.
PETROUS PYRAMID A
FIGURE 7–46. Cholesterol granuloma. Axial spin density (A) and axial T2-weighted (B) magnetic resonance images.
A mass of high signal intensity in both sequences is demonstrated in the left petrous apex. The areas of signal void
within the mass are produced by deposits of hemosiderin.
the mass except for its capsule. With CT, a congeni- geniculate ganglion and extend into the internal
tal cholesteatoma of the petrous apex is difficult to auditory canal. Facial paralysis is often the first
differentiate from a cholesterol granuloma cyst that symptom. Computed tomography shows a poorly
occurs in extensively pneumatized petrous pyra- defined lytic lesion containing an almost pathogno-
mids. The two lesions can be differentiated by MRI monic bony spiculation13 (Figure 7–48, A). With
because congenital cholesteatomas produce a signal MRI, the tumor is of medium signal intensity in T1
of medium intensity in the T1 images and high images, undergoes a strong enhancement after injec-
intensity in T2, whereas cholesterol granulomas have tion of contrast, and contains linear areas of signal
a similar high signal in both T1 and T2 sequences. void owing to bony spiculae (Figure 7–48, B).
Areas of signal void are often observed in cholesterol
granulomas produced by deposits of hemosiderin
(Figure 7–46).
A
FIGURE 7–49. Paget’s disease, axial section of the left
temporal bone. Notice the severe demineralization of the
petrous pyramid and mastoid with thinning of the otic
capsule, particularly of the cochlea.
B FACIAL NERVE
Computed tomography is the study of choice of the
FIGURE 7–48. Hemangioma, right petrous pyramid. facial nerve canal. The examination should be per-
A, Axial computed tomographic section; B, axial T1- formed in two or three planes to visualize the vari-
weighted magnetic resonance image after contrast. The ous segments of the canal. Magnetic resonance
anterior aspect of the right petrous pyramid is eroded by imaging visualizes the facial nerve itself, particularly
an enhancing soft tissue mass (arrowheads) extending when the nerve is thickened.
into the attic, labyrinthine segment of the facial nerve
canal, and fundus of the internal auditory canal. Note Congenital Anomalies Congenital anomalies
the characteristic bony spiculation within the tumor involve the size and course of the facial canal. The
mass (arrows). canal may be partially or completely absent, hypo-
plastic, or unusually narrow. Minor variations of the
course of the facial nerve are common and of no clin-
Paget’s Disease Paget’s disease often affects the ical significance. More severe anomalies should be
calvarium and the base of the skull, including the identified to avoid serious damage to the nerve dur-
petrous pyramids. The disease usually spreads from ing surgery. The horizontal segment may be dis-
the petrous apex laterally and produces a typical placed inferiorly to cover the oval window or lie
washed-out appearance of the involved pyramid exposed on the promontory. In congenital atresia of
caused by extensive demineralization (Figure 7–49). the external auditory canal, the mastoid segment of
The internal auditory canal is usually involved first, the facial canal is rotated laterally. The rotation varies
followed by the otic capsule, which first becomes from minimal obliquity to a true horizontal course.
224 Ballenger’s Otorhinolaryngology
A
A
FIGURE 7–54. Left acoustic schwannoma, postinfusion study. A, Horizontal computed tomographic (CT) section. B,
Coronal CT section. The left internal auditory canal appears grossly expanded and eroded. A large tumor mass fills the
canal and the cerebellopontine cistern. Notice the displacement to the right of the brainstem and fourth ventricle.
tumor is large, it outlines the convex medial aspect Thin MRIs are obtained in the axial or coronal
of the mass, obstructing the canal (Figure 7–55). plane prior to and after injection of paramagnetic
Magnetic resonance imaging is the study of agents. In the precontrast image, the tumor is
choice for diagnosis of acoustic schwannomas with- brighter than cerebrospinal fluid and isointense to
out exposing the patient to ionizing radiation and gray matter. In the postcontrast study, the mass
without the necessity for spinal puncture.14,15 undergoes a marked enhancement as the contrast
FIGURE 7–55. Left acoustic schwannoma. A, The computed tomographic pneumocisternogram demonstrates a tumor
mass filling the left internal auditory canal and slightly protruding into the cerebellopontine cistern. Notice the unin-
volved portion of the eighth cranial nerve extending from the medial aspect of the tumor to the brainstem. B, The right
cerebellopontine cistern and internal auditory canal are well filled by air. The eighth cranial nerve courses from the
brainstem through the cistern to the internal auditory canal.
Imaging of the Temporal Bone 227
FIGURE 7–56. Right vestibular schwannoma. Right and left coronal T1-weighted magnetic resonance images after
contrast. An enhancing soft tissue mass fills the right internal auditory canal.
concentrates within the tumor with consequent tumors. The lesion has a signal intensity less than the
shortening of the T1 relaxation time (Figures 7–56 brain in the T1 sequences. In the T2 images, the
and 7–57). These images clearly show the size of the lesion has variable characteristics, either a patho-
tumor within the internal auditory canal and cere- gnomonic further decrease in signal intensity or a
bellopontine cistern, as well as possible extension into nonspecific increase in brightness. After intravenous
the modiolus, which carries a poor prognostic value injection of gadolinium DTPA, in the T1 images
unless the cochlea is sacrificed at surgery.16 Extension meningiomas show a marked increase in signal
of the tumor within the facial canal is usually indica- intensity similar to that seen in acoustic schwanno-
tive of a schwannoma arising from the facial nerve. mas. Unlike the latter tumor, meningiomas usually
arise in the cerebellopontine cistern and spare the
Meningiomas Meningiomas account for approxi- fundus or the entire internal auditory canal (see Fig-
mately 3 to 4% of the cerebellopontine angle ure 7–47).
A B
FIGURE 7–57. Left acoustic schwannoma. Axial magnetic resonance images. A, T2 fast spin echo. B, T1 postcontrast.
An enhancing soft tissue mass partially fills the left internal auditory canal and protrudes into the cerebellopontine cis-
tern. Note that the tumor is well seen in the fast spin echo image (A) as a filling defect within the bright signal of the
cerebrospinal fluid (arrow).
228 Ballenger’s Otorhinolaryngology
The external ear is composed of the auricle, the bodies that make their way medial to this point are
external auditory canal (EAC), and the epithelial more difficult to remove.
surface of the tympanic membrane. Diseases of the The EAC serves as a channel for sound trans-
external ear include trauma, infections, and neo- mission to the middle ear and also protects the mid-
plasms. dle and inner ear from foreign bodies and fluctuation
ANATOMY
The auricle is composed of fibroelastic cartilage to
which the skin and a small amount of subcutaneous
tissue are closely attached. The skin on the external
(anterior) surface of the auricle is attached firmly to
the underlying cartilage, with the connective tissue of
the dermis condensing to form perichondrium. The
skin on the undersurface or posterior surface of the
auricle, by contrast, has a true subcutaneous layer.
This feature of the auricular integument, combined
with the exposed position of the auricle, is responsi-
ble for the majority of clinical problems that involve
the auricle: trauma, exposure, and infection. Fluid
accumulation consequent to these processes results
in separation of perichondrium from the cartilage.
Unless this separation is promptly relieved, necrosis
of cartilage will result because of interference with its
perfusion from the vessels of the perichondrium. The
topography of the auricle is determined by the con-
tour of its underlying cartilaginous frame (Figure
8–1). The auricle is attached to the skull by a series of
ligaments, muscles, and skin.
The EAC is approximately 2.5 cm in length and
is divided into bony and cartilaginous parts. The
medial two-thirds is osseous, and the lateral one-
third is cartilaginous (Figure 8–2). Because of the
oblique position of the tympanic membrane, the FIGURE 8–1. The right auricle showing the principal
posterosuperior part of the canal is about 6 mm anatomic features of its lateral surface. Reproduced with
shorter than the anteroinferior portion. The permission from Schuknecht HF, Gulya AJ. Anatomy of
osseous-cartilaginous junction forms an isthmus the temporal bone with surgical implications. Philadel-
that is the narrowest segment of the EAC. Foreign phia: Lea & Febiger; 1986.
230
Diseases of the External Ear 231
of temperature. The dehiscences in the anterior wall (C2–3). The extrinsic muscles of the ear are supplied
of the cartilaginous portion of the canal are known as by the facial nerve (cranial nerve VII).
the fissures of Santorini, which may allow spread of The lymphatic drainage of the EAC is an
tumor or infection from the EAC into the parotid important channel for the spread of infections or
gland or temporomandibular joint. The epithelial neoplasms. The anterior and superior parts of the
lining of the EAC is continuous with the epithelial EAC drain to the preauricular lymphatics in the
covering of the auricle and the outer layer of the tym- parotid gland and the superior deep cervical lymph
panic membrane. The exfoliated squamous cell nodes. The inferior portion of the EAC drains into
epithelium and earwax migrate in a lateral direction, the infra-auricular lymph nodes near the angle of
serving a self-cleansing function. the mandible. The posterior part of the EAC drains
The skin of the bony canal is much thinner into the postauricular lymph nodes and the superior
than that of the cartilaginous portion, about 0.2 mm deep cervical lymph nodes.
in thickness, and is continuous with the epithelial
layer of the tympanic membrane (see Figure 8–2).
There are no glands or hair follicles in the subcuta-
TRAUMA TO THE EXTERNAL EAR
neous layer. Because of the thinness of the skin in Trauma to the external ear is common in all age
the bony EAC, it can be easily traumatized, for groups. The unprotected auricle is at risk for all
example, during the removal of cerumen. kinds of trauma including cold or hot thermal injury
The skin of the cartilaginous part of the EAC is and blunt or sharp injury resulting in ecchymosis,
thicker, averaging from 0.5 to 1 mm, with four lay- hematoma, laceration, or fracture.
ers of epidermis and a true subcutaneous layer. It
contains hair follicles and sebaceous and apocrine
glands (Figure 8–3).
AURICULAR HEMATOMA
The external ear is innervated by contributions Hematoma of the auricle usually develops after blunt
from the trigeminal (cranial nerve V), facial (cranial trauma and is common among wrestlers and boxers.
nerve VII), glossopharyngeal (cranial nerve IX), and The mechanism usually involves traumatic disruption
vagal (cranial nerve X) nerves, as well as from the of a perichondrial blood vessel. Blood accumulation
cervical plexus through the greater auricular nerve in the subperichondrial space results in separation of
232 Ballenger’s Otorhinolaryngology
Sebaceous gland
Capillary network
Hair
Duct of
Epidermis sebaceous gland
Ductal
Ductal opening opening
(hair removed)
perichondrium from the cartilage. If the cartilage is secured bolsters (Figure 8–5). The incision should be
fractured, blood seeps through the fracture line and placed in the scapha, paralleling the helix. Sufficient
extends to the subperichondrial plane on both sides.1 exposure should be obtained to remove the entire
This creates a bluish swelling, usually involving the hematoma and to inspect the cavity. If delay has
entire auricle, although it may be confined to the resulted in some organization, sharp ring curettes
upper half. If the lesion is not treated early, the blood may be used to remove the clot. Dental rolls are cut to
organizes into a fibrous mass, causing necrosis of the proper size, applied to both sides of the auricle, and
cartilage because of interference with its circulation. tied using through-and-through nylon or silk sutures.
This mass forms into a twisted scar, especially after An antibiotic ointment is applied over the incision.
repeated trauma, creating the deformity known as The dental rolls are left in place for 7 to 14 days.
“cauliflower ear” (Figure 8–4).
Treatment is based on evacuation of the
hematoma and application of pressure to prevent
LACERATIONS
reaccumulation of blood. Simple needle aspiration is Auricular lacerations with or without loss of parts
inadequate treatment and frequently results in fibro- of the auricle are common from sharp trauma.
sis and organized hematoma. The most effective treat- Excellent results are possible if sound surgical prin-
ment for auricular hematoma is adequate incision ciples are applied. An attempt should be made to
and drainage with through-and-through suture- repair, preserving all remaining viable tissue. When
Diseases of the External Ear 233
BURNS
Burns are traditionally classified in three degrees of
severity: erythema (first degree), blistering (second
degree), and full-thickness destruction (third degree).
Burns caused by scalding liquids or fire are often full
thickness. Untreated, they may lead to perichondritis.
It is important to avoid pressure on the ear, and gen-
tle cleansing and topical antibiotic applications are
used. Prophylactic use of antipseudomonal antibiotics
is advocated. The antibiotic may be injected subperi-
chondrially at several different injection sites over the
anterior and posterior surfaces of the auricle.3 Appli-
cation of mafenide acetate (Sulfamylon) cream after
cleaning the wound is recommended. In the late stage,
débridement and skin grafting may be necessary. Peri-
chondritis and chondritis should be treated with
antibiotic iontophoresis, early débridement, and
FIGURE 8–4. Cauliflower ear resulting from auricular
grafting.
hematoma.
the auricle is not totally severed, it can be reattached
most of the time.
CERUMEN
Cerumen is a combination of the secretions produced
by sebaceous (lipid-producing) and apocrine (ceru-
FROSTBITE minous) glands admixed with desquamated epithelial
The auricle is particularly susceptible to frostbite debris. This combination forms an acidic coat that
because of its exposed location and lack of subcuta- aids in the prevention of EAC infection. The pH of
neous or adipose tissue to insulate the blood vessels. the cerumen is high in diabetic patients compared
The anesthesia that develops in the area exposed to with 6.5 to 6.8 in the normal EAC.4 There are genet-
severe cold deprives the patient of any warning of ically and racially determined differences in the
impending danger. Initially, there is vasoconstric- physical characteristics of cerumen that vary its
tion, leaving the ear, especially the edges of the helix, appearance and consistency and may be associated
blanched and cold to the touch. Hyperemia and with immunoglobulin and lysozyme content.5 Some
edema follow and are caused by a marked increase in individuals have a scanty amount, and others tend to
capillary permeability. Ice crystallization of the form obstructive masses. The geriatric and mentally
intracellular fluid may be primarily responsible for retarded populations have a tendency to accumulate
this, as well as cellular necrosis in the surrounding excess cerumen. Accumulation of cerumen represents
tissues. The ear becomes swollen, red, and tender, the most common and routine otologic problem. It
and bullae may form under the skin, resembling a may interfere with the clinician’s view of the tympanic
first-degree burn. membrane, cause hearing loss and discomfort, or
234 Ballenger’s Otorhinolaryngology
Perichondrium
Cartilage
Hematoma
A B
become a source of infection. Some patients make helps to prevent head movement and to perform
routine attempts to remove cerumen with cotton this procedure painlessly.
swabs, making it worse by pushing cerumen medially. If impaction of hard cerumen persists or is too
Several techniques are available for the painful to remove, the patient may be sent home
removal of cerumen and may be used in a variety of with instructions for using an agent to soften the
ways. Before starting to remove cerumen, one cerumen. Such agents include a variety of common
should make sure that the patient does not have a corticosteroid and antibiotic otic drops, cerumi-
history of tympanic membrane perforation. If per- nolytic solutions (Cerumenex), or hydrogen perox-
foration is suspected, the irrigation method should ide. Following its use for a few days, the patient is
not be used. The irrigation method works best for re-examined and the softened remaining cerumen
soft and greasy cerumen. The canal may be irrigated can be removed with irrigation or suction. This
with warm water, either with a syringe or with a approach is particularly useful in pediatric patients.
pressure-driven irrigating bottle (Figure 8–6). The
canal is straightened by pulling the auricle up and
back. The water stream is directed along the supe-
FOREIGN BODIES
rior canal wall, and outflow is caught in a basin held Foreign bodies in the EAC are found most fre-
below the ear. Remaining irrigating solution or quently in the pediatric age group or in mentally
residual cerumen can be suctioned out using a Fra- retarded institutionalized patients. Any objects small
zier No. 5 or 7 suction catheter. An alternative enough to enter the EAC can become prospective
method is the use of a cerumen curette to dislodge foreign bodies. These include animate, inanimate, or
and remove the cerumen. First the cerumen and mineral objects. They may cause symptoms of irri-
desquamated layer of epithelium are gently sepa- tation, pain, and hearing loss.
rated from the canal wall with a ring curette, and The removal of a foreign body can be safely
the loosened cerumen is grasped with an alligator done under direct visualization, preferably under an
forceps and teased out. The use of an operating operating microscope with the patient in a supine
microscope with the patient in a supine position position. Instruments helpful for this task include
Diseases of the External Ear 235
Cerumen
the alligator forceps, ring curettes, and hooks. Inan- fracture of the anterior canal wall. The patient is
imate objects located lateral to the isthmus of the treated for this fracture by repositioning lacerated or
canal are removed with an alligator forceps or by avulsed tissue and bone in the canal and packing the
placing a hook or ring curette behind it and pulling canal with antibiotic-saturated gauze. Fractures of the
it out. Suctioning with Frazier suction catheters is canal can be a part of temporal bone fractures. Lon-
useful in removing an object with a smooth surface gitudinal temporal bone fractures may extend into the
that is hard to grasp. Irrigation can be used in certain bony ear canal, usually passing through the bony tym-
instances. Objects located medial to the isthmus of panic ring at the junction of the scutum and the tym-
the canal are more difficult to remove and may panomastoid suture. Blood with cerebrospinal fluid
require local or general anesthesia. may drain for a while. There may be an area of ecchy-
Some foreign bodies may incite more inflam- mosis over the mastoid (Battle’s sign). These fractures
matory reaction and be damaging. Vegetable and usually heal spontaneously with an occasional steno-
plant debris can adhere to the skin of the EAC or sis remaining in the bony annulus. If the patient
tympanic membrane. Miniature round batteries develops a conductive hearing loss owing to ossicular
used for cameras and hearing aids, once placed in damage or cholesteatoma caused by entrapped skin
the canal, can cause reaction and damage canal skin in the fracture line, tympanoplasty and ossiculoplasty
or even the tympanic membrane. A live insect in the or tympanomastoidectomy may be required later.
EAC should be immobilized before removal by
instilling mineral oil or alcohol into the canal.
The best chance for removal of a foreign body in
INFECTION AND INFLAMMATION OF
the EAC is the first attempt. When it fails, the ear may THE EXTERNAL EAR
become extremely painful, and proper anesthesia may Infection and inflammation may involve skin or car-
be necessary. Four-quadrant canal skin injection with tilage of the auricle, EAC, or epithelial layer of the
a local anesthetic agent is sufficient in adults. For tympanic membrane. It may be acute or chronic.
young children, it is best to use general anesthesia. The infectious agent may be bacterial, fungal, viral,
or mixed.
FRACTURES OF THE EXTERNAL AUDITORY
CANAL AURICLE
A strong blow to the mandible can drive the Cellulitis of the Auricle Cellulitis is a bacterial
mandibular condyle into the ear canal, resulting in infection that usually follows abrasion, laceration, or
236 Ballenger’s Otorhinolaryngology
ear piercing. The auricle is red, swollen, painful, and have been found in these patients.6 Auricular carti-
tender to manipulation. It is usually caused by gram- lage is most commonly involved, whereas nasal and
positive cocci such as Staphylococcus or Streptococcus laryngeal cartilages are less frequently involved.7 The
and rarely other microorganisms such as Pseudo- typical patient presents with a red, swollen tender
monas. In the absence of a history of trauma, a topi- auricle. Recurrent episodes may result in a floppy
cal allergic reaction or relapsing polychondritis and distorted auricle. The disease may involve both
should be considered. Treatment includes oral or auricles simultaneously, or there may be alternate
intravenous antibiotic and wound care. Erysipelas is a involvement. The patient may develop a saddle
cellulitis caused by group A β-hemolytic Streptococcus deformity with destruction of nasal septum and
and may involve the auricle. It is marked by systemic hoarseness and subglottic stenosis owing to involve-
toxicity with fever and chills, erythema, pain, and ment of the larynx or trachea.
swelling. It is contagious. Treatment of choice is oral Treatment of relapsing polychondritis includes
or intravenous penicillin G and wound care. corticosteroid, salicylate, or indomethacin for acute
episodes. Dapsone (Avlosulfon), 100 mg once or
Allergic Dermatitis of the Auricle Allergic der- twice daily after an initial trial of 50 mg/day, has
matitis of the auricle is characterized by localized been successfully used for chronic disease with sys-
erythema, swelling, and itching in the area of aller- temic manifestations.8
gen exposure. A patient with neomycin allergy, who
has been using eardrops containing neomycin, will
present with swelling and redness in the area
EXTERNAL AUDITORY CANAL
exposed to the drops, such as the meatus, EAC, and Although the EAC is a well-protected and self-
inferior part of the auricle. A patient with metal cleansing structure, various forms of infection may
allergy will present with a red swollen ear lobule develop in the EAC. Otitis externa is one of the most
owing to contact with the earring. Treatment common diseases in clinical practice.
includes removal of the allergen, topical corticos-
teroid cream, and oral antihistamines. Acute Localized Otitis Externa (Furuncle) Acute
localized otitis externa is an infection of a hair folli-
Perichondritis and Chondritis Perichondritis or cle, beginning as a folliculitis but usually extending
chondritis is a bacterial infection of perichondrium to form a small abscess or furuncle. The infecting
or cartilage of the auricle. This condition may follow microorganism is usually Staphylococcus aureus. It
inadequately treated auricular cellulitis, acute otitis involves the lateral cartilaginous portion of the EAC,
externa, accidental or surgical trauma, or multiple usually at the meatus. Pain is severe in this condi-
ear piercing in the scapha. The affected ear is painful, tion, and examination is difficult owing to pain and
red, and swollen and drains serous or purulent exu- swelling. If the abscess occludes the canal, hearing
dates. The surrounding soft tissues of the face and loss may develop. Discharge is not usually present
neck may be affected. The most common pathogen until the abscess ruptures.
is Pseudomonas. Acute localized otitis externa should be treated
In the early stage, oral fluoroquinolone antibi- the same as an abscess in any part of the body. If it is
otics (ciprofloxacin [Cipro], levofloxacin [Lev- seen before suppuration has taken place, resolution
aquin]), local antibiotic drops, and débridement are may occur with the use of topical and systemic antibi-
sufficient. In the advanced stage with involvement of otics. If a localized abscess has formed, it should be
regional lymph nodes and surrounding soft tissue, treated by incision and drainage and topical antibi-
the patient may need to be hospitalized with aggres- otic ointment with or without oral antibiotics.
sive intravenous antibiotics using ceftazidime or flu-
oroquinolones and local treatment. Topical antibiotic Acute Diffuse Otitis Externa (Swimmer’s Ear)
irrigation with indwelling catheters may be tried. ETIOLOGY/PREDISPOSING FACTORS. Acute diffuse otitis
externa is a bacterial infection of the EAC and the
Relapsing Polychondritis Relapsing polychondri- most common form of otitis externa. It is caused by
tis is an autoimmune disease manifested by inter- the removal of the protective lipid film from the
mittent episodes of inflammation of cartilage canal, allowing bacteria to enter. It usually begins
throughout the body. Type II collagen antibodies with itching in the canal and skin maceration and
Diseases of the External Ear 237
local trauma from scratching the canal with a cotton severe stage, the clinician often sees evidence of
swab, bobby pin, fingernail, or other object. Predis- extension of infection beyond the EAC to involve
posing factors include frequent swimming; a warm adjacent soft tissues and cervical lymph nodes.
and humid climate; a narrow and hairy ear canal;
presence of exostosis in the canal; trauma or foreign Treatment Certain principles of management must
body in the canal; impacted or absent cerumen; use be observed in every case of otitis externa. These are
of hearing aids or earplugs; diabetes or an immuno- frequent inspection and cleansing of the canal, con-
compromised state; skin conditions such as eczema, trol of pain, use of specific medication appropriate
seborrhea, and psoriasis; and excessive sweating. to the type and severity of the disease, acidification
Absence of cerumen may be a predisposing factor of the canal, and control of predisposing causes. Fre-
because the act of cerumen removal may be trau- quent inspection with cleaning using suction-
matic and lead to breaks in the fragile EAC skin, and débridement under an operating microscope and
cerumen serves an antimicrobial role through phys- drying of the ear canal is the single most important
ically protecting the EAC skin; establishing a low- step in obtaining resolution of all forms of otitis
pH, inhospitable environment for pathogens; and externa.
containing compounds such as lysozyme. The preinflammatory and mild stage of
The usual pathogens for acute diffuse otitis inflammation can be managed with thorough clean-
externa are Pseudomonas aeruginosa, Proteus mirabilis, ing and débridement of the canal, preferably under
or S. aureus. Culture of the canal is usually not done a microscope. Acidifying/antiseptic agents such as
except for recurrent or recalcitrant infections. gentian violet may be applied. Antibiotic-hydrocor-
tisone drops can be used for a few days. Patients are
DIAGNOSIS/STAGE OF DISEASE. The typical patient advised to avoid water and resist using cotton swabs
presents with one or all of the symptoms including or digital manipulation of the ear canal.
pain, itching, fullness, and hearing loss. On physical In the moderate stage of inflammation, treat-
examination, there are various degrees of tenderness ment may include gentle cleaning-débridement of the
and narrowing of the ear canal with red swollen canal and application of acidifying/antiseptic/ antibi-
skin. Clear to purulent exudates may be present. One otic agents. If the canal is severely swollen, a cotton or
of the classic signs is pain elicited by pulling the auri- Pope wick may be inserted and otic drops instilled on
cle upward and backward. it. A variety of eardrops are available for treatment.
Senturia and colleagues proposed three clinical Most of the eardrops contain a combination of
stages of otitis externa: preinflammatory, acute antipseudomonal antibiotics with or without corti-
inflammatory, and chronic inflammatory.9,10 The costeroids (neomycin sulfate, colistin sulfate [Corti-
acute inflammatory stage may be mild, moderate, or sporin], ofloxacin [Floxin], ciprofloxacin hydro-
severe. The preinflammatory stage begins when the chloride [Cipro HC]). Most of these agents are acidic
stratum corneum becomes edematous owing to the to inhibit the proliferation of bacteria and fungi. The
removal of the protective lipid layer and acid mantle major adverse reaction to the use of an acidic agent is
from the canal, resulting in itching, edema, and the burning on application. Ophthalmic preparations
sensation of fullness. The mild acute inflammatory tobramycin and dexamethasone (gentamicin, [Tebra-
stage is characterized by increased itching and pain. dex], ciprofloxacin [Ciloxan]) are pH neutral and
Mild erythema and edema are present on examina- may be tolerated better than otic drops. An additional
tion. As inflammation increases to the moderate advantage of ophthalmic drops is a low viscosity,
phase, the patient complains of intermediate pain allowing improved penetration. Fluoroquinolone
and itching. The lumen of the EAC is decreased by antibiotics, such as ciprofloxacin and ofloxacin, may
edema and debris from the thickened, irritated skin be a better choice because of an appropriate antimi-
(Figure 8–7). Secretions are exudative and more pro- crobial spectrum and low ototoxicity, especially for
fuse. In the severe inflammatory stage, the canal patients with neomycin sensitivity.11–13 Instillation of
lumen becomes completely obstructed because of otic powder containing a combination of cipro-
the increasing hyperemia, edema, and purulent otor- floxacin/chloramphenicol, amphotericin B (Fungi-
rhea. The patient complains of intense pain, espe- zone), and hydrocortisone is helpful to deliver high
cially on chewing or tragal manipulation. In the doses of medications locally. An oral analgesic is often
238 Ballenger’s Otorhinolaryngology
needed. System antibiotics are usually not necessary. the EAC. The canal can be painted with gentian vio-
Patients are advised to avoid any predisposing factors. let, and otic powder may be applied. Painting the
In the severe stage, the lumen of the EAC may canal with triamcinolone/nystatin (Mycolog) cream
be swollen shut by edema and debris to such a helps to relieve pruritus and clear chronic otitis
degree that antibiotic drops cannot be instilled into externa. Patients are instructed not to touch the EAC
the canal. As discussed above, a cotton or Pope wick or use a cotton swab.
must be gently inserted into the canal to carry the
topical medication to the affected canal skin. After 2 SURGICAL TREATMENT. In case of medical treatment
or 3 days, the canal usually opens, permitting clean- failure, especially with canal stenosis, surgical proce-
ing and instillation of the medication. If infection dures are indicated to restore canal patency and
extends beyond the limit of the EAC, oral anti- hearing. Canalplasty with skin graft can be used to
pseudomonal quinolone antibiotics (eg, ciproflox- enlarge the canal (Figures 8–8 and 8–9).14,15 The
acin, levofloxacin) should be used in adults. For abnormal canal skin is removed entirely. The
pediatric patients, intravenous ceftazidime should be denuded canal is enlarged, using diamond burs, to
considered. an optimum size, increasing gradually in diameter. A
split-thickness skin graft is harvested from the upper
Chronic Otitis Externa Chronic otitis externa is a medial surface of the arm with a dermatome. The
low-grade, diffuse infection and inflammation of the graft is placed in the canal to cover all exposed sur-
EAC that persist for months or years. It is character- faces. A “rosebud” type of packing with Owen’s silk
ized by pruritus and dry hypertrophic skin of the strips and cotton balls is placed over the skin graft
EAC. It results in a thickening of the EAC skin and for 2 weeks (see Figure 8–9). Crusting may occur for
progressive narrowing of the lumen of the EAC several weeks and requires meticulous removal and
(postinflammatory stenosis). Although bacterial or cleansing until complete healing takes place.
fungal infection is the main cause of chronic otitis
externa, skin conditions, such as seborrheic der- PREVENTION. Preventive measures are recommended
matitis, psoriasis, neurodermatitis, and sensitization in patients who demonstrate a propensity for recur-
to an otic drop, can result in chronic otitis externa. rent episodes of otitis externa. Patients are instructed
The goal of treatment is to prevent the stenosis not to touch or place any objects such as cotton
and restore the EAC skin to its normal healthy state. swabs, paper clips, or any other objects into the
Antibiotics and corticosteroid otic drops can canal. Swimmers are instructed to use earplugs and
decrease the inflammation and edema of the EAC. are advised to use alcohol-vinegar (1:1) drops after
The routine use of antibiotic otic drops such as swimming.
neomycin is not recommended because of the high
risk of sensitization. The most important treatment Necrotizing (Malignant) External Otitis Malig-
is frequent inspection and thorough débridement of nant external otitis is a progressive, potentially lethal
Diseases of the External Ear 239
infection of the EAC, surrounding tissue, and skull the stylomastoid foramen, and cranial nerve IX, X,
base typically seen in elderly diabetic or other or XI palsies occur when the jugular foramen
immunocompromised patients. The term malignant becomes involved. The jugular vein may become
external otitis was first coined and presented in a thrombosed, progressing to a lateral sinus thrombo-
case series by Chandler in 1968.16 Diabetic patients sis, which usually ends in death.
were almost exclusively the population at risk. How-
ever, a number of cases of malignant external otitis DIAGNOSIS. A high index of suspicion for malignant
without diabetes have been documented.17,18 Most of external otitis is needed in diabetic or immunocom-
these patients had an underlying disease that promised patients with otitis externa. Granulation
resulted in neutropenia or immunosuppression, tissue in the floor of the EAC near the bony-carti-
such as leukemia, treatment with bone marrow– laginous junction is a typical otoscopic finding.
suppressive drugs, and acquired immune deficiency Patients usually complain of severe otalgia. Facial
syndrome. Pseudomonas aeruginosa is the most com- nerve paralysis and jugular foramen syndrome are
mon pathogen in malignant otitis externa. poor prognostic signs.
A culture of purulent discharge usually reveals P.
PATHOPHYSIOLOGY. The infection begins in the EAC. aeruginosa. Sensitivity testing to all antipseudomonas
The local infection in the EAC progresses to celluli- antibiotics should be sought. The erythrocyte sedi-
tis, chondritis, osteitis, and, finally, osteomyelitis. mentation rate is a nonspecific test but is useful in fol-
The disease may gain access to the osseous auditory lowing the response to antibiotics. A biopsy of the
canal and skull base through Santorini’s fissures. granulation tissue in the EAC is necessary to exclude
From there, the infection usually progresses along carcinoma of the ear canal or Aspergillus skull base
the base of the skull. Once access to the bony skull osteomyelitis since they have clinical and radiologic
base has occurred, there is progressive replacement findings similar to those in necrotizing external otitis.
of compact bone with granulation tissue. Facial Radiologic examinations are required to deter-
nerve paralysis occurs when there is involvement of mine the extent of disease. High-resolution com-
240 Ballenger’s Otorhinolaryngology
puted tomography (CT) is recommended to assess ent, together with the use of high doses of antibi-
the extent of disease at initial evaluation.19 It is of lit- otics specific for Pseudomonas for an extended
tle use in monitoring the resolution of infection period of time. Daily débridement of the EAC is per-
because remineralization is required for the bony formed, and culture of débrided material and sensi-
changes to return to normal. Magnetic resonance tivity testing should be repeated during the initial
imaging (MRI) is of no use in detecting bony phase of management.
changes, but it is better for evaluation and follow-up Antipseudomonal otic drops are instilled with
of soft tissue involvement, especially meningeal placement of a wick when necessary. Standard
enhancement and changes within the osseous antibiotic therapy has been aminoglycosides com-
medullary cavity.19 bined with either an antipseudomonal penicillin or
Bony involvement in patients with early malig- cephalosporin for dual-drug therapy as primary
nant external otitis can be detected with technetium intervention. Special precaution must be taken
scan (bone scan).20 Although it is nonspecific, bony during aminoglycoside treatment because of
involvement can be detected when there is absence nephrotoxicity and ototoxicity. Blood levels must
of destruction on CT scans.21 But a technetium scan be obtained regularly to ensure adequate dosage.
may remain positive even after the resolution of Creatinine levels should be obtained three times a
osteomyelitis. Thus, it is not useful for therapeutic week to measure renal function. Electrolyte distur-
monitoring. bances such as hypokalemia may occur; therefore,
A gallium scan is a sensitive indicator of infec- regular determination of electrolytes should be
tion. In the presence of infection, there is increased performed. Periodic hearing tests should be
uptake of gallium, which may occur in soft tissue or obtained if possible, particularly of the uninvolved
bone. The gallium scan becomes negative as the ear. Because of potential nephrotoxicity/ototoxic-
infection clears. Therefore, the gallium scan is best ity of aminoglycosides, oral quinolones (eg,
for monitoring resolution of disease and is useful in ciprofloxacin) have been used successfully as an
determining duration of antimicrobial therapy.20,22,23 alternative to treat malignant external otitis.24–26
Quinolone antibiotics have the advantage of being
TREATMENT. The standard treatment is hospitaliza- equally effective whether administered parenterally
tion of the patient and treatment of diabetes, if pres- or orally. The duration of antimicrobial therapy
Diseases of the External Ear 241
pathologic examination is required in each case. induration (Figure 8–14). They occur more often on
Most of these adenomas may be removed through a the helix. The treatment of choice for squamous cell
transmeatal approach, although with large growths,
an endaural incision may be needed. Any mass
occurring within the EAC should be removed for
histologic examination.32 Lesions thought to be
polyps, granulomas, or other benign tumors have
proved to be malignant on occasion, usually squa-
mous cell carcinoma. Because these tumors are often
associated with chronic discharge from the ear, the
patient with such discharge, especially associated
with pain and bleeding, should be considered to
have a malignant tumor.
carcinoma of the auricle is wide excision and recon- growth in the EAC, which is clinically difficult to dif-
struction (Figure 8–15). Frozen sections to check the ferentiate from an aural polyp, granulation tissue,
margins of excision should be done at the time of and otitis externa. When a tumor is found in the
resection. A full-thickness skin graft from the neck canal, the location, size, and extent of the tumor
to the defect is an excellent method of reconstruc- should be thoroughly evaluated under an operating
tion, especially for the central area farther away from microscope. Malignancy should be suspected when-
the helix. ever otalgia or bleeding is associated with the tumor
and a biopsy should be taken with local anesthesia
Basal Cell Carcinoma of the Auricle Basal cell using a cupped biopsy forceps. A difficult diagnostic
carcinoma presents as painless, well-circumscribed challenge is the differentiation of carcinoma from
ulcers with raised margins. The tumors are often malignant external otitis. The presentation of malig-
found in the preauricular or postauricular areas as nant external otitis may be indistinguishable from
well as on the helix and anterior surface of the auri- that of carcinoma of the EAC.
cle. Treatment is excision, as described above. The Either CT or MRI is helpful in defining the
surgical margin need not be as large as that for squa- extent of a carcinoma. Computed tomography is
mous cell carcinoma. unsurpassed for assessing the integrity of osseous
structures of the temporal bone and middle ear.
Squamous Cell Carcinoma of the External Audi- Magnetic resonance imaging is superior to CT in the
tory Canal Malignant tumors can arise from the evaluation of soft tissues and may be used to assess
EAC, middle ear, and temporal bone. The tumor dural, intracranial, and extracranial soft tissue
type, clinical presentation, prognosis, and treatment involvement.
are determined by the anatomic location of the Treatment consists of wide surgical excision
tumor. When patients present with advanced neo- and postoperative radiation therapy. Anterior canal
plasms, it may not be possible to define the sites of tumors may spread through Santorini’s fissures into
origin. The majority of cancers of the middle ear a preauricular lymph node.34 If the tumor has
and mastoid originate in the EAC. Squamous cell extended anteriorly and medially, the excision
carcinoma is the most common malignant tumor should include the cartilaginous and bony anterior
found in the EAC and middle ear space. canal wall, the superficial lobe of the parotid gland,
Carcinoma arising from the EAC often mimics and possibly the condyle of the mandible. When a
chronic suppurative ear disease. Common symp- malignant tumor is small, involving the posterior
toms include pain, otorrhea, bleeding, fullness, and part of the EAC, and has not extended to the drum-
decreased hearing. The most common finding is a head, a complete modified radical mastoidectomy is
done. If the tumor is close to the drumhead, a radi- 9. Senturia BH. Etiology of external otitis. Laryngo-
cal mastoidectomy is performed. If a malignant scope 1945;55:227–93.
tumor is extensive and involves the middle ear and 10. Senturia BH, Marcus MD, Lucente FE. Diseases of
mastoid, subtotal or total temporal bone resection the external ear: an otologic-dermatologic manual.
may be needed. 2nd ed. New York: Grune & Stratton; 1980.
11. Brownlee RE, Hulka GF, Prazma J, Pillsbury HC.
Malignant Melanoma Melanomas of the external Ciprofloxacin. Use as a topical otic preparation. Arch
ear are rare. Melanoma may occur either on the Otolaryngol Head Neck Surg 1992;118:392–6.
auricle or in the EAC, more commonly in the former 12. Jones RN, Milazzo J, Seidlin M. Ofloxacin otic solu-
location. Diagnosis should be suspected when a pig- tion for treatment of otitis externa in children and
mented lesion begins to increase in size or change in adults. Arch Otolaryngol Head Neck Surg 1997;123:
color. Lymphatic spread, treatment, and prognosis 1193–200.
are greatly influenced by location. Tumors on the 13. Simpson KL, Markham A. Ofloxacin otic solution. A
helical rim carry a better prognosis than those in the review of its use in the management of ear infec-
central areas, tragus or retroauricular regions. Treat- tions. Drugs 1999;58:509–31.
ment is wide excision. 14. Paparella MM, Meyehoff WL, Morris MS, DaCosta
S. Surgery of the external ear. In: Paparella MM,
Shumrick DA, editors. Otolaryngology. 3rd ed.
ACKNOWLEDGMENT
Philadelphia: WB Saunders; 1991 p. 1259–70.
The material presented in this chapter is based on 15. Jung TT. Canalplasty. Oper Tech Otolaryngol Head
the following: Austin DF. Diseases of the external ear. Neck Surg 1996;7:27–33.
In: Ballenger JJ, Snow JB, editors. Otorhinolaryngol- 16. Chandler JR. Malignant external otitis. Laryngo-
ogy head and neck surgery. 15th ed. Philadelphia: scope 1968;78:1257–94.
Williams & Wilkins; 1996. p. 974–88. 17. Ress BD, Luntz M, Telischi FF, et al. Necrotizing
external otitis in patients with AIDS. Laryngoscope
1997;107:456–60.
REFERENCES 18. Gordon G, Giddings NA. Invasive otitis externa due
1. Jahn AF. Traumatic disorders of the external ear. In: to Aspergillus species: case report and review. Clin
Ludman H, Wright T, editors. Diseases of the ear. 6th Infect Dis 1994;19:866–70.
ed. London: Arnold; 1998. p. 299–305. 19. Grandis JR, Curtin HD, Yu VL. Necrotizing (malig-
2. Heggers JP, Robson MC, Manavalen K, et al. Experi- nant) external otitis: prospective comparison of CT
mental and clinical observations on frostbite. Ann and MR imaging in diagnosis and follow-up. Radi-
Emerg Med 1987;16:1056–62. ology 1995;196:499–504.
3. Baers HA. Otologic aspects of ear burns. Am J Otol 20. Parisier SC, Lucente FE, Som PM, et al. Nuclear
1981;2:235–42. scanning in necrotizing progressive “malignant”
4. Driscoll PV, Ramachandrula A, Drezner DA, et al. external otitis. Laryngoscope 1982;92:1016–9.
Characteristics of cerumen in diabetic patients: a key 21. Slattery WH, Brackmann DE. Skull base osteomyelitis.
to understanding malignant external otitis? Oto- Malignant external otitis. Otolaryngol Clin North Am
laryngol Head Neck Surg 1993;109:676–9. 1996;29:795–806.
5. Bojrab DI, Bruderly T, Abdulrazzak Y. Otitis externa. 22. Stokkel MP, Takes RP, van Eck-Smit BL, Baatenburg
Otolaryngol Clin North Am 1996;29:761–82. de Jong RJ. The value of quantitative gallium-67 sin-
6. Foidart JM, Abe S, Martin GR, et al. Antibodies to gle-photon emission tomography in the clinical
type II collagen in relapsing polychondritis. N Engl management of malignant external otitis. Eur J Nucl
J Med 1978;299:1203–7. Med 1997;24:1429–32.
7. McAdam LP, O’Hanlan MA, Bluestone R. Relapsing 23. Stokkel MP, Boot CN, van Eck-Smit BL. SPECT gal-
polychondritis, prospective study of 23 patients and lium scintigraphy in malignant external otitis: initial
a review of the literature. Medicine 1976;55:193–215. staging and follow-up. Case reports. Laryngoscope
8. Barranco VP, Minor DB, Soloman H. Treatment of 1996;106:338–40.
relapsing polychondritis with dapsone. Arch Derma- 24. Levenson MJ, Parisier SC, Dolitsky J, Bindra G.
tol 1976;112:1286–8. Ciprofloxacin: drug of choice in the treatment of
248 Ballenger’s Otorhinolaryngology
malignant external otitis (MEO). Laryngoscope 30. Tran LP, Grundfast KM, Selesnick SH. Benign lesions
1991;101:821–4. of the external auditory canal. Otolaryngol Clin
25. Sade J, Lang R, Goshen S, Kitzes-Cohen R. Cipro- North Am 1996;29:807–25.
floxacin treatment of malignant external otitis. Am 31. Headington JT. Epidermal carcinomas of the integu-
J Med 1989;87:138S–41S. ment of the nose and ear. In: Batsakis JG, editor.
26. Gehanno P. Ciprofloxacin in the treatment of malignant Tumors of the head and neck. 2nd ed. Baltimore:
external otitis. Chemotherapy 1994;40 Suppl 1:35–40. William & Wilkins; 1979. p. 420–30.
27. Lucente FE. Fungal infections of the external ear. 32. Friedman I. Pathologic lesions of the external audi-
Otolaryngol Clin North Am 1993;26:995–1006. tory meatus. J R Soc Med 1990;83:34–7.
28. Piepergerdes MC, Kramer BM, Behnke EE. Keratosis 33. Shockley WW, Stucker FJ. Squamous cell carcinoma
obturans and external auditory canal cholesteatoma. of the external ear: a review of 75 cases. Otolaryngol
Laryngoscope 1980;90:383–91. Head Neck Surg 1987;97:308–12.
29. Pierre G, Jean-Christophe D, Monique D. External 34. Kuhel WI, Hume CR, Selesnick SH. Cancer of the
auditory canal cholesteatoma. Arch Otolaryngol external auditory canal and temporal bone. Oto-
Head Neck Surg 1997;123:62–5. laryngol Clin North Am 1996;29:827–52.
CHAPTER 9
249
250 Ballenger’s Otorhinolaryngology
sionally, infection may involve only the tympanic of the theory have proposed that there are essentially
membrane (myringitis), without involving the two types of ET obstruction resulting in middle ear
mucosa of the middle ear space. effusion: mechanical and functional. Mechanical
This chapter deals primarily with two disease obstruction may be either intrinsic or extrinsic.
processes: acute otitis media (AOM) and chronic oti- Intrinsic mechanical obstruction is usually caused
tis media with effusion (COME). Acute otitis media by inflammation of the mucous membrane of the
represents the rapid onset of an inflammatory ET or an allergic diathesis causing edema of the
process of the middle ear space associated with one tubal mucosa. Extrinsic mechanical obstruction is
or more symptoms or local or systemic signs. These caused by obstructing masses such as adenoid tissue
usually include otalgia, fever, irritability, anorexia, or nasopharyngeal neoplasms.
vomiting, diarrhea, or otorrhea. Physical examina- Some observers believe that infants and
tion usually reveals a thickened, erythematous or younger children may suffer from functional ET
bulging tympanic membrane with limited or no obstruction as a result of either decreased tubal stiff-
mobility to pneumatic otoscopy. Erythema of the ness or an inefficient active opening mechanism.
tympanic membrane may be an inconsistent finding Proponents believe that either form of obstruction
and may be absent in certain systemic illnesses such results in inadequate ventilation of the middle ear
as immune deficiency, when the patient cannot with resulting negative middle ear pressure. This
mount a sufficient inflammatory response to present theory supports the development of a rational med-
this more classic finding. The acute onset of fever, ical or surgical approach to alleviate the obstruction
otalgia, and, on occasion, a purulent discharge is usu- and thus overcome negative pressure.
ally evidence of AOM. Following such an episode, the The ET has three functions (1): ventilation of
patient may move into a subacute or even chronic the middle ear associated with equalization of air
phase in which fluid is present in the middle ear pressure in the middle ear with atmospheric pres-
space, although active infection may be absent. sure, (2) protection of the middle ear from sound
Chronic otitis media with effusion indicates and secretions, and (3) drainage of middle ear secre-
the presence of asymptomatic middle ear fluid, usu- tions into the nasopharynx with the assistance of
ally resulting in conductive hearing loss. The tym- the mucociliary system of the ET and middle ear
panic membrane may present numerous physical mucous membrane.
findings including thickening, opacification, and The second etiologic theory was first suggested
impaired mobility. An air-fluid level and/or bubbles by Brieger in 1914 and proposes an inflammatory
may be observed through a translucent tympanic origin to OM.6 Since that time, several other authors
membrane. This entity is distinguished from AOM have supported this theory. In 1958, Senturia
in that the signs and symptoms of acute infection reported a 41% incidence of positive bacterial cul-
are lacking (eg, otalgia, fever, otorrhea). tures in 130 specimens taken from patients with a
diagnosis of “serous otitis media.”6 Other series have
supported this finding.7 Sade’s observation that the
ETIOLOGY basic histopathologic mechanism in otitis media
with effusion (OME) is an inflammatory hypertro-
Eustachian tube (ET) dysfunction is considered the phy of the middle ear mucous membrane and
major etiologic factor in the development of middle hyperplasia of its mucous glands also tends to sup-
ear disease. Politzer first proposed the ex vacuo the- port an inflammatory basis.8
ory of OM in 1867.5 The theory postulates that Protein analysis of middle ear effusions indi-
chronic negative pressure, secondary to ET malfunc- cates a higher concentration of total protein, lactate
tion, results in the development of a transudate into dehydrogenase, malate dehydrogenase, and acid
the middle ear space. Numerous experiments have phosphatase than in serum. This finding has led to
been carried out by many authors to substantiate the speculation that this material represents an exu-
this theory. It is traditionally maintained that the date rather than a transudate, giving further evi-
effusion is sterile; therefore, therapy should be aimed dence that this is an inflammatory process. Some
chiefly at relieving ET dysfunction. Most proponents proponents of the inflammatory theory feel, how-
Otitis Media and Middle Ear Effusions 251
ever, that inflammation occurs secondary to ET dys- gen immune complexes in their serum and middle
function; thus, the inflammatory response is not the ears versus a non–OM-prone cohort. Immunoglob-
primary etiologic factor. ulin may be the predominant immune mechanism
Numerous other factors may well contribute to in the middle ear. It is felt that bacteria may actually
the development of middle ear disease. These include cause immunosuppression of cell-mediated immu-
allergy, ciliary dysfunction, nasal and/or sinus dis- nity. Immunoglobulin A is thought to be a late
ease, and immaturity of the immune system. defense mechanism and may actually prevent bacte-
In the last 10 years, the role of allergy in OME riolysis by IgG and complement, acting as a blocking
has been extensively investigated.9,10 Otitis media in antibody. Others have proposed an IgE-mediated
the pediatric population is felt to be associated with hypersensitivity reaction to viral antigens.
allergy in 5 to 80% of cases. Inhalant allergies are felt “Immune tolerance” is the concept that immu-
to play a greater role than food allergies. Most stud- nization through the oral or pulmonary route may
ies have been unable to demonstrate, however, an modulate the middle ear immune response. Studies
increase in serum immunoglobulin E (IgE) in chil- have shown that oral immunization after systemic
dren with OME.11 sensitization actually increased immune-mediated
Allergic rhinitis, itself, is not felt to be the cause OME. Vaccines are now becoming available, includ-
of OME. A viral or bacterial infection may prime the ing the recently US Food and Drug Administration
environment, which, in response, produces inflam- (FDA)-approved pneumococcal conjugate vaccine.13
matory mediators. These mediators begin the phys-
iologic cycle, creating ET dysfunction, pressure
gradients, and transudation of fluid.12 MICROBIOLOGY
Middle ear mucosa is rarely the target organ.
The nasopharynx is felt to be the major site of action Numerous studies have documented the microbiol-
with subsequent spread via the ET to the middle ear. ogy of OM.14,15 Approximately 30% of middle ear
Allergy is felt to affect ET function in several ways. effusions demonstrate known pathogens for OM.16
Nasal obstruction can occur secondary to mast cell Although the treatment of AOM is directed toward
degranulation with increased vascular permeability, the elimination of the bacteria from the middle ear
increased mucosal blood flow, and increased mucus space, viruses may also play an important etiologic
production. Retrograde extension of inflammatory role in this disease process.17 The most common bac-
mediators from the anterior nose to the nasophar- terial pathogens responsible for acute infection
ynx as well as allergen contact with the nasopharynx include Streptococcus pneumoniae and nontypable
can cause ET edema and obstruction with a second- Haemophilis influenzae. These two microorganisms
ary increase in the pressure gradient through nitro- account for approximately 60% of the cases associ-
gen gas exchange and subsequent transudation of ated with bacterial infection. Group A Streptococcus,
fluid.12 Branhamella catarrhalis, Staphylococcus aureus, and
Animal models have demonstrated immune- gram-negative enteric bacteria are less frequent
mediated inflammation as a contributing factor in causes of OM (Figure 9–1).
the pathogenesis of OME. The role of immune com- Because of the difficulty in obtaining viral cul-
plexes in experimental models has also been estab- tures, fewer specific data are available regarding their
lished. Normal middle ear mucosa is not felt to be occurrence in patients with OM. However, respira-
immunocompetent tissue. During inflammation, tory syncytial virus accounts for a majority of the
however, it is transformed into a secretory epithe- viral infections of the middle ear space.17 Otitis
lium containing multiple goblet cells with infiltra- media may accompany exanthematous viral infec-
tion of macrophages and lymphocytes. This tions such as infectious mononucleosis and measles.
immune response may result from circulating anti- Over the years, chronic effusions have been
bodies that enter the middle ear through increased thought to be sterile. However, more recent studies
vascular permeability. have confirmed the presence of bacteria in middle
Otitis media–prone children have been shown ear fluid, and studies show that the bacterial spec-
to have higher levels of IgG antibody and IgG-anti- trum closely resembles that found in AOM.18 This
252 Ballenger’s Otorhinolaryngology
information becomes increasingly important when ily confirmed when there is a definite air-fluid level or
consideration is given to the treatment of patients when bubbles are clearly visible within the middle ear
with both of these disease processes (Figure 9–2). space (Figure 9–4). However, findings commonly
associated with OME include a severely retracted
tympanic membrane with apparent foreshortening of
DIAGNOSIS the handle of the malleus and a reduction in tym-
In most cases, a careful history and physical exami- panic membrane mobility (Figure 9–5). Occasionally,
nation will lead to the accurate diagnosis of OM. the tympanic membrane may be dull or thickened
A careful history should elicit classic symptoms and have an amber hue (Figure 9–6). In severe cases,
of OM. In the patient with the acute form of the dis- middle ear fluid may become purplish or blue, indi-
ease, otalgia, fever, irritability, vomiting, and diar- cating hemorrhage within the tympanic cavity.
rhea may be present. Less frequently, otorrhea, The color of the tympanic membrane is
vertigo, and facial paralysis may be associated with important but is not conclusive in making a diagno-
an acute infection of the middle ear space. In those sis. An erythematous tympanic membrane alone
patients in whom infection has spread into the mas-
toid air cell system and beyond, swelling of the
postauricular area may be present.
In COME, hearing loss may be the only symp-
tom. The most definitive part of the diagnosis is an
appropriate physical examination to confirm the
presence or absence of middle ear pathology. A
complete examination of the head and neck should
be undertaken first to identify the possibility of any
predisposing condition such as craniofacial anom-
aly, nasal obstruction, palatal defect, or adenoid
hypertrophy. In patients with unilateral OM, the
nasopharynx should be visualized to rule out the
possibility of neoplasm.
Otoscopy represents the most critical part of the
examination to establish the diagnosis of OM (Figure
9–3). Use of the pneumatic otoscope is essential. The FIGURE 9–2. Bacterial incidence in chronic otitis media
existence of chronic middle ear effusion is most eas- with effusion.
Otitis Media and Middle Ear Effusions 253
in the acute process. Some have recommended with- 24 hours in four divided doses for 10 days. In chil-
holding antimicrobial agents in certain cases.20 How- dren allergic to penicillin, a combination of erythro-
ever, in light of the fact that suppurative compli- mycin, 40 mg/kg every 24 hours, and sulfisoxazole,
cations have markedly declined during the antibiotic 120 mg/kg every 24 hours in four divided doses, may
era, antibiotic therapy is still strongly recommended be substituted. If β-lactamase-producing H. influen-
in the acute process.20 zae or B. catarrhalis is suspected, either amoxicillin-
The standard initial treatment for AOM is clavulanate, 40 mg/kg every 24 hours in three
amoxicillin, 40 mg/kg every 24 hours in three divided doses, or trimethoprim-sulfamethoxazole,
divided doses, or ampicillin, 50 to 100 mg/kg every 8 mg/kg of trimethoprim and 40 mg/kg of sul-
episodes. In the latter group, chronic hearing loss acute suppurative disease. Numerous associated fac-
becomes an additional major issue, especially as it tors must be considered; thus, a careful history
impacts speech and language development.1 should be taken for the possibility of underlying
Several options are available for those patients allergy, sinus disease, or nasopharyngeal obstruction,
who clear their effusion between episodes. The first which may be secondary to hypertrophic adenoids
option includes antibiotic therapy for each separate or even neoplasm.
episode; a second option would be the use of antibi- Numerous methods of management have
otic prophylaxis on a prolonged basis, whereas the been advocated over the years for the persistent
third would include myringotomy and ventilation form of the disease. Antihistamine-sympath-
tube insertion. The administration of pneumococcal omimetic amine preparations were used frequently
vaccine also may be useful. to clear the effusion. However, controlled clinical
Amoxicillin, or a suitable substitute in peni- trials have demonstrated a lack of efficacy.23 The use
cillin-allergic patients, may be given once daily at of corticosteroids, either applied topically in the
bedtime as prophylaxis. This form of therapy is usu- nose or given systematically, has been reported to
ally administered during the months in which OM be advantageous in clearing middle ear fluid.24
has its highest prevalence. Unfortunately, there is a paucity of data to demon-
In children in whom the middle ear does not strate efficacy; therefore, their use cannot be
clear between acute episodes, ventilation tubes may strongly recommended at this time.
be necessary to address the concomitant hearing loss The most effective medical therapy used to this
associated with the process. Their use may also be point has been antibiotic administration. Numerous
necessary in those patients with antibiotic allergy or trials have concluded that some patients may
intolerance. respond to a 21- to 30-day course of full-dose antibi-
otic therapy.25 The demonstration of viable bacteria
in the middle ear effusions of chronically diseased
CHRONIC OTITIS MEDIA WITH EFFUSION ears has led to this recommendation. In light of the
Medical Therapy Chronic otitis media with effu- similarity of the bacterial spectrum, the same
sion may occur as a sequela to AOM or in patients antibiotics recommended for AOM may be used in
who have had no documented recent episodes of this disease. This form of therapy is strongly rec-
Otitis Media and Middle Ear Effusions 257
ommended in any child who has not received be tympanostomy tube placement. There have been
antibiotic treatment before consideration is given to no good randomized controlled trials to examine the
myringotomy and ventilation tube insertion and/or risk-to-benefit ratio.27 Relapses have been demon-
adenoidectomy. strated within several weeks after treatment. The
Historically, there was debate as to whether effects of nasal corticosteroids or immunotherapy
OME should be treated with antibiotics since there on OME have not been studied.
exists a certain spontaneous resolution rate. Physi-
cians in other countries have traditionally not Surgery The use of ventilation tubes with or with-
treated OM with antibiotics as frequently as is done out adenoidectomy has become the ultimate treat-
in the United States. Rosenfeld and Post’s meta- ment of COME. This surgical intervention
analysis of studies of antibiotic therapy for OME immediately corrects the conductive hearing loss
found a statistically significant efficacy for short- associated with the middle ear process and dimin-
term resolution of OME.16 Gates stated that approx- ishes the patient’s tendency toward recurrent infec-
imately 40% of children with OME treated with tion. It should be strongly considered in the
antibiotics still have an effusion after 30 days, following situations:
whereas 10% have a documented effusion 3 months 1. Recurrent AOM
after initial therapy.26 Another factor that has not a. Unresponsive to antibiotic therapy
been studied well to date is what the impact of b. Significant antibiotic allergy or intolerance
COME is on language development and learning in 2. Negative middle ear pressure with impending
the child with conductive hearing loss secondary to cholesteatoma
COME and at what time point this deficit becomes 3. Chronic effusion of the middle ear space with a
an unacceptable risk. The success of prophylactic duration of greater than 3 months
antibiotic therapy for OME had also not been stud- a. Conductive hearing loss of greater than 15 dB
ied in a systematic fashion. b. Nasopharyngeal neoplasm for which treatment
In children with concomitant disease of the such as radiation therapy may be necessary
upper respiratory tract such as chronic sinusitis or
adenoiditis, consideration must be given to the Although some controversy exists over the use
simultaneous control of these diseases. In addition, of ventilation tubes, they do provide a safe method
systemic problems such as allergy or immunodefi- for normalizing middle ear pressure and, in most
ciency must also be addressed if long-term reversal cases, restoring hearing to normal. They are usu-
of the middle ear abnormality is to be achieved. ally associated with minimal morbidity, although
With the emerging role of allergy in OME, the tympanosclerosis or persistent perforation may be
role of corticosteroid therapy has been re-examined. seen in a few instances. In most circumstances, it is
Investigators have demonstrated that a brief course difficult to determine whether these findings are a
of oral corticosteroids is efficacious for the short- result of the underlying middle ear pathology with
term cure of OME. The proposed therapeutic mech- middle ear atelectasis or secondary to the ventila-
anisms include stabilization of phospholipids to tion tube itself. Numerous types of tubes are avail-
prevent arachidonic acid formation and subsequent able for ventilation of the middle ear space, but,
inflammatory mediator formation, possible decrease basically, they are all designed to provide equaliza-
in peritubal lymphoid tissue size, enhanced secretion tion of pressure across the tympanic membrane
of ET surfactant, and reduced middle ear fluid vis- (Figure 9–8). Some designs favor intubation of
cosity by action on mucoproteins.27 The risks of oral greater duration but also carry a slight risk of an
corticosteroid therapy in children remain a concern, increased incidence of persistent perforation upon
however. Studies have demonstrated an increase in extrusion.
the development of AOM if corticosteroids are not Depending on the age of the patient, tube
prescribed with antibiotics, transient depression in insertion may be carried out under local or general
adrenal function, and the potential for disseminated anesthesia.
varicella infection and its complications. Because of It is usually advisable to allow spontaneous
these risks, Rosenfeld recommends a trial of antibi- extrusion of the tubes to occur. Most tympanostomy
otics and corticosteroids only if the next step would tubes remain in the tympanic membrane for
258 Ballenger’s Otorhinolaryngology
approximately 6 to 12 months, with some extruding space, controlling hearing loss secondary to middle
earlier and some later. ear effusion, and controlling recurrent infection.
The most common complication of tube inser- Adenoidectomy may be useful as an adjunct to
tion is otorrhea. This may be secondary to either myringotomy in the treatment of middle ear effu-
reflux of nasopharyngeal secretions, especially dur- sion.28 Removal of adenoid tissue improves the ven-
ing an upper respiratory infection, or as a result of tilatory function of the ET, thus allowing for
pathogens entering the middle ear through the appropriate equalization of pressure. The adenoid
lumen of the ventilation tube. It is commonly has been felt to play a role in OM in two ways: when
believed that contaminated water that is allowed to hypertrophic, by causing mechanical obstruction of
enter the middle ear through the tympanostomy the ET, and when small, as a bacterial reservoir.29 The
tube may result in AOM media with otorrhea. In adenoid is thought to be an important site for pri-
these instances, the external ear canal should be mary contact of inhaled microorganisms. Two stud-
carefully cleaned and a culture obtained from the ies are frequently cited regarding the use of
middle ear by aspirating through the tympanostomy adenoidectomy in OME. Gates demonstrated greater
tube. After this has been accomplished, oral antibi- long-term efficacy in the treatment of OM in chil-
otics should be initiated as well as topical antibiotic dren 4 to 6 years of age when adenoidectomy
therapy. The usual treatment includes the use of was added to tympanostomy tube placement or
antibiotic agents commonly prescribed for other myringotomies even if this was the first surgical
forms of AOM. intervention in a child.26 Paradise et al, on the other
To avoid this possible complication, water hand, recommend adenoidectomy only if a child
protection of the ears is usually advised when con- fails initial tympanostomy tube placement.30 Studies
tamination may be a possibility. This may be accom- have also shown that the recurrence rate of AOM
plished through the use of earplugs or cotton may be reduced by adenoidectomy.30 In addition,
covered with petrolatum jelly, both of which can be other confounding factors may warrant adenoidec-
inserted into the ear canal to provide adequate pro- tomy such as evidence of chronic adenoiditis, nasal
tection. In summary, tympanostomy tubes can pro- obstruction, or recurrent or chronic sinusitis sec-
vide a useful means of ventilating the middle ear ondary to nasal obstruction.
Otitis Media and Middle Ear Effusions 259
13. Lieu TA, Ray GT, Black SB, et al. Projected cost-effec- otitis media) in children. N Engl J Med 1983;
tiveness of pneumococcal conjugate vaccination of 308:297–301.
healthy infants and young children. JAMA 2000;283: 24. Schwartz RH, Puglese J, Schwartz DM. Use of a short
1460–8. course of prednisone for treating middle ear effu-
14. Bluestone CD, Klein JO. Microbiology in otitis sion: a double-blind cross-over study. Ann Otol Rhi-
media in infants and children. Philadelphia: WB nol Laryngol 1980;89 Suppl 68:296–300.
Saunders; 1988. 25. Healy GB. Antimicrobial therapy of chronic otitis
15. Bluestone CD. Current therapy for otitis media and media with effusion. Int J Pediatr Otorhinolaryngol
criteria for evaluation of new antimicrobial agents. 1984;8:13–7.
Clin Infect Dis 1992;14 Suppl 2:S197–203. 26. Gates GA. Adenoidectomy for otitis media with effu-
16. Rosenfeld RM, Post JC. Meta-analysis of antibiotics sion. Ann Otol Rhinol Laryngol 1994;103:54–8.
for the treatment of otitis media with effusion. Oto- 27. Rosenfeld RM. New concepts for steroid use in oti-
laryngol Head Neck Surg 1992;106:378–86. tis media with effusion. Clin Pediatr 1992;31:615–21.
17. Mein JO, Teele DW. Isolation of viruses and 28. Gates GA, Avery CS, Phihooa TJ, et al. Effectiveness
mycoplasmas from middle ear effusions: A review. of adenoidectomy and tympanostomy tubes in the
Ann Otol Rhinol Laryngol 1976;85 Suppl 25:140–4. treatment of chronic otitis media with effusion. N
18. Healy GB, Teele DW. The microbiology of chronic Engl J Med 1987;317:1444–88.
middle ear effusions in young children. Laryngo- 29. Honjo I, Takahashi H, Sudo M, et al. Pathophysio-
scope 1977;87:1472–8. logical and therapeutic considerations of otitis media
19. Bluestone CD. Role of surgery for otitis media in the with effusion from viewpoint of middle ear ventila-
era of resistant bacteria. Pediatr Infect Dis J 1998;17: tion. Int J Pediatr Otorhinolaryngol 1998;43:105–13.
1090–8. 30. Paradise JL, Bluestone CD, Rogers KD. Efficacy of
20. VanBuchem FL, Peters MF, Van’t Hof MA. Acute oti- adenoidectomy for recurrent otitis media: results
tis media: a new treatment strategy. Par Med J (Clin) from parallel random and non random trials. Pedi-
Res 1985;290:1033–7. atr Res 1987;21:286–91.
21. Jacobs MR. Drug-resistant Streptococcus pneumo- 31. Black S, Shinefield H, Fireman B, et al. Efficacy,
niae: rational antibiotic choices. Am J Med 1999;106 safety, and immunogenicity of heptavalent pneumo-
Suppl 5A:19S–25S. coccal conjugate vaccine in children. Northern Cali-
22. Teele DW, Mein JO, Rosner BA. Epidemiology of oti- fornia Kaiser Permanente Vaccine Study Center
tis media in children. Ann Otol Rhinol Laryngol Group. Pediatr Infect Dis J 2000;19:187–95.
1980;89:5–6. 32. Berman S, Roark R, Luckey D. Theoretical cost effec-
23. Cantekin EI, Mendel EM, Bluestone CD, et al. Lack tiveness of management options for children with
of efficacy of a decongestant-antihistamine combi- persisting middle ear effusions. Pediatrics 1994;93:
nation for otitis media with effusion (“secretory” 353–63.
CHAPTER 10
261
262 Ballenger’s Otorhinolaryngology
patients underwent placement of one or more sets of negative pressure. As a result, the TM is retracted
pressure equalization tubes. medially. In atelectatic or adhesive OM, the middle
ear space is partially or completely obliterated. In
long-standing atelectasis, patients are at risk for sec-
PATHOGENESIS ondary acquired cholesteatomas.
Chronic otitis media is an insidious process, and Poor mastoid pneumatization is also associated
patients tend to present with long-standing disease. with chronic middle ear disease.15 Although pneuma-
As a result, the etiology and natural course of this tization is not completed until adulthood, the major-
process remain obscure, although several credible ity of the process takes place during the first 5 years
theories have been advanced. of life. Infancy and early childhood infections occur-
ring during this period are thought to prevent nor-
mal cellular development of the mastoid and thus
CONTINUUM THEORY lead to chronic middle ear disease. Temporal bone
Traditionally, COM has been thought to follow a histopathologic studies also demonstrate that infec-
bout of acute otitis media (AOM) that resulted in tion of a pneumatized cleft incites sclerosis, oblitera-
TM perforation. However, this direct correlation has tion of air cells, and chronic middle ear disease in the
fallen out of favor for several reasons. First, AOM is setting of poor mastoid pneumatization.9
one of the most common childhood diseases. Com- Ventilating tubes can be placed within an
paratively speaking, COM is quite rare. In addition, atelectatic TM in an attempt to equalize the pressure
the majority of TM perforations secondary to AOM and allow the TM to return to its normal anatomic
result in complete healing of the drumhead.9 Second, position. Fifty percent of patients with pressure
whereas streptococcal otitis media, which causes equalization tubes experience at least one episode of
necrotizing infections resulting in large perforations, otorrhea, and 3% will have symptoms persisting
is seldom seen today, the incidence of COM has beyond 6 weeks.16 After extrusion of the tube, the
remained constant.10 Third, in a study of 200 patients majority of iatrogenic TM perforations will heal.
with TM perforations, only 50% clearly recalled an Residual perforation rates are 2 to 3% for button or
acute, painful ear infection associated with the onset grommet tubes but as high as 47% for T tubes.17,18
of otorrhea. Instead, 40% described the insidious Continued eustachian tube dysfunction, persistent
onset of drainage or gradual hearing loss.5 otorrhea, and ingrowth of squamous cell epithelium
Although COM may not result directly from a through the defect can prevent spontaneous healing.
single episode of AOM, it has been suggested that all In accordance with the continuum theory, patients
cases of otitis media represent different stages in a are then at risk for secondary infections and COM.
continuum of events.11–13 For example, histologic
studies have demonstrated that persistent effusion in CHRONIC OTITIS MEDIA WITHOUT
chronic secretory otitis media leads to degradation
of the fibrous layer of the TM. Loss of the fibrous
CHOLESTEATOMA
layer results in a weakened, atrophic, two-layered Recurrent infections of the middle ear generally
drumhead that is vulnerable to atelectasis or perfo- result in irreversible mucosal changes. Histologic
ration and hence chronic middle ear disease.9,14 studies have shown that as the inflammatory process
enters the chronic phase, there is a shift in cellular
population from infiltrating leukocytes toward
ATELECTATIC AND ADHESIVE OTITIS MEDIA mononuclear cells such as macrophages, lympho-
It is acknowledged that eustachian tube dysfunction cytes, and plasma cells.19 These mononuclear cells
plays an important role in the development of secrete inflammatory mediators and growth factors
COM.15 The eustachian tube serves to ventilate the that increase capillary permeability and lead to
middle ear so that pressure equalization occurs edema and hyperemia of the middle ear mucosa. In
between this space and the surrounding environ- chronic inflammation, the mucosa undergoes meta-
ment. In persisting eustachian tube dysfunction, plasia from a single layer of ciliated cuboidal or
especially as seen in Down syndrome and cleft columnar epithelium to mucosa resembling that of
palate, the middle ear space is continually exposed to the respiratory tract with increased numbers of gob-
264 Ballenger’s Otorhinolaryngology
let and glandular cells. Consequently, there is an pinched off during the formation of the TM. Con-
increase in the volume and viscosity of the mucus. sequently, squamous cell epithelium trapped in the
These changes further overwhelm the already com- middle ear with an intact drumhead leads to con-
promised mucociliary clearance capability of patients genital cholesteatoma formation.
suffering from chronic middle ear disease.19,20 The pathogenesis of acquired cholesteatoma has
Granulation tissue consisting of vascular con- been debated for well over a century. Although no
nective tissue with inflammatory infiltrates has been single theory has been universally accepted, the most
found to be the prominent pathologic feature of popular explanation for attic cholesteatomas is the
COM. Granulation tissue was identified in over 95% invagination theory.26 Eustachian tube dysfunction is
of the temporal bones studied from individuals with thought to cause retraction of the TM. The pars flac-
a history of COM.21 Tympanosclerosis was present cida, lacking a fibrous layer, is more vulnerable to this
in 43%, cholesteatoma in 36%, and cholesterol gran- effect. As the retraction pocket deepens, desquamated
uloma in 21% of patients in one large histologic keratin accumulates and cannot be cleared from the
study of temporal bone pathology. A pathologic pocket, and a cholesteatoma develops. On otoscopic
review of 800 temporal bones revealed that granula- examination, it may appear that the patient has a per-
tion tissue had both a higher prevalence and more forated TM, but closer examination reveals an intact
generalized distribution when compared to drumhead with an attic retraction pocket. The term
cholesteatoma.22 Both studies demonstrated identi- primary acquired cholesteatoma is applied to describe
cal pathologic changes within the middle ear cleft this mechanism of cholesteatoma formation.
regardless of the presence of a TM perforation. It has also been theorized that cholesteatomas
As granulation tissue matures, it becomes may develop as a result of the ingrowth of squamous
dense and fibrotic with decreased vascularity. This cell epithelium from the lateral surface of the TM
process leads to scarring and adhesions associated through a perforation. Convincing evidence comes
with the ossicular chain and TM.23 Irreversible from a study of cytokeratin 10, which is found in
changes such as subepithelial edema and mucope- both the meatal epidermis and cholesteatoma matrix
riosteal fibrosis occur deep to the epithelial lining.24 but not in the middle ear mucosa.27
As the inflammation persists, sclerosis, along with The implantation theory proposes that squa-
new bone formation, can cause a reduction in mas- mous cell epithelium is displaced into the middle ear
toid and antral pneumatization. Other late changes owing to surgery, trauma, or a foreign body. The
such as bone erosion, tympanosclerosis, and choles- prevalence of cholesteatomas following tympanos-
terol granuloma are discussed in detail below. tomy tubes is only 0.5%.28 However, it is thought
that ventilation tubes probably prevent far more
CHRONIC OTITIS MEDIA WITH cholesteatomas than they cause.
Another, less popular concept is the metaplasia
CHOLESTEATOMA theory in which healthy cuboidal cells transform into
Congenital cholesteatomas are thought to result squamous cell epithelium in chronic inflammation.
from an error in embryogenesis that causes squa- Although in situ metaplasia has been demonstrated,
mous epithelial cell arrest behind an intact TM. actual formation of cholesteatoma has not been
This theory has gained popularity since the identi- proven.29 In addition, this theory does not explain the
fication of an “epidermoid formation,” consisting of common location of cholesteatomas in the postero-
squamous cells in the anterior epitympanum of superior aspect of the middle ear despite diffuse
developing fetal temporal bones.25 This location mucosal inflammation throughout the entire middle
coincides with the most common location of con- ear space. Lastly, it is proposed that cholesteatomas
genital cholesteatomas. The epidermoid formation may develop from papillary ingrowth of basal cells
plays a role in organizing the formation of the tym- through the basement membrane.30
panic ring, medial layer of the TM, and epithelial
lining of the eustachian tube. It is not generally
found beyond 33 weeks gestation, but failure to
BONE EROSION
atrophy is thought to result in congenital Bone erosion is an important aspect of COM
cholesteatomas. Another theory is that squamous because it can lead to various complications ranging
cell epithelium intended for the external canal is from hearing loss and labyrinthine fistula to facial
Chronic Otitis Media 265
nerve paralysis and life-threatening intracranial deposits are seen within the TM. In this setting, the
complications. Originally, it was believed that pres- term myringosclerosis is sometimes applied to indi-
sure from the cholesteatoma itself led to necrosis of cate that the process is restricted to the TM. Micro-
bone. However, experimental evidence is lacking. scopically, hyalinization of collagen and deposition
Cholesteatomas have been found to exert pressures of calcium are found within the lamina propria.
between 1.31 and 11.88 mm Hg. These pressures fall Tympanosclerosis need not be limited to the TM. It
well below the capillary perfusion pressure of 25 mm may extend into the middle ear cleft to involve the
Hg. For this reason, it is unlikely that cholesteatoma, ossicular heads and basement membrane of the
which is often associated with a perforation and middle ear mucosa. If the oval window is involved,
open cavity, can produce enough pressure to occlude stapes fixation may result and contribute to a signif-
directly capillary flow and cause tissue anoxia. How- icant conductive hearing loss.
ever, it is thought that the pressure exerted on adja-
cent bone by cholesteatoma causes bone erosion
through the activation of osteoclasts.31 CHOLESTEROL GRANULOMA
Histologic examination of the lytic zone Cholesterol crystals are frequently found within the
between the submucosa and the necrotic bone submucosal lining of ears with COM. The process
reveals marked capillary proliferation along with probably results from hemorrhage into the mucosa
infiltration of histiocytes that contain lysosomal of the middle ear or within obstructed mastoid air
enzymes such as protease, hyaluronidase, cathepsin, cells, with the crystals representing breakdown prod-
and acid phosphatase.32 For this reason, it is argued ucts of the erythrocyte cell membrane. A foreign
that hyperemia in the setting of osteolytic enzymes, body response to these crystals leads to formation of
as opposed to anoxia, is responsible for bony ero- a cholesterol granuloma. On macroscopic examina-
sion. Animal and human studies further support this tion, a yellow-brown murky viscous material is
theory.33 In bone erosion, osteoclasts, which are found within the middle ear space or within the
known to be responsible for bone reabsorption, and obstructed mastoid cells. Microscopically, the cho-
collagenase have been identified. Prostaglandin E2 lesterol crystals, foreign body giant cells, and associ-
and interleukin-1α are among various other media- ated inflammatory cells are identified.
tors found to regulate bone reabsorption.34
Studies clearly demonstrate that bone erosion
occurs in COM with or without the presence of DIAGNOSIS
cholesteatoma.33,35 Although the true mechanism is
not fully understood, it is generally accepted that HISTORY
inflammation is a major factor since granulation tis- Approximately one-third of individuals with COM
sue is often associated with ossicular erosion.36 The have their diagnosis made as an incidental finding
inflammatory process is thought to lead to infiltra- during routine physical examination. However,
tion and activation of osteoclasts and mononuclear when symptomatic, the two hallmark presenting
cells containing various proteolytic enzymes. Micro- symptoms are otorrhea and hearing loss. Pain is
scopically, a subepithelial layer of granulation tissue unusual with COM and indicates either a reactive
has been identified adjacent to eroded bone. The cel- external otitis or the possibility of a developing
lular components of this layer are identical in cases intratemporal or intracranial complication.
with and without cholesteatoma.37 The higher fre- The nature of the otorrhea is helpful in describ-
quency of bone destruction in the setting of ing the specific type of COM. Profuse, intermittent,
cholesteatoma may be related to the excellent envi- mucoid drainage is commonly noted in chronic sup-
ronment cholesteatomas provide for persistent bac- purative otitis media without cholesteatoma. Mal-
terial infection and chronic inflammation. odorous otorrhea is rare in this setting. Conversely,
patients with COM associated with cholesteatoma
often describe scant but persistent, purulent, and
TYMPANOSCLEROSIS
foul-smelling otorrhea. Blood-stained drainage is
Tympanosclerosis is common in patients with a his- often noted with granulation tissue or polyps. It is
tory of recurrent AOM, COM, or multiple ventila- important to realize that cholesteatoma is frequently
tion tubes. Macroscopically, white crescent-shaped hidden beneath this abnormal inflammatory tissue.
266 Ballenger’s Otorhinolaryngology
Some patients with chronic middle ear disease standpoint, this hearing loss is less significant com-
will have normal hearing or only mild hearing loss pared with the conductive losses caused by COM.
because the granulation tissue or cholesteatoma suc- One proposed mechanism for SNHL is that
cessfully transmits sound energy to the inner ear. inflammatory toxins cross the round window mem-
When present, hearing loss is usually conductive or brane, entering the scala tympani and causing irre-
mixed in nature. versible cochlear damage. In this setting, one would
The degree of hearing loss will depend on the expect high-frequency hearing thresholds to be
size and location of the TM perforation and the sta- most affected owing to the tonotopic arrangement
tus of the middle ear. Large perforations will gener- of the cochlea, with high frequencies stimulating
ally cause greater hearing loss compared with smaller those cells closer to the round window in the basal
defects. In addition, perforations overlying the poste- turn. One retrospective review, limited to those
rior part of the mesotympanum, and thus the round patients diagnosed with unilateral COM with
window niche, usually cause more severe degrees of cholesteatoma, showed statistically significant inter-
conductive hearing loss because the TM is no longer aural differences in both speech discrimination
protecting the round window membrane from direct scores and pure-tone thresholds at 4,000 Hz inde-
sound energy transfer. As a result, there is reduction pendent of patient age.41 Given that speech discrim-
of the “baffle” effect, leading to a change in the ination is believed to be significantly influenced by
cochlear mechanics.38 Ossicular chain involvement high-frequency cochlear function, these findings
will also cause conductive hearing loss. Chronic oti- lend support to the theory of inflammatory toxins
tis media is often associated with bone erosion, lead- entering the inner ear. However, temporal bone
ing to discontinuity of the ossicular chain. The long studies of individuals with a history of COM failed
process of the incus is particularly vulnerable to to demonstrate histologic changes associated with
postinflammatory necrosis, resulting in discontinuity inflammation near the round window membrane,
or fibrous union at the incudostapedial joint. Tym- even though an interaural difference in bone-con-
panosclerosis may also arise in the setting of chronic duction thresholds was appreciated. 42 Thus,
inflammation. Usually, this is limited to fairly inno- although there is convincing evidence demonstrat-
cent changes in the TM but may involve the middle ing a relationship between COM and SNHL, the
ear as well. As a result, the stapes footplate or other clinical implications and actual mechanism of
ossicles may become fixed. Finally, fibrosis or inflam- injury remain to be determined.
matory granulation tissue within the middle ear can
lead to limitation of TM and ossicular mobility.
Patients who have previously undergone a
PHYSICAL EXAMINATION
tympanoplasty with or without mastoidectomy for Examination should include inspection of the pinna
treatment of middle ear disease will often be left and postauricular region. Any scars from prior oto-
with a grafted TM that may be thickened, poorly logic surgery should be noted. Otoscopic examina-
mobile, and lacking the normal conical shape. Such tion with the use of a binocular microscope is
changes, along with a shallow middle ear space and imperative. Care should be taken to clear all ceru-
disruption of the ossicular chain, will also lead to men and debris from the external auditory canal
conductive hearing loss. (EAC) so that the entire drumhead is visible. The
Although an association between COM and EAC should be evaluated for signs of secondary oti-
conductive hearing loss is clearly acknowledged, the tis externa as well as scarring, which, again, would
relationship to sensorineural hearing loss (SNHL) suggest prior surgery. The presence and specific
remains controversial. Several retrospective studies location of aural polyps and granulation tissue
have compared the preoperative bone-conduction should be noted. Attention is then turned to the TM.
thresholds of diseased ears to the normal contralat- The size and location of any perforation should be
eral ears in patients with unilateral COM. These detailed in the medical record, usually in the form of
results have demonstrated an association between a diagram or photograph. Chronic otitis media in
SNHL and COM.39,40 However, the magnitude of the absence of cholesteatoma is usually associated
hearing loss was small, ranging between 5 and 12 dB with a central perforation, whereas cholesteatomas
depending on the frequency tested. From a clinical are commonly observed in the setting of defects in
Chronic Otitis Media 267
the pars flaccida or marginal perforations of the TM. is reason to believe that the poor scores are owing to
Depending on the size of the perforation, as well as an inability to present a stimulus intense enough to
the presence of granulation tissue and polyps, the obtain the maximal discrimination score.
middle ear mucosa can often be examined. In the
case of a dry perforation, the mucosa may appear
completely normal. However, otorrhea is usually
RADIOGRAPHIC STUDIES
associated with edematous, inflamed mucosa. An With the advent of high-resolution computed
attempt should be made to suction the middle ear tomography (CT) in the 1980s, temporal bone plain
space free of all secretions. If microbiologic speci- films and polytomography have essentially become
mens are indicated, fluid should be obtained from obsolete. The advantages of CT scanning over these
the middle ear, rather than the EAC, and it should be traditional studies include superior definition of
sent for both aerobic and anaerobic cultures. Perfo- both bone and soft tissue detail and lower levels of
rations of the TM can also provide an opportunity exposure to radiation compared with polytomogra-
to inspect the middle ear bony structures. Particular phy (Figure 10–1).
attention is focused on bone erosion and ossicular Standard temporal bone CT technique
disruption. Depending on the patient’s age and pain involves 1.5 mm sequential cuts in both the axial
threshold, the microscopic examination and clean- and coronal projections. The axial images should
ing might have to be performed in the operating extend from the arcuate eminence superiorly to the
room with the use of sedation. jugular fossa inferiorly. These views will be most
The physical examination should also include a helpful in evaluating the sinus tympani, facial
fistula test if the patient reports vestibular symp- recess, lateral semicircular canal, ossicles, and hori-
toms, inspection of the nasopharynx, including the zontal portion of the facial nerve. The coronal
eustachian tube orifices, and gross assessment of images span from the bony portion of the
hearing with a 512 Hz tuning fork. eustachian tube anteriorly to the posterior semicir-
cular canal posteriorly and will be of value in assess-
ing Prussak’s space, the tegmen tympani, the
AUDIOMETRIC TESTING ossicles, and the perigeniculate and vertical seg-
Every initial evaluation for COM should include
audiometric testing with air and bone pure-tone
thresholds. Appropriate clinical masking is impera-
tive as patients often have bilateral involvement and
mixed hearing loss. The degree of hearing loss is
often helpful in determining the extent of the mid-
dle ear disease. Perforations of the TM can account
for 15 to 20 dB of conductive hearing loss. When
perforations are accompanied by ossicular chain
damage, the hearing loss can increase to between 30
and 50 dB. Finally, ossicular chain disruption with
an intact drumhead can account for 55 to 65 dB of
conductive hearing loss.
Speech discrimination testing is also useful.
Specifically, speech reception thresholds can help
determine whether a patient is a candidate for mid-
dle ear reconstructive surgery. Usually, the speech
discrimination and hearing loss correlate, but a
small percentage of patients have an unexpectedly FIGURE 10–1. Axial computed tomographic scan
low speech reception threshold and thus may bene- showing inflammatory soft tissue (arrow) filling the right
fit less from surgical intervention. Furthermore, ears middle ear with a large fibrotic polyp extending into the
with very poor speech discrimination scores are not external auditory canal and obscuring visualization of
suitable for middle ear reconstruction unless there the tympanic membrane.
268 Ballenger’s Otorhinolaryngology
SPECIAL CONSIDERATIONS
Histiocytosis X, an uncommon idiopathic disease
associated with proliferation of histiocytes, can
present in a fashion that mimics COM.48 The most
common otologic symptom is middle ear suppura-
A tion or otorrhea. Other manifestations include otitis
externa, SNHL, vertigo, and mastoid destruction.
Poor response to antibiotics, the presence of granu-
lation tissue in the absence of suppuration, or
associated signs of histiocytosis X such as hepato-
splenomegaly, diabetes insipidus, bone lesions, and
exophthalmos should alert one to this possibility. A
mastoidectomy is often required to obtain tissue for
diagnosis. A high index of suspicion is necessary
because treatment of histiocytosis X entails low-
dose radiation and occasionally chemotherapy.
Eosinophilic granuloma, a related idiopathic condi-
tion that usually has a monostotic presentation,
may present in a similar fashion. Again, the diagno-
sis is made based on histologic examination of tis-
B
sue obtained at surgery. These conditions should recovered from a single culture. In addition, nearly
always be suspected when there is bone destruction one half of all COM is caused by a combination of
in the absence of cholesteatoma. aerobic and anaerobic microorganisms.50
Another rare cause of COM is tuberculosis.
Patients present with thin, odorless otorrhea that is
often insidious and painless. Multiple TM perfora-
MEDICAL MANAGEMENT
tions are typically found on otoscopic examination. The treatment of COM generally begins with local
Labyrinthine involvement can lead to SNHL. Diag- care of the ear and outpatient medical management.
nosis is important because patients require treat- For medical management to be successful, aural toi-
ment with multiple antituberculous agents. After let is imperative. This intervention requires repeat
successful medical eradication of active infection, microscopic examination of the ear and diligent suc-
tympanoplasty may be performed. tioning. The main goal is to remove debris from the
A final consideration in the evaluation of EAC overlying the TM and middle ear cleft so that
COM is the potential complication of Meniere’s dis- topical antimicrobial agents can successfully pene-
ease, which has been found to occur subsequent to, trate to the middle ear mucosa. For patients with
and in some cases simultaneously with, COM.49 In otorrhea secondary to cholesteatoma, the hope is to
such patients, endolymphatic hydrops develops that minimize granulation tissue and perhaps achieve a
is secondary to the chronic inflammation, leading to dry ear prior to surgical intervention. However, this
vertigo and/or fluctuating SNHL. The differential is not always feasible, and some refractory cases will
diagnosis includes labyrinthine fistula and toxic require surgery to eliminate the otorrhea.
(serous) labyrinthitis. It may be possible to reduce the amount of gran-
ulation tissue contributing to the ongoing otorrhea,
particularly in the infected mastoid cavity. Before pro-
BACTERIOLOGY ceeding, one must be reasonably convinced that the
Although a severe episode of AOM can precede critical landmarks are properly identified and that
COM, the microorganisms responsible for each diag- there is not a dural defect with an encephalocele pres-
nosis differ significantly. Whereas Streptococcus pneu- ent. Judicious suctioning of immature granulation tis-
moniae, Haemophilus influenzae, and Moraxella sue or polyps may be undertaken provided that the
catarrhalis are the common microorganisms respon- otologist is certain of the landmarks in the cavity. Once
sible for AOM, Staphylococcus aureus and Pseudo- the base of the granulation tissue is reached, topical
monas aeruginosa are the common aerobic isolates in cautery with silver nitrate or 30% trichloroacetic acid
COM. Both are indigenous microorganisms. Staphy- is helpful. Silver nitrate is more hemostatic. Sometimes
lococcus aureus is a gram-positive coccus that col- topical 2% gentian violet is helpful as an astringent if
onizes the nares. Pseudomonas aeruginosa is a the bed of granulation remains active despite initial or
gram-negative rod that is extremely common in moist repeated treatment. If the granulation tissue is of sig-
environments and is generally found colonizing the nificant thickness or if a polyp is present, cup forceps
EAC. Thus, it is not surprising that it is often an may be needed to reach the base of the granulation. A
important pathogen in chronic middle ear disease. wick may be indicated if significant canal edema has
Anaerobic microorganisms may also play an resulted from secondary otitis externa.
important role in COM. Individual isolates and Most often, it is appropriate to proceed to sur-
percentages differ somewhat from study to study, gery if the ear does not respond to microscopic
most likely because of differences in culture tech- débridement and ototopical management. However,
nique.50 However, when fastidious microbiologic if more aggressive medical management is contem-
techniques are employed, the most common anaer- plated to avoid surgery or to obtain a dry ear prior
obic microorganisms cultured include Fusobac- to surgery, any soft tissue that is removed from the
terium sp, pigmented Prevotella, Bacteroides fragilis, external canal or mastoid cavity should be sent for
and Porphyromonas (previously known as Bac- microbiologic culture and sensitivity testing. When
teroides melaninogenicus).51 otorrhea is cultured, specimens should ideally be
Overall, COM should be viewed as a polymi- obtained from direct middle ear aspiration rather
crobial disease since multiple isolates are usually than from the ear canal whenever possible. Care
Chronic Otitis Media 271
must be taken to avoid contaminating the aspirate More recently, fluoroquinolone antibiotics
with debris from the EAC since microorganisms col- such as ciprofloxacin and ofloxacin have gained
onizing this region, Pseudomonas in particular, are popularity because of their antipseudomonal prop-
recovered from the middle ear space in only 50% of erties, minimal bacterial resistance, lack of ototoxic-
cases.52 Cultures with sensitivity are necessary to ity, and potential oral route of administration.
guide antibiotic therapy because most patients with Studies have found topical ciprofloxacin to be as effi-
COM have been treated with multiple prior antibi- cacious as topical tobramycin and to be superior to
otic regimens. For this reason, it is not surprising topical gentamicin.57,58 According to US Food and
that two-thirds of all COM patients are infected with Drug Administration (FDA) regulations, fluoro-
β-lactamase-producing microorganisms.53 quinolones are contraindicated in children, pregnant
Topical medications may include antibiotics, women, and nursing mothers.
antifungals, antiseptics, and corticosteroid prepara- Studies have revealed that the addition of top-
tions alone or in combination with other medica- ical corticosteroids in combination with antimicro-
tions. If otorrhea is profuse, it may be helpful to have bial agents improves response rates compared with
the patient irrigate the ear daily with a body tem- placebo or corticosteroids alone. 59,60 The anti-
perature half-strength solution of acetic acid (50% inflammatory properties of corticosteroids are
white vinegar diluted with warm water) prior to thought to allow increased antibiotic levels in the
application of otic drops. middle ear mucosa by decreasing tissue edema.
Popular topical antimicrobial agents have Currently, the ototopical combination that provides
included aminoglycosides such as gentamicin, the best profile of efficacy and safety consists of a
tobramycin, and neomycin in combination with fluoroquinolone and corticosteroid preparation in
polymyxin B sulfate because of their antipseudo- suspension form. This preparation is significantly
monal properties. Controversy has surrounded more costly than traditionally prescribed eardrops.
these agents since animal studies have demon- The use of systemic antibiotics in COM is lim-
strated ototoxic effects.54,55 However, human stud- ited by several factors. Once again, antibiotic pene-
ies have failed to show evidence that otic drops tration into the middle ear may be hampered by
cause SNHL in patients with COM.56 This discrep- mucosal edema. Systemic aminoglycosides carry a
ancy may be primarily attributed to the fact that risk of ototoxicity and require parenteral adminis-
the animals used in these experimental models tration with monitoring of serum levels. Oral
have a round window membrane that is much ciprofloxacin has proven to be a safe and effective
thinner than in humans, particularly when there is treatment for adults with COM; however, safety in
no reactive inflammation. Furthermore, the round patients under 18 years of age has not been estab-
window niche is extremely shallow and completely lished.61 Thus, the pediatric population is limited to
exposed in these experimental animals, but it tends parenteral antibiotics such as broad-spectrum peni-
to be deep and often protected by a mucosal cillins, cephalosporins, and aminoglycosides.
pseudomembrane in humans.55 More importantly, Patients with a TM perforation should be
most otolaryngologists believe that the risk of instructed about the importance of keeping their ear
SNHL from uncontrolled infection owing to COM canal and middle ear dry. An ear plug or a cotton
itself is greater than the risk associated with poten- ball impregnated with petrolatum jelly should be
tially ototoxic drops. used when showering, and ear plugs should be worn
The use of neomycin in ototopical prepara- when swimming. Hearing aid molds can cause an
tions continues to be extremely widespread owing to increase in middle ear humidity, which may initiate
long-standing prescribing habits and low cost, or perpetuate mucosal infection. For this reason,
despite the fact that almost no strains of patients with recalcitrant otorrhea who are resistant
Pseudomonas remain sensitive to this medication. In to medical treatment and are not candidates for
addition, there is a fairly high incidence of localized tympanoplasty should be fitted with bone-conduc-
and diffuse allergic reactions to the topical use of tion hearing aids or osseointegrated bone-anchored
neomycin. For these reasons, preparations contain- hearing aids.
ing neomycin should eventually fade from the oto- Medical management of COM may be difficult
topical armamentarium. for both the patient and the physician. Multiple
272 Ballenger’s Otorhinolaryngology
office visits are often required for adequate aural toi- • Tympanoplasty—an operation involving explo-
let. In addition, patients are asked to comply with a ration of the middle ear cleft through a transcanal
regimen that may include not only daily irrigation approach or through a postauricular incision. This
but also multiple administrations of otic drops is performed to eradicate disease from the middle
throughout the day. Medical treatment usually ear, repair TM defects, and reconstruct the ossicu-
requires 14 to 21 days. It is disappointing that up to lar chain. This procedure is frequently performed
50% of patients will have actively draining ears even in conjunction with a mastoidectomy.
when diligently compliant with a combination of • Canalplasty—an operation to widen the bony por-
corticosteroid and antibiotic drops.59 tion of the EAC, generally performed to improve
access and visualization for tympanoplasty and
postoperative care. This is often required for promi-
SURGICAL MANAGEMENT nent bony overhangs associated with the tympa-
The primary goal of surgery for COM is to eradicate nomastoid and tympanosquamous sutures.
disease and obtain a dry, safe ear. Restoration of • Ossiculoplasty—a procedure to reconstruct the
hearing is by necessity a secondary consideration ossicular chain.
because any attempt at middle ear reconstruction
Open (Canal Wall Down) Mastoidectomy Tech-
will fail in the setting of persistent inflammation and
niques These procedures have as their unifying
otorrhea.
theme a surgical strategy involving removal of vary-
Absolute indications for surgical intervention
ing portions of the bony EAC to obtain improved
include impending or established intratemporal or
access to the epitympanic and mesotympanic spaces
intracranial complications as described in Chapter
for management of chronic ear disease. These
11. Various pathologic conditions within the middle
approaches also leave some or all of the diseased
ear, such as cholesteatoma and chronic fibrotic gran-
spaces of the temporal bone permanently exterior-
ulation tissue, are irreversible and require elective
ized to help avoid recurrent disease:
surgical attention. In addition, patients with otor-
rhea failing to respond to medical treatment are sur- • Radical mastoidectomy—an operation to eradicate
gical candidates, as well as those who respond but or exteriorize extensive middle ear disease by
are left with a correctable conductive hearing loss or removing the posterior bony ear canal to open the
a TM defect. middle ear, mastoid, and epitympanum into one
There are numerous surgical techniques used common cavity. In doing so, remnants of the tym-
to address COM. Ultimately, the procedure chosen panic membrane, malleus, and incus are removed,
will depend on the nature and extent of the disease, leaving only the remaining portions of the stapes.
as well as the surgeon’s training and experience. If The TM is not reconstructed, and the eustachian
possible, it is ideal to restore eustachian tube func- tube may be left open or permanently obstructed
tion prior to surgical intervention. However, with tissue grafts.
attempts at performing eustachian tuboplasty have • Modified radical mastoidectomy—differs from a
been found to be extremely cumbersome and inef- radical mastoidectomy in that an attempt is made
fective. Studies have proven that transtympanic ven- to preserve or reconstruct the middle ear. Some-
tilation can lead to successful surgical results, even in times healthy TM and ossicular remnants are pre-
the setting of eustachian tube dysfunction.62 served. In the classic Bondy modified radical
procedure, atticoantral cholesteatoma is exterior-
ized without disturbing the intact pars tensa of
NOMENCLATURE IN SURGERY FOR CHRONIC the TM or the intact ossicular chain. This proce-
OTITIS MEDIA dure is appropriate in the rare instance when the
disease extends from the pars flaccida region lat-
• Myringoplasty—an operation limited to super- eral to the ossicles with extension into the
ficial repair of TM defects, without exploration antrum. More commonly, the ossicles are en-
of the middle ear cleft. These are generally gulfed or eroded by disease, and primary or
performed in an office or ambulatory operating staged reconstruction is required. When associ-
room setting. ated middle ear reconstruction is performed,
Chronic Otitis Media 273
many surgeons still apply the term modified rad- • Obliteration technique—a procedure in which
ical mastoidectomy, but the procedure is more muscle or a musculoperiosteal flap is used to oblit-
appropriately called an open or canal wall down erate a portion of the cavity following a canal wall
mastoidectomy with tympanoplasty. down mastoidectomy. If successful, the size of the
• Atticotomy—removal of ear canal bone including defect is minimized, which may avoid the need for
the lateral wall (scutum) of the epitympanum to long-term cavity care.
expose and exteriorize limited attic disease, usu- • Canal wall reconstructive technique—reconstruc-
ally lateral to healthy ossicles. tion of the posterior canal wall may be undertaken
• Atticoantrostomy—a strategy that ultimately cre- following a canal wall down mastoidectomy, either
ates a defect similar to the modified radical mas- primarily or at a later operation. In doing so, an
toidectomy by pursuing a posterior extension of attempt is made to convert the open cavity into a
the atticotomy approach. The surgeon’s intent is closed cavity.
to exteriorize rather than resect the matrix of the
cholesteatoma. The operation is performed by
entering the attic from the ear canal and then pro- ANESTHESIA AND PATIENT PREPARATION
ceeding posteriorly, gradually removing posterior
ear canal bone and exposing disease in the aditus Otologic surgery can be performed using local or
and antrum until it is fully exteriorized. This general anesthesia. The length of the procedure,
approach is appealing in that it exposes only that patient’s age and ability to cooperate, and the antic-
portion of the mastoid affected by disease; how- ipated level of stimulation must all be factored into
ever, it provides limited opportunity to identify the decision. Children will obviously require general
the surgical landmarks needed to prevent injury to anesthesia. However, local anesthesia may be pre-
the facial nerve. ferred in cases primarily involving ossicular recon-
• Meatoplasty—an operation performed to widen struction since it is possible to assess hearing
the cartilaginous and bony external auditory mea- improvement intraoperatively. When surgery involves
tus of patients undergoing a canal wall down pro- the TM, some surgeons will request that the anes-
cedure. The operation allows postoperative thesiologist avoid use of nitrous oxide, which may
inspection of the mastoid cavity and routine increase middle ear pressure and interfere with posi-
cleaning of debris from the mastoid bowl. tioning of the graft or TM.
Facial nerve monitoring is recommended in
congenital temporal bone anomalies because of the
Closed (Intact Canal Wall) Mastoidectomy associated risk of injury to a malpositioned facial
Techniques nerve. Monitoring is also recommended for revision
• Cortical mastoidectomy—removal of disease that is cases if the surgeon is uncertain of prior anatomic
limited to the mastoid antrum and air cell system, modifications or if the canal of the facial nerve is
preserving the posterior bony EAC wall. Generally, known to be dehiscent. Some surgeons advocate the
when this operation is performed without a tym- routine use of a facial nerve monitor in every
panoplasty, it is for chronic mucosal disease rather chronic ear operation. Although this is a controver-
than cholesteatoma. The middle ear contents are sial issue, those on both sides of the argument
not disturbed, although a tympanostomy tube strongly agree that monitoring is no substitute for
may be placed for improved ventilation. detailed knowledge of temporal bone anatomy and
• Tympanoplasty with intact canal wall mastoidec- adequate technical preparation on the part of the
tomy—an operation in which disease is removed surgeon.63
from the mastoid and middle ear while preserving The use of perioperative, prophylactic antibi-
the posterior bony wall of the EAC. Often the otics has been debated for decades. Many surgeons
mesotympanum is exposed by developing a poste- advocate the preoperative use of a broad-coverage
rior tympanotomy through the facial recess. Mid- antibiotic such as a cephalosporin, although con-
dle ear reconstruction may be performed trolled studies have suggested that the use of antibi-
primarily, but it is often staged in cholesteatoma otics does not reduce the risk of postoperative
cases. infection.64
274 Ballenger’s Otorhinolaryngology
Local injection of 1 or 2% lidocaine with a connective tissue graft in the hope that squamous
epinephrine (1:100,000) provides excellent vasocon- cell epithelium will migrate over the graft and seal
striction for transcanal procedures. More concen- the perforation. Various grafting materials are avail-
trated epinephrine solutions prepared by the surgeon able. Autogenous temporalis fascia is used most
or an assistant might provide improved vasocon- often because it is readily available through a postau-
striction, but errors in preparation have led to fatal ricular incision and is extremely effective. Other
consequences owing to the induction of cardiac alternatives include tragal perichondrium, perios-
arrhythmias. A 27- or 30-gauge needle mounted on teum, and vein. Preserved homograft materials such
a 1 mL syringe is recommended for ear canal injec- as cadaveric TM, dura, and heart valve have limited
tions. The most important injection is along the thick application because of concern for viral infection
vascular strip region of the canal skin, lying between and the transmission of Creutzfeldt-Jakob disease.
the tympanomastoid and tympanosquamous The two classic types of tympanoplasty are the
sutures. A subperiosteal injection will dissect freely lateral technique and the medial technique. The
under the skin and provide excellent vasoconstriction terms lateral and medial refer to the final relation-
and anesthesia. Another subperiosteal injection infe- ship of the graft to the fibrous layer of the TM rem-
rior to the tympanomastoid suture will control nant and the annulus tympanicus. In both
bleeding from the inferior canal wall skin. Slow infil- approaches, the graft is secured medial to the
tration will avoid the formation of a bleb beneath the malleus handle, if present. The lateral technique is
canal skin that may obscure the surgical field. When more technically demanding, but many surgeons
performing surgery under local anesthesia, addi- believe that it provides more reliable results when
tional injections should be made at the bony-carti- repairing large anterior or pantympanic defects. It is
laginous junction in all four quadrants. In addition, also useful when the ear canal anatomy is unfavor-
the local anesthetic is injected into the scalp overly- able, requiring an extensive canalplasty. The medial
ing the mastoid for postauricular procedures. Such technique tympanoplasty is commonly employed
injections are made prior to preparation of the ear to for smaller perforations in the posterior and central
allow adequate time for vasoconstriction. portions of the TM. However, with careful attention
Most cases will not require extensive shaving to surgical principles, this technique can be applied
of hair. Instead, adhesive drapes can be used to keep regardless of the size or location of the defect.
hair out of the surgical field. The ear and postauric-
ular region are prepared in the standard fashion, rec- Incisions Although various incisions have been
ognizing that it is not possible to sterilize the ear described in the past, the two most common
canal completely. If the patient has an open middle approaches used today are the transcanal tympa-
ear cleft owing to a TM perforation, a cotton ball nomeatal flap and the postauricular approach with
should be placed in the canal to prevent ingress of creation of a vascular strip. Each incision has advan-
the antiseptic solution. tages and disadvantages. Ultimately, the ear canal
anatomy, the position of the perforation, and the
surgeon’s judgment will determine the approach
TYMPANOPLASTY selected.
Hearing restoration is of secondary importance in The tympanomeatal flap is created by making
the surgical management of COM since any attempt longitudinal canal incisions superiorly, along the
at tympanoplasty and ossicular chain reconstruction tympanosquamous suture line (12 o’clock) and infe-
will fail in the setting of persistent otorrhea, inflam- riorly (6 o’clock). The incisions extend laterally from
mation, and eustachian tube dysfunction. Eradica- the TM approximately 6 to 8 mm and are connected
tion of mucosal disease remains the priority, and if by a transverse incision parallel to the annulus. Ele-
it is not reasonable to reconstruct the ossicular chain vation of the skin and periosteum anteriorly creates
at the first operation, middle ear reconstruction can a medially based U-shaped flap. The tympanomeatal
be performed at a later date. flap allows for excellent exposure of the posterior
part of the mesotympanum and is ideal for perfora-
Graft Material and Tympanoplasty Techniques tions located in this area. The flap is usually elevated
The goal of tympanoplasty is to repair the TM with using a transcanal approach and does not require a
Chronic Otitis Media 275
postauricular incision. Closure is simple, postopera- temporalis fascia or loose connective tissue lateral to
tive pain is modest, and the ear heals quickly. How- the fascia can be harvested and set aside to dry (Fig-
ever, it is important to realize that in inexperienced ure 10–6). To ensure adequate exposure, the soft tis-
hands, the transcanal approach can be cumbersome sue elevation continues to the zygomatic root,
owing to limited exposure imposed by the use of a exposing the superior portion of the bony canal. The
speculum and the ear canal configuration. ear canal skin is elevated and the vascular strip is
The major disadvantage of the transcanal incised, exposing the lumen of the bony EAC and
approach using a tympanomeatal flap is poor expo- the TM defect (Figure 10–7). Although the vascular
sure of the anterior mesotympanum. As the flap is strip approach provides excellent exposure of the
reflected forward, it remains within the surgical field middle ear, it does have certain drawbacks. The
and obscures visualization of this area. As a result, approach requires a postauricular incision and thus
anterior perforations are difficult to address, espe- increases postoperative discomfort. Proper elevation
cially in the setting of a prominent anterior canal and replacement of the vascular strip can be techni-
wall bulge. It is also difficult to visualize and address cally challenging, and there may be some residual
irreversible mucosal disease in the protympanum areas of exposed bone after it is replaced. As a result,
and eustachian tube orifice, both of which may con- healing may be delayed and problematic.
tribute to surgical failures by preventing satisfactory Regardless of the approach selected, 1 to 2 mm
postoperative eustachian tube function. The swing- of tissue at the margin of the TM perforation should
ing door technique may be used to improve anterior be excised (Figure 10–8). This disrupts the mucocu-
exposure. The tympanomeatal flap is bisected by an taneous junction at the border of the perforation
incision that extends medially through the annulus and starts the wound healing process essential to
and TM remnant into the posterior margin of the successful tympanoplasty. It is also essential to
perforation. The divided tympanomeatal flap can be remove any squamous cell epithelium that might
reflected superiorly and inferiorly for increased have extended under the edge of the perforation
exposure. Separating the drumhead remnant from onto the medial surface of the TM. Retained
the malleus handle may also be helpful in improving squamous elements can later develop into a
exposure to the anterior mesotympanum. cholesteatoma, requiring repeat surgical interven-
The postauricular, vascular strip approach is tion. In addition, any portions of the TM that are
an alternative means to achieve excellent exposure
of the entire mesotympanum. A superior ear canal
incision is made longitudinally along the tympa-
nosquamous suture line. An inferior incision is
made along the tympanomastoid suture line. These
incisions outline the so-called vascular strip, the
thickest and most vascular portion of the ear canal
skin. A medial incision is made parallel to the annu-
lus, connecting the two longitudinal incisions.
These incisions may be made through the ear canal
at the beginning of the procedure. However, they
are positioned more reliably when they are fash-
ioned from behind after the posterior canal skin has
been elevated through the postauricular incision.
Some surgeons elect not to divide the vascular strip
from the squamous cell epithelium of the TM, pre-
ferring instead to use this connection to simplify FIGURE 10–6. A right ear is pictured. The postauricu-
elevation of squamous cell epithelium from the lar incision has been made, exposing the temporal bone
fibrous remnant. and external meatus. A temporalis fascia graft is being
The postauricular incision is carried down to harvested. Reproduced with permission from Telian SA,
the level of the temporalis fascia superiorly and the Kemink JL. Lateral technique tympanoplasty. Oper Tech
mastoid cortex inferiorly. If a TM graft is planned, Otolaryngol Head Neck Surg 1992;3:214–9.
276 Ballenger’s Otorhinolaryngology
Medial Technique Tympanoplasty As a result of anatomic position, and the ear canal is filled with
the potential disadvantages discussed above, many Gelfoam and a cotton ball.
otologic surgeons prefer the medial technique tym-
panoplasty. When the connective tissue graft is Atelectatic Tympanic Membrane Nonperforated
placed medial to the TM remnant, the risk of TMs as seen in atelectatic and adhesive otitis media
retained squamous cell epithelium beneath the graft may also require tympanoplasty if there is signifi-
and the subsequent development of cholesteatoma is cant conductive hearing loss, retraction pockets with
essentially eliminated. early cholesteatoma formation, or persistent infec-
A medial technique tympanoplasty begins by tion. The atrophic, scarred TM is excised with
elevating a tympanomeatal flap through a transcanal preservation of the tympanic annulus. A tragal car-
or postauricular approach, exposing the middle ear tilage graft may be used to support the connective
(see Figures 10–7 and 10–8). The drum may be com- tissue graft in an attempt to prevent recurrence.
pletely elevated off the malleus handle, depending Gelfilm (Upjohn, Kalamazoo, Michigan), or Silastic
on the exposure required. The surgeon must take sheeting may be placed in an attempt to maintain
care to remove all squamous cell epithelial ingrowth ventilation of the middle ear cleft.
on the medial surface of the TM remnant and
malleus handle. Any irreversible mucosal disease is Postoperative Care Patients should refrain from
then removed from the middle ear. Unlike the lateral strenuous exercise, air travel, and vigorous nose
technique tympanoplasty, the fibrous layer of the blowing during the immediate postoperative period
TM has been elevated and will not provide support to help prevent graft dislocation. The patient is
for the connective tissue graft. Therefore, the middle examined approximately 1 to 2 weeks following the
ear and eustachian tube orifice are filled with surgery, at which point the cotton ball is removed
Gelfoam to prevent medial displacement of the from the lateral canal and superficial Gelfoam is suc-
graft. The connective tissue graft is seated medial to tioned. Corticosteroid-antibiotic eardrops are pre-
the handle of the malleus and TM remnant (Figure scribed for use two times a day. The patient should
10–14). The tympanomeatal flap is returned to its be examined every 2 weeks until healing is complete.
All Gelfoam should be removed by the second or
third postoperative visit. It is not unusual to require
8 to 12 weeks for complete healing, and crusting is
common for the first few months. The ear should be
observed periodically for the development of
delayed healing problems, lateralization of the graft,
or severe anterior blunting, which may require
repeat surgery. If a pearl of cholesteatoma develops
between the TM remnant and the graft, it will
become evident on otoscopic examination. These
cholesteatoma pearls are generally only a minor nui-
sance if detected early and can often be treated by
simple marsupialization and extraction in the office
without anesthesia.
ductive hearing loss measuring 10 dB or less if the and Creutzfeldt-Jakob disease limits the use of
ossicular chain was intact at the time of surgery.67 homografts.
CORTICAL MASTOIDECTOMY
Tympanoplasty failures often occur with eustachian
tube dysfunction and persistent inflammatory dis-
ease. For this reason, a cortical mastoidectomy is
often recommended as an adjuvant to tympano-
plasty.76,77 The goal is to eliminate all irreversible
mucosal disease, improve mastoid ventilation, and
FIGURE 10–17. If the anatomic relationships are favor- increase the buffering action of the mastoid cavity by
able, the incus may be sculpted to connect the malleus enlarging its volume. In accordance with Boyle’s law,
handle directly to the stapes capitulum. More commonly, significant changes in middle ear pressure may be
the stapes is eccentrically placed posterior to the malleus better tolerated with minimal effect on the position
handle, requiring an interposition graft that hooks onto of the TM.
the malleus and bridges the gap between the tympanic A cortical mastoidectomy is usually performed
membrane and the stapes head. through a postauricular incision. On children under
Chronic Otitis Media 283
2 years of age, the mastoid tip has not fully devel- tion of the mastoid tip air cells may be performed
oped, and care must be taken to avoid injury to the not only to increase the cavity volume but also to
superficially positioned facial nerve. The incision is remove all mucosal disease that could potentially
carried down to the mastoid cortex, and soft tissue is lead to future infection. On opening the mastoid tip,
elevated to expose the surface landmarks of the digastric ridge is defined medially. On occasion,
Macewen’s triangle. The superior boundary is the dissection of the zygomatic root is necessary to
temporal line extending posteriorly from the achieve adequate exposure of the epitympanum.
zygoma. This line corresponds to the probable level It is important to realize that in the setting of
of the tegmen mastoideum, the bony plate separat- chronic inflammation, the temporal bone tends to
ing the middle cranial fossa from the mastoid air be sclerotic, limiting easy access to some of the
system. The posterior boundary is a vertical line tan- important landmarks that often serve to guide the
gential to the posterior bony canal wall. Macewen’s surgeon. It is vital to identify the tegmen and follow
triangle is also bound by the bony projection of the it forward to the antrum if injury is to be avoided.
posterosuperior external auditory meatus known as Liberal use of irrigation is essential, and final polish-
the spine of Henle. Contained within these bound- ing of the tegmen plate with a diamond bur reduces
aries is a collection of bony perforations know as the bleeding.
cribriform area. The mastoid antrum is directly deep
to this area. INTACT CANAL WALL TYMPANOPLASTY WITH
After identifying the surface landmarks, the
cortex of the mastoid is opened using a large cutting
MASTOIDECTOMY
bur. Dissection should always proceed from a lateral In an attempt to expose and eradicate middle ear dis-
to medial direction, beveling all bony overhangs to ease better while preserving normal anatomic rela-
allow adequate exposure of the cavity. The tegmen tionships for improved sound conduction, the
tympani and sigmoid sinus must be identified and posterior tympanotomy approach was introduced.78
clearly defined to avoid injury. In doing so, the sin- This technique allows access from a cortical mas-
odural angle is opened. The petrosquamous septum, toidectomy defect into the posterior mesotympanum
also known as Körner’s septum, is removed and all by removal of the bony wall between the fossa incudis,
mastoid air cells anteromedial to the sigmoid sinus the second genu of the facial nerve, and the chorda
are opened (Figure 10–19). At this point, the mas- tympani. Since the access point into the middle ear is
toid antrum, the short process of the incus, and the the facial recess of the posterior part of the tympa-
horizontal semicircular canal are identified. Dissec- num, this operation is often referred to as a “facial
recess approach.” Alternative names for this approach
include closed cavity tympanoplasty with mastoidec-
tomy, intact canal wall tympanoplasty with mas-
toidectomy, and combined-approach tympanoplasty.
The major advantage of the intact canal wall
tympanoplasty with mastoidectomy is the avoid-
ance of a mastoid bowl that requires lifelong clean-
ing. In addition, healing is more rapid, and water
exposure precautions are unnecessary. By avoiding a
mastoid cavity and the associated meatoplasty,
patients can usually wear hearing aids within the
canal. However, these advantages come with a
higher risk of residual and recurrent disease. The
overall rate of recidivism is reported to range
between 5 and 71% depending on the surgeon’s
FIGURE 10–19. The cortical mastoidectomy is com- experience, although most series report rates in the
pleted. Disease in the mastoid antrum has been exposed, vicinity of 25%.79,80 Preservation of the posterior
with wide beveling of the cortical margins and skele- canal wall limits visualization and access to the mid-
tonization of the tegmen and sigmoid sinus plates. dle ear, especially to disease within the important
284 Ballenger’s Otorhinolaryngology
regions of the epitympanum, facial nerve, and oval the facial recess, a variably pneumatized triangle
window. As a result, residual middle ear disease may bounded laterally by the TM, medially by the second
be left behind in any of these locations. genu and descending portion of the facial nerve,
With respect to recurrent disease, an intact superiorly by the bone of the fossa incudis, and infe-
canal wall preserves a large cavity that must be ven- riorly by the chorda tympani. The bony EAC must
tilated by a marginally functional eustachian tube. If be thinned to allow access for the facial recess dis-
negative pressure persists, retraction pockets may section and eventual visualization of the most pos-
recur and lead to the formation of recurrent terior mesotympanic structures, such as the round
cholesteatomas. Interventions such as the placement window and the stapedius tendon. Dissection should
of Silastic sheeting within the middle ear may parallel the path of the facial nerve and chorda tym-
decrease the rate of postoperative adhesions and pani nerve. Copious irrigation will reduce the risk of
retraction pockets.81,82 The middle ear mucosa is thermal injury to these nerves and will allow identi-
allowed to regenerate, and the plastic sheeting may fication through intact thin bone of both the white
be removed at a later date if ossicular reconstruction neural sheath and associated capillary vessels. This
is undertaken at a second-stage procedure. In some process is known as “skeletonizing” the nerve and
cases, the presence of Silastic may be counterpro- should be accomplished without exposing the nerve
ductive by leading to intense middle ear fibrosis, fur- sheath. The facial nerve may be skeletonized and fol-
ther compromising ventilation. Reconstruction of lowed medially along the floor of the facial recess
canal wall defects that result from bone erosion by into the middle ear space.
disease or the surgical approach itself has decreased Successful completion of the facial recess
the incidence of retraction pockets and associated approach will allow visualization of the long process
recurrent disease.83 of the incus, the incudostapedial joint, the stapes
Because an intact canal wall tympanoplasty superstructure, the distal tympanic segment of the
with mastoidectomy does not address the problem of facial nerve, the round window niche, and possibly
negative pressure in the middle ear, ideal candidates the eustachian tube orifice and the cochleariform
are individuals with large pneumatized mastoids and process. However, the oval window and stapes foot-
well-aerated middle ear clefts. Patients with small plate are difficult to assess owing to the angle of
sclerotic mastoids and poor eustachian tube function visualization and the position of the facial nerve.
are often better served by removing the posterior The anterior epitympanum and sinus tympani are
canal wall as described in the next section. impossible to assess through the facial recess, and
As a result of the high rate of recidivism asso- residual disease can be left in these areas unless visu-
ciated with an intact canal wall tympanoplasty with alized and removed through the ear canal. Often in
mastoidectomy procedures, most surgeons advo- the presence of cholesteatoma, the incus is eroded or
cate a second-stage procedure when treating requires removal. In this setting, the epitympanic
cholesteatoma. This is especially true for children dissection can be extended through the fossa
since cholesteatomas in this population seem to incudus into the facial recess, improving visualiza-
behave more aggressively.78,82,84 This second proce- tion of the mesotympanic structures (Figure 10–20).
dure usually takes place between 6 and 18 months After removing all disease from the mastoid
postoperatively. During the operation, the middle and middle ear, Gelfilm or Silastic sheeting may be
ear and mastoid are explored for residual disease. If placed in the middle ear space if extensive mucosal
the middle ear is healthy, ossicular chain recon- dissection was required. This is placed in an attempt
struction is completed at that time. In the future, to prevent adhesions between the TM graft and any
the use of endoscopes may replace the need for exposed bone of the cochlear promontory, facial
open second-look procedures in select cases.85 recess, and epitympanum. The TM graft is then
Intact canal wall tympanoplasty with mas- placed. If there is a scutum defect owing to erosion
toidectomy can be a technically challenging proce- of the superior ear canal bone, this may be recon-
dure. A postauricular approach is used, and the structed using a HA attic reconstruction plate or an
order of middle ear exploration and mastoidectomy autogenous cartilage graft. Tragal cartilage may be
remains the surgeon’s decision. On completion of harvested with attached perichondrium and
the cortical mastoidectomy, attention is turned to trimmed to the size of the scutum defect (Figure
Chronic Otitis Media 285
skin are elevated, and a crescent-shaped portion of smaller cavity with a smoother lining and will help
the conchal cartilage is excised. The underlying soft prevent mucosalization of the antrum during the
tissues are excised, and hemostasis is obtained (Fig- healing phase.
ure 10–25). At the conclusion of the surgery, the meatus is
After removal of the posterior canal wall, the tacked open by suturing the base of the skin flaps
grafted TM cannot be returned to its original posteriorly to the mastoid periosteum. These sutures
anatomic location at the end of the procedure. must be placed strategically to avoid distortion of the
Instead, it must be draped from the anterior annu- pinna’s natural appearance. The periosteal layer is
lus over the facial ridge and the horizontal semicir- closed, and the conchal bowl and EAC skin flap are
cular canal. In doing so, a shallow middle ear space rotated medially into the defect. Ideally, the medial
is created. If the stapes remains intact and the foot- edge of the skin flap will reach onto the posterior
plate is mobile, the TM graft can be seated directly aspect of the fascia graft used to graft the middle ear
on the stapes capitulum to allow adequate sound and line the antrum. The grafts are covered with a
conduction. If the facial ridge is fairly high, it may be layer of Gelfoam, and the mastoid cavity is filled with
necessary to place a sculpted ossicle head or a piece antibiotic ointment. Merocel packs are placed later-
of cartilage from the meatoplasty over the stapes to ally in the meatus and expanded with otic drops to
improve contact with the graft. In the absence of a prevent early collapse of the meatoplasty, which
stapes, a sculpted incus can be interposed, or a com- could lead to stenosis. A mastoid dressing is then
mercially available TORP may be selected. Some of applied and kept in place for 24 to 48 hours. Since the
these are specifically designed with short necks to meatoplasty wound tends to have persistent oozing
accommodate the shallow middle ear space associ- of blood, a light dressing may be needed subse-
ated with an open cavity. If the entire cholesteatoma quently for several more days. The packing and
matrix has been removed, the fascia graft should be superficial Gelfoam are removed at the first postop-
large enough to resurface the antrum and obliterate erative visit, about 10 days after the operation. Open
any perilabyrinthine air cells. This will result in a cavities take a considerable amount of time to heal,
on the order of 6 to 10 weeks. During this period,
patients are seen every 2 to 3 weeks for débridement
of the cavity and management of granulation tissue.
Early granulations are suctioned away, and the base is
cauterized with silver nitrate or 30% trichloroacetic
acid. Early neomembrane formation should be rec-
ognized and disrupted before fibroblast ingrowth
causes mature scars that result in unfavorable cavity
anatomy. Ototopical drops with an antibiotic and a
corticosteroid should be continued until there is no
granulation tissue and the cavity is lined with skin. As
the healing progresses, immature squamous cell
epithelium that tends to weep and form crusts may
be painted with gentian violet. Patients can also par-
ticipate in cavity hygiene during this later healing
phase by performing daily irrigations with dilute
acetic acid. Postoperative visits may become less fre-
quent after this stage, although newly healed cavities
FIGURE 10–25. The successful canal wall down mas- tend to form crusts that may lead to inflammation
toidectomy requires a generous meatoplasty with and cavity infections. These crusts should be
removal of conchal cartilage and underlying soft tissues, removed at each visit, and any underlying granula-
with beveling of the cavity edges. This drawing demon- tion tissue may be cauterized.
strates grafting of the middle ear cleft and draping of the Long-term care entails visits every 6 months
graft into the posterior cavity, where it is overlaid with to 1 year, depending on the condition of the mas-
the vascular strip. toid cavity. Microscopic examination and removal
Chronic Otitis Media 289
of all crusts should be performed. Patients prone to mastoid cavity cleaning as well as water exposure
accumulation of dry crust benefit from application precautions.
of baby oil or mineral oil to the cavity once or twice
a week. Some cavities require the ongoing use of
occasional dilute vinegar irrigations, particularly if
MASTOID CAVITY OBLITERATION
they are prone to infection from swimming, from The mastoid cavity created by a radical or modified
hearing aid use, or during the humid months of radical mastoidectomy is at risk for chronic infec-
summer. tion and persistent drainage. In the setting of a
potentially large cavity, some surgeons elect to per-
form a mastoid obliteration procedure. The goal of
RADICAL MASTOIDECTOMY the procedure is to provide a dry ear that is compat-
Radical mastoidectomy entails exteriorization of the ible with the use of a hearing aid and also to elimi-
entire middle ear and mastoid by combining a canal nate the need for annual cavity cleaning.
wall down mastoidectomy with removal of the TM Various materials such as bone pate, cartilage,
and the ossicles (with the exception of the stapes if acrylic, and HA cement have been used to obliterate
present). In doing so, the mastoid, middle ear, and the mastoid cavity. Free abdominal fat grafts have
EAC become one common cavity. There is no attempt been used; however, postoperative atrophy must be
at middle ear reconstruction, and patients are left with taken into consideration. Many surgeons prefer the
a substantial conductive hearing loss. Given this sig- use of regional soft tissue flaps because of the
nificant functional deficit, radical mastoidectomy is associated blood supply. Such alternatives include
considered a last resort, usually after previous surgical pedicled temporalis muscle or postauricular mus-
attempts have failed or when it is not possible to culoperiosteal flaps as described by Rambo and
remove mesotympanic cholesteatoma. Radical mas- Palva, respectively.91,92
toidectomy is also indicated if middle ear ventilation The major disadvantage associated with oblit-
is impossible owing to complete inadequacy of eration of the mastoid is that disease can be buried
eustachian tube function. within the cavity. A CT scan may be required to
The incision, mastoidectomy, and removal of evaluate patients adequately for recurrent disease.
the posterior canal wall follow that described above. Thus, contraindications to mastoid obliteration
In addition, all remnants of the TM as well as the include widespread cholesteatoma and infected bone
malleus and incus are excised. The inferior aspect at the time of surgery. Generally, if the surgeon
of the tympanic ring is drilled down to remove observes the surgical principles and postoperative
disease in the hypotympanic air cells and allow care guidelines outlined above, the need for a mas-
communication between the cavity and the hypo- toid obliteration procedure would be unusual.
tympanum. The eustachian tube mucosa is in- Rarely, the surgeon may elect to perform a
verted, and the orifice is sealed with an ossicular complete closure of the external canal to isolate the
remnant, bone chips, muscle, or fascia in an attempt cavity internally rather than a meatoplasty to exteri-
to prevent access of nasopharyngeal inflammation orize it. This is most suitable when treating chronic
and secretions into the cavity. A meatoplasty is inflammation without cholesteatoma in the setting
required for postsurgical care and surveillance. of a profound hearing loss in the involved ear. In
Postoperative care follows that of a canal wall down such a case, the need for extended healing and long-
tympanoplasty with mastoidectomy. term cavity care are obviated. The modified Rambo
Despite the extensive nature of this surgery, closure is recommended to provide a cosmetically
aural drainage may persist owing to mucosalization acceptable and problem-free external closure (Fig-
of the middle ear space from the eustachian tube or ure 10–26).93 Care must be taken to remove all squa-
the hypotympanic cells. This is a particular problem mous elements from the ear deep to the point of
if both ears are involved. In such cases, use of con- closure. The primary and potentially serious risk of
ventional hearing aids may be impossible, and a such a procedure is the development of an expand-
bone-conduction hearing aid or bone-anchored ing undetectable cholesteatoma in the temporal
hearing aid is indicated. Other disadvantages of the bone. This may grow silently for many years, causing
radical mastoidectomy include lifelong need for no symptoms until a serious problem such as facial
290 Ballenger’s Otorhinolaryngology
5. Sade J, Halevy A. The natural history of chronic oti- 21. da Costa SS, Paparella MM, Schachern PA, et al. Tem-
tis media. J Laryngol Otol 1976;90:743–51. poral bone histopathology in chronically infected
6. Harker LA, Koontz FP. The bacteriology of ears with intact and perforated tympanic mem-
cholesteatoma. In: McCabe BF, Sade J, Abramson M, branes. Laryngoscope 1992;102:1229–36.
editors. Cholesteatoma: first international confer- 22. Meyerhoff WL, Kim CS, Paparella MM. Pathology of
ence. Birmingham (AL): Aesculapius; 1977. p. 264–7. chronic otitis media. Ann Otol Rhinol Laryngol
7. Kemppainen HO, Puhakka HJ, Laippala PJ, et al. Epi- 1978;87:749–60.
demiology and aetiology of middle ear cholesteatoma. 23. Schuknecht HF. Pathology of the ear. Philadelphia:
Acta Otolaryngol (Stockh) 1999;119:568–72. Lea and Febiger; 1993.
8. Tos M. Incidence, etiology and pathogenesis of 24. Jahn AF, Farkashidy J. Newer perspectives on the
cholesteatoma in children. Adv Otorhinolaryngol pathology of chronic otitis media. J Otolaryngol
1988;40:110–7. 1980;9:131–42.
9. Youngs R. Chronic suppurative otitis media— 25. Michaels L. An epidermoid formation in the devel-
mucosal disease. In: Ludman H, Wright T, editors. oping middle ear: possible source of cholesteatoma.
Diseases of the ear. New York: Oxford University J Otolaryngol 1986;15:169–74.
Press; 1998. p. 374–85. 26. Sie KC. Cholesteatoma in children. Pediatr Clin
10. Austin DF. Chronic otitis media. In: Ballenger JJ, North Am 1996;43:1245–52.
Snow JB, editors. Otorhinolaryngology head and 27. Lee RJ, Mackenzie IC, Hall BK, Gantz BJ. The nature
neck surgery. Baltimore: Williams and Wilkins; 1996. of the epithelium in acquired cholesteatoma. Clin
p. 1010–36. Otolaryngol 1991;16:168–73.
11. Wright T, Ludman H. Introduction to middle ear 28. Van Cauwenberge P, Vermeersch H, Otte L, Klu-
and mastoid disease. In: Wright T, Ludman H, edi- tyskens M. Relationship between secretory otitis and
tors. Diseases of the ear. New York: Oxford Univer- cholesteatoma. Epidemiological aspect. In: Tos M,
sity Press; 1998. p. 331–4. Thomsen J, Peitersen E, editors. Cholesteatoma and
12. Giebink GS. Otitis media update: pathogenesis and mastoid surgery. Amsterdam: Kugler & Ghedini;
treatment. Ann Otol Rhinol Laryngol 1992;101: 1989. p. 319–24.
21–3. 29. Sade J, Babiacki A, Pinkus G. The metaplastic and
13. Yoon TH, Schachern PA, Paparella MM, Aeppli DM. congenital origin of cholesteatoma. Acta Otolaryn-
Pathology and pathogenesis of tympanic membrane gol (Stockh) 1983;96:119–29.
retraction. Am J Otol 1990;11:10–7. 30. Ruedi L. Pathogenesis and surgical treatment of the
14. Sade J, Berco E. Atelectasis and secretory otitis media. middle ear cholesteatoma. Acta Otolaryngol (Stockh)
Ann Otol Rhinol Laryngol 1976;85:66–72. 1979; 361:1–45.
15. Andreasson L. Correlation of tubal function and vol- 31. Orisek BS, Chole RA. Pressures exerted by experi-
ume of mastoid and middle ear space as related to mental cholesteatomas. Arch Otolaryngol Head
otitis media. Ann Otol Rhinol Laryngol 1976;82: Neck Surg 1987;113:386–91.
198–203. 32. Thomsen J, Bretlau P, Kristensen HK. Bone resorp-
16. McClelland CA. Incidence of complications from tion in chronic otitis media. A light-microscopical
use of tympanostomy tubes. Arch Otolaryngol Head and histological investigation of acid phosphatase
Neck Surg 1980;106:97–9. activity. Acta Otolaryngol (Stockh) 1975;79:400–8.
17. Larsen PL, Tos M, Stangerup SE. Progression of 33. Gantz BJ, Maynard J, Bumsted RM, et al. Bone
drum pathology following secretory otitis media. In: resorption in chronic otitis media. Ann Otol Rhinol
Lim DJ, et al, editors. Recent advances in otitis Laryngol 1979;88:693–700.
media. Philadelphia: BC Decker; 1988. p. 34–8. 34. Kurihara A, Toshima M, Yuasa R, Takasaka T. Bone
18. Von Schoenberg M, Wengraf CL, Bleeson M. Results destruction mechanisms in chronic otitis media with
of middle ear ventilation with Goode’s tubes. Clin cholesteatoma: specific production by cholesteatoma
Otolaryngol 1989;14:503–8. tissue in culture of bone-resorbing activity attribut-
19. Wright CG, Meyerhoff, WL. Pathology of otitis able to interleukin-1 alpha. Ann Otol Rhinol Laryn-
media. Ann Otol Rhinol Laryngol 1994;103:24–7. gol 1991;100:989–98.
20. Yeger H, Minaker E, Charles D, et al. Abnormalities 35. Chole RA. Osteoclasts in chronic otitis media,
in cilia in the middle ear in chronic otitis media. Ann cholesteatoma, and otosclerosis. Ann Otol Rhinol
Otol Rhinol Laryngol 1988;97:186–91. Laryngol 1988;97:661–6.
292 Ballenger’s Otorhinolaryngology
36. Sade J, Halevy A. The aetiology of bone destruction in 52. Brook I. Chronic otitis media in children: microbio-
chronic otitis media. J Laryngol Otol 1974;88:139–43. logical studies. Am J Dis Child 1980;134:564–6.
37. Thomsen J, Bretlau P, Balslev Jorgensen M. Bone 53. Brook I. Prevalence of beta lactamase producing
resorption in chronic otitis media. The role of bacteria in chronic otitis media. Am J Dis Child
cholesteatoma, a must or an adjunct? Clin Otolaryn- 1985;139:280–3.
gol 1981;6:179–86. 54. Kohonen A, Tarkanen J. Cochlea damage by ototoxic
38. Mills P. Management of chronic suppurative otitis antibiotics by intratympanic application. Acta Oto-
media. In: Kerr A, Booth JB, editors. Scott-Brown’s laryngol (Stockh) 1969;68:90–7.
otolaryngology. Oxford (England): Butterworth- 55. Brummet RE, Harris RF, Lindgren JA. Detection of
Heinemann; 1997. 3/10/1-11. ototoxicity from drugs applied topically to the mid-
39. Blakley BW, Kim S. Does chronic otitis media cause dle ear space. Laryngoscope 1976;86:1177–87.
sensorineural hearing loss? J Otolaryngol 1998;27: 56. Fairbanks DNF. Antimicrobial therapy for chronic oti-
17–20. tis media. Ann Otol Rhinol Laryngol 1981;90:58–62.
40. Noordzij JP, Dodson EE, Ruth RA, et al. Chronic oti- 57. Fradis M, Brodsky A, Ben-David J, et al. Chronic oti-
tis media and sensorineural hearing loss: is there a tis media treated topically with ciprofloxacin or
clinically significant relation? Am J Otol 1995;16: tobramycin. Arch Otolarygol Head Neck Surg
420–3. 1997;123:1057–60.
41. Eisenman DJ, Parisier SC. Is chronic otitis media 58. Tutkun A, Ozagar A, Koc A, et al. Treatment of
with cholesteatoma associated with neurosensory chronic ear disease. Topical ciprofloxacin vs topical
hearing loss? Am J Otol 1998;19:20–5. gentamicin. Arch Otolaryngol Head Neck Surg
42. Walby AP, Barrera A, Schuknecht HF. Cochlear 1995;121:1414–6.
pathology in chronic suppurative otitis media. Ann 59. Browning GG, Gatehouse S, Calder IT. Medical
Otol Rhinol Laryngol 1983;103:3–19. management of active chronic otitis media: a con-
43. Blevins NH, Carter BL. Routine preoperative imaging trolled study. J Laryngol Otol 1988;102:491–5.
in chronic ear surgery. Am J Otol 1998;19:527–35. 60. Crowler JA, Simpson D. Medical treatment of
44. Mafee MF, Levin BC, Applebaum EL, et al. chronic otitis media: steroid or antibiotic with
Cholesteatoma of the middle ear and mastoid. Oto- steroid ear-drops? Clin Otolaryngol 1991;16:142–4.
laryngol Clin North Am 1988;21:265–93. 61. Gehanno P. Multicenter study of the efficacy and
45. Koltai PJ, Earnes FA, Parnes SM, et al. Comparison safety of oral ciprofloxacin in the treatment of chronic
of computed tomography and magnetic resonance suppurative otitis media in adults. The French Study
imaging in chronic otitis media with cholesteatoma. Group. Otolaryngol Head Neck Surg 1997;117:83–90.
Arch Otolaryngol Head Neck Surg 1989;115:1231–3. 62. Sheehy JL. Testing eustachian tube function. Ann
46. Jackler RK, Dillon WP, Schindler RA. Computed Otol Rhinol Laryngol 1981;90:562–5.
tomography in suppurative ear disease: a correlation 63. Roland PS, Meyerhoff WL. Intraoperative facial
of surgical and radiographic findings. Laryngoscope nerve monitoring: what is its appropriate role? Am J
1984;94:746–52. Otol 1993;14:1.
47. Campbell JP, Pillsbury HC. The use of computerized 64. Jackson CG. Antimicrobial prophylaxis in ear sur-
tomographic imaging in revision mastoid surgery gery. Laryngoscope 1988;98:1116–23.
for chronic otitis media. Am J Otol 1990;11:387–94. 65. Doyle PJ, Schluening AJ, Echevarria J. Tympanoplasty:
48. McCaffrey TV, McDonald TJ. Histiocytosis X of the should grafts be placed medial or lateral to the tym-
ear and temporal bone: review of 22 cases. Laryngo- panic membrane? Laryngoscope 1972;82:1425–30.
scope 1979;89:1735–42. 66. Plester D, Pulsakar A. The anterior tympanomeatal
49. Paparella MM, deSousa LC, Mancini F. Meniere’s angle: the aetiology, surgery, and avoidance of blunt-
syndrome and otitis media. Laryngoscope 1983;93: ing and annular cholesteatoma. Clin Otolaryngol
1408–15. 1981;6:326–8.
50. Brook I. Role of anaerobic bacteria in chronic otitis 67. Sheehy JL, Anderson RG. Myringoplasty: a review of
media and cholesteatoma. Int J Pediatr Otorhino- 472 cases. Ann Otol Rhinol Laryngol 1980;89:331–4.
laryngol 1995;31:153–7. 68. Brackmann DE, Sheehy JL, Luxford WM. TORPs and
51. Brook I. Otitis media: microbiology and manage- PORPs in tympanoplasty: a review of 1042 opera-
ment. J Otolaryngol 1994;23:269–75. tions. Otolaryngol Head Neck Surg 1984;92:32–7.
Chronic Otitis Media 293
69. Grote JJ. Reconstruction of the middle ear with 81. Sheehy JL. Tympanoplasty with mastoidectomy — a
hydroxylapatite implants: long-term results. Ann reevaluation. Laryngoscope 1970;80:1212–30.
Otol Rhinol Laryngol Suppl 1990;144:12–6. 82. Brackmann DE. Tympanoplasty with mastoidec-
70. Kessler A, Potsic WP, Marsh RR. Total and partial tomy: canal wall up procedures. Am J Otol 1993;14:
ossicular replacement prostheses in children. Oto- 380–2.
laryngol Head Neck Surg 1994;110:302–3. 83. Weber PC, Gantz BJ. Cartilage reconstruction of the
71. Daniels RL, Rizer FM, Schuring AG, Lippy WL. Par- scutum defects in canal wall up mastoidectomies.
tial ossicular reconstruction in children: a review of Am J Otolaryngol 1998;19:178–82.
62 operations. Laryngoscope 1998;108:1674–81. 84. Sismanis A, Hutchinson L, Abedi E. Chronic otitis
72. Rupa V, Krishnaswami H, Job A. Autograft ossicle selec- media: surgical failures and management. Am J Otol
tion in cholesteatomatous ear disease: histopathological 1989;10:460–5.
considerations. J Laryngol Otol 1997;111:807–9. 85. Rosenberg SI, Silverstein H, Hoffer M, Nichols M.
73. Brackmann DE, Sheehy JL. Tympanoplasty: TORPs Use of endoscopes for chronic ear surgery in chil-
and PORPs. Laryngoscope 1979;89:108–14. dren. Arch Otolaryngol Head Neck Surg 1995;
74. Silverstein H, McDaniel AB, Lichtenstein R. A com- 121:870–2.
parison of PORP, TORP, and incus homograft for 86. Cody DTR, McDonald TB. Mastoidectomy for
ossicular reconstruction in chronic ear surgery. acquired cholesteatoma. Follow up to 20 years.
Laryngoscope 1986;96:159–65. Laryngoscope 1984;94:1027–8.
75. Emmett JR, Shea JJ Jr, Moretz WH Jr. Long-term 87. Bondy G. Totalaufmeisselung mit Erhaltung von
experience with biocompatible ossicular implants. Trommelfell und Gehork nochelchen. Monatsschr
Otolaryngol Head Neck Surg 1986;94:611–6. Ohrenheilkd 1910;44:15–23.
76. Jackler RK, Schindler RA. Myringoplasty with simple 88. Toner JG, Smyth GDL. Surgical treatment of
mastoidectomy: results in eighty-two consecutive cholesteatoma: a comparison of three techniques.
patients. Otolaryngol Head Neck Surg 1983;91:14–7. Am J Otol 1990;11:247–9.
77. Ruhl CM, Pensak ML. Role of aerating mastoidec- 89. Dodson EE, Hashisaki GT, Hobgood TC, Lambert
tomy in noncholesteatomatous chronic otitis media. PR. Intact canal wall mastoidectomy with tym-
Laryngoscope 1999;109:1924–7. panoplasty for cholesteatoma in children. Laryngo-
78. Naclerio R, Neely JG, Alford BR. A retrospective scope 1998;108:977–83.
analysis of the intact canal wall tympanoplasty with 90. Nadol JB. Causes of failure of mastoidectomy for
mastoidectomy. Am J Otol 1981;2:315–7. chronic otitis media. Laryngoscope 1985;95:410–3.
79. Sheehy JL. Mastoidectomy: the intact canal wall pro- 91. Rambo JHT. Primary closure of the radical mas-
cedure. In: Brackmann DE, Shelton C, Arriaga MA, toidectomy wound; a technique to eliminate postop-
editors. Otologic surgery. Philadelphia: WB Saun- erative care. Laryngoscope 1958;68:1216–27.
ders; 1994. p. 211–24. 92. Palva T. Mastoid obliteration. Acta Otolaryngol
80. Parisier SC, Hanson MB, Han JC, et al. Pediatric Suppl (Stockh) 1979;360:152–4.
cholesteatoma: an individualized, single stage 93. Meyerhoff WL, Stringer SP, Roland PS. Rambo pro-
approach. Otolaryngol Head Neck Surg 1996;115: cedure: modification and application. Laryngoscope
107–14. 1988;98:795–6.
CHAPTER 11
Complications of acute and chronic otitis media first two decades of life. Table 11–1 illustrates the age
can cause grave morbidity and even mortality. Even distribution of extracranial (cranial), intracranial,
though the incidence and prevalence of these com- and combined complications in a large series of
plications have dramatically declined, their poten- patients from the rural Natal province in South
tial gravity requires physicians to have a thorough Africa. Nearly 80% of cranial complications and
understanding of the diagnosis and management of 70% of intracranial complications occurred in chil-
each one. Because of the decreased prevalence of dren in their first two decades of life. Cranial com-
these complications and changes in the health care plications, led by postauricular abscess, most
delivery system, many otolaryngologists-in-train- commonly occurred in children under age 6 years.1
ing today have no opportunity to see patients with In a series of 93 intracranial and cranial complica-
these problems. This chapter first provides an tions of otitis media that occurred in Turkey during
overview of the complications of acute and chronic the 1990s, 58% were present in patients under age 20
otitis media, including their etiology, pathology, years.2 For unexplained reasons, males are affected
pathophysiology, diagnosis, and treatment. The lat- nearly twice as often as females.
ter part of the chapter presents a review of each People who are poor, live in overcrowded sur-
complication. roundings, and have poor personal hygiene, poor
Cranial and intracranial complications of oti- health, decreased resistance to infection, inadequate
tis media can occur in individuals of any age, but health education, and limited access to medical care
they occur much more commonly in children in the have the highest incidence of these complications.
TABLE 11–1. Age Distribution of 268 Patients with Complications of Otitis Media between January 1985
and December 1990.
Cranial Intracranial Cranial and Intracranial
Age (yr) (n = 87) (n = 150) (n = 31)
% % %
0–50 33.3 8.0 6.5
6–10 23.0 21.3 19.4
11–20 21.8 39.3 38.7
21–30 9.2 8.6 12.9
31–40 3.4 12.6 9.7
41–50 5.7 6.0 6.5
51–60 3.4 0.6 3.2
> 60 0.0 3.3 3.2
294
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 295
For example, most of the current reports of otogenic ACUTE OTITIS MEDIA
brain abscesses come from South Africa and devel-
oping countries. Only an occasional reported series An estimated 85% of all children experience at least
is from North America. Although the number of one episode of acute otitis media, making it the most
patients with acquired or iatrogenic immunodefi- common bacterial infection of childhood.3 Predis-
ciency has increased, large series of patients with posing factors include being of a young age or the
complications of otitis media have not been male sex, receiving bottle feedings, and being
reported in patients with human immunodeficiency exposed to a daycare environment, crowded living
virus (HIV) infection or acquired immune defi- conditions, or smoking within the home. Medical
ciency syndrome (AIDS) or in those receiving conditions such as cleft palate, Down syndrome, and
immunosuppressive therapy following organ trans- mucous membrane abnormalities such as cystic
plantation, even though such individuals do have fibrosis, ciliary dyskinesia, and immunodeficiency
suppurative ear disease. states also predispose individuals to otitis media.
Table 11–2 shows the classification of cranial Acute otitis media is a bacterial infection of the
and intracranial complications, and Table 11–3 middle ear space characterized by vascular dilatation
illustrates the relative frequencies of those compli- and proliferation (manifested externally by ery-
cations reported in two recent series.1,2 The domi- thema), mucosal edema, exudation, bacterial prolif-
nant cranial complication is postauricular abscess, eration, white blood cell infiltration, and pus
and the dominant intracranial complication is formation. Acute otitis media refers only to an acute
meningitis. Unlike many areas of medicine, the infection that arises de novo, from a previously nor-
complications tend to occur multiply, especially the mal middle ear, rather than an acute clinical infec-
intracranial complications, as shown in Tables 11–4 tion arising in a chronically abnormal middle ear,
and 11–5. Whereas all of the complications origi- such as one with long-standing otitis media with
nate from infection in the pneumatized spaces of effusion. This distinction is important because the
the middle ear and mastoid, the mechanisms by pathophysiology of the otitis and the development
which complications occur in acute otitis media dif- of complications are different in acute versus
fer from those leading to complications in chronic chronic otitis media. Acute otitis media may resolve
otitis media. Therefore, these two entities are briefly completely and spontaneously with or without treat-
discussed separately. ment, or it may cause a complication while remain-
ing in its acute stage. Conversely, it may persist into therapy. After treatment, the physician should docu-
a subacute or chronic state. Factors that favor the ment that the acute otitis media has completely
acute infection progressing to a subacute or chronic resolved by otoscopy and a normal tympanogram. If
otitis media include microorganism virulence, the complication was intracranial, a computed
decreased host resistance, and inadequate or inap- tomographic (CT) scan or a magnetic resonance
propriate antibiotic therapy. image (MRI) should be obtained.
After the first few weeks of life, acute suppurative
otitis media is caused primarily by three microor-
ganisms: Streptococcus pneumoniae, Haemophilus
CHRONIC OTITIS MEDIA
influenzae, and Branhamella catarrhalis, compro- Whereas acute otitis media is primarily a middle ear
mising roughly 30, 20, and 10% of isolates, respec- infection that extends into the contiguous mastoid,
tively.3 Optimal treatment for acute suppurative chronic otitis media often displays a dominant mas-
otitis media with complications includes appropri- toid infection with concurrent otitis media. In the
ate antibiotic treatment of the underlying infection mastoid, infection persists in the numerous small air
for 10 days, in addition to tympanocentesis, or cells easily or more easily than it does in the rela-
myringotomy and placement of a ventilating tube. tively large single cell of the middle ear. Chronic oti-
Tympanocentesis is used primarily to obtain mate- tis media is present when an infectious process
rial for culture to identify the offending microor- persists for a period longer than the 1 to 3 weeks
ganism and its antibiotic sensitivities, but it can also usually necessary for acute otitis media to resolve in
somewhat reduce the bacterial population. Doing a a previously normal ear. Chronic otitis media can
myringotomy and tube placement also provides the occur with or without a cholesteatoma when there is
physician with material to identify the involved a tympanic membrane perforation. A third type of
microorganism while simultaneously allowing the chronic otitis media is emerging, especially in young
physician to remove most of the bacteria from the children who develop persistent otorrhea with a
middle ear space and to introduce topical antibiotic patent middle ear ventilating tube.
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 297
TABLE 11–4. Intracranial Complications in 181 Patients with Otitis After Singh and Maharaj1
Complication n No. with Associated Complications AC%
Meningitis 22 4 18.2
Brain abscess 93 15 16.1
Subdural empyema 36 12 33.3
Epidural abscess 19 19 100.0
Lateral sinus thrombosis 36 10 27.8
AC% = percentage of patients with each complication who also had additional cranial or intracranial complication(s). Adapted
from Singh B and Maharaj TJ.1
When the infection in the middle ear and mas- water. A series of events, including treatment with
toid will not resolve, mucosal edema and exudation antibiotic drops, treatment with oral antibiotics,
increase, and the mucous glands and secretory ele- repeated contamination, repeated cultures and sensi-
ments proliferate. Mucosal edema in the small spaces tivities, increasing patient and physician frustration,
between the mesotympanum and the epitympanum decreasing patient compliance, and fungal over-
and in the aditus between the epitympanum and growth, frequently results in resistant microorganisms
mastoid antrum block the normal pathways for aer- developing. The resistant bacteria most often found
ation and decrease both oxygenation and vascularity. are Pseudomonas aeruginosa, Achromobacter xylosoxi-
At the same time, the blockage prevents topical dans, and even methicillin-resistant Staphylococcus
antibiotic and anti-inflammatory agents from reach- aureus. It is also common to have a clinically signifi-
ing the attic and mastoid. Radiographically, the mas- cant fungal infection of both the external auditory
toid air cell system is partly or completely opaque, canal and the middle ear and mastoid. Although the
reflecting the loss of aeration. author has not seen cranial and intracranial compli-
These changes are accompanied by a dramatic cations from this type of infection, granulation tissue
change in the bacterial flora from acute to chronic he has noted at surgery suggests that possibility.
otitis media and mastoiditis. Harker and Koontz cul- Patients with intracranial or multiple compli-
tured 30 cholesteatomas at surgery and isolated at cations often appear more systemically ill than they
least one anaerobic microorganism in 67% of the should be from otitis alone. They can present with
cases, at least one aerobic microorganism in 70%, toxicity or with obtundation, manifesting depressed
and both aerobes and anaerobes in 50%.4 In 57% of
the cholesteatomas, multiple microorganisms were TABLE 11–5. Interrelationship of Intracranial
cultured, and in 30%, five or more bacteria were Complications
identified. Even when there was no clinical infection,
anaerobic microorganisms, such as Propionibac- Complication n Men BA EA SE LST
terium acnes, were frequently isolated. Significantly, Meningitis 22 — 2 — 1
the study showed that an ear with a cholesteatoma is
Brain abscess 93 — 3 9 3
highly likely to harbor multiple bacteria of both
anaerobic and aerobic types. Multiple micro- Subdural
organisms and anaerobic bacteria also have been empyema 36 — 9 2 1
identified frequently in chronic otitis media without Epidural abscess 19 2 3 2 5
cholesteatoma.
Lateral sinus
Chronic otitis media that develops in patients
thrombosis 36 1 3 5 1
with indwelling middle ear ventilating tubes has a dif-
ferent bacterial flora. In most instances, these cases Adapted from Singh B and Maharaj TJ.1
begin during an upper respiratory infection or when Men = meningitis; BA = brain abscess; EA = epidural abscess;
the external auditory canal is contaminated with SE = subdural empyema; LST = lateral sinus thrombosis.
298 Ballenger’s Otorhinolaryngology
levels of consciousness that can vary from lethargy bone fracture, congenital dehiscences, or other con-
to total unresponsiveness. Focal neurologic signs ditions that removed the intervening bone. The
may be absent, subtle, or florid. The physical exam- mechanisms by which bone is actively resorbed,
ination of the ear itself usually does little to pinpoint although incompletely understood, probably include
a specific complication unless there is an obvious enzymatic degradation, suppuration, and decreased
postauricular, cervical, or temporal abscess. blood supply.
PATHOPHYSIOLOGY DIAGNOSIS
Sometimes a complication occurs during the first History Because a thorough understanding of the
few days of an episode of acute otitis media. This can chronology of the events is critical to determining
result from bacteremia accompanying acute otitis the pathophysiology, the clinician must obtain a
media initiating a hematogenous complication such complete history of the present illness. The clinician
as meningitis, or the bacteria proliferating in the must establish when the patient’s ear was last free of
middle ear can gain access to adjacent or distant disease and perfectly normal to differentiate acute
structures and continue the infection at the new otitis media from chronic otitis media because the
location. A patient may develop partial or complete bacteriology, medical treatment, and most probable
facial paralysis if he or she has a congenital dehis- complications are different for each. Answers to
cence of the bony fallopian canal above the stapes. If questions such as (1) when did a physician last
there are preformed pathways leading to the examine the involved ear? (2) what is the past history
meninges or the labyrinth, patients with acute otitis and treatment of the patient’s otitis media? (3) did
media are at risk of developing meningitis, subdural the patient use an antibiotic for otitis media in the
effusion, or suppurative labyrinthitis. Developmen- involved ear in the past month? and (4) what were
tal labyrinthine abnormalities, such as enlarged the order of appearance and the magnitude of the
vestibular aqueducts or Mondini’s deformity, often different symptoms that comprise the present prob-
have such pathways. In older children and adults, lem? are essential to an accurate diagnosis. Finally,
bacteria can propagate along preformed pathways the physician must obtain any objective evidence
left from previous surgery or temporal bone frac- that the ear was normal recently (tympanogram,
tures. But with acute otitis media, rarely is there radiographic study that included the ears). The
granulation tissue formation or bone destruction; physician must gather from the patient or a knowl-
complications develop by hematogenous dissemina- edgeable accompanying person or through tele-
tion or by direct extension of infection along pre- phonic contact with physicians’ offices and hospitals
formed pathways. Accordingly, the usual medical information about the involved ear including previ-
treatment of the acute otitis media will resolve the ous diagnoses, all operations, and recent medical
otitis portion, and mastoidectomy is not necessary. and surgical treatment.
Therefore, it is critical to know that the middle ear Symptoms of acute otitis media include pain,
was normal before the current bout of otitis media fever, and fussiness, but otorrhea is relatively
began. uncommon. The cardinal symptom of chronic oti-
In chronic otitis media and mastoiditis, com- tis media is painless, purulent drainage. Changes in
plications are always associated with some combina- the drainage may suggest the possibility of a com-
tion of bone destruction, granulation tissue plication. The cessation of drainage with the onset
formation, or the presence of cholesteatoma. Bacte- of pain suggests the presence of aditus or epitym-
ria gain access to the involved structures most com- panic block with increased pressure within the
monly by direct extension from mastoid infection mastoid. The onset of imbalance or vertigo at the
and by infecting and propagating along veins leading same time suggests the possibility of imminent
from the mastoid to adjacent structures. Direct labyrinthitis.
extension can come about as a result of bone resorp- Intracranial complications, most notably
tion from cholesteatoma or osteitis, or it can occur meningitis, intraparenchymal brain abscess, and
without bone erosion if the patient has preformed subdural empyema, can alter the patient’s level of
pathways from previous mastoid surgery, temporal consciousness. Fifteen percent of Singh and
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 299
Maharaj’s patients were drowsy on admission, 18% Changes in the patient’s symptoms and the physical
were stuporous, and 2% presented in coma.1 Estab- signs provide valuable information for understand-
lishing the chronology of this alteration of senso- ing the evolving pathophysiology and determining
rium will help the physician differentiate among the appropriate treatment.
diagnoses of brain abscess, meningitis, and subdural Begin the otologic examination with an assess-
empyema. A brain abscess takes weeks to develop, ment of the color, size, shape, and position of the
whereas it takes only a few hours to several days for pinna compared with the opposite side. Make note
meningitis and subdural empyema to be fulminant of any erythema, tenderness, or drainage and any
and progress to coma. evidence of trauma, excoriation, or protrusion out-
In eliciting the patient’s past history, social his- ward or downward. Next observe the regions adja-
tory, family history, and review of systems, the clini- cent to the auricle and note any swelling, erythema,
cian should gather not only information relevant to tenderness, purulent drainage, or fluctuance.
the present illness but also all of the information the Examine the external auditory canal and tym-
anesthesiologist needs to evaluate a patient for a sev- panic membrane using a microscope and fine suc-
eral-hour surgical procedure. tion. If purulent secretions are present, culture them.
Document the presence of any edema and whether
Physical Examination The vital signs, especially it primarily affects the posterior superior bony canal
the temperature, provide a pretreatment baseline wall or if it affects the entire canal circumference.
and one parameter for following the course of the Make a drawing of the tympanic membrane illus-
disease and the treatment; however, if the patient has trating any perforation, granulation tissue, or
previously received oral or parenteral antibiotics, he epithelial debris and any erosion of the scutum. Per-
or she may present without a fever. Some patients form pneumatic otoscopy looking for conjugate
remain afebrile during the entire course of illness, deviation of the eyes that strongly suggests the pres-
despite having significant cranial or even intracra- ence of a labyrinthine fistula. Make a clinical impres-
nial complications, but the temperature curve can sion whether the patient has acute otitis media,
sometimes provide useful information (see “Lateral chronic otitis media with perforation, or a choles-
Sinus Thrombosis”). teatoma before obtaining any imaging studies.
A complete neurologic examination is essen- The tympanic membrane may appear normal
tial. Make a thorough mental assessment of the or near normal even when an otitic complication is
patient, and note any alteration in mental state. Eval- present because it reflects only the status of the mid-
uate the station and gait and perform Romberg’s and dle ear medial to it. Whereas mastoid infection
sharpened Romberg’s tests. Evaluate the motor and always begins with a middle ear infection, suppura-
sensory function of the extremities and perform a tion in these two locations may proceed differently
complete cranial nerve evaluation, including an in that the middle ear may revert to normal or near
assessment of vision, extraocular muscle function, normal under treatment, whereas the mastoid may
facial nerve function, and facial sensation. Note not. Especially in the presence of an aditus block, the
whether there is nystagmus, either in the straight- middle ear may appear nearly or completely normal
ahead cardinal position or with the eyes deviated 30 after several courses of antibiotics, whereas symp-
degrees to the left and to the right. Evaluate cerebel- toms from the mastoid persist (see “masked mas-
lar function by checking the alternate motion rate of toiditis”). When evaluating a patient with any
the extremities, determining if past pointing is pres- infectious condition that could be caused by acute or
ent or absent, and performing the finger-to-nose chronic otitis media, the clinician should obtain a
test. Assess ocular saccades and smooth pursuit. It is CT scan to rule out chronic otitis as the cause even
critical to determine if nuchal rigidity is present and, if the tympanic membrane appears normal and
if so, to perform Kernig’s and Brudzinski’s tests. there is no history of ear disease.
Observe the optic disks with an ophthalmoscope to
determine if papilledema is present. Write down all Laboratory Examination The complete blood cell
of your positive and negative findings so that there is count will document the patient’s relative degree of
a written record of the patient’s status at a specific leukocytosis and ensure that his or her hemoglobin
time to compare to any subsequent changes. and hematocrit are adequate for safe general anes-
300 Ballenger’s Otorhinolaryngology
thesia. The individual health needs of the patient and diagnosing intracranial complications because
the necessity for a general anesthetic will determine paramagnetic contrast agents such as gadolinium-
the need for any other hematologic studies. DTPA (diethylenetriamine pentaacetic acid) cross
the blood-brain barrier in areas of cerebritis or
Imaging Techniques Computed tomographic abscess. Meningeal enhancement is much more eas-
scanning is essential for all patients suspected of ily seen with MRI than with CT scanning in which
having complications of otitis media. It is a fast and the adjacent bony skull often obscures the meninges.
reliable method for assessing the status of the mid- The T2-weighted images of an MRI can demonstrate
dle ear and mastoid air cell system and diagnosing intraparenchymal edema from subtle brain infection
intracranial complications of otitis media.5,6 It is much earlier than can a CT scan. When otitic com-
unparalleled for showing the bony details of the plications are suspected, the clinician usually obtains
middle ear, epitympanic, and mastoid structures and both CT and MRI scans if the patient’s condition
documenting the degree to which the normally aer- allows because much of the information from the
ated pneumatized spaces may be opacified by the two studies is complementary.
inflammatory process. It clearly shows demineral-
ization and loss of the bony septae of air cells in coa- Lumbar Puncture To determine the presence of
lescent mastoiditis and reveals erosion of the bony meningitis, the physician must perform a lumbar
plates covering the sigmoid sinus and cerebellum or puncture, measure the patient’s cerebrospinal fluid
tegmen of the middle ear and mastoid, even erosions (CSF) pressure at the beginning and end of the pro-
of the bony labyrinth itself. Computed tomographic cedure, examine the CSF sample for the presence of
scans must include views taken in an algorithm to bacteria on direct smear, and determine the concen-
assess soft tissue changes and wide (“bone”) algo- trations of glucose, chloride, and protein for com-
rithm views to evaluate bone erosion. parison with their concentrations in serum. Lumbar
Computed tomographic scans can help to puncture should be undertaken only after ophthal-
establish the specific primary otologic diagnosis moscopic examination and CT scan have ruled out
(acute otitis media, chronic otitis media, choles- significant increased intracranial pressure that could
teatoma) as well as the diagnosis of several of the result in herniation of the cerebellar tonsils during
specific cranial and intracranial complications of or after the procedure. Lumbar puncture is con-
otitis media. In addition to their diagnostic value, traindicated in the presence of brain abscess and
CT scans are useful to assess the results of therapy subdural empyema.
and to provide a baseline post-treatment study of
the mastoid for comparison in case of further
complications. TREATMENT
When the patient is somnolent or unstable and Although each complication has its own separate
when intracranial complications are suspected, CT treatment, there are certain general management
scanning may be the initial study of choice because principles for treating the underlying otitis. For
it is fast and gives the health care team better access each patient, the treatment of the underlying acute
to the patient during the study than MRI does. Even or chronic otitis media and the treatment of any
without enhancement, CT scanning may be an ade- complications can be medical or surgical and can
quate diagnostic tool for a febrile, stuporous patient be administered sequentially or concurrently. In
with meningeal irritation when ruling out the pres- nearly all instances of complications resulting from
ence of an intraparenchymal brain abscess or com- acute otitis media, appropriate antibiotic therapy
municating hydrocephalus prior to performing will be sufficient to resolve the otitis without any
lumbar puncture to establish the diagnosis of need for surgery. This will usually include aspira-
meningitis. However, when using CT to diagnose tion by tympanocentesis or myringotomy, as previ-
cerebritis, cerebral abscess, subdural empyema, and ously discussed.
ventriculitis, intravenous injection of an iodinated When the complications have resulted from
contrast agent is essential. chronic otitis media and mastoiditis, initial antibi-
Magnetic resonance imaging is a far more otic therapy should employ broad-spectrum antibi-
sensitive imaging technique than CT scanning for otics effective against anaerobic as well as aerobic
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 301
microorganisms. In all of these cases, some form of brain abscess, follow-up evaluation with enhanced
mastoidectomy will be required. When surgery is MRI 2 to 4 weeks after treatment is recommended.
necessary for intracranial complications, the neuro-
surgeon operates first, immediately followed by the
otologist performing a mastoidectomy at the same CRANIAL (INTRATEMPORAL)
sitting if the patient’s condition permits. In most COMPLICATIONS
instances (except for brain abscess and subdural
empyema), both the chronic otitis media and its
COALESCENT MASTOIDITIS
complications are treated entirely through the mas- Etiology Sometimes when a patient has acute oti-
toid. When both neurosurgery and otologic surgery tis media and mastoiditis that persists unabated for
are necessary, the surgeons must carefully and 2 to 4 weeks, coalescent mastoiditis sets in. This is an
methodically plan and coordinate the order of the acute progressive clinical infection with correspon-
procedures, patient preparation, draping, and inci- ding changes in the bone and mucoperiosteum of
sions to decrease the duration of general anesthesia the mastoid air cell system. Coalescent mastoiditis is
and to optimize the chances of a safe and effective a disease of the young, especially males. Most
surgical result. patients are 4 years old or younger. Bacterial viru-
Performing a mastoidectomy under these cir- lence and decreased host resistance are important in
cumstances is difficult because vascularity increases its etiology, but mastoid development also plays a
and landmarks are more obscured. The following role. The condition rarely develops in children who
general principles are helpful guidelines. After have had chronic ear disease or in those with poorly
removal of the mastoid cortex, complete all bony pneumatized mastoids containing few air cells.
dissection using diamond instead of cutting burs Rather, it tends to occur in patients with well-devel-
and use copious suction-irrigation. This will mini- oped air cell systems that contain numerous small
mize the chance of inadvertent trauma to important pneumatic spaces and in those who have had little or
underlying structures. If preoperative scanning iden- no previous otologic disease.
tified the sites of the complications, complete the
surgery in the portions of the mastoid away from the Pathology Initially, hyperemia and edema of the
complication sites first. This will improve hemosta- mucoperiosteal lining of the mastoid air cells block
sis and visibility. When no cholesteatoma is associ- the narrow aditus and disrupt aeration. The mucous
ated with the mastoiditis, leave the external auditory membrane thickens, and impaired ciliary function
canal wall intact unless visibility is inadequate.1 prevents normal middle ear drainage through the
Remove the canal wall and perform an open cavity eustachian tube. The serous exudate becomes puru-
procedure in the presence of cholesteatoma. lent as inflammatory cells accumulate. Continued
The rate of mortality in these cases correlates inflammation, hyperemia, and accumulation of
most with the patient’s level of consciousness on purulent debris cause venous stasis, localized acido-
admission. In the South African series, mortality was sis, and decalcification of the bony septae. The osteo-
1% when patients were fully conscious, 7% when clastic activity in the inflamed periosteum softens
drowsy, 30% when stuporous, and 67% when com- and decalcifies the bony partitions, causing the small
atose.1 The complications most likely to be lethal are air cells to coalesce into a larger cavity.7
brain abscess, meningitis, and subdural empyema.
Postoperative follow-up is an essential part of Pathophysiology As the infection grows, pressure
the general treatment of patients who experienced within the mastoid cavity increases and conditions
life-threatening complications of acute or chronic oti- become progressively more favorable for it to extend
tis. Even when the patient responded perfectly, the beyond the confines of the mastoid. In the presence
surgeon should seriously consider follow-up CT scan of such an intense inflammation and infection,
to confirm objectively the status of the mastoid at the phlebitis and periphlebitis are common and spread
termination of treatment because there is a risk of the infection to the adjacent meninges, sigmoid
recurrence or emergence of new intracranial compli- sinus, cerebellum, and temporal lobe.8 The infection
cations. In patients who have experienced lateral sinus sometimes extends directly to the meninges, sigmoid
thrombosis, epidural abscess, subdural empyema, or sinus, labyrinth, or facial nerve because of bone ero-
302 Ballenger’s Otorhinolaryngology
sion. The most common pathway for infection to children under the age of 2 years, so there is risk of
extend beyond the mastoid is through the lateral surgical injury to the facial nerve. However, the
cortex behind the ear. Less commonly, it can extend author’s experience with cochlear implant surgery in
to the soft tissues in the upper portion of the neck children 12 to 24 months of age suggests that the
(see “Bezold’s Abscess”) and rarely to the soft tissue facial nerve does not exit through the lateral surface
anterior and superior to the auricle either by direct of the mastoid in this age group as is commonly
extension through eroded bone or by phlebitis and taught, and the risk of facial nerve injury in this age
periphlebitis. Go et al reviewed the records of 118 group is not substantial.
children with acute mastoiditis at Texas Children’s It is equally true that appropriate intravenous
Hospital between 1986 and 1998 and found only 8 antibiotics for a minimum of 3 to 6 weeks also will
patients in whom the mastoiditis had caused an eradicate the disease process in the majority of
intracranial complication.9 infected infants who have no additional complica-
tions. The therapeutic choice for a specific patient
Diagnosis The symptoms and signs of coalescent will depend on the clinical factors present and
mastoiditis—purulent otorrhea, fever, toxicity, and regional preferences. At the end of medical therapy,
ear pain—are the same as those seen in patients it is essential to document that the disease process
with uncomplicated acute otitis media. The has been completely eradicated. The patient should
strongest historical suggestion of coalescent mas- continue receiving antibiotic therapy until a CT scan
toiditis is the chronology of the infection in which produces evidence that the mastoid air cell system is
purulent drainage or significant otalgia persists for 2 no longer opacified and the middle ear is normally
or more weeks, recurs after 10 to 14 days, or signifi- aerated.
cantly worsens after that time interval. As a group,
children with coalescent mastoiditis look sicker and
have more toxicity with higher and more persistent CHRONIC MASTOIDITIS
fevers than those with acute otitis media. Older chil- Etiology Chronic mastoiditis can occur in associ-
dren may be able to localize the pain to the postau- ation with a long-standing tympanic membrane
ricular area rather than the ear canal. Physical perforation, with cholesteatoma, or as a complica-
findings that are most helpful include mastoid ten- tion from an infection following placement of a
derness to percussion, mastoid erythema, and sag- middle ear ventilating tube. As noted above, venti-
ging of the posterior superior external auditory lating tube mastoiditis tends to occur in young chil-
canal wall. dren who have experienced water contamination
The clinician should order a complete blood and have undergone cultures and treatment with
count and hematologic studies followed by CT scan- multiple antibiotic drops and oral antibiotics. Mas-
ning, which can establish the diagnosis by docu- toiditis with tympanic membrane perforation
menting the breakdown of the bony air cell walls occurs when an episode of acute otitis media with
and opacification of the pneumatized spaces. If any perforation pursues a course of chronic infection
suggestion of an intracranial complication exists, the rather than resolving or developing into coalescent
clinician should obtain an enhanced MRI scan. mastoiditis. Chronic mastoiditis of this type may
also begin when an uninfected ear with a long estab-
Treatment The treatment for coalescent mastoidi- lished central perforation becomes infected, the
tis can be either medical or surgical. Without ques- infection extends to the mastoid, and the ear contin-
tion, complete mastoidectomy with ventilating tube ues to drain chronically. Even though cholesteatoma
placement in conjunction with appropriate antibi- frequently remains uninfected for long periods of
otic therapy provides prompt, precise eradication of time, it tends to suppurate, form granulation tissue,
all infected tissue in an expeditious, cost-effective and erode bone. Once any type of mastoiditis causes
manner. However, because the increased vascularity continuous purulent drainage for 8 or more weeks,
and granulation tissue greatly increase the difficulty the likelihood of a complete resolution with antibi-
of the operation, it should not be undertaken lightly. otics significantly decreases. Chronic mastoiditis
Another consideration is that pneumatization has requires surgical intervention to heal, and an
not progressed to incorporate the mastoid tip in infected cholesteatoma requires surgical ablation,
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 303
cavity with its capsule. When mastoiditis has pro- TEMPORAL ROOT ABSCESS
duced an abscess, the case for excision and drainage
The soft tissues above and even those anterior to the
in conjunction with mastoidectomy is much
auricle can become infected and form an abscess
stronger. Only in the most unusual of circumstances
from suppuration that involves the cells of the zygo-
would treatment by prolonged antibiotics and
matic process of the temporal bone. As is the case
drainage of the abscess without mastoidectomy be
with postauricular and Bezold’s abscesses, temporal
appropriate.
root abscesses can form by direct extension through
eroded zygomatic process cells or by phlebitis and
BEZOLD’S ABSCESS periphlebitis. The clinical picture can be very con-
fusing because abscesses in this location are rare, but
In his 1913 textbook Diseases of the Ear, Kerrison
there are so few other etiologic possibilities. Com-
gave the following description of Bezold’s abscess:
puted tomographic scanning is always recom-
This condition is caused by a perforation in the mended to rule out mastoiditis as the source, and
bony plate forming the inner surface of the tip of the surgery is the appropriate treatment.
mastoid. It occurs presumably in cases in which the
tip cells are especially large and in which the bony
plate forming the inner or medial wall of the tip is
very thin, and the outer cortex thick. Pus escaping
PETROUS APICITIS
through such a perforation burrows downward in the A petrous apex can be undeveloped (sclerotic), can
neck beneath the sternomastoid, or may be confined contain marrow, or can exhibit some degree of
between layers of the deep cervical fascia.11 pneumatization. Pneumatization of the petrous apex
The cervical infection develops into an develops in only 30% of temporal bones.8 Much has
abscess in the upper neck deep to the sternoclei- been written about the different cell tracts that
domastoid muscle. Bezold’s abscess can also extend into and pneumatize the petrous apex. These
develop without any erosion or penetration of the cells can extend into the apex from above (supra-
inner and outer cortex of the mastoid if phlebitis labyrinthine; Figure 11–2, A and B), behind (retro-
and periphlebitis propagate the infection to the labyrinthine; Figure 11–3, A and B), beneath
same area. Because infants have limited mastoid (infralabyrinthine; Figure 11–4, A and B), and/or in
pneumatization, Bezold’s abscess occurs more front of the labyrinth (anterior labyrinthine). Petrous
commonly in older children in whom pneumati- apicitis is essentially mastoiditis that occurs in the
zation has extended into the mastoid tip and in petrous apex. It is rare because infection in sclerotic
adults who have either chronic mastoiditis or or marrow-containing petrous apices is uncommon
cholesteatoma. and the prevalence of pneumatization is low. Petrosi-
The diagnosis of Bezold’s abscess is often not tis develops by direct extension of a mastoid infec-
considered immediately in young patients with tion, but the mastoid may respond to medical or
deep, tender, upper cervical masses because surgical treatment without resolution of the apical
inflamed lymph nodes from many causes are so infection. Just as there can be disjunction between the
common. If the history and physical examination state of infection in the middle ear and the mastoid,
do not reveal a specific cause, the clinician should the same disjunction can exist between the mastoid
obtain a CT scan to identify or rule out a mastoid and the petrous apex.
source. The pathology of the infection can mirror that
The recommended treatment is complete sur- seen in coalescent mastoiditis with dissolution of thin
gical excision of the mastoid pathology, drainage of cellular septi and coalescence, or it can form granula-
the abscess, and removal of any associated granula- tion tissue and erode bone like chronic mastoiditis.
tion tissue. The surgeon should use bipolar electro- Only rarely does cholesteatoma extend to the apex.
cautery, copious suction irrigation, and coarse Imaging studies will usually include both CT and
diamond burs to allow him or her to visualize the MRI. A CT scan will show the bony details of the sep-
pathology adequately and exenterate thoroughly all tae of the air cells and the size and contour of the apex
of the diseased cells. The surgeon should drain both as a whole. Magnetic resonance imaging will differen-
the mastoid and the abscess cavity. tiate marrow from mucus or CSF. Both CT and MRI
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 305
A B
FIGURE 11–2. Petrous apex pneumatization via the supralabyrinthine cell tract at the level of the vestibule (A) and
posterior semicircular canal (B).
studies are essential to establish opacification of the The symptomatology of infection in the
air cells in the suspected petrous apex. When one petrous apex reflects the innervation of the air cells
petrous apex is well pneumatized, a small sclerotic or and the structures adjacent to the apex itself. Whereas
marrow-containing apex on the opposite side can be increased pressure within the mastoid air cell system
misinterpreted as a pneumatized apex opacified by causes pain in the region of the mastoid and the ear,
fluid or infection unless both studies are obtained. increased pressure in the petrous apex is usually
A B
FIGURE 11–3. Petrous apex pneumatization via the retrolabyrinthine cell tract at two levels (A and B) of the internal
auditory canal and vestibule.
306 Ballenger’s Otorhinolaryngology
A B
FIGURE 11–4. Petrous apex pneumatization via the infralabyrinthine cell tract in the right temporal bone at the level
of the internal auditory canal.
referred to the retro-orbital area or deep within the apex depends on the portion of the apex that is
skull. Patients with petrous apicitis have symptoms of involved and which air cell tracts connect the apex to
infection in the middle ear and mastoid, as well as the mastoid. In some temporal bones, the apex can
symptoms from the apex. The most common symp- be reached by a route posterior to the posterior semi-
toms from infection in the petrous apex are retro- circular canal (see Figure 11–3, A and B); in others,
orbital pain from irritation of the contiguous the best route is infralabyrinthine (see Figure 11–4, A
trigeminal ganglion in Meckel’s cave, paralysis of the and B). In a small percentage of temporal bones, lim-
sixth cranial nerve as it passes through Dorello’s canal ited drainage can be achieved by removing cells
abutting the apex, or dysfunction of the facial, extending over the top of the superior semicircular
acoustic, or vestibular nerves as they course through canal and through its center (the “hole in the dough-
the temporal bone. In 1904, Gradenigo described the nut”; see Figure 11–2, A and B). The original anterior
triad of retro-orbital pain, sixth nerve paralysis, and petrous apex drainage procedure described by Julius
otorrhea, which has since been known as Gradenigo’s Lempert incorporated a radical mastoidectomy oper-
syndrome.8 Only a minority of patients with petrous ation and is rarely done today.12 The middle cranial
apicitis exhibit the full triad today. fossa approach can provide excellent access to obtain
How petrous apicitis is best treated depends on material for culture and to remove infected tissue
its duration, its severity, and whether additional com- when the air cell tracts from the mastoid to the apex
plications are present. Because the labyrinth, carotid are inadequate. Postoperative CT scans are useful to
artery, and internal auditory canal are housed in the verify that the disease has been excised and as a ref-
petrous pyramid, it is difficult or impossible to excise erence for future studies.
all of the air cells, which is done so routinely in the
mastoid. Therefore, prolonged antibiotics are neces-
sary, even when surgery is performed. When necrotic
LABYRINTHINE FISTULA
bone is obvious, surgical drainage is a necessary A labyrinthine fistula results from the erosion of the
adjunct to intravenous antibiotic therapy. Even par- endochondral bone of the bony labyrinth. The loss of
tial apicectomy can reduce the bacterial load suffi- this bone allows the underlying endosteum, peri-
ciently to allow antibiotics and host defenses to lymph, and structures of the endolymphatic com-
control the disease. The best surgical approach to the partment to move when the pressure in the external
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 307
auditory canal is changed. Motion of the fluids in the feel suddenly off balance when they hear a sudden
endolymphatic compartment brings on the symp- loud sound, which is called Tullio’s phenomenon, or
toms of labyrinthine fistulae. Almost all labyrinthine when they push on their external ear canal, for
fistulae affect the lateral semicircular canal; the supe- example, when cleaning their ear with a washcloth.
rior and posterior semicircular canals, vestibule, and After obtaining a history that suggests the pres-
cochlea are rarely involved. Cholesteatoma is the ence of a fistula, the physician should perform the
cause in nearly all cases, and fistulae were seen to fistula test, a specific maneuver that can establish the
occur in 7% of the cholesteatomas in Gersdorff and diagnosis. The examiner occludes the external audi-
Nouwen’s large series.13 Higher percentages have tory canal with the pneumatic otoscope and alter-
been reported, but the actual incidence is unknown. nately increases and decreases the pressure slightly
Most reports of labyrinthine fistulae are from tertiary so that pressure changes are transmitted from the
care referral centers that include many patients with canal to the middle ear and mastoid air cell system
large or previously operated cholesteatomas, which through either an intact or a perforated tympanic
artificially elevates the incidence. On the other hand, membrane. During the test, the patient is told to
studies reviewing suppurative complications of otitis look directly ahead at a specific object, and the
media often do not include labyrinthine fistulae if the physician observes the patient’s eyes for any hori-
fistula is not infected or does not cause significant zontal deviation. In a normal ear, changes in exter-
symptoms or if the surgeon first detects it at opera- nal canal pressure cause no motion of the eyes and
tion. no symptoms. When a lateral canal fistula is present,
The mechanisms by which a cholesteatoma positive pressure transmitted from the external audi-
causes bone erosion are not fully understood, but tory canal compresses the lateral semicircular canal
the dense endochondral bone first becomes dem- endosteum and causes utriculopetal endolymph
ineralized and then is absorbed so that a progres- flow. This produces a positive fistula sign, conjugate
sively smaller amount of bone exists between the deviation of the eyes away from the side of the com-
endosteal membrane overlying the perilymph and pression. Negative external auditory canal pressure
the cholesteatoma matrix above it. When the bone is produces a conjugate deviation toward the ear being
completely resorbed, the surgeon can see what tested. The patient may become slightly nauseated
appears to be a “blue line” parallel to the underlying or perceive a to-and-fro motion of the environment
semicircular canal lumen because the illuminating during the test. Only 55 to 70% of patients with lat-
light at the blue line is no longer reflected off the eral canal erosions have a positive fistula test, but in
dense bone but is absorbed into the underlying fluid. those patients, it is a highly reliable indication that a
Manolidis recently reviewed the records of 111 fistula is present and allows the surgeon to plan the
inner-city Texas patients with labyrinthine fistulae operation so that he or she can avoid entering the
and looked for any coexisting complications.14 Two fistula during surgery. Inadvertently opening a
associations were prominent. The facial nerve was labyrinthine fistula usually causes total loss of hear-
involved with cholesteatoma or was damaged by the ing in that ear.15 Computed tomographic scanning
cholesteatoma in 60% of the patients, and dehis- also can suggest the diagnosis. Images in the bone
cences of the tegmen occurred in 39%. The majority algorithm will show erosion of the lateral semicircu-
of these patients had two or more operations, with lar canal and any other signs of cholesteatoma.
an average of 2.6 operations per patient. Surgeons Surgery is the recommended treatment for
should suspect a triad of complications: lateral semi- labyrinthine fistulae. Usually, the surgeon will
circular canal fistula, facial nerve exposure, and remove the posterior external auditory canal wall
tegmen erosion in all patients undergoing revision and perform an open-cavity mastoidectomy. If the
surgery for cholesteatoma or in patients with pri- patient has no other complications, the temporal
mary acquired cholesteatomas that developed in bone is well pneumatized, and the exposure of the
well-pneumatized mastoids. lateral semicircular canal is good, the surgeon can
Labyrinthine fistulae cause mostly vestibular consider performing a canal wall up technique.
symptoms. Patients describe short periods of imbal- Whether the canal wall is left up or removed, the
ance, dysequilibrium, or vertigo but have normal surgeon completes the operation and removes all of
equilibrium most of the time. Some recall that they the cholesteatoma except for a small area around
308 Ballenger’s Otorhinolaryngology
the fistula site. After carefully removing the overly- Sometimes the progression to complete paralysis is
ing cholesteatoma debris without disturbing the rapid. Facial nerve paralysis secondary to
matrix, the surgeon looks for the “blue line” that cholesteatoma is also most likely to involve the nerve
identifies the site of the fistula and the thin layers of in the middle ear because it is there where most
lateral semicircular canal bone on either side. The cholesteatomas arise. Extensive erosion of the hori-
surgeon develops a dissection plane between the zontal segment of the fallopian canal is especially
cholesteatoma matrix and the endosteum using common in large, uninfected primary acquired
high microscopic magnification and a flat dissector cholesteatomas. When there is no infection, the nerve
that is 2 to 3 mm wide. The matrix is elevated with usually retains normal function. An erosive
a fine microsuction to improve visualization of the cholesteatoma can expose the facial nerve anywhere
dissection plane. A small piece of tissue or a thin in the temporal bone and cause paralysis. In these
cap of bone is placed over the site and secured with cases, the onset of the paralysis is usually gradual, and
fibrin glue or packing after the cholesteatoma is suc- sometimes the progression is so slow that patients do
cessfully removed. If the endosteum is torn, it is best not seek medical attention for months. When the
to replace the matrix and terminate the procedure. onset of facial paralysis is this slow, the paralysis is
Spontaneous vestibular symptoms usually more likely to persist after surgical treatment.
improve after the fistula is repaired, but symptoms The clinical presentation of facial paralysis is
from ear canal pressure changes may persist for some discussed more fully in Chapter 24. Facial nerve dys-
time, and a positive fistula sign will persist until there function secondary to temporal bone infection is
is a regrowth of bone over the site of the fistula. The not usually accompanied by significant pain or a
principal risk in removing the cholesteatoma matrix facial tic but is simply expressed as muscle weakness
from the fistula is total or partial loss of hearing, or paralysis.
which occurs in less than 20% of carefully managed When facial paralysis is caused by acute otitis
fistula cases.16 media, appropriate antibiotic therapy for the acute
otitis may be adequate, although myringotomy with
evacuation of the purulent material and reduction
FACIAL NERVE PARALYSIS of the numbers of bacteria is recommended. When
Facial nerve paralysis can result from acute otitis facial nerve paralysis follows chronic suppurative
media, chronic otitis media without cholesteatoma, otitis media (with or without cholesteatoma), the
or cholesteatoma. Bacteria reach the nerve because of surgeon should remove the infection surrounding
a congenital dehiscence of the bony fallopian canal or the nerve as part of the mastoidectomy. The sur-
because the canal is eroded by granulation tissue or geon should address the diseased area of the facial
cholesteatoma. Facial nerve function is lost because nerve after the rest of the operation is completed in
of edema secondary to pressure and inflammation or the same way that he or she would manage a
because suppurative neuritis destroys the neural ele- labyrinthine fistula. The surgeon gradually ap-
ments. If the edema persists, avascular necrosis of the proaches the granulation tissue or cholesteatoma
axons can lead to axonal degeneration. overlying the nerve from the proximal and distal
Facial paralysis in young children that is caused portions of the nerve that are uninvolved by the
by acute otitis media is frequently incomplete and chronic infection using diamond burs to carefully
probably occurs only in infants with congenital remove the bone of the fallopian canal on both sides
dehiscence of the fallopian canal in the middle ear of the diseased portion. The surgeon uses a flat
adjacent to the stapes. Facial weakness in these cases blunt instrument to dissect the chronic inflamma-
rarely lasts longer than 3 weeks even when complete tory tissue from the nerve while elevating the dis-
paralysis is present. eased tissue with a small suction tip. It may be
Facial nerve paralysis secondary to chronic oti- necessary to use sharp dissection to separate the
tis media without cholesteatoma also usually affects inflammatory tissue from the epineurium. The out-
the horizontal portion of the facial nerve near the come for surgical decompression of the facial nerve
stapes.17 In these cases, the clinical course of the secondary to chronic suppurative otitis media
paralysis is more likely to be prolonged, with a grad- primarily depends on whether the nerve has under-
ual progression from slight weakness to full paralysis. gone complete degeneration before surgery.
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 309
ACUTE SUPPURATIVE LABYRINTHITIS tion and acute or chronic otitis media, no specific
diagnostic studies are necessary. Although there is
Bacterial invasion of the labyrinth is always promptly no possibility of reversing the clinical course, appro-
followed by total loss of both auditory and vestibular priate antibiotic treatment for 10 days is recom-
function. Usually, acute otitis media extends into the mended to eradicate the labyrinthine infection and
labyrinth through a weakened or dehiscent oval win- prevent propagation to the meninges. Other thera-
dow membrane, as seen in congenital labyrinthine peutic measures are dictated by the underlying oti-
deformities, such as Mondini’s deformity and tis, but labyrinthectomy is not necessary in
enlarged vestibular aqueduct syndrome, and in indi- labyrinthitis secondary to acute otitis media.
viduals who have undergone stapes surgery.
Although it is not proven, suppurative labyrinthitis
may be a common mechanism for unilateral anacu- ENCEPHALOCELE AND CEREBROSPINAL FLUID
sis in children with Mondini’s deformity. These chil- LEAKAGE
dren are at additional risk. The foramina of the
internal auditory canal opening into the medial Encephalocele (brain hernia, brain fungus, menin-
aspects of the labyrinth may also be weak or dehis- goencephalocele) and CSF leakage may be associated
cent, and those foramina and the cochlear aqueduct with other cranial or intracranial complications in
can permit bacterial infection to progress from the acute or chronic otitis media. Three different clinical
labyrinth to the meninges or vice versa. It is not patterns can occur.
known how frequently suppurative labyrinthitis Spontaneous CSF leakage from defects in the
causes meningitis or how often meningitis subse- tegmen tympani (less commonly the tegmen mas-
quently causes bacterial labyrinthitis, but both prob- toideum) have been reported in more than 50
ably occur, especially in the special population of patients who have not undergone previous otologic
children with congenital labyrinthine abnormalities. surgery.18,19 Seventy to 80% of the patients are over
Direct bacterial invasion of the labyrinth 45 years of age. The defects range in diameter from
through a cholesteatomatous lateral semicircular 2 mm to 2 cm and are sometimes multiple. Usually,
canal fistula is another cause of acute suppurative an encephalocele protrudes through the defect.
labyrinthitis. In this situation, infected granulation Although there is no agreement as to why the dura
tissue beneath the cholesteatoma matrix lies directly breaks down and allows cerebral herniation and CSF
on the endosteal membrane and the underlying per- leakage in these older patients, Jackson and associ-
ilymph. The bacteria causing the labyrinthitis are ates have suggested that aging, increased intracranial
those either of the underlying acute otitis media or pressure, low-grade inflammation, arachnoid granu-
of the cholesteatoma. The diagnosis is clinical. lation, and irradiation can play a part.20 Patients fre-
Within 30 to 60 minutes from the beginning of the quently present because of hearing loss owing to
infection, tinnitus and dizziness are followed by reduced ossicular motion from the middle ear fluid
whirling vertigo, pallor, diaphoresis, nausea, and or the encephalocele. Myringotomy and placement
vomiting. The vestibular symptoms continue at their of a ventilating tube release a profuse watery otor-
maximum for at least 8 to 12 hours even if the rhea that tests positive for CSF. Other patients pres-
patient is totally immobile and receiving intravenous ent with signs and symptoms of meningitis, and
antiemetics. Brisk labyrinthine nystagmus directed many of these patients have already experienced one
toward the opposite ear accompanies the vertigo. or more episodes of meningitis.
After continuing for several hours, the spontaneous Encephalocele and CSF leakage secondary to
vertigo and nystagmus gradually abate. Sympto- chronic otitis media occur when a cholesteatoma
matic improvement continues during the next few and granulation tissue erode through the bony
days, but any motion of the head will evoke vertigo plates that separate the mastoid from the temporal
and nausea. Over the next 2 or 3 weeks, central nerv- lobe and the cerebellum and then erode through
ous system compensation occurs, and normal or the dura. The mastoid and epitympanic tegmen are
near-normal balance is restored. The tinnitus also involved more frequently than the cerebellar plate.
abates, but all hearing is lost. It usually takes many months to years for a
When the physician recognizes the typical clin- cholesteatoma to cause this degree of bone erosion,
ical picture in a patient with a predisposing condi- cerebral prolapse, and dural erosion.
310 Ballenger’s Otorhinolaryngology
Traumatic encephalocele and CSF leakage are source of CSF leakage that can lead to meningitis.
the most common pattern. Although a few of these Patients with syndromic or nonsyndromic congenital
cases occur secondary to temporal bone fracture, the stapes fixation, Mondini’s dysplasia, and enlarged
great majority are the consequence of an operation vestibular aqueducts are also at risk for a bacterial
in which portions of the tegmen or cerebellar plates middle ear infection spreading to the CSF. The path-
were removed and the dura was exposed or trauma- way can be obvious, as, for example, when a “peri-
tized. In these cases, both the disease process and the lymph gusher” is discovered during stapes surgery, or
surgery contribute to the bony and dural trauma it can be more subtle, as when there are microscopic
that facilitates the development of an encephalocele, disruptions of the continuity of the oval or round
CSF leakage, and intracranial complications. windows, internal auditory canal, and cochlear aque-
Management of temporal bone encephalocele duct. Meningitis can occur even in individuals with
requires prompt surgical repair. Jackson and associ- normal middle ear and labyrinthine anatomy if acute
ates have written an excellent review of this subject.20 otitis media complicates conditions such as traumatic
The size of the bony defect and the volume of her- stapes dislocation or perilymphatic fistula and then
niated brain are two of the important factors in progresses to acute suppurative labyrinthitis.
choosing a surgical approach. Small defects usually The predominant symptom of meningitis is a
can be adequately managed through the mastoid, generalized, severe headache. The patient will tend
but multiple and large defects are best repaired by a to lie quietly, vomit frequently, and exhibit photo-
combination of transmastoid and middle cranial phobia and general hyperesthesia. The patient’s level
fossa approaches. Jackson et al recommended a com- of consciousness may be normal, somnolent, stu-
bined transmastoid intradural middle cranial fossa porous, or unresponsive. Fever, often high and sus-
approach for large encephaloceles. To reduce the risk tained, is nearly universal. Nuchal rigidity and pain
of infection, the defects are usually repaired with when the clinician attempts to flex the patient’s neck
autogenous graft materials. are ominous signs that should compel the clinician
to perform other neurologic tests. In Brudzinski’s
sign, passive flexion of the head on the chest is fol-
INTRACRANIAL COMPLICATIONS lowed by involuntary flexion of both thighs and
both legs. In Kernig’s sign, when the patient is in the
MENINGITIS supine position and one thigh is flexed to a right
Meningitis is by far the most common intracranial angle, attempts at passive extension at the knee are
complication of acute and chronic otitis media. In accompanied by pain and resistance owing to spasm
Gower and McGuirt’s series of 100 consecutive of the hamstring muscles. Fundoscopic examination
patients with intracranial complications of acute and may reveal the presence of papilledema.
chronic otitis, 76 had meningitis, and 53 of those Whenever meningitis is suspected, a CT scan is
were under 2 years of age.21 In infants and toddlers, critical to rule out the presence of brain abscess,
the great majority of cases occur by hematogenous cerebritis, or subdural empyema and to determine
dissemination of infection during acute otitis media. that it is safe to perform lumbar puncture (ie,
Sometimes these patients are not included in reports intracranial pressure is not inordinately increased).
that document the complications of otitis, and the Cerebrospinal fluid from the lumbar puncture is
frequency of otogenic meningitis appears to be low.1 examined for intrathecal pressure, cells, bacteria,
Conditions that allow CSF to gain access to the glucose, protein, chloride, and other factors. Cere-
middle ear cavity predispose the patient to developing brospinal fluid pressure increases early in the course
or suffering a recurrence of bacterial meningitis. Cere- of the disease and protein and glucose concentra-
brospinal fluid otorrhea is common after lacerations tions increase in comparison to serum values as the
of the dura by longitudinal temporal bone fractures disease progresses, but bacteria are not present until
and occasionally is seen in patients who sponta- late in the disease.
neously develop defects of the tegmen of the middle When meningitis is secondary to acute otitis
ear or mastoid with associated encephaloceles. Unrec- media or acute otitis media with suppurative
ognized injury to the dura of the posterior or middle labyrinthitis, antibiotic treatment of the meningitis
cranial fossa during mastoid surgery is an overlooked is also adequate treatment for the otitis, and no sur-
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 311
gery is indicated. Tympanometry and otoscopy polymorphs migrate into local capillaries, producing
should be performed after treatment is complete to endothelial swelling and focal cerebritis. The tissue
document that the middle ear has returned to nor- becomes edematous, hemorrhagic, and necrotic. The
mal. However, when meningitis develops from abscess may vary greatly in size. Often it has an irreg-
chronic otitis media and mastoiditis, the mastoid ular shape and is multilocular. At first, the capsule is
must be exenterated, and all disease must be excised. poorly defined, but over time it firms and can be eas-
Even though the patient has already had a CT scan ily stripped from the underlying edematous brain.25
before the lumbar puncture, an enhanced MRI In addition to manifesting symptoms and
should be obtained to rule out the presence of any signs of general intracranial sepsis, patients with
additional intracranial complications. The neuro- cerebellar abscesses often exhibit coarse horizontal
logic condition of the patient determines the timing nystagmus, dysmetria, dysdiadochokinesia, or action
of the surgery, and the mastoidectomy should be per- tremor. Temporal lobe abscess may cause homony-
formed as soon as the patient is stable. Meningitis is mous visual field defects, contralateral hemiparesis,
one of the gravest complications of acute or chronic and other focal signs listed below for subdural
otitis. Further, meningitis appears to be more lethal empyema. The physician should carefully examine
when secondary to chronic otitis media and mas- the patient and the imaging studies because up to
toiditis than when it is a hematogenous complication two-thirds of patients with intraparenchymal
of acute otitis media in the first 2 years of life. abscesses will have more than one intracranial
complication.23
The physician should immediately begin
BRAIN ABSCESS broad-spectrum intravenous antibiotics directed at
The incidence and mortality of intraparenchymal both aerobic and anaerobic microorganisms. If
brain abscesses have decreased considerably. Nearly imaging studies suggest no other complications and
all reports in the past two decades come from centers the patient’s condition is stable, neurosurgical
outside North America and Western Europe. How- drainage or abscess excision is performed within the
ever, recent reports from Africa and Asia, where new first 24 hours of admission, followed immediately
imaging techniques are used, have documented sub- by mastoidectomy performed through a separate
stantial improvements in diagnosis and therapy and surgical field. Mortality has decreased to approxi-
clarified some aspects of surgical treatment. Yen and mately 10%.
associates’ recent series of 122 consecutive patients
seen in a Taiwan hospital between 1981 and 1994
revealed that otitis was the third most common
SUBDURAL EMPYEMA
cause of intraparenchymal brain abscess, exceeded Subdural empyema is a fulminating purulent infec-
only by those associated with cyanotic congenital tion that develops between the dura and the pia-
heart disease and those secondary to head injury or arachnoid membranes. It is one of the most
neurosurgery.22 Seventy-five percent of abscesses immediate of neurosurgical emergencies. It com-
occurred in males, principally from the lower prises only about 20% of all cases of localized
socioeconomic classes. In the 1990s, four reports intracranial bacterial infection, and an otitic origin is
from India, Turkey, and South Africa discussed 149 uncommon compared to bacterial contamination
patients with otogenic brain abscesses.1,2,23,24 (from trauma or a neurosurgical operation), suppu-
Abscesses from acute and chronic otitis media rative paranasal sinus disease, or meningitis. At least
occurred nearly always on the same side as the otitis two-thirds of the cases occur in men, and most
and nearly equally in the temporal lobe or cerebel- occur during the second decade of life. The abscess
lum. Almost three-fourths were secondary to usually begins by direct spread from adjacent
cholesteatoma, half occurred in patients in the sec- infected bone or by retrograde venous propagation.
ond decade of life, and two-thirds affected males. Once infection enters the subdural space, pus forms
A brain abscess begins when bacteria propagate rapidly and spreads widely. Thrombophlebitis of
in and around venous channels leading from the cortical veins is virtually guaranteed. Swelling,
mastoid into the adjacent brain parenchyma. As soon necrosis, and infarction of the cortex account for
as the bacteria arrive in the cortex or white matter, many of the clinical features and explain how a
312 Ballenger’s Otorhinolaryngology
barely detectable, thin layer of subdural pus can dural space (usually bilaterally) that varies from 5 to
cause such devastating consequences as raised 100 mL.27 This problem is less common after
intracranial pressure, focal signs, and seizures.26 meningitis from other microorganisms. Its fre-
Clinically, patients exhibit a cascade of symp- quency has also decreased since universal immu-
toms that begins with a severe headache, the most nization against H. influenzae has dramatically
persistent symptom. The temperature rises dra- reduced the incidence of meningitis. Uninfected
matically as the disease progresses. General malaise, subdural collections after meningitis are called
chills, and nuchal rigidity indicate that the patient “subdural effusions.” If bacteria are evident on
is becoming seriously ill. After an unpredictable direct examination of the fluid, the collections are
period of time, the patient’s level of consciousness called “infected subdural effusions,” and if the fluid
may abruptly decline and focal signs and symp- is grossly purulent, they are classified as “subdural
toms may develop. Most patients with collections empyemas.” In this age group, subdural collections
of pus on the left side of the brain develop aphasia from meningitis secondary to chronic otitis media
and a progressive contralateral hemiparesis. Paral- that require otologic attention are rare.
ysis of conjugate gaze to the contralateral side and
deviation of the eyes toward the side of the lesion
are also common. Jacksonian seizures are common
EPIDURAL ABSCESS
at this stage, and papilledema may be evident. In Epidural abscess results from bone erosion caused
patients with subdural empyema in the posterior by cholesteatoma, granulation tissue, or coalescence.
fossa, localizing signs are often absent, but marked In addition to the bone erosion, an intense inflam-
neck stiffness and papilledema are always present. matory response to the infection results in granula-
The entire clinical picture of subdural empyema tion tissue formation and forms an abscess between
may develop in as little as a few hours or as long as the temporal bone and the dura mater. The involved
10 days. dura thickens in response to its contact with granu-
In a well-developed subdural empyema, a lation tissue on its surface (pachymeningitis).
contrast-enhanced CT scan will show a crescent- Although it can occur as the only complication of
shaped, low-density collection of pus displacing the chronic mastoiditis, epidural abscess is frequently
brain from the inner table of the skull, with associated with lateral sinus thrombophlebitis,
enhancement of the adjacent edge of cortex. Unfor- meningitis, and cerebritis or brain abscess. Rarely,
tunately, the scan may appear normal early in the epidural abscess can result from acute otitis and
course of the disease. When this happens, the mastoiditis in the same way as will be described for
clinician should obtain an enhanced MRI or repeat lateral sinus thrombosis.
the CT scan after a suitable time interval. Lumbar Most patients experience deep mastoid pain,
puncture is dangerous and is contraindicated but there are no signs or symptoms specifically
because it may precipitate transtentorial coning; attributable to epidural abscess, and many small
however, it may be unavoidable when the CT scan epidural abscesses without associated complica-
fails to detect the lesion and focal signs are absent tions are discovered only at surgery. If the abscess is
because meningitis and brain abscess must also be large enough, it can be detected on enhanced CT or
ruled out. MRI scans as a fluid-filled cavity between the tem-
Emergency neurosurgical drainage and appro- poral bone and the enhanced dura. Surgery is the
priate antibiotic therapy are necessary. The patient’s only recommended treatment. The surgeon per-
likelihood of survival will be related to his or her forms the type of mastoidectomy that is appropri-
level of consciousness at the time of surgery. The ate for the underlying otitis and mastoiditis. After
presence of localizing signs in any patient with removing the cortex, he or she should progressively
chronic otitis media whose level of consciousness is exenterate the air cells, proceeding from lateral to
declining requires immediate and decisive action. medial and from regions of less disease to those
Subdural empyema can also develop in with more disease. When the locus of pathology is
neonates as a complication of meningitis. Up to the cerebellar plate, the surgeon should first
30% of infants and children with H. influenzae smooth the tegmen mastoideum and tegmen tym-
meningitis develop a collection of fluid in the sub- pani and then thin the posterior aspect of the bony
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 313
external auditory canal and remove the tip cells to be caused by osteothrombophlebitis during acute
maximize exposure and hemostasis. Then the sur- otitis media and mastoiditis. In this situation (and
geon approaches the diseased area along the cere- in occasional cases of chronic mastoiditis), the
bellar plate from the superior, inferior, lateral, and, bony sinus plate is intact at the time of surgical
finally, medial directions, removing the overlying exploration.
bone until only a thin plate remains. Because the Because the sinus is a continuation of the cere-
dura has been thickened by the infection, blunt flat bellar dura mater, extension of an infection by only
instruments, such as a Freer elevator or large a few millimeters can result in the equally grave
curettes, can safely scrape the granulation tissue complications of meningitis, epidural abscess, sub-
from the abscess cavity and help the surgeon iden- dural empyema, cerebritis, or cerebellar abscess. In
tify the most centripetal extent of the abscess. The two recent series, 14 of 19 patients with lateral sinus
surgeon should remove all of the bone overlying thrombosis had one or more of these additional
the abscess using diamond burs, rongeurs, or complications.28,29
curettes until healthy dura without granulation tis- Although its frequent association with other
sue is evident on all margins of the abscess. When complications obscures its clinical picture, a diagno-
the abscess involves the tegmen, the surgeon should sis of lateral sinus thrombosis can be strongly sus-
change the order of the surgical steps to complete pected when there are signs and symptoms of
the surgery in the other areas first and address the septicemia such as chills and spiking fever or block-
tegmental abscess last. age of blood flow through the sinus. A picket-fence
fever pattern with diurnal temperature spikes that
exceed 103°F has been described with this condition
LATERAL SINUS THROMBOSIS for decades. Some recent articles have suggested that
Thrombosis of the lateral sinus usually forms as an this pattern is not seen as frequently, in part because
extension of a perisinus abscess that develops after many patients present with previous or current
mastoid bone erosion from cholesteatoma, granula- antibiotic therapy; however, Singh reported that the
tion tissue, or coalescence.27 The perisinus abscess majority of his 36 patients were on intravenous
exerts pressure on the dural outer wall of the sinus, antibiotics and still exhibited that fever pattern.30
and necrosis results. The necrosis extends to the Unless the patient has been transferred from another
intima and attracts fibrin, blood cells, and platelets, hospital, only the patient’s temperature on admis-
and a mural thrombus forms. The mural thrombus sion is available; nonetheless, the clinician who
becomes infected, enlarges, and occludes blood flow observes such a high fever spike should suspect the
through the sinus. Fresh thrombus can propagate in possibility of sigmoid sinus thrombophlebitis. Singh
a retrograde direction to the transverse sinus, the also noted that the neck pain in lateral sinus throm-
torcular Herophili, and even to the superior sagittal bosis may be mistakenly attributed to the neck stiff-
sinus. In the opposite direction, clot can extend via ness of meningitis, when it is actually pain and
the jugular bulb into the internal jugular vein in the tenderness occurring along the anterior border of
neck or via the inferior and/or superior petrosal the sternocleidomastoid muscle. Singh further iden-
sinuses to the cavernous sinus. The infected clot fre- tified percussion tenderness of the mastoid tip as
quently showers the bloodstream with bacteria, another important sign.
which give rise to the signs and symptoms of sep- More ominous are the signs of sudden
ticemia and the possibility of metastatic abscesses intracranial hypertension secondary to decreased
(most commonly to the lungs). venous drainage from the skull (see “Otitic Hydro-
Because of the relative frequencies of the var- cephalus” below). The most prominent sign is the
ious types of mastoiditis and the ages of those occurrence or sudden worsening of a severe
affected, lateral sinus thrombosis today is most headache. This is most likely to occur when the
common in adults or older children with choles- patient’s dominant venous drainage system is
teatoma and develops less commonly from the obstructed (the right side in 60% of individuals).
other types of chronic mastoiditis. In addition to More grave is progressive obtundation. This may
those cases arising by direct extension from bone herald the development of cerebral edema from
erosion, however, lateral sinus thrombosis can also increased intracranial pressure secondary to involve-
314 Ballenger’s Otorhinolaryngology
ment of the superior sagittal sinus or the cavernous surgeons recommend extending the exposure, inci-
sinus. It carries a very high mortality rate. sion, and clot evacuation proximally and distally
Imaging studies and lumbar puncture are until free bleeding occurs. The author recommends
essential to sort out the possible types of complica- a more conservative approach, extending the surgery
tions in obtunded patients. If the patient’s condition proximally and distally only as far as a grossly
permits, both enhanced CT scan and enhanced MRI infected clot is found to remove as much infection as
should be performed. The diagnosis can be made possible. The mastoid and cerebellar walls of the
preoperatively when the clinician identifies enhance- sinus are usually thickened and relatively tough as a
ment of the wall of the sigmoid sinus on CT scan, result of the chronic infection. The surgeon can
the Delta sign. Sinus wall enhancement is more sen- safely scrape them gently with a broad flat instru-
sitively evaluated by MRI, which also can document ment such as a Freer elevator to remove the infected
abscess formation within the sinus and can exclude tissue. Syms and associates reported treating six
nearby subdural empyema, cerebritis, or cerebellar patients with lateral sinus thrombosis and concomi-
abscess. tant additional intracranial complications with mas-
All patients with sigmoid sinus thrombosis will toidectomy without opening and evacuating the
require mastoidectomy to treat the underlying mas- lateral sinus clot.29 All patients survived, but the
toid disease adequately. Treatment controversies average hospital stay was more than 49 days—38
exist in the timing of the mastoid surgery and the days when the patient with the longest stay was
management of the infected clot and sinus wall. omitted. In contrast, Kaplan and Kraus’s 13 patients
When a brain abscess is also present, surgical underwent surgery that included incision of the
drainage of that abscess takes precedence over any sinus and evacuation of the clot or abscess.28 Their
mastoid procedure (see “Brain Abscess”). If the mean hospital stay was only 17 days.
patient’s condition permits, neurosurgical drainage
of the brain abscess should be followed in the same
anesthetic by expeditious mastoidectomy. When
OTITIC HYDROCEPHALUS
meningitis is present in conjunction with lateral Seventy years ago, Symonds described otitic hydro-
sinus thrombosis, mastoid surgery should be com- cephalus as a disease in which signs and symptoms of
pleted as soon as the patient is neurologically stable. acute hydrocephalus followed some form of otitis.31
Management of the clot can include anticoagu- Controversy and disagreement about the entity still
lation, ligation of the jugular vein in the neck, and exist today. Some authors view otitic hydrocephalus
opening the sinus and evacuating the infected clot. as a distinct clinical entity consisting of intracranial
Use of anticoagulants is rarely indicated, but it hypertension and resolved or resolving (usually
should be strongly considered when extension of the acute) otitis media without any relationship to lat-
clot to the transverse sinus or cavernous sinus is doc- eral sinus thrombophlebitis.21 Others view it as a
umented or suspected. Other considerations in these pathophysiologic consequence of lateral sinus
deteriorating patients include neurosurgical decom- thrombosis from any cause. The latter viewpoint
pression and corticosteroids. Similarly, ligation of the holds that whether symptoms will develop following
jugular vein in the neck should not be routine, but it lateral sinus occlusion depends on (1) the size of the
should be considered whenever there is evidence of involved lateral sinus relative to that of the opposite
extension of the clot into the neck and should be side, (2) the adequacy of the collateral venous net-
strongly considered when septic emboli are present. work including the cavernous sinus and the opposite
The sinus is usually addressed only after the inferior petrosal sinus, and (3) whether propagation
mastoidectomy portion of the operation has been of the process has occluded additional venous out-
completed. The surgeon then widely exposes the flow. The physician should recognize the possible
sinus and the adjacent dura by removing the overly- relationship among the symptoms, ear disease, lateral
ing bone with rough diamond burs. The surgeon sinus, and emergent nature of the condition.
passes an 18- or 20-gauge needle through the sinus In the early stages, a diffuse, severe headache
wall and, if there is no free blood on aspiration, dominates the clinical picture. In uncomplicated
makes a linear incision through the sinus wall and cases with (or occasionally without) medical man-
evacuates the abscess and any infected clot. Some agement, the continuous headache gradually ame-
Cranial and Intracranial Complications of Acute and Chronic Otitis Media 315
liorates and dissipates over 3 to 7 days as collateral 8. Neely JG. Complications of temporal bone infection.
venous outflow increases to accommodate arterial In: Cummings CW, editor. Otolaryngology-head and
inflow. If collateral venous drainage is inadequate neck surgery. 2nd ed. St. Louis: Mosby-Year Book;
and intracranial pressure remains elevated, signs of 1993. p. 2840–64.
the sensorium dulling or decreased visual acuity 9. Go C, Bernstein JM, de Jong AL, et al. Intracranial
from retinal vein occlusion will appear. The physi- complications of acute mastoiditis. Int J Pediatr
cian must recognize that these developments are an Otorhinolaryngol 2000;52:143–8.
extreme emergency, obtain immediate neurosurgi- 10. Samuel J, Fernandez C. Otogenic complications with
cal consultation, and begin high doses of intra- an intact tympanic membrane. Laryngoscope 1985;
venous corticosteroids and diuretics. Rapid 95:1387–90.
progression to coma and death is possible. 11. Kerrison PD. Diseases of the ear. Philadelphia &
In assessing any patient suspected of having London: JP Lippincott; 1913.
otitic hydrocephalus, the physician must make three 12. Lempert J. Complete apicetomy (mastoido-tym-
determinations: (1) whether the patient has pano-apicetomy), new technique for complete apical
increased intracranial pressure, (2) whether the exenteration of apical cartoid portion of petrous
patient has active acute or chronic mastoid infection, pyramid. Arch Otol 1937;25:144.
and (3) whether there is free flow of blood through 13. Gersdorff MC, Nouwen J. Labyrinthine fistula after
the involved lateral sinus. The physical examination cholesteatomatous chronic otitis media. Am J Otol
and the imaging studies are paramount in making 2000;21:32–5.
these determinations. The results of these inquiries 14. Manolidis S. Complications associated with
will allow the physician to formulate the appropriate labyrinthine fistula in surgery for chronic otitis media.
treatment of the mastoid, lateral sinus, and increased Otolaryngol Head Neck Surg 2000;123:733–7.
intracranial pressure. 15. Soda-Merhy A, Betancourt-Suarez M. Surgical treat-
ment of labyrinthine fistula caused by cholesteatoma.
Otolaryngol Head Neck Surg 2000;122:739–42.
REFERENCES 16. Bak-Pedersen K, Ostri B. Labyrinthine fistula in
1. Singh B, Maharaj TJ. Radical mastoidectomy: its chronic otitis media with cholesteatoma. In: Tos M,
place in otitic intracranial complications. J Laryngol editor. Cholesteatoma and mastoid surgery. Amster-
Otol 1993;107:1113–8. dam: Kugler & Ghedini; 1989. p. 1049–50.
2. Osma U, Cureoglu S, Hosgoglu S. The complications 17. Harker LA, Pignatari S. Facial nerve paralysis second-
of chronic otitis media: report of 93 cases. J Laryn- ary to chronic otitis media without cholesteatoma.
gol Otol 2000;114:97–100. Am J Otol 1992;13:372–4.
3. Gates GA. Acute otitis media and otitis media with 18. May JS, Mikus JL, Matthews BL, Browne JD. Sponta-
effusion. In: Cummings CW, editor. Otolaryngology- neous cerebrospinal fluid otorrhea from defects of
head and neck surgery. 3rd ed. St. Louis: Mosby-Year the temporal bone: a rare entity? Am J Otol
Book; 1998. p. 461–77. 1995;16:765–71.
4. Harker LA, Koontz FP. The bacteriology of 19. Lundy LB, Graham MD, Kartush JM, La Rouere MJ.
cholesteatoma. In: McCabe BF, Sade J, Abramson M, Temporal bone encephalocele and cerebrospinal
editors. Cholesteatoma: first international confer- fluid leaks. Am J Otol 1996;17:461–9.
ence. Birmingham (AL): Aesculapius; 1977. p. 264–7. 20. Jackson CG, Pappas DG, Manolidis S, et al. Brain
5. Latchaw RE, Hirsh WL, Yock DH. Imaging of herniation into the middle ear and mastoid: con-
intracranial infection. Neurosurg Clin North Am cepts in diagnosis and surgical management. Am J
1992;3:303–22. Otol 1997;18:198–206.
6. Dobben GD, Raofi B, Mafee MF, et al. Otogenic 21. Gower D, McGuirt WF. Intracranial complications
intracranial inflamations: role of magnetic resonance of acute and chronic infectious ear disease: a prob-
imaging. Top Magn Reson Imaging 2000;11:76–86. lem still with us. Laryngoscope 1983;93:1028–33.
7. Dew LA, Shelton C. Complications of temporal bone 22. Yen P-T, Chan S-T, Huang T-S. Brain abscess: with
infections. In: Cummings CW, editor. Otolaryngol- special reference to otolaryngologic sources of
ogy-head and neck surgery. 3rd ed. St. Louis: Mosby- infection. Otolaryngol Head Neck Surg 1995;113:
Year Book; 1998. p. 3047–75. 15–22.
316 Ballenger’s Otorhinolaryngology
23. Kurien M, Job A, Mathew J, Chandy M. Otogenic 27. Bell WE, McCormick WF. Neurologic infections in
intracranial abscess: concurrent craniotomy and mas- children. Philadelphia: WB Saunders; 1981.
toidectomy—changing trends in a developing country. p. 141–5.
Arch Otolaryngol Head Neck Surg 1998; 124:1353–6. 28. Kaplan DM, Kraus M. Otogenic lateral sinus throm-
24. Murthy P, Sukumar R. Otogenic brain abscess in child- bosis in children. Int J Pediatr Otorhinolaryngol 1999;
hood. Int J Pediatr Otorhinolaryngol 1991;22:9–17. 49:177–83.
25. Reid H, Fallon RJ. Bacterial Infections. In: Adams 29. Syms MJ, Tsai PD, Holtel MR. Management of lat-
JH, Duchen LW, editors. Greenfield’s pathology. New eral sinus thrombosis. Laryngoscope 1999;109:
York: Oxford University Press; 1992. p. 302–34. 1616–20.
26. Kerr RSC, Mitchell RG. Abscess. In: Swash M, 30. Singh B. The management of lateral sinus thrombo-
Oxbury J, editors. Clinical neurology. Edinburgh & sis. J Laryngol Otol 1993;107:803–8.
London: Churchill Livingstone; 1991. p. 886–98. 31. Symonds CP. Otitic hydrocephalus. Brain 1931;54:55.
CHAPTER 12
Otosclerosis
Herman A. Jenkins, MD, Omid Abbassi, MD, PhD
The term otosclerosis is derived from the Greek words acquires a spongy appearance (otospongiosis).8 On
for “hardening of the ear.” Although first recognized hematoxylin-eosin staining, it assumes a bluish
as a pathologic entity by Valsalva early in the eigh- coloration, referred to as the blue mantles of
teenth century,1 it was not until the mid-nineteenth Manasse.9 In the late stage, the reabsorbed bone is
century, with the observations of authors such as replaced with dense sclerotic bone—thus the name
Magnus,2 von Tröltsch,3 Politzer,4 and Toynbee,5 that otosclerosis.
the clinical presentation of the disease was clearly When involving the stapes, otosclerosis often
defined. Today, otosclerosis is recognized as an alter- starts from the fissula ante fenestram, although focal
ation in bony metabolism of the endochondral bone lesions involving the posterior annular ligament are
of the otic capsule. The ongoing process of resorption also seen. In general, it progresses from an anterior
and redeposition of bone results in fixation of the focal lesion to complete footplate involvement and,
ossicular chain and conductive hearing loss. in more advanced cases, may fill the oval window
niche entirely with new bone (obliterative otoscle-
rosis). In contrast, the round window is less fre-
PREVALENCE quently involved, and complete obliteration is a rare
Otosclerosis occurs most commonly among Cau- finding. Involvement of the cochlea can result in
casians,6 with an incidence of 1%, followed by Asians sensorineural hearing loss.
at 0.5%. It is far less common in African Americans.
In postmortem examinations of temporal bones,
Guild found evidence of a higher prevalence rate
ETIOLOGY
histologically, with 8.3% of Caucasians and 1% of Evidence for inflammatory and infectious causes has
African Americans manifesting the disease.7 been reported. A genetic component has long been
Although encountered in all age groups, usually the recognized, and transmission has generally been
clinical presentation occurs between the second and accepted to be autosomal dominant with incomplete
fifth decades of life. The disease process has a female penetrance. The gene for otosclerosis has not been
predominance of 2 to 1, and its progression tends to clearly identified, but authors in one study narrowed
accelerate with hormonal changes, particularly dur- its location to chromosome 15q25-26.10 Others have
ing pregnancy or the use of birth control pills. Bilat- related otosclerosis to the COL1A1 gene that encodes
eral disease is present in 80% of patients. for type 1 collagen. Investigators have noted its sim-
ilarities to osteogenesis imperfecta11 and Paget’s dis-
ease,12 both sharing lesions in the otic capsule nearly
HISTOPATHOLOGY identical to that of otosclerosis. A role for autoim-
The otosclerotic process is divided into two phases munity as been suggested, but the data remain
histologically. Bone resorption and increased vas- inconclusive.13
cularity characterize the early phase. When present Recent investigations on the role of infectious
near the periosteum of the middle ear, this hyper- agents have implicated the measles virus as having,
emia is responsible for Schwartze’s sign. As the at least, an inciting role in patients with a genetic
mature collagen content diminishes, the bone predisposition for otosclerosis.14 Elevated titers of
317
318 Ballenger’s Otorhinolaryngology
immunoglobulin G specific for measles virus anti- the early stages but cannot be elicited as stapes fixa-
gens have been found in the perilymph of patients tion proceeds. Speech discrimination is often normal,
with otosclerosis. Immunohistochemical evidence of except in patients with cochlear involvement. Clini-
measles antigen has also been demonstrated in active cally, other diagnostic studies such as high-resolution
otosclerotic foci, using reverse transcription poly- computed tomography (CT) and magnetic resonance
merase chain reaction amplification of measles virus imaging (MRI) are of little use in evaluation of oto-
ribonucleic acid.15 However, the actual role of the sclerosis. With high-resolution CT, however, one may
virus in producing the disease is not established. be able to identify the sclerotic lesion.
approach to stapes surgery. 22 In the intervening coagulants during the 2 weeks prior to the operation
years, techniques have changed, and new materials should be avoided, including anti-inflammatory
for reconstruction have been introduced; however, agents. Muscle relaxants in conjunction with anes-
the principles still remain basically the same. thetic agents are not recommended because of their
The surgical goal in otosclerosis is restoration effect on facial nerve activity. Perioperative antibi-
of the transmission mechanism for sound from the otics are at the surgeon’s discretion, but antiemetic
tympanic membrane, going through the ossicular agents are recommended.
chain to the oval window, bypassing the resistance of Whether a general or local technique is
the fixed stapes footplate. Today, a variety of tech- employed, injections of local anesthetics should be
niques are used to correct for stapes footplate fixa- administered in such a manner as to avoid uninten-
tion. Generally, the stapes arch is removed, and tional involvement of the facial nerve medial to the
either a perforation or a partial to complete removal mastoid tip. Sterility of the operative field is of para-
of the footplate is performed. A prosthetic implant is mount importance since a direct connection to the
employed to connect the incus to the oval window. labyrinth is established during parts of the opera-
tion. Routine operative site scrub technique, includ-
PATIENT SELECTION ing installation of antibacterial preparation solution
into the external auditory canal, is recommended.
Selection of patients for operation is based on audi- Facial nerve activity is monitored by direct vision of
ologic findings and physical examination. Preferred the face through a transparent occlusive drape.
are patients with normal middle ear aeration, free of
any infection or tympanic membrane perforation
and with a Rinne test that demonstrates bone con- SURGICAL TECHNIQUE
duction to be greater than air conduction. When Stapes surgery may be performed via an endaural or
bilateral disease presents, the worse hearing ear is anterior incisural incision. The endaural incision
treated first followed by the other ear several months requires use of a speculum held stationary with the
later. Experienced otologists should perform surgery left hand or a speculum holder assembly. In contrast,
on the only hearing ear, exclusively and with great the anterior incisura incision is held open using one
trepidation. or two self-retaining retractors, eliminating the need
to operate through a speculum. The cosmetic result
INFORMED CONSENT of the incision is rarely noticeable. The latter also
Preoperative consent is obtained, informing the provides direct access to the tragal cartilage if a peri-
patient of the risks of loss of hearing, vertigo, injury chondrial graft is desired.
to the facial nerve, loss or alteration of taste, tym- Regardless of the approach, a tympanomeatal
panic membrane perforation, prosthesis extrusion, flap is raised, the annulus is identified, and hemo-
prosthesis mobilization, and residual conductive stasis is established prior to entering the middle ear
hearing loss. Singers and musicians are informed of space. A 1% lidocaine with 1:100,000 epinephrine or
a possible change in quality of sound perception that an 1:1,000 epinephrine-soaked piece of Gelfoam is
may affect their professional performance. Individu- used in this step. The tympanomeatal flap is elevated
als who are exposed to or plan to be involved in anteriorly, and the chorda tympani nerve is dissected
activities associated with rapid and/or considerable free toward the malleus. A portion of the scutum
change in pressure, such as scuba diving and piloting should be curetted to expose the incus and the incu-
nonpressurized airplanes, are advised to refrain from dostapedial joint. Fixation of the stapes is deter-
stapedectomy. mined by palpation of the malleus while viewing the
suprastructure and footplate of the stapes.
The distance between the mid-shaft of the long
PERIOPERATIVE TREATMENT process of the incus and the footplate is measured
The operation may be performed under either gen- (Figure 12–1, A). The incudostapedial joint is sepa-
eral or local anesthesia. With improvements in anes- rated, and the stapedial tendon is severed. The stapes
thesia, more otologists are now performing the suprastructure is fractured inferiorly and removed
operation under general anesthesia. Use of any anti- from the middle ear (Figure 12–1, B).
320 Ballenger’s Otorhinolaryngology
Establishing contact with the perilymphatic tion is gradually enlarged with a handheld drill to
space may be done in several ways. The trend within 0.6 mm in diameter. The stapes replacement pros-
the last decade has moved to smaller fenestra to pro- thesis of choice is placed in the perforation and
tect the inner ear as much as possible. Typically, a attached to the incus. The length of the prosthesis
small fenestra is created, or the footplate is partially used is longer (by 0.25 mm) than the distance
removed. When the surgeon removes the footplate, between the medial aspect of the long process of the
a stapedectomy is performed. Depending on the incus and footplate, measured earlier, since the tip of
training and preference of the otologist, the poste- the prosthesis has to go through the footplate. The
rior half of the footplate is removed (Figure 12–2). addition of fresh clotted blood to the area also helps
In the technique demonstrated, the footplate is frac- reduce the risk of a perilymphatic fistula.
tured in half, with the posterior portion being Many otologists have advocated use of a laser in
removed. A perichondrial graft from the tragus or a performing a stapedotomy. The advantage of the
vein graft is placed over the defect, and the prosthe- laser is decreased manipulation of the suprastructure
sis is positioned over it and secured to the incus. and footplate. The thermal effect is negligible.23 The
In the stapedotomy technique, a perforation in disadvantage is the extra time, expense, and instru-
the footplate is made, just large enough to allow pas- mentation needed. Perkins and Curto popularized a
sage of the prosthesis. Figure 12–3 illustrates the combination laser stapedotomy with tissue coverage
technique popularized by Fisch in which a perfora- of the perforation.24 Figure 12–4 demonstrates this
technique. A vein graft is placed over a drilled hole in and decrease the chance of a perilymphatic fistula
a Teflon block. A prosthesis is placed in the hole, and formation. Patients are cautioned against blowing
the vein graft is allowed to dry and become adherent their noses and sneezing with their mouths closed.
to the prosthesis. Rosettes of charred bone are created Postoperative follow-up is scheduled in 1 week
by the laser and gently removed with a pick. The to remove the suture and packing and assess the
prosthesis and graft are positioned over the fenestra integrity of the tympanic membrane. Hearing test-
with the tip projecting into the vestibule, and the ing is done 4 to 6 weeks following the operation.
prosthesis is positioned under the incus.
PITFALLS
POSTOPERATIVE MANAGEMENT The pitfalls of the surgery include inadequate expo-
Postoperatively, the patient is sent home to bed and sure and anatomic variations. The endaural incision
to remain on light activity for several days. Pain and speculum produce a narrower opening when
management requires mild oral medication, and compared to the anterior incisura approach. The
antibiotics are not necessary. Postoperative vertigo is scutum can cover the long process of the incus and
treated with ondansetron (Zofran) or promethazine the posterior half of the stapes. Adequate removal of
(Phenergan). Stool softeners help reduce straining the scutum ensures proper visualization of the foot-
plate in the crucial stage of footplate perforation and overall rate of anacusis following stapes surgery is
prosthesis placement. An aberrant facial nerve may in the range of 1 to 2%.28
prohibit a stapedectomy, and relocation of the nerve,
which carries a risk of facial weakness and paralysis,
is not recommended. A dehiscent nerve has a higher
COMPLICATIONS
chance of facial nerve injury. The complications of the stapes surgery are immediate
Advanced otosclerosis with obliteration of the and delayed in nature. Immediate complications are
oval window requires drilling of the footplate and those occurring during the operation, such as facial
significant experience with temporal bone anatomy. nerve paralysis secondary to infusion of the local anes-
Sclerotic obstruction of the round window is of less thetic or injury, vertigo, and/or hearing loss caused by
importance since only a small opening over the suctioning of the perilymphatic fluid from the oval
round window is necessary to allow proper cochlear window during the operation or persistent postopera-
function. Drilling out the round window often tive perilymphatic leakage from the oval window. Bed
results in a severe hearing loss and is avoided. rest and light activities are recommended for vertigi-
If the footplate should drop into the vestibule, nous patients, and most recover shortly after the oper-
attempts should be made to remove it. However, this ation. Metallic taste and loss of taste caused by
should be done only if one can easily grasp the edge manipulation of or injury to the chorda tympani
and gently remove it. Never go fishing for bony frag- nerve are not uncommon. Labyrinthitis, although pos-
ments that descend into the vestibule, away from the sible, occurs rarely under sterile conditions.
annular rim. Delayed postoperative complications, includ-
During the stapedectomy, the protective func- ing perilymphatic fistula,31 granuloma,32 and pros-
tion of the stapedius muscle is destroyed. A new thesis dislocation, have been reported. Immediate
technique in which the stapedius muscle is left in treatment with antibiotics and rest is recommended.
place and the posterior crus of the fractured supra- Re-exploration should be entertained to correct for
structure is shaped and used as an autologous stapes the fistula should persistent vertigo occur. Granu-
replacement graft has been proposed and used. The loma formation can occur for totally unknown rea-
efficacy of this technique in preserving the acoustic sons and in the best of settings. Keeping all foreign
reflex is controversial. material, such as the talc powder of the glove and
bone dust, away from the footplate area may
decrease the chances of granulomas. A dislocated
RESULTS prosthesis requires re-exploration and revision.
Otosclerosis surgery has withstood the test of time
since its reinstitution in the 1950s. Shea, in his
review of 40 years of stapes surgery, reported clo-
REFERENCES
sure to within 10 dB of the preoperative bone-con- 1. Valsalva AM. Opera, hoc est, tractatus de aure
duction level in over 95% of patients.25 Glasscock humana. Venice: Pitteri; 1735.
et al reported over 91% closure to within 5 dB.26 2. Magnus A. Über Verlauf und Sektionsbefund eines
Both groups reported significantly less success in Falles von hochgradiger und eigenthumlicher
revision surgery. Persson et al contrasted stapedec- Gehorstorung. Arch Ohrenheilk 1876;11:244–51.
tomy and stapedotomy in the review of their 3. von Tröltsch A. Treatise on the diseases of the ear
series.27 They demonstrated that partial and total including the anatomy of the organ. New York:
stapedectomy had better results at all frequencies William Wood; 1869.
with the exception of 4 kHz. However, the hearing 4. Politzer A. Über primäre Erkrankung der knöcher-
results in this group tended to deteriorate more nen Labyrinthkapsel. Z Ohrenheilk 1894;25:309–27.
quickly than the stapedotomy patients. Others 5. Toynbee J. Diseases of the ear. Philadelphia: Blan-
have reported similar preservation of high fre- chard and Lea; 1860.
quencies with stapedotomy. 28 Outcome in the 6. Levin G, Fabian P, Stahle J. Incidence of otosclerosis.
training situation demonstrates significantly Am J Otol 1988;9:299–307.
poorer results.29 A definite learning curve in stapes 7. Guild SR. Histologic otosclerosis. Ann Otol Rhinol
surgery is present after training.30 The accepted Laryngol 1944;53:246–66.
Otosclerosis 323
8. Siebenmann F. Demonstration mikroscopischer und 20. Lempert J. Improvement in hearing in cases of oto-
makroscopischer Paraparate von Otospongiosis pro- sclerosis: a new, one stage surgical technic. AMA
gressiva. Papers Int Otol Congr 1912;9:207. Arch Otolaryngol 1938;28:42.
9. Manasse P. Neue Untersuchungen zur Otosklerosen- 21. Rosen S. Palpation of the stapes for fixation. AMA
frage. Z Ohrenheilk 1922;82:76–96. Arch Otolaryngol 1952;56:610.
10. Tomek MS, Brown MR, Mani SR, et al. Localization 22. Shea JJ. Fenestration of the oval window. Ann Otol
of a gene for otosclerosis to chromosome 15q25-26. Rhinol Laryngol 1958;67:932–51.
Hum Mol Genet 1988;7:285–90. 23. Coker NJ, Ator GA, Jenkins HA, et al. Carbon diox-
11. McKenna MJ, Kristiansen AG, Bartley ML, et al. ide laser stapedotomy, thermal effects in the
Association of COL1A1 and otosclerosis: evidence vestibule. Arch Otolaryngol 1985;111:601–5.
for a shared genetic etiology with mild osteogenesis 24. Perkins R, Curto FS. Laser stapedotomy: a compara-
imperfecta. Am J Otol 1998;19:604–10. tive study of prostheses and seals. Laryngoscope
12. Khetarpal U, Schuknecht HF. In search of pathologic 1992;102:1321–7.
correlates for hearing loss and vertigo in Paget’s dis- 25. Shea JJ. Forty years of stapes surgery. Am J Otol
ease. A clinical and histopathologic study of 26 tem- 1998;19:52–5.
poral bones. Ann Otol Rhinol Laryngol Suppl 1990; 26. Glasscock ME, Storper IS, Haynes D, Bohrer PS.
99:1–16. Twenty-five years of experience with stapedectomy.
13. Yoo TJ, Tomoda K, Stuart JM, et al. Type II collagen- Laryngoscope 1995;105:899–904.
induced autoimmune otospongiosis. A preliminary 27. Persson P, Harder H, Magnuson B. Hearing results in
report. Ann Otol Rhinol Laryngol 1983;92:103–8. otosclerosis surgery after partial stapedectomy, total
14. Niedermeyer HP, Arnold W. Otosclerosis: a measles stapedectomy and stapedotomy. Acta Otolaryngol
virus associated inflammatory disease. Acta Oto- (Stockh) 1997;117:94–9.
laryngol (Stockh) 1995;115:300–3. 28. Kursten R, Schneider B, Zrunek M. Long-term
15. McKenna MJ, Mills BG. Immunohistochemical evi- results after stapedectomy versus stapedotomy. Am J
dence of measles virus antigens in active otosclero- Otol 1994;15:804–6.
sis. Otolaryngol Head Neck Surg 1989;101:415–21. 29. Backous DD, Coker NJ, Jenkins HA. Prospective
16. Shambaugh GE, Scott A. Sodium fluoride for arrest study of resident-performed stapedectomy. Am J
of otosclerosis. Arch Otolaryngol 1964;80:263. Otol 1993;14:451–4.
17. Kessel J. Über das Ausschneiden des Trommelfelles 30. Hughes GB. The learning curve in stapes surgery.
und Mobilisieren des Steigbügels. Arch Ohrenheilk Laryngoscope 1991;101:1280–4.
1877;12:237. 31. Goodhill V. Variable oto-audiologic manifestations
18. Miot C. De la mobilisation de l’étrier. Rev Laryngol of perilymphatic fistulae. Rev Panam Otorhino-
1890;7:225. laringol Bronchoesofagol 1967;1:100–9.
19. Siebenmann F. Sur le traitement chirurgical de la scle- 32. Harris I, Weiss L. Granulomatous complications of
rose otique. Congr Int de Med Sect d’Otol 1900;13:170. oval window fat grafts. Laryngoscope 1962;72:870–85.
CHAPTER 13
Hearing impairment may be classified etiologically as and the longer arm is designated “q.” Chromosomes
either inherited or acquired and temporally as either are further labeled by the banding pattern that is pro-
prelingual (congenital) or postlingual (late in onset). duced by staining (see Figures 13–1, A and B). Band
Although useful, these types of classification belie the patterns are distinct for each chromosome and are
complex interaction of genetics and environment individually numbered (7q31 refers to chromosome
that make the study of hearing impairment, particu- 7, long arm, band three, one).
larly late-in-onset deafness, difficult. For example, Individuals inherit half of their autosomal
although presbycusis and noise-induced hearing loss chromosomes from their father and half from their
might be dismissed as the end result of accumulated mother. Therefore, every gene exists as a pair, with
age and environmental trauma, animal studies have one copy of paternal origin and the other copy of
shown that genetic background is an important maternal origin. Each copy is referred to as an allele.
determinate of final outcome. By focusing on con- The alleles of a gene pair may be identical, or subtle
genital hereditary hearing loss, the confounding differences may be present. If the alleles are identical,
effects of environment are minimized, and our an individual is said to be homozygous for that gene
understanding of the genetics of aural development pair; alternatively, if the alleles are different, an indi-
and auditory function is simplified. vidual is said to be heterozygous. For example, if a
Approximately 50% of congenital deafness is gene has two possible alleles, A and A′, and an AA′ by
inherited,1,2 and among school-aged children, 1 child AA′ mating occurs, the progeny will have genotypes
in 650 to 2,000 has some form of hereditary deaf- AA, AA′, or A′A′. If normal function of this gene is
ness.3,4 As the incidence of deafness owing to infec- essential for normal hearing, and A′ encodes an allele
tious and iatrogenic causes diminishes, and as our of the gene that is associated with hearing impair-
ability to diagnose abnormalities improves, the rela- ment, deafness could result. If progeny with geno-
tive importance of hereditary factors as causes of types AA′ or A′A′ are hearing impaired, one can
deafness increases. assume that A′ is dominant over A. Alternatively, if
all progeny have normal hearing except those with
genotypes A′A′, one can assume that A′ is recessive
PATTERNS OF INHERITANCE with respect to A. In the first case, both parents will
Genetic information is passed from one generation to be hearing impaired, whereas in the second case,
the next encoded in the human genome. The human only A′A′ progeny will be hearing impaired. These
genome is comprised of 46 chromosomes, 22 pairs of patterns of allele segregation are referred to as auto-
autosomes, and the sex chromosomes, XY in males somal dominant and autosomal recessive inheri-
and XX in females. The autosomes vary in size and tance, respectively (Figures 13–2, A and B).
can be arranged by karyotype from largest to smallest Deafness caused by genes on the X chromosome
(Figures 13–1, A and B). Variances in shape are caused is usually inherited as an X-linked recessive trait (Fig-
by the centromere, which divides a chromosome into ure 13–2, C). The deafness is rarely penetrant in a car-
two arms. A chromosome is described as metacentric rier female, but half of all sons are affected, and half
if the centromere is in the center, submetacentric if it of all daughters are carriers. If the affected gene is
is off center, or acrocentric if it is near an end. The inherited through the father, there are no affected off-
shorter of the two arms is designated “p” (for petite), spring, although all daughters are carriers. Mitochon-
324
Hereditary Hearing Impairment 325
A B
drial deafness is inherited only through the mother,5,6 these syndromes, one of the more useful is based on
and sons and daughters may be affected equally. the involved organ system (Table 13–1). Some of the
When hereditary deafness is classified by more common forms of syndromic hearing impair-
mode of inheritance, 60 to 70% of cases are autoso- ment are discussed in more detail with particular
mal recessive, 20 to 30% are autosomal dominant, reference to recent advances in the understanding of
and 2% are X-linked. 2,7 In nearly 33% of cases, their genetic basis (Table 13–2).
other phenotypic characteristics cosegregate with
the hearing loss. These types of hearing impairment AUTOSOMAL DOMINANT SYNDROMIC
are known as “syndromic” and make the unequivo-
cal diagnosis of hereditary deafness much easier. HEARING IMPAIRMENT
Typically, a wide range of phenotypes occurs, even Branchio-Oto-Renal Syndrome Although the
in individuals carrying the same deafness-causing association of branchial arch anomalies with hearing
genetic mutation, a phenomenon known as variable impairment has long been recognized, it was not
expressivity. An affected individual may exhibit a until 1975 that Melnick and colleagues described
few, some, or all of the phenotypic manifestations branchio-oto-renal (BOR) syndrome.9 Affected per-
typically associated with a particular genetic abnor- sons have branchial clefts or fistulae, otologic abnor-
mality. On rare occasions, an individual may have malities, and renal anomalies (Figure 13–3). The
no abnormal physical findings, and the genetic pattern of inheritance is consistent with autosomal
mutation is said to be nonpenetrant. In the absence dominant transmission, and although gene pene-
of cosegregating physical findings, inherited deaf- trance approaches 100%, there is considerable varia-
ness is said to be “nonsyndromic.” Nonsyndromic tion in expression. Disease prevalence approximates
deafness is subclassified by mode of inheritance as 1 in 40,000 in the general population, but in the Deaf
DFNA, DFNB, or DFN for dominant, recessive, or community, BOR syndrome may be responsible for
X-linked, respectively (DFN for deafness). Loci are over 2% of profound deafness.10
numbered in order of discovery. Mitochondrial Hearing impairment is the single most com-
deafness is designated by mutation type. mon trait of BOR and is found in over 90% of
affected individuals. The loss can be conductive, sen-
sorineural, or mixed, with differences occurring even
SYNDROMIC HEARING IMPAIRMENT
within families. Age of onset varies from early child-
Hearing loss has been described in over 400 syn- hood to young adulthood, and both stable and pro-
dromes.8 Although there are many classifications for gressive hearing loss have been reported.11–14
326 Ballenger’s Otorhinolaryngology
A B
Progressive loss is likely to be attributable to associ- identified in families with BOR syndrome; how-
ated temporal bone abnormalities such as a dilated ever, in about 70% of persons with a BOR syn-
vestibular aqueduct (DVA).13 Other associated tem- drome phenotype, EYA1 mutations cannot be
poral bone abnormalities include cochlear hypopla- found. This finding, together with marked pheno-
sia, bulbous internal auditory canals, deep posterior typic variability, has suggested to some investiga-
fossae, acutely angled promontories, and anomalous tors that BOR syndrome is a heterogeneous disease,
facial nerve course. Table 13–3 outlines the most a hypothesis recently confirmed with the identifi-
common features of BOR syndrome. Early studies cation of a second BOR syndrome locus on chro-
probably underestimated the true incidence of renal mosome 1p31.18
anomalies, which occur in up to 75% of cases and
include renal agenesis, renal hypoplasia, renal dys- Crouzon’s Disease Crouzon’s disease (CD) is
plasia, pelvic ureteral junction obstruction, and another autosomal dominant type of syndromic
polycystic kidneys. Glomerular lesions and vesi- hearing impairment, although one-third of cases
coureteral reflux progressing to renal failure have are attributable to new mutations. It is diagnosed
been described as well. in about 5% of newborns with craniosynostosis
In the early 1990s, the BOR gene was mapped and occurs with an estimated incidence of 1.65 in
to chromosome 8q, and in 1997, the causative gene 100,000 births.19 In addition to craniosynostosis, it
was cloned.15–17 This gene is a human homologue of is characterized by hypertelorism, midface
the Drosophila eyes absent gene (eya) and has been hypoplasia, and exophthalmos. 20 One-third of
called EYA1. Its expression pattern suggests a role in affected persons have conductive hearing loss sec-
the development of all components of the inner ear. ondary to external or middle ear abnormalities.
In the kidney, murine Eya1 plays a role in the devel- Frequently, there is an associated sensorineural
opment of the metanephric cells surrounding the component.21
“just-divided” ureteric branches. Mutations in fibroblast growth factor receptor
A variety of missense and nonsense muta- (FGFR) genes are implicated in a number of cran-
tions, as well as insertions and deletions, have been iosynostosis syndromes including CD.22 These genes
Hereditary Hearing Impairment 327
are tyrosine kinases that span the cell membrane and angle tumors; (2) a first-degree relative with NF2 and
are important in mitogenesis and cell migration, a unilateral eighth nerve tumor; (3) a first-degree rel-
development, and differentiation. FRGR2 mutations ative with NF2 and two of the following: neurofi-
cause CD.23 broma, meningioma, glioma, schwannoma, or
juvenile posterior subcapsular lenticular opacity.
Neurofibromatosis 2 Neurofibromatosis 2 (NF2) is The causative gene encodes a protein called
a central form of neurofibromatosis characterized by merlin that shows similarity to a group of cell mem-
bilateral vestibular schwannomas. Other features brane-cytoskeleton protein linkers that regulate cell
include meningiomas, spinal cord dorsal root adhesion and morphogenesis. Inactivation of merlin
schwannomas, and posterior subcapsular cataracts. in the mouse by targeted mutagenesis produces a
Criteria for diagnosis include one of the following24: variety of malignant tumors with a high rate of
(1) bilateral internal auditory canal/cerebellopontine metastasis, suggesting that merlin also functions as a
328 Ballenger’s Otorhinolaryngology
TABLE 13–2. Selected Causes of Syndromic Hearing Impairment with Genetic Features
Syndrome/Disease Locus Gene Function of Encoded Protein
Alport’s Xq22 COL4A5 Specific components of glomerular
2q36-2q37 COL4A3 basement membrane within the
2q36-2q37 COL4A4 kidney; in the cochlea, they are
found in the basilar membrane, parts
of the spiral ligament, and the stria
vascularis
Branchio-oto-renal
BOR1 8q13.3 EYA1 Human homologue of Drosophila eyes
BOR2 1q31 Unknown absent gene; plays a role in the
development of all components of
the inner ear
Crouzon’s 10q25-26 FGFR2 Member of the tyrosine kinase receptor
superfamily; has high affinity for
peptides that signal the transduction
pathway for mitogenesis, cellular
differentiation, and embryogenesis
Jervell and Lange-Nielsen
JLNS1 11p15.5 KVLQT1 Subunits of a voltage-gated potassium
JLNS2 21q22.1-q22.2 KCNE1 channel protein; important for
endolymph homeostasis
Neurofibromatosis
NF2 22q12 NF2 Merlin, a tumor suppressor
Pendred’s 7q21-34 PDS Chloride-iodide transporter
Stickler’s
STL1 12q13.11-13.2 COL2A1 Fibrillar collagens arrayed in a quarter-
STL2 6p21.3 COL11A2 staggered fashion; extracellular
STL3 1p21 COL11A1 matrix components
Treacher Collins 5q32-q33.1 TCOF1 Highly phosphorylated nucleolar
protein; a nuclear transcription
factor
Usher’s
USH1A 14q32 Unknown
USH1B 11q13.5 MYO7A Unconventional myosin—moves
actin filaments using actin-
activated adenosine
triphosphatase; maintains
stereocilia integrity; present in
inner and outer hair cells
USH1C 11p15.1 USH1C Harmonin, which may function as a
rafting protein in gating
complexes in the stereocilia
USH1D 10q CDH23 Important for the formation of tight
junctions
Continued
Hereditary Hearing Impairment 329
TABLE 13–2. Selected Causes of Syndromic Hearing Impairment with Genetic Features—Continued
Syndrome/Disease Locus Gene Function of Encoded Protein
USH1E 21q Unknown
USH1F 10 Unknown
USH2A 1q41 USH2A Usherin a possible component of basal
lamina and extracellular matrices; may
be involved in cellular adhesion
USH2B 3p23-24.2 Unknown
USH2C 5q14.3-q21.3 Unknown
USH3 3q21-q25 Unknown
Waardenburg’s
WS1 2q35 PAX3 A DNA-binding protein that is believed
to regulate the expression of other
genes; mutations result in neural
crest–derived melanocyte deficiency
WS2 3p14.1-p12.3 MITF Homodimeric transcription factor
WS3 2q35 PAX3 As above
WS4 13q22 EDNRB A receptor involved in the formation of
an endothelin signaling pathway
WS4 20q13.2-q13.3 EDN3 A transcription factor
WS4 22q13 SOX10 Required for development of early
neural crest–derived progenitor cells
tumor suppressor.26,27 A variety of mutations have and STL3, respectively.33–35 Because COL11A2 is not
been described, and it appears that there is some expressed in the eye, persons affected with STL2 do
genotype-phenotype correlation as truncating or not have myopia.
inactivating mutations lead to severe phenotypes
with an earlier age of onset, whereas missense muta- Treacher Collins Syndrome Treacher Collins syn-
tions are associated with milder disease and a later drome (TCS) is a disorder of craniofacial develop-
age of onset.28,29 ment affecting structures derived from the first
branchial arch. It is characterized by midface
Stickler’s Syndrome Stickler (STL) syndrome, also hypoplasia, micrognathia, macrostomia, colobomas
known as hereditary arthro-ophthalmopathy, is char- of the lower eyelids, downward slanting palpebral
acterized by marfanoid features, spondyloepiphyseal fissures, cleft palate, and conductive hearing loss
dysplasia, joint hypermobility, midface hypoplasia, owing to external and middle ear abnormalities.36
severe myopia, and varying degrees of Robin sequence Inner ear abnormalities are rare, although enlarge-
(cleft palate, micrognathia, and glossoptosis). Because ment of the utricle and aplasia of the horizontal
of the possibility of retinal detachment, ophthalmo- canal have been reported.37 The reported incidence
logic assessment is mandatory. Approximately 15% of of TCS is about 1 in 50,000 live births.38
affected individuals have a mixed hearing loss.30–32 The causative gene, TCOF1, encodes a protein
Gene linkage studies have demonstrated considerable called treacle that is structurally related to nucleolar
genetic heterogeneity, with mutations in COL2A1, phosphoproteins and may play a role in nucleolar-
COL11A2, and COL11A1 implicated in STL1, STL2, cytoplasmic transport.39 Up to 60% of affected per-
330 Ballenger’s Otorhinolaryngology
its ligand EDN3, or SOX10 (see Table 13-2). Recent offered to affected persons and their families to min-
studies have confirmed a complex interaction imize potential morbidity and mortality.52
between these genes, with SOX10 and PAX3 proteins
synergistically activating MITF expression.46–51 Pendred’s Syndrome Pendred’s syndrome (PS) is
Numerous different allele variants in these genes characterized by congenital sensorineural hearing
have been reported as causing deafness. loss and goiter. Prevalence estimates range from 1 to
7.5 per 100,000 newborns, suggesting that it may
account for up to 7.5% of all childhood deafness.53,54
AUTOSOMAL RECESSIVE SYNDROMIC HEARING The degree of hearing loss is variable but is most fre-
IMPAIRMENT quently profound and is associated with temporal
bone abnormalities ranging from a DVA to Mon-
Jervell and Lange-Nielsen Syndrome Jervell and dini’s dysplasia (Figure 13–5). Goiter may be appar-
Lange-Nielsen syndrome (JLNS) is characterized by ent at birth but typically presents in mid-childhood.
profound prelingual sensorineural hearing loss, syn- The thyroid defect involves organification of iodine
cope, and sudden death owing to a prolonged QT and can be diagnosed by administering perchlorate,
interval. The syndrome was first described in Norway, which releases unbound iodide from thyroid follic-
where its estimated prevalence is 1 in 200,000. Diag- ular cells. Despite this abnormality, affected individ-
nostic criteria include a QTc > 440 ms in males and uals usually remain euthyroid.
> 460 ms in females.52 Syncopal attacks are usually The disease is caused by mutations in PDS, a
associated with exertion or emotion, and with prompt member of the solute carrier 26 gene family. The
diagnosis and antiarrhythmic treatment, the high encoded protein pendrin transports chloride and
mortality rate can be significantly reduced. iodide and mediates the exchange of chloride and
Mutations in KCNQ1 and KCNE1, which formate, properties that suggest tissue-specific func-
encode subunits of a voltage-gated potassium chan- tion.55 In the thyroid gland, pendrin has been
nel protein, have been shown to cause JLNS. How- immunolocalized to the apical membrane of the thy-
ever, there is likely to be considerable genetic rocyte, where it may allow intracellular iodide to pass
heterogeneity as mutations have not been identified into the colloid space to be bound to thyroglobulin.
in a number of families. Some heterozygous indi- In the kidney, pendrin probably functions as a chlo-
viduals may have a prolonged QT interval in the ride/formate exchanger, which is important for chlo-
absence of hearing loss and are prone to life-threat- ride transport in the proximal tubule. The role of
ening arrhythmias. Genetic counseling should be pendrin in the inner ear is unknown.
*An affected individual must have at least two major criteria or one major criterion and two minor criteria. Criteria for Waarden-
burg’s syndrome type 2 have been suggested that include premature graying as a major criterion instead of dystopia canthorum.
W = Waardenburg index.
332 Ballenger’s Otorhinolaryngology
Over 45 different deafness-causing PDS muta- developmental milestones.61 They are late in sitting
tions have been reported, and although many families and walking and have absent ice-water responses to
have “private mutations,” in about half of affected per- caloric testing. Hearing loss is typically profound,
sons, one of three different mutations is found (L236P, and hearing aids are frequently ineffectual as a habil-
T416P, 1001+1G→A).56,57 PDS allele variants can be itation option. Accordingly, most persons with
identified in approximately 80% of multiplex families USH1 integrate into the Deaf community. Persons
segregating for either DVA or Mondini’s dysplasia, with USH2, in contrast, have normal vestibular
suggesting that mutations in this gene are the major function and usually have a moderate-to-severe
genetic cause of these two temporal bone anomalies. hearing loss. They use hearing aids effectively and
communicate orally. Persons with USH3 have pro-
Usher’s Syndrome Usher syndrome (USH) is the gressive vestibular and auditory dysfunction.
most common autosomal recessive syndromic form Initial visual problems with USH begin as nyc-
of hearing impairment. Characterized by blindness talopia or night blindness. This problem can occur
caused by retinitis pigmentosa and sensorineural in the preschool years, although visual acuity usu-
hearing loss, it is responsible for half of all deaf- ally remains good until the third decade. By the fifth
blindness in the United States and an estimated 3 to decade, 40% of persons with USH are blind; by the
10% of all congenital deafness.58 It can be classified seventh decade, this figure increases to 75%.62,63
into three different types based on clinical presenta- Constriction of the visual fields accompanies the loss
tion (Table 13–5). USH1 and USH2 are most com- in visual acuity. Studies of multiplex families have
mon, whereas USH3 is quite rare, accounting for documented considerable intrafamilial variation in
only 5 to 15% of all USH.59,60 the rate and degree of visual deterioration. Elec-
Vestibular dysfunction differentiates USH1 troretinography (ERG) may uncover early retinitis
from USH2. Persons with USH1 have vestibular are- pigmentosa and should be considered in all cases of
flexia and, as infants, fail to achieve normal motor congenital deafness to identify early USH.64
Hereditary Hearing Impairment 333
Usher’s syndrome demonstrates considerable mation of tight junctions. Mutations in this gene
genetic heterogeneity. To date, seven USH1 loci also cause DFNB12.
(USH1A-1G), three USH2 loci (USH2A-C), and one
USH3 locus have been identified.65–70 Five of the rel-
evant genes have been cloned, MYO7A, USH1C,
X-LINKED SYNDROMIC HEARING IMPAIRMENT
USH2A, and CDH23, and PCDH1S mutations in Alport’s Syndrome Progressive glomerulonephri-
which cause USH1B, USH1C, USH2A, and USH1D, tis, sensorineural hearing loss, and specific eye find-
and USH1F respectively.71–73 MYO7A is an uncon- ings characterize Alport’s syndrome (AS), which can
ventional myosin expressed mainly in inner and be inherited as an X-linked or autosomal disorder.
outer hair cells. In the eye, it is localized to microvilli To facilitate diagnosis, four clinical criteria were
projections in retinal pigmentary epithelial cells and established in 1988.75 In the presence of unexplained
photoreceptor cells. Because there are no mutational hematuria, a person can be considered affected if
hotspots, mutation detection in at-risk families three of the following criteria are met: (1) a positive
requires considerable work. Mutations in this gene family history of hematuria or chronic renal failure;
also cause DFNB2 and DFNA11. (2) electron microscopic renal biopsy evidence of
The USH1C gene encodes a PDZ domain– AS; (3) characteristic eye signs of anterior lenti-
containing protein called harmonin, which may conus, white macular flecks, or both; (4) high-fre-
function as a rafting protein in gating complexes in quency sensorineural hearing loss.
the stereocilia.72 Several different mutations have Since light microscopy of renal biopsy speci-
been found in USH1C patients. The USH2A gene mens is usually normal in children and because find-
encodes a protein designated usherin, which has ings are nonspecific in adults, electron microscopy is
both laminin epidermal growth factor and fibro- essential. This degree of resolution reveals splitting of
nectin type III domains.74 The 2299delG-allele vari- segmental areas of glomerular basement membrane,
ant is the most frequent mutation and is found in accompanied by thickening and electron-lucent areas
about 15% of persons with USH2A. The USH1D containing dense granulations. Serial biopsies
gene CDH23 is a member of the cadherin gene fam- demonstrate progressive deterioration.76 The eye
ily, and its encoded protein is important for the for- findings characteristic of AS are rarely noted in child-
334 Ballenger’s Otorhinolaryngology
HI = hearing impairment.
hood and may become apparent only with renal fail- Kearns-Sayre Syndrome Kearns-Sayre syndrome
ure. These include anterior lenticonus (conical pro- is a multisystem disorder characterized by progres-
jection of the anterior surface of the lens), macular sive ophthalmoplegia, pigmentary retinopathy, car-
flecks, and peripheral coalescing flecks. The progres- diac conduction abnormalities, and cerebellar ataxia.
sive myopia caused by anterior lenticonus is consid- It usually presents in the second decade. Mixed hear-
ered by some authors to be sufficient to diagnose ing loss may be an additional feature.25
AS.77 Hearing loss is postlingual, progressive, and
sensorineural. Maternally Inherited Diabetes and Deafness
The typical male with X-linked AS presents Studies of diabetic patients from different popula-
with hematuria at age 3 to 4 years, often following an tions have confirmed an association between dia-
upper respiratory tract infection. Toward the end of betes mellitus, sensorineural hearing loss, and
the first decade, hearing loss is detectable, and in the mitochondrial mutations.80,81 The hearing loss and
mid-teens, hypertension develops. By 25 years of the diabetes are felt to result from an impairment of
age, over 90% of affected males have abnormal renal oxidative phosphorylation. The most frequently
function.76 The clinical course in female carriers is found mutation, a 3243 A-to-G transition, is present
much more variable. Most are clinically asympto- in 2 to 6% of diabetic patients in Japan.81 Over 60%
matic through life. Although nearly all have evidence of these patients have hearing loss, which usually
of microscopic hematuria, about one-third will have develops after the onset of their diabetes. The same
macroscopic hematuria. One-third will develop mutation is also found in MELAS.
hypertension, whereas the risk of chronic renal fail-
MELAS Syndrome (Mitochondrial Encephalopathy,
ure may be as high as 15%.
Lactic Acidosis, and Stroke-Like Episodes) MELAS
X-linked AS is caused by mutations in
syndrome is a childhood disease characterized by inter-
COL4A5, a member of the type IV collagen gene
mittent vomiting, proximal limb weakness, and recur-
family.78 In a comprehensive review of the type IV
rent cerebral insults that resemble strokes and cause
collagen mutations, Lemmink and colleagues
hemiparesis and cortical blindness. MELAS syndrome
reported more than 160 different AS-causing muta-
is frequently associated with short stature. Hearing loss
tions in COL4A5.79 The mutation spectrum is broad;
occurs in approximately 30% of affected individuals.25
about 15% of affected males have large COL4A5
deletions, and in 30%, a variety of missense and MERRF Syndrome (Myoclonic Epilepsy and
nonsense mutations are found. In many patients, Ragged Red Fibers) Myoclonus, epilepsy, and
however, no mutations are identified. ataxia characterize MERRF. Dementia, optic atro-
phy, and hearing loss frequently occur. The degree of
MITOCHONDRIAL SYNDROMIC HEARING hearing loss is variable.25
IMPAIRMENT
NONSYNDROMIC HEARING
Hearing loss may be associated with a number of
syndromic mitochondrial diseases. Most frequent
IMPAIRMENT
are the acquired mitochondrial neuromuscular syn- Over 70 different nonsyndromic hearing impair-
dromes and maternally inherited diabetes mellitus ment loci have been mapped, and a number of the
associated with deafness. relevant genes have been cloned. The protein prod-
Hereditary Hearing Impairment 335
ucts of these genes include ion channels, membrane hair cell stereocilia during mechanoelectrical trans-
proteins, transcription factors, and structural pro- duction to be recirculated into the stria vascularis.85,87
teins. The most significant discovery in the field of
genetic deafness to date has been the finding that
mutations in Cx26 are responsible for over half of
AUTOSOMAL DOMINANT NONSYNDROMIC
moderate-to-profound congenital deafness in many
HEARING IMPAIRMENT world populations.88,89 In certain regions of the
Autosomal dominant modes of inheritance account Mediterranean, the prevalence may be as high as
for 15% of cases of nonsyndromic deafness 79%, although studies in India and Pakistan reveal a
(ADNSHI).82 The typical phenotype is one of much lower incidence.90,91 Numerous different deaf-
postlingual hearing loss that starts in the second to ness-causing allele variants have been identified. In
third decades of life and progresses until it is mod- the United States and much of northern Europe, the
erate to severe in degree. However, the frequencies most prevalent mutation is the deletion of a single
that are initially affected vary. For example, DFNA1, guanine nucleotide from a sequence of six guanines
DFNA6, DFN14, and DFNA15 are characterized by at positions 30 to 35. Referred to as the 35delG
a low-frequency hearing loss that progresses to mutation, this shift in codon reading frame results in
involve the remaining frequencies. With other loci, premature termination of translation.88 In the mid-
hearing loss starts in the mid- or high frequencies western United States, the carrier rate for this muta-
before progressing. The DFNA3, DFNA12, and tion is 2.5%, whereas the carrier rate for all
DFNA23 phenotypes are exceptional as they are deafness-causing Cx26 mutations is 3%.92 In the
congenital hearing losses on which age-related Mediterranean population, the carrier rate is even
changes become superimposed. Many of the genes higher and approaches 5%. Other “common” muta-
for ADNSHI have now been cloned (Table 13–6).25 tions are found in different populations, such as the
167delT mutation in Ashkenazi Jews.93
These discoveries have had immediate appli-
AUTOSOMAL RECESSIVE NONSYNDROMIC
cation to clinical practice. In many populations, a
HEARING IMPAIRMENT definitive diagnosis can now be made in 50% of
Up to 85% of cases of nonsyndromic hearing loss are cases of suspected hereditary hearing loss. This
inherited in a recessive mendelian fashion (ARN- ability to establish causality affects recurrence risk
SHI).83 The typical phenotype is more severe than in estimates and makes genetic counseling an impor-
ADNSHI and accounts for the majority of cases of tant part of the evaluation of hereditary deafness.
congenital profound deafness. However, DFNB8 is an However, the degree of hearing loss in a child with
exception as it presents as a postlingual progressive Cx26-related deafness cannot be used to predict the
hearing loss. To date, 30 ARNSHI loci have been iden- degree of deafness in another offspring. There can
tified and 8 genes cloned (see Table 13–6).25 The first be enough intrafamilial variability to make one
locus was published in 1994, 6 years after the first X- affected child a candidate for cochlear implanta-
linked locus and 2 years after the first dominant locus tion, whereas a sibling effectively uses hearing
were reported.84 Three years later, the gene responsi- aids94 (Figure 13–6).
ble for DFNB1, GJB2 (gap junction beta 2), was dis-
covered.85 This gene encodes connexin 26 (Cx26), one X-LINKED NONSYNDROMIC HEARING
of a class of proteins involved in gap junction forma-
IMPAIRMENT
tion. A group of six connexins oligomerize to form a
torus-like structure called a connexon. Two connex- X-linked nonsyndromic hearing impairment is rare
ons dock to form a transmembrane channel that links and makes up only 1 to 3% of nonsyndromic hear-
neighboring cells and facilitates the exchange of mol- ing loss. It exhibits considerable phenotypic hetero-
ecules up to 1 kD in size.86 Immunohistochemical geneity, but most affected males have a congenital
studies have demonstrated Cx26 expression in two hearing loss, which can vary from severe to pro-
groups of cochlear cells, supporting cells in the sen- found. Hearing loss is mild to moderate in carrier
sory epithelium and fibroblasts. It is postulated that females. The losses associated with DFN1 and DFN6
Cx26 gap junctions allow potassium ions that enter may be progressive.83
336 Ballenger’s Otorhinolaryngology
Mitochondrial mutations may play a role in age- Age-Related Hearing Loss Mitochondrial muta-
related hearing loss and have been implicated in a type tions may be a contributing factor to age-related
Hereditary Hearing Impairment 337
hearing loss (presbycusis). The number of mutation- get for aminoglycoside binding.98 In countries such
carrying mitochondria per cell increases with age, as China, where aminoglycosides are used fre-
resulting in progressive reduction in oxidative phos- quently, aminoglycoside-induced ototoxicity is a
phorylation capacity, the impact of which is tissue major cause of hearing loss. One study in Shanghai
dependent. Ueda and colleagues detected high rates found that 22% of the profoundly deaf had amino-
of mitochondrial DNA deletions in lymphocytes of glycoside-induced ototoxicity.99 In the United States,
persons with idiopathic sensorineural hearing loss over 15% of persons with aminoglycoside-induced
and noted that the number of deletions increased hearing loss carry this mutation, a point of major
with increasing hearing loss.96 They posited that at clinical relevance for the prevention of aminoglyco-
least some cases of sensorineural hearing loss should side hearing loss.100 Based on these data, it is prudent
be categorized as a mitochondrial phosphorylation to inquire about any family history of aminoglyco-
disease. Temporal bone studies have also shown an side ototoxicity prior to drug administration. Indi-
increased load of mitochondrial mutations in per- viduals who develop ototoxicity should be tested for
sons with age-related hearing loss when compared the 1555 mutation and offered family counseling if
with controls.97 the mutation is detected.
questions should focus on prenatal, perinatal, and brainstem response, which gives accurate hearing
postnatal history, specifically reviewing maternal ill- thresholds from 1 to 4 kHz.108 In older children or
nesses, drug use, alcohol intake, and smoking. Rec- adults, a standard audiogram can be obtained. The
ognized risk factors for hearing loss in the perinatal presence or absence of hearing loss in other family
period include low birth weight, prematurity, time members should be documented by formal audio-
spent in a neonatal intensive care unit, hyperbiliru- metric testing.
binemia, sepsis, use of ototoxic medications, and
birth hypoxia.101–104 Risk factors in the postnatal
period include viral illnesses such as mumps and LABORATORY TESTING
measles as well as bacterial meningitis.105 A record of Specific laboratory tests should be ordered on the
speech and language milestones can establish basis of the history, physical examination, and age of
whether the hearing loss is pre- or postlingual. How- the patient (Table 13–7). For example, if PS is sus-
ever, even deaf infants coo and babble naturally up to pected, a perchlorate challenge test can be obtained
the age of 6 months. A history of poor motor devel- to detect a defect in thyroid organification of iodide.
opment may indicate vestibular dysfunction. If AS is being considered, urinalysis should be per-
It is important to inquire about hearing loss in formed. An electrocardiogram should be ordered
first- and second-degree relatives, especially if the and the QT interval calculated if there is a history of
loss started before the age of 30 years. Consanguin- syncopal episodes or a family history of sudden
ity or common origins from ethically isolated areas infant death syndrome (SIDS), as might be seen with
should increase suspicion of hereditary deaf- JLNS. Serology can be used to rule out acquired
ness.106,107 If there are a number of family members causes of early deafness, such as cytomegalovirus
with hearing loss, constructing a pedigree may delin- infection, toxoplasmosis, and congenital rubella.
eate the mode of inheritance. Chromosomal karyotyping is indicated in a
child born to parents with a history of miscarriages,
PHYSICAL EXAMINATION when the constellation of anomalies in a child is not
recognizable as a previously reported syndrome, or if
Most cases of hereditary hearing impairment are
there are associated central nervous system or car-
nonsyndromic, so physical findings are absent. How-
diac defects. Genetic testing for most of the types of
ever, even in cases of syndromic hearing impair-
deafness discussed in this chapter is not yet clinically
ment, physical findings may be subtle. The physical
available; however, it is likely that in the next 5 years,
examination should include a general inspection
many new tests will be offered, making some older
and systematic evaluation of all systems. Note hair
tests obsolete.
color, the presence of a white forelock, facial sym-
metry, and skull shape. Fundoscopy, eye color, and
relative position should be noted, taking specific bio- RADIOLOGY
metric measurements in suspected cases of WS1.
Examine the ears for auricular pits or sinuses and Computed tomography of the temporal bones is the
skin tags, noting the shape and size of the pinnae single best radiologic test for the evaluation of hear-
and checking for abnormalities of the external ear ing impairment, with the reported incidence of
canal and tympanic membrane. Check the neck for anatomic abnormalities ranging from 6.8 to
branchial anomalies and thyroid enlargement and 28.4%.109,110 Cochlear abnormalities such as Mon-
the oral cavity for clefts. Note the number, size, and dini’s dysplasia and DVAs suggest the diagnosis of
shape of the digits and complete a thorough inspec- PS, although temporal bone anomalies are also seen
tion of the skin for areas of pigmentation/hypopig- with many other syndromes, including TCS and
mentation and café-au-lait spots. Do a complete BOR syndrome. If the latter is being considered,
neurologic examination, including tests of gait and renal ultrasonography should be performed.
balance to assess vestibular function.
OTHER CONSULTATIONS
AUDIOLOGY An ophthalmologic opinion should be obtained in
The test of choice for infants and young children all children with severe-to-profound hearing impair-
with suspected hearing impairment is the auditory ment as half will have ocular abnormalities.111
Hereditary Hearing Impairment 339
HI = hearing impairment; ABR = auditory brainstem response; CT = computed tomography; MRI = magnetic resonance imag-
ing; CP = cerebellopontine; CMV = cytomegalovirus; ERG = electroretinography; ECG = electrocardiography; BOR = bran-
chio-oto-renal syndrome.
Although most of these abnormalities are refractive essential for the development of age-appropriate
errors, the correction of which is essential, ERG may speech and language skills. Children whose hearing
uncover signs of early retinitis pigmentosa. Referral losses are identified and in whom intervention is
to a clinical geneticist should be requested to ensure instituted before 6 months of age show significant
that parents and patients adequately understand the advantage in communicative skill development com-
issues such as recurrence risk. pared with infants identified later.112 To achieve this
goal, newborn hearing screening programs have been
MANAGEMENT OF HEARING implemented in most states and linked to rehabilita-
tive programs. The level of habilitative intervention
IMPAIRMENT that is required depends on the degree of hearing
Early identification of hearing impairment in infants impairment. Counseling of the family, proper hear-
and young children and early rehabilitation are ing aid selection, hearing aid fitting, and continued
340 Ballenger’s Otorhinolaryngology
audiologic assessment are important. Schools that 6. Jaber L, Shohat M, Bu X, et al. Sensorineural deaf-
teach sign language, oral-aural communication, and ness inherited as a tissue specific mitochondrial dis-
a combination of both may be necessary. Cochlear order. J Med Genet 1992;29:86–90.
implantation may be an option in persons with 7. Grundfast KM. Hereditary hearing impairment in
severe and profound hearing impairment.113 children. Adv Otolaryngol Head Neck Surg 1993;7:
A variety of support systems exist, particularly 29–43.
on the World Wide Web. In the United States, the 8. Gorlin A, Toriello H, Cohen M. Hereditary hearing
National Institute on Deafness and Other Commu- loss and its syndromes. New York: Oxford University
nication Disorders established the Hereditary Hear- Press; 1995.
ing Impairment Resource Registry (HHIRR) 9. Melnick M, Bixler D, Silk K, et al. Autosomal domi-
(<www.boystown.org/hhirr>) to disseminate infor- nant branchio-oto-renal dysplasia. Birth Defects
mation on hearing impairment to professionals and Orig Artic Ser 1975;11:121–8.
families. The registry also collects information from 10. Fraser FC, Sproule JR, Halal F. Frequency of the
individuals interested in supporting and participat- branchio-oto-renal (BOR) syndrome in children
ing in research projects and lists relevant resources with profound hearing loss. Am J Genet 1980:7:
and links to other organizations. 341–9.
11. Cremers CWRJ, Fikkers-van Noord M. The earpits—
FUTURE DEVELOPMENTS deafness syndrome. Clinical and genetic aspects. Int
J Pediatr Otorhinolaryngol 1980;2: 309–22.
The rapid advances in the genetics and molecular 12. Fraser FC, Ling D, Clogg D, Nogrady B. Genetic
biology of hearing and deafness that occurred dur- aspects of the BOR syndrome—branchial fistulas,
ing the last decade of the twentieth century are con- ear pits, hearing loss and renal anomalies. Am J Med
tinuing at pace. Inexpensive genetic tests are Genet 1978;2:241–52.
becoming available for early detection of hearing 13. Chen A, Francis M, Ni L, et al. Phenotypic manifes-
impairment, and the use of these tests will ultimately tations of branchio-oto-renal syndrome. Am J Med
impact management decisions by better defining Genet 1995;58:365–70.
therapeutic and habilitative options. It is also 14. Gimsing S, Dyrmose J. Branchio-oto-renal dysplasia
becoming increasingly possible to identify individu- in three families. Ann Otol Rhinol Laryngol 1986;95:
als at risk for environmental damage (noise, drugs, 421–6.
age) to their hearing. In the next decades, it is likely 15. Smith RJ, Coppage KB, Ankerstjerne JK, et al. Local-
that physicians will be able to offer patients new, ization of the gene for branchiootorenal syndrome
practical, and effective treatments for sensorineural to chromosome 8q. Genomics 1992;14:841–4.
hearing impairment. 16. Kumar S, Kimberling WJ, Kenyon JB, et al. Autoso-
mal dominant branchio-oto-renal syndrome—
REFERENCES localization of a disease gene to chromosome 8q by
1. Morton NE. Genetic epidemiology of hearing impar- linkage in a Dutch family. Hum Mol Genet 1992;1:
ment. Ann N Y Acad Sci 1991;630:16–31. 491–5.
2. Marazita ML, Ploughman LM, Rawlings B, et al. 17. Abdelhak S, Kalatzis V, Heilig R, et al. A human
Genetic epidemiological studies of early-onset deaf- homologue of the Drosophila eyes absent gene
ness in the U.S. school-age population. Am J Genet underlies branchio-oto-renal (BOR) syndrome and
1993;46:486–91. identifies a novel gene family. Nat Genet 1997;15:
3. Sank D, Kallman FJ. The role of heredity in early 157–64.
total deafness. Volta Rev 1963;65:461. 18. Kumar S, Deffenbacher K, Marres HA, et al.
4. Brown KS. The genetics of childhood deafness. In: Genomewide search and genetic localization of a
McConnell F, Ward PH, editors. Deafness in child- second gene associated with autosomal dominant
hood. Nashville (TN): Vanderbilt University Press; branchio-oto-renal syndrome: clinical and genetic
1967. p. 177–202. implications. Am J Hum Genet 2000;66:715–20.
5. Anderson S, Bankier AT, Barrell BG, et al. Sequence 19. Cohen MM, Krieborg S. Birth prevalence studies of
and organization of the human mitochondrial the Crouzon syndrome: comparison of direct and
genome. Nature 1981;290:457–65. indirect methods. Clin Genet 1992;41:12–5.
Hereditary Hearing Impairment 341
20. Schiller JG. Craniofacial dysostosis of Crouzon: a 34. Vikkula M, Mariman EC, Lui VC, et al. Autosomal
case report and pedigree with emphasis on heredity. dominant and recessive osteochondrodysplasias
Pediatrics 1959;23:107. associated with the COL11A2 locus. Cell 1995;80:
21. Orvidas LJ, Fabry LB, Diacova S, McDonald TJ. 431–7.
Hearing and otopathology in Crouzon syndrome. 35. Richards AJ, Yates JR, Williams R, et al. A family with
Laryngoscope 1999;109:1372–5. Stickler syndrome type 2 has a mutation in the
22. Hollway GE, Suthers GK, Haan EA, et al. Mutation COL11A1 gene resulting in the substitution of
detection in FGFR2 craniosynostosis syndromes. glycine 97 by valine in alpha 1 (XI) collagen. Hum
Hum Genet 1997;99:251–5. Mol Genet 1996;5:1339–43.
23. Reardon W, Winter RM, Rutland P, et al. Mutations 36. Rovin S, Dachi SF, Borenstein DB, Cotter WB.
in the fibroblast growth factor receptor 2 gene cause Mandibulofacial dysostosis, a familial study of five
Crouzon syndrome. Nat Genet 1994;8:98–103. generations. J Pediatr 1964;65:215–21.
24. NIH Consensus Development Conference. Neurofi- 37. Sando I, Hemenway WG, Morgan WR. Histopathol-
bromatosis: conference statement. Arch Neurol ogy of the temporal bones in mandibulofacial dysos-
1988;45:475–8. tosis. Trans Am Acad Ophthalmol Otolaryngol
25. Van Camp G, Smith RJH. Hereditary hearing loss 1968;72:913–24.
home page. Available at: http://dnalab-www.uia.ac.be/ 38. Jahrsdoefer RA, Jacobson JT. Treacher Collins syn-
dnalab/hhh/ (accessed November 2000). drome: otologic and auditory management. J Am
26. Trofatter JA, MacCollins MM, Rutter JL, et al. A Acad Audiol 1995;6:93–102.
novel moesin-, ezrin-, radixin-like gene is a candi- 39. Isaac C, Marsh KL, Paznekas WA, et al. Characteri-
date for the neurofibromatosis 2 tumor suppressor. zation of the nucleolar gene product, treacle, in
Cell 1993;75:826. Treacher Collins syndrome. Mol Biol Cell 2000;11:
27. Gusella JF, Ramesh V, MacCollin M, Jacoby LB. Mer- 3061–71.
lin: the neurofibromatosis 2 tumor suppressor. 40. Edwards SJ, Gladwin AJ, Dixon MJ. The mutational
Biochim Biophys Acta 1999;1423:M29–36. spectrum in Treacher Collins syndrome reveals a
28. Kluwe L, Mautner VF. A missense mutation in the predominance of mutations that create a premature-
NF2 gene results in moderate and mild clinical phe- termination codon. Am J Hum Genet 1997;60:
notypes of neurofibromatosis type 2. Hum Genet 515–24.
1996;97:224–7. 41. Waardenburg PJ. A new syndrome combining devel-
29. Evans DGR, Trueman L, Wallace A, et al. Geno- opmental anomalies of the eyelids, eyebrows, and
type/phenotype correlations in type 2 neurofibro- nose root with pigmentary defects of the iris and
matosis (NF2): evidence for more severe disease head hair and with congenital deafness. Am J Hum
associated with truncating mutations. J Med Genet Genet 1951;3:195–253.
1998;35:450–5. 42. Read AP, Newton VE. Waardenburg syndrome. J
30. Knowlton RG, Struyk AF, Knobloch WH, et al. Med Genet 1997;34:656–65.
Genetic linkage analysis of hereditary arthro-ophthal- 43. Farrer LA, Grundfast KM, Amos J, et al. Waarden-
mopathy (Stickler syndrome) and the type II collagen burg syndrome (WS) type I is caused by defects at
procollagen gene. Am J Hum Genet 1989;45:681–6. multiple loci, one of which is near ALPP on chro-
31. Ahmad NN, Ala-Kokko L, Knowlton RG, et al. Stop mosome 2: first report of the WS consortium. Am J
codon in the procollagen II gene (COL2A1) in a Hum Genet 1992;50:902–13.
family with Stickler syndrome (arthro-ophthalmol- 44. Liu XZ, Newton VE. Waardenburg syndrome type 1:
ogy). Proc Natl Acad Sci U S A 1991;88:6624–7. phenotypic findings and diagnostic criteria. Am J
32. Winterpacht A, Hilbert M, Schwarze U, et al. Kniest Med Genet 1995;55:95–100.
and Stickler dysplasia phenotypes caused by collagen 45. Newton VE. Hearing loss and Waardenburg syn-
type II gene (COL2A1) defect. Nat Genet 1993;3:323–6. drome implications for genetic counselling. J Laryn-
33. Williams CJ, Ganguly A, Considine E, et al. A-2-->G gol Otol 1990;104:97–103.
transition at the 3′ acceptor splice site of IVS17 char- 46. Tassabehji M, Read AP, Newton VE, et al. Waarden-
acterizes the COL2A1 gene mutation in the original burg’s syndrome patients have mutations in the
Stickler syndrome kindred. Am J Med Genet human homologue of the Pax-3 paired box gene.
1996;63:461–7. Nature 1992;355:635–6.
342 Ballenger’s Otorhinolaryngology
47. Tassabehji M, Newton VE, Read AP. Waardenburg 62. Fishman GA, Kumar A, Joseph ME, et al. Usher’s
syndrome type 2 caused by mutations in the human syndrome. Ophthalmic and neuro-otologic findings
microphthalmia (MITF) gene. Nat Genet 1994;8: suggesting genetic heterogeneity. Arch Ophthalmol
251–5. 1983;101:1367–74.
48. Hoth CF, Milunsky A, Lipsky N, et al. Mutations in 63. Cherry PM. Usher’s syndrome. Ann Ophthalmol
the paired domain of the human PAX3 gene cause 1973;5:743–52.
Klein-Waardenburg syndrome (WS-III) as well as 64. Young NM, Mets MB, Hain TC. Early diagnosis of
Waardenburg syndrome type I (WS-I). Am J Hum Usher syndrome in infants and children. Am J Otol
Genet 1993;52:455–62. 1996;17:30–4.
49. Attie T, Till M, Pelet A, et al. Mutation of the endothe- 65. Kaplan J, Gerber S, Bonneau D, et al. A gene for
lin-receptor B gene in Waardenburg-Hirschsprung Usher syndrome type I (USH1A) maps to chromo-
disease. Hum Mol Genet 1995;4:2407–9. some 14q. Genomics 1992;14:979–87.
50. Edery P, Attie T, Amiel J, et al. Mutation of the 66. Smith RJ, Lee EC, Kimberling WJ, et al. Localization
endothelin-3 gene in the Waardenburg-Hirschsprung of two genes for Usher syndrome type I to chromo-
disease (Shah-Waardenburg syndrome). Nat Genet some 11. Genomics 1992;14:995–1002.
1996;12:442–4. 67. Sankila EM, Pakarinen L, Kaariainen H, et al. Assign-
51. Pingault V, Bondurand N, Kuhlbrodt K, et al. SOX10 ment of an Usher syndrome type III (USH3) gene to
mutations in patients with Waardenburg-Hirschsprung chromosome 3q. Hum Mol Genet 1995;4:93–8.
disease. Nat Genet 1998;18:171–3. 68. Wayne S, Der Kaloustian VM, Schloss M, et al. Local-
52. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. ization of the Usher syndrome type ID gene (Ush1D)
Jervell and Lange-Nielsen syndrome: a Norwegian to chromosome 10. Hum Mol Genet 1996;5:1689–92.
perspective. Am J Med Genet 1999;89:137–46. 69. Kimberling WJ, Weston MD, Moller C, et al. Local-
53. Marres HA. Congenital abnormalities of the inner ization of Usher syndrome type II to chromosome
ear. In: Ludman H, Wright T, editors. Diseases of the 1q. Genomics 1990;7:245–9.
ear. Bath (England): Arnold & Oxford University 70. Hmani M, Ghorbel A, Boulila-Elgaied A, et al. A
Press; 1998. p. 288–96. novel locus for Usher syndrome type II, USH2B,
54. Fraser GR. Association of congenital deafness with maps to chromosome 3 at p23-24.2. Eur J Hum
goitre (Pendred’s syndrome). Ann Hum Genet Genet 1999;7:363–7.
1965;28:201–48. 71. Weil D, Blanchard S, Kaplan J, et al. Defective myosin
55. Scott DA, Wang R, Kreman TM, et al. The Pendred VIIA gene responsible for Usher syndrome type 1B.
syndrome gene encodes a chloride-iodide transport Nature 1995;374:60–1.
protein. Nat Genet 1999;20:440–3. 72. Verpy E, Leibovici M, Zwaenepoel I, et al. A defect in
56. Van Hauwe P, Everett LA, Coucke P, et al. Two fre- harmonin, a PDZ domain-containing protein
quent missense mutations in Pendred syndrome. expressed in the inner ear sensory hair cells, underlies
Hum Mol Genet 1998;7:1099–104. Usher syndrome type 1C. Nat Genet 2000;6:51–5.
57. Coyle B, Reardon W, Herbrick JA, et al. Molecular 73. Eudy JD, Weston MD, Yao S, et al. Mutation of a gene
analysis of the PDS gene in Pendred syndrome. Hum encoding a protein with extracellular matrix motifs
Mol Genet 1998;7:1105–12. in Usher syndrome type IIa. Science 1998;280:
58. Rosenberg T, Haim M, Hauch AM, Parving A. The 1753–7.
prevalence of Usher syndrome and other retinal dys- 74. Weston MD, Eudy JD, Fujita S, et al. Genomic struc-
trophy-hearing impairment associations. Clin Genet ture and identification of novel mutations in ush-
1997;51:314–21. erin, the gene responsible for Usher syndrome type
59. Grondahl J, Mjoen S. Usher syndrome in four Nor- IIa. Am J Hum Genet 2000;66:1199–210.
wegian counties. Clin Genet 1986;30:14–28. 75. Flinter FA, Cameron JS, Chantler C, et al. Genetics of
60. Kimberling WJ, Moller CG, Davenport SL, et al. classic Alport’s syndrome. Lancet 1988;2:1005–7.
Usher syndrome: clinical findings and gene localiza- 76. Flinter F. Alport’s syndrome. J Med Genet 1997;34:
tion studies. Laryngoscope 1989;99:66–72. 326–30.
61. Moller CG, Kimberling WJ, Davenport SL, et al. 77. Govan JAA. Ocular manifestations of Alport’s syn-
Usher syndrome: an otoneurologic study. Laryngo- drome: a hereditary disorder of basement mem-
scope 1989;99:73–9. brane? Br J Ophthalmol 1983;67:493–503.
Hereditary Hearing Impairment 343
78. Barker DF, Hostikka SL, Zhou J, et al. Identification 93. Morell RJ, Kim HJ, Hood LJ, et al. Mutations in the
of mutations in the COL4A5 collagen gene in Alport connexin 26 gene (GJB2) among Ashkenazi Jews
syndrome. Science 1990;248:1224–7. with nonsyndromic recessive deafness. N Engl J
79. Lemmink HH, Schroder CH, Monnens LA, Smeets Med 1998;339:1500–5.
HJ. The clinical spectrum of type IV collagen muta- 94. Lefebvre PP, Van De Water TR. Connexins, hearing
tions. Hum Mutat 1997;9:477–99. and deafness: clinical aspects of mutations in the
80. Alcolado JC, Majid A, Brockington M, et al. Mito- connexin 26 gene. Brain Res Brain Res Rev 2000;32:
chondrial gene defects in patients with NIDDM. 159–62.
Diabetologia 1994;37:372–6. 95. Fischel-Ghodsian N. Mitochondrial mutations and
81. Kadowaki T, Kadowaki H, Mori Y, et al. A subtype of hearing loss: paradigm for mitochondrial genetics.
diabetes mellitus associated with a mutation of Am J Hum Genet 1998;62:15–9.
mitochondrial DNA. N Engl J Med 1994;330:962–8. 96. Ueda N, Oshima T, Ikeda K, et al. Mitochondrial
82. Van Laer L, McGuirt WT, Yang T, et al. Autosomal DNA deletion is a predisposing cause for sen-
dominant nonsyndromic hearing impairment. Am J sorineural hearing loss. Laryngoscope 1998;108:
Med Genet 1999;89:167–74. 580–4.
83. Lalwani, AK, Castelein CM. Cracking the auditory 97. Fischel-Ghodsian N, Bykhovskaya Y, Taylor K, et al.
genetic code: nonsyndromic hereditary hearing Temporal bone analysis of patients with presbycu-
impairment. Am J Otol 1999;20:115–32. sis reveals high frequency of mitochondrial muta-
84. Guilford P, Ben Arab S, Blanchard S, et al. A non- tions. Hear Res 1997;110:147–54.
syndrome form of neurosensory, recessive deafness 98. Prezant TR, Agapian JV, Bohlman MC, et al. Mito-
maps to the pericentromeric region of chromosome chondrial ribosomal RNA mutation associated
13q. Nat Genet 1994;6:24–8. with both antibiotic-induced and non-syndromic
85. Kelsell DP, Dunlop J, Stevens HP, et al. Connexin 26 deafness. Nat Genet 1993;4:289–94.
mutations in hereditary nonsyndromic sen- 99. Hu DN, Qui WQ, Wu BT, et al. Genetic aspects of
sorineural deafness. Nature 1997;387:80–3. antibiotic induced deafness: mitochondrial inheri-
86. Kumar NM, Gilula NB. The gap junction communi- tance. J Med Genet 1991;28:79–83.
cation channel. Cell 1996;84:381–8. 100. Fischel-Ghodsian N, Prezant TR, Chaltraw WE, et
87. Kikuchi T, Kimura R, Paul D, Adams J. Gap junctions al. Mitochondrial gene mutation is a significant
in rat cochlea: immunohistochemical analysis. Anat predisposing factor in aminoglycoside ototoxicity.
Embryol 1995;191:101–18. Am J Otolaryngol 1997;18:173–8.
88. Denoyelle F, Weil D, Maw MA, et al. Prelingual 101. Gerber S. Review of a high-risk register for congeni-
deafness: high prevalence of a 30delG mutation in tal or early onset deafness. Br J Audiol 1992;26: 77–90.
the connexin 26 gene. Hum Mol Genet 1997;6: 102. Sutton GJ, Rowe S. Risk factors for childhood sen-
2173–7. sorineural hearing loss in the Oxford Region. Br J
89. Maw MA, Allen-Powell DR, Goodey RJ, et al. The Audiol 1997;31:39-54.
contribution of the DFNB1 locus to neurosensory 103. Bamiou DE, Macardle B, Bitner-Glindzicz M, Siri-
deafness in a Caucasian population. Am J Hum manna T. Aetiological investigations of hearing loss
Genet 1995;57:629–35. in childhood: a review. Clin Otolaryngol 2000;25:
90. Gasparini P, Estivill X, Volpini V, et al. Linkage of 98–106.
DFNB1 to non-syndromic neurosensory autosomal- 104. Davis A, Wood S. The epidemiology of hearing
recessive deafness in Mediterranean families. Eur J impairment: factors relevant to planning of serv-
Hum Genet 1997;5:83–8. ices. Br J Audiol 1992;26:77–90.
91. Fukushima K, Ramesh A, Srisailapathy CR, et al. 105. Linthicum FH. Viral causes of sensorineural hear-
Consanguineous nuclear families used to identify a ing loss. Otolaryngol Clin North Am 1978;11:
new locus for recessive non-syndromic hearing loss 29–33.
on 14q. Hum Mol Genet 1995;4:1643–8. 106. Basil A. Childhood sensorineural hearing loss in con-
92. Green GE, Scott DA, McDonald JM, et al. Carrier sanguineous marriages. J Audiol Med 1994;3:151–9.
rates in the midwestern United States for GJB2 107. Naem Z, Newton V. Prevalence of sensorineural
mutations causing inherited deafness. JAMA 1999; hearing loss in Asian children. Br J Audiol 1996;30:
281:2211–6. 332–9.
344 Ballenger’s Otorhinolaryngology
108. Tomaski SM, Grundfast KM. A stepwise approach 111. Armitage IM, Burke JP, Buffin JT. Visual impair-
to the diagnosis and treatment of hereditary hear- ment in severe and profound sensorineural deaf-
ing loss. Pediatr Clin North Am 1999;46:35–47. ness. Arch Dis Child 1995;75:53–6.
109. Zalzal GH, Shott SR, Towbin R, Cotton RT. Value of 112. Downs MP, Yoshinaga-Itano C. The efficacy of
CT scan in the diagnosis of temporal bone diseases early identification and intervention for children
in children. Laryngoscope 1986;96:27–32. with hearing impairment. Pediatr Clin North Am
110. Bamiou D, Phelps P, Sirimanna T. Temporal bone 1999;46:79–87.
computed tomography findings in bilateral sen- 113. Nikolopoulos TP, O’Donoghue GM. Cochlear im-
sorineural hearing loss. Arch Dis Child 2000;82: plantation in adults and children. Hosp Med 1998;
257–60. 59:46–9.
CHAPTER 14
345
346 Ballenger’s Otorhinolaryngology
cholesteatoma. Canal fractures can also lead to formation, and stenosis of the canal. Most thermal
chronic infection, bone sequestration, and stenosis burns of the ear canal are caused by flash injuries,
of the canal. The development of any of these seque- fires, lightning strikes, or hot liquids such as oil. Like
lae may necessitate surgical débridement, grafting, burns elsewhere on the body, the depth and extent of
reconstruction, or meatoplasty to ensure a healthy the burn should be determined and documented.
open ear canal. Superficial thermal burns of the ear canal are usually
Penetrating injuries of the external auditory treated with the application of antibiotic ointment.
canal are usually caused by gunshot or stab wounds. If more than half of the ear canal is involved or has
Penetrating injuries in which the missile enters ante- third-degree burns, in addition to the application of
riorly through the parotid gland often involve the antibiotic ointment, the canal is stented with soft
external auditory canal; the mechanism is thought Silastic tubing. Canal stenting is performed in an
to involve dissipation of the missile’s energy on and effort to prevent stenosis of the canal, which leads to
reflection of the missile off the anterior aspect of the the trapping of squamous debris and ultimately a
mastoid process. Other factors that influence the destructive ear canal cholesteatoma. Stenosis of the
injury include the force and trajectory of the missile canal is treated aggressively with corticosteroid
and, if a bullet, its type, hardness, and caliber. As a injections, frequent dilations, and, in some cases,
consequence, facial nerve injury, tympanic mem- skin grafting or even meatoplasty.
brane perforation, and ossicular dislocation can Caustic burns are usually caused by a chemical
result from gunshot wounds of the external auditory spill or a foreign object such as an alkaline battery.
canal even when the apparent course of the missile Thermal and acid burns cause coagulation necrosis,
would not traverse these structures (Figure 14–1). whereas alkaline burns cause liquefaction necrosis,
The facial nerve is most likely to be injured at the which leads to much more extensive injury over
stylomastoid foramen apparently because it is rela- time. Kavanagh and Litovitz reported a series of bat-
tively fixed at that point. In the absence of any of tery-related injuries to the ear canal that were much
these additional injuries, gunshot wounds of the ear more frequent and severe than expected, including
canal require cleaning, a light dressing, and prophy- tympanic membrane perforation, exposed bone of
lactic antibiotics. Occasionally, the canal must be the ear canal, sensorineural hearing loss, ossicular
stented following a gunshot injury, and in this case, destruction, and facial paralysis.1 They also noted
a soft Merocel wick coated with ciprofloxacin and that otic drops must be withheld in these patients as
hydrocortisone otic drops is usually satisfactory. they provide an external electrolyte bath for the bat-
Lacerations of the external auditory canal can tery, enhancing leakage and generation of an exter-
occur either anteriorly or posteriorly and are often nal current with subsequent tissue electrolysis and
accompanied by partial avulsion of the auricle. hydroxide formation. The foreign body should be
These patients should be carefully evaluated for removed as soon as possible, under general anesthe-
injury to the facial nerve and the great vessels; radi- sia if needed.2 Once the injury has been assessed,
ographic studies including arteriography may be caustic burns are treated much like thermal burns
indicated in these patients. Most external auditory described earlier, with microscopic cleaning, antibi-
canal lacerations require cleaning, gentle débride- otic eardrops, and stenting if indicated. Because of
ment, and suturing to realign the various parts of the high incidence of exposed bone, skin grafting of
the ear canal and auricle. Surprisingly, stenosis does the ear canal is often indicated in these patients. Skin
not usually occur in these patients. grafting, tympanoplasty, and ossicular reconstruc-
Burns and caustic injuries to the ear canal tion should be delayed for 4 to 6 months, if possible,
often represent a potentially complicated situation to allow the full extent of the injury to be deter-
in that severe burns can lead to circumferential scar- mined.
ring and stenosis of the canal. Most of these injuries Welding injuries occur when hot slag or
are attributable to one of three mechanisms: a ther- molten metal enters the meatus, usually resulting in
mal burn, a caustic burn, or a welding injury. Ther- either a small and localized burn of the ear canal or
mal and caustic burns of the ear canal are usually a tympanic membrane perforation. In most patients,
associated with additional injury to the auricle, microscopic cleaning, ciprofloxacin and hydrocorti-
which may in itself lead to loss of cartilage, cicatrix sone otic drops, and observation are the only meas-
Trauma to the Middle Ear, Inner Ear, and Temporal Bone 347
including the facial nerve and the vestibular nerve as as a result of cauterization or devascularization of
well as the central nervous system. If the tympanic the tympanic membrane, much like welding
membrane perforation is dry, it should be observed injuries. These injuries are treated much like that
(ie, drops are not indicated). If there is drainage described earlier for welding injuries. Tym-
through the tympanic membrane perforation, the panoplasty should be delayed in these patients for
clinician should determine and note if the drainage 12 weeks because spontaneous healing may take
is consistent with cerebrospinal fluid (CSF). If a CSF that long.
leak is suspected, immediate CT scan of the tempo- Caustic injuries to the tympanic membrane can
ral bone should be obtained to rule out a fracture. If cause a perforation. With alkaline caustics, the tym-
the drainage is not consistent with CSF, oral antibi- panic membrane is damaged by liquefaction necro-
otics and ciprofloxacin and hydrocortisone otic sis, that is, the alkaline caustic penetrates the
drops should be prescribed. A history of vertigo or tympanic membrane, causing occlusion of the vas-
nausea and vomiting and an audiogram showing a culature that may extend farther than the visible per-
conductive hearing loss of more than 30 dB suggest foration. As a result, the size of the perforation may
disruption of the ossicular chain. Profound sen- not be fully appreciated until all of the inflamma-
sorineural loss also may signify oval window or tion resolves. Furthermore, after caustic injuries, the
cochlear damage. middle ear can develop an extensive granulation
Thermal injuries to the tympanic membrane reaction with scarification, ossicular fixation, and a
include welding and lightning injuries. Welding chronic infection. Caustic injuries also can lead to
injuries occur when hot slag enters the ear canal and canal blunting as the raw surfaces that surround the
passes through the tympanic membrane. Most of canal form a cicatrix, leading to narrowing of the ear
these injuries result in an inflammation in the mid- canal and loss of the vibratory surface of the tym-
dle ear with drainage. Panosian and Dutcher panic membrane. Similarly, following a caustic
reported two patients with facial paralysis caused by injury, chronic myringitis can develop on the sur-
hot slag in the middle ear.4 One of their patients also face of the tympanic membrane, creating a raw
sustained a sensorineural hearing loss. Welding weeping surface with granulation on the surface of
injuries often result in nonhealing perforations, the drumhead. Caustic injuries are initially treated
either as a result of infection or possibly because the with ciprofloxacin and hydrocortisone otic drops,
slag acts to cauterize or devascularize the tympanic oral antibiotics, and analgesics. Audiologic assess-
membrane as it passes through it. If infection occurs, ment and a complete neurotologic evaluation are
the patient is treated with ciprofloxacin and hydro- indicated in caustic injuries to determine the extent
cortisone otic drops and an oral antibiotic. If the per- of injury. When the ear has stabilized, and preferably
foration is dry, it should be observed for a period of when drainage has diminished, the middle ear and
12 weeks for spontaneous healing. If the drumhead tympanic membrane can be reconstructed.
does not heal, tympanoplasty should be performed. Tympanic membrane perforations historically
Lightning and electrocution injuries are not have a healing rate that approaches 80%. Kristensen
rare, and the most frequent ear injury is perforation reviewed more than 500 texts regarding the matter
of the tympanic membrane. The most common and found that the spontaneous healing rate
vestibular disturbance is transient vertigo. Other appeared to be 78.7% in 760 evaluable cases of trau-
clinical findings include sensorineural hearing matic tympanic membrane perforations of all sorts
impairment, conductive hearing loss, tinnitus, tem- seen within 14 days after injury.7 A relative, causally
poral bone fracture, avulsion of the mastoid process, related variation of spontaneous healing could be
burns of the ear canal, and facial nerve paralysis.5 demonstrated in this review, with air pressure/hand
Jones et al reported one patient with bilateral oval slap injuries the most likely to heal. Ruptures
window PLF following a lightning strike.6 The ini- induced by heat or corrosives, foreign objects, and
tial management of the patient struck by lightning water pressure were less likely to heal, perhaps
consists of life support measures. Thereafter, the because they were larger or more likely to be
patient should have a thorough audiovestibular infected. Rybak and Johnson also reported that
assessment. Tympanic membrane perforations water slap injuries were less likely to heal as a result
caused by lightning injury often do not heal, perhaps of infection.8
Trauma to the Middle Ear, Inner Ear, and Temporal Bone 349
Griffin reported 227 traumatic perforations including CT scans of the temporal bone, magnetic
treated in his practice from 1969 to 1977.9 He con- resonance imaging (MRI), and even arteriography
cluded that larger perforations, lightning and weld- may be indicated depending on the type of injury
ing injuries, and infected ears were less likely to heal. suspected.
Good hearing results were found regardless of the
method of tympanoplasty, although spontaneous
healing resulted in the best hearing outcome.
TEMPORAL BONE FRACTURES
Regardless of the method used, successful tym- Fractures of the temporal bone are caused by blunt
panoplasty requires adequate exposure, débridement injuries, and depending on the force and direction of
of middle ear granulation and scar tissue, de-epithe- the blow delivered, different types of fractures occur.
lialization of the perforation, and careful graft place- Blunt trauma can be delivered by an object striking
ment including support of the graft until healing the head or by the head being thrown against a solid
occurs. The author prefers to perform transcanal object. Traditionally, temporal bone fractures are
underlay tympanoplasty only on small perforations classified as either longitudinal (extracapsular) or
confined to the posterior portion of the tympanic transverse (capsular) with respect to the long axis of
membrane. In this circumstance, perichondrium the petrous portion of the temporal bone (Figure
harvested from the tragus is most often used as a 14–3). Both are basal skull fractures and are associ-
graft material because of ease of handling and ated with ecchymosis of the postauricular skin (Bat-
access. In larger perforations or perforations that tle’s sign).
extend anterior to the malleus, the author prefers to Longitudinal fractures are, by far, the most
perform postauricular underlay tympanoplasty, common, accounting for 70 to 90% of temporal
using temporalis fascia as the graft material. In this bone fractures, and typically result from a direct lat-
technique, large “swinging door” flaps, based on the eral blow to the temporal or parietal aspect of the
canal skin and normal tympanic membrane, are cre- head. The longitudinal fracture begins in the exter-
ated. These flaps can be advanced to cover the entire nal auditory canal and extends through the middle
mesotympanum if needed, a technique that is par- ear and along the long axis of the petrous pyramid.
ticularly useful in welding injuries as the adequacy of Characteristically, there is bleeding from the ear
the vasculature of the residual drumhead may be canal owing to laceration of its skin and from blood
uncertain. More information regarding tym- coming through the perforated tympanic mem-
panoplasty can be found in Chapter 10.
Penetrating trauma to the middle ear can, of
course, result in perforation of the tympanic mem-
brane, but unlike overpressure and thermal injury,
the incidence of ossicular disruption, facial nerve,
and other middle ear injuries is much greater. The
most common causes are low-velocity gunshots fol-
lowed by injury with a foreign object such as a stick
or instrument. This type of injury should be sus-
pected in patients with a tympanic membrane per-
foration, blood in the middle ear or ear canal, and
the presence of vertigo or dizziness, a conductive loss
greater than 25 dB, a sensorineural hearing loss, or a
facial paralysis. In these patients, the ear canal
should be gently suctioned and cleaned under
microscopic vision, and the tympanic membrane
and middle ear should be carefully inspected. A
complete neurotologic examination, including facial
nerve evaluation and examination for nystagmus, FIGURE 14–3. Drawing depicts the anatomy of the skull
gait stability, fistula test, Romberg’s test, and Dix- base. On the left is a longitudinal or extracapsular frac-
Hallpike test, should be performed. Imaging studies ture. On the right is a transverse or capsular fracture.
350 Ballenger’s Otorhinolaryngology
A B
FIGURE 14–6. A, Drawing depicts the placement of a partial ossicular reconstruction prosthesis. B, Drawing depicts
the placement of a total ossicular reconstruction prosthesis with an intact stapes superstructure. This technique pro-
vides better stabilization of the prosthesis, particularly if a graft is placed on the footplate.
gered vertigo, persistent unsteadiness, and often audiovestibular testing is not usually obtained unless
nausea. The vertigo in these patients lasts several the drumhead and canal have healed, in which case
minutes up to several hours. In the setting of an electronystagmographic (ENG) or a computer-
trauma, with progressive hearing loss and episodic ized dynamic posturographic test can add support
vertigo, a PLF should be suspected. The clinician for the abnormal physical examination findings. In
should remember that there are no specific patterns addition, imaging studies should be reviewed with
to diagnose conclusively a PLF. the radiologist to determine if a temporal bone frac-
The evaluation of patients suspected of having ture or some unsuspected central nervous system
PLF begins with a history and examination. The type injury has occurred. In most cases, however, unless
of trauma suffered and the degree of injury are ossicular disruption is particularly severe, a PLF is
important features of the history. Also, the precipi- not usually detected through imaging studies.
tating factors that lead to vertigo should be noted If a PLF is suspected, bed rest, corticosteroids,
including ear manipulation, straining, and head and even diuretics can be tried for a period of 2 to 3
positioning. Antecedent events such as increased tin- days to determine if spontaneous healing might
nitus, ear fullness, or hearing fluctuation prior to occur. If symptoms persist, the middle ear should be
vertigo are also significant. On examination, hemor- explored as soon as the patient’s condition allows.
rhage, laceration, and tympanic membrane perfora- Altered mental status and other injuries might delay
tion are all signs that point to the possibility of a middle ear exploration for a significant period of
PLF. In performing the neurotologic examination, time, unfortunately. The middle ear in these patients
special attention should be given to the evaluation can be explored either through a postauricular or
for spontaneous nystagmus, an abnormal Romberg’s transcanal approach, obtaining either temporalis fas-
test, a positive fistula sign, a positive Dix-Hallpike cia or tragal perichondrium for the repair. After ele-
sign, an unsteady gait, or an abnormal step test. vating the tympanomeatal flap, the middle ear
Audiometric assessment may show a mixed hearing structures are carefully visualized and the necessary
loss or a pure sensorineural hearing loss. Additional dissection is performed to visualize the stapes foot-
Trauma to the Middle Ear, Inner Ear, and Temporal Bone 353
plate and the round window niche. A subluxed stapes triggered by placing the affected ear in the down
should be carefuly elevated, as previously described, position. This condition can be diagnosed by per-
and secured in position using perichondrium and forming a Nylen-Bárány or Dix-Hallpike maneuver
fibrin glue. If the oval window is indeed intact, the and observing the nystagmus that is triggered.
surgeon should carefully inspect the round window Although this should ideally be performed with
niche and membrane. At this point, several maneu- Fresnel’s glasses, the nystagmus can be observed
vers are performed to visualize a PLF, including Tren- without them in the vast majority of patients. Typi-
delenberg positioning, neck compression, and cally, in this maneuver, the nystagmus has a rotary
Valsalva-like maneuver administered by the anesthe- motion, either clockwise or counterclockwise,
siologist. A PLF is likely present if fluid emanates toward the down and affected ear. Untreated, this
from the oval window or pools in the round window condition usually lasts 3 to 4 months and gradually
niche with these maneuvers. Whether or not a PLF is resolves. Treatment consists of vestibular suppres-
found, most authors apply a soft tissue patch to the sants such as alprazolam 0.50 mg or clonazepam
round and oval windows at this point. This should be 0.50 mg given twice daily in addition to antinause-
done carefully to line the windows with tissue, not ants such as meclizine or promethazine as needed.
invaginate the tissue into the vestibule or the scala Treatment also consists of vestibular rehabilitation
tympani. The soft tissue grafts are reinforced with or physical therapy, specifically using particle-repo-
Gelfoam, and the tympanomeatal flap is returned to sitioning maneuvers such as the modified Epley11 or
its normal position. The canal is filled with antibiotic Semont12 maneuver. In approximately 80% of
ointment or Gelfoam. Rest and avoiding heavy lifting patients, the symptoms are immediately alleviated
are recommended for 5 to 7 days to allow the tissue by this method of treatment.
seal to solidify. Following PLF repair, the episodic Post-traumatic vestibular dysfunction can also
vertigo significantly improves in the vast majority of be caused by shearing of labyrinthine membranes as
patients. However, the hearing results are much less a result of concussive forces. In this circumstance,
predictable as only 15 to 20% of patients demon- the patient may complain of chronic unsteadiness
strate substantial hearing improvement. The hearing rather than true vertigo. In these patients, the nature
threshold is usually stabilized, however. of the injury should be carefully investigated with
ENG as well as with computerized dynamic postur-
ography. A vestibular deficit on either study adds
POST-TRAUMATIC VESTIBULAR DYSFUNCTION support for this diagnosis as opposed to a postcon-
The most common type of post-traumatic vestibu- cussion syndrome. In cases of chronic unsteadiness,
lar dysfunction, by far, is benign paroxysmal posi- a program of vestibular rehabilitation therapy, as
tional vertigo (BPPV). This occurs in 50% of well as low doses of clonazepam, can be extremely
patients with temporal bone fractures and in 25% of helpful. Unfortunately, since many of these cases fol-
patients with a head injury without fracture. In this low automobile accidents, litigation issues often
circumstance, the dizziness usually begins within a cloud the exact severity of symptoms.
few days of the injury, although it can be delayed for Post-traumatic vestibular dysfunction also
several months. Post-traumatic BPPV is thought to occurs after transverse temporal bone fractures.
occur because deceleration forces disrupt the macula With a transverse fracture, a severe episode of ver-
of the utricle, with release of the otoconia that ordi- tigo occurs, which gradually improves, much like a
narily rest in a gel layer that covers the surface of the patient who has undergone a labyrinthectomy. Fol-
macula. The otoconia float into a dependent canal, lowing a transverse temporal bone fracture or a
most often the posterior semicircular canal, but the severe disruption of the stapes with total loss of
problem has been described in other canals. This hearing, the labyrinth repairs itself by a process
mechanism is commonly called canalithiasis. The called labyrithitis ossificans. This process is slow and
shifting of the mass of otoconia actually displaces takes several months before the semicircular canals
the fluid in the canal on head tilting. As a conse- ultimately ossify. Complete ossification, in effect,
quence, a short burst of vertigo occurs, with a typi- fixes the ampullae and maculae in solid bone so that
cal 5- to 7-second delay, lasting 20 to 30 seconds. they no longer respond to movement. If the
Typically, post-traumatic BPPV is unilateral and is vestibule or the posterior canal does not completely
354 Ballenger’s Otorhinolaryngology
ossify, symptoms such as movement-triggered ver- or without fracture, blast injuries, and extreme noise
tigo or positional vertigo can be noted in addition to exposure (ie, transient noise louder than 120 dB).
constant unsteadiness. Electronystagmographic These three mechanisms affect the cochlea in a sim-
examination usually reveals spontaneous nystagmus ilar fashion. Most often the hearing loss centers
and absent caloric responses in patients with trans- around 4 kHz, although more severe injuries can
verse fractures of the temporal bone. In sympto- certainly affect all of the frequencies. According to
matic patients, caloric excitability and positional Schuknecht, concussive forces on the cochlea result
nystagmus indicate residual function in the trauma- in a pressure wave that damages the outer hair cells
tized labyrinth. In these rare patients, a case can be in the basal turn of the cochlea, features identical to
made for a transmastoid labyrinthectomy to elimi- those seen with noise-induced hearing loss.13 Alter-
nate all vestibular function. natively, deceleration, blast injuries, and extreme
Post-traumatic vestibular dysfunction can also noise transmit forces to the stapes footplate that
occur if the central portion of the vestibular system result in disruption of the basilar membrane and the
is injured, such as that seen with cerebellar injury, organ of Corti, with resultant degeneration of the
brainstem nuclei injury, or even vestibular nerve spiral ganglion of the cochlea. Some common causes
avulsion. It should be noted here that these types of of this type of injury include air-bag detonation in
injuries nearly always involve multiple cranial nerve automobile accidents, gunshot blasts, and loud
injuries, widely varied neurologic dysfunction, and music speakers in vehicles and in night clubs.
prolonged unconsciousness following the injury. If high-frequency sensorineural hearing loss is
Careful evaluation with audiovestibular testing can found after a head injury, blast injury, or extreme
determine if a predominantly central vestibular noise injury, the author recommends bed rest, liberal
injury has occurred, as might be suggested by eye fluid intake, a short course of oral corticosteroids,
tracking abnormalities on ENG in the presence of and avoidance of loud noise. In some patients,
normal symmetric caloric tests or abnormal audi- improvement in thresholds is observed 2 weeks after
tory brainstem testing with normal otoacoustic the onset. If not, these patients should receive audi-
emissions. Treatment considerations in these tory rehabilitation, including use of a hearing aid.
patients might include vestibular rehabilitation ther- Post-traumatic hearing loss can also be found
apy, special glasses, and antinauseants. in injuries of the auditory nerve, brainstem, and tem-
poral cortex. Because of the severity of the injury,
most patients with this type of injury do not survive.
POST-TRAUMATIC COCHLEAR DYSFUNCTION However, the author has managed two documented
In addition to PLF, sensorineural hearing loss fol- and two likely cases of cochleovestibular nerve injury
lowing trauma can be attributable to a variety of in the last 20 years. In one patient, the
mechanisms including fracture of the otic capsule, cochleovestibular nerve was avulsed from the brain-
concussion of the inner ear without fracture, noise- stem, a situation discovered during the course of per-
or blast-induced injury, and central auditory path- forming a translabyrinthine facial nerve exposure in
way injury. Transverse fractures of the temporal which the facial nerve was followed from the stylo-
bone usually cross the vestibule or the basal turn of mastoid foramen to the brainstem. This patient had
the cochlea, resulting in total, sudden sensorineural bilateral temporal bone fractures and subsequently
hearing loss. The exact nature of the loss remains a required a hypoglossal nerve to facial nerve crossover
matter of conjecture, that is, it is possibly caused by procedure to reanimate the face. This patient was
loss of fluid mechanics, hair cell dysfunction, or vas- operated after a prolonged period of altered mental
cular injury to the cochlea. It does not appear that status and was discovered to have a complete facial
most transverse temporal bone fractures result in paralysis a year after the injury. The other three
significant cochlear neuronal injury. This is based on patients were seen after neurosurgical colleagues per-
the information that three of four cochlear implants formed microvascular decompression of the facial
performed in the United States on patients with and trigeminal nerves for hemifacial spasm or
transverse fractures are functioning extremely well. trigeminal neuralgia. In two of these patients, a com-
It is common to find high-frequency sen- plete hearing loss, vertigo, and facial palsy occurred,
sorineural hearing loss following head injury with findings that may have been owing to either stretch-
Trauma to the Middle Ear, Inner Ear, and Temporal Bone 355
ing of the cochleovestibular nerve or to occlusion of jugular bulb can be managed surgically by gaining
the vessels that feed the nerves. Neither of these transmastoid exposure of the sinus and placing
patients recovered auditory or vestibular function, extraluminal packing at the site of the injury.
although both regained modest House-Brackmann The most common vascular injury in the tem-
grade III (see Chapter 24) facial function. One of poral bone is to the lateral sinus with subsequent
these patients underwent a transmastoid labyrinthec- occlusion of the jugular bulb and lateral sinus.
tomy a year after the injury, and the labyrinth in this Venous occlusion rarely requires intervention,
case was not ossified, which suggests that the injury although delayed hydrocephalus is a concern in
could not be attributable to vascular occlusion. In a these patients. Occlusion of the petrous portion of
third patient who postoperatively had a 90 dB sen- the internal carotid artery is also common following
sorineural hearing loss, an abnormal auditory brain- injury. Arterial vascular occlusion is ordinarily man-
stem response, and normal otoacoustic emissions aged through careful observation with radiologic
(findings that clearly suggest an auditory neuron evaluation. In some patients, occlusion of the distal
injury), the hearing recovered to the 30 dB level at 6 part of the internal carotid artery is performed to
months. In patients with temporal lobe injury fol- prevent extension of a clot or an embolus into the
lowing head trauma, typically there are complaints downstream cerebral circulation. Occasionally, an
of difficulty understanding speech in noisy environ- aneurysm of the petrous or cavernous part of the
ments. In the few documented cases, speech under- internal carotid artery develops after a penetrating
standing is indeed diminished as measured with or blunt injury. Neurologic and radiologic consulta-
hearing-in-noise tests or synthetic sentence intelligi- tion is recommended in this circumstance also. In
bility testing. Rehabilitation in these circumstances these patients, the artery may be stented or may be
includes special listening devices and auditory train- bypassed using an external carotid or facial artery to
ing using neuroplasticity techniques (ie, fast forward middle cerebral artery bypass approach. In some
therapy to improve temporal processing). cases, an aneurysm can be occluded using intra-arte-
rial coils on the nondominant side.
In patients in whom the carotid artery is
VASCULAR INJURIES injured as it enters the skull, consultation with a vas-
Penetrating injuries of the temporal bone and skull cular surgeon or neurosurgeon is recommended. In
base can cause injuries to the major vessels either in expanding lesions, exploration and repair may be
the temporal bone or immediately outside the tem- indicated, and the otolaryngologist can provide
poral bone as these structures enter or exit from it. additional exposure of the region through mobiliza-
Vascular injury may include transection, laceration, tion and retraction of the mandible, parotid gland,
thrombosis, and aneurysm formation. Vascular and facial nerve branches.
injuries can be quite alarming because of the volume
of blood loss. Immediate management includes sta-
bilization of the cardiovascular system with fluid and
EUSTACHIAN TUBE INJURY
blood replacement, compression with dressings, and Penetrating injuries of the temporal bone occasion-
expedient evaluation with arteriography, MRI, mag- ally cause blockage of the eustachian tube, usually
netic resonance angiography, or high-resolution CT through cicatrix formation. This problem may not
scans. Furthermore, since cranial nerves are in close be appreciated for a period of time after the injury,
proximity to the internal carotid artery and jugular when persistent effusion in the middle ear space is
vein, an evaluation for their function should be car- noted. In some patients, a tympanostomy tube can
ried out as soon as possible. This specifically includes provide sufficient ventilation to keep the middle ear
cranial nerves VI through XII, with particular atten- open. In some patients, however, there is persistent
tion to the vagus, spinal accessory, and hypoglossal infection and drainage through the tympanostomy
nerves. Life-threatening hemorrhage can be quickly tube. In these patients, exploration of the eustachian
managed by an interventional neuroradiologist using tube through a transmastoid facial recess approach is
balloon occlusion, although this procedure is usually indicated. If the function of the eustachian tube can-
avoided because of the possibility of acute or delayed not be restored, the patient usually prefers leaving
stroke. Hemorrhage from the sigmoid sinus or the the drumhead intact and the use of a hearing aid.
356 Ballenger’s Otorhinolaryngology
INJURIES TO CHILDREN IN A BOMB BLAST 5. Ogren FP, Edmunds AL. Neuro-otologic findings in
the lightning-injured patient. Semin Neurol 1995;
As a direct result of the Oklahoma City truck bomb
15:256–62.
blast at the Alfred P. Murrah Federal Building, 816
6. Jones DT, Ogren FP, Roh LH, Moore GF. Lightning
adults and children were injured or killed. Among
the 19 pediatric patients killed in this tragedy, 17 suf- and its effects on the auditory system. Laryngoscope
fered skull fractures and 15 suffered cerebral evis- 1991;101:830–4.
ceration. A variety of other injuries were found in 7. Kristensen S. Spontaneous healing of traumatic
this group, including abdominal and thoracic tympanic membrane perforations in man: a century
injuries, amputations, extremity fractures, burns, of experience. J Laryngol Otol 1992;106:1037–50.
and contusions and lacerations.14 Nonfatal injuries 8. Rybak LP, Johnson DW. Tympanic membrane perfo-
occurred in 47 pediatric patients, 7 of whom re- rations from water sports: treatment and outcome.
quired hospitalization. Among the group hospital- Otolaryngol Head Neck Surg 1983;91:659–62.
ized, 2 suffered depressed skull fractures, 2 closed 9. Griffin WL. A retrospective study of traumatic tym-
head injuries, and 5 tympanic membrane perfora- panic membrane perforations in a clinical practice.
tions. A bomb blast is associated with a high inci- Laryngoscope 1979;89:261–82.
dence of cranial and temporal bone injury.
10. Goodhill V. Sudden deafness and round window
rupture. Laryngoscope 1971;81:1462–74.
REFERENCES
11. Epley JM. Particle repositioning for benign paroxys-
1. Kavanagh KT, Litovitz T. Miniature battery foreign mal positional vertigo. Otolaryngol Clin North Am
bodies in auditory and nasal cavities. JAMA 1986; 1996;29:323–31.
255:1470–2. 12. Semont A, Freyss G, Vitte E. Curing the BPPV with
2. Capo JM, Lucente FE. Alkaline battery foreign bod- a liberatory maneuver. Adv Otorhinolaryngol 1988;
ies of the ear and nose. Arch Otolaryngol Head Neck
42:290–3.
Surg 1986;112:562–3.
13. Schukneckt HF. Mechanism of inner ear injury from
3. Hallmo P. Extended high-frequency audiometry in
blows to the head. Ann Otol Rhinol Laryngol 1969;
traumatic tympanic membrane perforations. Scand
Audiol 1997;26:53–9. 78:253–62.
4. Panosian MS, Dutcher PO. Transtympanic facial 14. Quintana DA, Parker JR, Jordan FB, et al. The spec-
nerve injury in welders. Occup Med (Lond) 1994; trum of pediatric injuries after a bomb blast. J Pedi-
44:99–101. atr Surg 1997;32:307–10.
CHAPTER 15
Worldwide, exposure to excessive sound is the most and Bunch gave an excellent account of the audio-
common cause of acquired adult sensorineural hear- metric features of NIHL in 1939.4
ing loss. It is incurable but should be entirely pre- As a result of the technical advances of the Sec-
ventable. This chapter discusses the effect of noise ond World War, machinery became larger, more effi-
on the ear, noise-induced hearing loss (NIHL), and cient, and noisier, and as developing countries have
its prevention. rapidly industrialized, NIHL has become a global
Noise is any unwanted sound that at low inten- problem. Currently, with the advent of amplified
sity may be irritating and at high intensity may dam- music and inexpensive motorized transportation,
age hearing. Noise has physical, physiologic, and social, recreational, and community sound also plays
psychological connotations, all of which differ. Phys- a major disturbing role. So, although NIHL has been
ically, sound can be measured and is defined in well recognized for a century, its evaluation, accu-
terms of duration, frequency (measured in Hz), and rate quantification, and prevention have only
intensity measured in sound pressure levels (SPLs) recently become important. We each live in a per-
expressed as decibels (dB). Sound may be continu- sonal soundscape.
ous, intermittent, impulsive, or explosive.
EFFECT OF SOUND ON THE EAR
HISTORY Sound, depending on its intensity, may produce (1)
adaptation, (2) temporary threshold shift (TTS),
Although hearing loss produced by noise has been and (3) permanent threshold shift (PTS) in hearing.
known for centuries, it became a major problem Adaptation, which occurs whenever the ear is
with the discovery of gunpowder and a more wide- stimulated by sound, is a physiologic phenomenon,
spread problem with the Industrial Revolution. It and for sounds of 70 dB SPL or less, recovery occurs
was recognized in the United States, Germany, and within half a second.
the United Kingdom in the 1870s and 1880s. In Temporary threshold shift is a short-term
1886, Thomas Barr of Glasgow wrote, “It is famil- effect usually measured in minutes and hours rather
iarly known that boilermakers and others who work than seconds or days, in which the hearing threshold
in very noisy surroundings are extremely liable to elevates temporarily after exposure to noise. It
dullness of hearing. In Glasgow, we would have little occurs following intense sound stimulation. With a
difficulty finding hundreds whose sense of hearing low-frequency stimulus, the maximum threshold
has thus been damaged, by the noisy character of shift may occur an octave above the center frequency
their work.”1 Indeed, the riveting associated with of the stimulating tone; as the stimulating frequency
shipbuilding gave the generic title “boilermakers’ increases, the point of maximum shift moves closer
deafness” to NIHL. Barr’s work stands the test of to the stimulating tone. Tones of higher frequency
time as an excellent, well-conceived, and well-exe- cause more TTS than tones of lower frequency of
cuted epidemiologic survey. similar intensity. The amount of TTS increases for
The histology of noise-induced hearing loss in the duration and intensity of the sound exposure. It
the organ of Corti was already described by Haber- lasts from minutes to a few hours and is also a phys-
mann in 1890.2 Audiometrically, Fowler was the first iologic phenomenon. For further details on adapta-
to comment on the 4 kHz dip produced by noise,3 tion and TTS, the reader is referred to works by
357
358 Ballenger’s Otorhinolaryngology
rootlet at the level of the cuticular plate. The cilia fall from noise and aminoglycosides affects nerves as
over and ultimately are absorbed. With these greater well as hair cells. So protective strategies, although so
degrees of damage, intracellular changes also occur, far mainly based on hair cell protection from ROS,
including damage to lysosome granules, mitochon- also include protection of axons by neurotrophins.
dria, and the nucleus. As with other tissues in the The development of NIHL is also related to
body, there is a process of damage and repair. The feedback from the central nervous system (CNS).
repair with mild degrees of injury is within the cell That nerve supply of the outer hair cells is by effer-
itself; with greater degrees of injury, healing and scar ent fibers has been known for years, but their func-
formation occur by migration of other cells.14 An tion was poorly understood. It now appears that
elegant series of experiments by Gao et al demon- there is an active feedback system, which may be
strated, by means of electron photomicrographs, responsible for depressing the contractile activity of
responses of hair cells to intense and very intense outer hair cells, thereby diminishing the stimulus to
stimuli; in the former, the cilia flop slightly but do the associated inner hair cells. This may function to
not collapse, and they appear to recover completely; sharpen frequency discrimination and perhaps to
in the latter, they flop significantly and never eliminate the effect of low masking sound.
recover; indeed, they are scavenged and disappear.15 This mechanism may also explain why expo-
High levels of stimulation release excess of neuro- sure to enjoyable sound of equal intensity and dura-
transmitter in inner hair cells, which, in turn, leads tion produces less hearing loss than exposure to
to damage to associated nerve rootlets, which may be noise (eg, industrial of similar intensity and dura-
temporary or permanent.8 tion).
Over the past decade, the biochemical and As early as 1988, Canlon et al showed that prior
molecular basis of NIHL has become clearer; this is exposure to low-level sound “toughened” ears
leading to the possibility of fuller preventive and against subsequent exposure to harmful levels of
even curative strategies.16,17 It appears that oxidative sound.22 Prior toughening appears to work by up-
stress is a major cause of hair cell damage both in regulating the production of antioxidants such as
NIHL and antibiotic ototoxicity. Excessive stimula- glutathione.21
tion by noise produces toxic levels of reactive oxygen There has been much discussion in the
species (ROS), which damage phospholipids in cell literature about the role of other factors in noise
and nuclear membranes and deoxyribonucleic acid damage, including potentiation by exposure to other
(DNA); it increases intracellular Ca++ and up-regu- industrial toxins such as carbon monoxide and var-
lates cell death genes.18 There may be ways of pre- ious organic solvents. These will be described below.
venting or diminishing the formation of ROS, as, for
example, by increasing endogenous antioxidant sys-
tems by administering substances such as N-acetyl-
AUDITORY NERVE AND CENTRAL
cysteine. The administration of glutathione, a NERVOUS SYSTEM DAMAGE AFTER
powerful antioxidant, to guinea pigs prior to noise ACOUSTIC INJURY
exposure leads to less cochlear damage and hearing
There is also evidence of eighth nerve and CNS
loss than in matched noise-exposed animals that are
injury after chronic traumatic acoustic exposure.
not protected.19 Antioxidants also protect the inner
There certainly is good evidence of damage to the
ear of chinchillas from the damaging effects of
dendrites and nerve endings surrounding the hair
impulse noise.20 Glial cell line–derived neurotrophic
cells following acoustic overstimulation and, in
factor also provides protection from noise. It and
chronic preparations, spiral ganglion cell degenera-
heat shock protein (which protects hair cells against
tion spreading into the cochlear nucleus.23
excessive stimulation) are produced when the ear is
exposed to mild noise exposure and may account for
“toughening” of the ear to noise by prior sound PHYSIOLOGIC AND
exposure. Although promising, none of these mech- PSYCHOPHYSICAL CHANGES
anisms currently have any practical application in
humans.
TO NOISE EXPOSURE
It is also clear from the work of Puel and It has long been known, but only recently appreci-
Pujol,8 Duan et al,21 and Canlon et al22 that damage ated, that 90% of afferent nerve fibers from the
Occupational Hearing Loss 361
cochlea, which presumably carry information about place within the first 12 hours after noise exposure
sound stimulation to the CNS, arise from inner hair and is overwhelmingly complete within 48 hours,
cells, and yet damage to outer hair cells is associated although in detailed animal studies, slight recovery
with hearing loss from noise exposure. Outer hair continues for many weeks.28 This recovery is so slight
cells are overwhelmingly innervated by efferent that it is within the confidence limits of normal clin-
fibers, and it is becoming clear that stimulation of ical audiometric tests. However, after a single mas-
efferent fibers can alter the sensitivity of the cochlea sive insult such as an explosion, recovery may
by 20 or 30 dB. In other words, outer hair cells have continue for many weeks until the hearing loss is
a tuning effect on inner hair cells. Outer hair cells stable. This is usually accompanied by some PTS.
themselves contract in response to sound stimula-
tion, providing mechanical enhancement of the trav-
eling wave motion transmitted to inner hair cells. NOISE-INDUCED PERMANENT
The contractions produce audible sounds THRESHOLD SHIFT
detected as otoacoustic emissions (OAEs). These Noise-induced permanent threshold shift (NIPTS)
have been intensively studied to see if alteration of has many synonyms, one of the earliest being boiler-
OAEs after sound exposure can be used to predict makers’ deafness and the currently popular one being
susceptibility to noise exposure. To date, there are no NIHL. This is probably now the most common cause
definite outcomes.24 of acquired hearing loss in North American adults—
Much psychophysical work has been directed indeed throughout the world—and is overwhelmingly
toward single nerve fiber tuning curves, which have caused by chronic exposure to excessive sound levels
demonstrated a broadening of tuning curves of indi- in the workplace, whether civilian or military. It may
vidual nerve fibers following cochlear damage. At be potentiated by additional social and recreational
their most sensitive, they are less frequency selective noise exposure. The speed of onset and the degree of
than normal, and this is associated with outer hair cell loss are related to the total quantity of noise exposure
damage. In humans, the tuning curve of the cochlear (ie, its intensity and duration) and to the individual’s
nerve becomes broader with increasing hearing loss, susceptibility to damage by the noise. In general
and, certainly, damage from noise is associated with terms, industrial noise exposure is less intense but
reduced suprathreshold hearing function. more prolonged than military noise exposure.
It is difficult to quantify accurately the rela-
NOISE-INDUCED HEARING LOSS tionship between prolonged noise exposure and
hearing loss because, over the years, workplace noise
Intense acoustic overstimulation, whether acute or exposure changes, machinery is altered, jobs change,
chronic, can produce TTS and PTS. The noise source and hearing protection is provided. There are
may be continuous, intermittent, or mixed. Acoustic remarkably few long-term longitudinal studies
damage can also occur from a single intense sound equating hearing loss with noise exposure, and the
such as an explosion or even a single gunshot. Typi- likelihood of further studies in the future is becom-
cally, the first audiometric change in both TTS and ing increasingly remote because, as the hazards of
PTS is a drop in hearing at 3, 4, or 6 kHz, with nor- noise have been recognized, companies that are
mal hearing below and above these levels. This is interested enough to take regular noise measure-
known as an acoustic notch. In the early phases, the ments also provide hearing protection. The well-
subject usually recovers. It has long been known that studied group of jute workers in Dundee in the
the previously unexposed ear is more easily damaged 1960s is the benchmark against which most of this
by noise (green ears) than one accustomed to listen- work is measured.29
ing to loud sound,25 and there is recent evidence of
the “toughening of ears” by noise exposure.22 This is
a topic of great current interest and has been well NATURAL HISTORY OF NOISE-
reviewed by Hamernik and Ahroon26 and Yoshida INDUCED PERMANENT
and Liberman.27
The recovery period following TTS is of inter-
THRESHOLD SHIFT
est. It has been studied in detail by Mills28 in humans There is interest in the progress of NIPTS over time.
and in many animal studies. Most recovery takes What is the rate of growth of hearing loss? Does it
362 Ballenger’s Otorhinolaryngology
spread into other frequencies? Does the rate of is currently accepted that, within a significant range
increase level off, accelerate, or remain the same? with a lower boundary of safe sound and an upper
These are difficult questions to answer because of the boundary of sound so intense that it produces acute
lack of good longitudinal studies. It is unlikely that permanent damage, equal amounts of sound expo-
PTS will occur without TTS, and it is also unlikely sure produce equal amounts of damage. This is true
that PTS will be greater than TTS. Other than that, whether sound exposure is spread over a short or
there is little relationship between the two, and long period. In other words, a given sound experi-
attempts to predict PTS from TTS have not been suc- enced for 8 hours does as much harm as twice that
cessful. Permanent threshold shift usually starts in sound experienced for 4 hours or half that sound
the higher frequencies characteristically at 4 or per- experienced for 16 hours. The reader must remem-
haps at 3 or 6 kHz and gradually spreads into neigh- ber that decibels are a logarithmic scale. Doubling
boring frequencies. To begin with, the hearing loss is sound intensity is equivalent to a 3 dB increase in
asymptomatic, and only when it spreads into the SPL. Thus, a 93 dB sound is twice as intense as a
lower frequencies such as 2 kHz does it give rise to 90 dB sound, and a 103 dB sound is twice as intense
complaints. As time goes on, the notch disappears for as 100 dB sound. This equal energy concept, prom-
the hearing in the higher frequencies also worsens ulgated by Burns and Robinson,33 has been widely
(perhaps as a result of aging rather than noise) so adopted in Europe for many years and is gaining
that the audiogram becomes indistinguishable from acceptance in North America. However, it is now
many other sensorineural hearing losses. It is stated, suggested that if noise exposure is intermittent, as is
probably correctly, that after 10 years of exposure to usually the case in industry, the ear has time to
an average workplace noise, say between 90 and 94 recover and the 3 dB rule may be too strict. The best
dB, the loss in the higher frequencies stops worsen- fit is probably a 4 dB halving and doubling, although
ing, but gradually the loss spreads into the lower fre- no single rule fits all circumstances. This issue is well
quencies. The major part of the loss may occur quite reviewed by Ward.34
early in the first 2 or 3 years,30 and late losses are usu- The appropriate technique of evaluating the
ally contaminated with presbycusis, which becomes harmful effects of impact sound is still debated. Rifle
the dominant cause of worsening hearing. The rate of fire is a good example of military impact sound; a
spread and the degree of loss are related to both the drop forge, a pile driver, and a hammer blow are all
intensity of sound and the individual’s susceptibility examples of industrial impact noise. The character-
to noise. This is as important with sound exposure as istics of impact sound vary widely; they are meas-
with other physical insults such as response to sun- ured by rise and decay time and peak intensity and
light; individuals vary greatly, and, unfortunately, are difficult to measure because of the transient
there is no good way of predicting the unduly sus- nature of the sound. Hamernik and Hsueh give a
ceptible individual. In mice, it has been shown that good review of the nature and measurement of
there is a genetic susceptibility to hearing loss from impulse sound.35 It is probable that impulse noise is
noise, and it is postulated that the same is true in more damaging than steady-state noise of the same
humans, adding to predictive difficulties.31 If the intensity.
International Standards Organization (ISO) tables of Attempts have been made to codify risks into
risk are correct, it is probable that in later years too national and international standards for noise expo-
much hearing loss has been blamed on noise and too sure, which are used both to define the upper limit of
little on presbycusis. Furthermore, it appears that in safe exposure and to quantify the risk of hearing dam-
mice, a recessive gene (Ahl) that is responsible for age at various levels of intense sound. International
premature age-related hearing loss is also implicated standards have been based on the equal energy (3 dB
in excessive susceptibility to NIHL.32 If this is also halving and doubling) concept and were initially
true in humans, it may help explain some of the vari- embodied in ISO 1999 (New York, ISO, 1971) and
ability noted in response to sound exposure. revised as ISO 1999 (New York, ISO, 1984), and again
as ISO 1999 (1990[E]),36 which takes into account
such factors as other ear disease and aging. In North
DAMAGE RISK CRITERIA America, tables based on 5 dB halving and doubling
Many attempts have been made to define the rela- were introduced in the mid-1960s after a Committee
tionship between noise exposure and hearing loss. It On Hearing, Bioacoustics and Biomechanics
Occupational Hearing Loss 363
(CHABA) of the US National Research Council TABLE 15–1. Comparison of Hours of Equivalent
report in 1966 and codified in the Walsh-Healey Pub- Sound Exposure*
lic Contracts Act of 1969 (Federal Register 34, no. 96,
1969). Here it is assumed that the trading relationship Hours of Permitted Exposure LOSHA Leq
is 5 dB for halving and doubling of exposure, known 16 85 87
as LOSHA (US Occupational Safety and Health Admin-
istration), as opposed to the European 3 dB loudness 8 90 90
equivalent known as Leq. There is a significant, but in 4 95 93
practical terms frequently unnecessary, debate about 2 100 96
these trading relationships. It is important to know
1 105 99
that with a 90 dBA (dB on the A-weighted scale)
sound exposure for 8 hours a day, 5 days a week, 15% 0.5 110 102
of the population is at risk for significant hearing loss 0.25 115 105
after 10 years of exposure, and that for 85 dBA expo-
sure 8 hours a day, 5 days a week, after 10 years, only *Using an 8-hour 90 dBA baseline as allowed by LOSHA and Leq.
7% of the population is at risk. It is prudent, there-
fore, to initiate hearing conservation measures from
85 dB upward,37 and from a hearing conservation tinguishing the organic from the nonorganic com-
standpoint, little is to be gained from further dissec- ponents of this distressing but immeasurable com-
tion of these tables. Where they are significant is in plaint. There has been abundant literature about
attempting to equate total noise exposure in terms of tinnitus in recent years: the reader is referred to a
medicolegal investigations. Few jobs have a steady recent handbook edited by Tyler41 and to Chapter 22.
noise exposure throughout the working day or work-
ing week, and attempts to equate actual noise meas- WORSENING OF HEARING AFTER
urements at work over a period of years in which
several jobs have been held into a single risk figure for
NOISE EXPOSURE ENDS?
legal purposes are dramatically affected by which It is frequently asked if hearing loss from noise expo-
table of risk is used (Table 15–1). The tables of risk are sure can progress after removal from noise.
based on human hearing threshold changes and are Although hearing loss improves rather than worsens
difficult to correlate with histologic damage and hair after removal of chronic noise exposure, there is
cell destruction in noise-exposed animals. Better cor- considerable controversy in the literature about the
relation will be found as more subtle changes in hair interaction among noise, presbycusis, and progres-
cells are sought. The human studies are based on large sion of hearing loss. In mice strains that show pre-
samples of workers, including a large General Motors mature age-related hearing loss, which are also
study and studies of Austrian industrial workers. They usually susceptible to the effects of excessive noise
have been extensively evaluated in the literature in a exposure, there is a suggestion that after cessation of
series of publications by Passchier-Vermeer.38 noise exposure, hearing worsens more rapidly than
in similar but non–noise-exposed mice.31 The over-
whelming body of opinion, however, strongly sug-
TINNITUS gests that hearing loss that progresses after removal
Tinnitus is a distressing and frequent concomitant of of noise exposure is from some other cause. Tschopp
NIHL. Transient tinnitus is experienced commonly and Probst undertook a longitudinal study of hear-
after exposure to intense sound and almost invari- ing after exposure to a single sound; they found no
ably after a blast injury, but it usually clears. After worsening.42 The matter remains controversial and is
years of exposure, however, it may become perma- frequently raised in medicolegal claims.
nent and is present permanently in 50 to 60% of
those with NIHL,39 higher in those exposed to COMBINED EFFECTS OF
impact noise. The incidence and severity of tinnitus
usually increase with increased hearing loss. This OTOTRAUMATIC AGENTS
was not found by McShane et al in NIHL compen- Many things are known to injure the inner ear, for
sation claimants,40 highlighting the difficulty of dis- example, drugs, infections, trauma, age, and noise.
364 Ballenger’s Otorhinolaryngology
The ear is also affected by premature degenerative not demonstrated unequivocally. Studies by Macrea47
disorders such as familial hearing losses. Most of and others before him (summarized by Robinson48)
these agents have a final common pathway: they give some evidence for additivity, although they all
damage the hair cells and other structures of the say that there is no interaction. This matter is of con-
cochlea. There is great interest in and concern about siderable concern in terms of pension assessments,
how they interact: whether they are synergistic, addi- which are frequently made only at a time when pres-
tive, or protective. Is the noise-exposed ear more or bycusis might already be present. ISO 199936 implies
less affected by aging or is the effect additive? Is an an additive mechanism, which has been modeled by
old ear more likely to be damaged by noise than a Macrea (1991)47 and Dobie (1992).30 Robinson
young ear or is age irrelevant? Matters are com- reviewed the subject at length.48 It now seems that in
pounded by species differences among animals and later years, aging is a much more dominant cause of
between animals and man, and it is not always rea- worsening hearing than further noise exposure;
sonable to extrapolate from one to the other. indeed, at the higher frequencies by the age of 80,
Unfortunately, the ears that are most readily hearing is the same, whether the ear is noise exposed
studied and about which there is a large body of or not! The best model known to the author is that
knowledge, those of the guinea pig and chinchilla, of Corso, who gave a thoughtful discussion of the
do not necessarily behave in the same way as human topic and concluded that, at best, there is limited
ears. With this caveat, in guinea pigs it has been additivity.49 There is a good recent discussion by
shown that kanamycin given after noise exposure is Dobie that concluded that except for high noise
more damaging than kanamycin alone, although the exposure levels, the effects are additive.50
reverse is not true. Aminoglycoside antibiotics and Is an already noise-damaged ear more or less
excessive sound exposure both exert their effect on susceptible to damage from further noise exposure
hearing by releasing free oxygen radicals, which than an undamaged ear? This question is frequently
explains their synergy; it also suggests ways of pro- raised when hearing-impaired workers attempt to
tection by exposing the hair cells to antioxidants. move from one noisy industry to another only to
The ototoxic/cytotoxic drug cisplatin acts synergis- fail to find employment in the belief that, because of
tically with other ototoxic drugs and noise in the previous damage to their ears, their hearing is more
same way. likely to degenerate more rapidly than in a normal
Certain industrial solvents and chemicals are ear. The little existing evidence suggests that this is
ototoxic. Jet fuel and styrene are predominantly wrong and that the ear will continue to degenerate
vestibulotoxic but also appear to impair central at a steady rate with a natural history appropriate
auditory function. Rybak published an exhaustive for it.
review in which he suggested that there may be a
synergistic effect between inhaling styrene and noise
exposure. He draws similar conclusions about
ACOUSTIC TRAUMA
inhaled carbon disulfide.43 Toluene is the most com- Explosion and other single loud sounds can cause
monly used, most studied, and probably the most hearing loss. Early examples were “telephone ear,”
ototoxic industrial chemical. It produces hearing loss produced by static in early telephones. Other exam-
and potentiates the effect of noise exposure. 44 ples include workers inside metal tanks, the outside
Morata et al have provided convincing epidemio- of which is struck by sledge hammers, quarrymen
logic studies demonstrating the synergistic effects of too close to a blasting accident, and armed forces
noise exposure and toluene44,45 and between noise personnel near a single explosion. The most recent
and petrochemicals inhaled in the oil refining indus- examples are hearing loss produced by the inadver-
try. Noise and vibration act synergistically in those tent ringing of a cordless telephone into the ear of
who suffer from white hand and work in the cold the listener51 and the detonation of air bags in auto-
such as foresters using chain saws or shipbuilders.46 mobile accidents.52 Perhaps, globally, the most per-
The interaction between noise exposure and vasive examples at present are firecrackers and
aging is hotly debated. At most, it appears that pres- high-power weapons. An older but excellent review
bycusis is additive to noise change, and even this is of the topic is given by Phillips and Zajtchuk.53
Occupational Hearing Loss 365
be sought (eg, recreational, military, and occupa- no TTS. Authorities have legislated different time
tional). Even within the realm of occupational hear- periods out of noise for this, ranging from 6 months
ing loss, it is often difficult to attribute the cause to to 48 hours. It is the author’s view that if the
a specific employer and ultimately may become a claimant has been subjected to chronic noise expo-
matter of clinical skill and exquisite judgment to sure, a period of 48 hours free of noise is adequate
establish both the cause of the hearing loss and the for compensation assessment, and, in fact, anything
proportion of it that should be attributed to any much longer is impractical, particularly if the
given employer. employee is continuing to work. The situation is dif-
The responsibility of the assessing physician is ferent after a major blast accident or head injury, in
to the patient: to quantify the hearing loss accurately, which recovery may continue for a period of many
establish a diagnosis, and make a recommendation weeks, and a compensation assessment should not
about treatment or rehabilitation. If physical signs be undertaken for a minimum of 3 months after the
or symptoms suggest other ear disease, this should episode.
be followed through, and, in particular, causes of The types of tests to be undertaken vary by
asymmetric hearing loss should be investigated. It is local use rather than any intrinsic factors related to
possible to have an asymmetric hearing loss from the tests. They must be undertaken with properly
noise exposure, such as, for example, individuals calibrated equipment and in appropriately cali-
who fire guns off one shoulder, concert violinists, brated soundproof enclosures. Although screening
workers who use certain industrial equipment such tests make much use of the automatic Békésy
as rock drills, and people who drive farm tractors audiometry, a test to quantify hearing loss accurately
with one ear to the engine and the head constantly requires standard behavioral audiometry: air-con-
turned over the shoulder, protecting the other ear. A duction, bone-conduction, and speech reception
dosimeter study showed a 9 dB difference in sound thresholds. Further tests are undertaken as indicated.
level between the ears when using a heavy handheld If there is an asymmetric loss, site-of-lesion tests are
drill to make holes in a concrete form. Unequal hear- performed; if there is doubt about the accuracy of
ing thresholds were present in about 10% of a large the behavioral test, the appropriate special tests are
series of claimants for occupational hearing loss,69 performed.
much of which was attributable to other ear disease, Many audiometric tests are used to identify
as well as asymmetric industria1 exposure from exaggerated hearing loss, but there are few that
machinery and unequal damage to ears from explo- quantify it. Quantification for compensation pur-
sions at work. The significance of asymmetric hear- poses must be frequency-specific and parallel tonal
ing loss in military personnel has recently been audiometry. In unilateral hearing loss, the Stenger
evaluated by Caldera and Pearson70 There are recent test is effective. In bilateral hearing loss, electric
thoughtful discussions about the diagnosis of NIHL response testing is necessary, and in this group of
from a North American standpoint by Dobie50 and patients, slow vertex response (SVR) audiometry is
from a British view by Coles et al.71 the most effective. Auditory brainstem responses,
currently much in vogue, usually provide only a click
threshold, which gives a general idea of the level of
HEARING TESTS hearing but not a simulacrum of an audiogram. To
Hearing tests used in occupational hearing loss are obtain this by means of brainstem audiometry
of two types, screening and diagnostic. Screening requires expensive filtering techniques and a much
tests will be dealt with under “Hearing Conservation lengthier test. The relative merits of various evoked
Programs.” This section deals with diagnostic tests. response tests have been well described by Hyde et
The degree of accuracy required here is greater than al72 and the SVR audiometry in this type of patient
in routine clinical diagnostic audiology; it cannot be by Alberti et al.73 They use certain guidelines to iden-
overemphasized that the tester must be experienced tify the patient who should have SVR audiometry
in this type of work. The basis for most pension and and place considerable emphasis on the discrepancy
compensation awards is the pure-tone audiogram, between speech reception threshold and pure-tone
which must be accurate to be fair to both employer average and on the 500 Hz air-conduction thresh-
and employee. At the time of testing, there should be old. Klockhoff et al74 and Alberti et al75 both demon-
368 Ballenger’s Otorhinolaryngology
strated that the probability of a hearing loss of 40 dB elements: (1) noise hazard identification, (2) engi-
or greater at 500 Hz being caused by something neering controls, (3) personal hearing protection,
other than noise is high. These patients produce a (4) monitoring, (5) record keeping, (6) health edu-
high yield of other ear disease and of nonorganic cation, (7) enforcement, and (8) program evalua-
hearing loss. tion.
A good hearing conservation program is mul-
THERAPY AND REHABILITATION tidisciplinary, involving the industrial hygienist,
engineer, nurse, audiometric technician, and fre-
Experimental work suggests that symptoms of an quently supervisory audiologist and otologist. Good
acute traumatic hearing loss can be helped by the reviews of such programs are found in specific texts
use of hyperbaric oxygen76 or carbogen,77 but this on hearing conservation.79 Sound measurement is a
treatment does not have widespread acceptance. The skilled task devised to answer two questions: (1)
use of antioxidants is also still experimental in that What are the absolute sound levels in the work
there is no easy delivery system to the cochlea. place? and (2) What is the sound exposure of the
The clinical onset of occupational hearing loss individual? Carefully performed sound surveys
is usually insidious, but ultimately the complaints measuring sound levels throughout the plant and
are those of any sensorineural hearing loss: difficulty throughout the working day indicate the absolute
in distinguishing one voice from many, difficulty in environmental levels and help identify those who
hearing in crowds, family complaints about the may be exposed to potentially hazardous noise. The
loudness of the television set, and inattentiveness. exposure of individual workers, if the job is static,
The psychological impact on the worker and his or may be extrapolated from these measurements, but
her family has recently received considerable atten- it is far better to undertake individual noise dosime-
tion. Denial of problems, withdrawal, and lack of try studies. Dosimeters are small but expensive
family interaction may have a severe effect on inter- devices that sample and store the total sound
personal family relationships.66,67 received. The measurement of impact and impulsive
Much can be done to ameliorate the impair- noise is particularly difficult and may require special
ment with both specific and general devices. We have laboratory equipment.
found a telephone handset amplifier (obtainable A great effort must be made to have total col-
from most telephone companies), a louder bell, and laboration of the workforce; to be successful, it
a specific television amplifier to be the most useful. requires bottom up planning and implementation
Many patients use a hearing aid to amplify televi- and top down guidance.
sion, but this also amplifies all other sounds in the
environment, such as paper rustling, children cry-
ing, dishes clattering, and other people talking. A SOUND ABATEMENT AND
specific amplifier or television such as a headphone ADMINISTRATIVE CONTROL
or extension loudspeaker serves both to make the
sound louder and to improve the signal-to-noise The most effective way of reducing the risk of NIHL
ratio. Hearing aids are useful for and well accepted is to engineer out noise at the source by either
by those with NIHL.78 They should not be withheld. silencing machinery or enclosing it. It is sometimes
possible to retrofit machinery and provide sound-
HEARING CONSERVATION silencing barriers. Vicarious noise exposure should
be eliminated; for example, there is no need to have
PROGRAMS a workbench beside a drop forge and to expose the
Noise-induced hearing loss is incurable but largely mechanic, as well as the forge operator, to the noise
preventable. The technique of prevention is known of the forge. This happens all too often. In many
as hearing conservation. A hearing conservation industrial plants, it is possible to put the equipment
program has four main features: sound measure- operator inside a sound-enclosed booth and sepa-
ment, engineering and administrative controls, rate him from noisy machinery, for example, in
personal hearing protection, and audiometric mon- ships’ engine rooms, hydroturbine halls, and paper-
itoring of the population at risk, with the following making plants.
Occupational Hearing Loss 369
10. Liberman MC. Chronic ultrastructural changes in D, Salvi R, editors. New perspectives on noise
acoustic trauma. Serial section reconstruction of induced hearing loss. New York: Raven Press; 1980.
stereocilia and cuticular plates. Hear Res 1987;16: p. 105–35.
65–88. 24. Marshall L, Miller JL, Heller LM. DPOAES as screen-
11. Liberman MC, Dodds LW. Acute ultrastructural ing tool for NIHL. Noise and Health 2000;3:76–7.
changes in acoustic trauma. Serial section recon- 25. Glorig A. Noise and the ear. New York: Grune &
struction of stereocilia and cuticular plates. Hear Res Stratton; 1958.
1987;26:45–64. 26. Hamernik RP, Ahroon WA. Susceptibility of the
12. Kiang NYS, Liberman MC, Sewell WF, et al. Single noise-toughened auditory system to noise-induced
unit clues to cochlear mechanisms. Hear Res 1986;22: trauma. Hear Res 1999;132:140–8.
171–82. 27. Yoshida N, Liberman MC. Sound conditioning
13. Schacht J, Canlon B. Biochemistry of the inner ear. reduces noise-induced permanent threshold shift.
In: Alberti PW, Ruben RJ, editors. Otologic medicine Hear Res 2000;148:213–9.
and surgery. New York: Churchill Livingstone; 1988. 28. Mills JH. Threshold shifts as produced by a 90-
p. 151–78. day exposure to noise. In: Henderson D, Hamer-
14. Slepecky N. Overview of mechanical damage to the nik RP, Dosanjh D, Mills JH, editors. Effects of noise
inner ear—noise as a tool to probe cochlear func- on hearing. New York: Raven Press; 1976. p. 265–75.
tion. Hear Res 1986;22:307–21. 29. Taylor W, Pearson JCC, Mair A, et al. Study of noise
15. Gao WY, Ding DL, Zheng XY, et al. A comparison of and hearing in jute weaving. J Acoust Soc Am 1965;
changes in the stereocilia between temporary and 33:13–120.
permanent hearing losses in acoustic trauma. Hear 30. Dobie RA. The relative contributions of occupa-
Res 1992;62:27–41. tional noise and aging in individual loss of hearing.
16. Henderson D, McFadden SL, Zheng XY, et al. Inter- Ear Hear 1992;13:19–27.
vention possibilities for noise induced hearing loss. 31. Li HS, Borg E. Auditory degeneration after acoustic
In: Prasher D, Canlon B, editors. Cochlear pharma- trauma in two genotype mice. Hear Res 1993;68:
cology and noise trauma. London: NRN Publica- 19–27.
tions; 1999. p. 85–95. 32. Davis RR, Newlander JK, Ling X, et al. Genetic basis
17. Miller JM, Altschuler R. Prevention of noise-induced for susceptibility to noise-induced hearing loss in
hearing loss. Noise and Health 2000;3:83. mice. Hear Res 2001;155:82–90.
18. Ohinata Y, Miller JM, Altschuler R, Schacht J. Intense 33. Burns W, Robinson DW. Hearing and noise in
noise induces formation of vasoactive lipid peroxi- industry. London: HM Stationery Office; 1970.
dation products in the cochlea. Brain Res 2000; 34. Ward WD. The role of intermittence in PTS. J Acoust
878:163–73. Soc Am 1991;90:164–9.
19. Ohinataab Y, Yamasobac T, Schacht J, Miller JM. 35. Hamernik RP, Hsueh KD. Impulse noise—some def-
Glutathione limits noise-induced hearing loss. Hear initions, physical acoustics and other considerations.
Res 2000;146:28–34. J Acoust Soc Am 1991;90:189–96.
20. Henderson D, McFadden SL, Liu CC, et al. The role 36. ISO 1999. 2nd ed. New York: International Standards
of antioxidants in protection from impulse noise. Organization; 1990.
Ann N Y Acad Sci 1999;884:368–80. 37. Lutman ME. What is the risk of noise-induced hear-
21. Duan M, Agerman K, Ernfors P, Canlon B. Comple- ing loss at 80, 85, 90 dB(A) and above? Occup Med
mentary roles of neurotrophin 3 and N-methyl-D- (Lond) 2000;50:274–5.
aspartate antagonist in the protection of noise and 38. Passchier-Vermeer W. Noise induced hearing loss
aminoglycoside-induced ototoxicity. Proc Natl Acad from exposure to intermittent and varying noise. In:
Sci U S A 2000;97:597–602. Proceedings of International Congress on Noise as a
22. Canlon B, Borg E, Flock A. Protection against noise Public Health Problem. Washington (DC): US Envi-
trauma by pre-exposure to low level acoustic stimuli. ronmental Protection Agency; 1983. p. 169–200.
Hear Res 1988;34:197–200. 39. Axelsson A, Barreras ML. Tinnitus in noise induced
23. Liberman MC, Mulroy MJ. Acute and chronic effects hearing loss. In: Dancer AL, Henderson D, Salvi RJ,
of acoustic trauma: cochlear pathology and auditory Hamernik RP, editors. Noise induced hearing loss.
nerve pathophysiology. In: Hamernik RP, Henderson St. Louis: Mosby Year Book; 1992. p. 269–76.
372 Ballenger’s Otorhinolaryngology
40. McShane D, Hyde ML, Alberti PW. Tinnitus preva- 57. Axelsson A, Hellstrom PA, Altschuler R, Miller JM.
lence in occupational hearing loss claimants. Clin Inner ear damage from toy cap pistols and fire-crack-
Otolaryngol 1988;13:323–30. ers. Int J Pediatr Otorhinolaryngol 1991;21:143–8.
41. Tyler RS, editor. Tinnitus handbook. San Diego: Sin- 58. Clark WW. Noise exposure from leisure activities—
gular; 2000. a review. J Acoust Soc Am 1991;91:175–81.
42. Tschopp K, Probst R. Acute acoustic trauma. A ret- 59. Kramer MB, Wood D. Noise induced hearing loss in
rospective study of influencing factors in different rural school children. Scand Audiol 1982;11:279–80.
therapies in 268 patients. Acta Otolaryngol (Stockh) 60. Hughes KB. Sensorineural deafness due to compres-
1989;108:378–84. sion chamber noise. J Laryngol Otol 1976;90:803–7.
43. Rybak LP. Hearing—the effects of chemicals. Oto- 61. Kylen P, Stjernvall JE, Arlinger S. Variables affecting
laryngol Head Neck Surg 1992;106:677–86. the drill generated noise levels in ear surgery. Acta
44. Morata TC, Dunn DE, Kretschmer LW, et al. Effects Otolaryngol (Stockh) 1977;84:252–9.
of occupational exposure to organic solvents and 62. Man A, Winerman I. Does drill noise during mastoid
noise on hearing. Scand J Work Environ Health surgery affect the contralateral ear. Am J Otol 1985;
1993;19:245–54. 6:334–5.
45. Morata TC, Fiotini AC, Fischer FM, et al. Toluene 63. Von Gierke HE, Harris CS. On the potential associa-
induced hearing loss among rotogravure printing tion between noise exposure and cardiovascular dis-
workers. Scand J Work Environ Health 1997;23: ease. In: Berglund V, Karlsson J, Lindvall T, editors.
289–98. Noise as a public health problem. Part 1, ed. v. Stock-
46. Iki M, Kurumatami N, Hirata K, et al. Association holm: Swedish Council for Building Research; 1990.
between vibration-induced white finger and hearing 64. Stansfeld SA, Gallacher J, Babisch W, et al. Road traf-
loss in forestry workers. Scand J Work Environ fic noise, noise sensitivity and psychiatric disorder
Health 1986;12:365–70. —preliminary prospective findings from the Caer-
47. Macrea JM. Presbyacusis and noise induced perma- philly study. In: Vallet M, editor. Noise as a public
nent threshold shift. J Acoust Soc Am 1991;90:2513–6. health hazard. Vol 3. Bron: Institute Nationale
48. Robinson DW. Relation between hearing threshold de Recherche sur les Transports et leur Sécurité
level and its component parts. Br J Audiol 1991; (INRETS); 1993. p. 268–73.
25:93–103. 65. Bronzaft AL. The effects of noise on learning, cogni-
49. Corso JF. Age correction factor in noise-induced tive development and social behaviour. In: Fay TH,
hearing loss: a quantitative model. Audiology 1980; editor. Noise and health. New York: New York Acad-
19:221–32. emy of Medicine; 1991. p. 87–92.
50. Dobie RA. Medical-legal evaluation of hearing loss. 66. Hetu R, Lalonde M, Getty L. Psychosocial disadvan-
2nd ed. San Diego: Singular; 2001. tages associated with occupational hearing loss as
51. Singleton GT, Whitaker DL, Keim RJ, Kemker FJ. experienced in the family. Audiology 1987;26:141–52.
Cordless telephones: a threat to hearing. Ann Otol 67. Hallberg LR-M, Barreras ML. Living with a male with
Rhinol Laryngol 1984;93:565–8. noise induced hearing loss—experiences from the
52. Cunningham CD, Weber PC, Cure J. Neurotologic perspective of spouses. Br J Audiol 1993;27:255–61.
complications associated with deployment of airbags. 68. Alberti PW, Blair RL. Occupational hearing loss— an
Otolaryngol Head Neck Surg 2000;123:637–9. Ontario perspective. Laryngoscope 1987;92:535–9.
53. Phillips YY, Zajtchuk JT. Blast injuries of the ear in 69. Alberti PW, Symons F, Hyde ML. Occupational hear-
military operations. Ann Otol Rhinol Laryngol ing loss—the significance of asymmetrical hearing
Suppl 1989;140:3–4. thresholds. Acta Otolaryngol (Stockh) 1979;87:
54. Berglund B Lindvall T, Schwelas DH, editors. 255–63.
Guidelines for community noise. WHO 1999. 70. Caldera SR, Pearson CR. Risk management of asym-
www.who.int/peh/noise.guidelines2.html. 2001. metrical hearing impairment in an armed forces
55. Roy B, Das P. Status of road traffic noise in Calcutta population. J Laryngol Otol 2000;114:345–9.
metropolis, India. J Acoust Soc Am 1997;101:943–9. 71. Coles RR, Lutman ME, Buffin JT. Guidelines on
56. Gupta D, Vishwarama SK. Toy weapons and fire- the diagnosis of noise-induced hearing loss for
crackers—a source of hearing loss. Laryngoscope medicolegal purpose. Clin Otolaryngol 2000;25:
1989;99:330–4. 264–73.
Occupational Hearing Loss 373
72. Hyde ML, Alberti PW, Matsumoto N, et al. Auditory SUGGESTED READING
evoked potentials in audiometric assessment of
Alberti PW, editor. Personal hearing protection in indus-
compensation and medical-legal patients. Ann Otol
try. New York: Raven Press; 1980.
Rhinol Laryngol 1986;95:514–9.
73. Alberti PW, Hyde ML, Riko K. Exaggerated hearing Axelesson A, Borchgrevink HM, Hamernik RP, et al, edi-
loss in compensation claimants. J Otolaryngol 1987; tors. Scientific basis of noise-induced hearing loss.
16:362–6. New York: Thieme; 1996.
74. Klockhoff I, Drettner B, Svedberg A. Computerized Burns W. Noise and man. 2nd ed. London: Murray; 1973.
classification of the results of screening audiometry King PF, Coles RR, Lutman ME, Robinson DW. Assess-
in groups of persons exposed to noise. Audiology ment of hearing disability, guidelines for medicole-
1974;13:326–34. gal practice. London: Whurr; 1992.
75. Alberti PW, Morgan PP, Czuba I. Speech and pure Morata TC, Dunn DE, editors. Occupational hearing
tone audiometry as a screen for exaggerated hearing loss. Occupational medicine state of the art reviews.
loss in industrial claims. Acta Otolaryngol (Stockh) Vol 10. Philadelphia: Hanley Begus; 1995.
1978;85:328–31. Nilsson P, Arlinger S, editors. International symposium
76. Demaertelaere L, Van Opstal M. Treatment of on effects of impulse noise on hearing. Scand Audiol
acoustic trauma with hyperbaric oxygen. Acta 1971;Suppl 12.
Otorhinolaryngol Belg 1981;35:303–14. Prasher D, Luxon L, Pyykko I, editors. Advances in noise
77. Witter HL, Deko RC, Lipscomb DM, et al. Effects of research. Vol 2. Protection against noise. London:
pre-stimulatory carbogen inhalation on noise- Whurr; 1998.
induced temporary threshold shifts in humans and Rossi G, editor. Proceedings of the 4th International
chinchilla. Am J Otol 1980;1:227–32. Congress: noise as a public health hazard. Torino,
78. Riko K, Hyde MI, McShane D, Alberti PW. Hearing Italy: Amplifon; 1983.
aid usage in occupational hearing loss claimants. J Salvi RJ, Henderson D, Hamernik RP, Colletti V, editors.
Otolaryngol 1990;19:25–30. Basic and applied aspects of noise-induced hearing
79. Berger EH, Royster LH, Royster JD, et al. The noise loss. New York: Plenum Press; 1985.
manual. 5th ed. Akron (OH): American Industrial Schafer RM. The tuning of the world. Toronto: McClel-
Hygiene Association; 2000. land and Stewart; 1977.
80. Alberti PW. Active hearing protectors. In: Berglund Tobias JV, Jansen G, Ward WD, editors. Noise as a pub-
V, Karlsson J, Lindvall T, editors. Noise as a public lic health problem. Rockville (MD): American
health problem. Part 1, ed. V. Stockholm: Swedish Speech-Language-Hearing Association; 1980. ASHA
Council for Building Research; 1990. p. 79–87. Report 10.
81. Allen CH, Berger E. Development of a unique pas- Ward WD. Proceedings of the International Congress:
sive level-dependent hearing protector. J Acoust Soc noise as a public health problem. Washington (DC):
Am 1987;Suppl 81:55. US Environmental Protection Agency; 1973.
CHAPTER 16
Ototoxicity
Leonard P. Rybak, MD, PhD, John Touliatos, MD
Ototoxicity can be defined as the capacity of a drug ally about one-third of corresponding serum con-
or chemical to damage inner ear structure and/or centrations. Penetration of aminoglycosides across
function. The damage may occur in the auditory or the blood-brain barrier is minimal, except in
vestibular portion or in both parts of the inner ear. neonates.
A large number of agents with the propensity for Aminoglycosides are excreted in the urine by
ototoxicity exist. This chapter deals with several of glomerular infiltration; therefore, concentrations in
the more common drugs and chemicals likely to the urine may exceed those in the serum. Impaired
cause hearing loss and/or cochlear injury. These renal function reduces the rate of excretion and may
agents include aminoglycoside antibiotics, the anti- lead to accumulation in the body. Doses are fre-
neoplastic drugs cisplatin and carboplatin, loop quently adjusted downward in patients with
diuretics, and salicylates. The risk factors, phar- decreased renal function.
macokinetics, and monitoring of blood levels are In ototoxic doses, the cochleotoxic agents
discussed. (neomycin, kanamycin, amikacin, sisomycin,
lividomycin) appear to elicit patterns of injury to the
cochlea in experimental animals that are similar to
AMINOGLYCOSIDE ANTIBIOTICS the patterns seen in human temporal bones. These
Although they were not the first drugs with adverse compounds tend to cause selective destruction of
effects on the inner ear, it was the widespread use of the outer hair cells in the basal turn of the cochlea,
aminoglycoside antibiotics in the late 1940s and with progression toward the apex as the dose and
1950s as chemotherapy against tuberculosis that duration of treatment are increased.
drew the attention of the medical community to the Several prospective studies of aminoglycoside
problem of ototoxicity. ototoxicity have been carried out. Fee1 and Smith et
The aminoglycosides provide bactericidal al2 compared gentamicin ototoxicity with tobra-
activity against gram-negative aerobic bacteria and mycin ototoxicity and found cochlear damage in 10
include streptomycin, dihydrostreptomycin, tobra- to 16% of patients and vestibular toxicity in 5 to
mycin, gentamicin, neomycin, netilmicin, sisomicin, 15%.
amikacin, and kanamycin. Netilmicin appears to be The ototoxic potential of aminoglycoside
the least ototoxic drug in the group. administration is determined by total serum con-
Amikacin and kanamycin have more of an centration over time. In practice, however, monitor-
effect on the cochlea than on the vestibular system, ing peak and trough levels is more practical and
whereas streptomycin and gentamicin appear to provides reasonable protection against toxicity, as
exert greater effects on the vestibular system than on well as ensures that the therapy is adequate. Lerner
the cochlea, although auditory damage does occur and associates found an association of ototoxicity
with their use. However, with any of these drugs, with elevated mean trough levels.3
both auditory and vestibular toxicity can occur Moore et al reported that bacteremia, elevated
simultaneously. temperatures, liver dysfunction, and elevated serum
Because only about 3% of an orally adminis- urea nitrogen-to-creatinine ratios were risk factors
tered dose is absorbed from the gastrointestinal associated with ototoxicity in prospective double-
tract, these drugs usually are given parenterally. blind clinical trials of gentamicin, tobramycin, and
Tissue concentrations of aminoglycosides are usu- amikacin.4 In another study, univariate and multi-
374
Ototoxicity 375
variate analysis of risk factors of ototoxicity showed from the apoptotic cascade, and gene therapy to
only age as a predisposing factor for toxicity. enhance expression of genes that will synthesize
One of the newly identified risk factors may be neurotrophins or other protective substances.
genetic susceptibility. Hypersensitivity to aminogly-
coside ototoxicity can be transmitted by mothers as
a genetic trait. A mitochondrial deoxyribonucleic ANTINEOPLASTIC DRUGS:
acid (DNA) polymorphism, 1555G, is associated with CISPLATIN AND CARBOPLATIN
aminoglycoside-induced deafness.5 The basis for this
hypersensitivity to ototoxicity may be based on the
CISPLATIN
three-dimensional structure of the ribosome, favor- After a 1-hour intravenous infusion of 70 mg/m2 of
ing the binding of aminoglycoside, leading to dis- cisplatin, the plasma platinum concentrations were
ruption of protein synthesis and cell death in the found to have a biphasic clearance with half-life val-
cochlea.6 ues of 23 minutes and 67 hours. Seventeen percent
Acute damage to the cochlea is often preceded of the administered dose was excreted in the first 24
by tinnitus, although ototoxic effects can occur in hours. Renal excretion is primarily by glomerular fil-
the absence of tinnitus. The loss of hearing that tration. Ninety percent of cisplatin is bound to
results from the use of these drugs initially affects serum proteins,8 and this cisplatin-protein complex
the high frequencies. Since patients do not complain is inactive against tumor cells. The serum levels of
about or have noticeable hearing losses until they non–protein-bound platinum display different
have 30 dB losses that include frequencies as low as kinetics than those found for total platinum levels in
3,000 to 4,000 Hz, the detection of ototoxicity is dif- serum. It is not known whether toxic metabolites of
ficult unless audiometric monitoring is performed. cisplatin are formed either in the inner ear or in the
Monitoring is particularly important in high-risk other parts of the body. However, the liver has been
patients, such as those with renal insufficiency, those shown to convert cisplatin into nontoxic metabolites
on higher-than-usual drug doses, those with persist- within 1 hour.
ently elevated serum levels despite dosage adjust- Early after its introduction, standard cisplatin
ments, or those with some degree of a baseline doses were 50 mg/m2. Subsequent cisplatin treatment
hearing or balance disorder. When audiometric regimens have been developed using higher doses of
measurements are obtained, the usual definition of cisplatin (100 to 120 mg/m2 = high dose and 150 to
ototoxicity is a hearing loss of 10 dB bilaterally at 225 mg/m2 = very high-dose regimens). These
any frequency; some authors have used 20 dB as the increased-dosage regimens have resulted in a higher
cutoff. Again, since the usual threshold for percep- incidence of hearing loss than that observed with the
tion of hearing loss by patients is a 30 dB drop, there lower dosage of 50 mg/m2, as well as some different
will be at least that much of a loss by the time eval- perspectives on cisplatin-induced hearing loss. In a
uation of the patient’s complaints is begun. study of 54 patients receiving high-dose cisplatin,
The formation of free radicals (reactive oxygen Laurell and Jungnelius found that 81% of the
species, reactive oxygen metabolites) by aminogly- patients had significant threshold elevations (15 dB
cosides has come to the forefront as the etiologic or more at one frequency and 10 dB or more in three
mechanism responsible for ototoxicity. The observa- frequencies).9 After therapy, which ranged from one
tion that gentamicin may act as an iron chelator was to seven courses, 41% of the patients had significant
key to establishing that the formation of free radicals deterioration of hearing in the speech frequency
by aminoglycosides is an important mechanism in range of 500 to 2,000 Hz. Twenty-five percent of
the development of ototoxicity.7 patients lost 25% of their remaining high-frequency
Several protective models are currently being hearing after each course. Preexisting hearing loss did
investigated to prevent free radical–induced apop- not seem to predispose to ototoxicity, but advanced
totic cell death in cochlear hair cells. Those models age was slightly associated with risk of hearing loss.
that have been experimentally successful include The audiogram after the first course did not predict
administration of appropriate neurotrophins or future deterioration of hearing during treatment
growth factors, administration of caspase-specific with high-dose protocols. In this study, the ototoxic
inhibitors that remove the essential catalyst caspase risk was determined more by the amount of the sin-
376 Ballenger’s Otorhinolaryngology
gle dose than by the cumulative dose levels. No oto- ototoxicity may be more severe after bolus injection,
toxic effects were seen at a peak plasma concentration the ototoxic effects can be reduced by using slow
of less than 1 µg/L. Based on their findings, the infusion and dividing the doses over several
authors recommended that patients undergoing months.11 Bokemeyer et al evaluated a group of adult
high-dose cisplatin treatment undergo audiometric patients treated with cisplatin for testicular cancer.15
testing before the initiation of therapy and before Symptoms of ototoxicity persisted in 20% of patients
each of the subsequent courses. Less frequent testing (tinnitus and/or hearing loss). Ten percent had expe-
was deemed necessary for patients receiving low- and rienced completely reversible ototoxic symptoms that
moderate-dose treatment.9 lasted from 1 to 18 months after treatment. Statisti-
Kopelman et al reported that all of their cally significant risk factors for ototoxicity were (1) a
patients complained of decreased hearing after very high cumulative dose of cisplatin, (2) a history of
high-dose cisplatin administration (150 to 225 noise exposure, and (3) a high dose of vincristine,
mg/m2). Ototoxic reactions appear to be more likely which seemed to cause reversible ototoxic symptoms.
in patients with low serum albumin and in those Persistent ototoxicity may occur in about 20% of
with anemia.10 patients with testicular cancer who are treated at a
The exact incidence and severity of cisplatin- standard dose but may affect more than 50% of
induced auditory effects is difficult to assess because patients receiving cumulative doses of cisplatin
of inconsistencies including variable dosing in pre- exceeding 400 mg/m2. Previous noise exposure may
vious studies and the lack of complete data from also result in a threefold increased risk for cisplatin
patients too ill to cooperate for pretreatment and ototoxicity. Future studies should examine these risk
post-treatment audiograms. Symptoms that strongly factors as important stratification criteria for trials to
suggest cisplatin ototoxicity include otalgia, tinnitus, prevent or, at least, minimize cisplatin ototoxicity.
and subjective hearing loss. Tinnitus has been A new method of treatment for superficially
reported in 2 to 36% of patients receiving cisplatin. accessible tumors of the head and neck, esophagus,
Often the tinnitus is transient, lasting from a few and trunk has been reported. Cisplatin is injected as
hours up to a week after cisplatin therapy. The inci- a gel, which also contains epinephrine. The antitu-
dence of hearing loss among patients treated with mor agent was injected weekly for 4 weeks in 45
cisplatin has been as low as 9% and as high as 91%.11 patients. The initial dose of cisplatin was 1 mg/cm3
In patients with head and neck cancer treated with tumor volume and escalated up to 6 mg/cm3 as
cisplatin, about half develop hearing loss.12 The needed, depending on observed toxicities. The over-
hearing loss is usually bilateral and appears first at all objective tumor response was 50%, with 40%
high frequencies (6,000 and 8,000 Hz). Progression complete response with a median-response duration
to lower frequencies (2,000 and 4,000 Hz) may occur of 160 days. No dose-limiting cisplatin-related toxi-
with continued therapy. The hearing loss may be cities, such as nephrotoxicity, neurotoxicity, or oto-
asymmetric and may not appear until several days toxicity, were observed with this method.16
after treatment. Patients may experience some Children receiving high cumulative doses of
degree of reversibility, but when the hearing loss is cisplatin (above 540 mg/m2) have a high incidence of
profound, it appears to be permanent. Because the hearing loss, which is cumulative and dose depend-
hearing loss tends to occur at the higher frequencies, ent.17 However, a plateau effect has been reported
it may escape detection without audiometry. with no further deterioration of hearing at doses
Cochlear toxicity may be detected earlier with high- greater than 600 mg/m2. Still, a number of patients
frequency audiometry (up to 20 kHz) than with will develop more severe hearing losses in the 2,000
conventional audiologic testing.13 Speech discrimi- to 8,000 Hz range even after one or two courses of
nation scores may be markedly reduced when cis- therapy, showing exceptions to the plateau effect.18
platin ototoxicity occurs. The hearing loss may be Adults with a preexisting history of otologic prob-
gradual, progressive, and cumulative or may present lems are said to experience a higher incidence of
suddenly. Several patterns of hearing loss have been ototoxicity of cisplatin affecting both lower (1,000
described.14 to 8,000 Hz) and higher (10,000 to 18,000 Hz) fre-
The critical cumulative dose of cisplatin has quencies.19 Ototoxicity of cisplatin appears to be
been reported as 3 to 4 mg/kg body weight. Since enhanced by cranial irradiation.20
Ototoxicity 377
A study of otoacoustic emissions was carried had hearing loss in the speech frequencies that was
out in pediatric patients treated with cisplatin severe enough that hearing aids were recommended.
chemotherapy. Transient evoked otoacoustic emis- These children had all previously been treated with
sions could be measured in 11 of 12 patients studied. cisplatin, and several patients had previously
When the middle ear status was normal, a signifi- received aminoglycoside antibiotics. The investiga-
cant correlation was found between the transient tors concluded that high-dose carboplatin is oto-
evoked otoacoustic emissions and the pure-tone toxic, especially in children who have been exposed
threshold, and 90.5% of patients had a significant to previous platinum therapy or other ototoxic
sensorineural hearing loss at 8,000 Hz. Increased agents. They felt that in children in whom hearing
hearing loss was associated with young age at first losses are inevitable, owing to cumulative ototoxic
dose of cisplatin, high number of chemotherapy exposure, parents need to be properly informed of
cycles, and high cumulative dose of cisplatin.21 the balance of risks and benefits.26
Temporal bones removed from patients with Studies by Van Der Hulst et al19 and Kennedy et
25
cisplatin-induced hearing loss have demonstrated al have shown a significant incidence of hearing
the following: large, fused stereocilia; damage to the loss in carboplatin-treated patients. Seventy-five per-
cuticular plate of the outer hair cells; and extensive cent of patients treated with carboplatin had meas-
loss of sensory cells in the vestibular labyrinth in urable hearing loss in the former study, whereas 20%
specimens studied with scanning electron micros- of patients treated with carboplatin in the latter
copy.22 In addition to noting outer hair cell degener- study had hearing loss. The authors in the latter
ation in the basal turn of the cochlea, Strauss et al study stated that no clinically significant hearing loss
reported degeneration of spiral ganglion cells and occurred.26 On the other hand, cumulative sen-
cochlear neurons in patients with documented cis- sorineural hearing loss has been shown in 11 of 22
platin ototoxicity.23 However, the vestibular neurons children who received carboplatin chemotherapy.27
appeared normal. In a study of human temporal Carboplatin has been successfully used to treat
bones removed from patients treated with cisplatin, malignant brain tumors when administered in
radiation, or a combination of both treatments, the conjunction with osmotic blood-brain barrier dis-
spiral ganglion cells and inner and outer hair cells ruption with mannitol. Unfortunately, a larger
were decreased in number, and the stria vascularis percentage of patients developed high-frequency
was found to be atrophic. The otopathology identi- hearing loss when they were treated with this regi-
fied in these temporal bones also included vascular men. Twenty-nine patients received various doses of
changes, serum effusion, or fibrosis that accompa- the protective agent sodium thiosulfate, given intra-
nied sensorineural hearing losses.24 venously 2 hours after carboplatin. Doses of sodium
thiosulfate were escalated from 4 g/m2 to 8, 12, 16,
and 20 g/m2 in consecutive months. Audiograms
CARBOPLATIN were performed before treatment and monthly after
Clinical Studies Carboplatin is a newer analog of treatment with carboplatin. These audiograms were
cisplatin that was introduced into clinical trials in compared with those of 19 historical control
1981. This drug was found to have less nephrotoxic- patients who were treated similarly but who did not
ity than does cisplatin. Initial reports suggested that receive sodium thiosulfate. The incidence of hearing
carboplatin was also less ototoxic than is cisplatin. loss in the control group was 79% (15/19). The
The primary dose-limiting toxicity of carboplatin group of patients protected with sodium thiosulfate
has been bone marrow suppression.25 This toxic lost only 3.7 ± 2 dB at 8,000 Hz after one carboplatin
effect has been overcome by the use of autologous treatment, compared with the historical group,
stem cell rescue and/or the use of hematopoietic which had an average loss of 20.8 ± 5.9 dB. Patients
growth factors. This has allowed the use of higher in the sodium thiosulfate–treated group with excel-
doses of carboplatin and increased antitumor effec- lent baseline hearing had little change in hearing
tiveness. thresholds at 8 kHz after the second treatment (8.0
A study of children with neuroblastoma who ± 8.3 dB) compared with the historical control
were treated with higher-dose carboplatin (2 g/m2 patients with excellent baseline hearing (40.5 ± 8.6
total dose) showed that 9 of the 11 children (82%) dB). These findings support the concept that sodium
378 Ballenger’s Otorhinolaryngology
thiosulfate in doses of 16 or 20 g/m2 decreases car- allergic to furosemide or refractory to its diuretic
boplatin-induced hearing loss. Because the thiosul- effect.
fate does not seem to cross the blood-brain barrier, A study by Arnold et al revealed some mor-
there would appear to be no interference with the phologic effects in the temporal bones from a
antitumor action of carboplatin in these patients.28 patient who received a total of 5,000 mg of furo-
An intriguing study predicted carboplatin oto- semide plus 250 mg of ethacrynic acid over 5 days
toxicity in patients with ovarian cancer, who were before dying of renal failure.31 The inner and outer
treated with a combination of cisplatin and carbo- hair cells were normal at both the light and electron
platin. A total of 105 patients with ovarian cancer who microscopic levels, but the stria vascularis had
received up to six courses of carboplatin (300 mg/m2) marked cystic changes, as has been reported in ani-
were evaluated, and values for first-course carboplatin mal studies. The dark cell areas of the vestibular sys-
area under the curve (AUC = area under the plasma tem were found to have marked cystic changes, with
drug concentration versus time curve, a measure of dilation of the intracellular fluid spaces, suggesting
drug exposure) were determined retrospectively. effects on fluid transport within the inner ear.
Thrombocytopenia of grade 3 to 4 was found in 10% Tuzel summarized the reported incidence of
of patients with low AUC (< 4 mg/mL × min). No hearing loss, as documented by pure-tone audiome-
patients in the low AUC group had ototoxicity, but try in 179 patients treated with bumetanide and 62
12% of patients in the high AUC group were found to patients receiving furosemide.32 Among patients
have ototoxicity and 44.6% had thrombocytopenia. receiving bumetanide, only 2 (1.1%) had audiomet-
These data could prove valuable for prevention of ric changes of 15 dB or greater. Patients treated with
thrombocytopenia and ototoxicity for the first cycle of furosemide had a 6.4% incidence of hearing loss.
combined treatment with carboplatin and cisplatin.29 Tuzel did not report whether these hearing losses
were temporary or permanent. Although most cases
of loop diuretic ototoxicity are temporary and fully
LOOP DIURETICS reversible, some appear to be permanent. New loop
Loop diuretics are a group of potent synthetic drugs diuretics are being developed and tested in animals,
that act on the loop of Henle to inhibit the reab- and some may prove to be even less ototoxic than
sorption of sodium, potassium, and chloride ions by bumetanide when clinical trials are performed.
the Na+-K+-2Cl– cotransporter system. The ototoxi- Permanent, profound mid- and high-fre-
city of these agents has been reviewed.30 quency sensorineural hearing loss in a transplant
Most administered furosemide is excreted in patient receiving ethacrynic acid illustrates that
the urine. Furosemide essentially follows a three- deafness from loop diuretics continues to be a prob-
compartment pharmacokinetic model with an aver- lem that is clinically significant.33 Permanent hearing
age half-life for renal elimination of 291⁄2 minutes. loss has been reported in high-risk premature
Furosemide elimination decreases greatly in patients neonates treated with furosemide.34
with advanced renal failure, in whom the half-life
can be prolonged to 10 to 20 hours. Long half-lives
also have been observed in patients with congestive
SALICYLATES
heart failure, especially those undergoing long-term Orally administered salicylates are absorbed very
furosemide treatment. The plasma half-life of rapidly in the gastrointestinal tract, with an apparent
furosemide is approximately 45 to 92 minutes in half-life of 6 to 15 minutes. Absorption of salicylates
healthy subjects but is prolonged to approximately 3 is influenced significantly by gastric emptying time
hours in patients with renal failure. The gastroin- and by the presence of food in the stomach; food
testinal uptake of furosemide is high; most authors may more than double the absorption half-life of
have concluded that approximately 65% of an oral aspirin. Aspirin is broken down in the body to sali-
dose of furosemide is absorbed. Plasma levels cylic acid, with a biologic half-life of 15 to 20 min-
exceeding 50 mg/L are frequently associated with utes.35 Salicylates are distributed mainly to the
hearing disturbances.30 extracellular water compartments.36 Concentrations
Although the use of ethacrynic acid is very low of the salicylates are higher in the liver and kidney
currently, occasionally, it is used in patients who are than in the serum, whereas brain concentrations are
Ototoxicity 379
usually about 10% of those in the serum. Salicylates 10. Kopelman J, Budnick AS, Sessions RB, et al. Ototox-
are excreted mainly in the urine. icity of high-dose cisplatin by bolus administration
Salicylate concentrations of 20 to 50 mg/dL in in patients with advanced cancer and normal hear-
serum have been associated with hearing losses of ing. Laryngoscope 1988;98:858–64.
up to 30 dB.37 Human volunteers receiving aspirin at 11. Moroso MJ, Blair RL. A review of cisplatinum oto-
various doses experienced hearing loss and tinnitus toxicity. J Otolaryngol 1983;12:365–9.
at relatively low concentrations of total plasma sali- 12. Blakley BW, Gupta AK, Myers SF, Schwan S. Risk fac-
cylate. A linear relationship between hearing loss tors for ototoxicity due to cisplatin. Arch Otolaryn-
and unbound salicylate concentrations has been gol Head Neck Surg 1994;120:541–6.
reported.38 Hearing loss can be observed at salicylate 13. Fausti SA, Henry JA, Schaffer HI, et al. High-fre-
concentrations below 20 mg/dL, and there seems to quency monitoring for early detection of cisplatin
be no threshold for salicylate-induced hearing loss. ototoxicity. Arch Otolaryngol Head Neck Surg
The severity of tinnitus increases as plasma salicylate 1993;119:661–6.
concentrations exceed 40 mg/L. Work by Lue and 14. Blakley BW, Myers SF. Pattern of hearing loss result-
Brownell links the reversible salicylate ototoxicity ing from cisplatinum therapy. Otolaryngol Head
to reduction of lateral membrane stiffness in outer Neck Surg 1993;109:385–91.
hair cells.39 15. Bokemeyer C, Berger CC, Hartmann JT, et al. Analy-
sis of risk factors for cisplatin-induced ototoxicity in
patients with testicular cancer. Br J Cancer 1998;
REFERENCES 77:1355–62.
16. Burris HA, Vogul CL, Castro D, et al. Intratumoral
1. Fee WE. Aminoglycoside ototoxicity in the human. cisplatin/epinephrine-injectable gel as a palliative
Laryngoscope 1980;90 Suppl 24:1–19. treatment for accessible solid tumors: a multi-center
2. Smith CR, Lipsky JJ, Laskin OL, et al. Double blind pilot study. Otolaryngol Head Neck Surg 1998;
comparison of the nephrotoxicity and auditory tox- 118:496–503.
icity of gentamicin and tobramycin. N Engl J Med 17. Kluba J, Kluba U, von Sprecht H, Mittler U. Zur
1980;302:1106–9. Überwachung des Gehörs wahrend der ototoxischen
3. Lerner SA, Seligsohn R, Bhattacharya I, et al. Phar- Cisplatin-Therapie [Monitoring hearing during oto-
macokinetics of gentamicin in the inner ear peri- toxic cisplatin therapy]. Padiatr Grenzgeb 1990;29:
lymph of man. In: Lerner SA, Matz GJ, Hawkins JE, 19–23.
editors. Aminoglycoside ototoxicity. Boston: Little 18. Myers SF, Blakley BW, Schwan S, et al. The “plateau
Brown & Co.; 1981. p. 357–69. effect” of cisplatinum induced hearing loss. Oto-
4. Moore RD, Smith CR, Leitman PS. Risk factors for the laryngol Head Neck Surg 1991;1104:122–7.
development of auditory toxicity in patients receiving 19. Van Der Hulst RJ, Dreschler WA, Urbanus NA. High
aminoglycosides. J Infect Dis 1984;149:23–30. frequency audiometry in prospective clinical
5. Prezant TR, Agapian JV, Bohlman C, et al. Mito- research of ototoxicity due to platinum derivatives.
chondrial ribosomal RNA mutation associated with Ann Otol Rhinol Laryngol 1988;97:133–7.
both antibiotic-induced and nonsyndromic deaf- 20. Granowetter L, Rosenstock JG, Packer RJ. Enhanced
ness. Nat Genet 1993;4:289–94. cisplatinum neurotoxicity in pediatric patients with
6. Hutchin T, Haworth I, Higashi K, et al. A molecular brain tumors. J Neurooncol 1983;1:293–7.
basis for human hypersensitivity to aminoglycoside 21. Allen GC, Tiu C, Koike K, et al. Transient-evoked
antibiotics. Nucleic Acids Res 1993;21:4174–9. otoacoustic emissions in children after cisplatin
7. Forge A, Schacht J. Aminoglycoside antibiotics. chemotherapy. Otolaryngol Head Neck Surg 1998;
Audiol Neurootol 2000;5:3–21. 118:584–8.
8. Gormley PE, Bull JM, LeRoy AF, Cysyk R. Kinetics of 22. Wright CG, Schaefer SD. Inner ear histopathology in
cis-dichlorodiammineplatinum. Clin Pharmacol patients treated with cis-platinum. Laryngoscope
Ther 1971;25:351–7. 1982;92:1408–13.
9. Laurell G, Jungnelius U. High-dose cisplatin treat- 23. Strauss M, Towfighi J, Lord S, et al. Cisplatinum oto-
ment: hearing loss and plasma concentrations. toxicity: clinical experience and temporal bone
Laryngoscope 1990;100:724–34. histopathology. Laryngoscope 1983;93:1554–9.
380 Ballenger’s Otorhinolaryngology
24. Hoistad DL, Ondrey FG, Mutlu C, et al. Histopathol- histopathology in a case of human ototoxicity due to
ogy of human temporal bone after cis-platinum, loop diuretics. Acta Otolaryngol (Stockh) 1981;91:
radiation or both. Otolaryngol Head Neck Surg 399–414.
1998;118:825–32. 32. Tuzel IH. Comparison of adverse reactions to
25. Kennedy IC, Fitzharris BM, Colls BM, Atkinson CH. bumetanide and furosemide. J Clin Pharmacol
Carboplatin is ototoxic. Cancer Chemother Pharma- 1981;21:615–9.
col 1990;26:232–4. 33. Rybak LP. Ototoxicity of ethacrynic acid (a persist-
26. Parsons SK, Neault MW, Lehmann LE, et al. Severe ent clinical problem). J Laryngol Otol 1988;102:
ototoxicity following carboplatin-containing condi- 518–20.
tioning regimen for autologous marrow transplan- 34. Brown DR, Watchko JF, Sabo D. Neonatal sen-
tation for neuroblastoma. Bone Marrow Transplant sorineural hearing loss associated with furosemide: a
1998;22:669–74. case control study. Dev Med Child Neurol 1991;
27. Macdonald MR, Harrison RV, Wake M, et al. Oto- 33:816–23.
toxicity of the carboplatin: comparing animal and 35. Rowland M, Riegelman S. Pharmacokinetics of
clinical models at the Hospital for Sick Children. J acetylsalicylic acid and salicylic acid after intra-
Otolaryngol 1994;23:151–9. venous administration in man. J Pharm Sci 1968;
28. Neuwelt EA, Brummett RE, Doolittle ND, et al. First 57:1313–9.
evidence of otoprotection against carboplatin- 36. Hollister L, Levy G. Some aspects of salicylate distri-
induced hearing loss with a two-compartment sys- bution and metabolism in man. J Pharm Sci 1965;
tem in patients with central nervous system 54:1126–9.
malignancy using sodium thiosulfate. J Pharmacol 37. Myers EN, Bernstein JM. Salicylate ototoxicity: a
Exp Ther 1998;286:77–84. clinical and experimental study. Arch Otolaryngol
29. Obermair A, Speiser P, Thoma M, et al. Prediction of 1965;82:483–93.
toxicity but not of clinical course by determining 38. Day RO, Graham GG, Bieri D, et al. Concentration-
carboplatin exposure in patients with epithelial response relationships for salicylate-induced ototox-
ovarian cancer treated with a combination of carbo- icity in normal volunteers. Br J Clin Pharmacol
platin and cisplatin. Int J Oncol 1998;13:1023–30. 1989;28:695–702.
30. Rybak LP. Ototoxicity of loop diuretics. Otolaryngol 39. Lue AT, Brownell WE. Salicylate induced changes in
Clin North Am 1993;26:829–44. outer hair cell lateral wall stiffness. Hear Res
31. Arnold W, Nadol JB, Weidauer H. Ultrastructural 1999;135:163–8.
CHAPTER 17
381
382 Ballenger’s Otorhinolaryngology
Congenital CMV syndrome includes deafness these findings were similar to those seen in cases
and lesions of the eye, brain, liver, and spleen.10 It is (mumps, measles) known to be caused by viral
important to note, however, that most CMV- infections and different from the cochlear pathology
infected neonates do not demonstrate the full-blown (fibrous and osseous proliferation) seen after
CMV syndrome. Indeed, “asymptomatic” CMV ischemic deafness.20
infection causes more hearing loss than “sympto- Given the otopathologic similarity between
matic” (syndromic) CMV infection. Neonatal CMV ISSNHL and hearing loss of known viral origin, inves-
screening has shown an infection rate (virus cul- tigators looked for immunologic evidence of viral
tured from urine) of 1.3%11; 10% of these cases had infection in ISSNHL. Veltri and colleagues showed
either congenital or progressive hearing loss. Most that patients with ISSNHL frequently had serocon-
of the babies who had (or developed) hearing loss version (increasing antibody levels) for several
were otherwise healthy and would have been missed viruses, including mumps, influenza (coincidental?),
by conventional high-risk criteria for congenital measles, HSV, rubella, and CMV.21 Wilson focused
hearing loss. No vaccine is yet available to reduce or specifically on HSV, noting that 16% of ISSNHL
eliminate hearing loss from CMV. patients showed seroconversion compared with only
Neonatal herpes simplex virus (HSV) infection 4% of controls.22 The identification of DNA from
is associated with hearing loss in about 10% of HSV in human spiral ganglion23 and the development
cases.12 of an animal model for HSV neurolabyrinthitis24 have
Mumps (viral parotitis) is the prototypical added to suspicion that this virus may be an impor-
example of sudden unilateral hearing loss in child- tant cause of ISSNHL. Pitkaranta and colleagues
hood. Rare since the widespread use of the MMR noted that there are many negative serologic studies,
vaccine, mumps deafness occurred in about 5 of failing to implicate HSV or other viruses, but also
every 10,000 mumps cases13 and was usually unilat- noted that long-dormant neurotropic viruses can
eral. Like CMV, the mumps virus has been cultured reactivate and cause localized disease without trigger-
from the inner ear14 and causes cochlear lesions in ing changes in systemic immunoglobulin levels.25 This
experimental animals.15 Measles (rubeola virus) is true for herpetic cold sores, for example, and may
accounted for 3 to 10% of bilateral deafness in chil- also be true for diseases such as ISSNHL, Bell’s palsy,
dren prior to the MMR vaccine.16 and vestibular neuronitis. Unfortunately, the difficulty
The varicella-zoster (or herpes zoster) virus of inner ear culture or biopsy makes proving this
causes chickenpox in children and shingles in adults. hypothesis in individual cases impossible.
When the geniculate ganglion is involved, with facial
paralysis plus auricular bullae, it is called herpes
zoster oticus (HZO) or Ramsay Hunt syndrome.
VASCULAR
About 6% of HZO cases exhibit SNHL,17 making Diseases of blood vessels affect many organ systems
HZO probably the most common type of hearing and constitute some of the most important causes of
loss in adults in which a viral cause is reasonably cer- death and disability in developed countries. Risk fac-
tain. Herpes zoster viral deoxyribonucleic acid tors for vascular disease include diabetes, hyperten-
(DNA) has been identified in temporal bone tissue sion, obesity, and hyperlipidemia; controlling these
taken from a patient with HZO and sudden hearing risk factors can reduce the incidence of heart attacks,
loss.18 strokes, blindness, kidney failure, and premature
Human immunodeficiency virus (HIV) may death. Equally important (but uncontrollable) risk
cause hearing loss directly but more commonly factors include age, sex, and family history. Since no
makes the host more susceptible to other viruses, organ can survive without adequate blood supply
many of which (CMV, HSV, adenovirus) have been and since vascular disease affects so many different
cultured from the HIV-infected inner ear,19 as well as organ systems, it is natural that investigators have
to other infectious agents. looked for evidence that SNHL is linked to vascular
Schuknecht and Donovan first showed that disease (or to its risk factors). Given the intensity of
ears from patients who had suffered ISSNHL their efforts, the evidence is extremely weak.
demonstrated atrophy of the organ of Corti and tec- In other organ systems, vascular disease may
torial membrane and spiral ganglion cell losses; cause either gradual or sudden/stepwise deteriora-
Idiopathic Sudden Sensorineural Hearing Loss 383
tion of function. Congestive heart failure may who suffer ISSNHL have only one event, affecting
develop insidiously in some patients, whereas others only one ear. Studies of vascular disease and risk fac-
have sudden-onset myocardial infarctions. Even tors have shown only that diabetics with ISSNHL
when the disease process (eg, atherosclerotic nar- have a poorer prognosis,27 not that any of these fac-
rowing of arterial lumen) is gradual, the symptoms tors predict the likelihood of suffering ISSNHL.
and signs of dysfunction are often sudden, when a None of this proves that vascular disease is
critical point is reached or a new event such as totally irrelevant to ISSNHL. Inner ear hemorrhages
thrombosis or embolism totally shuts off blood flow. with sudden deafness do occur rarely in patients
If vascular disease is important for a particular organ with leukemia, sickle cell disease, and tha-
(eg, the cochlea), one should expect it to cause both lassemia,28–30 although the temporal bone
sudden and gradual changes in function. histopathologic findings after hemorrhage or
Unfortunately, otologists cannot yet measure ischemia are very different from those seen in
cochlear blood flow in clinical practice, so whether a patients who have suffered ISSNHL, as previously
person (or an ear) has cochlear ischemia cannot be discussed. Sudden SNHL may31 or may not32 be an
determined. Reliance must be placed on correlations occasional complication of cardiopulmonary bypass
between hearing loss and vascular disease risk fac- surgery (presumably owing to emboli). Until otolo-
tors (or established vascular disease elsewhere in gists are able to assess cochlear blood flow reliably
the body) and to a lesser extent on histopathologic and noninvasively in their patients, we will probably
evidence. never know much about the role of vascular disease
Consideration can begin with age-related hear- in ISSNHL (or SNHL in general); at this point in
ing loss (ARHL). Age is not really a cause of SNHL time, it appears to be somewhere between small and
but rather an association; still, after excluding com- negligible.
mon causes of SNHL (noise, head injury, etc), the
vast majority of people with adult-onset SNHL can-
not be labeled any more precisely than to call them
OTHER
age related. If vascular disease was an important Simmons postulated that double inner ear membrane
component of ARHL, it might be expected that breaks could be responsible for some cases of
patients (and longitudinal studies of ARHL) would ISSNHL,33 and it is hard to prove that he was wrong,
describe stepwise progression, with substantial but there is little evidence that he was right either.
asymmetry as one ear suffers ischemic events Because Simmons hypothesized that one of these
whereas the other escapes, at least for a while. The membrane breaks would involve the oval or round
rarity of such reports in ARHL should already cast window, producing a perilymph fistula (PLF), the
doubt on the vascular hypothesis, but those doubts 1980s saw a wave of enthusiasm for middle ear explo-
can momentarily be put aside and one might ask ration, looking for PLF, in patients with ISSNHL.
whether vascular disease and its risk factors are cor- Today, most otologists believe that PLFs do occur,
related with ARHL. For example, do diabetics have causing SNHL and dizziness, but almost exclusively
more hearing loss than nondiabetics of the same age in the context of identifiable barotrauma: after scuba
and sex? The extensive literature addressing this diving, violent nose blowing, or extreme exertion dur-
issue has been reviewed and can best be described as ing breath holding (eg, weight lifting with improper
inconclusive.26 If vascular disease is responsible for technique). In the absence of such a history, few otol-
some proportion of ARHL, its contribution is small. ogists would diagnose membrane breaks and/or PLF
Focusing on patients presenting with ISSNHL, or recommend therapy appropriate to such a diagno-
are some of these cases attributable to “vascular acci- sis (bed rest, middle ear exploration).
dents” (thrombosis, embolism, or hemorrhage)
affecting the cochlea? If vascular disease caused a
substantial fraction of ISSNHL, the incidence of
DIFFERENTIAL DIAGNOSIS
ISSNHL would be expected to be much higher in Table 17–1 shows that dozens of otologic and sys-
men than in women and to rise sharply with age; temic disorders have been associated with sudden
neither is true. Frequent recurrences and (over time) SNHL. Many of these disorders (eg, Meniere’s dis-
bilaterality would also be expected, yet most people ease, autoimmune inner ear disease) typically cause
384 Ballenger’s Otorhinolaryngology
rapidly progressive or fluctuating hearing loss rather injury. Others, such as multiple sclerosis, are usually
than truly sudden loss. The more important identi- missed when sudden SNHL is the first manifesta-
fiable causes of sudden SNHL (by definition, these tion. In areas where Lyme disease is endemic, it is
are not “idiopathic”) are clinically easy to diagnose, probably wise to ask patients with sudden SNHL
for example, meningitis, acoustic trauma, head about recent rash or arthralgia.
INVESTIGATIONS
TABLE 17–1. Some Causes of Sudden Sensorineural Patients presenting with sudden unilateral hearing
Hearing Loss loss without obvious antecedent cause should
receive a careful otologic history and examination, as
Infectious
well as an audiogram (including the Stenger test to
Meningitis (bacterial, fungal) detect functional hearing loss). Otoacoustic emis-
Labyrinthitis (bacterial, fungal, viral, parasitic, sions (OAEs) are sometimes present (implying spar-
spirochetal) ing of outer hair cells) in ISSNHL,34 but it is unclear
whether OAE testing is clinically useful, that is,
Traumatic whether the results can assist in selecting therapy.
Head injury (with/without fracture) Routine blood testing in ISSNHL is of dubious
Barotrauma (with/without perilymph fistula) value. Children with ISSNHL (rare!) should receive
a complete blood count as a screening test for
Acoustic trauma leukemia. If there are clinical clues pointing toward
Iatrogenic injury Lyme disease, confirmatory testing is indicated.
Neoplastic Patients with symptoms of systemic disease should
probably be referred to an internist rather than
Acoustic tumor receive blood tests selected by an otolaryngologist. If
Metastases (to meninges or temporal bone) corticosteroid therapy is being considered in a
Hematologic malignancies (leukemia, myeloma)
patient who has not been tested for diabetes in
recent years, a blood glucose test is probably in
Immunologic order.
Autoimmune inner ear disease About 1% of patients presenting with sudden
SNHL have acoustic tumors,35 and even complete
Systemic immune diseases (Cogan’s, Wegener’s
recovery does not completely rule out this diagnosis.
granulomatosis, polyarteritis, temporal arteritis)
When hearing in the affected ear is quite poor (> 60
Ototoxic dB at 2 kHz), magnetic resonance imaging (MRI)
Vascular (see text) with gadolinium contrast injection is the most
appropriate study to detect or rule out a tumor. For
Neurologic
patients with better hearing, either MRI or auditory
Multiple sclerosis brainstem response (ABR) testing (with MRI
Focal pontine ischemia reserved for patients showing abnormal ABR) may
be appropriate.
Metabolic
The increasingly frequent use of MRI in cases
Disturbance of iron metabolism of sudden SNHL has shed additional light on the eti-
Renal failure/dialysis ology. Precontrast films can document inner ear
hemorrhage in the rare cases associated with hema-
Miscellaneous
tologic disorders.29 Soon after the onset of hearing
Meniere’s disease loss, gadolinium enhancement of the cochlea is seen
Functional hearing loss in typical cases of ISSNHL, probably owing to a
transiently leaky blood-brain barrier.36 Six months
Adapted from Hughes GB et al.2 or more after onset, no fibrotic or osseous prolifera-
Idiopathic Sudden Sensorineural Hearing Loss 385
tion (such as would be expected after ischemic dam- regimen is prednisone, 1 mg/kg/day, for 7 to 10 days,
age) could be identified.37 with or without a taper. Useful oral antiviral drugs
have been available in recent years but have yet to be
found helpful for patients with ISSNHL.40
INTERVENTIONS The vascular hypothesis is extremely popular
Wilson et al showed, in a randomized clinical trial, in Europe, where treatments such as oral pentoxi-
that patients receiving oral corticosteroids achieved fylline and intravenous dextran (intended to reduce
substantial recovery (defined as more than 50% blood viscosity), apheresis (intended to remove low-
recovery vis-à-vis the uninvolved ear) more fre- density lipoprotein cholesterol from the blood), car-
quently than patients receiving placebo.38 This bene- bogen (a mixture of 10% carbon dioxide and 90%
fit was apparent only for “moderate” degrees of loss oxygen), and papaverine (intended to dilate blood
(Figure 17–1); 78% of patients in this category who vessels) are often used. None of these has been
received corticosteroids recovered at least half of shown to be superior to placebo.41–46
their loss, compared with 38% of those who received When a cause for sudden SNHL is found (see
placebo. Patients with mid-frequency losses did well Table 17–1), the case is not idiopathic, and the treat-
with or without steroids; those with profound losses ment should depend on the diagnosis. The manage-
did poorly regardless of treatment. ment of persistent tinnitus and hearing loss, when
Unfortunately, Wilson et al’s is the only ran- recovery is incomplete, is nonspecific. Some patients
domized trial of corticosteroid therapy to date. A choose to try hearing aids, but, for most, sympa-
nonrandomized study by Moskowitz and colleagues thetic counseling is the best approach.
showed benefits similar to those seen in the Wilson
et al study (89% recovery with corticosteroids, 44%
recovery without treatment).39 Many, if not most,
REFERENCES
otologists offer oral corticosteroids to patients with 1. Byl F. Sudden hearing loss: eight years’ experience
ISSNHL who have no contraindications (eg, dia- and suggested prognostic table. Laryngoscope 1984;
betes, active duodenal ulcer, tuberculosis). A typical 94:647–66.
Frequency (Hz)
386 Ballenger’s Otorhinolaryngology
2. Hughes GB, Freedman MA, Haberkamp TJ, Guay 16. Tieri L, Masi R, Marsella P, Pinelli V. Sudden deaf-
ME. Sudden sensorineural hearing loss. Otolaryngol ness in children. Int J Pediatr Otorhinolaryngol
Clin North Am 1996;29:393–405. 1984;7:257–64.
3. Megighian D, Bolzan M, Barion U, Nicolai P. Epi- 17. Harbert F, Young IM. Audiologic findings in Ramsay
demiological considerations in sudden hearing loss: Hunt syndrome. Arch Otolaryngol 1967;85:632–9.
a study of 183 cases. Arch Otorhinolaryngol 1986; 18. Wackym PA. Molecular temporal bone pathology: II.
243:250–3. Ramsay Hunt syndrome (herpes zoster oticus).
4. Karlberg M, Halmagyi GM, Buttner U, Yavor RA. Laryngoscope 1997;107:1165–75.
Sudden unilateral hearing loss with simultaneous 19. Davis LE, Rarey KE, McLaren LC. Clinical viral
ipsilateral posterior semicircular canal benign parox- infections and temporal bone histologic studies of
ysmal positional vertigo. Arch Otolaryngol Head patients with AIDS. Otolaryngol Head Neck Surg
Neck Surg 2000;126:1024–9. 1995;113:695–701.
5. Mattox DE, Simmons FB. Natural history of sudden 20. Schuknecht HF, Donovan ED. The pathology of
sensorineural hearing loss. Ann Otol Rhinol Laryn- idiopathic sudden sensorineural hearing loss. Arch
gol 1977;86:463–80. Otorhinolaryngol 1986;243:1–15.
6. Dobie RA. Drug treatments for sensorineural 21. Veltri RW, Wilson WR, Sprinkle PM, et al. The
hearing loss and tinnitus. In: Berlin CI, editor. implication of viruses in idiopathic sudden hearing
Neurotransmission and hearing loss: basic science, loss: primary infection or reactivation of latent
diagnosis and management. San Diego: Singular; viruses? Otolaryngol Head Neck Surg 1981;89:
1997. p. 147–59. 137–41.
7. Trybus RJ, Karchmer MA, Kerstetter PP, Hicks W. 22. Wilson WR. The relationship of the herpes virus
The demographics of deafness resulting from mater- family to sudden hearing loss: a prospective clinical
nal rubella. Am Ann Deaf 1980;125:977–84. study and literature review. Laryngoscope 1986;
8. Davis LE, James CG, Fiber F, McLaren LC. Cyto- 96:870–7.
megalovirus isolation from a human inner ear. Ann 23. Schulz P, Arbusow V, Strupp M, et al. Highly variable
Otol Rhinol Laryngol 1979;88:424–6. distribution of HSV-1-specific DNA in human
9. Keithley EM, Woolf NK, Harris JP. Development of geniculate, vestibular and spiral ganglia. Neurosci
morphological and physiological changes in the Lett 1998;252:139–42.
cochlea induced by cytomegalovirus. Laryngoscope 24. Stokroos RJ, Albers FW, Schirm J. The etiology of
1989;99:409–14. idiopathic sudden sensorineural hearing loss. Exper-
10. Stagno S, Reynolds DW, Amos CS, et al. Auditory imental herpes simplex virus infection of the inner
and visual defects resulting from symptomatic and ear. Am J Otol 1998;19:447–52.
subclinical congenital cytomegaloviral and toxo- 25. Pitkaranta A, Vasama J-P, Julkunen I. Sudden deaf-
plasma infections. Pediatrics 1977;59:669–78. ness and viral infections. Otorhinolaryngol Nova
11. Hicks T, Fowler K, Richardson M, et al. Congenital 1999;9:190–7.
cytomegalovirus infection and neonatal auditory 26. Dobie RA. Medical-legal evaluation of hearing loss.
screening. J Pediatr 1993;123:779–82. 2nd ed. San Diego: Singular; 2001.
12. Dahle AJ, McCollister FP. Audiological findings in 27. Wilson WR, Laird N, Moo-Young G, et al. The
children with neonatal herpes. Ear Hear 1988; relationship of idiopathic sudden hearing loss to
9:256–8. diabetes mellitus. Laryngoscope 1982;92:155–160.
13. Everberg G. Deafness following mumps. Acta Oto- 28. Schuknecht HF, Igarashi M, Chasin WD. Inner ear
laryngol (Stockh) 1957;48:397–403. hemorrhage in leukemia. A case report. Laryngo-
14. Westmore GA, Pickard BH, Stern H. Isolation of scope 1965;75:662–8.
mumps virus from the inner ear after sudden deaf- 29. Vakkalanka S, Ey E, Goldenberg RA. Inner ear hem-
ness. BMJ 1979;1:14–5. orrhage and sudden sensorineural hearing loss. Am
15. Tanaka K, Fukuda S, Terayama Y, et al. Experimental J Otol 2000;21:764–5.
mumps labyrinthitis in monkeys (Macaca irus)— 30. Tavin ME, Rubin JS, Camacho FJ. Sudden sen-
immunohistochemical and ultrastructural studies. sorineural hearing loss in haemoglobin SC disease. J
Auris Nasus Larynx 1988;15:89–96. Laryngol Otol 1993;107:831–3.
Idiopathic Sudden Sensorineural Hearing Loss 387
31. Plasse HM, Mittleman M, Frost JO. Unilateral sud- 39. Moskowitz D, Lee KJ, Smith HW. Steroid use in idio-
den hearing loss after open heart surgery: a detailed pathic sudden sensorineural hearing loss. Laryngo-
study of seven cases. Laryngoscope 1981;91:101–9. scope 1984;94:664–6.
32. Ness JA, Stakilwicz JA, Kaniff T, et al. Sensorineural 40. Stokroos RJ, Albers FW, Tenvergert EM. Antiviral
hearing loss associated with aortocoronary bypass treatment of idiopathic sudden sensorineural hear-
surgery: a prospective analysis. Laryngoscope 1993; ing loss: a prospective, randomized, double-blind
103:589–93. clinical trial. Acta Otolaryngol (Stockh) 1998;118:
33. Simmons FB. The double-membrane break syn- 488–95.
drome in sudden hearing loss. Laryngoscope 1979; 41. Fisch U. Management of sudden deafness. Otolaryn-
89:59–66. gol Head Neck Surg 1983;91:3–8.
34. Sakashita T, Minowa Y, Hachikawa K, et al. Evoked 42. Edamatsu H, Hasegawa M, Oku T, et al. Treatment of
otoacoustic emissions from ears with idiopathic sud- sudden deafness: carbon dioxide and oxygen inhala-
den deafness. Acta Otolaryngol Suppl (Stockh) tion and steroids. Clin Otolaryngol 1985;10:69–72.
1991;486:66–72. 43. Kallinen J, Laurikainen E, Laippala P, Grenman R.
35. Shaia FT, Sheehy JL. Sudden sensori-neural hearing Sudden deafness: a comparison of anticoagulant
impairment: a report of 1,220 cases. Laryngoscope therapy and carbogen inhalation therapy. Ann Otol
1976;86:389–98. Rhinol Laryngol 1997;106:22–6.
36. Mark AS, Seltzer S. Nelson-Drake J, et al. Labyrinthine 44. Kronenberg J, Almagor M, Bendet E, Kushnir D.
enhancement on gadolinium-enhanced magnetic res- Vasoactive therapy versus placebo in the treatment
onance imaging in sudden deafness and vertigo: cor- of sudden hearing loss: a double-blind clinical study.
relation with audiologic and electronystagmographic Laryngoscope 1992;102:65–8.
studies. Ann Otol Rhinol Laryngol 1992;101:459–64. 45. Probst R, Tschopp K, Ludin E, et al. A randomized,
37. Albers FWJ, Demerynck KMNP, Casselman JW. double-blind, placebo-controlled study of dextran/
Three-dimensional magnetic resonance imaging of the pentoxifylline medication in acute acoustic trauma
inner ear in idiopathic sudden sensorineural hearing and sudden hearing loss. Acta Otolaryngol (Stockh)
loss. ORL J Otorhinolaryngol Relat Spec 1994;56:1–4. 1992;112:435–43.
38. Wilson WR, Byl FM, Laird N. The efficacy of steroids 46. Suckfull M, Thiery J, Schorn K, et al. Clinical utility
in the treatment of idiopathic sudden hearing loss. A of LDL-apheresis in the treatment of sudden hearing
double-blind clinical study. Arch Otolaryngol 1980; loss: a prospective, randomized study. Acta Oto-
106:772–6. laryngol (Stockh) 1999;119:763–6.
CHAPTER 18
Perilymphatic Fistulae
Robert I. Kohut, MD
A perilymphatic fistula (PLF) is an abnormal The treatment methods that will be described
passage through the bony labyrinthine capsule that are the products of the experience of many otolo-
is permeable to perilymph, causing abnormal, gists, and these are still in a dynamic phase of devel-
sometimes reversible, cochlear or vestibular func- opment.
tion. The reader is encouraged to consider the
The author’s attention to this disorder thoughts shared in this chapter, to criticize them,
occurred with a patient encounter. This patient’s and help develop, through his/her own clinical expe-
severe vestibular symptoms had previously been rience and investigative efforts, further knowledge
incorrectly attributed to a central neurovascular concerning this disorder. Many in the recent past
event and later to psychological problems. The pres- have considered PLF as a nonentity. However, the
ence of a positive unilateral Hennebert’s sign/symp- preponderance of clinical and investigative data has
tom in this patient who had no other signs of given most of these clinicians reason to pause and
syphilis (and was proven to be free of syphilis) recognize the pathogenic process called PLF or
prompted the conclusion that the findings were perilymphic leaks. A very thorough review article
owing to a pathologic process in which the positive was published by Friedland and Wackym.2 Their
and negative air pressure applied to the external ear conclusion that PLF is an uncommon disorder
canal was transmitted to the inner ear. On explo- appears to be based on clinical reports, particularly
ration of the middle ear, fluid reaccumulation just the findings on endoscopic examination. The poten-
anterior to the stapes was observed, and this site was tial weakness of this type of examination is discussed
grafted. Dramatic rapid improvement occurred in elsewhere in this chapter and relates to the heat pro-
this patient.1 duced by the endoscope with possible evaporation of
The purpose of this chapter is to make avail- the minute quantity of perilymph present, thereby
able to the reader a set of diagnostic criteria to be precluding fluid detection.
used during clinical or research activities concern-
ing PLF that cause balance disorders, sensory hear- HISTORY OF PERILYMPHATIC
ing disorders, or both. To achieve this purpose, a
summary of historical facets and research activities
FISTULAE
extending over 20 years related to this disorder will In 1883, Gellé observed, during manipulation (with-
be reviewed. Following this review, discussion will out dislodgment) of a patient’s exposed stapes, that
concern a predictive masked experimental para- the patient suffered vertigo with each movement of
digm, which was used to test the diagnostic criteria. the ossicle. He attributed this to hypermobility of
In these experiments, the temporal bone histologic the stapes.3
diagnostic criteria were developed whereby clinical Hennebert, some 22 years later, observed that
events were predicted based on the presence of spe- compression and rarefaction of the air in the exter-
cific histologic findings. Then, using these histologic nal auditory canal in some patients, having intact
diagnostic criteria, another experiment was designed tympanic membranes, caused small-amplitude,
in which the presence of the histologic diagnostic brief, nystagmic movement of the eyes (Hennebert’s
criteria for each donor temporal bone pair was pre- sign).4 Some patients having this provoked nystag-
dicted on the basis of clinical chart data recorded mus also experienced a sense of displacement in
during life. space: vertigo (Hennebert’s symptom).5 Many, but
388
Perilymphatic Fistulae 389
not all, of Hennebert’s patients had syphilis. Since similar reports, which indicated that sudden or rap-
syphilis was a popular medical topic at that time, a idly progressive hearing loss11–15 in patients with or
generalization was developed wherein a patient with without vertigo, or even with vertigo alone, some
an intact tympanic membrane and with the findings having a positive fistula test (Hennebert’s sign or
of a nystagmic response to a fistula test (compres- symptom), could be caused by a PLF.12–17
sion and rarefaction of the air of the external canal) Okano and associates demonstrated a crack-
was considered to have syphilis. like formation about the oval window or connecting
A positive fistula test, before Hennebert, had the round window niche and the posterior semicir-
been observed in patients with bone-eroding ear dis- cular canal ampulla.18,19 Although not clinically cor-
ease such as cholesteatoma, and these were docu- related, these openings were suggested as a form of
mented surgically. Yet there was no evidence in opening between the middle ear and the inner ear,
Hennebert’s patients of an opening in the bony perhaps related to inner ear disease. This type of his-
labyrinthine capsule as seen in these bone-eroding tologic opening had not been considered by Ruttin.7
processes. In 1986, Kohut et al reported a relationship
Discovering no bone-eroding process and between patencies of the fissula ante fenestram
reflecting on Gellé’s observation, it seemed reason- (FAF) and/or patencies of the fissure connecting the
able to conclude that the symptoms were attributa- round window niche/posterior semicircular canal
ble to a hypermobile stapes. However, there were ampulla (round window fissure [RWF]) and specific
some who thought that the symptoms and/or signs fistula symptoms and signs.16 These findings were
caused by a positive fistula test in patients having an supported by subsequent studies wherein these
intact tympanic membrane were most like those of patencies could be predicted as being present or
patients having erosive otic disorders in which there absent histologically based on archival medical
was an opening through the bony labyrinthine cap- record data.17
sule joining the middle ear and the inner ear It appeared that histologic changes (noninter-
(labyrinthine fistula). Some of these individuals rupted formations of the FAF and/or RWF) could be
were prominent otologists such as Alexander, Lei- predicted on strict clinical data related to PLF. Clin-
dler, and McKenzie.1 ical prediction of pathologic findings, of course, is
When no fistula was found at surgery in the “acid test” for disorders such as appendicitis,
patients having an intact tympanic membrane and a Laënnec’s cirrhosis, malignancies, and other disor-
positive fistula test, the surgeons were criticized as ders related to histologically defined criteria. Cracks
having performed needless surgery. Note that the of the labyrinthine capsule in other areas existed in
surgery was performed without the availability of some of the temporal bone specimens examined;
the operating microscope. however, these never seemed to be related to clinical
The Nobel Laureate Robert Bárány, in 1910, signs or symptoms.17
concluded that because of the negative surgical find- Since specific clinical criteria for PLF were
ings and the previous proposals of stapes hypermo- related to vertigo and/or hearing loss, challenging
bility, the hypermobile stapes hypothesis seemed temporal bone histologic investigations included one
reasonable.6 This seemed to be confirmed later in by El Shazly and Linthicum in which patencies of the
1921, when Ruttin reported the histologic findings labyrinthine capsule were not found to be related to
of the temporal bones from a patient having a Hen- sudden sensory hearing loss.20 In this study, the
nebert’s sign: no abnormal labyrinthine fistulae were authors found that the presence of labyrinthine cap-
histologically identified.7 sule patencies did not predict the presence of sudden
This thought, that a positive Hennebert’s sign sensory hearing loss.20 This was not in disagreement,
was diagnostic of syphilis, was not re-examined until although, at first glance, it appears so, with the previ-
the advent of stapes surgery. In 1967, PLF were ous studies by Kohut et al and Hinojosa et al.21,22 The
reported as a postoperative complication of presence of sudden sensory hearing loss in Kohut et
stapedectomy for otosclerosis. The main concern al’s study predicted patencies of the labyrinthine cap-
here was hearing loss.8,9 One year later, Fee reported sule, not vice versa.21
a patient having a PLF caused by nonsurgical Again, El Shazly and Linthicum’s study tested
trauma.10 Over the next decade, this was followed by the hypothesis that patencies of the labyrinthine
390 Ballenger’s Otorhinolaryngology
capsule predicted sudden sensory hearing loss,20 not loma, neoplasia, or anatomically related neurologic
sudden hearing losses predicting the presence of disorders with symptoms and signs similar to PLF.
patencies. As such, the studies are not in conflict. These disorders can mimic symptoms and signs oth-
However, one small series of temporal bones erwise attributable to PFL. Symptoms and signs of
from patients having had sudden sensory hearing PLF are related to the vestibular system and cochlear
loss during life lacked the use of the necessary diag- function separately, even though they can be present
nostic exclusionary criteria for PLF described below. in combination.
In this series, no patencies of the FAF or RWF were As has been reviewed, the temporal bone
found. Yet in two specimen pairs (the only pairs that histopathologic/clinical studies tested specific clinical
met the diagnostic exclusionary criteria), there was criteria. The studies indicate that the probability and
histologic evidence of patencies of the central por- accuracy of these criteria are p < .001, sensitivity 59%,
tions of the stapes footplates. This condition has and specificity 91%. It appears reasonable to present
been seen by the author during surgery for PLF and the criteria used in these studies to the reader. A sen-
has been repaired with improvement of symptoms.23 sitivity of 59% suggests underdiagnosis; therefore, a
Current studies suggest that this histologic change is heightened alertness to the possibility of a PLF
not a normal variant.24,25 appears reasonable. Additional diagnostic refinements
In another temporal bone histopathologic are required to identify clinically the remaining 41%
study by the author and other colleagues, the preva- (100 – 59 = 41) of patients having PLF who are now
lence of patencies of the FAF or RWF using 200 tem- presumably misdiagnosed as having another disorder.
poral bone pairs from consecutive autopsies, These refining new diagnostic criteria remain the
therefore representing a cross-section of society, was responsibility of the readers or others to identify.
24%, which is surprisingly high. Logic compels one
to conclude that the prevalence of patients having
PLF symptoms and signs are magnitudes smaller.
DIAGNOSTIC EXCLUSIONARY
Therefore, the mere histologic presence of these spe- CRITERIA
cific patencies seems not to predict the presence of For all clinical considerations regarding PLF, ini-
symptoms of PLF during life. On the other hand, tially, there must be the exclusion of inflammation,
when hearing or balance symptoms had been pres- granuloma, neoplasia, or anatomically related neu-
ent during life, the presence of these labyrinthine rologic disorders. These are easily accomplished with
capsule patencies predicts the specific set of symp- a sedimentation rate, a microhemoagglutination
toms and signs related to PLF. One explanation to assay for antibodies to Treponema pallidum for
this seeming dilemma seems plausible, that is, there syphilis, magnetic resonance imaging for tumor, and
is another variable, perhaps distinguishable only a neurologic evaluation pertinent to this disorder as
with special histologic techniques. The author and regularly accomplished by otologists. All of the
his colleagues are engaged in an investigation testing above occur after arrival at the clinical suspicion of
the hypothesis that “some patencies are permeable PLF, which is developed following a detailed clinical
to fluid, some are not, and only those permeable to history and otoneurologic evaluation. The clinical
fluid are related to clinical manifestations.” So far, in elements that allow a heightened suspicion of PLF
preliminary studies, differences in proteoglycans are very specifically related to either hearing or bal-
(extracellular mucopolysaccharides bound to pro- ance or both, as described below.
tein chains in covalent complexes) appear to be so
related.26 Definitive studies await completion.
HEARING
COMMENTS REGARDING OVERALL For hearing, each patient with sudden sensory hear-
ing loss (hours to days) or rapidly progressive sen-
CLINICAL PERSPECTIVES sory hearing loss (weeks to months) is suspected of
The diagnostic criteria for PLF are simple but do having a PLF.
require specific exclusionary criteria: a PLF cannot After the hearing loss occurs, rapid evaluation
be accurately diagnosed if any of these exclusionary of these patients is required (no more than 3 days
disorder types are present: inflammation, granu- and preferably within several hours).
Perilymphatic Fistulae 391
When a positive result is present, it is supportive of 5 days of inpatient bed rest with the head of the bed
the diagnosis, but a negative result means nothing. elevated and bathroom privileges with help are
Therefore, specific surgical observations remain our required for patients who have been seen shortly
best form of confirmation of a PLF diagnosis. Diag- after the onset (weeks). Audiograms (bedside) are
nostic variables based on outcome analysis of treat- performed daily. If adequate improvement occurs,
ment should be judged and evaluated with caution, the patient is given the above restriction directions
considering the need for further refining of diagnos- and is discharged from the hospital. If there is no
tic criteria related to this disorder, which are not yet improvement, surgery is performed on the sixth day.
defined but are anticipated. There are also possible If there is worsening of hearing, surgery is per-
unrecognized treatment variables that may occur formed at the time of worsening.
coincidentally with the intended treatment changes
for other disorders when the correct diagnosis of
PLF has been missed.
SURGERY
There is a question regarding the value of Whenever possible, surgery is performed under
endoscopic middle ear examination for evidence of local anesthesia with minimal or no sedation to
perilymph.27 It appears that the endoscope becomes avoid postanesthetic straining and masking of
hot. Not only is this important to patient comfort, surgically related symptoms. Exposure of the
but perhaps even more significant in terms of diag- middle ear is accomplished using a standard
nostic accuracy. The volume of perilymph present at tympanomeatal flap designed to give generous
the specific sites of accumulation (FAF or RWF) is exposure of the oval window and round window
often just a few microliters, easily evaporated by niche. Care should be taken to provide visualization
modest amounts of heat. In fact, even at surgery, a of the area of the FAF just anterior to the stapes.
touch of the minute amount of fluid with a sharp- Also, although rarely involved, the area of the fos-
pointed instrument may be necessary to confirm its sula post fenestram (FPF) posterior to the stapes
presence by the resulting light-reflection change. should be considered. The RWF is located on the
floor of the round window niche extending anteri-
orly, often initially obscured by mucosal bands (not
MEDICAL MANAGEMENT to be confused with the round window membrane).
The initial treatment for PLF usually should be med- The surgical manipulations should be done in
ical management except for sudden sensory hearing such a way as to avoid blood entering the middle ear.
loss. Sudden hearing loss requires more intense and If such should occur, careful suctioning should be
immediate restrictions. The general elements of used to remove it. Use as small a suction tip as pos-
patient instructions are quite simple but specific and sible to avoid the “hair dryer” evaporation qualities
and relate to hydrodynamics: of air movement, which have the potential of evap-
orating the small quantities of perilymph present.
1. Keep the head above the level of the heart.
After exposure, carefully examine the area just
2. Avoid lifting anything over 10 pounds.
anterior to the stapes footplate for crystal clear fluid
3. Have someone elevate the head of the bed
collecting in minute quantities. Often there is a
4 inches by putting blocks under the headboard
roughened appearance or a minute cleft-like forma-
bedposts.
tion of the bony surface. With a 26-gauge suction
Equivalents of these should be recognized and tip, aspirate any fluid present in this area. Repeated
avoided (eg, straining at stool, vigorous sneezing reaccumulation of fluid often but not always takes
[should open mouth], and hard nose blowing). several minutes and is diagnostic of the presence of
These elements of management allow vestibu- perilymph.28 Not infrequently, the presence of fluid
lar symptom improvement in about 40% of patients; is not immediately apparent because its total volume
for hearing loss, it appears to be significantly less. is only a few microliters (total inner ear perilymph
These modifications should be followed for 6 weeks. volume is 76 µL). In these instances, touching the
If there is no significant improvement, surgery area(s) in question with a sharp needlepoint instru-
should be considered. Sudden hearing loss is a spe- ment will cause the fluid to flash a sparkle as its
cial consideration. For sudden sensory hearing loss, reflective surface is altered.
Perilymphatic Fistulae 393
Not infrequently, the perilymph is present only The first is placed in the area of leak source, with
under the mucosa. With careful surgical (non- subsequent pieces placed over and around the initial
bloody) mucosal reflection and subsequent suction piece to help hold it in position. The opening pro-
drying of the area in question, diagnostic reaccumu- ducing the fluid passage is only 50 µm in maximal
lation of fluid is observed unrelated to the distant diameter; therefore, the initial graft piece must be
reflected mucosal edges. If laser is used for mucosal very small and specifically placed. (It appears histo-
obliteration, removal of any char with a fine pick is logically that there is fibrous tissue ingrowth of this
necessary prior to observation for fluid as this can graft material and/or fibrous elements stimulated by
inhibit fluid flow. this graft material into the FAF. Interestingly, the
After diagnostic reaccumulation perilymph has RWF appears to seal differently, with a dense colla-
been observed, sampling of the fluid can be done. The gen formation.23)
author prefers to use glass micropipettes with a tip
size of about 10 µm. Often preuse tip breakage is Alternative Surgical Method There are some
necessary in that the usual micropipette has a tip size patients whose general condition may not allow
of 3 to 5 µm, too small to allow the fluid to rise in the surgery described above. Although the author
the pipette by capillary action. Often the fluid vol- has no experience with the method, it appears sim-
ume is so small that only the frustum of the pipette ple and has been reported as effective for post-
will fill, sometimes just a portion of the frustum. stapedectomy PLFs (JB Causse, personal
Other times, a whole pipette full can be obtained, communication, March 2001). Simply, autologous
about 10 µL. Surprisingly, there does not seem to be blood is injected into the middle ear through the
a relationship between fluid volume and symptom or tympanic membrane. Presumably, a fibrous seal
sign intensity. results owing to the sterile inflammatory response
After the surgical diagnosis (reaccumulation of to the blood.
fluid) has been made, graft site preparation is neces-
sary and is meticulously performed. The mucosa is Additional Surgical Considerations, Including
reflected or desiccated by laser away from the site of Recurrence For vestibular disorders caused by
fluid origin (FAF or RWF). Care must be taken at PLF, an operation can be considered successful if
the round window niche in that the singular nerve after 6 weeks the patient is significantly improved or
may be herniated and exposed at the middle ear sur- symptom free. Symptom fluctuation before 6 weeks
face.19 Any tissue debris, even the slightest amount, is not unusual. Any evidence of the return or wors-
must be removed and the mucosal edges reflected far ening of symptoms after a 6-week period of symp-
enough from the site to allow graft pieces to be tom improvement should be considered a
placed without a risk of overlaying any mucosal ele- recurrence. Recurrences will occur in about 25% of
ment. The mucosal edges must be identified as being patients. In this instance, medical management
free from the graft elements after graft replacement. should be followed as described above before con-
sidering reoperation, assuming hearing stability. If
Graft Materials The most effective graft material surgery is warranted, the procedures are as described
appears to be the loose areolar fibrous tissue overly- above with care to re-examine all areas of risk (FAF,
ing the temporalis muscle fascia. FPF, and RWF), even those seemingly not involved at
The graft material is easily obtained through a the time of the previous operation.
1 cm postauricular incision. Rarely will any preop- For hearing, although rapid improvement has
erative postauricular shaving be necessary. A piece been seen, it is not the rule. Stability is sought. Any
of graft 1 cm in diameter is more than enough. Once sudden worsening prompts measures considered for
obtained, the graft is minced in very fine pieces, sudden hearing loss (above).
almost pinpoint in size. These pieces are cut on a
hard surface, usually metal. Special Consideration Concerning Endolym-
The graft application to the recipient site is phatic Hydrops In histologic studies, endolym-
performed using slightly blunted needle-tip ear phatic hydrops has been seen at times to be present
picks. These picks are loaded with individual pieces in specimens from patients meeting the clinical
of graft by the person assisting the otologic surgeon. diagnostic criteria and diagnosed as having PLF dur-
394 Ballenger’s Otorhinolaryngology
ing life and having the predicted FAF or RWF paten- Unfortunately, this is not the rule for sensory hear-
cies histologically.17 ing loss. Usually, in this case, improvement is slow.
Similarly, clinical studies without histologic However, there are rare cases in which hearing is
confirmation of patients with PLFs have indicated improved dramatically in but a few days or even as
that some patients exhibit clinical findings consis- short as 12 hours. Just as infrequently, the author has
tent with the presence of endolymphatic hydrops. In observed cases in which socially inadequate hearing
these patients, an endolymphatic shunt appeared to has improved to socially functional hearing over the
be helpful to those who used an outcome analysis course of several years. The physiologic mechanisms
experimental study design.29 The only difference and dynamics of the inner ear causing hearing loss
between the histologic studies and the clinical study or vestibular symptoms remain unexplained. How-
is the number or percentage of patients so afflicted. ever, the dramatic sudden improvement in some
There appeared to be a greater frequency in the clin- suggests a bioelectric or biochemical process and not
ical study. This raises the additional question of pos- a biomechanical process.
sible long-term tissue changes in cases of
endolymphatic hydrops—a possible time-related Complications Few complications are experi-
resolution of the otherwise histologically identifiable enced by patients undergoing medical or surgical
tissue distention of endolymphatic hydrops. The PLF repair. Infection has been experienced by two
answer to this question will await appropriate clini- of the author’s patients, both of whom had allowed
cal/histologic studies. their ears to get wet before healing occurred. They
did not lose hearing or vestibular function. The
Postoperative Care After surgery for a PLF, the infection remained restricted to the external canal/
author has had patients remain in the hospital for 5 middle ear.
days, with the head of the bed elevated 30 degrees, The hoped for improvement in hearing some-
and has only allowed bathroom privileges with help. times does not occur, and progression of the hearing
The personal help is required because of the risk of loss continues. When the preoperative symptoms
falls. Immediate postoperative exacerbation of were vestibular only, a mild sensory hearing loss has
vestibular symptoms is not unusual. The 5 days of occurred in some patients postoperatively.
bed rest are ordered to avoid, as much as possible, In all instances, the author has advised the
graft dislodgment. The author has the experience of patients preoperatively that any complication is pos-
reoperating on the patients of other surgeons who sible (including death), particularly the risk to any
have experienced recurrence. The only apparent structure in the surgical field, specifying these struc-
change in care was the 5-day hospitalization fol- tures and their function.
lowed by 6 weeks of house confinement, and there
were the usual successes. All patients are reinstructed THOUGHTS REGARDING
regarding the physical restrictions required for med-
FUTURE NEEDED STUDIES
ical management (above).
Knowledge regarding the pathogenic mechanisms of
Unusual Locations of Perilymphatic Leak On a PLFs remains conjecture based on an extension of
few occasions, the author has observed the source of pilot studies concerning intracellular proteoglycans
perilymph leakage in the central portion of the stapes related to fluid. Definitive studies are needed, or the
footplate. In these instances, the surgical repair was disorder will remain a medical mystery.
performed as described above. Ballottement of the In that the disease mechanism related to PLF
mucosa of the stapes footplate may be necessary to appears to be bioelectric, there should be a search
give evidence of the trapped mucosal-covered fluid for measurement methods that are applicable in vivo
leaking from the stapes footplate defect. Again, the by which these phenomena can be identified, per-
defect may be minute, and recurrent fluid emission haps substituting for the sought perilymph indica-
may be the only evidence of a PLF. tors. The implications of this type of measurement
for other ear disease may indeed be more significant
Anticipated Postoperative Course Not infre- than its singular use for PLF.
quently, patients become dramatically improved or The current methods of treatment of PLF,
even free of their preoperative vestibular symptoms. developed clinically using the best techniques avail-
Perilymphatic Fistulae 395
able, remain crude: patching a minute hole and/or vestibular observations. Ann Otol Rhinol Laryngol
altering endolymph dynamics by manipulation of 1973;82:2–12.
the endolymphatic sac. Even in these two instances, 13. Facer GW, Farrell KH, Cody DT. Spontaneous peri-
the physiologic consequences remain an enigma. It lymph fistula. A medical emergency. Mayo Clin Proc
appears, however, that they help patients improve in 1973;48:203–6.
their health status. Is this “dumb luck?” 14. Healy GB, Strong MS, Sampogna D. Ataxia, vertigo,
Regarding PLF, as with all other disease, “what” and hearing loss. A result of rupture of the inner ear
remains the junior question, and “how” and “why” window. Arch Otolaryngol 1974;100:130–5.
the cascade of events are triggered are of paramount 15. Healy GB, Friedman JM, Strong MS. Vestibular and
importance. With about 25% of the population hav- auditory findings of perilymphatic fistula: a review
ing these temporal bone pathways, patencies, but of 40 cases. Trans Am Acad Ophthalmol Otolaryngol
apparently only a fraction of these having fluid per- 1976;82:44–9.
meable patencies, the questions “how” and “why” 16. Kohut RI, Hinojosa R, Budetti JA. Perilymphatic fis-
loom as all important.26 Proteoglycan dynamics may tula: a histopathologic study. Ann Otol Rhinol
provide insight.
Laryngol 1986;95:466–71.
17. Kohut RI, Hinojosa R, Ryu JH. Perilymphatic fistu-
lae: a single-blind clinical histopathologic study. Adv
REFERENCES Otorhinolaryngol 1988;42:148–52.
1. Kohut RI, Waldorf RA, Haenel JL, Thompson JN. 18. Okano Y, Myers EN, Dickson DR. Microfissure
Minute perilymph fistulas: vertigo and Hennebert’s between the round window niche and posterior canal
sign without hearing loss. Ann Otol Rhinol Laryngol ampulla. Ann Otol Rhinol Laryngol 1977;86:49–57.
1979;88:153–9. 19. Okano Y, Myers EN. Herniation of the singular nerve
2. Friedland DR, Wackym PA. A critical appraisal of into the round window niche. Arch Otolaryngol
spontaneous perilymphatic fistulas of the inner. Am 1976;102:478–81.
J Otol 1999;20:261–76. 20. El Shazly MA, Linthicum FH. Microfissures of the
3. Gellé R. Etude clinique du vertige de Menier dans ses temporal bones: do they have any clinical signifi-
rapports avec les lesions des fenetres ovales et ron- cance? Am J Otol 1991;12:169–71.
des. Arch Neurol (Paris) 1883;4:273. 21. Kohut RI, Hinojosa R, Ryu JH. Sudden-onset hearing
4. Hennebert C. Labyrinthite double, reflexe moteur loss in 11 consecutive cases: a temporal bone
oto-oculaire. Clin (Brux) 1905;19:214–5. histopathologic study with identification of perilym-
5. Ramadier J. L’epreuve pneumatique du vestibul dans phatic fistulae. Trans Am Otol Soc 1989:81–8.
l’heredo-syphilis auriculaire, le sign de las fistule 22. Hinojosa R, Kohut RI, Lee JT, Ryu JH. Sudden hear-
sans fistule (signe d’Hennerbert). Presse Med 1921; ing loss due to perilymphatic fistulae II. A quantita-
19:624. tive temporal bone histopathologic study. Trans Am
6. Bárány R. Fall von labyrinthlues. Monatssch Ohren- Otol Soc 1990:121–7.
heik 1910;11:40.
23. Kohut RI, Hinojosa R, Ryu JH. [In preparation]
7. Ruttin E. Uber Fiselsymptom ohne Fisel. Verh Ges
24. Kohut RI, Ryu JH. [In preparation]
Deutsch Hais-Hasen-U Ohrenarzte (Leipz) 1921;
25. Kohut RI, Hinojosa R, Ryu JH. The histological char-
8:286–97.
acteristics of the core of the fistula ante fenestram.
8. Harrison WH, Shambaugh GE, Derlacki EL, Clemis
Acta Otolaryngol Suppl (Stockh) 1991;48:158–62.
JD. Perilymph fistula in stapes surgery. Laryngoscope
1967;77:836–49. 26. Kohut RI, Hinojosa R, Ryu JH. [In preparation]
9. House HP. The fistula problem in otosclerotic sur- 27. Bottrill I, Perrault DR, Poe D. In vitro and in vivo
gery. Laryngoscope 1967;77:1410–26. determination of the thermal effect of middle ear
10. Fee FA. Traumatic perilymphatic fistulas. Arch Oto- endoscopy. Laryngoscope 1996;106:213–6.
laryngol 1968;88:477–80. 28. Selzer S, McCabe BF. Perilymph fistula: the Iowa
11. Stroud MH, Calcaterra TC. Spontaneous perilymph experience. Laryngoscope 1986;96:37–49.
fistulas. Laryngoscope 1970;80:479–87. 29. Fitzgerald DC. Perilymphatic fistulas and Meniere’s
12. Goodhill V, Brockman SJ, Harris I, Hantz O. Sudden disease. Clinical series and literature review. Ann
deafness and labyrinthine window ruptures. Audio- Otol Rhinol Laryngol 2001;110:430–6.
CHAPTER 19
396
Autoimmune Inner Ear Disease 397
Unlike other organs and tissues, the inner ear is nization of animals with crude extracts of inner ear
not amenable for biopsy for the express intent of tissues results in hearing loss in approximately one-
investigating the underlying immunopathogenesis third of subjects.36 Circulating monoclonal antibod-
of purported autoimmune disorders affecting it. ies against inner ear tissues also produce hearing
What little histopathology has been published from loss.37 Animal models of systemic autoimmune dis-
patients with suspected AIED shows fibrosis and/or ease, such as the MRL-Faslpr mouse model of SLE,
bone deposition in the labyrinth, consistent with the display hearing loss.38
late sequelae of inflammation.28–31 Specific immune
reactivity against inner ear antigens is often detected
in patients with suspected AIED, but the results vary.
ETIOLOGY
Lymphocyte migration assays using inner ear tissue Because of the relative rarity of this condition and its
as a target have been disappointing, providing at best recent recognition, as noted above, very few tempo-
low stimulation indexes.32 More promising results ral bones with a diagnosis of AIED have been evalu-
have been obtained with Western blotting. Signifi- ated. More studies have assessed the inner ears of
cantly more patients with suspected AIED show patients with systemic autoimmune disorders.
reactivity against a 68 kD antigen (Figure 19–5) than Recently, Sone et al assessed 14 temporal bones from
do matched normal-hearing or rheumatic con- 7 individuals with SLE.39 The duration of disease
trols.27,33 Autoimmune inner ear disease has also and ages varied widely. The most consistent findings
been associated with reactivity against antigens of were hair cell and spiral ganglion cell loss. However,
different molecular weights, especially 45 to 50 kD, unusual accretions were observed in the stria vascu-
30 kD, and 20 kD.34 Although reactivity of patient laris of 6 of 14 temporal bones.
sera against tissue sections of the inner ear has Animal models have been valuable adjuncts in
produced reproducible inner ear labeling,35 it does the study of AIED since the antigen and immuniza-
not appear to be as practical or as useful as immuno- tion history can be rigorously controlled, and
blotting. histopathology is routinely available. Initial studies
A number of animal studies have supported an using immunization of guinea pigs with bovine
autoimmune cause for some types of SNHL. Immu- inner ear extracts resulted in the development of
398 Ballenger’s Otorhinolaryngology
A B
FIGURE 19–2. A, Photomicrograph of a normal endolymphatic sac (ES) in the guinea pig inner ear. Hematoxylin and
eosin–stained paraffin section ( 20 original magnification). B, Photomicrograph of an ES from a guinea pig with
cochlear inflammation following cochlear challenge with a foreign protein to which the animal was sensitized ( 20 orig-
inal magnification).
hearing loss and mild inflammatory changes in the produced a 10 dB hearing loss in rats as well as a cel-
inner ears of a subset of animals.36 More recent work lular infiltrate into the perilymph.42,43 A monoclonal
has confirmed these findings and indicated that the antibody raised against cochlear tissues of approxi-
hearing losses induced by this procedure tend to be mately 68 kD that specifically reacts with supporting
modest. Bouman et al found that immunization of cells in the organ of Corti has been shown to pro-
animals with swine inner ear extracts produced duce high-frequency hearing loss in mice carrying
modest declines in compound action potentials the hybridoma.37 More recently, Nair et al infused
recorded from the guinea pigs 2 and 6 weeks after this antibody into the cochlear perilymph using an
immunization but no changes in the cochlear micro- osmotic minipump.44 After 13 days, an approxi-
phonic.34 This suggests that the events responsible mately 20 dB hearing loss developed, associated with
for hearing loss occurred at the level of the inner minor losses of hair cells.
hair cell and/or spiral ganglion neuron rather than at To explore the origin of lymphocytes in the
the level of the outer hair cell. Hearing losses were region of the endolymphatic sac and the reaction of
associated with increased Western blot reactivity to T cells to self-antigens in the inner ear, Iwai et al used
68 kD and other antigens.34 a model of graft-versus-host disease.45 T cells from
Immunization with specific proteins has also C57BL/6 mice injected into the systemic circulation
resulted in hearing loss. Based on the observation of BALB/c mice infiltrated and proliferated in the
that myelin protein P0 was associated with perisaccular region surrounding the endolymphatic
immunoreactivity against a 30 kD inner ear protein sac but not into other regions of the inner ear. These
in patients with AIED,40 Matsuoka et al immunized findings confirm the role of the endolymphatic sac
mice with purified bovine P0.41 They observed an region in mediating immunity in the inner ear, as
approximately 10 dB hearing loss and a mono- well as the communication of the normal sac with
cellular infiltrate in the eighth nerve within the circulating lymphocytes. This provides an additional
cochlear modiolus. Experimental autoimmune foundation for autoimmunity as an etiology in dis-
encephalomyelitis can be induced by immunization orders involving the sac, such as Meniere’s disease.
with the neuronal S-100β calcium-binding protein Animal models have also been used to study
and by passive transfer of T cells sensitized to this the relationship between systemic autoimmune dis-
antigen. Based on this earlier finding, Gloddek et al ease and the inner ear. The MRL-Faslpr mouse is used
found that passive transfer of S-100β-reactive T cells as a model of SLE owing to the accumulation of
Autoimmune Inner Ear Disease 399
autoreactive T cells normally eliminated by Fas- tion of antibody in or cellular infiltration of the
mediated apoptosis. This model also displays pro- cochlea in this strain.48
gressive hearing loss. Ruckenstein et al found that As better imaging becomes available, the local-
the most striking inner ear pathology in this model ization of inflammatory processes to specific regions
was observed in the stria vascularis,38 with progres- of the inner ear should become possible. Having this
sive, hydropic degeneration of intermediate cells, information will certainly improve our diagnostic
consistent with the strial pathology observed in capability as well as our knowledge of the basic
human SLE temporal bones as described above.39 In pathogenesis of this disorder.
addition, Ruckenstein and Hu observed the deposi-
tion of both complement-fixing and non–comple-
ment-fixing antibodies in the stria vascularis and, to
DIAGNOSIS
a lesser extent, in other structures.46 All antibodies Diagnosis of AIED is still problematic. There is no
were bound to the capillary walls and were not asso- universally accepted set of diagnostic criteria or
ciated with signs of inflammation. The same group diagnostic test for a condition that appears to have
found that systemic treatment with dexamethasone several independent etiologies. In general, in all cases
suppressed antibody deposition within the stria and of idiopathic, rapidly progressive, bilateral hearing
other structures of the inner ear.38 However, the loss, AIED should be suspected. However, there is no
treatment failed to suppress strial degeneration and doubt that involvement of the second ear may occur
hearing loss, suggesting that perhaps the hearing loss months or even years after presentation of symp-
seen in these animals had a genetic basis. In contrast toms in the first ear. Hearing loss may be manifested
to this result, Wobig et al found that systemic pred- as either diminished hearing acuity, decreased dis-
nisolone treatment protected hearing in MRL-Faslpr crimination, or both and may involve significant
mice.47 The Palmerston-North mouse is also fluctuations over time. In bilateral Meniere’s disease,
employed as a model of SLE with hearing loss. These with its triad of vestibular dysfunction, low-tone,
animals develop abnormal mineralization of con- fluctuant hearing loss, and tinnitus, AIED should
nective tissue in the region of the eighth nerve root also be suspected, especially when the second ear
within the modiolus. However, there is no deposi- becomes involved within a short period of time of
400 Ballenger’s Otorhinolaryngology
the first. Aside from an empiric trial with high-dose against the bovine HSP 70 (bHSP 70) has been
corticosteroids showing improved inner ear func- found to be correlated with AIED.52 However, pre-
tion, Western blot assays are currently the most absorption with bHSP 70 does not remove all reac-
widely used category of diagnostic test for AIED. tivity to the 68 kD inner ear antigen,52 and
The initial assays used for this purpose were based immunization of animals with HSP 70 does not
on proteins extracted from bovine inner ear tissue, appear to produce hearing loss.55 Antibodies against
and inner ear extracts are still used. Reactivity to an other antigens have also been implicated. Several
approximately 68 kD antigen was detected in a sig- investigators have reported that immunoreactivity to
nificant proportion of patients with AIED and inner ear proteins with molecular weights in the 42
Meniere’s disease.27,33,49–51 This or an antigen with to 45 kD range is also positively correlated with
shared epitopes was later shown to be present in kid- AIED, although with a lower level of specificity than
ney and to be a member of the heat shock protein the 68 kD protein or HSP 70. For example, Atlas et
(HSP) family.52,53 Reactivity against inner ear anti- al found that positive Western blots against 68
gens of other molecular weights, especially in the 45, and/or 42 to 45 kD inner ear proteins were present
30, and 20 kD ranges, has frequently been in significantly more patients with Meniere’s disease
reported.34,40 Few of these other antigens have been than in normal controls, whereas reactivity against
characterized or found to be present in statistically 35 to 36 and 20 kD proteins was not different in the
significant proportions of hearing loss versus con- two groups.51 Moreover, reactivity appeared to be
trol populations. For example, studies examining the related to disease state in that patients with active
antigenic profile of inner ear tissues consistently disease (at least one episode of vertigo within 1
demonstrate a multitude of antigens against which month) were significantly more likely to be positive
human sera reacts; however, these bands seen on than those with inactive disease. Other specific anti-
Western blot, failed to reach significance when care- genic targets have also been studied. Modugno et al
fully matched against controls.33,49,54 Immunoreactiv- observed antithyroid antibodies in 27% of patients
ity to a 30 kD antigen has been associated with with benign paroxysmal positional vertigo, signifi-
myelin protein P0.41 The 68 kD antigen has been cantly more than were observed in a group of
associated with HSP 70, and immunoreactivity normal controls.56 Using immunoblotting and
Autoimmune Inner Ear Disease 401
high level of reactivity in blood donor control sera.62 purpose, it is likely that over the next few years it will
This high rate of positivity in the control serum was be further refined:
unexplained and contradicts the previously low level
of positives in control sera as well as those high rates Type 1: Organ (Ear) Specific
of positivity reported by others.27,53,61 Serial serum • Rapidly progressive bilateral SNHL
samples revealed no correlation between antibody • All age ranges, although middle age is most com-
level and the clinical course of the disease. These mon
observations led them to question the clinical utility • No other clinical evidence of systemic autoim-
of the HSP 70 assay in Meniere’s disease. The answer mune disease
to whether a subset of patients with classic Meniere’s • Positive Otoblot (Western blot 68 kD or HSP 70)
disease is immune mediated is currently unclear. • Negative serologic studies (antinuclear antibody
A number of investigators have reacted patient [ANA], erythrocyte sedimentation rate, rheuma-
sera against tissue sections to detect immunoreactiv- toid factor (RF), C1q binding assay, etc)
ity against inner ear antigens. This technique has • Greater than 50% response rate to high-dose cor-
been used on a research basis since the 1980s, when ticosteroids
Arnold et al reported a high degree of labeling
within the cochlea with patient serum.63 Bachor et al Type 2: Rapidly Progressive Bilateral Sensorineural
detected immunoreactivity to rat cochlear sections Hearing Loss with Systemic Autoimmune Disease
in 14 of 15 patients showing progressive or sudden
• Rapidly progressive bilateral SNHL
hearing loss in the cochlea opposite an ear deafened
• Hearing loss often worst with flare of autoimmune
by trauma or inflammation.64 Using rat cryosections
condition
of the inner ear, Arbusow et al detected antibodies
• Other autoimmune condition is present (SLE,
against vestibular sensory epithelia in 8 of 12
ulcerative colitis, polyarteritis nodosa, vasculitis,
patients with idiopathic bilateral vestibular pathol-
rheumatoid arthritis, Sjögren’s syndrome)
ogy as compared with 1 of 22 healthy controls and 0
• Otoblot may be positive or negative
of 6 patients with systemic autoimmune disease.65
• Serologic studies will be positive in accordance
Ottaviani et al detected immunoreactivity against
with the illness (ie, ANA-high titers, RF positive,
endothelial cells using sections of rat kidney tissue in
circulating immune complexes)
8 of 15 patients with sudden hearing loss, as com-
• Corticosteroid responsive and may be managed
pared with 2 of 14 normal controls.66 Helmchen et al
with targeted therapies for underlying illness
observed positive but low levels of immunoreactiv-
ity against inner ear sections using serum from Type 3: Immune-Mediated Meniere’s Disease
patients with Cogan’s syndrome.67 However, unlike
anticorneal antibodies, the anticochlear immunore- • Bilateral, fluctuating SNHL with vestibular symp-
activity levels were not correlated with disease stage. toms that may predominate
• Subset of patients with delayed contralateral
endolymphatic hydrops or recent instability of
CLASSIFICATION OF AUTOIMMUNE better-hearing ear in a patient with burned out
INNER EAR DISEASE Meniere’s disease
Over the past two decades since McCabe’s published • Otoblot positive 37 to 58%; may show presence of
article on AIED,18 many patients have been diag- circulating immune complexes
nosed and treated for rapidly progressive SNHL and • Corticosteroid responsive; may require long-term
many have had their hearing maintained or even immunosuppression owing to relapses
improved with treatment. As a result of the growing
Type 4: Rapidly Progressive Bilateral Sensorineural
experience with patients with corticosteroid sensi-
Hearing Loss with Associated Inflammatory Disease
tive hearing loss, a pattern has begun to emerge that
(Chronic Otitis Media, Lyme Disease, Otosyphilis,
warrants a classification scheme to sort out patients
Serum Sickness)
better as they present with such a broad category of
inner ear dysfunction. Although the following clas- • Evidence of profound drop in hearing with long-
sification scheme is intended specifically for that standing chronic otitis media
Autoimmune Inner Ear Disease 403
• May show inflammation of the tympanic mem- and cyclophosphamide (Cytoxan). The former has
brane and perforations the advantage of being less toxic and has fewer long-
• Hearing loss progresses despite treatment of the term hematopoietic risks, such as the development
infectious agent (treponemal or rickettsial) of neoplasia.68 If MTX is used, it should be given as
• Otoblot negative; serologic tests for the underlying an oral dose 7.5 to 20 mg weekly with folic acid. The
disease may be positive; patient should be evalu- patient should be monitored closely for toxicity with
ated for granulomatous disease and vasculitis by complete blood count, platelets, blood urea nitro-
biopsy if tissue is available gen, creatinine, liver function tests, and urinalysis. It
• Corticosteroid responsive and may require long- should be noted that the prednisone-sparing effects
term immunosuppression of MTX may take 1 to 2 months to achieve; there-
• Serum sickness has been reported after vaccina- fore, prednisone should be maintained until such
tions, although anecdotal effects are obtained. Also, if high-dose prednisone
has not been effective in restoring hearing, it is
Type 5: Cogan’s Syndrome unlikely that MTX will offer additional efficacy.
Therefore, for patients with severe hearing losses,
• Sudden onset of interstitial keratitis and severe
positive 68 kD Western blots, and nonresponsiveness
vestibuloauditory dysfunction
to prednisone or MTX therapy, consideration
• Otoblot negative for 68 kD but positive for 55 kD
should be given to a trial of cyclophosphamide.26 At
antigen
oral doses of 1 to 2 mg per day taken each morning
• Responds to high-dose corticosteroids, although
with liberal amounts of fluid, the risk of hemor-
becomes resistant over long term
rhagic cystitis or drug effects on the bladder can be
minimized. Again, appropriate monitoring of
Type 6: Autoimmune Inner Ear Disease-Like
peripheral blood counts is required. Cyclophos-
• Young patients with idiopathic rapidly progressive phamide should not be administered to children,
bilateral SNHL leading to deafness and the risk of permanent sterility should be out-
• Severe ear pain, pressure, and tinnitus lined. If, on the other hand, no response to high-
• Otoblot and all serology negative dose prednisone is achieved, and the patient is 68 kD
• May have an unrelated, nonspecific inflammatory Western blot negative, it may be futile to continue
event that initiates ear disease potentially toxic drugs, with little evidence for AIED
• Not responsive to immunosuppressive drugs, as the cause. As this field continues to evolve, there
although they are tried are, however, no hard and fast rules, and a practi-
tioner may be justified in trying cytotoxic drugs on
an empiric basis because unrelenting progressive
TREATMENT deafness is a serious handicap for a previously nor-
Once a diagnosis of AIED is established or consid- mal-hearing person. Luetje recommended plasma-
ered highly presumptive, high-dose prednisone is pheresis for difficult to manage patients,69 and this
the mainstay of treatment for this condition. Early can be a useful adjunct to the above-mentioned
institution of 60 mg of prednisone daily for a month immunosuppressive drugs. At the time of writing, a
is now widely used as short-term or lower-dose multi-institutional clinical trial is under way to com-
long-term therapy and has either been ineffective or pare the efficacy of MTX and prednisone versus
fraught with the risk of relapse. Prednisone is then prednisone alone for the management of AIED. The
tapered slowly if a positive response to therapy is results of this trial should help to delineate appro-
obtained. If during the taper hearing suddenly falls, priate therapy for suspected AIED.
reinstitution of high-dose prednisone is indicated. Parnes et al noted that local corticosteroids
One sensitive predictor of imminent relapse can be appear to be more effective in the treatment of other
the appearance of loud tinnitus in one or both ears. autoimmune disorders, such as corneal inflamma-
If patients show corticosteroid responsiveness but tion owing to Cogan’s syndrome.70 They therefore
attempts at taper result in relapse, the addition of a investigated the pharmacokinetics of hydrocorti-
cytotoxic drug should be considered. The most sone, methylprednisone, and dexamethasone in per-
widely used of these agents are methotrexate (MTX) ilymph and endolymph after oral, intravenous, or
404 Ballenger’s Otorhinolaryngology
intratympanic administration. Dexamethasone was autoimmune disorders provides strong evidence that
found to be largely excluded from the cochlea by the autoimmune processes can damage the labyrinth
blood-labyrinthine barrier. Both methylprednisone but does not speak to the issue of organ-specific dis-
and hydrocortisone reached inner ear fluid after sys- ease. Animal models of hearing loss and/or vestibu-
temic administration, attenuated presumably by the lar dysfunction secondary to immunization with
blood-labyrinthine barrier. Much higher levels of all inner ear antigens provide stronger evidence of spe-
three drugs were observed in cochlear fluid after cific autoimmunity.
intratympanic administration, with rapid declines Autoimmune inner ear disease is difficult to
over a 6- to 24-hour period. Similar results were diagnose. Although it is generally agreed that the
noted by Chandrasekhar et al.71 Parnes et al also condition should be bilateral and rapidly progres-
reported that repeated intratympanic administra- sive, the involvement of the second ear may take
tion of corticosteroids in a small series of patients months or even years to manifest. Although rapidly
with hearing loss of diverse origins was followed by progressing conditions are more readily held to be
improvement in some patients, but no control group autoimmune, AIED is increasingly considered as a
was included.70 In contrast, Yang et al found that potential cause of Meniere’s disease and as a less
local immunosuppression had no effect on experi- likely cause of sudden hearing loss.
mental immune-mediated SNHL in an animal Improved diagnostic tests are clearly required.
model.72 It should be noted that local effects are not, No one test appears to be positive in more than 30 to
of course, the only basis for the therapeutic efficacy 40% of patients who otherwise fit the criteria for
of immunosuppressants. By decreasing peripheral autoimmune disease. One possible explanation for
blood leukocytes, these agents reduce the population this is that rapidly progressive SNHL has a number
of cells that can be recruited to the inner ear to par- of different causes, including autoimmune, viral,
ticipate in immune and inflammatory damage. An genetic, developmental, vascular, and perhaps meta-
experiment designed to prevent entry of cells into bolic. Many of these cannot be separated by their
the cochlea using antibodies to ICAM-1 did show a presentation; therefore, it would not be unusual or
reduced number of infiltrated inflammatory cells in unexpected for many of these patients to have nega-
the cochlea following antigen challenge.73 Although tive antibody testing, and some who were not
the inflammation was not entirely prevented, such a autoimmune might even improve with corticos-
strategy may be worth pursuing. An analogous situ- teroids (eg, viral). Another possibility is that autoim-
ation exists for ocular immune disorders such as munity exists to a variety of inner ear antigens.
uveitis. Despite the greater accessibility of the eye to Given the variety of autoimmune disorders that can
topical drugs than the inner ear, ophthalmologists affect the inner ear, the variety of antigens with
would never consider local therapy in lieu of high- which sera from patients with AIED will react, and
dose corticosteroids for these disorders. Perhaps a the fact that immunization with a variety of proteins
lesson taken from their experience might lessen the can lead to hearing loss in animal models, this would
enthusiasm that currently exists for treatment solely appear to be a strong possibility.
by local middle ear corticosteroid instillation. The usefulness of Western blotting for anti-
bodies directed against the 68 kD or HSP 70 antigen
as diagnostic assay seems clear, although there is lit-
DISCUSSION tle evidence to support an etiologic role for HSP 70.
Debate continues as to whether AIED exists as a sep- It is possible that HSP 70 shares one or more epi-
arate entity. Some authors prefer to refer to this con- topes with an inner ear antigen, although reactivity
dition as immune-mediated inner ear disease. to widely variable epitopes of HSP 70 60 argues
Clearly, the evidence for specific autoimmunity is against this. Alternatively, HSP 70 immunoreactiv-
indirect. Hearing and vestibular problems that are ity may all be a well-correlated epiphenomenon,
diagnosed as autoimmune in origin are often perhaps produced by immunization of self-proteins
responsive to corticosteroids. Although this suggests during inflammatory responses arising from other
that the condition involves inflammation, one can- causes. Lastly, initial studies with serum tested by
not infer the involvement of specific immunity. The Western blotting were with the use of 68 kD inner
fact that inner ear disease is often present in systemic ear tissue as the target antigen. After the recognition
Autoimmune Inner Ear Disease 405
that HSP 70 showed results similar to 68 kD by 10. Woolf NK, Harris JP, Ryan AF, et al. Hearing loss in
several investigators, a number of groups have experimental cytomegalovirus infection of the
adopted HSP 70 as the target for immunologic guinea pig inner ear: prevention by systemic immu-
testing. In fact, this may be the wrong approach if nity. Ann Otol Rhinol Laryngol 1985;94:350–6.
HSP 70 merely shares epitopes with but is not the 11. Darmstadt GL, Keithley EM, Harris JP. Effects of
actual antigen in 68 kD inner ear immunoreactiv- cyclophosphamide on the pathogenesis of cyto-
ity. Future studies will certainly improve our megalovirus-induced labyrinthitis. Ann Otol Rhinol
knowledge of the actual antigenic target(s) in- Laryngol 1990;99:960–8.
volved in AIED. 12. Harris JP, Fukuda S, Keithley EM. Spiral modiolar
Despite uncertainty over etiology and difficul- vein: its importance in inner ear inflammation. Acta
ties in diagnosis, this condition is frequently respon- Otolaryngol (Stockh) 1990;110:357–65.
sive to treatment with immunosuppressive drugs. 13. Stearns GS, Keithley EM, Harris JP. Development of
Since there are few forms of SNHL that can be high endothelial venule-like characteristics in the
treated other than symptomatically, AIED represents spiral modiolar vein induced by viral labyrinthitis.
a unique opportunity to reverse SNHL and vestibu- Laryngoscope 1993;103:890–8.
lar disorders. For this reason alone, the diagnosis 14. Takahashi M, Harris JP. Analysis of immunocompe-
should be considered when symptoms are appropri- tent cells following inner ear immunostimulation.
ate, and both clinical and basic research on this con- Laryngoscope 1988;98:1133–8.
dition is warranted. 15. Suzuki M, Harris JP. Expression of intercellular
adhesion molecule-1 during inner ear inflammation.
Ann Otol Rhinol Laryngol 1995;104:69–75.
REFERENCES 16. Keithley EM, Woolf NK, Harris JP. Development of
morphological and physiological changes in the
1. Harris JP. Immunology of the inner ear: response of cochlea induced by cytomegalovirus. Laryngoscope
the inner ear to antigen challenge. Otolaryngol Head 1989;99:409–14.
Neck Surg 1983;91:18–32. 17. Chen MC, Harris JP, Keithley EM. Immunohisto-
2. Harris JP. Immunology of the inner ear: evidence of chemical analysis of proliferating cells in a sterile
local antibody production. Ann Otol Rhinol Laryn- labyrinthitis animal model. Laryngoscope 1998;
gol 1984;93:157–62. 108:651–6.
3. Harris JP, Ryan AF. Immunobiology of the inner ear. 18. McCabe BF. Autoimmune sensorineural hearing
Am J Otolaryngol 1984;5:418–25. loss. Ann Otol Rhinol Laryngol 1979;88:585–9.
4. Harris JP, Woolf NK, Ryan AF. Elaboration of sys- 19. Schiff M, Brown M. Hormones and sudden deafness.
temic immunity following inner ear immunization. Laryngoscope 1974;84:1959–81.
Am J Otolaryngol 1985;6:148–52. 20. Clemis JD, Mastricola PG, Schuler-Vogler M.
5. Woolf NK, Harris JP. Cochlear pathophysiology Sudden hearing loss in the contralateral ear in post-
associated with inner ear immune responses. Acta operative acoustic tumor: three case reports. Laryn-
Otolaryngol (Stockh) 1986;102:353–64. goscope 1982;92:76–9.
6. Ma C, Billings P, Harris JP, Keithley EM. Characteri- 21. Teryama Y, Saski Y. Studies on experimental allergic
zation of an experimentally induced inner ear (isoimmune) labyrinthitis in guinea pigs. Acta Oto-
immune response. Laryngoscope 2000;110:451–6. laryngol (Stockh) 1963;58:49–61.
7. Tomiyama S, Harris JP. The endolymphatic sac: its 22. Hughes GB, Barna BP, Kinney SE, et al. Autoimmune
importance in inner ear immune responses. Laryn- endolymphatic hydrops: five-year review. Otolaryn-
goscope 1986;96:685–91. gol Head Neck Surg 1988;98:221–5.
8. Tomiyama S, Harris JP. The role of the endolym- 23. Moskowitz D, Lee KJ, Smith HW. Steroid use in idio-
phatic sac in inner ear immunity. Acta Otolaryngol pathic sudden sensorineural hearing loss. Laryngo-
(Stockh) 1987;103:182–8. scope 1984;94:664–6.
9. Harris JP, Woolf NK, Ryan AF, et al. Immunologic 24. Ariyasu L, Byl FM, Sprague MS, Adour KK. The ben-
and electrophysiological response to cytomegaloviral eficial effect of methylprednisone in acute vestibular
inner ear infection in the guinea pig. J Infect Dis vertigo. Arch Otolaryngol Head Neck Surg 1990;
1984;150:523–30. 166:700–3.
406 Ballenger’s Otorhinolaryngology
25. Harris JP, Ryan AF. Fundamental immune mecha- 40. Cao MY, Gersdorff M, Deggouj N, et al. Detection of
nisms of the brain and inner ear. Otolaryngol Head inner ear disease autoantibodies by immunoblot-
Neck Surg 1995;112:639–53. ting. Mol Cell Biochem 1995;146:157–63.
26. McCabe BF. Autoimmune inner ear disease. In: 41. Matsuoka H, Cheng KC, Krug MS, et al. Murine
Bernstein J, Ogra P, editors. Immunology of the ear. model of autoimmune hearing loss induced by
New York: Raven Press; 1987. p. 427–35. myelin protein P0. Ann Otol Rhinol Laryngol
27. Harris JP, Sharp PA. Inner ear autoantibodies in 1999;108:255–64.
patients with rapidly progressive sensorineural hear- 42. Gloddek B, Lassmann S, Gloddek J, Arnold W. Role
ing loss. Laryngoscope 1990;100:516–24. of S-100beta as potential autoantigen in an autoim-
28. Schuknecht HF. Ear pathology in autoimmune dis- mune disease of the inner ear. J Neuroimmunol
ease. Adv Otorhinolaryngol 1991;46:50–70. 1999;101:39–46.
29. Hoistad DL, Schachern PA, Paparella MM. Autoim- 43. Gloddek B, Gloddek J, Arnold W. A rat T-cell line
mune sensorineural hearing loss: a human temporal that mediates autoimmune disease of the inner ear
bone study. Am J Otolaryngol 1998;19:33–9. in the Lewis rat. ORL J Otorhinolaryngol Relat Spec
30. Jenkins HA, Pollak AM, Fisch U. Polyarteritis nodosa 1999;61:181–7.
as a cause of sudden deafness: a human temporal 44. Nair TS, Prieskorn DM, Miller JM, et al. KHRI-3
bone study. Am J Otolaryngol 1981;2:99–107. monoclonal antibody-induced damage to the inner
31. Keithley EM, Chen MC, Linthicum F. Clinical diag- ear: antibody staining of nascent scars. Hear Res
noses associated with histologic findings of fibrotic 1999;129:50–60.
tissue and new bone in the inner ear. Laryngoscope 45. Iwai H, Tomoda K, Sugiura K, et al. T cells infiltrat-
1998;108:87–91. ing from the systemic circulation proliferate in the
32. Hughes GB, Barna BP, Kinney SE, et al. Predictive endolymphatic sac. Ann Otol Rhinol Laryngol
value of laboratory tests in “autoimmune” inner ear 1999;108:1146–50.
disease: preliminary report. Laryngoscope 1986; 46. Ruckenstein MJ, Hu L. Antibody deposition in the
96:502–5. stria vascularis of the MRL-Fas(lpr) mouse. Hear
33. Gottschlich S, Billings PB, Keithley EM, et al. Assess- Res 1999;127:137–42.
ment of serum antibodies in patients with rapidly 47. Wobig RJ, Kempton JB, Trune DR. Steroid-respon-
progressive sensorineural hearing loss and Meniere’s sive cochlear dysfunction in the MRL/lpr autoim-
disease. Laryngoscope 1995;105:1347–52. mune mouse. Otolaryngol Head Neck Surg 1999;
34. Bouman H, Klis SF, Meeuwsen F, et al. Experimental 121:344–7.
autoimmune inner ear disease: an electrocochleo- 48. Khan DC, DeGagne JM, Trune DR. Abnormal
graphic and histophysiologic study. Ann Otol Rhi- cochlear connective tissue mineralization in the
nol Laryngol 2000;109:457–66. Palmerston North autoimmune mouse. Hear Res
35. Soliman AM, Zanetti F. Improvements of a method 2000;142:12–22.
for testing autoantibodies in sensorineural hearing 49. Shin SO, Billings PB, Keithley EM, Harris JP. Com-
loss. Adv Otorhinolaryngol 1988;39:13–7. parison of anti-heat shock protein 70 (anti-hsp70)
36. Harris JP. Experimental autoimmune sensorineural and anti-68-kDa inner ear protein in the sera of
hearing loss. Laryngoscope 1987;97:63–76. patients with Ménière’s disease. Laryngoscope
37. Nair TS, Raphael Y, Dolan DF, et al. Monoclonal 1997;107:222–7.
antibody induced hearing loss. Hear Res 1995; 50. Moscicki RA, San Martin JE, Quintero CH, et al.
83:101–13. Serum antibody to inner ear proteins in patients
38. Ruckenstein MJ, Sarwar A, Hu L, et al. Effects with progressive hearing loss. JAMA 1994;272:
of immunosuppression on the development of 611–6.
cochlear disease in the MRL-Fas(lpr) mouse. Laryn- 51. Atlas MD, Chai F, Boscato L. Ménière’s disease: evi-
goscope 1999;109:626–30. dence of an immune process. Am J Otol 1998;
39. Sone M, Schachern PA, Paparella MM, Morizono 19:628–31.
N. Study of systemic lupus erythematosus in tem- 52. Billings PB, Keithley EM, Harris JP. Evidence linking
poral bones. Ann Otol Rhinol Laryngol 1999; the 68 kilodalton antigen identified in progressive
108:338–44. sensorineural hearing loss patient sera with heat
Autoimmune Inner Ear Disease 407
shock protein 70. Ann Otol Rhinol Laryngol 1995; ing disorders. Acta Otolaryngol (Stockh) 1985;99:
104:181–8. 437–44.
53. Bloch DB, San Martin JE, Rauch SD, et al. Serum 64. Bachor E, ten Cate WJ, Gloddek B, Ehsani N.
antibodies to heat shock protein 70 in sensorineural Immunohistochemical detection of humoral auto-
hearing loss. Arch Otolaryngol Head Neck Surg antibodies in patients with hearing loss in the last
1995;121:1167–71. hearing ear. Laryngorhinootologie 2000;79:131–4.
54. Yamanobe S, Harris JP. Inner ear specific autoanti- 65. Arbusow V, Strupp M, Dieterich M, et al. Serum
bodies. Laryngoscope 1993;103:319–25. antibodies against membranous labyrinth in
55. Trune DR, Kempton JB, Mitchel CR, Heferneider patients with “idiopathic” bilateral vestibulopathy. J
SH. Failure of elevated heat shock protein 70 anti- Neurol 1998;245:132–6.
bodies to alter cochlear function in mice. Hear Res 66. Ottaviani F, Cadoni G, Marinelli L, et al. Anti-
1998;116:65–70. endothelial autoantibodies in patients with sudden
56. Modugno GC, Pirodda A, Ferri GG, et al. A rela- hearing loss. Laryngoscope 1999;109:1084–7.
tionship between autoimmune thyroiditis and 67. Helmchen C, Arbusow V, Jager L, et al. Cogan’s syn-
benign paroxysmal positional vertigo? Med Hypoth drome: clinical significance of antibodies against the
2000;54:614–5. inner ear and cornea. Acta Otolaryngol (Stockh)
57. Yamawaki M, Ariga T, Gao Y, et al. Sulfoglucuronosyl 1999;119:528–36.
glycolipids as putative antigens for autoimmune 68. Sismanis A, Thompson T, Willis HE. Methotrexate
inner ear disease. J Neuroimmunol 1998;84:111–6. therapy for autoimmune hearing loss: a preliminary
58. Lopez-Gonzalez MA, Lucas M, Sanchez B, et al. report. Laryngoscope 1994;104:932–4.
Autoimmune deafness is not related to hyperreactiv- 69. Luetje CM. Theoretical and practical implications
ity to type II collagen. Acta Otolaryngol (Stockh) for plasmapheresis in autoimmune inner ear disease.
1999;119:690–4. Laryngoscope 1989;99:1137–46.
59. Hirose K, Wener MH, Duckert LG. Utility of labora- 70. Parnes LS, Sun AH, Freeman DJ. Corticosteroid
tory testing in autoimmune inner ear disease. Laryn- pharmacokinetics in the inner ear fluids: an animal
goscope 1999;109:1749–54. study followed by clinical application. Laryngoscope
60. Bloch DB, Gutierrez JA Jr, Guerriero V, et al. Recog- 1999;109:1–17.
nition of a dominant epitope in bovine heat-shock 71. Chandrasekhar SS, Rubinstein RY, Kwartler JA, et al.
protein 70 in inner ear disease. Laryngoscope Dexamethasone pharmacokinetics in the inner ear:
1999;109:621–5. comparison of route of administration and use of
61. Rauch SD, San Martin JE, Moscicki RA, Bloch KJ. facilitating agents. Otolaryngol Head Neck Surg
Serum antibodies against heat shock protein 70 in 2000;122:521–8.
Meniere’s disease. Am J Otol 1995;16:648–52. 72. Yang GS, Song HT, Keithley EM, Harris JP. Intra-
62. Rauch SD, Zurakowski D, Bloch DB, Bloch KJ. Anti- tympanic immunosuppressives for prevention of
heat shock protein 70 antibodies in Meniere’s dis- immune-mediated sensorineural hearing loss. Am J
ease. Laryngoscope 2000;110:1516–21. Otol 2000;21:499–504.
63. Arnold W, Pfaltz R, Altermatt HJ. Evidence of 73. Takasu T, Harris JP. Reduction of inner ear inflam-
serum antibodies against inner ear tissues in the mation by treatment with anti-ICAM-1 antibody.
blood of patients with certain sensorineural hear- Ann Otol Rhinol Laryngol 1997;106:1070–5.
CHAPTER 20
The value and function of the vestibular system may include the peripheral organs, the vestibular division
often be underestimated when considering the vari- of the eighth cranial nerve (CN), the vestibular
ous special senses that we possess. However, of all of nuclei, and the projections to and from the vestibu-
the special senses, unilateral loss of the vestibular lar nuclei. The peripheral organs are endolymph-
system may cause the most significant detriment for filled membranous sacs suspended in the perilymph
our daily function and survival.1 This chapter of the bony labyrinth and consist of two otolith
discusses the common disorders that affect the organs, the saccule and the utricle, and three orthog-
vestibular system and provides a framework for eval- onally oriented semicircular ducts. The saccule is
uation, diagnosis, and treatment of patients with joined to the cochlear duct (scala media) via the
vestibular disorders. The common disorders affect- ductus reuniens. The sensory receptors (vestibular
ing the peripheral vestibular system include benign hair cells) are located in the cristae of the semicircu-
paroxysmal positional vertigo (BPPV), Meniere’s lar ducts and the maculae of the saccule and utricle.
disease, and vestibular neuronitis. The most com- The cristae respond to angular acceleration associ-
mon disorder of the vestibular nerve is a vestibular ated with head rotation, and the maculae are stimu-
schwannoma (VS), accounting for 80% of all cere- lated by linear acceleration caused by translational
bellopontine angle (CPA) lesions.2 This chapter also or tilting head movements. The cristae are normally
discusses some of the other common (meningiomas not sensitive to gravity, and this information is
and epidermoids) and uncommon tumors of the transduced by the maculae. The vestibular organs
CPA that present by injuring the cochleovestibular are innervated by the superior (utricle, lateral and
system. superior semicircular ducts) and inferior (saccule
and posterior semicircular duct) vestibular nerves.
SIMPLIFIED VESTIBULAR ANATOMY The posterior semicircular duct is innervated by the
posterior branch of the inferior vestibular nerve that
AND FUNCTION passes through the foramen singulare. The superior
A brief review of vestibular anatomy and function, and inferior vestibular nerves travel in the internal
nystagmus, and central compensation to vestibular auditory canal (IAC) with the cochlear and facial
injury will facilitate the discussion of peripheral nerves. The vestibular nerves join with the cochlear
vestibular disorders and explain the lack of signifi- nerve to form CN VIII, which crosses the CPA to
cant vestibular symptoms in patients with CPA reach the vestibular nuclei. The vestibular nuclei are
tumors. The vestibular system provides positional located in the pons and have primary projections to
information at rest and positioning information the oculomotor, spinal, cerebellar, autonomic, and
during movement. This information allows us to cerebral areas.3
have visual tracking, perception of space, sense of The vestibular nerves have a baseline tonic fir-
direction, and postural balance during movement ing rate. The fundamental strategy of the vestibular
and rest. The components of the vestibular system system is to compare the relative change in the fir-
408
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 409
ing rate based on the response of paired peripheral tagmus, vomiting, and a sense of falling toward the
organs located in each temporal bone for any given side of the injury.4 Vertigo is defined as the illusion
head movement. For example, a brief head rotation of movement. However, the chief complaint of
to the right in the horizontal plane causes deflec- patients with injury to the vestibular system is usu-
tion of the cupulae of the right and left horizontal ally not vertigo but dizziness. If the complaint is
semicircular ducts. The right cupula is deflected clarified to be vertigo, the duration, periodicity, and
toward the ampullated end of its semicircular duct, circumstance of the vertigo and the presence of
which leads to an increase in the firing rate of the other neurologic signs or symptoms allow for cate-
right vestibular nerve, and the opposite effect occurs gorization of the vertigo. The proximity of the
at the left horizontal duct and left vestibular nerve vestibular system to the auditory system often causes
(Ewald’s laws). This information regarding right vertigo to be coupled with hearing loss. Knowing the
angular acceleration is processed in the vestibular duration of the vertigo or dysequilibrium and the
nuclei and shared with the visual system to allow presence or absence of hearing loss allows narrowing
visual fixation during the head movement and the the differential diagnosis5–7 (Table 20–1). The vertigo
cerebellum and spinal areas to maintain balance may be caused by injury of the peripheral or central
and posture. The response of the visual and balance parts of the vestibular system. Often the presence of
systems to head movements provides a way to study other neurologic abnormalities leads to an investi-
the vestibular system and assess its function during gation for a central cause of the vertigo. However,
injury. The most studied response is the vestibular central vestibular injury caused by a mass lesion or
oculomotor-reflex (VOR). The VOR holds an image stroke may mimic a peripheral vestibular disorder.
on the retina during brief head movement. Under- In the section on vestibular neuronitis, the nystag-
standing the VOR allows us to predict how the eyes mus characteristic of peripheral versus central
should move in response to head movement. In the vestibular disorders is presented.
above example of a brief head movement to the The central compensation for vestibular injury
right, the right part of the vestibular system is stim- occurs via the cerebellum. The cerebellum provides
ulated relative to the left part of the vestibular sys- a “clamping” response to the injured vestibular sys-
tem. The VOR is manifest by contraction of the tem to reduce the effects of the abnormal vestibular
right medial rectus and left lateral rectus muscles. signal. In an acute injury, such as vestibular neu-
This allows the eyes to stay fixed on a point by rela- ronitis, the vertiginous response lasts 3 to 5 days, and
tively moving the eyes to the left as the head moves then the central compensation is able to modulate
to the right. A “fast” reset of the eyes by the oppos- the signal from the injured vestibular system.8 In
ing pair of eye muscles allows visual acquisition of episodic insults, such as that occur in Meniere’s dis-
a new object along the new line of sight. This rapid ease, the central compensation is not able to be as
type of eye movement to acquire a new target is effective, so with each new episode there are acute
called a saccade. If the right semicircular duct is vertiginous symptoms. In a slowly evolving process
persistently stimulated as in a warm caloric test, such as a VS, the central compensation occurs in step
these eye movements (slow phase to the left and fast with the vestibular dysfunction, and the patient may
phase to the right) become repetitive and are called have minimal to no vestibular symptoms. The cen-
jerk nystagmus. The fast phase of the eye movement tral compensation is enhanced by vestibular activity
is to the right; therefore, the nystagmus is called and delayed by prolonged use of medical vestibular
right-beating nystagmus. A few rules will allow pre- suppression. This observation has led to the devel-
dicting the expected nystagmus for stimulation of opment of vestibular rehabilitation programs.
the various semicircular ducts. The eye movements Vestibular rehabilitation programs use three strate-
occur in the same plane as the stimulated semicir- gies: (1) habituation exercises, which facilitate cen-
cular duct, and the fast phase is toward the side of tral compensation by extinguishing pathologic
the stimulated duct or away from an injured responses to head motion; (2) postural control exer-
vestibular organ (Ewald’s laws).1 cises; and (3) general conditioning exercises.
Injury to the peripheral or central vestibular Vestibular rehabilitation is critically important in the
system causes asymmetry in the baseline input into elderly since their ability to have optimal central
the vestibular centers, and this causes vertigo, nys- compensation is diminished.9
410 Ballenger’s Otorhinolaryngology
TABLE 20–1. Differential Diagnosis of Vertigo Based on Time Frame of Vertigo and Presence or Absence of
Hearing Loss
Duration of Vertigo Hearing Loss Absent Hearing Loss Present
Seconds Benign paroxysmal positional vertigo Perilymphatic fistula
Cholesteatoma
Minutes Vertebral/basilar artery insufficiency
Migraines
Hours Vestibulopathy Meniere’s disease
Days Vestibular neuronitis Labyrinthitis
Weeks Central nervous system lesions Vestibular schwannoma
Lyme disease Autoimmune processes
Multiple sclerosis Psychogenic
TABLE 20–2. Vestibular Evaluation occlusion in patients with resistant BPPV, free-float-
ing debris has been observed in the endolymph
1. Head and neck examination including evaluation and has been termed canalolithiasis.15 Electron
of cranial nerves microscopy of these particles shows that they are
2. Spontaneous and gaze-evoked nystagmus with likely otoconia originating from the macula of the
Fresnel glasses gravity-sensitive utricle.16
The cupula of the semicircular duct has the
Direction: fixed-peripheral, changing-central
same specific gravity as the endolymph and so is not
Form: jerk-peripheral, pendular-central sensitive to gravity. However, the debris in the semi-
Fixation: suppression-peripheral, enhanced- circular duct moves in response to gravity, and when
central the patient places the semicircular duct in a depend-
ent position, the particles move and entrain
3. Smooth pursuit: “Follow my fingers”
endolymph with them and cause deflection of the
4. Saccades: “Look to my left or right finger when I cupula. The unexpected gravity-sensitive response
say to” from the semicircular duct causes vertigo. The
Dysmetric: cerebellar majority of BPPV is caused by debris in the poste-
rior semicircular duct, but debris may also enter the
Slow: brainstem
horizontal and superior semicircular ducts.17
Late: frontal lobe
Dysconjugate: multiple sclerosis Natural History The natural history of BPPV
includes an acute onset and remission over a few
5. Head thurst months. However, up to 30% of patients may have
Normal: no refixation saccade symptoms for longer than 1 year. The majority of
Abnormal: refixation saccade (peripheral) patients will improve with a repositioning maneu-
ver. Patients may have unpredictable recurrences
6. Head shake: “10 degrees, 2 cycles/second, 20 and remissions, and the rate of recurrence may be
seconds” 10 to 15% per year.12 These patients may be re-
Normal: no nystagmus treated with a repositioning maneuver. A subset of
Abnormal: horizontal nystagmus-peripheral, patients who have adapted by not using certain
vertical nystagmus-central (brainstem) positions to avoid the vertigo or who have other
balance disorders will benefit from balance rehabil-
7. Dynamic visual activity: “Look at Snellen chart itation therapy.
with head shake”
Normal: < 3 line drop Symptoms and Signs The patient usually com-
plains of a sudden onset of vertigo that lasts 10 to 20
Abnormal: 3 or more line drop—bilateral
seconds with certain head movements. The trigger-
vestibular loss
ing movements include rolling over in bed into a lat-
8. Fixation suppression: “Look at your thumb during eral position, getting out of bed, looking up and
rotation” back, and bending over. The vertigo may be associ-
Normal: no nystagmus ated with nausea. The patients have normal hearing,
no spontaneous nystagmus, and normal neurologic
Abnormal: nystagmus-central (flocculus)
evaluations.10
9. Positional testing: Dix-Hallpike maneuver
Diagnostic Evaluation D IX -H ALLPIKE T EST.
Normal: no nystagmus
Benign paroxysmal positional vertigo is diagnosed
Abnormal: downbeat, fatigable, rotatory by observing a characteristic nystagmus when per-
nystagmus forming the Dix-Hallpike test10 (Figure 20–1). For
10. Cerbellum: finger to nose, rapid alternating testing the right PSCC, the patient sits on the exam-
movements, heel to shin ination table and turns the head 45 degrees to the
11. Posture: Romberg’s test
right. This places the PSCC in the sagittal plane. The
examiner stands facing the patient on the patient’s
412 Ballenger’s Otorhinolaryngology
pate or collapsed with a laser. The occlusion prevents appearance of the utricle, saccule, and endolym-
debris and subsequent endolymph movement to phatic sac.23 In 1870, Friedrich Goltz clarified the
deflect the cupula. There may be a temporary mixed function of the vestibular system by concluding that
hearing loss that usually recovers. The success rate the semicircular canals were responsible for mediat-
for PSCC occlusion is high. A more technically chal- ing equilibrium only and were not involved with
lenging surgical option with increased risk to hear- hearing. The next step in understanding the patho-
ing involves ablating the nerve supply of the PSCC genesis of Meniere’s disease was provided by Knapp
via a singular neurectomy.21 in 1871. He believed that Meniere’s disease was
caused by elevated intracochlear (endolymphatic)
pressure. The clinician’s ability to evaluate vertigo
MENIERE’S DISEASE and nystagmus with caloric, rotational, and galvanic
History and Pathogenesis Meniere’s disease or testing and to differentiate and categorize peripheral
endolymphatic hydrops is an idiopathic inner ear and central vestibular disorders was developed and
disorder characterized by attacks of vertigo, fluctu- introduced by Robert Bárány in the late nineteenth
ating hearing loss, tinnitus, and aural fullness.22 The and early twentieth century.
history of Meniere’s disease parallels our under- The treatment strategies for Meniere’s disease
standing of vestibular anatomy and physiology and were developed based on the mentioned advances in
provides a rationale for treatment of Meniere’s dis- vestibular anatomy and physiology. In 1902, Parry
ease and other vestibular disorders. The recognition performed a CN VIII division for vertigo in a patient
that hearing loss originated in the inner ear has been with suspected Meniere’s disease.23 In 1904, Milligan
long-standing. However, the recognition that vertigo and Lake performed a labyrinthectomy for vertigo,
was linked to the inner ear rather than only to cen- providing a safer alternative than CN VIII section.23
tral sources was first clearly described by Prosper The effectiveness of CN VIII section for Meniere’s
Meniere in 1861.23 In the decade following Meniere’s disease was shown by Dandy in 1928.23 These proce-
description, the function and microscopic anatomy dures caused hearing loss, so hearing preservation
of the vestibular system were further refined. In treatments were developed.23 In 1931, McKenzie per-
1869, Boettcher described the normal microscopic formed a selective vestibular neurectomy.24 The the-
414 Ballenger’s Otorhinolaryngology
ory of increased endolymphatic pressure prompted Meniere’s disease. In recent studies, a decrease in
Portman to open the endolymphatic sac (ES) via a type II vestibular hair cells has been demonstrated in
transmastoid approach in 1926.23 The patients had Meniere’s disease. The role and significance of the
improvement in vertigo and hearing preservation. decrease of these type II hair cells are currently not
The medical management proposed by Frustenberg known.31 The ES has been shown to be important in
in 1934 to treat the increased endolymphatic pres- inner ear metabolic homeostasis. The ES secretes
sure included a low-sodium diet and ammonia salts glycoprotein conjugates in response to osmotic chal-
(acting as diuretics).23 lenges, and preliminary studies have shown alter-
In 1938, Hallpike and Cairns made the most ation in glycoprotein metabolism in Meniere’s
significant advance in understanding the pathogen- disease. There has been no conclusive proof of an
esis of Meniere’s disease by describing the infectious agent related to Meniere’s disease.30,32
histopathology of Meniere’s disease.25 They noted The role of allergy and immune mechanisms
gross dilation of the saccule and scala media with in Meniere’s disease is under investigation. The
obliteration of the perilymph spaces of the vestibule “seat” of immunity in the inner ear may be the ES.
and scala vestibuli and confirmed the concept of The ES is able to process antigens and mount a local
endolymphatic hydrops. Their descriptions caused antibody response. The ES may be vulnerable to
the treatment strategies to focus on the labyrinth. In immune injury because of the hyperosmolarity of
the 1940s and 1950s, Cawthorne popularized the its contents and the fenestrations in its vasculature.
transmastoid labyrinthectomy as the standard of These two properties increase the risk of immune
care for Meniere’s disease.23 In 1948, Fowler used complex deposition and injury. Immunoglobulin
streptomycin, an aminoglycoside, to perform a (Ig) G deposition is seen in the ESs of patients
chemical labyrinthectomy.23 The development of the undergoing ES shunt procedures. Meniere’s patients
operative microscope by Nylén allowed House to also have elevated IgM complexes and C1q compo-
perform the first microsurgical vestibular nerve sec- nent of complement and low levels of IgA com-
tions in 1960.26 The microsurgical approach plexes in their serum. Patients with Meniere’s
improved preservation of hearing and maintenance disease have also shown vulnerability to autoim-
of facial nerve function. The 1990s have seen a resur- mune (cytotoxic) reactions. Thirty percent of
gence in the use of intratympanic gentamicin (a patients with Meniere’s disease had autoantibodies
vestibular selective aminoglycoside) for the treat- to an inner ear antigen by Western blot analysis. The
ment of Meniere’s disease.23,27 response of some patients with Meniere’s disease to
The cause of the endolymphatic hydrops seen corticosteroid therapy and the increased rate of
by Hallpike and Crains in 1938 continues to elude expression of certain human leukocyte antigens
us. The cause of Meniere’s disease has been attrib- (A3, Cw7, B7, and DR2) in Meniere’s disease sup-
uted to anatomic, infectious, immunologic, and port the presence of an underlying immune mech-
allergic factors. The focus of most studies has been anism.33 A similar argument may be made regarding
on the endolymphatic duct and sac, the basic prem- Meniere’s disease and allergy. A significant percent-
ise being that there is increased endolymphatic fluid age (50%) of patients with Meniere’s disease have
owing to impaired reabsorption of the endolym- concomitant inhalant and/or food allergy, and
phatic fluid in the endolymphatic duct and sac. A treating these allergies with immunotherapy and
histopathologic study has shown blockage in the diet modification has improved the manifestations
longitudinal flow of endolymph in the endolym- of their allergy and their Meniere’s disease. The fen-
phatic duct, ES, utricular duct, saccular duct, and estrated blood vessels of the ES may be vulnerable
ductus reuniens.28 Hebbar and colleagues have to vasoactive mediators, such as histamine, that are
reported that the ES in patients with Meniere’s dis- released during an IgE-mediated allergic reaction.
ease is smaller, has less absorptive tubular epithe- Some have suggested a synergistic role of allergy or
lium, and has increased perisaccular fibrosis.29 A viral infection in potentiating the immune abnor-
blinded, controlled study, however, did not show any malities in Meniere’s disease.34
difference in the connective tissue or fibrosis sur-
rounding the ES in Meniere’s disease.30 The vestibu- Epidemiology The incidence of Meniere’s disease
lar duct has also been found to be smaller in ranges from 10 to 150 cases in 100,000 persons per
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 415
year. There is no gender bias, and patients typically TABLE 20–3. Diagnostic Scale for Meniere’s Disease
present in the fifth decade of life. A new diagnosis of of the American Academy of Otolaryngology-Head
Meniere’s disease in someone less than 20 or over 70 and Neck Surgery*
years is unusual. There is no right or left ear
predilection for the disease.35 Certain Meniere’s disease
Definitive Meniere’s disease, plus histopathologic
Natural History Meniere’s disease is characterized
confirmation
by remissions and exacerbations, making it difficult
to predict its future behavior in any individual Definitive Meniere’s disease
patient based on the patient’s own history, diagnos- Two or more episodes of vertigo of at least 20 min
tic evaluations, or epidemiologic profiles. The initial
Audiometrically documented hearing loss on at least
manifestation may be vertigo or hearing loss, but
one occasion
within 1 year of onset, the typical syndrome (attacks
of vertigo, tinnitus, fluctuating hearing loss, and Tinnitus and aural fullness
aural fullness) is present. Longitudinal studies have Probable Meniere’s disease
shown that after 10 to 20 years, the vertigo attacks
One definite episode of vertigo
subside in most patients and the hearing loss stabi-
lizes to a moderate-to-severe level (50 dB HL). Audiometrically documented hearing loss on at least
Meniere’s disease usually affects one ear initially, but one occasion
the risk of developing Meniere’s disease in the other Tinnitus and aural fullness
ear appears to be linear with time. Twenty-five to
45% of patients may develop disease in the second Possible Meniere’s disease
ear.35,36 Episodic vertigo without documented hearing loss
Sensorineural hearing loss, fluctuating or fixed, with
Symptoms and Signs Meniere’s disease occurs
as episodic attacks lasting for hours. The four dysequilibrium but without definitive episodes
symptoms and signs include unilateral, fluctuating *In all scales, other causes must be excluded using any techni-
sensorineural hearing loss; vertigo lasting minutes cal methods (eg, imaging, laboratory, etc). Adapted from Com-
to hours; constant or intermittent tinnitus typi- mittee on Hearing and Equilibrium.22
cally increasing in intensity before or during the
vertiginous attack; and aural fullness. The acute
attack is also associated with nausea and vomiting, AUDIOLOGY. Audiologic assessment initially shows a
and following the acute attack, patients feel low-frequency or low- and high-frequency (inverted
exhausted for a few days. Table 20–3 shows the V) sensorineural hearing loss. As the disease pro-
diagnostic scale for Meniere’s disease created by gresses, there is a flat sensorineural hearing loss.36 A
the Committee on Hearing and Equilibrium of the glycerol dehydration test involves measuring serial
American Academy of Otolaryngology-Head and pure-tone thresholds and discrimination scores dur-
Neck Surgery.22 As emphasized in the diagnostic ing diuresis.38 The diagnosis of Meniere’s disease is
scale, the diagnosis of Meniere’s disease is based on supported if there is improvement in the patient’s
the longitudinal course of the disease rather than hearing. The test is positive in only 50% of patients
on a single attack. suspected of having Meniere’s disease.
action potential (SP/AP) is elevated.39 The SP/AP Deelen and Huizing, in a hydrochlorothiazide, dou-
lacks the specificity or sensitivity to use it to diag- ble-masked, placebo-controlled, crossover study,
nose Meniere’s disease consistently or to predict its showed that diuretics seem to improve the vestibu-
clinical course.37 lar complaints but have no effect on hearing or
tinnitus.43 Some patients benefit from dietary
VESTIBULAR TESTING. Vestibular testing (electronys- restrictions on caffeine, nicotine, alcohol, and
tagmography [ENG] with caloric testing) shows theophylline-containing foods (chocolate). Acute
peripheral vestibular dysfunction. The caloric attacks are managed with vestibular suppressants
response decreases during the first decade of the (meclizine, diazepam) and antiemetic medications
disease and usually stabilizes at 50% of normal (prochlorperazine suppository). The majority of
function.40 patients are controlled with conservative manage-
ment. Medically refractory patients with serviceable
SEROLOGY. Fluorescent treponemal antibody absorp- hearing may undergo intratympanic gentamicin
tion is mandatory in any patient given the diagnosis therapy, ES surgery, or vestibular nerve section.
of an idiopathic disease since syphilis may perfectly Patients without serviceable hearing may undergo
imitate Meniere’s disease. Autoimmune inner ear intratympanic gentamicin therapy or transmastoid
disease may present initially with a Meniere’s pic- labyrinthectomy.
ture. The distinguishing characteristics of an auto-
immune inner ear disease include a more aggressive AMINOGLYCOSIDE. Intratympanic gentamicin was
course and early bilateral involvement. Autoimmune introduced by Schuknecht in 1957 and has seen a
serologic tests may also be helpful. A promising test resurgence in the 1990s by the work of Nedzelski and
is a Western blot looking for anticochlear antibodies others.27 Intratympanic gentamicin is absorbed into
that can bind to a 68 to 70 kD antigen.41 the inner ear primarily via the round window and
selectively damages the vestibular hair cells relative to
IMAGING. Magnetic resonance imaging with gadolin- the cochlear hair cells. Gentamicin may also decrease
ium contrast allows the exclusion of retrocochlear endolymph production by affecting dark cells in the
pathology, such as a VS. An imaging scan is not stria vascularis.44 Intratympanic gentamicin has
mandatory with a classic course of Meniere’s disease nearly a 90% vertigo control rate with a follow-up of
leading to a clinical diagnosis. Imaging should be
at least 2 years, and the extent of hearing loss depends
obtained if the initial presentation or course is
on the protocol for gentamicin delivery. A variety of
unusual or if surgical management is planned.
treatment protocols (daily, biweekly, weekly, monthly
Management In considering the management of injections) using fixed-dose or titration end-point
Meniere’s disease, an observation by Dandy rings regimens exist, but few trends are present. Treatments
true: “The syndrome is one that lends itself well for are stopped if there is persistent hearing loss. Vertigo
a time to statistical conclusions because of the control is nearly always obtained if vestibular func-
marked variations in the frequency of attacks. Some tion is ablated. However, the risk of hearing loss
patients will go for months or even years between increases as the total dose and frequency of gentam-
attacks and what is done last gets the credit for the icin injections are increased. Current protocols are
free interval…”24 Since the introduction of amino- reducing the dose and frequency of injections to
glycoside therapy in 1948, no significant conceptual decrease hearing loss and still obtain vertigo control.
advances have been made in the treatment of Vertigo control may be obtained with some residual
Meniere’s disease. The current treatments focus on vestibular function present, and this residual func-
relieving vertigo without further injuring the hear- tion may be useful if patients develop bilateral
ing. Hearing may be temporarily improved or stabi- Meniere’s disease. Recent studies with weekly or
lized by the current treatments, but the hearing does monthly injections have shown nearly 90% vertigo
not have long-term stability. control with 7 to 17% < 30 dB hearing loss and less
than 1% ≥ 30 dB hearing loss.27,44,45
MEDICAL TREATMENT. The primary management of
Meniere’s disease involves a low-sodium diet (1,500 SURGERY. Patients who have failed medical and gen-
mg/d) and diuretics (hydrochlorothiazide).42 Van tamicin treatment may require surgical intervention.
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 417
Endolymphatic sac surgery and vestibular nerve sec- shunt surgery provides a nondestructive option for
tions preserve hearing, whereas labyrinthectomy patients who fail medical or aminoglycoside therapy
ablates hearing. and have good hearing. The role of endolymphatic
surgery is currently in decline with the renewed
ENDOLYMPHATIC SAC. Endolymphatic sac surgery interest in intratympanic aminoglycoside therapy.
involves a mastoidectomy and locating the ES on the
posterior fossa dura (Figure 20–3, A). The sac is VESTIBULAR NERVE SECTION. Vestibular nerve section
medial to the sigmoid sinus and inferior to the provides a definitive treatment of unilateral Men-
PSCC. The ES is also located along an imaginary line iere’s disease in patients with serviceable hearing.
(Donaldson’s line) in the plane of the horizontal Ninety-five percent of patients achieve vertigo con-
semicircular canal. The ES may be decompressed or trol, and hearing is preserved in over 95% of
have a shunt placed that communicates into the sub- patients.37 The vestibular neurectomy may be
arachnoid space or mastoid cavity. The “sham” approached via a retrosigmoid or middle fossa
study, a double-masked, placebo-controlled com- approach (Figure 20–3, B). These procedures are
parison of the endolymphatic mastoid shunt versus described in detail in the CPA section. The risk to
a cortical mastoidectomy, by Thomsen et al showed the facial nerve is less than 1% in the retrosigmoid
that ES surgery provides no greater benefit than per- approach and less than 5% in the middle fossa
forming a cortical mastoidectomy.46 A 9-year follow- approach. The advantage of the middle fossa
up showed 70% control of vertigo in both surgical approach is sectioning the vestibular nerves in the
groups.47 Reanalysis of the sham study suggested a IAC lateral to where they join the cochlear nerve in
greater benefit in the ES surgery group, and a recent the CPA.49 The patients are acutely vertiginous and
study with a 5-year follow-up showed an 88% func- have nystagmus (fast phase away from the operated
tional level 1 or 2 response after an endolymphatic ear) for a few days until central compensation takes
mastoid shunt operation.48 The success rates have effect. The hearing appears to degenerate in the
great variation in the literature, so the benefit of ES postoperative patient in accordance with the natural
surgery is not universally accepted. Endolymphatic history of Meniere’s disease.
FIGURE 20–3. Two hearing-preserving operations for Meniere’s disease include endolymphatic sac (ES) surgery and
vestibular nerve section. A, Endolymphatic sac surgery (left ear) involves a mastoidectomy and locating the ES on the
posterior fossa dura (PFD). The sac is located posterior to the mastoid segment of the facial nerve (7), inferior to the
posterior semicircular canal (PSCC), and superior to the jugular bulb (JB). The ES may be decompressed or have a
shunt placed that communicates into the mastoid cavity. Endolymphatic shunt surgery provides a nondestructive
option for patients who fail medical or aminoglycoside therapy and have good hearing. LSCC and SSCC = lateral and
superior semicircular canals. B, Vestibular nerve section provides a definitive treatment of vertigo in patients with serv-
iceable hearing. The vestibular neurectomy may be approached via a retrosigmoid or middle fossa approach. The art-
work shows a completed left retrosigmoid vestibular neurectomy with sectioning of the vestibular nerve (v) and
preservation of the cochlear nerve (c). 8 = vestibulocochlear nerve near the pons; 5 = trigeminal nerve; Fl = flocculus;
Ch = choroid plexus. Reproduced with permission from Jackler RK.50
418 Ballenger’s Otorhinolaryngology
LABYRINTHECTOMY. A transmastoid labyrinthectomy lasts a few days with complete or at least partial
with fenestration of the bony semicircular canals recovery within a few weeks to months. Some
and vestibule and removal of the membranous neu- patients (15% in one study) may have significant
roepithelium provides control of vertigo in nearly all vestibular symptoms even after 1 year.55 Recurrent
patients with unilateral Meniere’s disease and poor attacks in the same or contralateral ear have been
hearing. The rate of control may decline by 10 years reported but are unusual. Some patients may later
owing to development of vertebral basilar artery develop BPPV. The majority of patients have com-
insufficiency (aging), poorer vision, and develop- plete recovery. The few patients who have persistent
ment of Meniere’s disease in the contralateral ear. vestibular symptoms should have vestibular rehabil-
The complete loss of unilateral vestibular function itation therapy.
owing to the labyrinthectomy leads to unsteadiness
in up to 30% of patients.51 Symptoms and Signs The presentation of ves-
tibular neuronitis includes the sudden onset of
vertigo with nausea and vomiting. The patient has
VESTIBULAR NEURONITIS
normal hearing and a normal neurologic examina-
A case of vestibular neuronitis was described in 1909 tion. The patient may have postural instability
by Ruttin, and the term vestibular neuronitis was toward the injured ear but is still able to walk with-
coined by Hallpike in 1949.52 Vestibular neuronitis is out falling. The patient usually does not have a
the third most common cause of peripheral vestibu- headache. The patient has spontaneous nystagmus
lar vertigo following BPPV and Meniere’s disease.53 characteristic of an acute peripheral vestibular
The presentation includes acute vertigo. Like injury. The nystagmus is usually horizontal with a
Meniere’s disease, the pathogenesis is not known, torsional component and is suppressed by visual fix-
but the majority of patients recover, with no seque- ation. The reduction in vestibular signal in the
lae. The primary role of the physician is to rule out injured ear leads to relative vestibular excitation in
a central cause of the acute vertigo. The treatment is the opposite ear. The result is that the slow phase of
primarily supportive care. nystagmus is toward the injured ear and the fast
phase is away from the injured ear. The nystagmus is
Epidemiology Vestibular neuronitis has no gen-
intensified by looking toward the fast phase and is
der bias and typically affects middle-aged people.
decreased by looking toward the slow phase or
Less than half of the patients will have an antecedent
toward the injured ear. This principle is Alexander’s
or concurrent viral illness.52
law. The direction of the nystagmus does not change
Pathogenesis The proposed causes of vestibular with changes in the direction of gaze.56
neuronitis include viral infection, vascular occlu-
Diagnostic Evaluation The diagnosis of vestibular
sion, and immune mechanisms. The evidence to
neuronitis is based on the constellation of findings
support a viral cause is limited by lack of pathologic
described above. The need for further evaluation is
tissue to study, and the evidence based on serocon-
version remains unconvincing. Therefore, support necessary only if there is a concern for a central cause
for the viral cause remains rare and circumstantial. of the acute vertigo or the acute vertigo does not sub-
The study of the available temporal bones of patients stantially improve in 48 hours.56 The primary central
with vestibular neuronitis shows a spectrum of cause for acute vertigo lasting days is a brainstem or
injury. There may be no abnormality seen to signif- cerebellar stroke. In the majority of cases, there will
icant degenerative changes in the vestibular nerve, be other neurologic findings: diplopia, dysmetria,
Scarpa’s ganglia, and vestibular neuroepithelium. dysarthria, motor and sensory deficits, abnormal
The injury is often seen in the superior vestibular reflexes, inability to walk without falling, and central
nerve. In terms of a vascular cause, there was no evi- nystagmus. Central nystagmus is not affected by
dence of vascular occlusion affecting the vestibular visual fixation and may change directions with
system in any of the temporal bones studied.52,54 changes in gaze. Purely vertical or purely torsional
nystagmus is highly suggestive of a central disorder.57
Natural History The natural history of vestibular In the event of an isolated inferior cerebellar stroke,
neuronitis includes an acute attack of vertigo that the presentation may be indistinguishable from
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 419
vestibular neuronitis. Twenty-five percent of patients TABLE 20–4. Cerebellopontine Angle (CPA) Lesions
with risk factors for stroke who present with vertigo,
nystagmus, and postural instability have had an infe- Common CPA lesions
rior cerebellar stroke.58 Therefore, patients with sig- Schwanommas (cranial nerves VIII, VII, V)
nificant risk factors for stroke should have an
Meningiomas
imaging study if they present with acute vertigo, nys-
tagmus, and postural instability. Epidermoids
Congenital rest lesions
VESTIBULAR TESTING. Vestibular testing in vestibular
Epidermoids
neuronitis shows an absent or reduced caloric
response in the injured ear in the majority of Arachnoid cysts
patients. The caloric responses eventually become Lipomas
normal in 42% of patients.59
Vascular lesions
IMAGING. Magnetic resonance imaging with empha- Hemangiomas
sis on identification of both infarction and hemor- Paragangliomas (glomus jugulare tumors)
rhage in the brainstem and cerebellum is obtained in
patients with risk factors for stroke, patients with Aneurysms
additional neurologic abnormalities, and patients Hemangioblastomas
who do not show improvement within 48 hours. Intra-axial tumors
The other option is a computed tomographic (CT)
scan with thin cuts evaluating the brainstem, cere- Medulloblastomas
bellum, and fourth ventricle. Astrocytomas
Gliomas
Management SUPPORTIVE CARE. The primary man-
agement includes symptomatic and supportive care Fourth ventricle tumors
during the acute phase of the illness. Patients are Hemangioblastomas
given vestibular suppressants and antiemetics to con-
trol the vertigo, nausea, and vomiting. These medica- Lesions extending from the skull base
tions are withdrawn as soon as possible to not Cholesterol granulomas
interfere with the central vestibular compensation.8 Glomus complex tumors
Chordomas
CEREBELLOPONTINE ANGLE TUMORS Chondrosarcomas
The CPA consists of a potential cerebrospinal fluid Metastases
(CSF)-filled space in the posterior cranial fossa
bounded by the temporal bone, cerebellum, and
brainstem. The CPA is traversed by CNs V to XI, and
the facial (VII) and vestibulocochlear (VIII) nerves
are most prominent. Cerebellopontine angle tumors sion of the neurovascular structures in and around
account for 10% of all intracranial tumors (Table the CPA. The classic description of these symptoms
20–4). Nearly 90% of all CPA tumors are VSs by Cushing includes initially unilateral hearing loss,
(acoustic neuromas) and meningiomas.60 Other vertigo, nystagmus, altered facial sensation, facial
CPA lesions include congenital rest lesions (epider- pain that later progresses to facial palsy, vocal cord
moids, arachnoid cysts, lipomas), schwannomas of palsy, dysphagia, diplopia, respiratory compromise,
other CNs, intra-axial tumors, metastases, vascular and death (Table 20–5). This description highlights
lesions (paragangliomas, hemangiomas), and lesions the untreated natural history of CPA tumors.62
extending from the skull base (cholesterol granulo- The treatment of CPA tumors includes obser-
mas, chordomas).61 Cerebellopontine angle lesions vation, surgical removal, and irradiation. The key
become clinically symptomatic by causing compres- clinical developments in the management of CPA
420 Ballenger’s Otorhinolaryngology
TABLE 20–5. Cerebellopontine Angle Syndrome men of Luschka, opens into the CPA. Cranial nerves
V to XI traverse the cephalic and caudal extent of the
Unilateral hearing loss CPA. The central structures crossing the CPA to and
Tinnitus from the IAC are the facial (CN VII) and vestibulo-
cochlear (CN VIII) nerves, respectively.64
Vertigo
Cranial nerves VII and VIII are covered with
Hypesthesia and neuralgia central myelin provided by neuroglial cells as they
cross the CPA and carry a sleeve of posterior fossa
Nystagmus dura into the IAC. The transition to peripheral
Facial palsy myelin made by Schwann cells occurs at the medial
opening of the IAC. The vestibulocochlear nerve
Vocal cord palsy divides into three nerves: the cochlear nerve and the
superior and inferior vestibular nerves in the lateral
Dysphagia
extent of the CPA or medial part of the IAC. The
Diplopia IAC is divided into four quadrants by a vertical crest,
called Bill’s bar, and a transverse crest. The CN VII
Respiratory compromise comes to lie in the anterosuperior quadrant and is
Death anterior to the superior vestibular nerve and supe-
rior to the cochlear nerve, whereas the inferior
vestibular nerve lies in the posteroinferior quadrant
and is inferior to the superior vestibular nerve and
posterior to the cochlear nerve (see Figure 20–4).
tumors include placing an emphasis on earlier diag- The anterior inferior cerebellar artery (AICA) is the
nosis by Cushing in 1917 and a dogma change in main artery in the CPA and is the source of the
1925 by Dandy from rapid tumor enucleation to labyrinthine artery. The labyrinthine artery courses
meticulous, hemostatic total tumor removal.63 Fun- via the IAC and is an end artery for the hearing and
damental technical advances allowing diagnosis and balance organs. The AICA has a variable relationship
surgical removal include the advent of modern to CN VII and VIII and to the IAC.64
imaging and the introduction of the surgical micro-
scope by House and Doyle in 1961. House helped Common Cerebellopontine Angle Lesions The
create the field of neurotology and brought the sur- three most common tumors of the CPA are schwan-
gical management of CPA tumors into the modern nomas, meningiomas, and epidermoids. Each of
era.23,24 these tumors has a similar clinical presentation, and
The focus of this section includes understand- they are primarily differentiated by their imaging
ing the anatomy of the CPA; describing the patho- characteristics. The treatment for these three lesions
genesis of VSs, meningiomas, and epidermoids; and is surgical resection without injuring the neurovas-
providing a clinical context to diagnose, counsel, and cular structures of the CPA.
treat patients with various CPA tumors.
VESTIBULAR SCHWANNOMAS. Vestibular schwannomas
Anatomy The CPA is roughly triangular shaped in are nerve sheath tumors of the superior and inferior
the axial plane and is filled with CSF (Figure 20–4). vestibular nerves.65 They arise in the medial part of
The superior boundary is the tentorium, and the the IAC or lateral part of the CPA and cause clinical
inferior boundary is the cerebellar tonsil and symptoms by displacing, distorting, or compressing
medullary olives. The anterior border is the poste- adjacent structures in the CPA.
rior dural surface of the petrous bone and clivus,
and the posterior border is the ventral surface of the EPIDEMIOLOGY. Vestibular schwannomas, incorrectly
pons and cerebellum. The medial border is the cis- called acoustic neuromas, are by far the most com-
terns of the pons and medulla, and the apex is the mon tumor involving the CPA.2 Vestibular schwan-
region of the lateral recess of the fourth ventricle. nomas make up 80% of CPA tumors and 8% of all
The lateral opening of the fourth ventricle, the fora- intracranial tumors. Various epidemiologic studies
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 421
FIGURE 20–4. In the axial plane, the cerebellopontine angle (CPA) has a triangular shape. The CPA is bounded by the
cerebellum (Cb), petrous bone, and brainstem. Cranial nerves V (5) to XI traverse the cephalic and caudal extent of
the CPA. The central structures crossing the CPA to and from the internal auditory canal (IAC) are the facial (7) and
vestibulocochlear nerves (8), respectively. The vestibulocochlear nerve divides into three nerves: the cochlear nerve (C)
and the superior (SV) and inferior vestibular (IV) nerves in the lateral extent of the CPA or medial part of the IAC.
The inset diagram shows a cross-section of the IAC. The IAC is divided into four quadrants by a vertical crest, called
Bill’s bar, and a transverse crest. The facial nerve comes to lie in the anterosuperior quadrant and is anterior to the supe-
rior vestibular nerve and superior to the cochlear nerve, whereas the inferior vestibular nerve lies in the posteroinfe-
rior quadrant and is inferior to the superior vestibular nerve and posterior to the cochlear nerve. CO = cochlea; GG =
geniculate ganglion; ME = middle ear; EAC = external auditory canal; M = mastoid; SCC = semicircular canals; SS =
sigmoid sinus; 4V = fourth ventricle; P = pons. Reproduced with permission from Jackler RK.50
ganglia in the IAC having the highest concentration ponents, and therefore has a firm to soft texture
of Schwann cells.67 depending on the solid to cystic components.
Recent studies have improved our molecular
Microscopic. Microscopic evaluation shows the
understanding of VSs. Vestibular schwannomas
surface connective tissue capsule to be only 3 to 5
occur owing to mutations in the gene for the tumor
µm in thickness.75 The classic histologic findings
suppressor protein merlin, located on chromosome
include areas of densely packed cells with spindle-
22q12.68,69 Merlin is a cytoskeletal protein and may
shaped nuclei and fibrillar cytoplasm intermixed
have a role in cell-cell contact inhibition.70 The for- with hypocellular areas containing vacuolated, pleo-
mation of VSs requires mutations of both copies of morphic cells. These dense regions are called Antoni
the merlin gene. One functioning merlin gene will A areas, and the hypocellular regions are called
prevent the formation of VSs. Somatic mutations in Antoni B areas. Within the Antoni A areas, the pal-
both copies of the merlin gene will result in spo- isades of the nuclei are termed Verocay bodies.76 His-
radic VSs. The probabilities of two spontaneous, tologic sections also show prominent, thick-walled
independent mutations at one locus predict a uni- vessels. As stated earlier, the cell of origin is the
lateral VS presenting in the fourth to sixth decade Schwann cell, so VS sections stain with S-100
of life.71 immunoperoxidase.
In contrast, familial VSs occurring in NF2
require only one somatic mutation event. In NF2, NATURAL HISTORY. The natural history of VSs
patients inherit one mutated merlin gene and one includes a slow rate of growth in the IAC and then
normal merlin gene. A mutation in the normal allele into the cistern of the CPA. Studies show that peri-
leads to bilateral VSs by the age of 20. Therefore, ods of growth are intermixed with periods of quies-
NF2 is autosomal recessive at the gene level since cence. The average growth rate is 1.8 mm/year.77 This
disease expression requires mutations in both alleles slow growth causes progressive and often insidious
of the gene, but the inheritance is autosomal domi- symptoms and signs as there is displacement, distor-
nant (pseudodominant) since inheritance of one tion, and compression of the structures first in the
mutated allele often leads to the disease state. Neu- IAC and then in the CPA. This slow growth via cel-
rofibromatosis 2 is a central form of neurofibro- lular proliferation provides a predictable progression
matosis, with patients having central nervous system of symptoms and signs. Occasionally, the tumor may
tumors including schwannomas, meningiomas, and undergo rapid expansion owing to cystic degenera-
gliomas. The great majority of these patients will tion or hemorrhage into the tumor. A rapid expan-
develop bilateral VSs. In comparison, patients with sion causes rapid movement along the subsequently
NF1 (von Recklinghausen’s disease) have intra- and described phases of VS symptoms and may cause
extracranial tumors, and less than 5% of these rapid neurologic deterioration.
patients will form unilateral VSs.72,73 Interestingly, The initial intracanalicular growth affects the
the cranial evaluation of two children recovered vestibulocochlear nerve in the rigid IAC and causes
from a 4,000-year-old burial site showed widened unilateral hearing loss, tinnitus, and vertigo or dyse-
IACs. These siblings likely had VSs owing to NF2.74 quilibrium. These three symptoms are the typical
Genetic screens for the NF2 mutation have presenting complaints of not only patients with VS
been developed and are the basis for genetic coun- but also of those with other lesions of the CPA.
seling for family members of NF2 patients. The Interestingly, the motor component of the facial
severity of mutation involving the merlin gene in nerve is resistant to injury during this phase of
NF2 can predict the severity of disease manifesta- growth, and patients have normal facial function.
tion.71 The study of VSs in NF2 has provided insight The tumor then grows into the CPA cistern and
into not only this disease but also the cause of spo- grows freely without causing significant new symp-
radic VSs and has demonstrated a very interesting toms because structures in the CPA are initially dis-
genetic inheritance mechanism. placed without injury (Figure 20–5, A). As the tumor
approaches 3 cm, the tumor abuts on the boundaries
PATHOLOGY. Gross. Vestibular schwannomas have a of the CPA and results in a new set of symptoms and
smooth surface with a yellow to gray color. The signs. Compression of the CN V causes corneal and
tumor is usually solid, with occasional cystic com- midface numbness or pain. Further distortion of CN
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 423
VIII and now CN VII causes further hearing loss and Twenty percent will have an episode of sudden
dysequilibrium, as well as facial weakness or spasms. hearing loss.80 The improvement of hearing loss
Brainstem distortion leads to narrowing of the with or without treatment does not rule out retro-
fourth ventricle (Figure 20–5, B). Further growth cochlear disease. The level of hearing loss is not a
leads to the final clinical spectrum described by clear predictor of tumor size.
Cushing in the CPA syndrome.62 The patient devel- Tinnitus is present in 65% of patients. The tin-
ops cerebellar signs owing to compression of the nitus is most often constant, with a high-buzzing
flocculus and cerebellar peduncle. The patient also pitch. This symptom is often not reported by
develops obstructive hydrocephalus owing to closure patients because of the focus on the accompanying
of the fourth ventricle. The increasing intracranial hearing loss. Similarly, because of the central com-
pressure manifests in ocular changes, headache, pensation for the slowly evolving vestibular injury,
mental status changes, nausea, and vomiting. If the patients tolerate and adapt well to the dysequilib-
VS continues to grow without intervention, death rium. The majority of patients will have self-limiting
occurs owing to respiratory compromise.78 episodes of vertigo. The dysequilibrium is initially
mild and constant and often does not prompt a
S YMPTOMS AND S IGNS . Hearing loss is present in medical visit. Dysequilibrium is present in 60% of
95% of patients with VSs.78,79 Conversely, 5% of patients.
patients will have normal hearing, so unilateral Facial and trigeminal nerve dysfunction occurs
vestibular or facial complaints without hearing loss after the auditory and vestibular impairments.
do not rule out retrocochlear disease. Of the Patients usually have midface (V2) numbness and
patients with hearing loss, most will have slowly often have an absent corneal reflex. The motor sup-
progressive hearing loss with noise distortion. ply of the trigeminal nerve to the muscles of masti-
FIGURE 20–5. Axial T1-weighted magnetic resonance images with gadolinium show the progressive growth pattern of
a vestibular schwannoma. Vestibular schwannomas are centered in the internal auditory canal (IAC), expand the IAC,
are globular in shape, and enhance with gadolinium. A, Vestibular schwannoma involves the IAC and cistern of the
cerebellopontine angle. The tumor has solid and cystic components. B, Vestibular schwannoma has expanded the IAC
and is causing significant compression of the brainstem and cerebellum. The brainstem distortion leads to narrowing
of the fourth ventricle. (Courtesy of Nancy J. Fischbein.)
424 Ballenger’s Otorhinolaryngology
cation is rarely affected. The sensory component of intensity. This phenomenon is called rollover. Poor
the facial nerve is first affected, which causes numb- SDSs are present in about one half of the patients
ness of the posterior part of the external auditory with VSs. An abnormal SDS should trigger an imag-
canal and is referred to as Hitzelberger’s sign. Facial ing evaluation, but a normal SDS does not rule out
weakness or spasm occurs in 17% of patients and a VS. Loss of the acoustic reflex or acoustic reflex
usually leads to a diagnosis of VS within 6 decay is noted in most patients with VSs, but normal
months.78,79 acoustic reflexes do not preclude a VS. In summary,
With large VSs or tumors that have undergone asymmetric hearing loss, out-of-proportion deterio-
rapid expansion, patients will have visual complaints ration in the SDS, and abnormal acoustic reflexes
of decreased visual acuity and diplopia owing to mandate an imaging evaluation to rule out a retro-
compromise of CN II, IV, or VI. Hydrocephalus cochlear lesion. The majority of patients with VSs
leads to complaints of headache, altered mental will have one of these abnormalities on audiologic
status, nausea, and vomiting; on examination, analysis. The minority of the patients with subtle
patients have increased intracranial pressure and complaints and normal auditory evaluations fall
papilledema. Compression of the lower CNs IX and into an area of diagnostic dilemma.82 The likelihood
X causes dysphagia, aspiration, and hoarseness, and of having a retrocochlear lesion may be very small,
examination reveals a poor gag reflex and vocal cord but the patient or physician may feel compelled by
paralysis. the patient’s complaints to obtain audiometric test-
ing. There is no clear management algorithm, and
DIAGNOSTIC EVALUATION. The average patient will
the physician must make a decision whether imaging
require 4 years from the onset of symptoms to diag-
evaluation is needed. Regardless of the decision, the
nosis. The diagnostic dilemma lies in choosing the
most important part of the diagnostic plan should
appropriate patient to pursue audiologic and imag-
include patient counseling regarding the future
ing studies. Although 5% of patients with VSs may
symptoms and signs of CPA tumors and the need
present in an atypical fashion, the majority of
for planned follow-up.
patients will present with complaints of unilateral
hearing loss or hearing distortion, unilateral tinni- Vestibular Testing. Vestibular testing does not
tus, vertigo or dysequilibrium, or facial numbness, provide a sensitive or specific means of diagnosing
weakness, or spasm. These patients with unilateral VSs. The most common test obtained to evaluate
auditory, vestibular, and facial complaints are not a vestibular complaints is ENG with caloric testing. An
diagnostic dilemma and need to undergo careful ENG in a patient with a VS will show reduced caloric
evaluation to rule out retrocochlear disease. The ini- response in the affected ear. The extent of vestibular
tial step in the evaluation includes an audiologic function present predicts the amount of postopera-
assessment. If the audiologic assessment suggests a tive vertigo. The location of the VS on the inferior or
retrocochlear lesion, then imaging of the CPA is per- superior vestibular nerve may also be predicted by
formed to rule out a retrocochlear lesion. Vestibular the ENG since the ENG primarily evaluates the lat-
testing lacks specificity in diagnosing VSs. eral semicircular canal. The lateral semicircular canal
is innervated by the superior vestibular nerve.83
Audiology. The standard auditory evaluation
should include pure-tone audiometry, speech dis- Auditory Brainstem Response. Auditory brain-
crimination scores (SDSs), acoustic reflex thresh- stem response (ABR) is the measured electrical
olds, and acoustic reflex decay. Pure-tone audiometry response of the cochlea and its brainstem pathway to
of patients with VSs shows asymmetric, down-slop- short-duration broad-band clicks. The evoked
ing, high-frequency, sensorineural hearing loss in response is a characteristic waveform with five iden-
almost 70% of patients. The hearing may also be tifiable peaks (I to V). The absolute latency or tim-
normal, or the hearing loss may involve only the low ing of each wave is recorded. In patients with VSs,
frequencies or have a flat, trough, or peak configura- the ABR is partially or completely absent, or there is
tion.81 Retrocochlear hearing loss causes SDSs to be a delay in the latency of wave V on the affected side.
lower than predicted by the pure-tone thresholds. The delay may be an absolute delay based on nor-
This out-of-proportion depression of SDSs is fur- mative data or a delay compared to the latency of
ther accentuated when retested at a higher speech wave V on the other side. An interaural delay of wave
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 425
V greater than 0.2 ms is considered abnormal. Over- intracanalicular tumors unless there is bony expan-
all, ABR has a sensitivity of > 90% and a specificity sion of the IAC.
of 90% in detecting VS. However, when only con-
sidering intracanalicular tumors, 18 to 33% of MANAGEMENT. Surgery. The primary management
tumors will be missed.84 As the detection limits and for VSs is surgical removal. The roles of observa-
costs of imaging studies have improved, the role of tion and radiotherapy are currently for patients
ABR in diagnosis of VS has dramatically declined. In who cannot tolerate a surgical procedure or have a
the future, there will likely be no clear role for ABR life span of less than 5 years. The role of radiother-
in VS diagnosis. apy is expanding. The majority of patients will
undergo surgical excision because the natural his-
Imaging. Magnetic resonance imaging with
tory of VSs is to grow and eventually cause
gadolinium contrast provides the gold standard for
significant compression of the structures sur-
VS diagnosis or exclusion.85 The MRI scan also allows
rounding the CPA, as described above. In addition,
for surgical planning. Typically, a series of T1-
the ability to accomplish total tumor removal with
weighted images in which CSF is dark and fat is the least morbidity is generally related to the size of
bright, a T1-weighted image with gadolinium con- the tumor, so significant surgical delay is not
trast, and a T2-weighted image in which CSF is bright recommended.
are obtained. The images are in 2 to 4 mm contigu- Surgical approaches to the CPA include
ous or overlapping slices. The various lesions within translabyrinthine, retrosigmoid, and middle fossa
the CPA may be differentiated based on their varying craniotomies (Figure 20–6, A). The appropriate
imaging and enhancing characteristics. The MRI approach for a particular patient is based on the
characteristics of a VS include a hypointense globu- hearing status, size of the tumor, extent of IAC
lar mass centered over the IAC on a T1-weighted involvement, and experience of the surgeon (Table
image with enhancement when gadolinium is added. 20–6). The approaches are either hearing preserving
Vestibular schwannomas are iso- to hypointense on or ablating. The retrosigmoid and middle fossa
T2-weighted images86 (see Figure 20–5). The two approaches are hearing preserving. However, they
detractors to the many advantages of MRI, including have limitations of exposure to all aspects of the
lack of radiation exposure, are the time and cost of CPA and IAC. The middle fossa approach is well
each scan. These two issues are being addressed by suited to patients with good hearing and a tumor
developing imaging sequences that focus on the CPA less than 2 cm. The retrosigmoid approach is well
and do not use contrast administration. One exam- suited to patients with good hearing and a tumor
ple is a high-resolution fast spin echo T2-weighted less than 4 cm and not involving the lateral part of
sequence.87 This scanning strategy uses CSF as the the IAC. The lateral part of the IAC is usually only
contrast agent. Fast spin echo T2-weighted scans can directly accessible via a retrosigmoid approach by
be done in 15 to 20 minutes and cost less compared removing the PSCC. The violation of the PSCC will
with a standard MRI with intravenous contrast lead to hearing loss. The translabyrinthine approach
administration. The drawback is a slight loss in sen- causes total hearing loss and so is appropriate for
sitivity owing to false-negative readings of very small patients with poor hearing (pure-tone average
tumors. The steady improvements in the quality and > 30 dB) or patients with good hearing and tumors
cost of MRIs have made MRI the preferred diagnos- not accessible by the hearing-preserving approaches.
tic modality for CPA tumors. The surgical technique for these procedures will be
In situations for which MRI cannot be used or briefly described. Three critical issues inherent to all
is not accessible, a CT scan with iodine contrast or three techniques are the extent of exposure of the
an ABR offers a reasonable alternate screening IAC and CPA, identification and preservation of the
modality. A CT scan with contrast provides consis- facial nerve, and extent of brain retraction. These
tent identification of CPA tumors over 1.5 cm or operations use electrophysiologic monitoring of CN
CPA tumors that at least have a 5 mm CPA compo- VII and an ABR in hearing-preserving approaches.
nent. Vestibular schwannomas appear as ovoid The use of high-speed drills, craniotomies, and
masses centered over the IAC with nonhomogenous operating microscopes has brought VS removal into
enhancement. A CT scan with contrast can miss the modern age.50,88
426 Ballenger’s Otorhinolaryngology
TABLE 20–6. Surgical Approaches to the Cerebellopontine Angle and Their Indications
Hearing preserving
Retrosigmoid: good hearing and tumor not involving the lateral internal auditory canal
Middle fossa: good hearing and tumor less than 2 cm, internal auditory canal tumors
Hearing ablating
Translabyrinthine: poor hearing or larger tumors not accessible by other approaches
Translabyrinthine Approach. The primary ap- ital approach used by neurosurgeons to address
proach for removal of VS is the translabyrinthine most posterior fossa lesions. The retrosigmoid
approach. The boundaries of the approach include approach is a versatile approach with a panoramic
the facial nerve and cochlear aqueduct anteriorly, view of the CPA from the foramen magnum inferi-
middle fossa dura superiorly, posterior fossa dura orly to the tentorium superiorly (Figure 20–6, B).
posteriorly, and jugular foramen inferiorly (see Fig- The medial two-thirds of the IAC are also accessible
ure 20–6, A). These boundaries are approached via without violating the inner ear; therefore, hearing is
the familiar postauricular incision. A complete canal preserved.
up mastoidectomy is accomplished, with identifica- The surgical technique starts with a curvilinear
tion of the incus, tegmen, sigmoid sinus, and facial skin incision 6 cm behind the ear over the retromas-
nerve. A compete labyrinthectomy is then performed toid region. The soft tissue and posterior nuchal
with medial skeletonization of the middle and poste- musculature are elevated to expose the mastoid and
rior fossa dura and decompression of the sigmoid retromastoid bone. A 5 × 5 cm craniotomy is per-
sinus to the jugular foramen. After bony skeletoniza- formed with the sigmoid sinus as the anterior
tion of the IAC, the dura of the IAC is opened and the boundary and the transverse sinus the superior
facial nerve is identified medial to the vertical crest boundary. Elevation of a bone plate is technically
(Bill’s bar). Once the facial nerve is identified in the difficult, so the bone may be removed by drilling.
fundus or lateral aspect of the IAC, tumor removal The bone fragments are collected and will be
occurs from lateral to medial along the IAC. In large replaced during closure. The bone fragments will
tumors, the tumor is debulked internally, and then the reform a bone plate and prevent adherence of the
tumor capsule is removed from the surrounding musculature to the dura. If decompression of the
structures including the facial nerve. After tumor sigmoid sinus is needed for exposure, a mastoidec-
removal, abdominal fat is placed into the defect. tomy may also be performed. The dura is then
The three advantages of the translabyrinthine opened along the sigmoid sinus, and the cerebellum
approach are the ability to remove tumors of all is seen. The CSF from the cisterna magnum should
sizes, minimal retraction of the brain, and the abil- be released prior to retracting the cerebellum.
ity to visualize directly and preserve the facial nerve. Medial retraction of the cerebellum allows visualiza-
The rate of facial nerve preservation is 97%. The rate tion of the CPA. To address the IAC component of
the tumor, the posterior bone of the IAC should be
of CSF leak presenting under the incision or drain-
removed. The bone dust created is carefully confined
ing through the nose via the eustachian tube is 5%.
and removed to prevent meningeal irritation. The
The majority of these CSF leaks resolve with conser-
extent of IAC skeletonization is limited by the prox-
vative management, which includes mastoid dress-
imity to the inner ear. The endolymphatic duct and
ing and fluid restriction.89 There is a minimal risk of
sac serve as landmarks to the proximity of the PSCC
meningitis associated with a CSF leak.
and allow preservation of the inner ear and hearing.
Retrosigmoid Approach. The retrosigmoid ap- The facial nerve is normally anterior to the tumor, or
proach is a modification of the traditional suboccip- its position is ascertained with facial nerve monitor-
428 Ballenger’s Otorhinolaryngology
ing. The tumor removal is as previously described. to identify, and the IAC dura may have to be identi-
After tumor removal and hemostasis, air cells along fied medially by drilling toward the porus acousti-
the IAC and mastoid are closed with bone wax or cus. Once the IAC is identified and well skeletonized
bone cement to eliminate paths for CSF leak. A fat or medially, the bone removal continues laterally. How-
muscle graft may also be placed into the petrosal ever, the extent of IAC skeletonization laterally is
defect to prevent CSF leak. The dura mater is limited by the basal turn of the cochlea anteriorly
closed, and the bone plate or bone pate is replaced. and superior semicircular canal posteriorly. The IAC
The musculature and soft tissue are meticulously dura is opened posteriorly to avoid injury to the
closed.90 facial nerve. The tumor is dissected free of the facial
The primary advantage of the retrosigmoid nerve and removed in a medial to lateral direction.
approach relative to the translabyrinthine approach Any air cells are sealed, and the dural defect is cov-
is the ability to preserve hearing in properly selected ered with a fat or muscle plug. The craniotomy bone
tumors. If hearing preservation is not an issue, the flap is replaced, and the incision is closed.
retrosigmoid approach allows a versatile approach The middle fossa approach is unique com-
to the CPA and IAC. The relative disadvantages com- pared with the posterior fossa craniotomies
pared with the translabyrinthine approach include (translabyrinthine, retrosigmoid) because the entire
persistent postoperative headache, increased diffi- IAC is accessible without violating the inner ear. This
culty in resolving CSF leaks, need for cerebellar exposure allows removal of intracanalicular tumors
retraction, and inability to have direct access to the while preserving hearing. The limitations of the
facial nerve. The combination of intradural drilling middle fossa approach include tumors with a greater
leading to meningeal irritation by bone dust and dis- than 1 cm cisternal component. In situations of
section of suboccipital musculature causes nearly hearing preservation, an extended middle fossa
10% of patients to have a persistent, severe postop- approach with further removal of bone around the
erative headache.91 In the case of extensive pneuma- IAC and elevation or division of the superior pet-
tization of the IAC and mastoid, the air cells may be rosal sinus and tentorium allows improved exposure
difficult to seal completely, and the inability to into the CPA. The relative merits of the procedure
address the aditus ad antrum or the eustachian tube with increased temporal lobe retraction and limited
causes CSF leaks to be persistent despite conservative access to the posterior fossa in the event of bleeding
treatment. The extent of cerebellar retraction is min- relative to a retrosigmoid approach continue to be
imal in small tumors, but the amount of retraction defined. The disadvantages of the middle fossa
increases with larger tumors. The surgical control of approach include temporal lobe retraction and pos-
the facial nerve is adequate in the retrosigmoid sible poor surgical position of the facial nerve rela-
approach, but the exposure of the facial nerve is tive to the tumor. Temporal lobe retraction may
superior in the translabyrinthine approach. cause transient speech and memory disturbances
and auditory hallucinations. The facial nerve, espe-
Middle Fossa Approach. The middle fossa ap-
cially if the tumor originates from the inferior
proach provides a hearing-preserving approach to
vestibular nerve, will be between the surgeon and the
intracanalicular tumors with a less than 1 cm cister-
tumor. The increased manipulation of the facial
nal component. The surgical technique involves an
inverted U-shaped incision centered over the ear. nerve during tumor removal increases the risk of
The temporal muscle is reflected inferiorly to expose transient facial paresis.
the squamous portion of the temporal bone. A 5 × 5 Operative Complications. The intraoperative
cm temporal craniotomy is performed and is cen- complications for all three approaches include vas-
tered over the zygomatic root. Extradural elevation cular injury, air embolism, parenchymal brain
of the temporal lobe is accomplished to reveal the injury, and cranial nerve injury.92 The AICA origi-
temporal bone. The greater superficial petrosal nerve nates from the basilar artery and supplies the
leading to the geniculate ganglion reveals the ante- labyrinthine artery and the lower portion of the
rior, lateral boundary of the IAC, and the arcuate cerebellum and the vein of Labbé, which can be the
eminence reveals the posterior boundary of the IAC only venous drainage of the temporal lobe, are vul-
(Figure 20–6, C). These landmarks may be difficult nerable during VS surgery. In the event of an air
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 429
embolism via an open vein, the patient should be nerve fibers are preserved. Almost half of patients
placed into a left lateral and Trendelenburg position will have vertigo or imbalance beyond the postoper-
to trap the air in the right ventricle and then the air ative period, but these symptoms have a minimal
can be aspirated via a central venous catheter. The impact on daily activities. The rapidity of vestibular
cerebellum during a retrosigmoid craniotomy and compensation after unilateral vestibular loss is deter-
the temporal lobe during a middle fossa craniotomy mined by the patient’s efforts to exercise and chal-
are at risk from retraction injury. lenge the vestibular system. Patients who continue
to have dysequilibrium in the extended postopera-
Postoperative Complications. Postoperative com-
tive period should have vestibular rehabilitation
plications include hemorrhage, stroke, venous
therapy. Facial nerve function is also best predicted
thromboembolism, syndrome of inappropriate by tumor size. In smaller tumors, over 90% of
antidiuretic hormone, CSF leak, and meningitis.92 patients will have House-Brackmann grade 1 or 2
Postoperative hemorrhage will manifest as neuro- function (grade 1 is normal and grade 6 is complete
logic and cardiovascular deterioration and will paralysis). If all sizes are considered, approximately
require evacuation. Studies have shown that postop- 80% of patients will ultimately have grade 1 or 2
erative low-molecular-weight heparin in addition to function.96
compression stockings and intermittent pneumatic The rehabilitation of facial nerve injury is based
compression devices may reduce the risk of throm- on general principles of nerve injury, recovery, and
boembolism in high-risk patients (elderly, obese) rehabilitation. If the nerve is transected intraopera-
without increasing the risk of an intracranial bleed.93 tively, the nerve should be repaired primarily if pos-
The most common complication is a CSF leak, sible or with a greater auricular interposition graft.
which occurs in 10 to 15% of patients either via the Postoperative function may be predicted in an
wound or via a pneumatic pathway to the eustachian anatomically intact nerve by the intraoperative stim-
tube. The majority of these leaks resolve with con- ulability of the nerve. If the nerve can be stimulated
servative care, which includes placing wound sutures at less than 0.2 V, there is an over 85% chance of
at the leak site, replacing the mastoid dressing, grade 1 or 2 function at 1 year.97 The lack of facial
decreasing intracranial pressure with acetazolamide, function (grade 6) at 1 year and no reinnervation
restricting fluid intake, and resting in bed. Some potentials on electromyography (EMG) should lead
patients will also require a lumbar subarachnoid to a hypoglossal-facial transposition, interposition
drain, and a very few patients will need surgical re- nerve graft, or a cross-facial graft. If facial rehabilita-
exploration.94 A related complication is meningitis. tion has been delayed and there is electrical silence of
Meningitis occurs in 2 to 10% of patients and may the facial muscle on EMG, muscle transpositions
be aseptic, bacterial, or lipoid owing to irritation with the temporalis or masseter muscle to the lip give
from the fat graft. The distinction between aseptic improved tone and symmetry to the lower face. The
and bacterial meningitis is necessary because the upper face can be rehabilitated with a brow lift and
gold weight for the eyelid. The eye must be protected
treatment for aseptic meningitis is a corticosteroid
with lubrication, ointment, and eye bubble if there is
with taper and for bacterial meningitis is antibi-
incomplete eye closure or lack of sensation to the
otics.95 Delayed meningitis should be considered
cornea owing to trigeminal nerve involvement. Lack
bacterial and is likely to be caused by a CSF leak.
of eye care will lead to corneal injury and blindness.
Prognosis and Rehabilitation. Patients are most In summary, all three approaches have mortal-
concerned about deafness, imbalance, and facial ity rates of less than 1% with an over 90% rate of
nerve weakness. The most important factors for tumor removal and facial nerve preservation.92 The
hearing preservation are tumor size and preopera- translabyrinthine approach has facial nerve preser-
tive hearing level. Hearing preservation ranges from vation rates as high as 98%. The retrosigmoid
20 to 70%. Patients with good contralateral hearing approach allows 50% hearing preservation, and the
tolerate the unilateral loss or may be helped with a middle fossa approach allows up to 70% hearing
CROS (contralateral routing of signals) hearing aid, preservation.98,99 The recurrence rate is less than
and patients with poor contralateral hearing may be 1.5%, and the majority of patients feel that they can
rehabilitated with a cochlear implant if the cochlear return to full preoperative activities by 3 months.100
430 Ballenger’s Otorhinolaryngology
These three approaches allow the management of radiation dose. The current trend has been to lower
most CPA tumors. A small subset of patients will not the marginal radiation dose, and long-term tumor
be surgical candidates and will require observation control with these current dosing plans is under
or radiation therapy. investigation.104 Since VSs have a slow growth rate,
these studies will require 5- to 10-year follow-ups to
Observation. The predictable correlation bet-
be confident about tumor control. Studies have
ween VS size and significant neurologic symptoms
shown control rates from 85 to over 95%. The hear-
and the relative slow growth of VSs allow observa-
ing preservation rate decreases each year after radia-
tion to be a management option for VSs. Patients
tion and stabilizes after 3 years at 50%. The rate of
may be observed if their life expectancy is shorter
facial nerve dysfunction varies from 3 to 50% based
than the growth time required for the VS to cause
on the radiation dose at the margin of the tumor
significant neurologic symptoms. The growth pat-
and the length of the facial nerve in the radiation
tern of the VS should be assessed in these patients
field. Approximately 20% of patients will have
with a second radiologic evaluation in 6 months and
trigeminal neuropathy. The persistence and extent of
then yearly radiologic evaluations. Studies have
these neuropathies with the lower dosing protocols
shown that 15 to 24% of patients undergoing con-
continue to be studied. Hydrocephalus is also a com-
servative management will require surgery or stereo-
plication of radiation.105,106
tactic radiation.101,102 If the growth rate in the first
As the long-term effectiveness and sequelae of
year exceeds 2 to 3 mm per year, the patient will
stereotactic radiation are further defined, the indica-
likely need treatment for the VS. The patient should
tions for radiation therapy will become further
understand the opportunity costs of conservative
defined. Radiation therapy is useful in patients in
management, including having to treat a tumor that
whom arrest of tumor growth is acceptable. These
is larger and less amenable to hearing preservation
patients have either short life expectancies or high
procedures and/or stereotactic radiation.
surgical risk. Stereotactic radiation may improve
Stereotactic Radiation. The goal of stereotactic hearing preservation in patients with 2 to 3 cm VSs
radiation is to prevent further growth of the VS compared to microsurgery. Radiation therapy in
while preserving hearing and facial nerve function. large tumors (> 3 cm) or tumors causing brain com-
This goal directly differs from the goal of complete pression will exacerbate symptoms owing to initial
tumor removal in microsurgical therapy. The mech- tumor swelling.107
anism of stereotactic radiation relies on delivering
NONVESTIBULAR SCHWANNOMAS. Vestibular schwan-
radiation to a specific intracranial target by using
nomas represent over 95% of all CPA schwannomas.
several precisely collimated beams of ionizing radi-
In addition to CN VIII, schwannomas of CNs V, VII,
ation. The beams take various pathways to the target
IX, X, XI, and XII can involve the CPA.108 Cerebello-
tissue, creating a sharp dose gradient between the
pontine angle schwannomas share clinical, patho-
target tissue and the surrounding tissue. The ioniz-
logic, and imaging characteristics. The primary
ing radiation causes necrosis and vascular fibrosis,
treatment, similar to that for VSs, is surgical resec-
and the time course of effect is over 1 to 2 years.
tion. The surgical approach is based on the location
There is an expected transient swelling of the tumor
for 1 to 2 years. The ionizing radiation is most com- of the schwannoma and the patient’s hearing status.
monly delivered using a 201-source cobalt 60 Resection of cranial nerve schwannomas may lead
gamma-knife system. The standard linear accelera- to significant CN dysfunction, so preoperative CN
tor can also be adapted to deliver stereotactic radia- function and postoperative rehabilitation are impor-
tion. The practical aspects include that the patient tant issues to consider.
wears a stereotactic head frame, computer-assisted FACIAL NERVE SCHWANNOMAS. Facial nerve schwan-
radiation planning using a MRI, and a single treat- nomas most commonly occur at the geniculate gan-
ment for delivery of the radiation.103 glion but can involve any portion of the facial nerve.
The success of stereotactic radiation to arrest Similar to VSs, facial nerve schwannomas present
tumor growth depends on the dose of radiation with hearing loss, tinnitus, and imbalance (CPA
delivered. However, the rate of cranial neuropathies, symptoms). Facial nerve symptoms, such as facial
including hearing loss, is decreased by lowering the spasm or weakness, usually present with larger
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 431
tumors. Audiovestibular testing shows abnormality nomas, meningiomas are a more heterogeneous
in acoustic reflex testing because of impairment of group of tumors in regard to pathology, anatomic
CN VII motor supply to the stapedius muscle. Facial location, and treatment outcome. The majority of
nerve schwannomas are associated with reduction these tumors are benign and slow growing, and 1%
of electroneuronographic potentials on the ipsilat- will become symptomatic. Meningiomas differ in
eral side even when there is no clinically evident pathogenesis, anatomic location, and imaging char-
palsy. Imaging often does not allow differentiation acteristics from VSs but are nearly indistinguishable
between a VS and a facial nerve schwannoma. Dis- in terms of clinical presentation and audiovestibular
tinguishing features on imaging of facial nerve testing. Meningiomas are primarily managed by sur-
schwannomas include expansion of the fallopian gical excision.
canal, extension from the geniculate ganglion into
the middle fossa, and location of the schwannoma PATHOGENESIS. Meningiomas arise from arachnoid
in the anterosuperior portion of the IAC (a position villi cap cells and are located along dura, venous
eccentric to the axis of the IAC).108 These schwan- sinuses, and neurovascular foramina. Meningiomas
nomas may be observed until facial nerve function are most commonly sporadic but may occur in
has deteriorated or a neurologic complication familial syndromes such as NF2, Werner’s syndrome,
becomes imminent as resection usually requires and Gorlin’s syndrome. More than one-third of
division and grafting of the facial nerve. Mimetic patients with NF2 have meningiomas. Molecular
function following interposition grafting is poor.109 studies have shown deletions in chromosome 22 in
The best facial function attainable is a House- nearly 75% of meningiomas. Specifically, mutations
Brackmann grade 3. in the NF2 gene, merlin, have been shown in 30 to
35% of meningiomas. Although the majority of
TRIGEMINAL NERVE SCHWANNOMAS. Trigeminal nerve
meningiomas are benign, 5% are malignant. Chro-
schwannomas initially present with ipsilateral facial
mosomal abnormalities in 1p, 6q, 9p, 10q, and 14q
hypesthesia, paresthesias, neuralgia, and difficulties
with chewing.110 Trigeminal nerve schwannomas are seen in more aggressive or malignant menin-
arise from the gasserian ganglion in the middle fossa giomas.113
and grow posteriorly to involve the CPA or arise PATHOLOGY. Gross. Meningiomas may be globular or
from the root of the nerve and directly involve the flat (en plaque) and have a firm, gritty consistency
anterior part of the CPA and Meckel’s cave. These with a thin capsule. They are densely adherent to the
tumors frequently involve both the middle and pos- dura and may either cause reactive hyperostosis of
terior fossae, and a combined approach may be nec- the underlying bone or infiltrate the bone via haver-
essary for resection. sian canals. Hyperostosis is seen in 25% of menin-
LOWER CRANIAL NERVE SCHWANNOMAS. Schwanno- giomas.114
mas of CNs IX, X, and XI cause smooth enlargement Microscopic. Meningiomas have an epithelial
of the jugular foramen and may grow superiorly into and mesenchymal differentiation. These tumor cells
the CPA or inferiorly into the parapharyngeal space. generally have a uniform distribution. Some menin-
Cranial nerve IX, X, and XI schwannomas produce giomas may demonstrate a papillary pattern inter-
symptoms based on their CN functions and so cause spersed in the uniform distribution. Calcification of
hypesthesia and weakness of the palate, vocal cord, the tips of these papillary whorls leads to the forma-
and shoulder, respectively. Patients will present with tion of calcospherite or psammoma bodies. The
dysphagia, hoarseness, and shoulder weakness. Cere- ratio of epithelial to mesenchymal differentiation
bellopontine angle involvement will also lead to CPA
and the presence of psammoma bodies are the basis
symptoms. Schwannomas of CN XII cause hemiat-
for histologic classification of meningiomas. The
rophy of the tongue and expansion of the hypoglos-
four groups include meningotheliomatous (syncy-
sal canal. The treatment is surgical removal and
tial), transitional, fibrous, and angiomatous.115 The
rehabilitation of the patient’s functional deficit.111
syncytial type is the most common category. The
MENINGIOMAS. Meningiomas are the second most syncytial type is usually benign and lacks papillary
common CPA tumors and account for 3 to 10% of whorls or psammoma bodies. The transitional type
tumors at this location.112 Compared with schwan- has an increased amount of connective tissue and
432 Ballenger’s Otorhinolaryngology
psammoma bodies relative to the syncytial type. The The broad-based attachment to the petrous wall
transitional type lies histologically between the leads to an obtuse bone-tumor angle. There is no
syncytial and fibrous types. The fibrous type has widening of the IAC. Also, unlike VSs, meningiomas
increased connective tissue, mesenchymal differenti- more commonly herniate into the middle fossa. T1-
ation, and some psammoma bodies. The angioma- weighted enhanced images can show an enhancing
tous types may actually be sarcomas rather than dural tail (meningeal sign) adjacent to the bulk of
meningiomas and have a more aggressive growth the tumor in 50 to 70% of meningiomas.121
pattern with bone invasion. The microscopic identi-
MANAGEMENT. The two primary management options
fication of a malignant meningioma includes
are observation and surgery. Observation is indi-
increased mitotic figures, atypical mitosis, necrosis,
cated in patients with limited life expectancy or in
lack of cellular uniformity, and brain invasion.116
whom the expected morbidity of surgical excision is
SYMPTOMS AND SIGNS. From the onset of symptoms, not justified. Surgical treatment ideally consists of
meningiomas take an average of 5 years to be diag- total meningioma removal, excision of a cuff of sur-
nosed. The typical patient is a woman in her fourth rounding dura, and drilling of the underlying bone.
or fifth decade of life. Unlike VSs, there is a 2 to 1 The surgical approach is based on the tumor loca-
female bias.117 Meningiomas presenting in younger tion and the patient’s hearing status. In contrast to
patients or multiple meningiomas in the same VSs, the anatomic location of posterior fossa menin-
patient should prompt an evaluation for NF2. The giomas is varied (Figure 20–8). The site of the
most common complaints are the same as those meningioma is a major determinant of the types of
attributable to VSs and include unilateral hearing morbidity from the tumor and the success of treat-
loss (80%), vertigo or imbalance (75%), and tinnitus ment. A simple classification differentiates whether
(60%). Symptoms and signs more common with the tumor is present medial or lateral to the IAC.
meningiomas relative to VSs include trigeminal neu- Meningiomas medial to the IAC are more common.
ralgia (7 to 22%), facial paresis (11 to 36%), lower These meningiomas commonly arise along the infe-
CN deficits (5 to 10%), and visual disturbances rior petrosal sinus and may involve the petrous apex,
(8%).112,117,118 lateral part of the clivus, and Meckel’s cave. Menin-
giomas lateral to the IAC involve the sigmoid sinus,
DIAGNOSTIC EVALUATION. Auditory-Vestibular Evalu-
jugular bulb, and superior petrosal sinus. In an
ation. The hearing loss has no characteristic audio-
uncommon pattern, meningiomas may be centered
metric pattern. The SDSs suggest a retrocochlear
on the IAC and closely mimic a VS. Internal auditory
lesion in 50% of patients. The ABR may be normal
canal meningiomas may invade the inner or middle
in 25% of patients.119
ear. Meningiomas may also be superior to the IAC
Imaging. Imaging provides the diagnosis of and be considered midpetrosal meningiomas.112
meningioma and allows the differentiation between Meningiomas lateral to the IAC are reached via
meningioma and VS120 (Table 20–7). A CT scan a retrosigmoid approach. The facial nerve in lateral
without contrast shows an iso- or hyperdense mass meningiomas is most often displaced anteriorly and
with areas of calcification in 10 to 26% and provides so does not lie between the surgeon and the tumor.
information regarding hyperostosis or bony inva- Therefore, the facial nerve is less traumatized during
sion. Meningiomas enhance homogeneously with tumor removal. The retrosigmoid approach also
CT contrast, and 90% of meningiomas can be allows hearing preservation. Limited intracanalicu-
detected by contrast-enhanced CT.114 Magnetic res- lar meningiomas may be managed by the middle
onance imaging is the study of choice for the diag- fossa approach, especially if hearing preservation is
nosis of meningiomas. Meningiomas are hypo- to possible. Meningiomas involving the IAC and
isointense on T1-weighted images and have a vari- having poor hearing are reached via the trans-
able intensity on T2-weighted images. Areas of calci- labyrinthine approach. If the tumor invades the
fication appear dark on both T1-weighted and cochlea and has anteromedial extension to the clivus
T2-weighted images (Figure 20–7). Unlike VSs, or Meckel’s cave, a transcochlear approach should be
meningiomas are broad based (sessile) and are usu- considered122 (see Figure 20–6, A). The transcochlear
ally not centered over the porus acusticus internus. approach sacrifices hearing and requires rerouting
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 433
of the facial nerve. Sixty percent of CPA menin- than cause compression. Epidermoids are treated by
giomas involve the middle fossa and may require a surgical excision, but total removal is more difficult
combined middle and posterior fossa craniotomy. than with VSs because epidermoids become adher-
The type of posterior fossa craniotomy in the com- ent to normal structures.128
bined approach will depend on the need for hearing
preservation and the extent of surgical exposure PATHOGENESIS. Epidermoids likely develop from
required. ectodermal inclusions that become trapped during
Total tumor removal is accomplished in 70 to embryogenesis. These ectodermal inclusions lead to
85% of patients with meningiomas. Incomplete a keratinizing squamous cell epithelium in the CPA.
tumor removal is often associated with adherence of The squamous cell epithelium produces a cyst filled
the meningioma to the brainstem or cavernous sinus with sloughed keratinaceous debris.129
involvement.123 The long-term recurrence after total PATHOLOGY. The gross appearance is that of a
tumor removal is between 10 and 30%, whereas that nodular cyst. The cyst is lined with squamous cell
of subtotal removal is over 50%.124 Hearing preserva- epithelium, and the cyst is filled with lamella of
tion is more likely than in VSs and approaches 70%. desquamated keratinaceous debris. The majority of
The facial nerve function has a 17% rate of deterio- epidermoids are benign, but there are a few reports
ration from preoperative levels.125 The other compli- of squamous cell carcinoma arising in epider-
cations include gait disturbance and CSF leak (8%).
moids.130
The operative mortality is between 1 and 9%.126
Adjunctive therapies include external beam SYMPTOMS AND SIGNS. The presentation is similar to
and stereotactic radiation therapy. Radiation therapy other CPA lesions, with hearing loss being the most
should be considered in cases of inoperable tumors, common symptom. Epidermoids have a higher rate
subtotal resection, recurrent tumors, and malignant of preoperative facial (40%) and trigeminal (50%)
tumors. Retrospective reviews of patients in whom nerve involvement relative to VSs. Patients may pres-
subtotal tumor removals were carried out have ent with hemifacial spasm, facial hypesthesia, neu-
shown that external beam radiation reduces recur- ralgia, or wasting of the muscles of mastication.131
rence rates.127 The role of stereotactic radiation ther-
apy in meningiomas continues to be defined. DIAGNOSTIC EVALUATION. Auditory-Vestibular Evalu-
ation. Auditory-vestibular testing does not provide
EPIDERMOIDS. Epidermoids are much less common any distinguishing patterns for epidermoids.
than VSs or meningiomas. They account for approx-
imately 5% of CPA lesions. Epidermoids are slow Imaging. On CT, epidermoids are hypodense
growing and often grow to a large size before caus- compared to brain. A distinguishing characteristic
ing CPA symptoms because they initially grow relative to VSs and meningiomas is that epidermoids
around structures via paths of least resistance rather show no enhancement with intravenous contrast.
434 Ballenger’s Otorhinolaryngology
FIGURE 20–8. Meningiomas arise from arachnoid villi cap cells and are located along dural edges, venous sinuses, and
neurovascular foramina. The site of the meningioma is a major determinant of types of morbidity from the tumor and
the success of treatment. A simple classification differentiates whether the tumor is present medial or lateral to the inter-
nal auditory canal (IAC). Meningiomas medial to the IAC commonly arise along the inferior petrosal sinus and may
involve the petrous apex, lateral part of the clivus, and Meckel’s cave. Meningiomas lateral to the IAC involve the sig-
moid sinus, jugular bulb, and superior petrosal sinus. In an uncommon pattern, meningiomas may be centered on the
IAC or superior to the IAC and considered a midpetrosal meningioma. Reproduced with permission from Jackler RK.50
Paragangliomas (Glomus Jugulare Tumors) Glomus voids.137 Magnetic resonance angiography (MRA)
jugulare tumors arise from paraganglionic tissues and traditional angiography provide information on
(chief cells) and have intracranial extension in 15% involvement of the great vessels and allow preoper-
of patients. These tumors are slow growing and ative embolization of larger tumors. The treatment
present initially with pulsatile tinnitus and conduc- requires surgical excision. Jugular bulb involvement
tive hearing loss. Further growth at the jugular fora- may be addressed by a transmastoid neck approach.
men causes lower cranial neuropathies, and then Extension to the carotid artery or intracranial exten-
intracranial extension into the posterior fossa may sion will require an infratemporal fossa approach.138
lead to sensorineural hearing loss and dizziness.136
Paragangliomas have a variable appearance on CT HEMANGIOMAS. Hemangiomas of the temporal bone
scans, but bone algorithms show the extent of tem- often involve the geniculate ganglion and the inter-
poral bone involvement. Paragangliomas cause nal auditory meatus. Hemangiomas are benign,
irregular expansion of the jugular foramen, whereas slow-growing vascular hamartomas. Hemangiomas
lower CN schwannomas cause smooth enlargement involving the geniculate ganglion cause progressive
of the jugular foramen. Paragangliomas have a salt facial paresis. Patients also complain of facial
and pepper appearance on T2-weighted MRI and twitches, tinnitus, and facial pain. Hearing loss, if
have pronounced enhancement with gadolinium. present, is conductive owing to middle ear involve-
Magnetic resonance imaging also shows the extent ment. Facial paresis occurs sooner with heman-
of intracranial involvement and the presence of flow giomas than with facial nerve schwannomas.
436 Ballenger’s Otorhinolaryngology
with CPA symptoms. The treatment is primarily require immunohistochemistry stains since chon-
surgical. drosarcomas, unlike chordomas, do not stain posi-
tively with epithelial tissue markers.147
CHOLESTEROL GRANULOMAS. The petrous apex of the
temporal bone lies anterior and medial to the inner Metastases Metastatic disease from lung, breast,
ear and posterior and lateral to the clivus and con- skin (melanoma), prostate, nasopharynx, lym-
tains pneumatized air cells in one-third of temporal phoma, and kidney are the most common extra-
bones. Obstruction of these air cells leads to inflam- axial malignant neoplasms of the CPA.148 In contrast
mation and hemorrhage into the air cells. The phago- to benign lesions of the CPA, malignant lesions of
cytosis of red cells leads to deposition of cholesterol the CPA cause rapid progression of CPA symptoms.
crystals and a foreign body reaction in the petrous On imaging, the lesions are small and isointense to
apex. This process leads to a cholesterol granuloma brain on T1-weighted and T2-weighted MRI and
that may extend beyond the petrous apex to involve enhance with gadolinium. There is a high likelihood
the CPA. Patients may have CPA symptoms in addi- of parenchymal brain metastases and bilateral CPA
tion to symptoms of headache and sixth nerve dys- lesions. The extent of treatment is based on the
function. The key differential diagnosis in the petrous extent of the metastatic and primary disease and
apex and CPA of a cholesterol granuloma is an epi- includes multimodality treatment with surgical
dermoid. The distinguishing factor is that cholesterol biopsy or resection, radiation, and chemotherapy.
granulomas are hyperintense on T1-weighted and T2- The other aspect of treatment includes relieving
weighted images, whereas epidermoids are hypo- symptoms of hydrocephalus or brainstem compres-
intense on T1-weighted images. The treatment is sion. The primary extra-axial malignancies of the
surgical drainage rather than complete excision when CPA are exceedingly rare and include lymphomas,
symptomatic. The petrous apex may be accessed via squamous cell carcinomas, malignant VSs, and
a transmastoid or transcanal approach.144,145 malignant meningiomas.61
9. Shepard NT, Telian SA. Programmatic vestibular 25. Hallpike CS, Cairns H. Observation on the pathol-
rehabilitation. Otolaryngol Head Neck Surg 1995; ogy of Meniere’s syndrome. J Laryngol Otol 1938;
112:173–82. 53:625–54.
10. Dix R, Hallpike CS. The pathology, symptomatology, 26. House WF. Surgical exposure of the internal audi-
and diagnosis of certain common disorders of the tory canal and its contents through the middle cra-
vestibular system. Proc R Soc Med 1952;54:341–54. nial fossa. Laryngoscope 1961;71:1363–85.
11. Froehling DA, Silverstein MD, Mohr DN, et al. 27. Harner SG, Driscoll CL, Facer GW, et al. Long-term
Benign positional vertigo: incidence and prognosis follow-up of transtympanic gentamicin for Men-
in a population-based study in Olmsted County, iere’s syndrome. Otol Neurotol 2001;22:210–4.
Minnesota. Mayo Clin Proc 1991;66:596–601. 28. Schuknecht HF, Ruther A. Blockage of longitudinal
12. Furman JM, Cass SP. Benign paroxysmal positional flow in endolymphatic hydrops. Eur Arch Otorhino-
vertigo. N Engl J Med 1999;341:1590–6. laryngol 1991;248:209–17.
13. Baloh RW, Honrubia V, Jacobson K. Benign posi- 29. Hebbar GK, Rask-Andersen H, Linthicum FH. Three-
tional vertigo: clinical and oculographic features in dimensional analysis of 61 human endolymphatic
240 cases. Neurology 1987;37:371–8. ducts and sacs in ears with and without Meniere’s dis-
14. Schuknecht HF. Cupulolithiasis. Arch Otolaryngol ease. Ann Otol Rhinol Laryngol 1991;100:219–25.
1969;90:765–78. 30. Wackym PA, Sando I. Molecular and cellular pathol-
15. Parnes LS, McClure JA. Free-floating endolymph ogy of Meniere’s disease. Otolaryngol Clin North
particles: a new operative finding during posterior Am 1997;30:947–60.
semicircular canal occlusion. Laryngoscope 1992; 31. Tsuji K, Velazquez-Villasenor L, Rauch SD, et al.
102:988–92. Temporal bone studies of the human peripheral
16. Welling DB, Parnes LS, O’Brien B, et al. Particulate vestibular system. Meniere’s disease. Ann Otol Rhi-
matter in the posterior semicircular canal. Laryngo- nol Laryngol Suppl 2000;181:26–31.
scope 1997;107:90–4. 32. Gibson WP, Arenberg IK. Pathophysiologic theories
17. Honrubia V, Baloh RW, Harris MR, Jacobson KM. in the etiology of Meniere’s disease. Otolaryngol Clin
Paroxysmal positional vertigo syndrome. Am J Otol North Am 1997;30:961–7.
1999;20:465–70. 33. Dornhoffer JL, Arenberg IK. Immune mechanisms
18. Epley JM. The canalith repositioning procedure: for in Meniere’s syndrome. Otolaryngol Clin North Am
treatment of benign paroxysmal positional vertigo. 1997;30:1017–26.
Otolaryngol Head Neck Surg 1992;107:399–404. 34. Derebery MJ. The role of allergy in Meniere’s dis-
19. Brandt T, Daroff RB. Physical therapy for benign ease. Otolaryngol Clin North Am 1997;30:1007–16.
paroxysmal positional vertigo. Arch Otolaryngol 35. Green JD, Blum DJ, Harner SG. Longitudinal fol-
1980;106:484–5. lowup of patients with Meniere’s disease. Otolaryn-
20. Parnes LS, McClure JA. Posterior semicircular canal gol Head Neck Surg 1991;104:783–8.
occlusion for intractable benign paroxysmal posi- 36. Katsarkas A. Hearing loss and vestibular dysfunction
tional vertigo. Ann Otol Rhinol Laryngol 1990; in Meniere’s disease. Acta Otolaryngol (Stockh)
99:330–4. 1996;116:185–8.
21. Gacek RR. Technique and results of singular neurec- 37. Ruckenstein MJ. Vertigo and dysequilibrium with
tomy for the management of benign paroxysmal associated hearing loss. Otolaryngol Clin North Am
positional vertigo. Acta Otolaryngol (Stockh) 1995; 2000;33:535–62.
115:154–7. 38. Klockhoff I, Lindblom U. Endolymphatic hydrops
22. Committee on Hearing and Equilibrium. Guidelines revealed by glycerol test. Preliminary report. Acta
for the diagnosis and evaluation of therapy in Otolaryngol (Stockh) 1966;61:459–62.
Meniere’s disease. Otolaryngol Head Neck Surg 39. Schmidt PH, Eggermont JJ, Odenthal DW. Study of
1995;113:181–5. Meniere’s disease by electrocochleography. Acta Oto-
23. Lustig LR, Lalwani A. The history of Meniere’s dis- laryngol Suppl (Stockh) 1974;316:75–84.
ease. Otolaryngol Clin North Am 1997;30:917–45. 40. Stahle J, Friberg U, Svedberg A. Long-term progres-
24. Jackler RK, Whinney D. A century of eighth nerve sion of Meniere’s disease. Acta Otolaryngol Suppl
surgery. Otol Neurotol 2001;22:401–16. (Stockh) 1991;485:78–83.
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 439
41. Gottschlich S, Billings PB, Keithley EM, et al. Assess- 57. Hood JD, Korres S. Vestibular suppression in periph-
ment of serum antibodies in patients with rapidly eral and central vestibular disorders. Brain 1979;
progressive sensorineural hearing loss and Meniere’s 102:785–804.
disease. Laryngoscope 1995;105:1347–52. 58. Norrving B, Magnusson M, Holtas S. Isolated acute
42. Devaiah AK, Ator GA. Clinical indicators useful vertigo in the elderly; vestibular or vascular disease?
in predicting response to the medical management Acta Neurol Scand 1995;91:43–8.
of Meniere’s disease. Laryngoscope 2000;110(11): 59. El-Kashlan HK, Telian SA. Diagnosis and initiating
1861–5. treatment for peripheral system disorders: imbal-
43. van Deelen GW, Huizing EH. Use of a diuretic ance and dizziness with normal hearing. Otolaryn-
(Dyazide) in the treatment of Meniere’s disease. A gol Clin North Am 2000;33:563–78.
double-blind cross-over placebo-controlled study. 60. Mahaley MS, Mettlin C, Natarajan N, et al. Analysis
ORL J Otorhinolaryngol Relat Spec 1986;48:287–92. of patterns of care of brain tumor patients in the
44. Kaplan DM, Nedzelski JM, Chen JM, Shipp DB. United States: a study of the Brain Tumor Section of
Intratympanic gentamicin for the treatment of uni- the AANS and the CNS and the Commission on
lateral Meniere’s disease. Laryngoscope 2000;110: Cancer of the ACS. Clin Neurosurg 1990;36:347–52.
1298–305. 61. Eisenman D, Voigt EP, Selesnick SH. Unusual tumors
45. Atlas JT, Parnes LS. Intratympanic gentamicin titra- of the internal auditory canal and cerebellopontine
tion therapy for intractable Meniere’s disease. Am J angle. In: Jackler RK, Driscoll CLW, editors. Tumors
Otol 1999;20:357–63. of the ear and temporal bone. Philadelphia: Lippin-
46. Thomsen J, Bretlau P, Tos M, Johnsen NJ. Placebo cott, Williams and Wilkins; 2000. p. 236–75.
effect in surgery for Meniere’s disease. A double- 62. Cushing H. Tumors of the nervus acusticus and the
blind, placebo-controlled study on endolymphatic syndrome of the cerebellopontile. Philadelphia: WB
sac shunt surgery. Arch Otolaryngol 1981;107:271–7. Saunders; 1917.
47. Bretlau P, Thomsen J, Tos M, Johnsen NJ. Placebo 63. Dandy W. Results of removal of acoustic neuromas by
effect in surgery for Meniere’s disease: nine-year fol- the unilateral approach. Arch Surg 1941;42:1027–33.
low-up. Am J Otol 1989;10:259–61. 64. Lang J. Clinical anatomy of the cerebellopontine
48. Pensak ML, Friedman RA. The role of endolym- angle and internal acoustic meatus. Adv Otorhino-
phatic mastoid shunt surgery in the managed care laryngol 1984;34:8–24.
era. Am J Otol 1998;19:337–40. 65. Stewart TJ, Liland J, Schuknecht HF. Occult schwan-
49. LaRouere MJ. Surgical treatment of Meniere’s nomas of the vestibular nerve. Arch Otolaryngol
disease. Otolaryngol Clin North Am 1996;29: 1975;101:91–5.
311–22. 66. Tos M, Charabi S, Thomsen J. Clinical experience
50. Jackler RK. Atlas of neurotology and skull base sur- with vestibular schwannomas: epidemiology, symp-
gery. St. Louis: Mosby; 1996. tomatology, diagnosis, and surgical results. Eur Arch
51. Levine SC, Glasscock M, McKennan KX. Long-term Otorhinolaryngol 1998;255:1–6.
results of labyrinthectomy. Laryngoscope 1990;100: 67. Tallan EM, Harner SG, Beatty CW, et al. Does the
125–7. distribution of Schwann cells correlate with the
52. Nadol JB. Vestibular neuritis. Otolaryngol Head observed occurrence of acoustic neuromas? Am J
Neck Surg 1995;112:162–72. Otol 1993;14:131–4.
53. Strupp M, Brandt T. Vestibular neuritis. Adv Otorhi- 68. Rouleau GA, Wertelecki W, Haines JL, et al. Genetic
nolaryngol 1999;55:111–36. linkage of bilateral acoustic neurofibromatosis to a
54. Schuknecht HF, Kitamura K. Second Louis H. Clerf DNA marker on chromosome 22. Nature 1987;329:
Lecture. Vestibular neuritis. Ann Otol Rhinol Laryn- 246–8.
gol Suppl 1981;90:1–19. 69. Rouleau GA, Merel P, Lutchman M, et al. Alteration
55. Matsuo T, Sekitani T. Vestibular neuronitis: neuroto- in a new gene encoding a putative membrane-organ-
logical findings and progress. ORL J Otorhinolaryn- izing protein causes neuro-fibromatosis type 2.
gol Relat Spec 1985;47:199–206. Nature 1993;363:515–21.
56. Hotson JR, Baloh RW. Acute vestibular syndrome. N 70. Shaw RJ, McClatchey AI, Jacks T. Regulation of the
Engl J Med 1998;339:680–5. neurofibromatosis type 2 tumor suppressor protein,
440 Ballenger’s Otorhinolaryngology
merlin, by adhesion and growth arrest stimuli. J Biol small acoustic neuromas. Laryngoscope 1992;102:
Chem 1998;273:7757–64. 961–4.
71. Irving RM. The molecular pathology of tumours of 85. Saeed SR, Woolford TJ, Ramsden RT, Lye RH. Mag-
the ear and temporal bone. J Laryngol Otol 1998; netic resonance imaging: a cost-effective first line
112:1011–8. investigation in the detection of vestibular schwan-
72. National Institutes of Health Consensus Develop- nomas. Br J Neurosurg 1995;9:497–503.
ment Conference. Neurofibromatosis conference 86. Curtin HD, Hirsch WL. Imaging of acoustic neuro-
statement. Arch Neurol 1988;45:575–8. mas. Otolaryngol Clin North Am 1992;25:553–607.
73. Kanter WR, Eldridge R, Fabricant R, et al. Central 87. Shelton C, Harnsberger HR, Allen R, King B. Fast
neurofibromatosis with bilateral acoustic neuroma; spin echo magnetic resonance imaging: clinical
genetic, clinical and biochemical distinctions from application in screening for acoustic neuroma. Oto-
peripheral neurofibromatosis. Neurology 1980;30: laryngol Head Neck Surg 1996;114:71–6.
851–9. 88. Jackler RK. Overview of surgical neurotology. In:
74. Pirsig W, Ziemann-Becker B, Tesschler-Nicola M. Jackler RK, Brackmann DE, editors. Neurotology. St.
Acoustic neuroma: four thousand years ago. In: Tos Louis: Mosby; 1994. p. 651–84.
M, Thomson J, editors. Proceedings of the First 89. Jackler RK, Pitts LH. Selection of surgical approach
International Conference on Acoustic Neuroma. to acoustic neuroma. Otolaryngol Clin North Am
Amsterdam: Kugler; 1992. p. 7–12. 1992;25:361–87.
75. Kuo TC, Jackler RK, Wong K, et al. Are acoustic neu- 90. Catalano PJ, Jacobowitz O, Post KD. Prevention of
romas encapsulated tumors? Otolaryngol Head Neck headache after retrosigmoid removal of acoustic
Surg 1997;117:606–9. tumors. Am J Otol 1996;17:904–8.
76. Nager GT. Acoustic neurinomas. Pathology and dif- 91. Ruckenstein MJ, Harris JP, Cueva RA, et al. Pain sub-
ferential diagnosis. Arch Otolaryngol 1969;89:252–79. sequent to resection of acoustic neuromas via sub-
77. Selesnick SH, Johnson G. Radiologic surveillance of occipital and translabyrinthine approaches. Am J
acoustic neuromas. Am J Otol 1998;19:846–9. Otol 1996;17:620–4.
78. Matthies C, Samii M. Management of 1000 vestibu- 92. Samii M, Matthies C. Management of 1000 vestibu-
lar schwannomas (acoustic neuromas): clinical pres- lar schwannomas (acoustic neuromas): surgical
entation. Neurosurgery 1997;40:1–10. management and results with an emphasis on com-
79. Selesnick SH, Jackler RK, Pitts LW. The changing plications and how to avoid them. Neurosurgery
clinical presentation of acoustic tumors in the MRI 1997;40:11–23.
era. Laryngoscope 1993;103:431–6. 93. Agnelli G, Piovella F, Buoncristiani P, et al. Enoxa-
80. Selesnick SH, Jackler RK. Atypical hearing loss in parin plus compression stockings compared with
acoustic neuroma patients. Laryngoscope 1993; compression stockings alone in the prevention of
103:437–41. venous thromboembolism after elective neuro-
81. Neary WJ, Newton VE, Laoide-Kemp SN, et al. A surgery. N Engl J Med 1998;339:80–5.
clinical, genetic and audiological study of patients 94. Gormley WB, Sekhar LN, Wright DC, et al. Acoustic
and families with unilateral vestibular schwanno- neuromas: results of current surgical management.
mas. II. Audiological findings in 93 patients with Neurosurgery 1997;41:50–60.
unilateral vestibular schwannomas. J Laryngol Otol 95. Ross D, Rosegay H, Pons V. Differentiation of asep-
1996;110:1120–8. tic and bacterial meningitis in postoperative neuro-
82. Lustig LR, Rifkin S, Jackler RK, Pitts LH. Acoustic surgical patients. J Neurosurg 1988;69:669–74.
neuromas presenting with normal or symmetrical 96. Wiegand DA, Ojemann RG, Fickel V. Surgical treat-
hearing: factors associated with diagnosis and out- ment of acoustic neuroma (vestibular schwannoma)
come. Am J Otol 1998;19:212–8. in the United States: report from the Acoustic Neu-
83. Huygen PL, Hoogland GA. Vestibular and ocular roma Registry. Laryngoscope 1996;106:58–66.
motor manifestations of cerebellopontine angle 97. Lalwani AK, Butt FY, Jackler RK, et al. Facial nerve
tumours. Adv Otorhinolaryngol 1984;34:57–70. outcome after acoustic neuroma surgery: a study
84. Wilson DF, Hodgson RS, Gustafson MF, et al. The from the era of cranial nerve monitoring. Otolaryn-
sensitivity of auditory brainstem response testing in gol Head Neck Surg 1994;111:561–70.
Meniere’s Disease, Vestibular Neuronitis, Paroxysmal Positional Vertigo, and Cerebellopontine Angle Tumors 441
98. Irving RM, Jackler RK, Pitts LH. Hearing preserva- 112. Thomas NW, King TT. Meningiomas of the cere-
tion in patients undergoing vestibular schwannoma bellopontine angle. A report of 41 cases. Br J Neu-
surgery: comparison of middle fossa and retrosig- rosurg 1996;10:59–68.
moid approaches. J Neurosurg 1998;88:840–5. 113. Irving RM. Meningiomas of the internal auditory
99. Rowed DW, Nedzelski JM. Hearing preservation in canal and cerebellopontine angle. In: Jackler RK,
the removal of intracanalicular acoustic neuromas Driscoll CLW, editors. Tumors of the ear and tem-
via the retrosigmoid approach. J Neurosurg 1997;86: poral bone. Philadelphia: Lippincott, Williams and
456–61. Wilkins; 2000. p. 219–35.
100. Samii M, Matthies C. Management of 1000 114. Valavanis A, Schubiger O, Hayek J, Pouliadis G. CT
vestibular schwannomas (acoustic neuromas): of meningiomas on the posterior surface of the
hearing function in 1000 tumor resections. Neuro- petrous bone. Neuroradiology 1981;22:111–21.
surgery 1997;40:248–62. 115. Russell DS, Rubinstein LJ. Pathology of tumors of
101. Deen HG, Ebersold MJ, Harner SG, et al. Conserv- the nervous system. 4th ed. Baltimore: Williams
ative management of acoustic neuroma: an out- and Wilkins; 1977.
come study. Neurosurgery 1996;39:260–6. 116. Langford LA. Pathology of meningiomas. J Neu-
102. Glasscock ME, Pappas DG, Manolidis S, et al. Man- rooncol 1996;29:217–21.
agement of acoustic neuroma in the elderly popu- 117. Matthies C, Carvalho G, Tatagiba M, et al. Menin-
lation. Am J Otol 1997;18:236–42. giomas of the cerebellopontine angle. Acta Neu-
103. Lunsford LD, Linskey ME. Stereotactic radiosurgery rochir Suppl 1996;65:86–91.
in the treatment of patients with acoustic tumors. 118. Baguley DM, Beynon GJ, Grey PL, et al. Audio-
Otolaryngol Clin North Am 1992;25:471–91. vestibular findings in meningioma of the cerebello-
104. Flickinger JC, Kondziolka D, Niranjan A, Lunsford pontine angle: a retrospective review. J Laryngol
LD. Results of acoustic neuroma radiosurgery: an Otol 1997;111:1022–6.
analysis of 5 years’ experience using current meth- 119. Hart MJ, Lillehei KO. Management of posterior
ods. J Neurosurg 2001;94:1–6. cranial fossa meningiomas. Ann Otol Rhinol
105. Kondziolka D, Lunsford LD, McLaughlin MR, Laryngol 1995;104:105–16.
Flickinger JC. Long-term outcomes after radio- 120. Lalwani AK, Jackler RK. Preoperative differentia-
surgery for acoustic neuromas. N Engl J Med 1998; tion between meningioma of the cerebellopontine
339:1426–33. angle and acoustic neuroma using MRI. Otolaryn-
106. Kaylie DM, Horgan MJ, Delashaw JB, McMenomey gol Head Neck Surg 1993;109:88–95.
SO. A meta-analysis comparing outcomes of 121. Tokumaru A, O’Uchi T, Eguchi T, et al. Prom-
microsurgery and gamma knife radiosurgery. inent meningeal enhancement adjacent to
Laryngoscope 2000;110:1850–6. meningioma on Gd-DTPA-enhanced MR images:
107. Driscoll CLW. Vestibular schwannnoma. In: Jackler histopathologic correlation. Radiology 1990;175:
RK, Driscoll CLW, editors. Tumors of the ear and 431–3.
temporal bone. Philadelphia: Lippincott, Williams 122. Langman AW, Jackler RK, Althaus SR. Meningioma
and Wilkins; 2000. p. 172–218. of the internal auditory canal. Am J Otol
108. Lalwani AK. Meningiomas, epidermoids, and 1990;11:201–4.
other nonacoustic tumors of the cerebellopon- 123. Arriaga M, Shelton C, Nassif P, Brackmann DE.
tine angle. Otolaryngol Clin North Am 1992;25: Selection of surgical approaches for meningiomas
707–28. affecting the temporal bone. Otolaryngol Head
109. Storper IS, Glasscock ME, Jackson CG, et al. Man- Neck Surg 1992;107:738–44.
agement of nonacoustic cranial nerve neuromata. 124. Mirimanoff RO, Dosoretz DE, Linggood RM, et al.
Am J Otol 1998;19:484–90. Meningioma: analysis of recurrence and progres-
110. Samii M, Migliori MM, Tatagiba M, Babu R. Surgi- sion following neurosurgical resection. J Neurosurg
cal treatment of trigeminal schwannomas. J Neu- 1985;62:18–24.
rosurg 1995;82:711–8. 125. Schaller B, Heilbronner R, Pfaltz CR, et al. Pre-
111. Moffat DA, Ballagh RH. Rare tumours of the cere- operative and postoperative auditory and facial
bellopontine angle. Clin Oncol 1995;7:28–41. nerve function in cerebellopontine angle menin-
442 Ballenger’s Otorhinolaryngology
giomas. Otolaryngol Head Neck Surg 1995;112: 137. Olsen WL, Dillon WP, Kelly WM, et al. MR imag-
228–34. ing of paragangliomas. AJR Am J Roentgenol
126. Kallio M, Sankila R, Hakulinen T, Jaaskelainen J. 1987;148:201–4.
Factors affecting operative and excess long-term 138. Green JD, Brackmann DE, Nguyen CD, et al. Sur-
mortality in 935 patients with intracranial menin- gical management of previously untreated glo-
gioma. Neurosurgery 1992;31:2–12. mus jugulare tumors. Laryngoscope 1994;104:
127. Miralbell R, Linggood RM, de la Monte S, et al. The 917–21.
role of radiotherapy in the treatment of subtotally 139. Lo WW, Shelton C, Waluch V, et al. Intratemporal
resected benign meningiomas. J Neurooncol 1992; vascular tumors: detection with CT and MR imag-
13:157–64. ing. Radiology 1989;171:445–8.
128. Yamakawa K, Shitara N, Genka S, et al. Clinical 140. Shelton C, Brackmann DE, Lo WW, Carberry JN.
course and surgical prognosis of 33 cases of Intratemporal facial nerve hemangiomas. Oto-
intracranial epidermoid tumors. Neurosurgery laryngol Head Neck Surg 1991;104:116–21.
1989;24:568–73. 141. Papazian M,Paparella M,Hames E,Frisk J. Aneurysms
129. Nager GT. Epidermoids involving the temporal of the temporal bone. Ear Nose Throat J 1993;72:
bone: clinical, radiological and pathological 474–84.
aspects. Laryngoscope 1975;85:1–21. 142. House JL, Burt MR. Primary CNS tumors present-
130. Abramson RC, Morawetz RB, Schlitt M. Multiple ing as cerebellopontine angle tumors. Am J Otol
complications from an intracranial epidermoid 1985; Suppl:147–53.
cyst: case report and literature review. Neuro- 143. Ahn MS, Jackler RK. Exophytic brain tumors mim-
surgery 1989;24:574–8. icking primary lesions of the cerebellopontine
131. Mohanty A, Venkatrama SK, Rao BR, et al. Experi- angle. Laryngoscope 1997;107:466–71.
ence with cerebellopontine angle epidermoids. 144. Sabin HI, Bordi LT, Symon L. Epidermoid cysts and
Neurosurgery 1997;40:24–30. cholesterol granulomas centered on the posterior
132. Uchino A, Hasuo K, Matsumoto S, et al. Intracra- fossa: twenty years of diagnosis and management.
nial epidermoid carcinoma: CT and MRI. Neuro- Neurosurgery 1987;21:798–805.
radiology 1995;37:155–8. 145. Brodkey JA, Robertson JH, Shea JJ, Gardner G.
133. Samii M, Tatagiba M, Piquer J, Carvalho GA. Sur- Cholesterol granulomas of the petrous apex: com-
gical treatment of epidermoid cysts of the cerebel- bined neurosurgical and otological management. J
lopontine angle. J Neurosurg 1996;84:14–9. Neurosurg 1996;85:625–33.
134. Haberkamp TJ, Monsell EM, House WF, et al. 146. Gay E, Sekhar LN, Rubinstein E, et al. Chordomas
Diagnosis and treatment of arachnoid cysts of the and chondrosarcomas of the cranial base: results
posterior fossa. Otolaryngol Head Neck Surg 1990; and follow-up of 60 patients. Neurosurgery 1995;
103:610–4. 36:887–97.
135. Schuhmann MU, Ludemann WO, Schreiber H, et 147. Brooks JJ. Immunohistochemistry of soft tissue
al. Cerebellopontine angle lipoma: a rare differen- tumors: progress and prospects. Hum Pathol 1982;
tial diagnosis. Skull Base Surg 1997;7:199–205. 13:969–74.
136. O’Leary MJ, Shelton C, Giddings NA, et al. Glomus 148. Yuh WT, Mayr-Yuh NA, Koci TM, et al. Metastatic
tympanicum tumors: a clinical perspective. Laryn- lesions involving the cerebellopontine angle. AJNR
goscope 1991;101:1038–43. Am J Neuroradiol 1993;14:99–106.
CHAPTER 21
Presbyacusis
John H. Mills, PhD, Paul R. Lambert, MD
Presbyacusis is defined generally as the hearing loss the auditory nerve to the auditory brainstem and
associated with increasing chronologic age. It is a temporal lobe. Before reviewing the pertinent lit-
common problem today and will become even more erature on presbyacusis, it is necessary to review
significant in the future. Currently, according to the terminology.
National Center for Health Statistics, some 20 mil-
lion Americans have impaired hearing, and approx-
imately 75% of these people are over age 55. In the
TERMINOLOGY
25-year period between 1976 and 2000, the number There are several definitions of the term presbyacu-
of persons below age 75 increased by 23%, the num- sis. Indeed, even the spelling is an issue, that is, pres-
ber between age 75 and 84 increased by 57%, and byacusis versus presbycusis. Here we use
the number over age 84 increased by 91%. Indeed, “presbycusis.” It is used loosely to describe a seem-
by the year 2030, the elderly will comprise 32% of ingly endless list of genetic, environmental, and dis-
the population, an increase of 250%. As many as 60 ease states that can cause hearing loss in an older
to 75% of these older persons will have clinically sig- person. Often presbyacusis is used to refer to hearing
nificant hearing loss. Because of the increasing num- loss purely caused by the natural process of aging.
ber of older Americans, high-prevalence problems More often, hearing loss is called presbyacusis if the
such as age-related hearing loss and other chronic person is beyond the fifth decade, without consider-
disabling conditions (balance, vision, arthritis) will ation of disease, genetics, or other factors. In many
place extensive and novel demands on the health studies, older persons are considered homogeneous
care system. and are grouped regardless of hearing levels or are
grouped if their hearing loss exceeds an arbitrary
criterion.
BACKGROUND Some of the confusion associated with the use
The medical-scientific history of presbyacusis is rel- of the term can be eliminated or reduced by the
atively recent and rich. Although Toynbee in 1849 appropriate use of the terms presbyacusis, socioacu-
was perhaps the first to write about age-related hear- sis, and nosoacusis.3 A generic definition of presby-
ing loss and to prescribe a treatment (application of acusic is age-related hearing loss (or threshold shift)
solutions of silver nitrate or mercurous chloride to that is the effect of aging in combination with life-
the external auditory canal),1 Zwaardemaker in 1891 long exposures to nonoccupational noise, ototoxic
is credited with the first accurate description of pres- agents, diet, drugs, and other miscellaneous factors.
byacusis.2 With the clever use of Dalton whistles, A more restrictive, precise definition of presbyacusis
Zwaardemaker demonstrated that older persons had is hearing loss that increases as a function of chrono-
far more difficulty detecting high-pitched sounds logic age and is attributable to “aging” per se. This
than younger persons. By the use of bone-conduc- “purely aging” hearing loss probably has a genetic
tion testing, he correctly considered age-related basis. It may be correlated with age-related deterio-
hearing loss to be of cochlear origin. Since the 1930s, ration or declines in other senses, especially balance,
anatomic and histopathologic changes have been vision, and touch.
observed at nearly every location in the aging audi- Socioacusis is defined as the hearing loss pro-
tory system from the external ear with collapsing duced primarily by exposure to nonoccupational
ear canals to neural degeneration extending from noise in combination with lifestyle factors such as
443
444 Ballenger’s Otorhinolaryngology
diet and exercise. Nosoacusis is the hearing loss shows age-related permanent threshold shifts at
attributable to diseases with ototoxic effects. Thus, audiometric frequencies for males and females.
the hearing loss assessed in a person into the fifth These data are referred to as Data Base A in the ISO
decade and beyond is the combined result of aging, 1999 standard and are considered to represent highly
nosoacusis, socioacusis, and possibly, for many per- screened subjects. That is, the data in Figure 21–1, A,
sons, exposure to occupational noise. It is important represent “pure aging” effects as well as socioacusis.
for medical and legal reasons to differentiate presby- Most of the hearing loss attributable to occupational
acusis from socioacusis, nosoacusis, and occupa- hearing loss has been eliminated, although a small
tional hearing loss. nosoacusic effect may be present. Figure 21–1, B,
gives epidemiologic data, referred to as Data Base B
ADDITIVITY OF PRESBYACUSIS, in the ISO 1999 standard, which are considered to
reflect “pure aging” effects, socioacusis, some nosoa-
SOCIOACUSIS, AND NOSOACUSIS cusis, and some effects attributable to occupational
Most laboratory (with animals) and field studies hearing loss. As shown in Figure 21–1, hearing loss
indicate that hearing losses caused by exposure to in the higher frequencies is measurable by age 30; it
noise are additive (in decibels) with the hearing loss increases systematically to age 60 (and beyond), is
attributed to presbyacusis (in the strict sense of the largest at 4 and 6 kHz, and is much larger in males
word).4 A small sensorineural hearing loss (SNHL) than in females. There are also significant differences
of 25 dB at age 25, for example, seemingly has little between Figure 21–1, A (Data Base A), and Figure
social or medical relevance; however, by age 70, a 21–1, B (Data Base B), presumably owing to differ-
hearing loss of 25 dB caused almost totally by the ences in subject selection. Small effects caused by
aging process is added to the existing SNHL. The occupational noise and nosoacusis were eliminated
result is a moderate-to-severe SNHL of 50 dB. In in Data Base A. Significant debate exists currently
other words, a seemingly minor hearing loss at a about the appropriateness and validity of Data Base
young age becomes a severe loss when the effects of A and B, particularly in a medicolegal context
presbyacusis become evident. involving the assessment of occupational noise-
Rules for combining hearing losses attributa- induced hearing loss.
ble to presbyacusis, nosoacusis, and socioacusis are Data from Figure 21–1, A and B, have been
not always straightforward. In the medicolegal replotted in Figure 21–2 to show the average hearing
assessment of hearing loss, it is assumed that pres- loss at 0.5, 1, 2, and 3 kHz as a function of chrono-
byacusic effects (aging plus socioacusis plus nosoa- logic age. The mean hearing loss at these particular
cusis) add in decibels to the hearing loss produced audiometric test frequencies is especially meaningful
by noise. As stated above, this approach is supported because this combination of test frequencies com-
by some laboratory and field data for groups of sub- prises those used in the computation of hearing
jects under a limited set of exposure conditions; handicap as recommended by the American Acad-
however, for individual subjects and for complicated emy of Otolaryngology-Head and Neck Surgery
noise exposures, the procedures for allocation of (AAO). As Figure 21–2 shows, hearing loss increases
hearing loss into different components are contro- systematically from age 20 through age 75. There are
versial.4 at least two remarkable features to Figure 21–2. One
is that the largest difference between the worst case
(males, Data Base B) and best case (females, Data
EPIDEMIOLOGY Base A) is about 5 dB. One could suggest, perhaps
Over the past 25 years or so, there has been a signif- strongly, that much of the debate about Data Base A
icant epidemiologic effort to describe hearing levels and B is “much ado about nothing,” that is, 5 dB.
as a function of chronologic age. Two sets of data This line of thinking is supported by the fact that,
have survived extensive scrutiny and are now part of even at age 75, the hearing loss is only about 20 dB.
an international standard, International Standards According to the AAO 1979 definitions of hearing
Organization (ISO) 1999, “Acoustics: Determination handicap, the average hearing loss at 0.5, 1, 2, and 3
of Occupational Noise Exposure and Estimation of kHz must exceed 25 dB to be considered a hearing
Noise-Induced Hearing Impairment.” Figure 21–1, A, handicap. In other words, according to the data of
Presbyacusis 445
Figure 21–2 and the AAO 1979 definition of hearing questionnaires such as the Hearing Handicap Inven-
handicap, substantially less than 50% of the popula- tory for the Elderly.6 The correspondence between
tion, male or female, have a hearing handicap even at objective, audiologic measures of hearing handicap
age 75. and subjective measures from self-reports and ques-
Other less selective epidemiologic data suggest tionnaires suggests that the AAO measure of handi-
that the prevalence of hearing handicap among cap tends to overestimate handicap for older persons
older persons is substantially higher than that indi- with mild-to-moderate hearing losses and to under-
cated by the epidemiologic data used in the ISO estimate handicap for older persons with severe
1999 standard. Using 1,662 subjects from the famous hearing losses. Of course, there are many reasons for
Framingham study of cardiovascular disease, Gates discrepancies between subjective and audiologic
et al reported that 55% met or exceeded the AAO estimates of hearing handicap. One general rule
1979 medicolegal definition of hearing handicap.5 emerges from questionnaires and epidemiologic
The difference between the results of Gates et al and studies of hearing handicap in older persons,
those of ISO 1999 reflect sampling differences and namely, that the pure-tone average (PTA) of 0.5, 1, 2,
the inclusion of subjects older than age 75 in the and 3 kHz must exceed about 30 dB before most
Gates et al sample. older persons consider themselves to have a hearing
In addition to an audiologic assessment, hear- problem. Thus, there are indeed millions of older
ing handicap can be assessed more subjectively using hearing-handicapped persons in the United States.
446 Ballenger’s Otorhinolaryngology
Although much of the discussion has centered kHz, when 10 and 19 year olds are compared with 20
on the audiometric frequencies from 0.5 to 3 kHz, to 29 year olds, is not straightforward. One point of
one of the more dramatic features of age-related view is that these age-related changes in hearing
hearing loss is the decline of auditory sensitivity at thresholds, as well as systematic declines in the num-
higher frequencies.7,8 Figure 21–3, A, shows increas- ber of outer hair cells starting at birth and continu-
ing hearing loss from age 20 to 29 to age 50 to 59 for ing throughout the lifetime of the individual,10 are
test frequencies at and above 8 kHz. By age 50 to 59, genetically determined, age-dependent events. That
the hearing loss at 16 kHz is greater than 60 dB. Fig- is, these age-related events are totally endogenous in
ure 21–3, B, shows longitudinal threshold changes origin. They are independent of exogenous factors
(the same group of observers) over the age range of such as diet, exposure to environmental noise
70 to 81 years, including thresholds for test frequen- (socioacusis), and disease (nosoacusis). As part of
cies up to 8 kHz. Hearing levels at 4 and 8 kHz the Framingham heart study, Gates and colleagues
exceed 50 dB by age 70 and at 8 kHz exceed 70 dB by have estimated the role of genetics in age-related
age 79. Hearing loss at frequencies above 8 kHz is hearing loss.11 Their heritability estimates suggest
even more pronounced and is not predictable by that as much as 55% of the variance associated with
hearing levels in the 1 to 4 kHz range.9 Clearly, there age-related hearing loss is attributable to the effect of
is a dramatic age-related decline in auditory sensi- genes. These heritability estimates of age-related
tivity at high frequencies. It appears that hearing loss hearing loss are similar in magnitude to those
starts in the second decade (or earlier) in the fre- reported for hypertension and hyperlipidemia, are
quency range between 16 and 20 kHz, proceeds sys- much stronger in women than in men, and can be
tematically in magnitude in the 16 kHz region, and used to support the point of view that age-related
spreads systematically downward in the frequency changes in the ear and hearing reflect the combined
domain. By the eighth decade, the hearing loss is effect of genetics, socioacusis, and nosoacusis. In
moderate to severe, even at 1 and 2 kHz. some views of presbyacusis, socioacusis is given a
The interpretation of epidemiologic data that major role, almost surely because of the famous
show a loss of high-frequency sensitivity at 16 to 20 Mabaan study.12
Presbyacusis 447
fied four types or categories of presbyacusis: (1) sen- exceed 40 dBA. In addition to control of the acoustic
sory, characterized by atrophy and degeneration of environment, none of the animals received antibi-
the sensory and supporting cells; (2) neural, typified otics or other drugs. Conductive hearing loss was
by loss of neurons in the cochlea and central nervous eliminated as a potential source of the measured
system (CNS); (3) metabolic, characterized by atro- hearing loss. Clearly, environmental noise, drugs,
phy of the lateral wall of the cochlea, especially the disease, and trauma did not have a causative role in
stria vascularis; and (4) mechanical, where the inner the hearing losses observed in the aging animals.
ear changes its properties with a resulting inner ear Thus, the notion that presbyacusis is not an aging
conductive hearing loss. Each of these categories was effect per se but the combined effect of socioacusis
hypothesized to have a characteristic audiometric and nosoacusis is not supported by laboratory
configuration (ie, sloping, flat) and therefore to be experiments with several species of animals.
audiometrically identifiable. In subsequent studies, Perhaps the most dramatic feature of age-
considerable difficulty was encountered in correlat- related hearing loss in laboratory animals is the vari-
ing the audiometric configuration with histopatho- ability between animals. For example, in a
logic observations and in differentiating one type of longitudinal study of aging gerbils, some animals, at
presbyacusis from another on the basis of the audio- the one extreme, had normal or nearly normal audi-
metric configuration.14 The problem is that the tory sensitivity from 1 to 16 kHz, whereas at the
audiometric configurations of older persons do not other extreme, some animals did not respond to sig-
form clearly defined categories, and histopathologic nals presented at levels of 80 dB SPL. The variability
changes at the level of light and electron microscopy of this magnitude is remarkable given that chrono-
are almost always observed at multiple sites in a logic age, environment (temperature, humidity, air
given aging ear. quality), acoustic history, and diet of the animals
In 1993, Schuknecht and Gacek revised the tra- were virtually identical. These data and others
ditional categories of presbyacusis described above.15 involving different inbred strains of mice suggest a
The revision is based on hundreds of observations of strong genetic role for age-related hearing loss, at
human temporal bones and is summarized by the least in laboratory animals.
following: In addition to a qualitative/quantitative corre-
spondence between age-related hearing loss meas-
1) Sensory cell losses are the least important type
ured in aging rodents and audiograms of 60- to
of loss in the aged; 2) neuronal losses are con-
70-year-old humans,16 many of the histopathologic
stant and predictable expressions of aging;
observations made on human temporal bones have
3) atrophy of the stria vascularis is the predom-
been confirmed and extended on experimental ani-
inant lesion of the aging ear; 4) no anatomical
mals.17–19 In aging rodents, there is usually a small
correlation for a gradual descending hearing loss
loss of sensory (outer) hair cells in the most basal
…reflect a cochlear conductive loss; and 5) 25%
and the most apical regions of the cochlea. Nerve
cannot be classified using light microscopy.
loss, as indicated by loss of spiral ganglion cells, is
This conclusion by Schuknecht and Gacek is pronounced throughout the cochlea. The lateral wall
important for at least two reasons. One is that the of the cochlea, including the stria vascularis, usually
significance of sensory cell losses is de-emphasized shows degeneration originating in both the base and
in presbyacusis. The second is that the dominance of apex and extending to midcochlear regions as the
strial degeneration is emphasized. These two points animal ages; however, in some animals, there is a
bring a consensus to human temporal bone results patchy loss of stria vascularis. Thus, in several
and those obtained from experiments with animals. species of animals, anatomic studies of cochlear
In many species of animals, auditory thresh- material demonstrate at least three of the histo-
olds estimated from electrophysiologic potentials pathologic conditions described in humans by
arising from the auditory nerve and brainstem Schuknecht and colleagues, namely, sensory, neural,
increase as a function of chronologic age.16,17 The and metabolic presbyacusis.13 In animals, all three
age-related decline in auditory function occurs in types are usually present in each animal.
animals who are born and reared in acoustically As with humans, the most prominent (domi-
controlled environments where sound levels rarely nant) type of presbyacusis in laboratory animals
Presbyacusis 449
10 dB. In other words, as the signal intensity is from the pathologic basis of most forms of noise-
increased, the amplitude of the CAP increases by a induced or drug-induced hearing loss.
fraction of that observed in young animals with nor- Otoacoustic emissions, both transient evoked
mal hearing or young animals with noise-induced or and distortion product, are nonlinear phenomena
drug-induced hearing losses. These shallow input- that are assumed to reflect the integrity of sensory
output functions of the CAP are also reflected in cells, especially outer hair cells. Given this assump-
shallow input-output functions of auditory brain- tion, one would expect to find very high correlations
stem responses (ABRs). Thus, what appears to be between loss of outer hair cells and changes in otoa-
abnormal function of the auditory brainstem in coustic emissions; however, inconsistent relations
older animals reflects only the abnormal output of among distortion products, threshold measures, and
the auditory nerve. The reduced amplitudes of sensory cell pathology have been reported from
action potentials observed in aging ears are probably widely different types of experiments. Indeed, there
reflective of asynchronous or poorly synchronized are reports of normal emissions in the presence of
neural activity in the auditory nerve. The pathologic missing outer hair cells as well as reduced emissions
basis of asynchronized activity in the auditory nerve in the presence of a complete complement of outer
is unknown but probably involves the nature of the hair cells.25 In the aging ear of experimental animals
synapse between individual auditory nerve fibers with a minimal, if any, loss of outer hair cells, dis-
and the attachment to the inner hair cell, primary tortion-product emissions are reduced somewhat in
degeneration of spiral ganglion cells, and reductions amplitude but are clearly present and robust.26 In
in the endolymphatic potential, which are described aging human ears, transient emissions are present in
below. about 80% of persons with a PTA hearing level bet-
A second major difference between the presby- ter than 10 dB, present in about 50% with PTA of 11
acusic ear and the ear with noise-induced hearing to 26 dB, and absent in about 80% with a PTA
loss is the endolymphatic potential, that is, the 80 to greater than 26 dB. Thus, the presence of a transient
90 mV DC resting potential in the scala media of the otoacoustic emission suggests excellent hearing lev-
cochlea.18 In aging animals, this DC potential is often els for most persons, whereas its absence reveals very
reduced significantly and proportionally to little. Indeed, the major application of otoacoustic
losses/degeneration of the stria vascularis. Moreover, emissions may be in hearing screening of infants.
in experimental animals, hearing losses can be A recent development is the association of
reduced by introducing a DC voltage into scala mitochondrial deoxyribonucleic acid (mtDNA)
media and raising a low endolymphatic potential, deletions with SNHL and age-related hearing loss.
that is, 15 mV, to a value approaching 60 to 70 mV. Ueda et al, using DNA specimens extracted from
Degeneration of the stria vascularis with the result- peripheral blood leukocytes, found a higher rate of
ant decline in the endocochlear potential has given mtDNA deletions in patients with SNHL than in
rise to the “dead battery theory” of presbyacusis. controls.27 Seidman, in a rat study, tied mtDNA dele-
A third difference between the physiology of tions to presbyacusis and mtDNA deletions to reac-
the aging ear and the ear with noise-induced or tive oxygen metabolites (ROMs).28 These are highly
drug-induced injury of the cochlea involves the non- toxic molecules that can damage mitochondrial
linear phenomenon of two-tone rate suppression, DNA, resulting in the production of specific mtDNA
that is, activity of the auditory nerve elicited by one deletions. Thus, compounds that block or scavenge
tone is suppressed or eliminated by the addition of a ROMs should attenuate age-related hearing loss.
second tone of different frequency.24 In ears of quiet- Rats were assigned to treatment groups including
reared aging animals, the mechanism of two-tone controls, caloric restriction, and treatment with sev-
rate suppression appears to remain intact. In con- eral antioxidants, including vitamins E and C, and
trast, in noise-induced or drug-induced injury of the were allowed to age in a controlled environment.
cochlea, a reduction or complete loss of two-tone The calorie-restricted groups maintained the best
rate suppression may be the first indicator of injury hearing, the lowest quantity of mtDNA deletions in
of the cochlea, usually outer hair cells. These data are brain and ear tissues, and the least amount of outer
an excellent indicator that the pathologic basis of hair cell loss. The antioxidant-treated subjects had
age-related hearing loss is fundamentally different better hearing than the controls and a slight trend
Presbyacusis 451
for fewer mtDNA deletions. The controls had the loss is almost surely substantial but remains largely
poorest hearing, the most mtDNA deletions, and the unknown.
most outer hair cell loss. These data suggest that
nutritional and pharmacologic strategies may prove PERCEPTION OF AUDITORY
to be an effective treatment that would limit age-
related increases in ROM production, reduce
SIGNALS AND SPEECH
mtDNA deletions, and thus reduce age-related hear- In addition to age-related declines in auditory sen-
ing loss. Reactive oxygen metabolites (or reactive sitivity, there are age-related declines in differen-
oxygen species) and oxidative stress have also been tial sensitivity for intensity, frequency, and time.
implicated in noise-induced hearing loss, ototoxic Until recently, these age-related declines in the
hearing loss, and cumulative injury that presents as basic properties of the ear and hearing were almost
age-related hearing loss. It is speculated that there is always measured in older persons with significant
a genetic impairment of antioxidant protections that hearing losses. Thus, it was nearly impossible to
leads to the production of both age-related and separate the effects of a hearing loss from the
noise-induced hearing loss by placing the cochlea in effects of aging. Recently, however, both discrimi-
a state of vulnerability.29,30 Although an age-related nation in intensity and discrimination in fre-
hearing loss gene has been identified, the murine Ahl quency have been shown to decline with age only
mutation,31,32 the discovery of the molecular/genetic at low frequencies and independently of any hear-
basis of presbyacusis, noise-induced hearing loss, ing loss.33 These results are important because they
and SNHL in general are truly just beginning. are negative effects measured in the presence of
In summary, animal experiments conducted normal hearing and may very well represent age-
under strict conditions show age-related declines in related declines in information processing capabil-
auditory function that indicate a pure aging hearing ity. It remains unclear whether these age-related
loss. Most of the pathologic anatomy associated with declines represent age-related effects of the audi-
this “pure aging” hearing loss is in the cochlea, where tory periphery or CNS.
the dominant pathology is degeneration of the stria The term “phonemic regression” was coined to
vascularis. In experimental animals, most of the describe a disproportionate difficulty in speech per-
hearing loss can be accounted for by anatomic, phys- ception relative to the magnitude of hearing loss of
iologic, and biochemical changes in the auditory older persons. Later, many studies of speech dis-
periphery. Indeed, there is no need to include the crimination and other complex listening tasks
auditory CNS in an explanation of age-related hear- showed results with older subjects that were difficult
ing loss, even when the criterion measure of age- to explain solely on the basis of the audiogram
related hearing loss is derived from potentials arising alone. With the ready availability of many published
from the auditory brainstem. Nearly all changes articles showing degenerative changes in the audi-
observed in auditory brainstem potentials can be tory brainstem and cortex of older persons, there
explained by alterations in the auditory periphery. evolved a viewpoint that a significant component of
Explanations of age-related changes in audi- age-related hearing loss is attributable to the decline
tory brainstem potentials in terms of alterations in of the auditory CNS. Of course, the auditory CNS is
the auditory periphery run counter to the current involved in age-related hearing loss; however, the
dogma that there is a significant, perhaps dominant, extent of the involvement of the CNS in presbyacu-
component of presbyacusis that involves degenera- sis is currently receiving much debate. Here we
tion of the auditory CNS. Indeed, there are signifi- examine the CNS issue beginning with data on
cant, age-related changes in the auditory CNS speech discrimination by older persons.
involving subtle to gross changes in anatomy and Perhaps the largest qualitative/quantitative
neurochemistry. One prominent change is a reduc- description of speech discrimination as a function
tion in γ-aminobutyric acid (GABA) affecting neu- of age and hearing loss is provided by Jerger from
ral inhibition. Another is increases in the release of the clinical records of 2,162 patients.34 Figure 21–5
aspartate in the cochlear nucleus following cochlear shows percent correct on phonetically balanced
injury and leads to increased excitatory neurotrans- (PB) words as a function of chronologic age. The
mission. The role of the CNS in age-related hearing parameter on the figure is the PTA of 0.5, 1, and
452 Ballenger’s Otorhinolaryngology
2 kHz. Figure 21–5 shows that speech discrimina- that performance on all tests were not affected by
tion declines systematically as a function of chrono- age. That is, when hearing levels were equated, there
logic age; however, the decline with age is were no age-related declines in performance on tests
dramatically dependent on hearing loss. That is, for of speech discrimination in persons over the age
subjects with very little hearing loss (less than 30 range of 55 to 84 years. In additional analyses using
dB), the decline with age is measurable but small partial correlations, Dubno et al showed significant
through age 70. On the other hand, for subjects gender effects, that is, significant declines with age
with moderate-to-severe hearing losses, the decline for males in word recognition, SSI, and SPIN in
with age is noteworthy, particularly for persons high-context sentences.36 Age-related declines were
between the ages of 45 and 85 with hearing losses of not observed for females.
40 to 49 dB, 50 to 59 dB, and 60 to 69 dB. In other There are many additional studies of speech
words, when hearing loss as indicated by the PTA is discrimination using background noises, degraded
held constant, speech discrimination scores speech signals, reverberation, and other variations
decreased between the ages of 40 and 80 for moder- that resulted in more difficult listening tasks than the
ate (greater than 40 dB) to severe (60 dB) hearing usual speech discrimination test, which is done in
losses. In contrast, age had very little effect as long quiet listening conditions.36,37 Many of these studies
as the PTA is less than about 30 to 39 dB. A remark- show age-related effects; however, the interpretation
able and perhaps the most noteworthy feature of of many of these data showing age-related declines
Figure 21–5 is that persons over the age range of 50 in auditory behavior is not straightforward because
to 80 perform as well as 25 year olds as long as their the subjects usually have significant hearing loss, as
average hearing loss at 0.5, 1, and 2 kHz is less than indicated by the audiogram. Accordingly, some per-
35 dB or so. This fact runs counter to the stereotype sons believe that there is a large CNS component to
of 70- to 80-year-old persons. presbyacusis, whereas others believe and have shown
Performance on tests of speech discrimination that speech discrimination by older persons is pre-
by older persons is shown (Figure 21–6) for PB dictable given the audiometric hearing loss and the
words, three versions of the Speech Perception in audibility of the speech material. Indeed, as much as
Noise (SPIN) test, and synthetic sentence identifica- 95% of the variance in speech discrimination results
tion (SSI).35 Subjects in whom hearing levels were can be accounted for on the basis of the audio-
nearly identical (± 3 dB) were placed into three age gram.38 In other cases for which predictions of per-
groups over the range from 55 to 84 years. Statistical formance by older persons under noisy listening
analysis of the speech discrimination data showed conditions are in error by 20 to 25%, it is still not
Presbyacusis 453
necessary to invoke the involvement of the CNS, “poor quality” and reduced amplitude, probably
although this is usually the interpretation. reflecting pathology of the cochlea and auditory
Although there are large individual differences nerve as well as a reduction in synchronized neural
in auditory behavior among individuals that are pre- activity. For young subjects with normal and abnor-
dictable by individual differences in auditory thresh- mal hearing, auditory thresholds measured behav-
olds, there are many age-related declines in auditory iorally are about 10 dB better than auditory
behavior that are not strongly associated with audi- thresholds estimated from the ABR. For aging sub-
tory thresholds. This is most evident using binaural jects, this behavioral/ABR disparity is 20 dB, reflect-
listening tasks conducted under acoustically stressful ing the poor quality/low amplitude of the ABR.
conditions. In many binaural experiments using Other evoked potentials show inconsistent results.
older subjects, age-related declines are observed that The P300 arising from the auditory cortex shows
appear to be independent of peripheral hearing loss; age-related declines, whereas the amplitude-modu-
however, it is often difficult to separate truly central lated following response may remain unaffected by
processing disorders from disorders initiated by a aging. In contrast, the frequency-modulated follow-
pathologic input from the aging cochlea. ing response may be enhanced in older subjects, per-
haps reflecting the well-documented age-related
decline in GABA. Although much of this research is
AUDITORY EVOKED POTENTIALS in progress, it appears that evoked potentials pro-
With the development of straightforward techniques duced by short-duration signals (onset responses
to measure evoked potentials arising from the audi- such as ABR and CAP) are decreased in amplitude in
tory nerve, brainstem, and auditory cortex, there has older subjects, whereas those evoked potentials pro-
been significant progress in evaluating the aging duced at higher levels in the CNS by long-duration
auditory nervous system of human subjects. In signals may be unaffected or even increased in
regard to the ABRs, most studies show age-related amplitude. Age-related increases could reflect a
declines in the amplitude of wave V, which should be number of factors, including efforts by the CNS to
interpreted to reflect peripheral hearing loss rather compensate for peripheral deficits or age-related
than changes in the brainstem. Even in older persons changes in the excitatory/inhibitory balance of the
with excellent hearing levels, ABR waveforms are of auditory CNS.
454 Ballenger’s Otorhinolaryngology
ALLEVIATION/TREATMENT REFERENCES
Assuming that any problems with the external and 1. Toynbee J. On the pathology and treatment of the
middle ear are diagnosed and treated, that other deafness attendant upon old age. Mon J Med Sci
medical issues are under control, and a diagnosis of 1849;1–12.
presbyacusis in the general sense, the best treatment 2. Zwaardemaker H. Der Verlust on hohen Torten mit
currently available is a hearing aid. The successful zunehmendern Alter. Ein neues Gesetz. Arch Ohr-
use of hearing aids by older persons and the hearing nas Kehlkopfheil 1891;32:53–6.
impaired in general is mixed. There is a literature of 3. Ward WD. Effects of noise exposure on auditory sen-
substantial magnitude that reports on the successful sitivity. In: Neff DW, editor. Handbook of physiology.
or unsuccessful use of hearing aids by the elderly. Section 9: reactions to environmental agents. Bethesda
Many older persons who would clearly benefit from (MD): American Physiology Society; 1977. p. 1–15.
an aid do not use one. The reasons for not using an 4. Dobie RA. Medical-legal evaluation of hearing
aid or being a dissatisfied user include cost, stigma of loss. Albany (NY): Singular Thomson Learning;
a hearing handicap and of being old, difficulty in 2001.
manipulating controls, and too little benefit, partic- 5. Gates GA, Cooper JC, Kannel WB, Miller NJ. Hear-
ularly in the presence of background noise. ing in the elderly: the Framingham cohort, 1983–85.
In a large group of older persons (N = 516) Ear Hear 1990;11:247–56.
who are participants in a longitudinal study of age- 6. Matthews LJ, Lee FS, Mills JH, Schum DJ. Audio-
related hearing loss, 53% (n = 272) are candidates metric and subjective assessment of hearing handi-
for a hearing aid. Candidacy by very conservative cap. Arch Otolaryngol Head Neck Surg 1990;
audiologic criteria is a speech reception threshold 116:1325–30.
greater than 30 dB in the better ear or hearing level 7. Stelmachowicz PG, Beauchaine KA, Kalberer A,
greater than 40 dB at 3 and 4 kHz in the better ear. Jesteadt W. Normative thresholds in the 8- to 20-kHz
Using these criteria, nearly half (n = 131 of 272) of range as a function of age. J Acoust Soc Am 1989;
those who are considered to be excellent candidates 86:1384–91.
have never tried a hearing aid, and only 38% (n = 8. Moller MB. Hearing in 70 and 75 year old people:
104 of 272) of candidates were successful hearing aid results from a cross-sectional and longitudinal pop-
users. Thirty-seven persons, for one or several rea- ulation study. Am J Otolaryngol 1981;2:22–9.
sons, were dissatisfied hearing aid users. Of those 9. Matthews LJ, Lee FS, Mills JH, Dubno JR. Extended
who did not meet the conservative criteria for a high-frequency thresholds in older adults. J Speech
hearing aid (n = 244), our clinical judgment sug- Lang Hear Res 1997;40:208–14.
gested that at least 40 to 50% of these persons would 10. Bredberg G. Cellular pattern and nerve supply of the
benefit from an aid. Clearly, the older persons in our human organ of corti. Acta Otolaryngol Suppl
longitudinal study were uninformed about hearing (Stockh) 1968;236:1–135.
aids, poorly served, or underserved. Indeed, it is our 11. Gates GA, Couropmitree NN, Myers RH. Genetic
opinion that as a result of excellent advances in hear- associations in age-related hearing thresholds. Arch
ing aid technology in combination with improved Otolaryngol Head Neck Surg 1999;125:654–9.
fitting techniques, nearly every older hearing- 12. Rosen S, et al. Presbycusis study of a relatively noise-
impaired person should be considered a potential free population in the Sudan. Ann Otol Rhinol
candidate for a hearing aid. Laryngol 1962;71:727–37.
13. Schuknecht HF. Pathology of the ear. Cambridge
(MA): Harvard University Press; 1974.
ACKNOWLEDGMENT 14. Suga F, Lindsay JR. Histopathological observations
Preparation of this chapter was supported by NIH of presbyacusis. Ann Otol Rhinol Laryngol 1976;
(P01 DC00422). Lois J. Matthews provided data on 85:169–76.
hearing aid use and transient otoacoustic emissions. 15. Schuknecht HF, Gacek MR. Cochlear pathology in
Nancy Smythe assisted in preparation of the figures presbycusis. Ann Otol Rhinol Laryngol 1993;102
and final document. Suppl 158:1–16.
Presbyacusis 455
16. Mills JH, Schmiedt RA, Kulish LF. Age-related sorineural hearing loss. Laryngoscope 1998;108:
changes in auditory potentials of mongolian gerbil. 580–4.
Hear Res 1990;46:301–10. 28. Seidman MD. Effects of dietary restriction and
17. Willcott JF. Aging and the auditory system. In: antioxidants on presbyacusis. Laryngoscope 2000;
Anatomy, physiology, and psychophysics. San Diego: 110:727–38.
Singular Publishing Group; 1991. 29. Ohlemiller KK, McFadden SL, Ding D-L, et al. Tar-
18. Schulte BA, Schmiedt RA. Lateral wall Na, K-ATPase geted mutation of the gene for cellular glutathione
and endocochlear potentials decline with age in peroxidase (Gpx1) increases noise-induced hearing
quiet-reared gerbils. Hear Res 1992;61:35–46. loss in mice. J Assoc Res Otolaryngol 2000;1:243–54.
19. Gratton MA, Schulte BA. Alterations in micro- 30. McFadden SL, Ding D, Burkard RF, et al. Cu/Zn
vasculature are associated with atrophy of the stria SOD deficiency potentiates hearing loss and cochlear
vascularis in quiet-aged gerbils. Hear Res 1995; pathology in aged 129, CD-1 mice. J Comp Neurol
82:44–52. 1999;413:101–12.
20. Gratton MA, Schmiedt RA, Schulte BA. Age-related 31. Li HS. Genetic influences on susceptibility of the
decreases in endocochlear potential are associated auditory system to aging and environmental factors.
with vascular abnormalities in the stria vascularis. Scand Audiol 1992;Suppl 36:1–39.
Hear Res 1996;102:181–90. 32. Erway LC, Willott JF. Genetic susceptibility to noise-
21. Thomopoulos GN, Spicer SS, Gratton MA, Schulte induced hearing loss. In: Axelsson A, editor. A scien-
BA. Age-related thickening of basement membrane tific basis of noise-induced hearing loss. New York:
in stria vascularis capillaries. Hear Res 1997;111: Thieme; 1996. p. 56–64.
31–41. 33. He NJ, Dubno JR, Mills JH. Frequency and intensity
22. Sakaguchi N, Spicer SS, Thomopoulos GN, Schulte discrimination measured in a maximum-likelihood
BA. Increased laminin deposition in capillaries of procedure from young and aged normal-hearing
the stria vascularis of quiet-aged gerbils. Hear Res subjects. J Acoust Soc Am 1998;103:553–65.
1997;105:44–56. 34. Jerger J. Audiological findings in aging. Adv Otorhi-
23. Sakaguchi N, Spicer SS, Thomopoulos GN, Schulte nolaryngol 1973;20:115–24.
BA. Immunoglobulin deposition in thickened base- 35. Dubno JR, Lee FS, Matthews LJ, Mills JH. Age-
ment membranes of aging strial capillaries. Hear Res related and gender-related changes in monaural
1997;108:83–91. speech recognition. J Speech Lang Hear Res
24. Schmiedt RA, Mills JH, Adams JC. Tuning and 1997;40:444–52.
suppresion in auditory nerve fibers of aged gerbils 36. Dubno J, Dirks D, Morgan D. Effects of age and mild
raised in quiet or noise. Hear Res 1990;45:221–36. hearing loss on speech recognition in noise. J Acoust
25. Hamernick R, Qiu W. Correlations among evoked Soc Am 1984;76:87–96.
potential thresholds, distortion product oto- 37. Schum DJ, Matthews LJ, Lee FS. Actual and pre-
acoustic emissions and hair cell loss following dicted word recognition performance of elderly
various noise exposures in the chinchilla. Hear Res hearing impaired listeners. J Speech Hear Res
2000;150:245–57. 1991;34:636–42.
26. Boettcher FA, Gratton MA, Schmiedt RA. Effects of 38. Humes LE, Christopherson L, Cokely C. Central
age and noise on hearing. Occup Med 1995; auditory processing disorders in the elderly: fact or
10:577–91. fiction? In: Katz J, Stecker N, Henderson D, editors.
27. Ueda N, Oshima T, Ikeda K, et al. Mitchochondrial Central auditory processing. St. Louis: Mosby Year
DNA deletion is a predisposing cause for sen- Book; 1992. p. 141–9.
CHAPTER 22
456
Tinnitus and Hyperacusis 457
severe effects of tinnitus in their lives.1–4,18 The preva- within the central auditory pathways and central
lence of tinnitus in adults with hearing problems is nervous system.12,36–38 The neurophysiological model
very high (59 to 86%), and it is estimated that tinni- of tinnitus combines all of the levels and differenti-
tus is present in 50% of patients with sudden hear- ates between the perception of tinnitus versus tinni-
ing loss, 70% with presbycusis, and 50 to 90% with tus-induced activation of nonauditory structures
noise-induced hearing loss.19 in the brain.7,12,37–39 Table 22–1 summarizes the
The prevalence of tinnitus increases signifi- approaches to the mechanisms of tinnitus.19,29,37,40–44
cantly with aging, but people of all ages experience
tinnitus.2,4,8 Although frequently not reported, chil-
TINNITUS AS A SYMPTOM OF MEDICALLY
dren are also affected by tinnitus, and the estimated
prevalence is similar to that reported in adults. TREATABLE DISEASES
Nodar, in a sample of 2,000 children, reported the Tinnitus may also be a part of more complex med-
average prevalence of 15%, with 13.3% for children ical conditions. The most common ones are listed in
with normal hearing and 58.6% with hearing loss.20 Table 22–2.37,45
Similar data were reported by others with a general
prevalence in the range of 15 to 29% in healthy chil-
dren and approximately 50% in children with oto- DECREASED SOUND TOLERANCE
logic problems or hearing loss.21,22 A significant Tinnitus is frequently accompanied by decreased
proportion of children reported having problems sound tolerance (oversensitivity to sound),3,6,12,17,46–51
with tinnitus including sleep disturbance (42%), which, in many cases, is a sum of hyperacusis and
problems with concentration (47%), and sensitivity misophonia.46,52
to sound (33%).23 In younger healthy children (age
5 to 16 years), 29% have tinnitus, and 9.6% reported
their tinnitus as troublesome.21
DEFINITIONS
Extensive studies have been performed in an There is no generally accepted definition for
attempt to link various factors with tinnitus preva- decreased sound tolerance to suprathreshold
lence.1,2,8,14 Hearing loss, specifically the extent of sounds, although a variety of terms have been pro-
high-frequency impairment in the worse ear, is one posed, with hyperacusis used most frequently.
of the main predicting factors for tinnitus.2 Con- According to Stedman’s Medical Dictionary,53 hyper-
ductive hearing loss seems to be a separate factor,24 acusis is defined as “Abnormal acuteness of hearing
and noise exposure has been correlated with tinnitus due to increased irritability of the sensory neural
as well.14 Tinnitus is also experienced by those with mechanism. Syn: auditory hyperesthesia,” with
normal hearing; 18% of tinnitus patients were hyperesthesia defined as “Abnormal acuteness of
reported to have normal hearing.24 sensitivity to touch, pain, or other sensory stimuli”
Other epidemiologic factors do not appear to or, according to American Heritage Dictionary, as “An
be correlated with tinnitus. There is no clear effect of abnormal or pathological increase in sensitivity to
gender on tinnitus prevalence, although pregnancy sensory stimuli, as of the skin to touch or the ear to
has been shown to increase significantly the proba- sound.”54 It has been recognized that decreased
bility of tinnitus.25 Neither smoking, coffee, nor alco- sound tolerance might reflect physical discomfort or
hol has been shown to increase tinnitus prevalence be related to a fear of sound.6
directly.26–28 We proposed the approach to decreased sound
tolerance based on neurophysiology, recognizing the
systems that can be involved, the auditory system
MECHANISMS AND MODELS (both peripheral and central parts) and the limbic
Our knowledge of the mechanisms of tinnitus is still and autonomic systems, and consequently propose
limited and based more on theoretical speculations the following definitions. Hyperacusis can be
than on strong research data or stringent clinical defined as abnormally strong reactions to sound
studies. Past models were focused on peripheral occurring within the auditory pathways. At the
mechanisms,29–35 whereas recent models tend to behavioral level, it is manifested by a subject experi-
involve or even focus on processing information encing physical discomfort as a result of exposure to
458 Ballenger’s Otorhinolaryngology
moderate/weak sound that would not evoke such limbic systems without abnormally high activation
reaction in the average population. The strength of a of the auditory system, resulting from enhanced
reaction is linked to the physical characterization of connections between the auditory and limbic sys-
a sound, for example, its spectrum and intensity. tems. At the behavioral level, patients have a gener-
Misophonia and phonophobia can be defined as ally negative attitude to sound (misophonia, from
abnormally strong reactions of the autonomic and Greek: miso meaning strong dislike, hate) or could
Adapted from Spoendlin H;19 Tonndorf J;29,41 Jastreboff PJ;37,44 Pujol R;40 Zenner H-P and Ernst A;42 LePage EL.43
Tinnitus and Hyperacusis 459
specifically be afraid of sound (phonophobia; pho- TABLE 22–2. Medical Conditions That May Be
bia, fear). The strength of a reaction will be only par- Associated with Tinnitus
tially determined by the physical characterization of
a sound and will depend on the patient’s previous Conductive hearing losses
evaluation of a sound (eg, potential threat, beliefs that Otitis media
it can be harmful), the patient’s psychological pro-
Cerumen impaction
file, and the context in which the sound is presented.
Note that neither hyperacusis nor phonopho- Ossicular stiffness/discontinuity
bia has any relation to the threshold of hearing, Otosclerosis
which can be normal or can reflect hearing loss.
Sensorineural hearing losses
Most frequently, decreased sound tolerance
results from a combination of hyperacusis and Meniere’s disease
phonophobia. It is important to assess the presence Presbycusis
and the extent of both phenomena in a patient as
each needs to be treated using different methods. Cochlear otosclerosis
Terms used in the literature do not differentiate Vestibular schwannoma
these problems, and since the reported decreased Sudden hearing loss
sound tolerance is typically dominated by hyperacu-
sis, we will use the term hyperacusis in describing Hormonal changes
reports in the literature. As misophonia is a new Pregnancy
term, and phonophobia is commonly used, in this Menopause
chapter, when the word “phonophobia” is used, it
actually denotes “misophonia/phonophobia.” Thyroid dysfunction
Additionally, note that the term recruitment is Some medications or withdrawal from them
not related to a decreased sound tolerance or hyper- Somatosounds
acusis. Recruitment refers to unusually rapid growth
of loudness as the level of a tone is increased, occurs Produced by structures adjacent to the ear
in association with hearing loss, and is purely a Pulsatile
cochlear phenomenon. It might coexist with hyper-
Neoplasm
acusis, but there is no functional link between these
two phenomena. Arterial
Venous
PREVALENCE AND EPIDEMIOLOGY OF Beginning of intracranial hypertension
DECREASED SOUND TOLERANCE Great vessel bruits
There are limited data available on the prevalence of Nonpulsatile
hyperacusis. Questionnaires provide an assessment
Tensor tympani myoclonus
of hyperacusis prevalence in the general population.
Recent data gathered from 10,349 randomly selected Tensor veli palatini myoclonus
subjects showed that 15.3% reported hyperacusis.17 Patent eustachian tube
Patients being evaluated for other otologic
Produced by structures in the ear
problems frequently undergo audiologic evaluation,
which involves assessment of speech discomfort level Spontaneous otoacoustic emissions
and pure-tone LDLs. There are no good normative Produced by joint abnormalities
data. Several studies indicated that in the normal
Temporomandibular joint disorders
population, LDLs are in the range of 90 to 110 dB
SPL, with varied results depending on the specific Adapted from Jastreboff PJ;37 Perry BP and Gantz BJ.45
method used (eg, stimuli: pure tone, warble tone,
noise; presentation: free field, insert earphones,
headphones; and instructions given to patients).55–57
460 Ballenger’s Otorhinolaryngology
The results tend to cluster within 95 to 110 dB SPL TABLE 22–3. Methods Used for Evaluation
for frequencies from 500 to 8,000 Hz, which corre- of Tinnitus
spond to approximately 90 to 100 dB HL.55,58
Hyperacusis and tinnitus frequently coexist, and Interview/questionnaires
it has been postulated that in some patients, hypera- Psychoacoustic
cusis might actually be a pretinnitus state.12 Approxi-
Perceptual location
mately 40% of tinnitus patients exhibit decreased
sound tolerance, with 27% requiring specific treat- Pitch
ment for hyperacusis.46,59,60 Conversely, study of 100 Loudness
patients with hypersensitivity to sound showed that
Maskability
86% of them suffered from tinnitus.61 Considering
the clinical observation that approximately 27% of Postmasking effects
tinnitus patients required treatment for hyperacusis Physiologic
and 86% of hyperacusis patients reported tinnitus
and accepting that about 4 to 5% of the general pop- Otoacoustic emissions
ulation have clinically significant tinnitus, it is possi- Efferent-mediated suppression of otoacoustic
ble to estimate that significant hyperacusis exists in emissions
approximately 1 to 1.5% of the general population. Spontaneous auditory nerve activity
An even larger proportion has some hyperacusis that,
although detectable in questionnaires, is not suffi- Auditory brainstem responses
ciently strong to initiate intervention. Late cortical potentials
Positron emission tomography/single photon
EVALUATION OF TINNITUS emission tomography
We do not have any objective method to detect and Functional magnetic resonance imaging
measure tinnitus. Therefore, interview and psychoa- Magnetoencephalography
coustic characterization are typical approaches in
clinical practice, sometimes expanding into the direc- Adapted from Jastreboff PJ et al;46,69 Penner MJ;66 Lind O;67
tion of physiologic testing. New advances in research McKee GJ and Stephens SD;68 Jacobson et al;70,71 Martin et al.72
offer the possibility to detect tinnitus in an objective
manner using imaging techniques62–65 or magnetoen-
as headache, neck pain, and jaw pain.1,6,73 Tinnitus
cephalography.13 These techniques are very promis-
can be very intrusive and may cause difficulty with
ing but cannot yet be implemented into clinical
sleep and concentration and a decreased ability to
practice owing to their complexity and cost. Table
participate in everyday activities and social events; it
22–3 lists the methods used for evaluation of tinnitus.
may also create problems in relationships. A detailed
interview, aimed at characterizing the specifics and
PROBLEMS EVOKED BY TINNITUS degree of tinnitus impact on patients, coupled with
As tinnitus can present as part of a complex medical otolaryngologic evaluation, provides the most thor-
condition, full physical examination is needed to ough assessment and allows the practitioner to
exclude all medically treatable problems that can be address all of the issues that need to be considered,
linked to tinnitus. Even though tinnitus is classified including potential intervention of a psychologist/
as a symptom and not a disease, it does require treat- psychiatrist to accompany the commencement of a
ment as it can cause significant emotional and specific tinnitus-oriented treatment.
somatic distress and can significantly influence
patients’ quality of life, particularly if allowed to HYPERACUSIS AND MISOPHONIA AS A
become a chronic problem. The list of reported asso-
PROBLEM
ciated complaints is long and includes emotional
problems such as irritation, annoyance, anxiety, and Decreased sound tolerance can have an extremely
depression; hearing problems such as difficulty with strong effect on patients’ lives and can be even more
speech comprehension; and somatic problems such debilitating than tinnitus. Whereas tinnitus may affect
Tinnitus and Hyperacusis 461
attention, sleep, work, and life enjoyment and make TABLE 22–4. Medical Conditions Linked to
social contact less rewarding, hyperacusis can prevent Hyperacusis
people from exposing themselves to louder environ-
ments and therefore prevent them from working and Tinnitus
interacting socially; it can also control a patient’s life. Bell’s palsy
In extreme cases, patients do not leave their homes,
Lyme disease
and their lives and the lives of their families are con-
trolled by the issue of avoidance of sound. Misopho- Williams syndrome
nia can have similar effects, and since it is inevitable in Ramsay Hunt syndrome
all cases with significant hyperacusis, misophonia fur-
Post-stapedectomy
ther enhances the effects of hyperacusis.
Perilymphatic fistula
narrow-band noise; etc.56,92,93 The approach we are TABLE 22–5. Review of Treatments for Tinnitus
pursuing incorporates modifications of the standard
procedure55 aimed at obtaining results dominated by Antireassurance
hyperacusis by decreasing the effects of the miso- Pharmacology
phonic component to a minimum. To achieve this, a
Surgery
situation is created during testing in which patients
have the feeling of full control over the maximal Electrical stimulation
sound level to which they will be exposed. 46 A Masking
detailed interview is needed with each patient to
Psychological approaches
determine the relative contribution of hyperacusis
and misophonia to decreased sound tolerance, Tinnitus retraining therapy
reflected in decreased values of LDLs. As normative Other approaches
data are not uniform and there is substantial indi-
vidual variability (even while using one method) in Biofeedback
measuring LDL,57 it is advisable to pay attention to Temporomandibular joint treatment
the potential presence of hyperacusis when average Acupuncture
LDL values are lower than 95 to 100 dB HL.
Hyperbaric oxygen therapy
TABLE 22–6. Drugs Frequently Prescribed for TABLE 22–7. Conditions Used in Electrical
Treatment for Tinnitus Stimulation for Suppression of Tinnitus
Local anesthetics (lidocaine, procaine, tocainide, Sites of stimulation
flecainide) Behind the ear lobe/around the ear
Sedatives (diazepam, flurazepam, oxazepam, Mastoid
alprazolam)
Near cheeks
Antidepressants (nortriptyline, trimipramine)
External auditory canal
Anticonvulsants (carbamazepine, clonazepam, amino-
oxyacetic acid, lamotrigine, baclofen) Promontory
Analysis of the problems reported by tinnitus events, its strength is irrelevant, as the extent of acti-
patients, who exhibit a strong emotional reaction to vation of the limbic and autonomic nervous systems
its presence, a high level of anxiety, and psychoso- depends on the strength of negative associations
matic problems, indicated that the limbic and auto- linked to tinnitus and the susceptibility of the feed-
nomic nervous systems are crucial in individuals back loops to modification.114 It appears that tinni-
with clinically relevant tinnitus. It was postulated tus-related neuronal activity may result from
that the sustained activation of the limbic and auto- compensatory processes that occur within the
nomic nervous systems is essential in creating dis- cochlea and the auditory pathways to minor dys-
tress and, therefore, clinically relevant tinnitus.12 function at the periphery.12,37
Tinnitus-related neuronal activity is processed Notably, once plastic modifications of neu-
by the parts of the central nervous system involved ronal connections occur, the peripheral signal itself
in memory and attention. It is possible to distinguish may become of little importance, as is similarly
several feedback loops, with two major categories: observed in chronic pain.38 Indeed, there are clear
loops involving the conscious perception of tinnitus similarities between tinnitus and chronic pain,
and those that act at a subconscious level (Figure including the phenomenon of prolonged exacerba-
22–1), with the subconscious loop dominant in tion of tinnitus as a result of exposure to sound,
most patients.7,39 It is further suggested that the acti- which is observed in some patients.52,59
vation of the limbic and autonomic nervous systems The neurophysiological model includes several
by tinnitus-related neuronal activity follows the systems of the brain involved in analysis of clinically
principles of conditioned reflexes.39,52 relevant tinnitus. All levels of the auditory pathways,
The processing of tinnitus-related neuronal starting from the cochlea through the subcortical
activity occurs in a dynamic balance scenario, with centers and ending at the auditory cortex, are essen-
continuous modification of the weights of synaptic tial in creating the perception of tinnitus.12 When
connections. Both learning and memory have a subjects are not bothered or annoyed by tinnitus,
physiologic basis in the modification of the strength auditory pathways are the only pathways involved,
of synaptic connections.113 A continuous presence of and tinnitus-related neuronal activity is constrained
tinnitus, combined with attention given to it, results within the auditory system. Therefore, although sub-
in plastic modifications of synaptic connections, jects are perceiving tinnitus, they are not disturbed
yielding the modification of receptive fields corre- by it.2,39,114
sponding to the tinnitus signal and its subsequent In approximately 20% of those with tinnitus,
enhancement.37,39 Recently, this postulate has been strong negative emotions are induced, which, in
proven using magnetoencephalography.13 turn, evoke a variety of physiological defense mech-
Whereas the initial signal provided by the anisms of the brain. The limbic and autonomic
auditory system is needed to start the cascade of nervous systems play a crucial role, and improper
activation of these systems by tinnitus-related neu- 22–2).110,114–116 This initial association can be coinci-
ronal activity results at the behavioral level in the dental, without any real dependence. These types of
problems described by patients. The connections associations of sensory stimuli are constantly created
between the auditory, limbic, and autonomic sys- in normal life.
tems with various cortical areas, as proposed in the As long as the sensory stimulus is limited in
neurophysiological model of tinnitus, are outlined time and there is no functional link between stimu-
in Figure 22–1.6,7,12,37,39,60 lus and reinforcement, this conditioned reflex will
The model points out that the sustained acti- gradually disappear (habituate) owing to passive
vation of the limbic and autonomic nervous systems extinction of the reflex (the sensory stimulus is pres-
is responsible for the distress induced by clinically ent but is not accompanied by a reinforcement) (see
relevant tinnitus. Activation of both systems can be Figure 22–2). Since the 1930s, habituation has been
achieved through two routes. The first includes stim- defined as “The extinction of a conditioned reflex by
ulation of the autonomic and limbic systems from repetition of the conditioned stimulus, … the
higher-level cortical areas, which are involved in our method by which the nervous system reduces or
awareness, verbalization, and beliefs. The second inhibits responsiveness during repeated stimula-
arises from the subconscious and provides stimula- tion.”115 Habituation of perception of this stimulus
tion from the lower-level auditory centers. The acti- will follow in the same manner as for all unimpor-
vation going through these two routes changes the tant stimuli.
strength of synaptic connections, enhancing the Notably, there are two different types of habitu-
stimulation of the limbic and autonomic nervous ation. The first, habituation of reaction, is defined as
systems by the tinnitus-related neuronal activity “disappearance of a reaction to a neutral stimulus due
during the process of development of tinnitus as a to its repetitive appearance without reinforcement.”117
clinical problem. The second, habituation of perception, occurs when
The question of how the neutral signal of awareness of this particular stimulus disappears (Fig-
tinnitus can evoke persistent strong distress can ure 22–3).7 Habituations of reaction and perception
be answered by the principles of conditioned are natural processes. Habituation is a crucial charac-
reflexes.115 Basically, to create a conditional reflex, the teristic of brain function necessitated by the brain’s
temporal coincidence of sensory stimuli with nega- inability to perform two tasks requiring complete
tive (or positive) reinforcement is sufficient (Figure attention simultaneously. When forced to carry out
two tasks concurrently that require full consciousness, quently of the “fight or flight” category), which fur-
the brain uses its function of task switching by actu- ther reinforces memory patterns associated with this
ally devoting consciousness to only one task at a time. stimulus. Consequently, if the previous assessment
Recently, brain areas involved in task switching have of the importance of a stimulus has been confirmed,
been indicated by a functional magnetic resonance this specific stimulus becomes even more important,
imaging study.118 If forced to monitor all of the and its next appearance will result in faster identifi-
incoming sensory stimuli, our brain would not be cation, even in the presence of other competing
able to perform any tasks, except that of switching stimuli, preventing the habituation of this stimulus.
perception from one sensory stimulus to the other, In the case of auditory stimuli, our auditory system
ultimately paralyzing us in our actions. becomes tuned into recognizing specific patterns of
To solve this problem, the central nervous sys- sound that have negative links. Under such condi-
tem screens and categorizes all stimuli at the sub- tions, the natural habituation of the tinnitus signal
conscious level. If the stimulus is new and unknown, becomes impossible. In everyday life, this results in
it is passed to a higher cortical level, where it is per- people having problems with their work, concentra-
ceived and evaluated. However, in the case of a stim- tion, and sleep.
ulus to which we have previously been exposed, the A simplistic description of the above process
stimulus is compared with patterns stored in mem- can be outlined to a patient as increased concern for
ory. If the stimulus was classified as nonimportant tinnitus results in an increase of its significance,
and does not require action, it is blocked at the sub- which ultimately increases the amount of time a per-
conscious level of the auditory pathways and does son pays attention to it. This is a classic feedback
not produce any reactions or reach the level of loop or the “vicious circle” scenario, which increases
awareness. The reaction to this stimulus and its per- patients’ level of distress up to the limit of mental
ception is habituated. In everyday life, habituation and physical endurance. At this stage, the patient will
occurs to the majority of sensory stimuli surround- move from acute tinnitus, which can be easily
ing us. relieved by proper counseling, into a chronic stage,
However, if a specific stimulus was once classi- which is much more difficult to deal with.
fied as important and, on the basis of comparison In the case of tinnitus, it is impossible to
with the patterns stored in memory, was linked to remove the reactions induced by the excitation of
something unpleasant or dangerous, this stimulus is the sympathetic autonomic nervous system or even
perceived and attracts attention. Furthermore, the change them in a substantial manner. The solution
sympathetic part of the autonomic nervous system is to achieve the passive extinction of conditioned
activated, inducing reaction to this stimulus (fre- reflex, in which both stimulus (tinnitus) and nega-
tive reinforcement are continuously present, is to we cannot easily suppress tinnitus-related neuronal
decrease the magnitude of this negative reinforce- activity, but by increasing background neuronal
ment over a period of time. This will result in partial activity, we are effectively decreasing the strength of
weakening of the reflex but has to be applied consis- this signal, which activates the limbic and autonomic
tently to yield positive effects. Moreover, it is funda- nervous systems and which is being processed in all
mental that patients understand these principles of the centers involved. There is no simple propor-
so that the enhancement of this reflex by inducing tional relationship between the differences in tinni-
too much verbal thinking and beliefs can be mini- tus and background neuronal activity and the
malized. reactions induced by it. Nonetheless, we can achieve
Once activation of the autonomic nervous sys- a decrease of reactions induced by the tinnitus and,
tem is lowered, this decreases negative reinforcement through this, facilitate extinction of the conditioned
to a signal that is continuously present and gradually reflex.
decreases the strength of the conditioned reflex. This It is important to analyze the theoretical rela-
causes further decreases in the reaction. Once tinni- tionships existing between the physical intensity
tus has achieved a neutral status, its habituation is of sound and its effectiveness on tinnitus habitua-
inevitable as the brain is continuously habituating tion (Figure 22–4). Five principles influence this
to all types of stimuli, assuming that they are not relationship91,110,111,119: (1) stochastic resonance
significant. (enhancement of the signal by adding low-level
Consequently, retraining counseling (the first noise); (2) dependence of the signal’s strength on its
component of TRT) is oriented toward removal of contrast with the background; (3) total suppression
the patient’s negative associations with tinnitus and of the signal, preventing any retraining and conse-
reclassification of tinnitus into a category of neutral quently habituation; (4) partial suppression (“par-
stimuli. This is accomplished by educating the tial masking”), which does not prevent retraining
patients that their tinnitus results from a normal but does make it more difficult as the training is per-
compensatory mechanism, which occurs in the formed on a different stimulus than the original; and
auditory system, to typically minor changes in the (5) activation of limbic and autonomic nervous sys-
cochlea. As part of counseling, it is also important to tems by too loud or unpleasant sounds, yielding an
demystify the mechanisms through which tinnitus increase in tinnitus and contracting habituation.
may affect a patient’s life. Counseling in TRT is a It is intuitive that if the sound level is signifi-
teaching session aimed at providing patients with a cantly below the threshold level of detection, there is
new frame of reference by explaining potential no basis to believe that it asserts any effect on the
mechanisms of tinnitus generation, neurophysiolog- auditory system and tinnitus. On the other hand,
ical mechanisms through which tinnitus is influenc- when external sound becomes strong enough to
ing various aspects of their lives, and that by suppress detection of tinnitus-related neuronal
activating a naturally occurring mechanism of brain activity, by definition, any kind of retraining (includ-
function (habituation and the plasticity underlying ing habituation) is prevented because the brain can-
it), it is possible to achieve primarily habituation of not change reactions to a stimulus it cannot detect.
the tinnitus-induced reaction of the brain and the When the sound level is still below but close to
body and secondarily habituation of the tinnitus the threshold of detection, the phenomenon of sto-
perception. The clear goal of achieving an active and chastic resonance (eg, addition of a low level of noise
selective block of tinnitus-induced reactions is set can decrease the threshold of detection of the stim-
for the patients. ulus and enhance it when the stimulus is weak and
In addition to decreasing the strength of the close to the threshold of detection) comes into
activation of the limbic and autonomic nervous sys- play.117 Recently, the presence of stochastic resonance
tems, initiated during the counseling session, the has been shown at the level of hair cells and the
second component of TRT is sound therapy.91,110 All auditory nerve, and preliminary data indicate its
of our senses are working on the principle of differ- effect on the loudness of tinnitus.119–121 The effective
ences of the stimuli from the background, and the sound level inducing stochastic resonance covers a
perceived strength of a signal is not linked directly to range of about 15 to 20 dB, beginning from about
the physical strength of a stimulus. At this moment, –5 dB below the threshold of detection of the origi-
468 Ballenger’s Otorhinolaryngology
nal signal. Thus, owing to stochastic resonance, by helps in initiating and sustaining the process of pas-
adding low-level external noise (eg, by using sound sive extinction of conditioned reflexes that link tin-
generators set at the threshold of hearing), paradox- nitus to negative reactions.39,110 As the background
ical enhancement of the tinnitus signal occurs. This activity is the sum of spontaneous and evoked activ-
will, in turn, make habituation more difficult. The ities, a decrease in the difference between the tinni-
results of a study in which a comparison was per- tus signal and the background neuronal activity can
formed among groups with counseling only (includ- be achieved by exposing patients to additional exter-
ing advice on using environmental sounds), nal sound.
counseling combined with sound generators set at This principle, if working alone, would imply
the threshold of hearing, and counseling combined that we should use a sound that is as intense as pos-
with sound generators set close to the “mixing” point sible. Two other factors (3 and 4), however, become
fully support the prediction of the importance of dominant. First, once the tinnitus signal is sup-
stochastic resonance. The group that performed the pressed, habituation will not occur by definition
worst was the one with the sound level set close to owing to the lack of a signal to habituate (principle
the threshold of hearing, whereas the group that per- 3). Second, when the sound level surpasses the
formed the best was the one with the sound level set threshold of partial tinnitus suppression (“partial
at the “mixing point,” with the counseling-only masking”), it will modify not only the intensity but
group in the middle.122 also the quality of the tinnitus signal. Then retrain-
When sound level is increased further, the ing of neuronal networks will occur to the modified
mechanism involving the decreased difference tinnitus signal and not to the original one. Owing to
between the tinnitus signals and background neu- the generalization principle (eg, reaction can be
ronal activity becomes the dominant factor. As with induced to stimuli similar to the original, with the
all perception, the difference between signal and strength depending on the difference between the
background plays a dominant role. By decreasing the original and the modified signals), some habituation
difference between the tinnitus-related neuronal may still occur. The higher the external sound is
activity and the background ongoing neuronal activ- above the threshold of partial masking, the smaller
ity, the effective strength of the tinnitus signal its contribution to habituation. Finally, once a level
decreases, and this weaker signal is passed to the of total suppression is reached, the effectiveness of
higher-level cortical areas and, most importantly, to habituation is decreased to zero as the brain is
the limbic and autonomic nervous systems. This unable to retrain to an undetectable signal.
Tinnitus and Hyperacusis 469
The optimal setting of the sound level is dif- should be modified. This is one of the reasons why
ferent when hyperacusis is the dominant or only follow-up contacts are important; first, to continue
problem. In this situation, the effect of stochastic counseling, second, to check patient status; and
resonance is of secondary importance to the primary third, to modify protocol if necessary.
need not to overstimulate the auditory system. Typically, the first effects of TRT are seen in
Patients start with a sound level closer to their about 3 months, with clear improvement in about 6
threshold but as high as their sound sensitivity months, and many patients achieve a high level of
allows, with the aim to be above the range of sto- control of their tinnitus by about 12 months.47,52,59,125
chastic resonance. Once a partial reversal of hypera- Patients are advised to follow the TRT protocol for
cusis is achieved, the sound level can be increased approximately 18 months to prevent a relapse.
rapidly to address tinnitus directly. At this point, the Improvement in hyperacusis is typically faster, and
rules previously outlined for patients with tinnitus the success rate is higher than that of tinnitus with-
should be followed. out hyperacusis. The results from other centers and
The need to preserve stimulation in the low- ours using TRT show satisfactory results in over 80%
frequency range yields a strong recommendation for of patients.122,124–127
people who have relatively normal low-frequency
hearing to be provided with devices or hearing aids
with fittings as open as possible. It is not sufficiently TREATMENTS FOR HYPERACUSIS
appreciated that in the normal acoustic environment Treatments for hyperacusis go into two contrary
there is a high proportion of low-frequency sounds, directions. First, the most common approach is to
below 200 Hz, which provide constant stimulation advise patients to avoid sound and use ear protec-
of the auditory pathways. Since the majority of tion. This is based on reasoning that because
patients have relatively normal hearing in this fre- patients became sensitive to sound, this may indi-
quency range, they benefit from this stimulation. cate that they are more susceptible to sound expo-
Consequently, blocking the ear canal with closed ear sure and consequently need extra protection.
molds decreases the auditory input, and many Patients easily embrace this philosophy and start to
patients experience enhancement of tinnitus when protect their ears, even to the extent of using
their ears are blocked. earplugs in quiet environments. Unfortunately, this
Note that even the best hearing aids act as approach actually makes the auditory system even
earplugs in low frequencies when they are the in- more sensitive and further exacerbates hyperacusis.
the-canal type or are fitted with a closed mold as The second approach involves the desensitiza-
they are unable to reproduce frequencies below 200 tion of patients by exposure to a variety of sounds.
to 250 Hz owing to restriction based on the physics The desensitization approach has been promoted for
of sound generation by a loudspeaker. Note that some time with a variety of protocols and types of
hearing aids for patients with tinnitus are used pri- sounds used, such as the recommendation of using
marily as a part of sound therapy to provide extra sound with certain frequencies removed, short expo-
amplification of background sounds and only sec- sures to moderately loud sound, or prolonged ex-
ondarily for communicative purposes. Other tools posures to low-level sounds.50,52,128 According to
may also be used to enrich the auditory background principles of the neurophysiological model of tinni-
such as nature sounds, neutral music, or tabletop tus, the latter approach is recommended and is used
sound generators. as part of TRT. Note, that the misophonic compo-
Both counseling and sound use are dependent nent cannot be removed by desensitization, and a
on patient categorization, and issues related to separate approach needs to be implemented.
sound are summarized in Table 22–8. This catego-
rization provides general guidance for treatment Tinnitus Retraining Therapy for Decreased
with TRT.59,111 During the process of treatment, Sound Tolerance Tinnitus retraining therapy can
patients may move from one category to another help patients with both tinnitus and hyperacusis,
(eg, hyperacusis can be totally eliminated and con- and the presence of hyperacusis is one of the crucial
sequently the patient may move from category 3 to factors in categorization of the patients (see Table
1), and recommendations regarding sound use 22–8) and determining the optimal protocol for
470 Ballenger’s Otorhinolaryngology
Hyperacusis is significant sensitivity to environmental sounds typically associated with loudness discomfort levels below 100 dB
HL; Prolonged Sound-Induced Exacerbation of tinnitus/hyperacusis is when the effects persist to the following day; Subjective
Hearing Loss is perceived subjectively by patients as having a significant impact on their life; Impact on Life is the extent of
impact of tinnitus and/or hyperacusis on the patient’s life. Common treatment for each category involves counseling and the
use of an enriched auditory background.
their treatment. It is recommended that if hyperacu- There might be a need for a low setting of initial
sis is present, it has to be treated first. Although TRT sound level, which might bring patients to the range
offers only a treatment for tinnitus (not a cure), it of effects of stochastic resonance. The use of real-ear
can, in some patients, totally remove hyperacusis measurements, as a guide in setting and checking
and misophonia, thus providing a cure for these sound level for all patients with instrumentation
conditions.59,60,111 during initial and follow-up visits, is crucial in the
In some patients, tinnitus and hyperacusis are case of hyperacusis patients.
two manifestations of the same internal mechanisms The method of desensitization works on the
of increased gain within the auditory pathways, and auditory system and consequently will not affect
the improvement in hyperacusis results in the misophonia, which needs to be addressed using
improvement in tinnitus as well. Moreover, the active extinction of conditioned reflexes between the
removal of hyperacusis yields a decrease in general auditory and limbic systems. This is achieved in
anxiety and stress, which, in combination with practice by instructing patients to engage systemati-
proper counseling, significantly facilitates tinnitus cally in activities involving sound as a fundamental
habituation. component and that are pleasant (such as actively
A few parameters of the TRT protocol are of listening to music).
specific importance in treating patients with hyper-
acusis: avoidance of silence and continued exposure
to sound are even more important than for patients
CONCLUSION
with only tinnitus. The level of sound should be Tinnitus and hyperacusis are still challenging topics
better controlled during the treatment, which to study and symptoms to treat. Many questions
necessitates the use of wearable sound generators. remain unanswered. Mechanisms of tinnitus and
The sound used should never induce discomfort or hyperacusis are speculative and not yet proven. We
annoyance. do not yet have objective methods for detection and
The setting of sound generators for hyperacu- evaluation of tinnitus. We believe that the neuro-
sis is more complex than for tinnitus treatment. physiological model of tinnitus and TRT provide a
Tinnitus and Hyperacusis 471
promising approach that may ultimately result in a 12. Jastreboff PJ. Phantom auditory perception (tinni-
better understanding of tinnitus and in providing tus): mechanisms of generation and perception.
greater help to patients with tinnitus and hyperacusis. Neurosci Res 1990;8:221–54.
13. Muhlnickel W, Elbert T, Taub E, Flor H. Reorganiza-
tion of auditory cortex in tinnitus. Proc Natl Acad
REFERENCES Sci U S A 1998;95:10340–3.
1. McFadden D. Tinnitus: facts, theories, and treat- 14. Axelsson A, Ringdahl A. Tinnitus—a study of its
ments. Washington (DC): National Academy Press; prevalence and characteristics. Br J Audiol 1989;
1982. 23:53–62.
2. Coles RRA. Epidemiology, aetiology and classifica- 15. Leske MC. Prevalence estimates of communicative
tion. In: Reich GE, Vernon JA, editors. Proceedings of disorders in the U.S.A.: language, learning and
the Fifth International Tinnitus Seminar, 1995, Port- vestibular disorders. ASHA 1981;23:229–37.
land, OR, U.S.A. Portland (OR): American Tinnitus 16. George RN, Kemp S. A survey of New Zealanders
Association; 1996. p. 25–30. with tinnitus. Br J Audiol 1991;25:331–6.
3. Pilgramm M, Rychlick R, Lebisch H, et al. Tinnitus in 17. Fabijanska A, Rogowski M, Bartnik G, Skarzynski H.
the Federal Republic of Germany: a representative Epidemiology of tinnitus and hyperacusis in Poland.
epidemiological study. In: Hazell JWP, editor. Pro- In: Hazell JWP, editor. Proceedings of the Sixth
ceedings of the Sixth International Tinnitus Seminar, International Tinnitus Seminar, 1999, Cambridge,
1999, Cambridge, UK. London: Tinnitus and Hyper- UK. London: Tinnitus and Hyperacusis Center;
acusis Center; 1999. p. 64–7. 1999. p. 569–71.
4. Davis A, El Refaie A. Epidemiology of tinnitus. In: 18. Siwiec H. Epidemiology of tinnitus in Lublin dis-
Tyler R, editor. Tinnitus handbook. San Diego: Sin- trict. In: Hazell JWP, editor. Proceedings of the Sixth
gular, Thomson Learning; 2000. p. 1–23. International Tinnitus Seminar, 1999, Cambridge,
5. Heller MF, Bergman M. Tinnitus in normally hear- UK. London: Tinnitus and Hyperacusis Center;
ing persons. Ann Otol Rhinol Laryngol 1953; 1999. p. 572–3.
62:73–93. 19. Spoendlin H. Inner ear pathology and tinnitus. In:
6. Jastreboff PJ, Gray WC, Mattox DE. Tinnitus and Feldmann H, editor. Proceedings III International
hyperacusis. In: Cummings CW, Fredrickson JM, Tinnitus Seminar, Muenster 1987. Karlsruhe, Ger-
Harker LA, et al, editors. Otolaryngology head and many: Harsch Verlag; 1987. p. 42–51.
neck surgery. St. Louis: Mosby; 1998. p. 3198–222. 20. Nodar RH. Tinnitus aurium in school age children:
7. Jastreboff PJ. Tinnitus habituation therapy (THT) a survey. J Audiol Res 1972;12:133–5.
and tinnitus retraining therapy (TRT). In: Tyler R, 21. Mills RP, Albert DM, Brain CE. Tinnitus in child-
editor. Tinnitus handbook. San Diego: Singular, hood. Clin Otolaryngol 1986;11:431–4.
Thomson Learning; 2000. p. 357–76. 22. Mills RP, Cherry JR. Subjective tinnitus in children
8. Davis A. The aetiology of tinnitus: risk factors for with otological disorders. Int J Pediatr Otorhino-
tinnitus in the UK population—a possible role for laryngol 1984;7:21–7.
conductive pathologies? In: Reich GE, Vernon JA, 23. Gabriels P. Children with tinnitus. In: Reich GE, Ver-
editors. Proceedings of the Fifth International Tin- non JA, editors. Proceedings of the Fifth Interna-
nitus Seminar, 1995, Portland, OR, U.S.A. Portland tional Tinnitus Seminar, 1995, Portland, OR, U.S.A.
(OR): American Tinnitus Association; 1996. p. Portland (OR): American Tinnitus Association;
38–45. 1996. p. 270–5.
9. Stephens D. A history of tinnitus. In: Tyler RS, edi- 24. Stouffer JL, Tyler RS. Characterization of tinnitus by
tor. Tinnitus handbook. San Diego: Singular, Thom- tinnitus patients. J Speech Hear Disord 1990;55:
son Learning; 2000. p. 437–48. 439–53.
10. Feldmann H. History of tinnitus research. In: Shul- 25. Gurr P, Owen G, Reid A, Canter R. Tinnitus in preg-
man A, editor. Tinnitus diagnosis and treatment. nancy. Clin Otolaryngol 1993;18:294–7.
Philadelphia: Lea & Febiger; 1991. p. 3–37. 26. Kemp S, George RN. Diaries of tinnitus sufferers. Br
11. Feldmann H. Pathophysiology of tinnitus. In: Kita- J Audiol 1992;26:381–6.
hara M, editor. Tinnitus: pathophysiology and man- 27. Zelman S. Correlation of smoking history with hear-
agement. Tokyo: Igaku-Shoin; 1988. p. 7–35. ing loss. JAMA 1973;223:920.
472 Ballenger’s Otorhinolaryngology
28. Ronis ML. Alcohol and dietary influences on tinni- ination and tinnitus. Acta Otolaryngol (Stockh)
tus. J Laryngol Otol 1984;98 Suppl 9:242–6. 1981;91:469–79.
29. Tonndorf J. The analogy between tinnitus and pain: 42. Zenner H-P, Ernst A. Cochlear-motor, transduction
a suggestion for a physiological basis of chronic tin- and signal-transfer tinnitus. Eur Arch Otolaryngol
nitus. Hear Res 1987;28:271–5. 1993;249:447–54.
30. Tonndorf J. Stereociliary dysfunction, a case of sen- 43. LePage EL. A model for cochlear origin of subjective
sory hearing loss, recruitment, poor speech discrim- tinnitus: excitatory drift in the operating point of
ination and tinnitus. Acta Otolaryngol (Stockh) inner hair cells. In: Vernon J, Møller AR, editors.
1981;91:469–79. Mechanisms of tinnitus. Boston: Allyn & Bacon;
31. Kiang NYS, Moxon EC, Levine RA. Auditory-nerve 1995. p. 115–47.
activity in cats with normal and abnormal cochleas. 44. Jastreboff PJ. Processing of the tinnitus signal within
In: Wolstenholme GEW, Knight J, editors. Ciba the brain. In: Reich GE, Vernon JA, editors. Proceed-
Foundation Symposium on Sensorineural Hearing ings of the Fifth International Tinnitus Seminar,
Loss. London: Churchill; 1970. p. 241–73. 1995, Portland, OR, U.S.A. Portland (OR): American
32. Salvi RJ, Ahroon WA. Tinnitus and neural activity. J Tinnitus Association; 1996. p. 58–67.
Speech Hear Res 1983;26:629–32. 45. Perry BP, Gantz BJ. Medical and surgical evaluation
33. Penner MJ. Two-tone forward masking patterns and and management of tinnitus. In: Tyler R, editor. Tin-
tinnitus. J Speech Hear Res 1980;23:779–86. nitus handbook. San Diego: Singular, Thomson
34. Møller AR. Pathophysiology of tinnitus. Ann Otol Learning; 2000. p. 221–41.
Rhinol Laryngol 1984;93:39–44. 46. Jastreboff PJ, Jastreboff MM, Sheldrake JB. Audiomet-
35. Eggermont JJ. On the pathophysiology of tinnitus: a rical characterization of hyperacusis patients before
review and a peripheral model. Hear Res 1990; and during TRT. In: Hazell JWP, editor. Proceedings of
48:111–24. the Sixth International Tinnitus Seminar, 1999, Cam-
36. Langner G, Wallhdusser-Franke E. Computer simu- bridge, UK. London: Tinnitus and Hyperacusis Cen-
lation of a tinnitus model based on labelling of tin- ter; 1999. p. 495–8.
nitus activity in the auditory cortex. In: Hazell JWP, 47. Jastreboff PJ, Gray WC, Gold SL. Neurophysiological
editor. Proceedings of the Sixth International Tinni- approach to tinnitus patients. Am J Otol 1996;17:
tus Seminar, 1999, Cambridge, UK. London: Tinni- 236–40.
tus and Hyperacusis Center; 1999. p. 20–5. 48. Jastreboff PJ, Hazell JWP. A neurophysiological
37. Jastreboff PJ. Tinnitus as a phantom perception: approach to tinnitus: clinical implications. Br J
theories and clinical implications. In: Vernon J, Audiol 1993;27:1–11.
Møller AR, editors. Mechanisms of tinnitus. Boston: 49. Wolk C, Seefeld B. The effects of managing hypera-
Allyn & Bacon; 1995. p. 73–94. cusis with maskers (noise generators). In: Hazell
38. Møller AR. Pathophysiology of severe tinnitus JWP, editor. Proceedings of the Sixth International
and chronic pain. In: Hazell JWP, editor. Proceedings Tinnitus Seminar, 1999, Cambridge, UK. London:
of the Sixth International Tinnitus Seminar, 1999, Tinnitus and Hyperacusis Center; 1999. p. 512–4.
Cambridge, UK. London: Tinnitus and Hyperacusis 50. Hazell JWP, Sheldrake JB. Hyperacusis and tinnitus. In:
Center; 1999. p. 26–31. Aran J-M, Dauman R, editors. Tinnitus 91. Proceedings
39. Jastreboff PJ. The neurophysiological model of tin- IV International Tinnitus Seminar, Bordeaux, France,
nitus and hyperacusis. In: Hazell JWP, editor. Pro- 1991. Amsterdam: Kugler Publications; 1992. p. 245–8.
ceedings of the Sixth International Tinnitus 51. Bartnik G, Fubijunska A, Ragowski M. Effects of tin-
Seminar, 1999, Cambridge, UK. London: Tinnitus nitus retraining therapy (TRT) for patients with tin-
and Hyperacusis Center; 1999. p. 32–8. nitus and subjective hearing loss versus tinnitus only.
40. Pujol R. Neuropharmacology of the cochlea and tin- Scand Audiol 2001;Suppl:206–8.
nitus. In: Aran J-M, Dauman R, editors. Tinnitus 91. 52. Jastreboff PJ, Jastreboff MM. Tinnitus retraining
Proceedings IV International Tinnitus Seminar, Bor- therapy (TRT) as a method for treatment of tinnitus
deaux, France, 1991. Amsterdam: Kugler Publica- and hyperacusis patients. J Am Acad Audiol 2000;
tions; 1992. p. 103–7. 11:156–61.
41. Tonndorf J. Stereociliary dysfunction, a cause of sen- 53. Stedman’s medical dictionary. 26th ed. Baltimore:
sory hearing loss, recruitment, poor speech discrim- Williams & Wilkins; 1995. Hyperacusis.
Tinnitus and Hyperacusis 473
54. American heritage dictionary. 3rd ed. Boston: Soft- 69. Jastreboff PJ, Ikner CL, Hassen A. An approach to
Key International; 1994. Hyperacusis. objective evaluation of tinnitus in humans. In Aran
55. Hood JD, Poole JP. Tolerable limit to loudness: its J-M, Dauman R, editors. Tinnitus 91. Proceedings
clinical and physiological significance. J Acoust Soc IV International Tinnitus Seminar, Bordeaux,
Am 1966;40:47–53. France, 1991. Amsterdam: Kugler Publications; 1992.
56. Cox RM, Alexander GC, Taylor IM, Gray GA. The p. 331–40.
contour test of loudness perception. Ear Hear 70. Jacobson GP, Ahmad BK, Morgan J, et al. Auditory
1997;18:388–400. evoked cortical magnetic field (M100-M200) meas-
57. Byrne D, Dirks D. Effects of acclimatization and dep- urements in tinnitus and normal groups. Hear Res
rivation on non-speech auditory abilities. Ear Hear 1991;56:44–52.
1996;17 Suppl:29S–37S. 71. Jacobson GP, Calder JA, Newman CW, et al. Electro-
58. Stephens SD, Anderson C. Experimental studies on physiological indices of selective auditory attention
the uncomfortable loudness level. J Speech Hear Res in subjects with and without tinnitus. Hear Res
1971;14:262–70. 1996;97:66–74.
59. Jastreboff PJ. Categories of the patients and the treat- 72. Martin WH, Schwegler JW, Shi J, et al. Developing an
ment outcome. In: Hazell JWP, editor. Proceedings of objective measurement tool for evaluating tinnitus:
the Sixth International Tinnitus Seminar, 1999, Cam- spectral averaging. In: Vernon JA, Reich G, editors.
bridge, UK. London: Tinnitus and Hyperacusis Cen- Proceedings of the Fifth International Tinnitus Sem-
ter; 1999. p. 394–8. inar, 1995, Portland, OR, U.S.A. Portland (OR):
60. Jastreboff PJ. Tinnitus. In: Gates GA, editor. Current American Tinnitus Association; 1996. p. 127–34.
therapy in otolaryngology head and neck surgery. St. 73. Hallberg LR-M, Erlandsson SI. Tinnitus characteris-
Louis: Mosby, 1998. p. 90–5. tics in tinnitus complainers and noncomplainers. Br
61. Anari M, Axelsson A, Elies W, Magnusson L. Hyper- J Audiol 1993;27:19–27.
sensitivity to sound—questionnaire data, audiom- 74. Adour KK, Wingerd J. Idiopathic facial paralysis
etry and classification. Scand Audiol 1999;28:219–30. (Bell’s palsy): factors affecting severity and outcome
62. Lockwood AH, Salvi RJ, Coad ML, et al. The func- in 446 patients. Neurology 1974;24:1112–6.
tional neuroanatomy of tinnitus: evidence for limbic 75. Fallon BA, Nields JA, Burrascano JJ, et al. The neu-
system links and neural plasticity. Neurology 1998; ropsychiatric manifestation of Lyme borreliosis. Psy-
50:114–20. chiatr Q 1992;63:95–117.
63. Melcher JR, Sigalovski I, Levine RA. Tinnitus-related 76. Nields JA, Fallon BA, Jastreboff PJ. Carbamazepine
fMRI activation patterns in human auditory nuclei. in the treatment of Lyme disease-induced hyperacu-
In: Hazell JWP, editor. Proceedings of the Sixth sis. J Neuropsychiatr Clin Neurosci 1999;11:97–9.
International Tinnitus Seminar, 1999, Cambridge, 77. Klein AJ, Armstrong BL, Greer MK, Brown FR.
UK. London: Tinnitus and Hyperacusis Center; Hyperacusis and otitis media in individuals with
1999. p. 166–70. Williams syndrome. J Speech Hear Disord 1990;
64. Lockwood AH, Wack DS, Burkard RF, et al. The 55:339–44.
functional anatomy of gaze-evoked tinnitus and sus- 78. Wayman DM, Pham HN, Byl FM, Adour KK. Audi-
tained lateral gaze. Neurology 2001;56:472–80. ological manifestations of Ramsay Hunt syndrome.
65. Andersson G, Lyttkens L, Hirvela C, et al. Regional J Laryngol Otol 1990;104:104–8.
cerebral blood flow during tinnitus: a PET case study 79. McCandless GA, Goering DM. Changes in loudness
with lidocaine and auditory stimulation. Acta Oto- after stapedectomy. Arch Otolaryngol 1974;100:
laryngol (Stockh) 2000;120:967–72. 344–50.
66. Penner MJ. Linking spontaneous otoacoustic emis- 80. Fukaya T, Nomura Y. Audiological aspects of idio-
sions and tinnitus. Br J Audiol 1992;26:115–23. pathic perilymphatic fistula. Acta Otolaryngol Suppl
67. Lind O. Transient-evoked otoacoustic emissions and (Stockh) 1988;456:68–73.
contralateral suppression in patients with unilateral 81. Waddell PA, Gronwall DMA. Sensitivity to light and
tinnitus. Scand Audiol 1996;25:167–72. sound following minor head injury. Acta Neurol
68. McKee GJ, Stephens SD. An investigation of nor- Scand 1984;69:270–6.
mally hearing subjects with tinnitus. Audiology 82. Vingen JV, Pareja JA, Storen O, et al. Phonophobia in
1992;31:313–7. migraine. Cephalalgia 1998;18:243–9.
474 Ballenger’s Otorhinolaryngology
83. Gopal KV, Daly DM, Daniloff RG, Pennartz L. San Diego: Singular, Thomson Learning; 2000. p.
Effects of selective serotonin reuptake inhibitors on 377–98.
auditory processing: case study. J Am Acad Audiol 99. Hazell JWP, Jastreboff PJ, Meerton LE, Conway MJ.
2000;11:454–63. Electrical tinnitus suppression: frequency depend-
84. Lader M. Anxiolytic drugs: dependence, addiction ence of effects. Audiology 1993;32:68–77.
and abuse. Eur Neuropsychopharmacol 1994;4:85–91. 100. Olanow CW, Brin MF, Obeso JA. The role of deep
85. Oen JM, Begeer JH, Staal-Schreinemachers A, Tijm- brain stimulation as a surgical treatment for
stra T. Hyperacusis in children with spina bifida; a Parkinson’s disease. Neurology 2000;55(12 Suppl
pilot-study. Eur J Pediatr Surg 1997;7 Suppl 1:46. 6):60–6.
86. Henkin RI, Daly RL. Auditory detection and percep- 101. Martin WH, Shi Y-B, Burchiel KJ, Anderson VC.
tion in normal man and in patients with adrenal Deep brain stimulation effects on hearing function
cortical insufficiency: effect of adrenal cortical and tinnitus. In: Hazell JWP, editor. Proceedings of
steroids. J Clin Invest 1968;47:1269–80. the Sixth International Tinnitus Seminar, 1999,
87. Jastreboff PJ, Mattox DE. Treatment of hyperacusis Cambridge, UK. London: Tinnitus and Hyperacu-
by aspirin. In: Abstracts of the 21st Midwinter Re- sis Center; 1999. p. 68–72.
search Meeting, Association for Research in Otolaryn- 102. Tyler RS. Tinnitus in the profoundly hearing-
gology, St. Petersburg Beach, FL, 1998. www.aro.org. impaired and the effects of cochlear implants. Ann
88. Boettcher FA, Salvi RJ. Functional changes in the Otol Rhinol Laryngol Suppl 1995;165:25–30.
ventral cochlear nucleus following acute acoustic 103. Tyler RS, Kelsay D. Advantages and disadvantages
overstimulation. J Acoust Soc Am 1993;94:2123–34. reported by some of the better cochlear-implant
89. Gerken GM. Alteration of central auditory process- patients. Am J Otol 1990;11:282–9.
ing of brief stimuli: a review and a neural model. J 104. Portmann M, Cazals Y, Negrevergne M, Aran J-M.
Acoust Soc Am 1993;93:2038–49. Temporary tinnitus suppression in man through
90. Marriage J, Barnes NM. Is central hyperacusis a electrical stimulation of the cochlea. Acta Oto-
symptom of 5-hydroxytryptamine (5-HT) dysfunc- laryngol (Stockh) 1979;87:294–9.
tion? J Laryngol Otol 1995;109:915–21. 105. Vernon J. Attemps to relieve tinnitus. J Am Audiol
91. Jastreboff PJ. Optimal sound use in TRT—theory Soc 1977;2:124–31.
and practice. In: Hazell JWP, editor. Proceedings of 106. Vernon J, Schleuning A. Tinnitus: a new manage-
the Sixth International Tinnitus Seminar, 1999, ment. Laryngoscope 1978;88:413–9.
Cambridge, UK. London: Tinnitus and Hyperacusis 107. Schleuning AJ, Johnson RM, Vernon JA. Evaluation
Center; 1999. p. 491–4. of a tinnitus masking program: a follow-up study
92. Ricketts TA, Bentler RA. The effect of test signal type of 598 patients. Ear Hear 1980;1:71–4.
and bandwidth on the categorical scaling of loud- 108. Johnson RM. The masking of tinnitus. In: Vernon
ness. J Acoust Soc Am 1996;99:2281–7. JA, editor. Tinnitus treatment and relief. Boston:
93. Hawkins DB, Walden BE, Montgomery A, Prosek Allyn and Bacon; 1998. p. 164–86.
RA. Description and validation of an LDL procedure 109. Wilson PH, Henry JL. Psychological management
designed to select SSPL90. Ear Hear 1987;8:162–9. of tinnitus. In: Tyler R, editor. Tinnitus handbook.
94. Dobie RA. A review of randomized clinical trials in San Diego: Singular, Thomson Learning; 2000. p.
tinnitus. Laryngoscope 1999;109:1202–11. 263–79.
95. Pulec JL. Tinnitus: surgical therapy. Am J Otol 110. Jastreboff PJ. How TRT derives from the neuro-
1984;5:479–80. physiological model. In: Hazell JWP, editor. Pro-
96. Møller MB, Møller AR, Jannetta PJ, Jho HD. Vascu- ceedings of the Sixth International Tinnitus
lar decompression surgery for severe tinnitus: selec- Seminar, 1999, Cambridge, UK. London: Tinnitus
tion criteria and results. Laryngoscope 1993;103: and Hyperacusis Center; 1999. p. 87–91.
421–7. 111. Jastreboff PJ, Jastreboff MM. Tinnitus retraining
97. Berliner KI, Shelton C, Hitselberger WE, Luxford therapy. In: Baguley D, editor. Perspectives in tin-
WM. Acoustic tumors: effect of surgical removal on nitus management. New York: Thieme; 2001. p.
tinnitus. Am J Otol 1992;13:13–7. 51–63.
98. Dauman R. Electrical stimulation for tinnitus 112. Jastreboff PJ, Hazell JWP, Graham RL. Neurophys-
supression. In: Tyler R, editor. Tinnitus handbook. iological model of tinnitus: dependence of the
Tinnitus and Hyperacusis 475
minimal masking level on treatment outcome. International Tinnitus Seminar, 1999, Cambridge,
Hear Res 1994;80:216–32. UK. London: Tinnitus and Hyperacusis Center;
113. Albus JS. A theory of cerebellar function. Math 1999. p. 99–105.
Biosci 1971;10:25–61. 123. Jastreboff PJ, Jastreboff MM, Mattox DE. Statistical
114. Jastreboff PJ, Jastreboff MM. The neurophysiolog- analysis of the progress of tinnitus treatment dur-
ical model of tinnitus and its practical implemen- ing Tinnitus Retraining Therapy (TRT). In:
tation: current status. In: Myers EN, Bluestone CD, Abstracts of the 24th Midwinter Research Meeting.
Brackman DE, Krause CJ, editors. Advances in oto- Association for Research in Otolaryngology, St.
laryngology-head and neck surgery. Vol 15. St. Petersburg Beach, FL, 2001. www.aro.org.
Louis: Mosby; 2001. p. 135–47. 124. Sheldrake JB, Hazell JWP, Graham RL. Results of
115. Konorski J. Conditioned reflexes and neuronal tinnitus retraining therapy. In Hazell JWP, editor.
organization. Cambridge (UK): Cambridge Uni- Proceedings of the Sixth International Tinnitus
versity Press; 1948. Seminar, 1999, Cambridge, UK. London: Tinnitus
116. Konorski J. Integrative activity of the brain. and Hyperacusis Center; 1999. p. 292–6.
Chicago: University of Chicago Press; 1967. 125. Bartnik G, Fabijanska A, Rogowski M. Our experi-
117. Thompson RF, Donegan NH. Learning and mem- ence in treatment of patients with tinnitus and/or
ory. In: Adelman G, editor. Encyclopedia of neuro- hyperacusis using the habituation method. In:
science. Boston: Birkhauser; 1987. p. 571–4. Hazell JWP, editor. Proceedings of the Sixth Inter-
118. Koechlin E, Basso G, Pietrini P, et al. The role of national Tinnitus Seminar, 1999, Cambridge, UK.
the anterior prefrontal cortex in human cognition. London: Tinnitus and Hyperacusis Center; 1999. p.
Nature 1999;399:148–51. 415–7.
119. Jastreboff PJ, Jastreboff MM. Potential impact of 126. Heitzmann T, Rubio L, Cardenas MR, Zofio E. The
stochastic resonance on tinnitus and its treat- importance of continuity in TRT patients: results
ment. In: Abstracts of the 23rd Midwinter Meet- at 18 months. In: Hazell JWP, editor. Proceedings
ing. Association for Research in Otolaryngology, of the Sixth International Tinnitus Seminar, 1999,
St. Petersburg Beach, FL, 2000. www.aro.org. Cambridge, UK. London: Tinnitus and Hyperacu-
120. Jaramillo F, Wiesenfeld K. Mechanoelectrical trans- sis Center; 1999. p. 509–11.
duction assisted by Brownian motion: a role for 127. Herraiz C, Hernandez FJ, Machado A, et al. Tinni-
noise in the auditory system. Nat Neurosci 1998; tus retraining therapy: our experience. In: Hazell
1:384–8. JWP, editor. Proceedings of the Sixth International
121. Morse RP, Evans EF. Enhancement of vowel coding Tinnitus Seminar, 1999, Cambridge, UK. London:
for cochlear implants by addition of noise. Nat Tinnitus and Hyperacusis Center; 1999. p. 483–4.
Med 1996;2:928–32. 128. Vernon J, Press L. Treatment for hyperacusis. In:
122. McKinney CJ. An evaluation of the TRT method. Vernon JA, editor. Tinnitus treatment and relief.
In: Hazell JWP, editor. Proceedings of the Sixth Boston: Allyn and Bacon; 1998. p. 223–7.
CHAPTER 23
Cochlear Implants
Richard T. Miyamoto, MD, Karen Iler Kirk, PhD
Hearing loss poses a monumental obstacle to the the electrical signal across the skin from the external
acquisition and maintenance of effective communi- unit to the implanted electrode array is most com-
cation skills. The perception and the production of monly accomplished by the use of electromagnetic
speech are highly dependent on the ability to process induction or radiofrequency transmission. The criti-
auditory information. Early identification of hear- cal residual neural elements stimulated appear to be
ing loss is an important first step in managing the the spiral ganglion cells or axons. Damaged or miss-
effects of hearing impairment. Once identified, the ing hair cells of the cochlea are bypassed.
level of residual hearing, if any, must be determined
and an appropriate sensory aid recommended. Con-
ventional amplification is usually the initial proce-
COCHLEAR IMPLANT SYSTEMS
dure of choice. If little or no benefit is realized with Multichannel, multielectrode cochlear implant sys-
hearing aids, cochlear implants become therapeutic tems are designed to take advantage of the tonotopic
options. Communication skills and needs must be organization of the cochlea. The incoming speech
assessed and a communication mode selected. A signal is filtered into a number of frequency bands,
sophisticated multidisciplinary team approach that each corresponding to a given electrode in the array.
addresses the varied needs of the deaf recipient is Thus, multichannel cochlear implant systems use
required. Essential components of the aural/oral place coding to transfer spectral information in the
(re)habilitation program include listening skill speech signal as well as encode the durational and
development, speech therapy, speech-reading train- intensity cues of speech.
ing, and language instruction.
Djourno and Eyries first described direct elec-
trical excitation of the auditory nerve in 1957.1 Since
NUCLEUS COCHLEAR IMPLANT SYSTEMS
then, increasingly more sophisticated cochlear The Nucleus 22-channel cochlear implant manufac-
implants have been developed. Cochlear implants tured by Cochlear Ltd. of Australia was the first mul-
seek to replace a nonfunctional inner ear hair cell tichannel cochlear implant to receive US Food and
transducer system by converting mechanical sound Drug Administration (FDA) approval for use in
energy into electrical signals that can be delivered to adults and children, and it has been used in more
the cochlear nerve in profoundly deaf patients. The patients than any other cochlear implant system
essential components of a cochlear implant system worldwide.2 The Nucleus CI24M cochlear implant
are a microphone, which picks up acoustic informa- received FDA approval for adults and children in
tion and converts it to electrical signals; an externally 1998.
worn speech processor that processes the signal Early speech processing strategies (F0F2 and
according to a predefined strategy; and a surgically F0F1F2) for the Nucleus 22-channel cochlear
implanted electrode array that is in the cochlea near implant used feature extraction strategies that con-
the auditory nerve. veyed information about key speech features such as
The processed signal is amplified and com- the amplitude and frequency of vowel formants and
pressed to match the narrow electrical dynamic range the fundamental frequency of voiced sounds. The
of the ear. The typical response range of a deaf ear to third-generation speech processing strategy,
electrical stimulation is on the order of only 10 to 20 MPEAK, encoded additional high-frequency infor-
dB, even less in the high frequencies. Transmission of mation by stimulating two of three more basal fixed
476
Cochlear Implants 477
electrodes; the goal was to provide additional infor- tion (SAS), filters and then compresses the incoming
mation that would yield improved consonant recog- speech signal for simultaneous presentation to the
nition scores. corresponding enhanced bipolar electrodes. The rel-
Three processing strategies are currently avail- ative amplitudes of information in each channel and
able for use with the Nucleus cochlear implants. Two the temporal details of the waveforms in each chan-
of the strategies use the n-of-m approach, in which nel convey speech information.
the speech signal is filtered into m bandpass channels
and the n highest envelope signals are selected for
each cycle of stimulation.3 The spectral peak MEDICAL ELECTRONIC (MED-EL) COCHLEAR
(SPEAK) strategy is the most widely used with the IMPLANT SYSTEM
Nucleus 22-channel cochlear implant and is available The Combi 40+ cochlear implant system manufac-
to users of either the Nucleus 22-channel or the tured by the Med-El Corporation in Innsbruck, Aus-
Nucleus CI24M system. This strategy filters the tria, is currently undergoing clinical trials in the
incoming speech signal into 20 frequency bands; on United States. The Med-El cochlear implant has 12
each stimulation cycle, six electrodes (on average) are electrode pairs and has the capability of deep elec-
stimulated at a rate that varies adaptively from 180 to trode insertion into the apical regions of the cochlea.8
300 pulses per second. An n-of-m strategy using This device uses the CIS processing strategy and has
much higher rates of stimulation, known as the the capacity to provide the most rapid stimulation
Advanced Combined Encoder (ACE) strategy, can be rate of any of the cochlear implant systems currently
implemented in the new Nucleus CI24M device. The
available. Both body-worn and ear-level speech
third processing strategy available with the Nucleus
processors (the CIS Pro+ and Tempo+, respectively)
CI24M system is the Continuous Interleaved Sam-
are available for the Med-El cochlear implant.
pling (CIS) strategy.4 The CIS strategy filters the
speech signal into a fixed number of bands, obtains
the speech envelope, and then compresses the signal NEW DEVELOPMENTS IN COCHLEAR IMPLANT
for each channel. On each cycle of stimulation, a ELECTRODE DESIGN
series of interleaved digital pulses rapidly stimulates
consecutive electrodes in the array. The CIS strategy New designs of the internal electrode array have
is designed to preserve fine temporal details in the recently been introduced for the Nucleus and Clar-
speech signal by using high-rate, pulsatile stimuli. ion cochlear implants. The Nucleus Contour elec-
Two different speech processors are available trode array is a curved electrode that is straightened
for new Nucleus cochlear implant recipients. The by a stylet for insertion purposes. After surgical
body-worn SPRINT processor (Cochlear Ltd., placement into the scala tympani, the stylet is with-
Australia) can implement any of the three current drawn. The electrode then assumes its preformed
speech processing strategies. The ear-level ESPRIT shape, more closely approximating the modiolar
speech processor (Cochlear Ltd., Australia) can wall of the cochlea (Figure 23–1). The Clarion HiFo-
currently implement only the SPEAK processing cus electrode is positioned closer to the modiolar
strategy. wall by inserting a separate positioner into the scala
tympani. Because the spiral ganglion cells are
thought to be the sites stimulated by cochlear
CLARION COCHLEAR IMPLANT SYSTEM
implants, directing the electrodes toward the modi-
The Clarion multichannel cochlear implant system olus and further positioning the array may improve
is manufactured by Advanced Bionics Corporation spatial specificity of stimulation and reduce the cur-
(Sylmar, Calif.).5–7 This device has been approved by rent need to drive the electrodes.9
the FDA for use in adults (1996) and children
(1997). The Clarion multichannel cochlear implant
has an eight-channel electrode array. Two process- PATIENT SELECTION
ing strategies can be implemented through a body- The selection of cochlear implant candidates is a
worn processor. The first is CIS, described above, complex process that requires careful consideration
which is used to stimulate monopolar electrodes. of many factors. Current selection considerations are
The second strategy, Simultaneous Analog Stimula- as follows.
478 Ballenger’s Otorhinolaryngology
free of infection, and the tympanic membrane poralis muscle to give added thickness. A subpe-
should be intact. If these conditions are not met, riosteal pocket is created for positioning the implant
medical or surgical treatment before implantation is induction coil (Figure 23–2). A bone pocket well tai-
required. The management of middle ear effusions lored to the device being implanted is created, and
in children who are under consideration for cochlear the induction coil is fixed to the cortex with a fixa-
implantation or who already have a cochlear implant tion suture or periosteal flaps.
deserves special consideration. Conventional antibi- Following development of the skin incision, a
otic treatment usually accomplishes this goal, but mastoidectomy is performed. The horizontal semicir-
when it does not, treatment by myringotomy and cular canal is identified in the depths of the mastoid
insertion of tympanostomy tubes may be required. antrum, and the short process of the incus is identi-
Removal of the tube several weeks before cochlear fied in the fossa incudis. The facial recess is opened
implantation usually results in a healed, intact tym- using the fossa incudis as an initial landmark. The
panic membrane. When an effusion occurs in an ear facial recess is a triangular area bound by (a) the fossa
with a cochlear implant, no treatment is required as incudis superiorly, (b) the chorda tympani nerve lat-
long as the effusion remains uninfected. Chronic oti- erally and anteriorly, and (c) the facial nerve medially
tis media, with or without cholesteatoma, must be and posteriorly (Figure 23–3). The facial nerve can
resolved before implantation; this is accomplished usually be visualized through the bone without expos-
with conventional otologic treatments. Prior ear sur- ing it. The round window niche is visualized through
gery that has resulted in a mastoid cavity does not the facial recess about 2 mm inferior to the stapes.
contraindicate cochlear implantation, but this situa- Occasionally, the round window niche is posteriorly
tion may require mastoid obliteration with closure positioned and is not well visualized through the
of the external auditory canal or reconstruction of facial recess or is obscured by ossification. Particularly
the posterior bony ear canal. in these situations, it is important not to be misdi-
rected by hypotympanic air cells. Entry into the scala
tympani is accomplished best through a
PSYCHOLOGICAL ASSESSMENT cochleostomy created anterior and inferior to the
Psychological testing is performed for exclusionary annulus of the round window membrane. A small
reasons to identify subjects who have organic brain fenestra slightly larger than the electrode to be
dysfunction, mental retardation, undetected psy- implanted (usually 0.5 mm) is developed. A small dia-
chosis, or unrealistic expectations. Valuable infor- mond bur is used to “blue line” the endosteum of the
mation related to the family dynamics and other scala tympani, and the endosteal membrane is
factors in the patient’s milieu that may affect implant removed by using small picks. This approach bypasses
acceptance and performance are assessed. the hook area of the scala tympani, allowing direct
insertion of the active electrode array (Figure 23–4).
After insertion of the active electrode array, the
SURGICAL IMPLANTATION cochleostomy area is sealed with small pieces of fascia.
Cochlear implantation in both children and adults
requires meticulous attention to the delicate tissues
and small dimensions. Skin incisions are designed to
SPECIAL SURGICAL CONSIDERATIONS
provide access to the mastoid process and coverage Cochlear Dysplasia In cases of cochlear dysplasia,
of the external portion of the implant package while a CSF gusher may be encountered on fenestrating
preserving the blood supply of the postauricular the cochlea while performing the cochleostomy. The
skin. The incision used at the Indiana University flow of CSF has been successfully controlled by
Medical Center has eliminated the need to develop a entering the cochlea through a small fenestra, allow-
large postauricular flap. The inferior extent of the ing the CSF reservoir to drain off, inserting the elec-
incision is made well posterior to the mastoid tip to trode into the cochleostomy, and tightly packing the
preserve the branches of the postauricular artery. electrode at the cochleostomy with fascia. It is
From here the incision is directed posterior-superi- postulated that the source of the leak is through the
orly and then superiorly, without a superior-anterior lateral end of the internal auditory canal. Supple-
limb. In children, the incision incorporates the tem- mentally, a lumbar drain can be placed to reduce the
482 Ballenger’s Otorhinolaryngology
CLINICAL RESULTS
Cochlear implants are an established therapeutic
option for selected deaf adults and children. How-
ever, there remains a wide range of performance
with current implant systems. Some cochlear
implant recipients can communicate without the
benefit of speech reading and are able to communi-
cate on the telephone without a telephone code,
FIGURE 23–4. A, Electrode introduced into the basal whereas others use their implants primarily to re-
turn of the cochlea. B, Electrode in the scala tympani establish environmental contact and enhance their
(C, cross-section of the basal turn on the cochlea). D, speech-reading abilities. This variation in perform-
Receiver-stimulator with a redundant loop of electrode ance levels is thought to relate to biologic and cog-
in the mastoid. nitive factors. It would be expected that poor
auditory nerve survival or atrophic central auditory
systems would correlate with poor performance,
Complications Complications have been infre- whereas a more intact auditory nervous system
quent with cochlear implant surgery and can largely should permit better results, given a well-designed
be avoided by careful preoperative planning and and fitted cochlear prosthesis.30
meticulous surgical technique. Among the most
commonly encountered problems are those associ-
ated with the incision and postauricular flap and
PERFORMANCE RESULTS IN ADULTS
facial nerve injury.28 Using the incision we describe, Early Nucleus cochlear implant systems using fea-
we have experienced only one flap breakdown in our ture extraction speech processing strategies yielded
pediatric cochlear implant population. (This moderate vowel and consonant recognition31 but
occurred several years postoperatively after head only limited auditory-only word recognition.32
trauma.) We experienced one transient delayed However, with each successive generation of Nucleus
facial paresis and one CSF gusher in a child with a speech processing strategy, substantial gains were
Mondini deformity.29 Several additional patients achieved in open-set word and sentence recognition
with the large vestibular aqueduct syndrome have and were reported with mean word and sentence
also had gushers. recognition scores of 36 and 74%, respectively, for
Because children are more susceptible to otitis adults with the SPEAK strategy.33–38 Similar per-
media than adults, justifiable concern has been formance levels have been reported for adults who
expressed that a middle ear infection could cause an use either the Clarion or the Med-El cochlear
implanted device to become an infected foreign body, implant system.39,40 Compared with the results
requiring its removal. Two children in our series expe- obtained with previous generations of cochlear
rienced a delayed mastoiditis (several years after the implants, adults who use the current devices achieve
implant surgery), resulting in a postauricular abscess. higher word recognition skills and acquire those
These patients were treated by incision and drainage skills at a faster rate. Many adults now demonstrate
and intravenous antibiotics without the need to substantial speech understanding as early as 3
remove the implant. Of even greater concern is that months following cochlear implantation.41 On aver-
infection might extend along the electrode into the age, multichannel cochlear implant systems provide
484 Ballenger’s Otorhinolaryngology
moderate to good levels of auditory-only speech tion benefits in children, just as in adults. Many chil-
understanding to the majority of adult users. How- dren with current cochlear implant devices achieve
ever, a great deal of variability in performance at least moderate levels of open-set word recogni-
remains. Some adults are unable to understand any tion. For example, Cohen et al reported word recog-
speech through listening alone, whereas others can nition scores for a group of 19 children that ranged
communicate successfully on the telephone. As Wil- from 4 to 76% words correct with a mean of 44%.53
son and his colleagues pointed out, a number of Similarly, Osberger et al reported average scores of
within-subject factors also contribute to successful approximately 30% correct on a more difficult
cochlear implant use.42 Two such factors are age at measure of isolated word recognition in children
implantation and duration of deafness.41,43–47 Specif- with the Clarion cochlear implant.54 The develop-
ically, patients who are implanted at a young age and ment rate of postimplant auditory skills seems to be
have a shorter period of auditory deprivation are increasing as cochlear implant technology improves
more likely to achieve good outcomes. The findings and as children are implanted at a younger age.53–55
regarding other predictive factors have been less Furthermore, comparison studies have shown that
conclusive. For example, Gantz et al found that the speech perception abilities of pediatric cochlear
measures of cognitive ability were not associated implant recipients meet or exceed those of their
with patient performance,32 whereas Cohen et al peers with unaided pure-tone average thresholds
reported that measures of IQ were significantly asso- ≥ 90 dB HL who use hearing aids.56,57
ciated with good speech perception skills.44 Other A number of demographic factors have been
factors that have been found to significantly corre- shown to influence performance results in children
late with adult outcomes include speech-reading with cochlear implants. Early results suggested better
ability44,45 and degree of residual hearing.45,48 speech perception performance in children deafened
at an older age, with a corresponding shorter period
of deafness.52,58,59 However, when only children with
PERFORMANCE RESULTS IN CHILDREN prelingual deafness (ie, < 3 years) were considered,
Postlingually deafened adults and children use the age at onset of hearing loss was no longer a signifi-
information transmitted by a cochlear implant to cant factor.60 It is evident that earlier implantation
make comparisons to previously stored representa- yields superior cochlear implant performance in chil-
tions of spoken language. However, the majority of dren.61–66 Although the critical period for implanta-
children who receive cochlear implants have con- tion of congenitally or prelingually deafened children
genital or prelingually acquired hearing loss. These has not been determined,67 preliminary evidence sug-
children must use the sound provided by a cochlear gests that implantation prior to age 3 years may yield
implant to acquire speech perception, speech pro- improved results.68–70 Finally, the variables of com-
duction, and spoken language skills. Furthermore, munication mode and/or unaided residual hearing
because young children have limited linguistic skills also influence speech perception performance.71–74
and attention spans, the assessment of performance Oral children, and those who have more residual
in this population can be quite challenging. To eval- hearing prior to implantation, typically demonstrate
uate the communication benefits of cochlear superior speech understanding. This has led to some
implant use in children effectively, a battery of tests controversy regarding whether to implant the better-
that are developmentally and linguistically appro- or the poorer-hearing ear.48,72
priate should be employed.49,50
Speech Intelligibility and Language Im-
Speech Perception Outcomes In early investiga- provements in speech perception are the most direct
tions, children who used the Nucleus cochlear benefit of cochlear implantation. However, if chil-
implant with a feature extraction strategy demon- dren with cochlear implants are to succeed in the
strated significant improvement in closed-set word hearing world, they must also acquire intelligible
identification (ie, the ability to identify words from speech and their surrounding linguistic system. The
a limited set of alternatives) but very limited open- speech intelligibility and language abilities of chil-
set word recognition.51,52 The introduction of newer dren with cochlear implants improve significantly
processing strategies yielded greater speech percep- over time67,75–78 and, on average, exceed those of their
Cochlear Implants 485
age- and hearing-matched peers with hearing DC00064, RO1 DC00423, and K23 DC00126 and by
aids.77,78 Speech intelligibility and spoken language Psi Iota Xi.
acquisition are significantly correlated with the
development of auditory skills.76,79 Although a great REFERENCES
deal of variability exists, the best pediatric cochlear
implant users demonstrate highly intelligible speech 1. Djourno A, Eyries C. Prothese auditive par excita-
and age-appropriate language skills. These superior tion electrique a distance du nerf sensoriel a l’aide
performers are usually implanted at a young age and d’un bobinage inclus a demeure. Presse Med
are educated in an oral/aural modality.76 1957;35:14–7.
2. Clark GM, Tong YC, Dowell RC, et al. A multiple-
channel cochlear implant: an evaluation using non-
CONCLUSION sense syllables. Ann Otol Rhinol Laryngol 1981;
Cochlear implants are an appropriate sensory aid for 90:227–30.
selected deaf children and adults who receive mini- 3. Wilson BS. Strategies for representing speech infor-
mal benefit from conventional amplification. mation with cochlear implants. In: Niparko JK, Kirk
Improvements in technology and refinements in KI, Robbins AM, et al, editors. Cochlear implants:
candidacy criteria have secured a permanent role for principles and practices. Philadelphia: Lippincott
cochlear implantation. With improved postoperative Williams & Wilkins; 2000. p. 129–70.
performance, a clear justification for implanting not 4. Wilson BS, Lawson DT, Finley CC, et al. Coding
only patients with bilateral profound sensorineural strategies for multichannel cochlear prostheses. Am
hearing loss but also patients with severe sen- J Otol 1991;12 Suppl 1:56–61.
sorineural hearing loss has been established. Patients 5. Schindler RA, Kessler DK. The UCSF/Storz cochlear
as young as 12 months of age may be implanted implant: patient performance. Am J Otol 1987;
under current FDA guidelines for clinical trials, and 8:247–55.
experience with even younger children is accumu- 6. Schindler RA, Kessler DK. Clarion cochlear implant:
lating. phase I investigational results. Am J Otol 1993;
Wide intersubject performance variability con- 14:263–72.
tinues to exist. However, most postlingually deaf- 7. Kessler DK, Schindler RA. Progress with a multi-
ened adults with current cochlear implants achieve strategy cochlear system: the Clarion. In: Hochmair-
auditory-only word recognition and communicate Desoyer IJ, Hochmair ES, editors. Advances in
very effectively when auditory cues are combined cochlear implants. Wein, Austria: Manz; 1994.
with speech reading. The best adult recipients can p. 354–62.
converse fluently without speech-reading cues. Chil- 8. Gstoettner WK, Baumgartner WD, Franz P, et al.
dren using cochlear implants have acquired speaking Cochlear implant deep insertion surgery. Laryngo-
and listening skills and have developed a spoken lan- scope 1997;107:544–6.
guage system that is beyond what previously could 9. Wilson BS. Cochlear implant technology. In:
be achieved with hearing aids. Children who are Niparko JK, Kirk KI, Robbins AM, et al, editors.
implanted at a young age and use oral communica- Cochlear implants: principles and practices.
tion have the best prognosis for developing intelligi- Philadelphia: Lippincott Williams & Wilkins; 2000.
ble speech and age-appropriate language abilities. p. 109–27.
Challenges remain in effectively assessing 10. Berliner KI. Selection of cochlear implant patients.
peripheral auditory neuronal survival and matching In: Schindler RA, Merzenich MM, editors. Cochlear
electrically transmitted signals to the future poten- implants. New York: Raven Press; 1985. p. 395–402.
tial of the central auditory system in deaf subjects. 11. Horn KL, McMahon NB, McMahon DC, et al. Func-
tional use of the Nucleus 22-channel cochlear
implant in the elderly. Laryngoscope 1991;101:
ACKNOWLEDGMENT 284–8.
This work was supported in part by National Insti- 12. Waltzman SB, Cohen NL. Implantation of patients
tutes of Health National Institute on Deafness and with prelingual long-term deafness. Ann Otol Rhinol
Other Communication Disorders grants RO1 Laryngol 1999;108:84–7.
486 Ballenger’s Otorhinolaryngology
13. Matsushima JI, Shepard RK, Seldon HL, et al. Elec- 28. Hoffman RA, Cohen NL. Complications of cochlear
trical stimulation of the auditory nerve in deaf kit- implant surgery. Ann Otol Rhinol Laryngol 1995;104
tens: effects on cochlear nucleus morphology. Hear Suppl 166:420–2.
Res 1991;56:133–42. 29. Miyamoto RT, Young M, Myres WA, et al. Complica-
14. Lenarz T. Cochlear implantations in children under tions of pediatric cochlear implantation. Eur Arch
the age of two years. Adv Otorhinolaryngol 1997; Otorhinolaryngol 1996;253:1–4.
52:204–10. 30. Kessler DK, Loeb GE, Barker MJ. Distribution of
15. Yune HY, Miyamoto RT. Medical imaging in speech recognition results with the Clarion cochlear
cochlear implant candidates. Am J Otol 1991;12 prosthesis. Ann Otol Rhinol Laryngol 1995;104
Suppl:11–7. Suppl 166:283–5.
16. Jensen J. Tomography of the inner ear in deaf chil- 31. Blamey PJ, Dowell RC, Brown AM, et al. Vowel and
dren. Radiological demonstration of two cases with consonant recognition of cochlear implant patients
the Mondini malformation. J Laryngol Otol 1967; using formant-estimating speech processors. J
81:27–35. Acoust Soc Am 1987;82:48–57.
17. Mangabeira-Albernaz PL. The Mondini dysplasia: 32. Gantz B, Tyler RS, Abbas PJ, et al. Evaluation of five
from early diagnosis to cochlear implant. Acta Oto- different cochlear implant designs: audiologic assess-
laryngol (Stockh) 1983;95:627–31. ment and predictors of performance. Laryngoscope
18. Miyamoto RT, McConkey AJ, Myres WA, et al. 1988;98:1100–6.
Cochlear implantation in the Mondini inner ear 33. Skinner MW, Holden LK, Holden TA, et al. Perfor-
malformation. Am J Otol 1986;7:258–61. mance of postlinguistically deaf adults with the
19. Jackler RK, Luxford WM, House WF. Sound detec- Wearable Speech Processor (WSP III) and Mini
tion with the cochlear implant in five ears of four Speech Processor (MSP) of the Nucleus multi-elec-
children with congenital malformations of the trode cochlear implant. Ear Hear 1991;12:3–22.
cochlea. Laryngoscope 1987;97 Suppl 40:15–7. 34. Hollow RD, Dowell RC, Cowan RS, et al. Continuing
20. Silverstein H, Smouha E, Morgan N. Multichannel improvements in speech processing for adult
cochlear implantation in a patient with bilateral cochlear implant patients. Ann Otol Rhinol Laryngol
Mondini deformities. Am J Otol 1988;9:451–5. Suppl 1995;166:292–4.
21. Tucci DL, Telian SA. Cochlear implantation in 35. Parkinson AJ, Tyler RS, Woodworth GG, et al. A
patients with cochlear malformations. Arch Oto- within-subject comparison of adult patients using
laryngol Head Neck Surg 1995;121:833–8. the Nucleus F0F1F2 and F0F1F2B3B4B5 speech pro-
22. Schuknecht HF. Mondini dysplasia: a clinical and cessing strategies. J Speech Hear Res 1996;39:261–77.
pathological study. Ann Otol Rhinol Laryngol 36. Holden LK, Skinner MW, Holden TA. Speech recog-
1980;89 Suppl 65:1–23. nition with the MPEAK and SPEAK speech-coding
23. Hinojosa R, Marion M. Histopathology of profound strategies of the Nucleus cochlear implant. Oto-
sensorineural deafness. Ann N Y Acad Sci 1983; laryngol Head Neck Surg 1997;166:163–7.
405:459–84. 37. Staller S, Menapace C, Domico E, et al. Speech per-
24. McElveen JT, Carrasco VN, Miyamoto RT, Lin- ception abilities of adult and pediatric Nucleus
thicum FH. Cochlear implantation in common implant recipients using the Spectral Peak (SPEAK)
cavity malformations using a transmastoid labyrin- coding strategy. Otolaryngol Head Neck Surg
thotomy approach. Laryngoscope 1997;107:1032–6. 1997;117(3 Pt 1):236–42.
25. Miyamoto RT, Kaiser AR. Facial nerve anomalies in 38. Fraysee B, Diller N, Klenzer T, et al. Cochlear
cochlear implantation. Adv Otorhinolaryngol implants for adults obtaining marginal benefit from
2000;57:131–3. acoustic amplification. Am J Otol 1998;19:591–7.
26. Gantz BJ, McCabe BF, Tyler RS. Use of multichannel 39. Schindler RA, Kessler DK, Barker M. Clarion patient
cochlear implants in obstructed and obliterated performance: an update on the clinical trials. Ann
cochleas. Otolaryngol Head Neck Surg 1988;98: Otol Rhinol Laryngol 1995;104 Suppl 166:269–72.
72–81. 40. Helms J, Muller J, Schon F, et al. Evaluation of per-
27. Steenerson RL, Gary LB, Wynens MS. Scala vestibuli formance with the COMBI 40 cochlear implant in
cochlear implantations for labyrinthine ossification. adults: a multicentric clinical study. ORL J Otorhi-
Am J Otol 1990;11:360–3. nolaryngol Relat Spec 1997;59:23–35.
Cochlear Implants 487
41. Geier LL, Fisher LM, Barker EJ, et al. The effect of 54. Osberger MJ, Zimmerman-Phillips S, Barker M,
long-term deafness on speech recognition in Geier L. Clinical trials of the CLARION cochlear
postlingually deafened adult Clarion cochlear implant in children. Ann Otol Rhinol Laryngol
implant users. Ann Otol Rhinol Laryngol 1999; 1999;177 Suppl 108:88–92.
108:80–3. 55. Young NM, Carrasco VN, Grohne KM, Brown CJ.
42. Wilson BS, Lawson DS, Finley CC, et al. Importance Speech perception of young children using Nucleus
of patient and processor variables in determining 22-channel or Clarion cochlear implants. Ann Otol
outcomes with cochlear implants. J Speech Hear Res Rhinol Laryngol 1999;108:99–103.
1993;36:373–9. 56. Meyer TA, Svirsky MA, Kirk KI, Miyamoto RT.
43. Blamey PJ, Pyman BC, Clark GM, et al. Factors pre- Improvements in speech perception by children with
dicting postoperative sentence scores in postlin- profound prelingual hearing loss: effects of device,
gually deaf adult cochlear implant patients. Ann communication mode, and chronological age. J
Otol Rhinol Laryngol 1992;101:342–8. Speech Lang Hear Res 1998;41:846–58.
44. Cohen NL, Waltzman SB, Fisher SG, et al. A prospec- 57. Svirsky MA, Meyer TA. Comparison of speech per-
tive, randomized study of cochlear implants. The ception in pediatric Clarion cochlear implant and
Department of Veterans Affairs Cochlear Implant hearing aid users. Ann Otol Rhinol Laryngol
Study Group. N Engl J Med 1993;328:233–7. 1999;108 Suppl 177:104–9.
45. Gantz B, Woodworth G, Knutson JF, et al. Multivari- 58. Osberger MJ, Todd SL, Berry SW, et al. Effect of age
ate predictors of audiological success with multi- at onset of deafness on children’s speech perception
channel cochlear implants. Ann Otol Rhinol abilities with a cochlear implant. Ann Otol Rhinol
Laryngol 1993;102:909–16. Laryngol 1991;100:883–8.
46. Battmer RD, Gupta SP, Allum-Mecklenburg DJ, et al. 59. Fryauf-Bertschy H, Tyler RS, Kelsay DM, et al. Per-
Factors influencing cochlear implant perceptual per- formance over time of congenitally deaf and postlin-
formance in 132 adults. Ann Otol Rhinol Laryngol gually deafened children using a multichannel
Suppl 1995;166:185–7. cochlear implant. J Speech Hear Res 1992;35:913–20.
47. Shipp D, Nedzelski J, Chen J, Hanusaik L. Prognos- 60. Miyamoto RT, Osberger MJ, Robbins AM, et al.
tic indicators of speech recognition performance in Prelingually deafened children’s performance with
postlinguistically deafened adult cochlear implant the Nucleus multichannel cochlear implant. Am J
users. Adv Otorhinolaryngol 1997;52:74–7. Otol 1993;14:437–45.
48. Rubinstein JT, Miller CA. How do cochlear prosthe- 61. Fryauf-Bertschy H, Tyler RS, Kelsay DM, et al.
ses work? Curr Opin Neurobiol 1999;9:399–404. Cochlear implant use by prelingually deafened chil-
49. Kirk KI, Diefendorf AO, Pisoni DB, et al. Assessing dren: the influences of age at implant and length of
speech perception in children. In: Mendel L, Dan- device use. J Speech Lang Hear Res 1997;40:183–99.
hauer J, editors. Audiological evaluation and man- 62. Miyamoto RT, Kirk KI, Robbins AM, et al. Speech
agement and speech perception training. San Diego: perception and speech intelligibility in children with
Singular; 1997. p. 101–32. multichannel cochlear implants. Adv Otorhino-
50. Kirk KI. Challenges in the clinical investigation of laryngol 1997;52:198–203.
cochlear implant outcomes. In: Niparko JK, Kirk KI, 63. O’Donoghue GM, Nikolopoulos TP. Speech percep-
Mellon NK, et al, editors. Cochlear implants: princi- tion in children after cochlear implantation. Am J
ples and practices. Philadelphia: Lippincott-Raven; Otol 1999;19:762–7.
2000. p. 225–59. 64. Nikolopoulos TP, O’Donoghue GM, Archbold SM.
51. Miyamoto RT, Osberger MJ, Robbins AJ, et al. Com- Age at implantation: its importance in pediatric
parison of sensory aids in deaf children. Ann Otol cochlear implantation. Laryngoscope 1999;109:
Rhinol Laryngol 1989;98(Suppl 8 Pt 2):2–7. 595–9.
52. Staller SJ, Beiter AL, Brimacombe J, et al. Pediatric 65. Lenarz T, Illg A, Lesinki-Schiedat A, et al. Cochlear
performance with the Nucleus 22-channel cochlear implantation in children under the age of two: the
implant system. Am J Otol 1991;12 Suppl:126–36. MHH experience with the Clarion cochlear implant.
53. Cohen NL, Waltzman SB, Roland JT, et al. Early Ann Otol Rhinol Laryngol 1999;108:44–9.
results using the Nucleus C124M in children. Am J 66. Illg A, Lesinki-Schiedat A, von der Haar-Heise S, et
Otol 1999;20:198–204. al. Speech perception results for children implanted
488 Ballenger’s Otorhinolaryngology
with the Clarion cochlear implant at the Medical postoperative implant performance in children. Ann
University of Hannover. Ann Otol Rhinol Laryngol Otol Rhinol Laryngol Suppl 2000;185:44–6.
1999;108:93–8. 74. Hodges AV, Ash MD, Balkany TJ, et al. Speech per-
67. Brackett D, Zara CV. Communication outcomes ception results in children with cochlear implants:
related to early implantation. Am J Otol 1998; contributing factors. Otolaryngol Head Neck Surg
19:453–9. 1999;121:31–4.
68. Waltzman S, Cohen N, Shapiro W. Effects of 75. Allen MC, Nikolopoulos TP, O’Donoghue GM.
cochlear implantation on the young deaf child. Adv Speech intelligibility in children after cochlear
Otorhinolaryngol 1995;50:125–8. implantation. Am J Otol 1998;19:742–6.
69. Waltzman S, Cohen NL, Gomolin R, et al. Percep- 76. Moog JS, Geers A. Speech and language acquisition
tion and production results in children implanted in young children after cochlear implantation. Oto-
between two and five years of age. Adv Otorhino- laryngol Clin North Am 1999;32:1127–41.
laryngol 1997;52:177–80. 77. Svirsky MA. Speech intelligibility of pediatric
70. Waltzman SB, Cohen NL. Cochlear implantation in cochlear implant users and hearing aid users.
children younger than 2 years old. Am J Otol In: Waltzman SB, Cohen NL, editors. Cochlear
1998;19:158–62. implants. New York: Thieme; 2000. p. 312–4.
71. Cowan RS, DelDot J, Barker EJ, et al. Speech percep- 78. Svirsky MA, Robbins AM, Kirk KI, et al. Language
tion results for children with implants with different development in profoundly deaf children with
levels of preoperative residual hearing. Am J Otol cochlear implants. Psychol Sci 2000;11:153–8.
1997;18 Suppl:125–6. 79. Pisoni DB, Svirsky MA, Kirk KI, et al. Looking at the
72. Zwolan TA, Zimmerman-Phillips S, Ashbaugh CJ, et “Stars”: a first report on the intercorrelations
al. Cochlear implantation of children with minimal among measures of speech perception, intelligibility
open-set speech recognition skills. Ear Hear 1997; and language development in pediatric cochlear
18:240–51. implant users. Bloomington (IN): Indiana Univer-
73. Osberger MJ, Fisher LM. Preoperative predictors of sity; 1997.
CHAPTER 24
Facial Paralysis
Phillip A. Wackym, MD, John S. Rhee, MD
Facial nerve abnormalities represent a broad spec- The clinical observation of congenital extraoc-
trum of lesions, including numerous congenital and ular muscle paralysis and facial paralysis is the typi-
acquired causes.1 The patient who suffers with facial cal presentation of this disorder (Figure 24–1). No
paralysis experiences not only functional conse- mass lesions will be found on magnetic resonance
quences but also the psychological impact of a imaging (MRI). Ophthalmologic consultation and
change in self-image and impaired communicative management are mandatory. Reinnervation proce-
ability. In fact, a 1991 poll revealed that the level of dures such as crossfacial grafts or hypoglossal-facial
discomfort that Americans felt on meeting those nerve anastomosis yield poor results, either owing to
with facial abnormalities was second only to that the paucity of motor end plates or the atrophic sev-
associated with interacting with the mentally ill, and enth nerves. Significant improvements of resting
this discomfort far exceeded anxiety about encoun- tone and voluntary animation can result from tem-
tering the senile, mentally retarded, deaf, blind, and poralis muscle transposition, which brings in a new
those confined to a wheelchair.2 neuromuscular system.
489
490 Ballenger’s Otorhinolaryngology
the long bones. Increased bone density is seen radi- lacerum and foramen ovale. The resulting fracture is
ographically. Progressive optic atrophy, trigeminal described as a longitudinal temporal bone fracture.
hypesthesia, recurrent facial paralysis, and sen- This is the most common type of temporal bone
sorineural hearing loss are common. Complete fracture (approximately 90%) and is also the most
decompression of the intratemporal facial nerve common type of fracture associated with facial
should be performed in patients with recurrent facial nerve injury. The geniculate ganglion region of the
paralysis and radiographic evidence of osteopetrosis. facial nerve is most frequently injured. The indica-
tions for facial nerve decompression and exploration
are the same as those discussed in detail under the
ACQUIRED Bell’s palsy section of this chapter.
Trauma Approximately 90% of all congenital Frontal and particularly occipital blows to the
peripheral facial nerve paralysis spontaneously head tend to result in transverse fractures of the
improves, and most can be attributed to difficult temporal bone. More severe head injury is usually
deliveries, cephalopelvic disproportion, high forceps required to cause these fractures.10 Since they often
delivery, or intrauterine trauma. These types of con- extend through the internal auditory canal or
genital facial paralysis are often unilateral and par- across the otic capsule, hearing loss and vertigo
tial, especially involving the lower division of the commonly result. Although only 10 to 20% of tem-
facial nerve. Since these causes involve extratempo- poral bone fractures are transverse in orientation,
ral compression, surgical exploration or bony they cause facial nerve injury in approximately
decompression is not indicated.9 50% of patients. The anatomic region of the facial
Blunt trauma resulting in temporal bone frac- nerve most commonly injured is the labyrinthine
ture is best evaluated with high-resolution temporal segment.
bone computed tomographic (CT) scans (Figures Penetrating injuries to the extratemporal facial
24–2 and 24–3). Temporal and parietal blows to the nerve should be explored urgently to facilitate iden-
head may occur anywhere along a coronal arc, from tification of the transected distal branches using a
the vertex to the cranial base. When the vector of facial nerve stimulator. If primary repair is not pos-
force is directed toward the base, it classically passes sible, the principles of facial nerve repair using cable
toward the external auditory canal, deflects off the grafts, described later in this chapter, should be fol-
otic capsule, and extends anteromedially along the lowed. In infected wounds, urgent exploration and
anterior edge of the petrous bone to the foramen tagging of identified distal branches should precede
Facial Paralysis 491
Infection with the spirochete Borrelia burgdor- Hunt’s syndrome may have a variety of manifesta-
feri (Lyme disease) can result in facial paralysis. This tions. However, the original four classifications of the
tick-borne infection is endemic to the northeastern disease by Hunt included (1) disease affecting the
United States and is named for the town of Lyme, sensory portion of the CN VII, (2) disease affecting
Connecticut. Widespread infections have been the sensory and motor divisions of the CN VII, (3)
reported from the west coast, Midwest, and east disease affecting the sensory and motor divisions of
coast, as well as throughout Europe and Australia. the CN VII with auditory symptoms, and (4) disease
As is the case with other spirochete infections, the affecting the sensory and motor divisions of the CN
clinical manifestations of Lyme disease are protean. VII with both auditory and vestibular symptoms.
Facial diplegia has been reported in Lyme disease15 Herpes zoster oticus is the cause of 2 to 10% of
and should be considered in children presenting all cases of facial paralysis, including 3 to 12% of
with facial paralysis. Serologic diagnosis should be adults and approximately 5% of children.1,18–23
followed by antibiotic therapy. Tetracycline is con- Patients may experience paresis or complete paraly-
sidered to be the agent of choice; however, erythro- sis, with the poorest prognosis for recovery in the
mycin and penicillin have been successfully used. latter group. Approximately half of patients with
Ramsay Hunt syndrome retain some facial motor
VIRAL. RAMSAY HUNT SYNDROME (HERPES ZOSTER disturbance; only a few maintain a complete paraly-
OTICUS). James Ramsay Hunt (1872–1937), an sis.18–21
American neurologist, published his seminal article Based on the sensory distributions reflected by
associating the clinical syndrome that now bears his the VZV recrudescence observed by Hunt over his
name with herpetic inflammation of the geniculate career,16,24,25 the most common site of vesicular erup-
ganglion.16 Critical to the development of this tion is in the concha of the auricle (Figure 24–4). In
hypothesis was the publication of the pathologic addition, he described three other areas where vesi-
studies of Head and Campbell in 1900, which cles can be found during herpes zoster oticus: a
advanced a new hypothesis regarding the etiology of small strip of skin on the posteromesial surface of
herpes zoster.17 This work inspired Hunt to first pos- the auricle, the mucosa on the palate, and the ante-
tulate that the etiology of herpes zoster oticus was rior two-thirds of the tongue.24 In his final publica-
recrudescence of herpes varicella-zoster virus (VZV) tion, he detailed the sensory distributions of the
in the geniculate ganglion.16 Clinically, Ramsay facial nerve associated with the geniculate ganglion
that subserve the axonal transport of the recrudes- paralysis for a 60-year interval.32 Wackym et al used
cent VZV to form the vesicles visible during Ramsay a molecular approach to demonstrate the presence
Hunt syndrome. of VZV deoxyribonucleic acid (DNA) combined
With the advent of gadolinium diethylenetri- with traditional histopathologic techniques to the
amine pentaacetic acid (Gd-DTPA)-enhanced mag- study of the temporal bones from two patients with
netic resonance imaging (MRI), acute imaging of the Ramsay Hunt syndrome.30,33 The most consistent
facial nerve is possible throughout the clinical course observation was diffuse inflammatory infiltration
of Ramsay Hunt syndrome.26 Despite histopatho- throughout the involved facial nerve; in addition,
logic reports of diffuse inflammation along the several investigators have shown lymphocytic infil-
entire intratemporal facial nerve in the disor- tration of the geniculate ganglion, alteration of the
der,18,27–30 Korzec et al found that in three of the six geniculate ganglion somata, or both condi-
patients with Ramsay Hunt syndrome who were tions.18,27,29–31 Based on the models of VZV and her-
studied with Gd-DTPA MRI, enhancement of the pes simplex virus (HSV) latency and reactivation,34
involved nerve was localized to the geniculate gan- these findings are expected. Unlike HSV, which
glion, labyrinthine segment, and the premeatal remains dormant directly within sensory neuronal
regions of the affected facial nerve, whereas there somata, VZV remains latent within the non-neu-
was no enhancement at all in the remaining three ronal satellite cells surrounding each sensory neu-
patients.26 Likewise, in none of their six patients did ronal somata. With recrudescence, the replication
they find enhancement of the vertical or tympanic VZV virions are released from satellite cells into the
segments of the facial nerve. These findings suggest extracellular matrix, where some are taken up by the
that in the early stages of the clinical syndrome, the sensory cell body and transported via the axons back
majority of the inflammation is found near the to the skin or mucosa. This release of VZV into the
geniculate ganglion, whereas in the later stages, as extracellular matrix within the geniculate ganglion
examined postmortem, the inflammation has would cause an immune response that could result
extended throughout the intratemporal facial nerve. in inflammatory infiltrates throughout the intratem-
However, the senior author has seen diffuse poral facial nerve. Therefore, the diffuse lymphocytic
enhancement of the facial nerve on MRI examina- infiltration of the entire facial nerve remains consis-
tion of patients with Ramsay Hunt syndrome (Fig- tent with Hunt’s hypothesis.29,30,32 Furuta et al
ure 24–5). reported the distribution of VZV DNA in 11 (79%)
Blackley et al reviewed the histopathology of 14 trigeminal ganglia and in 9 (69%) of 13 genic-
associated with Ramsay Hunt syndrome in their one ulate ganglia collected at autopsy of adults.35 These
case and five others.27 Aleksic et al added another data suggest that latent VZV in the geniculate gan-
histologic case.31 Payten and Dawes reviewed the glion is a common biologic phenomenon; however,
pathologic studies of herpes zoster oticus with facial the small sample size and the lack of clinical history
regarding whether the patients experienced herpes patient who died 6 days after the onset of Bell’s
zoster oticus during their lifetime necessitate confir- palsy.46 Furuta et al found HSV DNA in 71% of
mation of these observations with a much larger geniculate ganglia and in 81% of trigeminal ganglia
sample size of well-characterized patients. in eight random autopsy specimens taken from
Other authors have suggested that Ramsay adult cadavers.48 These data suggest that latent HSV
Hunt syndrome represents a cranial polyneuropa- in the geniculate ganglion may be a common bio-
thy.28,36,37 Care must be taken in interpreting the logic phenomenon; however, the small sample size
histopathologic findings in each case as some may and the lack of clinical history regarding whether the
represent cephalic zoster with neuritis of multiple patients experienced Bell’s palsy during their lifetime
cranial nerves.28,37 Severe central neurologic deficits necessitate confirmation of these observations with
or multiple cranial motor neuropathies are well rec- a much larger sample size of well-characterized
ognized in cephalic zoster.38,39 patients. However, genetic, immunologic, vascular,
Surgical management with decompression of entrapment, and other infectious causes have all
the facial nerve in Ramsay Hunt syndrome has been been advanced in the etiology of Bell’s palsy.49
advocated by some authors (reviewed by Crabtree).19 Bell’s palsy is an acute, unilateral paresis or
Although the advent of facial electroneuronography paralysis of the facial nerve in a pattern consistent
(ENoG) has resulted in a better idea about which with peripheral nerve dysfunction (Figure 24–6).
patients with facial paralysis have severe facial nerve The onset and evolution are typically rapid, less than
injuries requiring surgical decompression,40 the dif- 48 hours, and the onset of paralysis may be preceded
fuse inflammatory edema common in Ramsay Hunt by a viral prodrome. The symptoms during the early
syndrome has led most clinicians to avoid comple- phase of facial paralysis include facial numbness,
tion of facial nerve decompression. epiphora, pain, dysgeusia, hyperacusis (dysacusis),
Experience with the use of intravenous acy- and decreased tearing. The pain is usually retroau-
clovir (Zovirax) during the acute presentation of ricular and sometimes radiates to the face, pharynx,
Ramsay Hunt syndrome suggests that antiviral med- or shoulder. Physical findings of this subtle polyneu-
ications may facilitate recovery and minimize the ritis include hypesthesia or dysesthesia of the CNs V
morbidity associated with facial paralysis.23,41–43 This and IX and of the second cervical nerve.50 Motor
intravenous route has more inherent expenses than paralysis of branches of the CN X is seen as a uni-
an oral route of administration. However, tissue lev- lateral shift of the palate or vocal cord paresis/
els of acyclovir delived by an oral route are not high paralysis.
enough to treat varicella-zoster infections. Alternate Recurrence of Bell’s palsy occurs in 7.151 to
1
antiviral agents such as valacyclovir (Valtrex) (1 g 12% of patients. In the series of 140 patients with
orally three times a day for 10 to 14 days) or famci- recurrent Bell’s palsy reported by Pitts et al, ipsilat-
clovir (Famvir) (500 mg orally three times a day for eral recurrences were as common as development of
10 days), which achieve adequate levels by an oral contralateral Bell’s palsy.51 Also of note in this series
route, are now available as an alternative to intra- was the observation that the incidence of diabetes
venous acyclovir for the treatment of patients with mellitus was 2.5-fold greater than nonrecurrent
Ramsay Hunt syndrome.44 Because the oral route is cases.
much more cost effective, this route is preferred. Gadolinium-enhanced MRI has been advo-
Likewise, oral corticosteroids have been advocated in cated as a diagnostic tool in assessing Bell’s palsy.
patients with Ramsay Hunt syndrome.45 Gadolinium enhancement of the normal facial nerve
does not occur. Therefore, enhancement of this
BELL’S PALSY. Bell’s palsy is responsible for 60 to 75% structure would be owing to increased extracellular
of all cases of facial paralysis. In the past, Bell’s palsy fluid from edema, inflammation, or neoplasm. Our
was defined as an “idiopathic facial paralysis” or as a observations with gadolinium-enhanced MRI in
mononeuropathy of undetermined origin. Recent Bell’s palsy, as well as those of others,26 are support-
observations have linked the cause to HSV 1.46,47 ive of Fisch’s hypothesis of axoplasmic damming at
Burgess et al, using polymerase chain reaction ampli- the meatal segment with subsequent edema and
fication, identified HSV 1 DNA in paraffin-embed- nerve conduction impairment (Figure 24–7).52
ded sections of the geniculate ganglion from a However, one study demonstrated that there was no
Facial Paralysis 495
prognostic significance of gadolinium enhancement ized, double-blind trial.53 Half of the patients
of the facial nerve on MRI in patients with Bell’s received a 10-day course of oral acyclovir (400 mg
palsy.26 Therefore, gadolinium-enhanced MRI is not five times per day) and prednisone. The control
indicated in every patient with facial paralysis. In group received prednisone and a placebo. All study
patients suspected of having a tumor from clinical or patients began treatment within 3 days of the onset
electrodiagnostic data, gadolinium-enhanced MRI, of facial paralysis. The placebo-prednisone group
along with high-resolution CT of the internal audi- had lower facial function recovery scores (House-
tory canal (IAC), fallopian canal, skull base, and Brackmann grade III or IV in 23%) and was almost
parotid, should be performed. three times as likely to have an unsatisfactory result
Adour and colleagues examined the outcome as the acyclovir-prednisone group (only 7% of the
of treating patients with Bell’s palsy with both acy- acyclovir-prednisone group had a House-Brack-
clovir and corticosteroids in a prospective, random- mann grade III or IV).
FIGURE 24–7. Magnetic resonance image (MRI) of facial nerve in Bell’s palsy. A, Non–gadolinium-enhanced axial MRI
shows normal-appearing seventh and eighth nerves within the right internal auditory canal (open arrow). B, Gadolinium-
enhanced axial MRI shows axoplasmic damming of the right facial nerve at the meatal foramen (solid arrow). This MRI
finding was confirmed at surgical decompression. Reproduced with permission; copyright © 1992 P. A. Wackym.
496 Ballenger’s Otorhinolaryngology
Electroneuronography provides a quantitative care is required during the active infection. Facial
assessment of facial nerve function and allows a rel- reanimation procedures are sometimes required
ative comparison between the normal and affected after adequate follow-up suggests that spontaneous
sides and will be discussed in more detail later in this recovery will not occur.
chapter. Our criteria for surgical decompression
include ENoG degeneration greater than 90% rela- Benign or Malignant Neoplasms Tumor involve-
tive to the unaffected side, no voluntary facial nerve ment of the facial nerve should be considered in
electromyographic (EMG) activity on the affected facial paralysis if one or more of the following clin-
side, and the operation within 14 days of onset.40,54,55 ical features are present: facial paralysis that pro-
Decompression is limited to the meatal and gresses slowly over 3 weeks, recurrent ipsilateral
labyrinthine segments through a middle cranial facial paralysis, facial weakness associated with mus-
fossa approach.55–57 Fisch and Esslen, in 1972, were cle twitching, long-standing facial paralysis (greater
the first to propose that the most likely site for neu- than 6 months), facial paralysis associated with other
ral compression and conduction block in Bell’s palsy CN deficits, or evidence of malignancy elsewhere in
was at the entrance to the meatal foramen, the nar- the body.
rowest bony point through which the facial nerve Several benign and malignant tumors can
passes.58 Interestingly, intraoperative evoked EMG involve the facial nerve along its intracranial,
documented the conduction block at this area in intratemporal, or extracranial course (Table 24–1).
94% of decompressed cases, and marked swelling Schwannoma is the most common primary tumor
proximal to this point was the typical observa- of the facial nerve. It is benign and usually involves
tion.58,59 Gantz et al published a prospective study in the labyrinthine, tympanic, and mastoid segments of
which a well-defined surgical decompression of the the facial nerve. Nerve resection and interpositional
facial nerve was performed in a population of nerve grafting may initially be necessary for restor-
patients with Bell’s palsy who exhibited the electro- ation of continuity60,61; however, decompression
physiologic features associated with poor outcomes will often give patients many years of facial nerve
(ENoG degeneration greater than 90% relative to the function before resection and grafting must be
unaffected side, no voluntary facial nerve EMG completed.
activity on the affected side).55 Subjects who did not The use of radiographic imaging is indicated if
reach 90% degeneration on ENoG within 14 days of the characteristics of the facial paralysis are suggestive
paralysis all returned to House-Brackmann grade I of a neoplasm. Radiographic studies should include
(n = 48) or II (n = 6) at 7 months after onset of the visualization of the entire course of the facial nerve,
paralysis. Control subjects self-selecting not to from the brainstem to the facial musculature.
undergo surgical decompression when > 90% Gadolinium-enhanced MRI (Figure 24–8) is
degeneration on ENoG and no motor unit poten- extremely useful in imaging solid tumors involving
tials on EMG were identified had a 58% chance of the facial nerve, and high-resolution CT scans are use-
having a poor outcome at 7 months after onset of ful in identifying bony erosion of the fallopian canal.
paralysis (House-Brackmann grade III or IV [n = Tumors may arise in the vicinity of the facial
19]). A group with similar ENoG and EMG findings nerve and cause facial weakness either by compres-
undergoing middle fossa facial nerve decompression sion or direct invasion. When the tumor is benign,
exhibited House-Brackmann grade I (n = 14) or II the continuity of the facial nerve should be pre-
(n = 17) in 91% of the cases. It is recommended served at all costs by sharp dissection and mobiliza-
that these criteria and this surgical algorithm be tion techniques. This is appropriate management,
followed. whether the nerve is compromised in the IAC by an
acoustic neuroma or in the parotid gland by a pleo-
OTHER VIRAL INFECTIONS. Other viral infections such morphic adenoma. A malignant process with direct
as primary chickenpox, mononucleosis, mumps, and invasion of the nerve usually mandates resection of
poliomyelitis can result in facial paralysis that may the involved portion of the nerve with immediate
or may not resolve spontaneously. For these specific interpositional nerve grafting. If the management of
viral infections, immunization, when available, is the the disorder involves chemotherapy or radiation
most effective preventive measure, and supportive therapy rather than surgical intervention, facial
Facial Paralysis 497
Continued
498 Ballenger’s Otorhinolaryngology
reanimation procedures may be indicated if there is spasm is caused by vascular compression of the
persistent facial nerve dysfunction. facial nerve.62 Trigeminal neuralgia, hemifacial
spasm, glossopharyngeal neuralgia, tinnitus, and dis-
Hemifacial Spasm Hemifacial spasm is typically a abling positional vertigo have all been associated
disorder of the fourth and fifth decades of life and with vascular compression.63 Microvascular decom-
occurs twice as often in women as it does in men. pression operations involve separating the compres-
Electrophysiologic and surgical observations indi- sive vessel from its point of contact with the CN root
cate that the facial nerve hyperactivity in hemifacial entry or exit zone and interposition of a prosthesis
(usually Teflon felt) to prevent further nerve com-
pression.62 Drawing from the experience with the
more common microvascular compression syn-
drome of the trigeminal nerve, large series have
reported that 62 to 64% of trigeminal neuralgia
patients have a compressive artery, 12 to 24% have a
compressive vein, 13 to 14% have both an artery and
a vein, and 8% have either a tumor or vascular mal-
formation pressing on the trigeminal nerve.64 The
initial failure rate for microvascular decompression
for trigeminal neuralgia is 2 to 7%, with a 3.5% per
year incidence of a major recurrence.65–67 In the
series of 1,185 patients who underwent microvascu-
lar decompression for trigeminal neuralgia reported
by Barker et al in 1996, there was a mean follow-up
of 6.2 years, and 30% of patients experienced a
major recurrence, with 11% requiring a second
microvascular decompression.68 The absence of a
clear site of arterial compression has been associated
with high recurrence rates.68,69 Patients found to have
only venous compression and no arterial compres-
sion are more likely to suffer a recurrence.68 Kureshi
and Wilkins reported their surgical experience with
FIGURE 24–8. Gadolinium-enhanced axial magnetic 31 posterior fossa re-explorations for recurrent or
resonance image shows an extensive facial neuroma with persistent trigeminal neuralgia and hemifacial
extension into the cochlea and internal auditory canal. spasm.70 They discovered 3 (10%) cases in which
Reproduced with permission; copyright © 2000 P. A. there was new or previously unrealized arterial com-
Wackym. pression of neural structures. Similarly, a series of
Facial Paralysis 499
nerve (CN VII) exits the brainstem at the pon- eases such as Bell’s palsy and Ramsay Hunt syn-
tomedullary junction approximately 1.5 mm ante- drome.52,59,75,77
rior to the vestibulocochlear nerve (CN VIII). The The intratemporal course of the facial nerve
facial nerve is smaller in diameter (approximately has three distinct anatomic regions: the
1.8 mm) than the oval CN VIII (approximately 3 labyrinthine, tympanic, and mastoid segments. The
mm in the largest diameter). A third smaller nerve, labyrinthine segment is shortest (approximately 4
the nervus intermedius, emerges between CN VII mm), extending from the meatal foramen to the
and CN VIII and eventually becomes incorporated geniculate ganglion. This segment travels anterior,
within the sheath of CN VII. After leaving the brain- superior, and lateral, forming an anteromedial angle
stem, CN VII follows a rostrolateral course through of 120 degrees with the IAC portion. The basal turn
the cerebellopontine cistern for 15 to 17 mm, enter- of the cochlea is closely related to the fallopian canal
ing the porus of the IAC of the temporal bone (Fig- and lays anteroinferior to the labyrinthine segment
ure 24–9). Other important structures in the of the facial nerve. At the lateral end of the
cerebellopontine cistern include the anterior infe- labyrinthine segment, the geniculate ganglion is
rior cerebellar artery (AICA) and the veins of the found, and the nerve makes an abrupt posterior
middle cerebellar peduncle. The AICA passes near change in direction, forming an acute angle of
or between CN VII and CN VIII; the veins are more approximately 75 degrees. Anterior to the genicu-
variable in position and number. On entering the late ganglion, the greater superficial petrosal nerve
IAC, the facial nerve occupies the anterosuperior exits the temporal bone through the hiatus of the
quadrant of this channel for 8 to 10 mm. Then it facial canal. The hiatus of the facial canal is quite
enters the fallopian canal at the fundus of the IAC. variable in its distance from the geniculate ganglion.
The IAC is anterior to the plane of the superior The hiatus of the facial canal also contains the vas-
semicircular canal (SSC). Superiorly, the bone over- cular supply to the geniculate ganglion region. The
lying the IAC is within a 60-degree angle, whose tympanic, or horizontal, segment of the nerve is
vertex is the SSC ampulla. At the entrance of the fal- approximately 11 mm long, running between the
lopian canal (meatal foramen), CN VII narrows to lateral semicircular canal superiorly and the stapes
its smallest diameter, 0.61 to 0.68 mm.75,76 Only the inferiorly, forming the superior margin of the fossa
pia and arachnoid membranes form a sheath ovale. Between the tympanic and mastoid segments,
around the nerve at this point since the dural the nerve gently curves inferiorly for about 2 to 3
investment terminates at the fundus of the IAC. mm. The mastoid, or vertical, segment is the longest
Many authors believe that the small diameter of the intratemporal portion of the nerve, measuring
meatal foramen is an important factor contribut- approximately 13 mm. As the nerve exits the stylo-
ing to the etiology of facial paralysis in certain dis- mastoid foramen at the anterior margin of the
grading system was chosen to avoid confusion with sufficient number of motor units to yield the repre-
the House-Brackmann classification. sentative maximal amplitude. A supramaximal bipo-
lar stimulation (galvanic) is provided to saturate the
Electroneuronography and Electromyography nerve and produce a complete and synchronous
The two most useful objective electrodiagnostic tests depolarization. The galvanic stimulation is typically
of facial nerve function are ENoG and EMG. delivered as rectangular pulses, with a duration of
200 µs and an interpulse interval of 1 s. The ampli-
tude of the evoked response is plotted as a function
FACIAL ELECTRONEURONOGRAPHY. Electroneuronogra-
of time after stimulation. Both the normal and
phy uses supramaximal electrical stimulation of the
affected sides are tested, and the amplitude of the
facial nerve at the level of the stylomastoid foramen
responses is compared. The percentage of degener-
to produce a compound muscle action potential.
ated fibers is calculated arithmetically, as follows:
This evoked electromyogenic response is recorded
with surface electrodes placed over the perioral Amplitude of
evoked response
(nasolabial) muscles since a large representative
Percentage of [in µV] Affected side
population of facial nerve fibers would be sampled
degenerated = 100 – –––––––––––––––––– × 100
by recording the evoked response from this group of fibers Amplitude of evoked
muscles. Needle electrodes are not used because response [in µV]
intramuscular needle electrodes would not sample a Normal side
Facial Paralysis 503
This electrodiagnostic test depends on the The timing for performing ENoG should take
physiologic premise of neural injury proposed by into consideration the time course of wallerian
both Seddon and Sunderland (see Table 24–2). degeneration. With a known complete transection of
Injuries that are limited to producing a conduction the facial nerve (eg, traumatic injury), 100% waller-
block within the nerve (neurapraxia) do not disrupt ian degeneration occurs over 3 to 5 days as the dis-
axoplasmic continuity and will continue to conduct tal axon slowly degenerates. Therefore, early testing,
a neural discharge if the electrical stimulus is pre- within 3 days of paralysis, may not be representative
sented distal to the conduction block. With more of the degree of injury, and as outlined above, the
severe injuries, axoplasmic disruption (axonotmesis) time course of degeneration may reflect the degree
or neural tubule disruption (neurotmesis) will result of injury. An important technical detail to be atten-
in wallerian degeneration distal to the site of injury. tive to is the need to stimulate the nerve at the stylo-
Nerve fibers that undergo wallerian degeneration mastoid foramen 10 to 20 times before making an
cannot propagate electrically evoked potentials dis- amplitude measurement. The initial stimulation will
tal to the injury. Axonotmesis, in contrast to neu- improve the synchronization within the nerve and
rotmesis, has a better prognostic outcome. With therefore improve the reliability of the test.
resolution of the neural injury, in a nerve that has As discussed earlier in this chapter, our criteria
undergone axonotmesis, the axon will regenerate for surgical decompression include ENoG degener-
through the intact neural tubule, potentially allow- ation greater than 90% relative to the unaffected
ing complete return of motor function to the mus- side, no voluntary facial nerve EMG activity on the
cle fiber innervated by that nerve fiber. The more affected side, and the operation within 14 days of
severely disrupted neural tubule injury of neu- onset.40,54,55 Decompression is limited to the meatal
rotmesis has the potential to regenerate in an and labyrinthine segments through a middle cranial
unsuccessful manner and can thereby result in fossa approach.55–57 Gantz et al published a prospec-
misdirection of fibers, clinically causing synkinesis tive study in which a well-defined surgical decom-
and incomplete return of motor function. Elec- pression of the facial nerve was performed in a
troneuronography can be used to differentiate nerve population of patients with Bell’s palsy who exhib-
fibers that have minor conduction blocks (neu- ited the electrophysiologic features associated with
rapraxia) from those that have undergone wallerian poor outcomes (ENoG degeneration greater than
degeneration; however, ENoG cannot differentiate 90% relative to the unaffected side, no voluntary
the type of wallerian degeneration (axonotmesis ver- facial nerve EMG activity on the affected side).55
sus neurotmesis). The severity of the injury can be Subjects who did not reach 90% degeneration on
inferred from the rate of degeneration after injury. ENoG within 14 days of paralysis all returned to
More rapid wallerian degeneration is associated with House-Brackmann grade I (n = 48) or II (n = 6) at
neurotmesis, whereas nerves that degenerate more 7 months after onset of the paralysis. Control sub-
slowly are more likely to exhibit axonotmesis.40,54,55 jects self-selecting not to undergo surgical decom-
504 Ballenger’s Otorhinolaryngology
pression when > 90% degeneration on ENoG and nerve EMG with placement of needle electrodes into
no motor unit potentials on EMG were identified the orbicularis oculi and orbicularis oris muscles.
had a 58% chance of having a poor outcome at 7 Instrumentation is crucial to successful expo-
months after onset of paralysis (House-Brackmann sure of the facial nerve. The largest diamond bur
grade III or IV [n = 19]). A group with similar ENoG that the operative site can safely accommodate
and EMG findings undergoing middle fossa facial should be used when the surgeon is near the fallop-
nerve decompression exhibited House-Brackmann ian canal. Cutting burs have the potential to catch
grade I (n = 14) or II (n = 17) in 91% of the cases. and jump unexpectedly and can consequently cause
It is recommended that these criteria and this surgi- severe injury to the nerve. Continuous suction-irri-
cal algorithm be followed. gation keeps the burs clean and also dissipates heat,
which can induce neural damage.
ELECTROMYOGRAPHY. Facial nerve EMG is important Blunt elevators, such as the Fisch raspatory
to use as an adjunctive tool when making decisions (Leibinger, Dallas, Texas), should be used to remove
regarding surgery. Early in the time course of recov- the final layer of bone over the nerve. These instru-
ery, regenerating nerve fibers conduct at differing ments are thin but strong enough to remove a thin
rates, producing dyssynchrony, and, therefore, overes- layer of bone. Stapes curettes are usually too large
timate the degree of wallerian degeneration based on and can cause compression injury to the nerve. If a
ENoG testing. In fact, it is possible to record “100% neurolysis is to be performed, disposable micro-
degeneration” with ENoG in patients with early blades are available (Beaver No. 59-10). Sharp dis-
recovery from Bell’s palsy while voluntary movement section is less traumatic than blunt elevation when
is observed. It is for this reason that a voluntary EMG the nerve must be lifted out of the fallopian canal.
is performed when the ENoG shows greater than 90% The medial surface of the nerve usually adheres to
degeneration within 14 days of injury and surgical the bone and contains a rich vascular supply. Cau-
decompression is being considered. Needle electrodes terization near the nerve should be performed only
are placed into the orbicularis oculi and orbicularis with an irrigating bipolar electrocautery, low cur-
oris muscles, and the patient is asked to make volun- rent, and insulated microforceps.
tary contractions. If voluntary contractions occur
during the first 2 weeks after the onset of paralysis, MIDDLE CRANIAL FOSSA (TRANSTEMPORAL)
early deblocking of the neural conduction block has
taken place, and a good recovery of facial function will
APPROACH: INTERNAL AUDITORY CANAL
most likely follow. It is also important to keep in mind PORUS TO TYMPANIC SEGMENT
that ENoG is useful only during the acute phase of The middle cranial fossa exposure is used to expose
the injury, between days 3 and 21, and after complete the IAC and labyrinthine segment of the facial nerve
loss of voluntary function. Electromyography is the when preserving existing auditory function is desir-
more useful single diagnostic study after 3 weeks of able.57,83 The geniculate ganglion and tympanic por-
facial paralysis. As will be discussed later in the chap- tion of the nerve can also be decompressed from this
ter, EMG testing is also important when deciding approach.
whether to perform nerve substitution procedures
and other reamination procedures. Technique The patient is placed supine on the
operating table with the head turned so that the
GENERAL PRINCIPLES IN FACIAL involved temporal bone is upward (Figure 24–11, A).
The hair is shaved 6 to 8 cm above and anterior to
NERVE SURGERY
the ear and 2 cm posterior to it. The surgeon is
Whenever the facial nerve is to be surgically exposed, seated at the head of the table with the instrument
several technical points must be observed. First, a nurse at the anterior side of the patient’s head. A
system for monitoring facial nerve function during 6 × 8 cm posteriorly based trapdoor incision, or a
the operation should be employed.82 Historically, preauricular incision, is marked in the hairline above
visual observation during critical stages of the oper- the ear (Figure 24–11, B). If exposure of the mastoid
ation was performed. However, the standard prac- is necessary, the inferior limb of the incision can be
tice for most otologists is to use intraoperative facial carried postauricularly (Figure 24–11, B, dashed
Facial Paralysis 505
FIGURE 24–11. Patient positioning and incision design for the middle cranial fossa approach. A, Patient is in the
supine position with the operated ear upward. Surgeon is seated at the vertex of the head. B, Posteriorly based trap-
door scalp incision (bold line). Surgical position illustrating the skin incision (solid line) for the middle cranial fossa
approach. The dashed line shows the extension of the scalp incision that is required to reach the mastoid area for total
facial nerve exposure. Design of anteriorly based temporalis muscle, fascia, and periosteal flap (thin line). C, Alterna-
tive preauricular incision for the middle cranial fossa approach if mastoid exposure is not necessary. Reproduced with
permission; copyright © 2001 P. A. Wackym.
line). The skin flap is elevated to expose the tempo- Branches of the middle meningeal artery are
ralis muscle and fascia. A 4 × 4 cm temporalis fascia occasionally embedded within the inner table of the
graft is harvested for use during closure of the IAC skull; therefore, elevation of the bone flap must be
dural defect. Alternatively, Alloderm (LifeCell Corp., performed in a controlled manner. Bipolar coagula-
Woodlands, Texas) can be used. An anteriorly based tion and bone wax may be necessary to control
trapdoor incision is used to elevate the temporalis bleeding. Elevation of the dura from the floor of the
muscle and periosteum (see Figure 24–11, B, thin middle fossa can be one of the most difficult steps.
line). Staggering the levels of the muscle and skin Blunt dissection and magnification greatly facilitate
incisions provides for a double-layer, watertight clo- dural elevation. The dura is elevated from the poste-
sure at the completion of the procedure. If exposure rior to anterior direction to prevent accidental injury
of the mastoid is not necessary, a preauricular inci- to an exposed geniculate ganglion and greater super-
sion is often used (Figure 24–11, C). ficial petrosal nerve. Bipolar coagulation is used to
The temporal root of the zygoma is exposed cauterize dural reflections within the petrosqua-
during elevation of the temporalis muscle. This mous suture before transection with scissors.
landmark represents the level of the floor of the The elevation proceeds until the petrous ridge
middle fossa. Dural fishhooks are placed in the skin is identified medially and the arcuate eminence,
and temporalis muscle flaps for retraction. A 3 × 5 cm meatal plane, and greater superficial petrosal nerve
bone flap for facial nerve decompression, or a are exposed anteriorly. No attempt is made to iden-
4 × 5 cm bone flap for tumor excisions, centered tify the middle meningeal artery and accompanying
above the temporal root of the zygoma is fashioned troublesome bleeding veins. The tip of a self-retain-
with a medium-cutting bur (3 mm). It is important ing retractor (Fisch, Leibinger) is placed at the
to keep the anterior and posterior margins of the petrous ridge anterior to the arcuate eminence and
craniotomy parallel to facilitate placement of the medial to the meatal plane (Figure 24–12). A
self-retaining retractor. medium diamond bur (2 to 3 mm) and a suction-
506 Ballenger’s Otorhinolaryngology
irrigation apparatus are used to identify the blue line consequently the most challenging portion of the
of the SSC. A preoperative Stenvers projection radi- dissection. At the meatal foramen, the facial nerve
ograph helps to determine the level of the SSC in turns anterior and slightly superior. The basal turn
relation to the floor of the middle fossa and the of the cochlea can be within 1 mm inferiorly, and
degree of pneumatization above the SSC (Figure the ampulla of the SSC can be directly posterior to
24–13). the nerve. The labyrinthine segment is followed to
Drilling begins posterior to the arcuate emi- the geniculate ganglion. If the facial nerve needs to
nence over the mastoid air cells until the dense yel- be exposed distal to the geniculate ganglion (eg, as
low bone of the otic capsule is identified. Otic with facial neuromas or with some traumatic
capsule bone is slowly removed until the blue outline injuries to the facial nerve), the tegmen tympani is
of the SSC is seen. The IAC is located by removing removed with care to avoid injury to the head of the
bone with a 60-degree angle anterior to the blue line malleus and incus. The tympanic segment is easily
of the SSC and with the vertex based at the SSC seen to turn abruptly posterior; it is followed to
ampulla. This dissection is continued until approxi- where it courses inferior to the lateral semicircular
mately 180 degrees of the IAC are exposed for facial canal. It is advisable to leave a thin shell of bone cov-
nerve decompressions (see Figure 24–12) or 270 ering the nerve until its entire course is identified.
degrees of the IAC are exposed for schwannomas. Small blunt elevators are used to remove the final
Because of the close proximity of the SSC and the layer of bone. The nerve is tightly confined within
basal turn of the cochlea, only approximately 120 the labyrinthine segment of the fallopian canal;
degrees of the circumference of the IAC can be safely larger curettes should be avoided to prevent com-
removed in its lateral 5 mm or so. The facial nerve pression injury. If the nerve is to be decompressed, a
occupies the anterosuperior portion of the IAC. Lat- neurolysis is the final step. A disposable microscalpel
erally, the vertical crest (Bill’s bar) marks the divi- (Beaver No. 59-10) is used to slit the periosteum and
sion between the superior vestibular nerve and the epineural sheath.
meatal foramen containing the facial nerve. Alternative methods to locate the facial nerve
The entrance to the fallopian canal is the nar- may be necessary, especially in traumatic cases. The
rowest, most delicate portion of the facial nerve and greater superficial petrosal nerve can be traced pos-
Facial Paralysis 507
teriorly to the geniculate ganglion, or the tegmen enables visualization of the entire course of the facial
tympani may be fractured and the tympanic seg- nerve and still preserves function of the inner ear.
ment visible through the fracture. The tympanic seg- The middle cranial fossa technique is the most com-
ment is then used to locate the geniculate ganglion monly used for decompression of the facial nerve in
and labyrinthine segments. Bell’s palsy52,57 and longitudinal temporal bone frac-
At the end of the procedure, a free temporalis tures. However, as described earlier in this chapter,
muscle graft is placed within the IAC and a corner this approach may be useful in the management of
piece of the bone flap is fashioned to cover the patients with schwannomas of CN VII or CN VIII, as
defects in the tegmen tympani and IAC (Figure well as with patients with Melkersson-Rosenthal
24–14). Alternatively, titanium mesh (Synthes Max- syndrome.
illofacial, Paoli, Pennsylvania) between layers of
Alloderm can be used. This prevents herniation of Postoperative Care/Complications and Their
the temporal lobe into the middle ear or IAC. The Management The anatomy of the floor of the
temporalis fascia previously harvested is placed over middle cranial fossa is quite variable and presents
the free bone graft to help seal the dural defect at the some difficulty in identification of landmarks. The
IAC. The craniotomy defect is then repaired using Stenvers projection radiograph provides important
titanium mesh (Synthes Maxillofacial) and hydrox- anatomic information regarding the degree of
yapatite cement (BoneSource, Leibinger), and the pneumatization above the SSC and should be per-
temporalis muscle is closed with interrupted formed in all cases to minimize the risk of surgical
absorbable sutures. The skin is closed in layers with injury to the SSC. In addition, the surgeon must
particular care in closing the galea. No drain is have a precise knowledge of three-dimensional
placed. A mastoid-type pressure dressing is applied. anatomy of the temporal bone. Many hours in a
temporal bone dissection laboratory are required to
Advantages and Uses The middle cranial fossa attain the delicate microsurgical skills that are nec-
route is the only method that can be used to expose essary for this type of surgery.
the entire IAC and labyrinthine segment with Middle cranial fossa facial nerve decompres-
preservation of hearing. This, in combination with sion can result in conductive and/or sensorineural
the retrolabyrinthine and transmastoid approaches, hearing loss. Conductive hearing loss can be sec-
508 Ballenger’s Otorhinolaryngology
FIGURE 24–14. Reconstruction following right middle cranial fossa facial nerve decompression. Temporalis muscle
is placed within the internal auditory canal (IAC) surgical defect to fill the dural and bony defect at the conclusion of
the facial nerve surgical decompression. Temporalis fascia or Alloderm (LifeCell Corp., Woodlands, Texas) is placed
over the floor of the middle cranial fossa and muscle graft. A free bone graft or titanium mesh (Synthes Maxillofacial,
Paoli, Pennsylvania) is placed perpendicular to the axis of the IAC to prevent herniation of the temporal lobe onto the
facial, cochlear, and vestibular nerves. Temporalis fascia or Alloderm is then used to seal the temporal lobe dura and
cover the bone graft or titanium mesh. Reproduced with permission; copyright © 2001 P. A. Wackym.
ondary to temporal lobe herniation or ossicular dis- lobe retraction required for complete exposure of
ruption during dissection in the attic. A free bone the IAC and fallopian canal. With adequate intraop-
graft, as already described, prevents temporal lobe erative hemostasis using the bipolar cautery, oxi-
herniation. Sensorineural hearing loss can result dized cellulose (Oxycel), and dural tacking sutures,
from direct injury to the inner ear by the drill expos- we have never had a clinically significant postopera-
ing the cochlea or semicircular canals or from trans- tive epidural hematoma develop.
lational injury by the drill striking an ossicle. Should Leakage of cerebrospinal fluid (CSF) must be
the SSC be entered during the surgical dissection, avoided to prevent meningitis. All exposed mastoid
the fenestration should be immediately occluded air cells must be obstructed with bone wax. A tem-
with bone wax. Injury to the internal auditory ves- poralis muscle–free graft is placed into the superior
sels within the IAC can also result in loss of inner ear aspect of the IAC to separate the posterior fossa
function. Loss of vestibular function can occur by from the extradural floor of the middle cranial fossa.
the same mechanisms. Temporalis fascia or Alloderm is then used to pro-
Postoperative intracranial complications vide a second layer of closure between the posterior
including meningitis, temporal lobe edema, and fossa and the extradural middle fossa. Meticulous
epidural hematoma formation are possible. Periop- care must be taken to ensure that there are no dural
erative antibiotics administered over 48 hours are dehiscences overlying the temporal lobe through
recommended. Fluid restriction and dexamethasone which CSF may drain. If these are identified, a tem-
(Decadron) are used for the first 3 days postopera- poralis fascia, muscle, or Alloderm patch must be
tively to minimize temporal lobe edema following used to repair the dural tears to prevent CSF leaks.
intraoperative retraction. In addition, our longer After a three-layer watertight closure of the tempo-
craniotomy flap decreases the amount of temporal ralis muscle, galea, and scalp, a mastoid-type dress-
Facial Paralysis 509
ing is applied daily for 5 days postoperatively. Should anastomosis in the cerebellopontine angle. At the
CSF leakage persist, a temporary lumbar fluid drain brainstem, two or three sutures are placed (Figure
is placed, and the patient is kept at bed rest. If the 24–15).
CSF leakage does not resolve within 5 to 7 days after When an interposition graft is required, the
placement of the lumbar drain, re-exploration of the greater auricular and sural nerves are the preferred
surgical field is indicated to identify and seal the area graft donor sources. The greater auricular nerve is
of CSF egress. readily available near the operative field if it is not
Uncontrolled bleeding or injury to the AICA involved in resection of a neoplasm and has approx-
poses the most serious complication during the imately the same diameter as that of the facial nerve.
operation; however, this is rare. The middle cranial It is easily located midway, perpendicular to a line
fossa approach does not provide adequate access to drawn between the mastoid tip and the angle of the
the entire cerebellopontine angle. The AICA and mandible. If a graft of greater than 8 to 10 cm is
accompanying veins can loop into the IAC. Control required, the sural nerve should be used. The sural
of bleeding of these vessels may require a suboccip- nerve has another advantage in that the peripheral
ital exposure. Injury to the AICA results in brain- portion of the nerve has many branches that can be
stem and cerebellar infarction of a variable degree, used to reconstruct the branching pattern of the
depending on its size and the area of its terminal facial nerve. There is little discomfort from removing
arterial supply. the sural nerve since it provides only a small area of
sensation to the lateral lower leg and foot. The sural
nerve is found immediately posterior to the lateral
NERVE REPAIR malleolus, along the saphenous vein. The nerve graft
Whenever the continuity of the facial nerve has been should be 10 to 20% larger in diameter than the
disrupted by trauma, iatrogenic injury, or tumor facial nerve and long enough to ensure a tension-
invasion, every effort should be made to restore its free anastomosis.
continuity. In some instances, an end-to-end reap-
proximation can be accomplished, but if any tension
occurs at the anastomotic site, an interposition nerve
FACIAL REANIMATION PROCEDURES
graft has a better chance of providing facial move- Contemporary strategies for management of
ment. All nerve repair techniques produce synkine- patients with facial paralysis have been a product of
sis, but sphincteric function of the mouth and eye is a gradual evolution of past clinical successes and
usually restored. Newer microsuture techniques and
instrumentation should be employed to enhance
return of function.
In general, the injured ends of the nerve should
be freshened at a 45-degree angle. Experimental evi-
dence has shown that cutting the nerve at this angle
exposes more neural tubules and improves regrowth
of the nerve.81,84 In addition, a fresh razor blade
induces less crush injury to the nerve than a scalpel
blade or scissors does. We have found that the per-
ineurium of CN VII does not hold 9-0 sutures, and
attempting to suture it increases trauma to the neu-
ral tubules. Removing a portion of the epineurium
before suturing prevents connective tissue growth at
the anastomotic site. If the epineurium is cleaned
from the end of the nerve for approximately only 0.5
mm, sutures can still be placed in the epineurium
for reapproximating the nerve segments. Three or FIGURE 24–15. Epineurial end-to-end nerve repair
four 9-0 nylon sutures are placed with jeweler’s for- using 9-0 nylon sutures. Reproduced with permission;
ceps or longer instruments (19 cm microforceps) for copyright © 2001 P. A. Wackym.
510 Ballenger’s Otorhinolaryngology
failures over the past 100 years. The surgeon must Eyebrow Ptosis of the eyebrow can have func-
consider the functional and cosmetic goals of recon- tional and cosmetic consequences. In the elderly
structive surgery, as well as the patient’s desires, patient, the functional loss of the frontalis and
expectations, and motivations. Functional deficits orbicularis oculi muscles is compounded by the loss
include incomplete eye closure, speech difficulties, of tissue elasticity and decrease in the bulk of the
oral incompetence, and nasal airway obstruction. subcutaneous tissue. This can lead to significant
The cosmetic deficiencies of facial asymmetry and brow ptosis and hooding of the upper eyelid, which
dysmorphism can be emotionally devastating for may cause lateral visual field compromise.
some patients. It is the achievement of facial balance The two most commonly used procedures to
and muscle coordination that continues to be the correct brow ptosis are the midforehead lift and the
more challenging and elusive goal. direct brow lift. Both procedures require direct skin
and subcutaneous tissue excision, followed by sus-
pension of the orbicularis oculi muscle to the frontal
MANAGEMENT OF UPPER THIRD OF THE FACE bone periosteum. Slight overcorrection is needed as
Eye Care Protection of the eye is paramount (Fig- the brow position will settle during the next few
ure 24–16). It is necessary to protect the cornea from weeks. The endoscopic approach for cosmetic
foreign bodies and drying. Dark glasses should be browlifting is not commonly used owing to the
worn during the day, artificial tears instilled at the severity of the brow ptosis associated with the com-
slightest evidence of drying, and a bland eye oint- plete loss of frontalis muscle function. However,
ment used during sleep. Patients who demonstrate a there have been some recent anecdotal reports of
poor Bell’s phenomenon or have trigeminal nerve successful outcomes using the endoscopic browlift
deficits are particularly at risk for corneal damage. technique.1,85
Taping of the eye closed is not usually recom-
mended, but early-exposure keratitis may require Upper Eye Lid Historically, tarsorrhaphy had been
patching or, rarely, a tarsorrhaphy. A formal oph- the standard of care in patients with facial paralysis.
thalmologic examination is recommended prior to Today, this procedure should be reserved for only
any surgical intervention. those patients with a severe risk for exposure kerati-
tis or those who have failed upper eyelid reanima-
tion procedures. The most commonly used
procedure is the insertion of a prosthetic, specifically
a gold weight implant or a palpebral wire spring.
In experienced hands, the palpebral wire
spring can produce excellent results, affording the
capability of mimicking, to some extent, the sponta-
neous blink. However, the insertion of the palpebral
wire spring is technically more difficult, with a
higher reported extrusion and infection rate. In
addition, these springs often need postoperative
adjustment for optimal function.1
Gold weight implantation is a relatively simple
procedure that is highly successful, well tolerated by
patients, and easily reversible if facial muscle func-
tion returns (Figure 24–17). The ideal candidates for
gold weight placement are those with the following
factors: some existing ability to lower the upper lid,
FIGURE 24–16. Inadequate eye care following a com- good Bell’s phenomenon, normal corneal sensation
plete facial paralysis owing to acoustic neuroma resection and tearing, prominent supratarsal lid crease, and
at another institution resulted in corneal opacification. nonprotruding eyes.
Reproduced with permission; copyright © 2000 P. A. Prefabricated gold weight implants come in
Wackym. weights ranging from 0.8 to 1.6 g. Custom weighting
Facial Paralysis 511
and the distal facial nerve trunk (Figure 24–21). Sev- innervates it, and branches off the internal maxillary
eral authors have reported functional results com- artery provide its blood supply. Preoperative evalua-
parable to the XII–VII crossover; however, the tion includes the assessment of the function and
problems of hypertonia and mass facial movements strength of the temporalis muscle.
have not been encountered.91,92 Kartush and Lundy To perform a temporalis muscle transposition
further modified this approach with anastomosis to procedure, the temporalis muscle and fascia are both
only the lower division of the facial nerve, thereby exposed by extending a modified facelift incision
reducing potential synkinesis.93 into the parietal region of the scalp (Figure 24–22).
The pretragal incision is carried down to the sub-
Muscle Transposition Procedures (Dynamic) dermal region, above the superficial muscu-
Regional muscle transposition can provide dynamic loaponeurotic system of the face. A tunnel is created
reanimation of the mouth in patients with long- from the zygomatic arch in a subdermal plane
standing facial paralysis (over 2 years). It is indicated
for patients with congenital facial paralysis (Möbius’
syndrome) or when facial nerve grafting or nerve
substitution techniques are contraindicated. It can
also be performed in conjunction with facial nerve
grafting or nerve substitution procedure in select
cases to augment results. The temporalis muscle is
most commonly used because of its length, con-
tractility, and favorable vector of pull. Masseter mus-
cle transposition can be useful following radical
parotid surgery or when the temporalis muscle is
not available.
FIGURE 24–21. Hypoglossal-facial interpositional nerve FIGURE 24–22. Temporalis muscle transfer for lower
graft technique. Approximately one-third of the face reanimation. A, Dotted lines indicate the lip-cheek
hypoglossal nerve (XII) is sectioned, distal to the and temporal incisions. B, Midportion of the temporalis
hypoglossal descendens. The nerve graft is sewn end to muscle is harvested. C, Temporalis muscle pulled
side with the hypoglossal nerve and end to end with the through subcutaneous cheek tunnel into the lip-cheek
facial nerve (VII). Reproduced with permission; copy- incision. Reproduced with permission; copyright © 2001
right © 2001 P. A. Wackym. P. A. Wackym.
Facial Paralysis 515
between the temporal fossa and the cheek-lip crease The static suspension procedure is most often
incision (adult) or the oral commissure incision used to lateralize the corner of the mouth and lip-
(children). The lateral portions of the zygomatic cheek crease. The procedure is similar in approach to
arch can be burred down to reduce the bulging the temporalis muscle transposition. The autograft
appearance of the muscle at this fulcrum point. Only or allograft is placed in a subcutaneous tunnel from
the midportion of the temporalis muscle is used. A the lip-cheek crease to the zygomatic arch. In cases
portion of the pericranium is dissected with the in which reinnervation of the facial muscles is
muscle and its fascia to create additional length. The expected, it is important not to injure the deeper
muscle is then transposed over the zygomatic arch, facial nerve branches when creating the tunnel.
through the subcutaneous tunnel, and into the lip- Sutures are used to secure the graft to the orbicularis
cheek incision. The muscle-fascia-pericranium com- oris muscle and lip-cheek incision, whereas wires or
plex is sutured to the orbicularis oris muscle near screws are used for anchoring at the zygomatic arch
the submucous layer of the corner of the mouth. (Figure 24–23).
Additional sutures are placed from the muscle to the A separate local suspension can also be per-
subdermal layer of the upper aspect of the lip-cheek formed to lateralize the nose in cases of alar valve
incision to accentuate the lip-cheek crease. Overcor- compromise. The nasal base is exposed with incisions
rection is necessary for an optimal final result. The along the alar-facial and nasolabial creases. An allo-
depression in the temporal area is corrected by rotat- graft or autograft is then sutured to the deep aspect
ing the remainder of the temporalis muscle into the of the nasal base. The nasal base is then pulled later-
deficient area. The redundant facial skin is resected ally to its desired position. After the periosteum of
as in a facelift, and wounds are closed in layers. Two zygomaticomaxillary buttress is exposed, the other
closed suction drains and a compressive dressing are end of the graft is fixated to the bone with a screw.
used for 48 hours postoperatively.
Ideally, the overcorrection of the lateral oral INNERVATED FREE MUSCLE TRANSFER
commissure and lip-cheek crease will resolve by 3 to
6 weeks. The results of the transposition should be The ideal indication for innervated free muscle trans-
evident by 4 to 6 weeks, with the patient able to pro- fer is in the patient with Möbius’ syndrome, for whom
duce a broad smile by tensing the temporalis muscle. both facial nerve and musculature are not available. It
Complications include infection, hematoma, and is also indicated as an alternative to regional muscle
seroma. The most common reasons for failure of the transfers or static procedures in patients with long-
procedure are inadequate overcorrection and suture standing facial paralysis (> 2 years). It is usually per-
dehiscence at the orbicularis oris–temporalis muscle formed as a two-stage procedure in which an initial
interface.94 crossfacial nerve graft is combined with a subsequent
free muscle transfer (most commonly, gracilis or ser-
Suspension Procedures (Static) Static suspension ratus anterior).97 Alternatively, the innervated free flap
procedures are indicated for those patients who are may be grafted to the hypoglossal nerve, performed as
not candidates for nerve substitution or dynamic a single-stage procedure.98
reanimation procedures. These procedures can pro- In select patients, this procedure provides the
vide permanent support, or, in cases in which rein- possibility for dynamic, mimetic movement that
nervation of the facial muscles is expected, static cannot be achieved by static procedures. The disad-
procedures can provide temporary or additional vantages, however, are manifold, including donor
support until reinnervation of the facial muscles is site morbidity, risk of vascular thrombosis, lengthy
complete. A variety of materials are available for operative time, long interval for reinnervation, and
static suspension procedures, ranging from auto- muscle bulkiness.
grafts (palmaris longus tendon, fascia lata tendon)
to alloplasts, such as Gore-Tex (GORE S.A.M., WL NEUROMUSCULAR FACIAL
Gore & Associates Inc., Flagstaff, Arizona) and acel-
lular human dermis (Alloderm).95,96 The choice of
RETRAINING TECHNIQUES
material is dependent on patient factors and desires, For patients who have experienced some recovery of
as well as the surgeon’s preference and experience. facial nerve function, and also for those patients who
516 Ballenger’s Otorhinolaryngology
A B
FIGURE 24–23. Static suspension procedure using allograft (Gore 2 mm nonreinforced sheet, W.L. Gore & Associates,
Inc., Flagstaff, Arizona). A, Strips of allograft placed in the subcutaneous cheek tunnel. B, Allograft anchored to the
malar eminence with a single titanium screw.
experience synkinesis, neuromuscular facial retrain- Likewise, the diagnostic methods and algorithms
ing therapy is an important treatment modality. that are used to make decisions regarding medical
These techniques can be applied before and after versus surgical management in acute facial paralysis
reanimation procedures to optimize outcome. In have been summarized. Anatomy and surgical prin-
general, these techniques can be used to address loss ciples were highlighted and treatment alternatives
of strength, loss of isolated motor control, muscle for reanimation or neuromuscular facial retraining
tension hypertonicity, and/or synkinesis. This outlined.
method combines techniques such as patient educa-
tion in basic facial anatomy, physiology, and kinesi-
ology; relaxation training; sensory stimulation;
REFERENCES
EMG biofeedback; voluntary facial exercises with 1. May M, Schaitkin BM, editors. The facial nerve. 2nd
mirror feedback; and spontaneously elicited facial ed. New York: Thieme Medical Publishers; 2000.
movements.99–101 Botulinum toxin injections may be 2. Harris L. Public attitudes toward people with dis-
used to augment the results of neuromuscular facial abilities. Report of a U.S. survey to the National
retraining when dealing with synkinesis and hyper- Organization on Disability. Washington (DC): 1991.
tonicity.102 3. McKusick VA. Mendelian inheritance in man. A cata-
log of human genes and genetic disorders. 12th ed.
Baltimore: The Johns Hopkins University Press; 1998.
SUMMARY 4. Huebner O. Über angeborenen Kernmangel (infan-
The etiology and pathogenesis of several disorders tiler Kernschwund, Möbius). Charite Ann 1900;25:
that produce facial paralysis have been reviewed. 211–43.
Facial Paralysis 517
5. Hanissian AS, Fuste F, Hayes WT, Duncan JM. Moe- 22. May M, Fria TJ, Blumenthal F, Curtin H. Facial
bius syndrome in twins. Am J Dis Child 1970;120: paralysis in children: differential diagnosis. Oto-
472–5. laryngol Head Neck Surg 1981;89:841–8.
6. Pitner SE, Edwards JE, McCormick WF. Observa- 23. Uri N, Greenberg E, Meyer W, Kitzes-Cohen R. Her-
tions on the pathology of the Möbius syndrome. J pes zoster oticus: treatment with acyclovir. Ann Otol
Neurol Neurosurg Psychiatry 1965;28:362–74. Rhinol Laryngol 1992;101:161–2.
7. Ebbesen F, Petersen W. Goldenhar’s syndrome: dis- 24. Hunt JR. The sensory field of the facial nerve. A fur-
cordance in monozygotic twins and unusual anom- ther contribution to the symptomatology of the
alies. Acta Paediatr Scand 1982;71:685–7. geniculate ganglion. Brain 1915;38:415–45.
8. Sieff CA, Chessells, Levinsky RJ, et al. Allogenic 25. Hunt JR. Geniculate neuralgia (neuralgia of the
bone-marrow transplantation in infantile malignant nervus facialis). A further contribution to the sen-
osteopetrosis. Lancet 1983;1:437–41. sory system of the seventh nerve and its neuralgic
9. Toh EHY, Wackym PA. Injury to the temporal bone conditions. Arch Neurol Psychiatry 1937;37:
and facial nerve in children. Facial Plast Surg Clin 253–85.
North Am 1999;7:223–9. 26. Korzec K, Sobol SM, Kubal W, et al. Gadolinium-
10. Feuerman T, Wackym PA, Gade GF, Becker DP. enhanced magnetic resonance imaging of the facial
Value of skull radiography, head computed tomo- nerve in herpes zoster oticus and Bell’s palsy: clini-
graphic scanning, and admission for observation in cal implications. Am J Otol 1991;12:163–8.
cases of minor head injury. Neurosurgery 27. Blackley B, Friedmann I, Wright I. Herpes zoster
1988;22:449–53. auris associated with facial nerve palsy and auditory
11. Glasscock ME, Schwaber MK, Nissen AJ, Jackson nerve symptoms: a case report with histopathologi-
CG. Management of congenital ear malformations. cal findings. Acta Otolaryngol (Stockh) 1967;63:
Ann Otol Rhinol Laryngol 1983;92:504–9. 533–50.
12. Lambert PR. Major congenital ear malformations: 28. Etholm B, Schuknecht HF. Pathological findings and
surgical management and results. Ann Otol Rhinol surgical implications in herpes zoster oticus. Adv
Laryngol 1988;97:641–9. Otorhinolaryngol 1983;31:184–90.
13. Takahashi H, Nakamura H, Yui M, Mori H. Analysis 29. Guldberg-Möller J, Olsen S, Kettel K. Histopathol-
of fifty cases of facial palsy due to otitis media. Arch ogy of the facial nerve in herpes zoster oticus. Arch
Otorhinolaryngol 1985;241:163–8. Otolaryngol 1959;69:266–75.
14. Sheehy JL. Cholesteatoma surgery in children. Acta 30. Wackym PA. Molecular temporal bone pathology: II.
Otorhinolaryngol Belg 1980;34:98–106. Ramsay Hunt syndrome (herpes zoster oticus).
15. Glasscock ME, Pensak ML, Gulya AJ, Baker DC. Laryngoscope 1997;107:1165–75.
Lyme disease. A cause of bilateral facial paralysis. 31. Aleksic SN, Budzilovich GN, Lieberman AN. Herpes
Arch Otolaryngol Head Neck Surg 1985;111:47–9. zoster oticus and facial paralysis (Ramsay Hunt syn-
16. Hunt JR. On herpetic inflammations of the genicu- drome): clinico-pathologic study and review of lit-
late ganglion. A new syndrome and its complica- erature. J Neurol Sci 1973;20:149–59.
tions. J Nerv Ment Dis 1907;34:73–96. 32. Payten RJ, Dawes DDK. Herpes zoster of the head
17. Head H, Campbell AW. Pathology of herpes zoster and neck. J Laryngol Otol 1972;86:1031–55.
and its bearing on sensory localization. Brain 33. Wackym PA, Popper P, Kerner MM, et al. Varicella-
1900;23:353–523. zoster DNA in temporal bones of patients with
18. Devriese PP. Facial paralysis in cephalic herpes Ramsay Hunt syndrome. Lancet 1993;342:1555.
zoster. Ann Otol Rhinol Laryngol 1968;77:1101–19. 34. Meier JL, Straus SE. Comparative biology of latent
19. Crabtree JA. Herpes zoster oticus. Laryngoscope varicella-zoster virus and herpes simplex virus infec-
1968;78:1853–78. tions. J Infect Dis 1992;166:S13–23.
20. Byl FM, Adour KK. Auditory symptoms associated 35. Furuta Y, Takasu T, Fukuda S, et al. Detection of vari-
with herpes zoster or idiopathic facial paralysis. cella-zoster virus DNA in human geniculate ganglia
Laryngoscope 1977;87:372–9. by polymerase chain reaction. J Infect Dis 1992;166:
21. Robillard RB, Hilsinger RL, Adour KK. Ramsay Hunt 1157–9.
facial paralysis: clinical analysis of 185 patients. Oto- 36. Aviel A, Marshak G. Ramsay Hunt syndrome: a cra-
laryngol Head Neck Surg 1986;95:292–7. nial polyneuropathy. Am J Otolaryngol 1982;3:61–6.
518 Ballenger’s Otorhinolaryngology
37. Schuknecht HF. Pathology of the ear. 2nd ed. 53. Adour KK, Ruboyianes JM, Von Doersten PG, et al.
Philadelphia: Lea & Febiger; 1993. Bell’s palsy treatment with acyclovir and prednisone
38. Gilbert GJ. Herpes zoster ophthalmicus and delayed compared with prednisone alone: a double-blinded,
contralateral hemiparesis: relationship of the syn- randomized controlled trial. Ann Otol Rhinol
drome to central nervous system granulomatous Laryngol 1996;105:371–8.
angiitis. JAMA 1974;229:302–4. 54. Dennis JM, Coker NJ. Electroneuronography. Adv
39. Pratesi R, Freemon FR, Lowry JL. Herpes zoster oph- Otorhinolaryngol 1997;53:112–31.
thalmicus with contralateral hemiplegia. Arch Neu- 55. Gantz BJ, Rubinstein JT, Gidley P, Woodworth GG.
rol 1977;34:640–1. Surgical management of Bell’s palsy. Laryngoscope
40. Coker NJ. Facial electroneurography: analysis of 1999;109:1177–88.
techniques and correlation with degenerating 56. Gantz BJ, Wackym PA. Facial nerve abnormalities.
motoneurons. Laryngoscope 1992;102:747–59. In: Bumstead RM, Smith JD, editors. Pediatric facial
41. Inamura H, Aoyagi M, Tojima H, et al. Effects of aci- plastic and reconstructive surgery. New York: Raven
clovir in Ramsay Hunt syndrome. Acta Otolaryngol Press; 1993. p. 337–47.
Suppl (Stockh) 1988;446:111–3. 57. Wackym PA, Andrews JC. Middle cranial fossa
42. Dickins JRE, Smith JT, Graham SS. Herpes zoster approach. In: Samii M, Cheatham M, Becker D, edi-
oticus: treatment with intravenous acyclovir. Laryn- tors. Atlas of cranial base surgery. Philadelphia: WB
goscope 1988;98:776–9. Saunders; 1995. p. 26–31.
43. Stafford FW, Welch AR. The use of acyclovir in Ram- 58. Fisch U. Prognostic value of electrical tests in acute
say Hunt syndrome. J Laryngol Otol 1986;100: facial paralysis. Am J Otol 1984;5:494–8.
337–40. 59. Gantz BJ, Gmur A, Fisch U. Intraoperative evoked
44. Beutner KR, Friedman DJ, Forszpaniak C, et al. electromyography in Bell’s palsy. Am J Otolaryngol
Valaciclovir compared with acyclovir for improved 1982;3:273–8.
therapy for herpes zoster in immunocompetent 60. Bergman I, May M, Wessle HB, Stool SE. Manage-
adults. Antimicrob Agents Chemother 1995;39: ment of facial palsy caused by birth trauma. Laryn-
1546–53. goscope 1986;96:381–4.
45. Harner SG, Heiny BA, Newell RC. Herpes zoster oti- 61. Lipkin AF, Coker NJ, Jenkins HA, Alford BR.
cus. Arch Otolaryngol 1970;92:632–6. Intracranial and intratemporal facial neuroma. Oto-
46. Burgess RC, Michaels L, Bale JF, et al. Polymerase laryngol Head Neck Surg 1987;96:71–9.
chain reaction amplification of herpes simplex viral 62. Wackym PA, King WA, Meyer GA, et al. Endoscope-
DNA from the geniculate ganglion of a patient with assisted surgery of the trigeminal, facial, cochlear or
Bell’s palsy. Ann Otol Rhinol Laryngol 1994;103: vestibular nerve. In: Wackym PA, Rice DH, Schaefer
775–9. SD, editors. Minimally invasive surgery of the head,
47. Murakami S, Mizobuchi M, Nakashiro Y, et al. Bell’s neck, and cranial base. Philadelphia: Lippincott
palsy and herpes simplex virus: identification of viral Williams & Wilkins; 2002. p. 101–16.
DNA in endoneural fluid and muscle. Ann Intern 63. Schwaber MK. Vascular compression syndromes. In:
Med 1996;124:27–30. Jackler RK, Brackmann DE, editors. Neurotology. St.
48. Furuta Y, Takasu T, Sato KC, et al. Latent herpes sim- Louis: Mosby-Year Book; 1994. p. 881–903.
plex virus type 1 in human geniculate ganglia. Acta 64. Rohrer D, Burchiel K. Trigeminal neuralgia and
Neuropathol (Berl) 1992;84:39–44. other trigeminal dysfunction syndromes. In: Barrow
49. Bauer CA, Coker NJ. Update on facial nerve disor- D, editor. Surgery of the cranial nerves of the poste-
ders. Otolaryngol Clin North Am 1996;29:445–54. rior fossa. Park Ridge (IL): American Association of
50. Adour KK, Byl FM, Hilsinger RL Jr, et al. The true Neurological Surgeons; 1993. p. 201–17.
nature of Bell’s palsy: analysis of 1000 consecutive 65. Apfelbaum R. Surgery for tic douloureux. Clin Neu-
cases. Laryngoscope 1978;88:787–811. rosurg 1984;31:346–50.
51. Pitts DB, Adour KK, Hilsinger RL. Recurrent Bell’s 66. Burchiel K, Clarke H, Haglund M. Long-term effi-
palsy: analysis of 140 patients. Laryngoscope cacy of microvascular decompression in trigeminal
1988;98:535–40. neuralgia. J Neurosurg 1988;69:35–8.
52. Fisch U. Surgery for Bell’s palsy. Arch Otolaryngol 67. Sweet W. Trigeminal neuralgia: problems as to
1981;107:1–11. cause and consequent conclusions regarding treat-
Facial Paralysis 519
ment. In: Wilkins RH, Rengachary S, editors. Neu- 81. Gidley PW, Gantz BJ, Rubinstein JT. Facial nerve
rosurgery update II. New York: McGraw-Hill; 1991. grafts: from cerebellopontine angle and beyond. Am
p. 366–72. J Otol 1999;20:781–8.
68. Barker FG, Jannetta PJ, Bissonette DJ, et al. The long- 82. Gantz BJ. Intraoperative facial nerve monitoring.
term outcome of microvascular decompression for Am J Otol 1985;6 Suppl:58–61.
trigeminal neuralgia. N Engl J Med 1996;334: 83. House W. Surgical exposure of the internal auditory
1077–83. canal and its contents through the middle cranial
69. Mendoza N, Illingworth RD. Trigeminal neuralgia fossa. Laryngoscope 1961;71:1363–85.
treated by microvascular decompression: a long- 84. Yamamoto E, Fisch U. Experiments on facial nerve
term follow-up study. Br J Neurosurg 1995;9:13–9. suturing. ORL J Otorhinolaryngol Relat Spec
70. Kureshi SA, Wilkins RH. Posterior fossa reexplo- 1974;36:193–204.
ration for persistent or recurrent trigeminal neural- 85. Rhee J, Gallo JF, Costantino PD. Endoscopic facial
gia or hemifacial spasm: surgical findings and rejuvenation. In: Wackym PA, Rice DH, Schaefer SD,
therapeutic implications. Neurosurgery 1998;43: editors. Minimally invasive surgery of the head,
1111–7. neck, and cranial base. Philadelphia: Lippincott
71. Wilkins RH. Cranial nerve dysfunction syndromes: Williams & Wilkins; 2002. p. 355–66.
evidence for microvascular compression. In: Barrow 86. May M. Gold weight and wire spring implants as
D, editor. Surgery of the cranial nerves of the poste- alternatives to tarsorraphy. Arch Otolaryngol Head
rior fossa. Park Ridge (IL): American Association of Neck 1987;113:656–60.
Neurological Surgeons; 1993. p. 155–63. 87. Kelly SA, Sharpe DT. Gold eyelid weights in patients
72. Liao JJ, Cheng WC, Chang CN, et al. Reoperation for with facial palsy: a patient review. Plast Reconstr
recurrent trigeminal neuralgia after microvascular Surg 1992;89:436–40.
decompression. Surg Neurol 1997;47:562–70. 88. Samii M. Rehabilitation of the face by facial nerve
73. Magnan J, Caces F, Locatelli P, Chays A. Hemifacial substitution. In: Fisch U, editor. Facial nerve surgery.
spasm: endoscopic vascular decompression. Oto- Birmingham (AL): Aesculapius Publishing Co.;
laryngol Head Neck Surg 1997;117:308–14. 1977. p. 224–45.
74. Graham MD, Kemink JL. Total facial nerve decom- 89. Conley J, Baker D. Hypoglossal-facial nerve anasto-
pression in recurrent facial paralysis and the Melk- mosis for reinnervation of the paralyzed face. Plast
ersson-Rosenthal syndrome: a preliminary report. Reconstr Surg 1979;63:63–72.
Am J Otol 1986;7:34–7. 90. Pensak ML, Jackson GG, Glasscock ME, Gulya AJ.
75. Eicher SA, Coker NJ, Alford BR, et al. A comparative Facial reanimation with the XII-VII anastomosis:
study of the fallopian canal at the meatal foramen analysis of the functional and psychological
and labyrinthine segment in young children and results. Otolaryngol Head Neck Surg 1986;94:
adults. Arch Otolaryngol Head Neck Surg 1990; 305–10.
116:1030–5. 91. May M, Sobel SM, Mester SJ. Hypoglossal-facial
76. Ge XX, Spector GJ. Labyrinthine segment and genic- nerve interpositional jump graft for facial reanima-
ulate ganglion of the facial nerve in fetal and adult tion without tongue atrophy. Otolaryngol Head
temporal bones. Ann Otol Rhino Laryngol 1981;90: Neck Surg 1991;204:818–26.
1–12. 92. Hammerschlag PE. Facial reanimation with jump
77. Jackson CG, Johnson GD, Hyams VJ, Poe DS. Patho- interpositional graft hypoglossal facial anastomosis
logic findings in the labyrinthine segment of the and hypoglossal facial anastomosis: evolution in
facial nerve in a case of facial paralysis. Ann Otol management of facial paralysis. Laryngoscope
Rhinol Laryngol 1990;99:327–9. 1999;109 Suppl:1–23.
78. Sunderland S. Nerves and nerve injuries. 2nd ed. 93. Kartush JM, Lundy LB. Facial nerve outcome in
New York: Churchill Livingstone; 1978. p. 258–9. acoustic neuroma surgery. Otolaryngol Clin North
79. Seddon HJ. Three types of nerve injury. Brain Am 1992;25:623–47.
1943;66:237–88. 94. May M, Drucker C. Temporalis muscle for facial
80. House JW, Brackmann DE. Facial nerve grading reanimation: a 13-year experience with 224 proce-
system. Otolaryngol Head Neck Surg 1985;93: dures. Arch Otolaryngol Head Neck Surg 1993;
146–7. 119:378–82.
520 Ballenger’s Otorhinolaryngology
95. Fisher E, Froedel JL. Facial suspension with acellular 99. Balliet R, Shinn J, Bach-y-Rita P. Facial paralysis
human dermal allograft. Arch Facial Plast Surg rehabilitation. Re-training selective muscle control.
1999;1:195–9. Int Rehabil Med 1982;4:67–74.
96. Konior RJ. Facial paralysis reconstruction with 100. Segal B, Zompa I, Danys I, et al. Symmetry and
Gore-Tex Soft Tissue Patch. Arch Otolaryngol Head synkinesis during rehabilitation of unilateral facial
Neck Surg 1992;118:1188–94. paralysis. J Otolaryngol 1995;24:143–8.
97. Ueda K, Harii K, Yaruada A. Long-term follow-up of 101. Brach JS, VanSwearingen JM, Lenert J, et al. Facial
nerve conduction velocity in cross-face nerve graft- neuromuscular retraining for oral synkinesis. Plast
ing for the treatment of facial paralysis. Plast Recon- Reconstr Surg 1997;99:1922–33.
str Surg 1994;93:1146–9. 102. May M, Croxson GR, Klein SR. Bell’s palsy: man-
98. Ueda K, Harii K, Yaruada A. Free neurovascular agement of sequelae using EMG rehabilitation,
muscle transposition for the treatment of facial botulinum toxin, and surgery. Am J Otol 1989;10:
paralysis using the hypoglossal nerve as a recipient 220–9.
motor source. Plast Reconstr Surg 1994;94:808–17.
CHAPTER 25
The skull base is a complex anatomic region that can approaches to skull base lesions.3 Both systems have
be the site of a diverse group of pathologic processes. been found to be reliable and accurate within 2 mm
Surgical access to this area is necessary for a variety for anatomic localization.
of neoplasms as well as nontumorous conditions Adjunctive use of endoscopy for posterior fossa
such as vertigo, facial paralysis, and hemifacial surgery and acoustic neuroma surgery has also been
spasm. found to be useful.4 Endoscopy provides better visu-
Treatment of skull base disorders can be quite alization than the microscope in certain areas of the
complex, but recent advances allow more accurate skull base, particularly in identifying neurovascular
assessment and more reliable outcomes. Improved structures, inspecting acoustic neuroma tumor
imaging techniques (especially magnetic resonance removal along the internal auditory canal (IAC), and
imaging [MRI]) allow more accurate planning of identifying open petrous air cells, thus lowering the
surgery and counseling of the patient. Diagnostic postoperative cerebrospinal fluid (CSF) leak rate.5,6
techniques such as auditory brainstem responses
(ABRs) and electronystagmography (ENG) allow
early identification of abnormalities. Intraoperative
ANATOMY
neural monitoring allows quicker, more reliable Superiorly, the floor of the cranial cavity, or skull
localization of important structures during surgery. base, serves as a support for the brain and intracra-
As more experience is reported in this area, ideas and nial structures. Inferiorly, it attaches to the facial
treatments are being refined and improved. bones anteriorly and serves as the attachment for the
An important aspect of skull base surgery, and head and neck muscles laterally and posteriorly. The
a large factor for optimal outcome, is cooperation floor of the cranial cavity is composed of the frontal,
among physicians. Consultation with a neuroradiol- ethmoid, sphenoid, temporal, and occipital bones
ogist maximizes the benefit of imaging techniques (Figure 25–1) and is broadly classified into the ante-
and allows interventional procedures such as rior, middle, and posterior fossae. Numerous foram-
embolization. Neurosurgical assistance is desirable ina allow passage of vascular and neural structures
when intracranial exposure is necessary. In selected between the intracranial and extracranial space. The
cases, participation of other physicians such as vas- area below the midlateral portion of the skull base
cular surgeons may also be beneficial. (essentially the temporal bone) is designated the
Recent advances in technology, including infratemporal fossa.
image guidance systems and endoscopes, are being
applied to skull base surgical procedures.
Image guidance systems consist of either an
ANTERIOR CRANIAL FOSSA
electromagnetic tracking system or an optical The anterior fossa is composed of the frontal bone
infrared tracking system.1,2 In the field of otolaryn- anteriorly and laterally, the cribriform plate of the
gology, the more common application has been in ethmoid bone centrally, and the body and lesser
sinus surgery, but recent interest has arisen for appli- wing of the sphenoid bone posteriorly and centrally.
cation to skull base procedures. Image guidance sys- Immediately anterior to the cribriform plate is the
tems are particularly appealing for middle fossa foramen cecum, through which an emissary vein
521
522 Ballenger’s Otorhinolaryngology
A B
FIGURE 25–1. A, View of the skull base from above shows the foramina discussed in the text (right), the three divi-
sions of the skull base (right), and the bones comprising this area (left). B, View of the skull base from below with the
foramina labeled on the right side of the figure and individual bones comprising the skull base on the left.
passes to the nasal cavity. The perforated cribriform The trigeminal nerve originates in the posterior cra-
plate allows passage of the olfactory nerve fibers nial fossa and enters the middle cranial fossa
traveling from the olfactory epithelium of the supe- through a fold of dura over the medial part of the
rior part of the nasal cavity to the olfactory bulb. The petrous ridge, Meckel’s cave. The fifth cranial nerve
sella turcica contains the pituitary gland in the pos- (gasserian) ganglion lies immediately anterior to this
terior central area of the anterior fossa at the junc- and rests over the horizontal portion of the carotid
tion with the middle and posterior fossae. The optic artery. From the gasserian ganglion, the three
chiasm rests anterior and superior to the pituitary in branches arise. The mandibular division of the
the chiasmic groove. The cavernous sinus lies lateral trigeminal nerve exits the cranial cavity anterome-
to the pituitary gland and sella turcica. dial to the foramen spinosum through the foramen
ovale. Further anteromedially, the foramen rotun-
dum allows for the exit of the maxillary branch of
MIDDLE CRANIAL FOSSA the trigeminal nerve in an anterior and horizontal
The middle fossa is formed by the greater wing of direction to the pterygopalatine space. The oph-
the sphenoid bone anterocentrally and the temporal thalmic branch of the trigeminal nerve, along with
bone centrally, laterally, and posteriorly. It extends cranial nerves III, IV, and VI and the ophthalmic
from the superior orbital fissure (greater wing of the vein, pass through the cavernous sinus and then
sphenoid) anteriorly to the superior petrosal sinus enter the orbit through the superior orbital fissure.
along the petrous ridge posteriorly and from the After entering the central portion of the temporal
cavernous sinus medially to the squamous portion bone from the neck, the carotid artery curves medi-
of the temporal bone laterally. Anteromedially, the ally 90 degrees and runs a near-horizontal course in
foramen spinosum allows passage of the middle a medial direction in the foramen lacerum before
meningeal artery into the cranial space, where it entering the intracranial space and passing through
courses laterally along the outer surface of the dura. the cavernous sinus.
Surgery of the Skull Base 523
Magnetic resonance imaging came into regular subsequently been surpassed by MRI. High-resolu-
use in the late 1980s. Soft tissue detail is significantly tion CT scanning of the temporal bone and skull
improved from previous techniques. Gadolinium base remains the best study of bony anatomy and of
diethylenetriamine pentaacetic acid (DTPA), a para- bone destruction by space-occupying lesions (Figure
magnetic contrast agent, allows definition of many 25–5). Intravenous iodine-based contrast can be
tissues and lesions. It is given intravenously, and, used to enhance soft tissue visualization.
unlike iodine compounds, adverse reactions to it are Angiography can be useful as both a diagnos-
extremely rare. In the CPA, MRI has allowed identi- tic and a treatment modality. Primary vascular
fication of smaller acoustic neuromas than in the abnormalities such as aneurysms, arteriovenous
past. Even very small acoustic neuromas that do not malformations, and arteriovenous fistulae are read-
show significant tissue distortion readily enhance ily seen on angiography. Vascular tumors such as
with gadolinium (Figure 25–4, A and B). One distinct glomus jugulare (Figure 25–6) and glomus vagale
advantage of MRI is that, in one “pass” through the can be clearly identified, with their blood supplies
scanner, complete information is entered into the delineated. Angiography is also useful to establish
computer and an image can be created in any plane, the patency, location, and relationship of the blood
most commonly the axial, coronal, or sagittal planes. vessels adjacent to the lesions.
A drawback of MRI is the complete lack of visualiza- In lesions that involve or are adjacent to the
tion of bone, making it difficult to evaluate any bony internal carotid artery, preoperative occlusion stud-
abnormality or soft tissue– bony interfaces. Magnetic ies are of predictive value when considering resec-
resonance imaging is contraindicated in patients with tion of the artery. After catheterization of the
metal implants such as pacemakers and surgical clips. internal carotid artery, the vessel is balloon occluded,
Claustrophobia and obesity can be relative con- and the patients are monitored. Patients tolerating
traindications, although newer “open” scanners fre- occlusion are at lower risk for neurogenic sequelae
quently allow enough room for obese patients and postoperatively if the artery is resected or damaged
help alleviate claustrophobic symptoms. during surgery.10
Computed tomography (CT) became the In vascular lesions such as glomus jugulare
prevalent imaging tool in the 1970s, and although it tumors, angiography with embolization has been
allowed the best soft tissue detail at the time, it has used as an isolated treatment modality but more
A B
FIGURE 25–4. Magnetic resonance image of a patient with a small right intracanalicular acoustic neuroma. A, The T1
image shows subtle contrast changes without significant internal auditory canal enlargement (arrow). B, Gadolinium
enhancement of the T1 image clearly delineates the tumor.
526 Ballenger’s Otorhinolaryngology
A B
FIGURE 25–5. Computed tomographic scan of the temporal bone in which a chondrosarcoma arises from the right
foramen lacerum. There is significant bone erosion of the petrous apex. A, Axial view demonstrates erosion of bone
along the horizontal portion of the carotid canal (black arrow) and the clivus portion of the sphenoid bone (open
arrow). B, Coronal view reveals bone erosion of the inferior aspect of the canal of the internal carotid artery (black
arrow) and hypoglossal canal (open arrow).
commonly is used as a preoperative adjunct. Preop- lesions). Although many of these are mass lesions,
erative embolization has been shown to decrease other entities, such as infectious diseases, inflamma-
significantly intraoperative blood loss in these tory abnormalities, and vascular compression syn-
patients.11,12 dromes, must be considered. Although malignant
lesions do occur, fortunately, most of the skull base
entities are benign. When evaluating a patient with
SKULL BASE DISORDERS a malignant skull base lesion, it is important to rule
There are a large variety of skull base disorders (see out the possibility of a metastasis from a regional or
Table 25–2 for differential diagnosis of skull base distant site.
TABLE 25–2. Differential Diagnosis of Skull Base lesions as well as malignant entities such as sinonasal
Lesions tumors and esthesioneuroblastoma.
Fibro-osseous lesions, fibrous dysplasia and
Glomus tumors ossifying fibroma, are common benign lesions of the
Meningiomas anterior part of the skull base. Fibrous dysplasia may
occur in monostotic (one site) or polyostotic (more
Neural tumors
than one site) forms. The monostotic form is the
Neurilemmoma (acoustic neuroma, facial nerve most common. Ossifying fibromas have a higher
schwannoma) growth rate than fibrous dysplasia. They are differ-
Neurofibroma entiated on CT from fibrous dysplasia by the appear-
Chordoma ance of a bony capsule. Another common lesion is
Carcinomas an osseous lesion, an osteoma. Osteomas frequently
Primary arise in the frontal and ethmoid sinuses and involve
Squamous cell carcinoma the anterior part of the skull base secondarily. Patho-
Basal cell carcinoma logic differentiation among these lesions is some-
Metastatic times difficult. Treatment of these lesions is
Squamous cell carcinoma (upper aerodigestive necessary only when functional problems arise or
tract, lung) cosmetic deformity occurs.13
Adenocarcinoma (kidney, breast, lung, salivary Two malignant lesions that can involve the
gland) anterior part of the skull base are paranasal sinus
Nasopharyngeal
carcinoma and esthesioneuroblastoma. Ethmoid
Primary cholesteatomas and, less commonly, frontal sinus tumors (most of
Rare lesions which are squamous cell carcinomas) involve the
Rhabdomyosarcoma anterior part of the skull base through direct exten-
Plasmacytoma sion. Wide surgical removal, usually in combination
Melanoma with radiation or chemotherapy, is necessary when
Giant cell tumor treatment for cure is planned. Esthesioneuroblas-
Osteoblastoma tomas are of neural crest origin and represent about
Lipoma 2% of all malignant nasal neoplasms. The cribriform
Chondrosarcoma plate is involved early as this lesion arises from the
Leukemia olfactory epithelium.14 Total gross removal may
Eosinophilic granuloma require craniofacial resection as well as orbital exen-
Dermoid/teratoma teration in addition to sinus eradication.
Histiocytosis
Hemangiopericytoma
Ewing’s sarcoma MIDDLE FOSSA/PETROUS APEX LESIONS
Petrositis Mass lesions of the middle cranial fossa and petrous
apex include benign entities such as cholesterol
granuloma, meningiomas, cholesteatomas, and
Some mass lesions may be unique to specific schwannomas. The latter three lesions are discussed
areas of the skull base, whereas others can arise in in more detail later in this chapter. Malignant lesions
more than one site. The following section will briefly such as chordoma, chondrosarcoma, and nasopha-
review lesions by location. The more important enti- ryngeal carcinoma can also affect this area.
ties will subsequently be discussed individually. Cholesterol granulomas are fluid-filled cysts
that may arise in any portion of the air cell system of
LESIONS OF THE ANTERIOR PART OF THE the temporal bone, more commonly in the petrous
apex. They occur in well-pneumatized temporal
SKULL BASE bones in air cells that are poorly ventilated. The neg-
Mass lesions of the anterior part of the skull base ative pressure causes a hemorrhage in the air cell.
include benign fibro-osseous lesions and osseous Once the blood begins to break down, there is a for-
528 Ballenger’s Otorhinolaryngology
eign body reaction to one of the breakdown compo- facial paresis. Computed tomography shows irregu-
nents, cholesterol.15 Cholesterol granulomas have a lar bony destruction with the contrast enhancement
propensity to affect cranial nerves. The patient usu- (see Figure 25–5). The lesion also brightly enhances
ally presents with hearing loss, although vertigo, on MRI. Total removal of the tumor is the optimum
facial paresis, and diplopia may be present. Diagno- treatment. Radiation therapy is controversial.
sis is usually confirmed with CT and MRI (Figure Nasopharyngeal cancer is discussed in Chapter
25–7). This lesion appears very bright on both T1- 60. Larger lesions can invade the skull base and pres-
and T2-weighted images. Treatment consists of sur- ent with symptoms of a skull base lesion.
gical drainage with maintenance of ventilation.16
Of the potentially malignant lesions, chor-
doma is relatively insidious. This neoplasm is
POSTERIOR FOSSA/INTERNAL AUDITORY
thought to arise from the primitive notochord, and CANAL LESIONS
the majority involve the petroclival area. Symptoms Most mass lesions of the posterior fossa are benign.
are caused by progressive involvement of adjacent Acoustic neuromas account for roughly 90% of the
cranial nerves. The typical CT shows an irregular lesions, whereas meningiomas account for about
mass with bony destruction. Magnetic resonance 5%. These will be discussed later. Other mass lesions
imaging reveals a low-intensity mass on T1 and T2, include epidermoids, lipomas, and arachnoid cysts.
with variable enhancement. Extensive surgery in The majority of the malignant lesions that do occur
combination with high-dose radiation therapy is the in this area are metastatic. Epidermoids arise from
treatment of choice.17 trapped rests of keratinized squamous epithelium
Chondrosarcomas are rare, comprising less and comprise 1% of CPA tumors.19 Careful removal
than 1% of skull base tumors.18 They are thought to of all squamous cell elements is necessary to prevent
arise from trapped embryologic rests in and around aseptic meningitis or recurrence.
the foramen lacerum. Hearing loss is the initial com-
plaint of most patients, although complaints may
include tinnitus, vertigo, unsteadiness, diplopia, and B
FIGURE 25–7. Patient with a large cholesterol granuloma of the left petrous apex. A, Bone window axial computed
tomographic scan shows soft tissue density replacing the entire left petrous apex (arrows). B, T1-weighted magnetic res-
onance image shows this bright lesion (arrow).
Surgery of the Skull Base 529
Lipomas can occur in the IAC and CPA. Inter- States, there is an incidence of approximately 1 in
nal auditory canal lipomas tend to present earlier 100,000, resulting in roughly 2,500 new cases diag-
because of neural compression, whereas CPA lipo- nosed each year. The name is a misnomer because
mas may not cause symptoms until they are much they actually arise from the Schwann cells surround-
larger. Diagnosis is made with MRI.20 Arachnoid ing the vestibular portion of the eighth cranial nerve.
cysts, which are collections of CSF trapped by Since Schwann cells are peripheral nerve entities,
arachnoid granulations, comprise about 1% of CPA then, by definition, these must arise in the IAC.
lesions. They are very frequently asymptomatic and Acoustic neuromas occur in two forms: spo-
are incidental findings on MRI (Figure 25–8). If radic and those associated with neurofibromatosis 2.
symptomatic, surgical treatment involves opening of The sporadic form constitutes well over 90% of all
the cyst wall.21 acoustic neuromas. Neurofibromatosis 2 is a rare
Metastatic lesions from any other location to autosomal dominant genetic disorder whose gene is
the CPA is possible. Fortunately, this occurrence is located on chromosome 22, resulting in bilateral
rare. Tumors most likely to metastasize are breast acoustic neuromas and other central nervous system
tumors, adenocarcinomas, prostrate cancers, and neoplasms.
clear cell tumors of the genital organs.22 Unilateral hearing loss is the most com-
mon presenting symptom. Other symptoms that may
occur are tinnitus, dysequilibrium, vertigo, headache,
SKULL BASE DISORDERS BY and aural fullness. Later symptoms can include facial
DIAGNOSIS numbness, facial weakness, and diplopia. When the
tumors are very large, neuropathies of cranial nerves
NEUROMA/SCHWANNOMA
III, IV, VI, IX, X, and XI, as well as cerebellar and
Acoustic Neuroma Acoustic neuromas are the brainstem compression, can occur.
most common lesion of the CPA, representing 90% of Acoustic neuromas are relatively slow-growing
all tumors in this area. Acoustic neuromas constitute tumors. Grossly, they appear yellow to gray and may
about 6% of all intracranial tumors. In the United have a cystic structure. Histopathologically, there are
morphologic patterns: Antoni A and Antoni B. Antoni
Type A is represented by small, densely packed spin-
dle-shaped cells with dark staining nuclei. In Antoni
A, the cells may have a whirled appearance referred to
as Verocay bodies. They have no clinical significance.
Antoni Type B refers to loosely packed vacuolated
cells. Nuclei appear large and atypical and are densely
staining. This is the predominant form in large
tumors. There may also be a mixed pattern. The pat-
tern does not correlate with the clinical presentation.
Staining for S-100 immunoperoxidase is confirma-
tory for a Schwann cell.
The introduction of MRI in the 1980s has rev-
olutionized the diagnosis of acoustic neuromas. Prior
to MRI, CT was employed. Computed tomography
was a valuable diagnostic tool if the tumor extended
into the CPA or there was widening of the porus
acusticus by the tumor. However, smaller intra-
canalicular tumors had to be diagnosed by air-con-
FIGURE 25–8. T1-weighted magnetic resonance image trast CT, requiring a lumbar puncture and injecting
shows an apparent soft tissue mass (arrow) in the cere- air in the subarachnoid space. Magnetic resonance
bellopontine angle in a patient who presented with imaging has made this procedure obsolete. Acoustic
headaches and vertigo. At surgical resection, an arach- tumors readily enhance with the injection of gadolin-
noid cyst was identified. ium (see Figure 25–4). Tumors as small as 2 to 3 mm
530 Ballenger’s Otorhinolaryngology
are easily seen. This allows for the diagnosis of vagal schwannomas are more common, whereas
acoustic neuromas prior to the onset of severe clini- ninth, eleventh, and twelfth cranial nerve schwan-
cal symptoms. Also, asymptomatic lesions that are nomas are rare. They are diagnosed with contrast
contained in the IAC can be readily followed. MRI, whereas CT can reveal expansion of the bone.
Surgical removal is the treatment of choice Surgical removal is the treatment of choice for
when the tumor is symptomatic or begins to extend symptomatic lesions.
beyond the IAC.23 Total removal with the preserva-
tion of the facial nerve should be attempted. The
choice of procedure, translabyrinthine, suboccipital,
MENINGIOMAS
or middle fossa, depends on the size of the tumor Meningiomas are the most common benign
and the status of the hearing. These approaches will intracranial tumors and can be found in all areas of
be discussed later in this chapter. In very large the skull base. In the CPA, they comprise 5% of all
tumors and in high-risk patients, there is a role for tumors. They are thought to arise from the arach-
subtotal removal of the tumor to relieve symptoms. noid villi. Unlike acoustic neuromas, they do not
Recently, stereotactic radiation or gamma knife originate in the IAC but arise broadly from the
has been advocated for treatment of acoustic neuro- petrous face. At presentation, meningiomas are usu-
mas. This involves a one-time dose of radiation ally larger than acoustic neuromas, probably because
focused on the center of the mass. The usual dose is they do not compress the contents of the IAC.
10 to 25 Gy. This causes shrinkage and necrosis of Symptoms are related to the impingement on sur-
the mass. It has been employed in the elderly and rounding structures; however, compared with
other high-risk patients. The drawbacks are lack of acoustic neuromas, they more commonly spare
elimination of the tumor and complications, includ- hearing. The gross appearance of a meningioma is a
ing hydrocephalus and cranial nerve neuropathies. yellow to gray globular mass.
For further elaboration, see Chapter 20. Microscopically, it is characterized by sheets of
polygonal cells. The boundaries of the cell are
Facial Nerve Neuroma Facial nerve neuromas are obscure. Nuclei contain chromatin and are pale
one of the few primary lesions of the nerve. Initial staining. Histologically, calcifications known as
symptoms may include facial paresis or facial mus- psammoma bodies can be seen. On MRI, menin-
cular fasciculations. They are found primarily in the giomas appear as well-circumscribed heterogeneous
intratemporal portion of the nerve, with the genic- masses that enhance with gadolinium, as well as have
ulate ganglion area being the most common. Mag- the dural tail sign (Figure 25–9). On CT scan, the
netic resonance imaging is helpful in the workup of calcifications may be visible. Angiography may also
patients with this lesion. These lesions are usually be helpful as these lesions tend to be vascular. Surgi-
removed when facial weakness is present. Patients cal removal is necessary when symptoms appear.24,25
are usually reluctant to have them removed when
they still have facial function, especially since the
CHOLESTEATOMA
result will be a temporary total paralysis. These
lesions are usually slow growing and can be watched Cholesteatomas of the petrous apex are thought to
for a period of time. Treatment is surgical removal arise from epithelial rests trapped during develop-
with nerve grafting. For further elaboration, see ment. The squamous cell debris begins to organize
Chapter 24. as a cyst, which starts a destructive process that may
erode bone. Another danger is secondary infection,
Other Neuromas Schwannomas of the other cra- which can cause intratemporal as well as intracra-
nial nerves are relatively unusual, but fifth and nial abscess formation. Presenting symptoms can
ninth, eleventh, and twelfthth nerve tumors must include hearing loss, otorrhea, facial paresis, or
occasionally be treated. The petrous apex (espe- diplopia. This diagnosis is also confirmed with a
cially with the fifth nerve) and the infratemporal combination of CT and MRI. Computed tomogra-
fossa can be involved. Symptoms are generally phy shows a smooth expansile lesion with bony
related to the involved nerve but can be caused by destruction. On MRI, the T1 intensity is low, whereas
compression of adjacent structures. Trigeminal and the T2 intensity is usually increased. This lesion does
Surgery of the Skull Base 531
History, Physical
Examination, Otomicroscopy
Audiometry
(pure tone),
tympanometry,
ABR
Catecholamine Positive
Screen
Imaging
CT Scan, MRI,
MR Angiography,
MR Venography
Conservative Ear
Procedure Bilateral Carotid Selective Renal Vein
Angiography Sampling
These patients should undergo high-resolution CT help distinguish a glomus tympanicum tumor from
with contrast injection. If the tumor is limited to a glomus jugulare tumor.31 Flow-sensitive weighting
the middle ear and there is no bony destruction, of the MRI can produce a magnetic resonance arte-
the tumor is classified as a glomus tympanicum riography and magnetic resonance venography that
tumor, and no further radiologic workup is are very useful in imaging glomus tympanicum
needed.28 If the CT shows any bony destruction lesions. The flow-sensitive modalities can indicate
or connection with the jugular bulb, an MRI is occlusion of the jugular bulb and vein, which can be
obtained, which helps to define any intracranial particularly helpful for identifying involvement of
extension or jugular vein or carotid artery involve- the jugular bulb itself. It must be remembered, how-
ment and also screens for the presence of a second ever, that an enhanced MRI involves T1 imaging that
glomus tumor in the head and neck.29,30 If workup produces a bright signal characteristic for fat, which
reveals a glomus jugulare tumor and the patient is is a major constituent of bone marrow. Thus, this
a surgical candidate, preoperative four-vessel characteristic may overestimate the degree of tumor
angiography is indicated. involvement when there is paraganglioma adjacent
to bone marrow–containing spaces such as the
Glomus Tumor Algorithm The characteristic petrous apex.32 A particular value of flow-weighted
salt-and-pepper appearance on MRI corresponds to MRI is that it can be a useful screening test for syn-
flow voids. Special subtraction MRI sequences may chronous paragangliomas.33 This study can identify
534 Ballenger’s Otorhinolaryngology
glomus tumors in the temporal bone and along the mastoid exposure of the lesion from below com-
carotids without the need for intra-arterial infu- bined with a middle fossa craniotomy to expose the
sion.34 After angiography, superselective emboliza- superior aspect of the defect.
tion of the tumor-feeding vessels is performed at the
same time. During cerebral angiography, the patency
INFECTIOUS LESIONS
of the venous drainage system of the opposite side
and the patency of the cerebral crossflow are evalu- Petrous apicitis is a coalescence of the cells in the
ated. A combination of CT, MRI, and angiography apex usually associated with a chronic infectious
clearly defines the extent of the disease and therefore process, mastoiditis, or cholesteatoma. Infectious
limits unexpected findings at the time of operation. agents include Staphylococcus, Haemophilus, or
Surgical removal is the treatment of choice. Pseudomonas. Symptoms include aural discharge,
Preoperative embolization can decrease operative retro-orbital pain, and a sixth nerve palsy
morbidity. Radiation therapy can be used alone; (Gradenigo’s syndrome). Possible sequelae can
however, it is usually reserved for patients with con- include intracranial abscess formation, meningitis,
current medical problems or the elderly, who may and other cranial nerve palsies. Computed tomogra-
be at higher risk for surgical complications. phy will reveal bony destruction with irregular bor-
ders. On MRI, the T1 image shows low signal
intensity; however, the lesion is very bright on T2.
ENCEPHALOCELES Gadolinium infusion shows a ring of enhancement
Encephaloceles are defined as intracranial contents around the lesion. Treatment includes intravenous
beyond the confines of the cranial vault. Various antibiotics and a surgical procedure to establish ade-
components may be extruding. In meningoceles, quate and sustained drainage and ventilation of the
only the meninges and CSF have herniated. petrous apex.
Encephalomeningoceles represent herniations of the
brain along with meninges, whereas hydroen-
VASCULAR COMPRESSION SYNDROMES
cephalomeningoceles represent the herniation of
ventricles along with the brain. Vascular compression syndromes are abnormal exci-
Encephaloceles can be divided into acquired and tation of the nerve owing to sustained contact with
spontaneous lesions. An acquired lesion is one that adjacent blood vessels. Prolonged contact of a blood
occurs secondary to an event such as trauma, chronic vessel to a neural sheath causes chronic excitation
infection, or surgery. Lesions are referred to as sponta- and reorganization of the cranial nerve nucleus,
neous if no preceding event is present. Spontaneous resulting in hyperfunction.36 Depending on the
lesions can be further subdivided into congenital and involved cranial nerve, this condition may result in
idiopathic lesions. Congenital lesions occur in 1 in hemifacial spasm, trigeminal neuralgia, or cochleo-
3,000 to 10,000 live births. They are more common in vestibular compression syndrome.
the anterior and posterior fossa. Congenital temporal Hemifacial spasm consists of involuntary facial
lobe herniations are rare but do occur. There are many muscle spasms. These usually begin with the orbic-
theories to try to explain temporal lobe herniations. ularis oculi and proceed to involve the lower parts of
Most patients with a herniation are found to have the face. Eventually, the patient can develop facial
multiple defects in the temporal bone. Arachnoid weakness thought to be caused by demyelination
granulations greater than 3 mm are thought to cause secondary to the compression. The unilaterality of
bony erosion, leading to herniation.35 this disorder helps to differentiate it from essential
Presentation is similar in all types of lesions. blepharospasm.
They can present with CSF rhinorrhea or otorrhea, Trigeminal neuralgia is characterized by pierc-
recurrent meningitis, serous otitis media, or a con- ing facial pain. Tactile stimulation of the face, pain,
ductive hearing loss. Diagnosis is made with a com- cold, or dental work can cause hyperactivity in the
bination of CT for bony detail and MRI for soft nucleus, resulting in the pain. Cochleovestibular
tissue detail. Surgical repair is necessary if they compression syndrome has been reported to result
become symptomatic. For lesions greater than 1.5 in continuous vertigo, hearing loss, nausea, tinnitus,
cm, the recommended treatment involves a trans- and imbalance.
Surgery of the Skull Base 535
In these patients, all other potential causes ditional radiation therapy. Commonly, patients
must be ruled out. For those failing more conserva- receive their total radiation dose in a single treatment.
tive treatment (ie, medical therapy to relieve symp- Thus, the risks should be less than traditional radia-
toms), surgical exploration of the nerve and tion, and the time involved is greatly reduced (1 day
decompressing the offending vascular structure are versus approximately 6 weeks). Its use is limited to
an option. In the CPA, this is usually the anterior somewhat smaller tumors (acoustic neuromas < 2
inferior cerebellar artery or posterior inferior cere- cm), and it appears to be an option for surgically
bellar artery, but veins may also be the culprits. unsuitable patients with appropriate-size tumors. The
obvious benefit is avoidance of a large, usually
intracranial surgical procedure. In the specific exam-
MANAGEMENT ple of acoustic neuroma, the initial risks are markedly
It is beyond the scope of this chapter to review the less than surgical intervention, but over time, the risks
treatment issues for each of the skull base disorders, to adjacent structures such as the facial or cochlear
but a general overview of available modalities and nerves approach or exceed the surgical risks. Halting
techniques is designed to give the reader some basis or limiting the growth of the tumor is the usual out-
for understanding their roles. come, with regression less commonly noted. Leskell
Some of the lesions discussed are malignant by first used the gamma knife in 1969.38 Local control
definition. The majority are benign but clinically rates on tumor growth were first reported to be 86%
“malignant” either because of the debility of symp- for unilateral tumors39; Flinkinger et al reported a
toms or their proximity to neural and vascular struc- local control rate of 89%.40 Maire et al reported a 6-
tures. The histologic classification, severity of year actuarial rate of 82% local control (no growth)
symptoms, and proximity to important structures with external beam radiation.41 Owing to the expense
play a role in treatment decision making. Treatment of gamma-knife radiation recently, development of
options generally include surgery, radiation, linear accelerator–based stereotactic radiation has
chemotherapy, or simple observation. Oncologic ensued. It is less expensive and used for conventional
chemotherapy has a limited role in the management radiation. Mendenhall et al treated patients with a lin-
of skull base lesions aside from an occasional pri- ear accelerator–based stereotactic radiation and
mary or metastatic cancer. This discussion centers reported a local control rate of 98% and actuarial
around mass lesions that require intervention or control rate of 95%.42
pathophysiologic disorders that have failed medical Although surgery is the mainstay for the treat-
therapy. ment of patients with acoustic neuromas, radiation
therapy has improved and now is considered an
alternative option for a certain subset of patients,
RADIATION especially patients who are not surgical candidates.41
External beam radiation has been used as an adjunct An occasional problem arises when tumors do not
to surgery in certain lesions such as olfactory neu- respond to radiation and require surgical treatment.
roblastoma. Primary radiation traditionally has been The surgical risks are increased since the radiation-
used in the more common benign lesions (such as damaged tissue is generally more difficult to dissect.
acoustic neuroma) in the elderly or medically dis-
abled, but treatment results vary. Primary risks
include damage to the brain and nerves and the
SURGERY
superficial structures such as skin as well as osteora- Considerations The skull base is an area dense
dionecrosis of the bone. with important neural, vascular, and structural enti-
More recently, stereotactically directed gamma ties. Preoperative discussions with patients must
radiation (“gamma knife”) has been discussed as a include a thorough review of the pathologic entity as
treatment option.37 Numerous cobalt sources well as the potential and planned morbidity of the
(approximately 200) are positioned in a hemispheric treatment. Each procedure and skull base area have
pattern oriented toward a common point. In this their own individual structures at risk.
technique, high doses of radiation are given to a more In the majority of accessible tumors, surgical
localized area in shorter periods of time than in tra- removal is the treatment of choice. Surgery also
536 Ballenger’s Otorhinolaryngology
allows access to particular structures such as the sev- TABLE 25–4. Complications and Sequelae of Skull
enth cranial nerve for microvascular decompression Base Surgery
and the eighth cranial nerve for vestibular neurec-
tomy. Success depends on many factors. Two impor- Cerebrospinal fluid leakage
tant aspects are accurate assessment of the clinical Meningitis
entity preoperatively and, of course, the skill of the Chemical
surgeon. The choice of surgical approach depends Bacterial
on the pathologic process and the expertise of the
Intracranial hemorrhage
surgeons(s).
Expected morbidity, such as loss of any resid- Wound infection
ual hearing in a translabyrinthine approach for Wound hematoma
acoustic neuroma removal, should be discussed and
Cerebrovascular accident/coma
weighed against the benefits of surgery in general
and specifically of a particular procedure/approach. Cranial nerve deficits
In the case of the translabyrinthine approach, External auditory canal stenosis
decreased risk to facial nerve and less cerebellar
retraction are the primary advantages. Urinary tract infection
Aspiration
Complications of Skull Base Surgery See Table
Pulmonary embolism
25–4 for complications of skull base surgery.
The more important complications result from Death
alteration of function of intracranial structures. Pneumonia
Infarction of intracranial structures, such as the
Adult respiratory distress syndrome
cerebellum or brainstem, from excessive retraction
or blood vessel damage can result in significant mor- Pneumothorax
bidity or death. Cerebellar dysfunction
Intracranial hemorrhage may occur in the
immediate or late postoperative period. Treatment Bulbar dysfunction
usually includes immediate opening of the wound Hydrocephalus
and return to the operating room for complete Seizures
drainage of the blood with identification and control
of the bleeding site. If identified and treated early,
there may be no residual sequelae, but important
functional defects are possible.
Complications may arise simply as a result of wound closures. Drainage may occur through the
entrance into the CSF-containing space. Meningitis nose (CSF rhinorrhea), the ear (CSF otorrhea), or
is a known risk and tends to occur between the third the incision. In the anterior approaches (craniofa-
and seventh postoperative days. Because of the fre- cial), the fluid will generally drain through the nose
quent postoperative malaise, head/neck discomfort, anteriorly, whereas in the posterior approaches, the
and fevers from meningeal irritation, meningitis can CSF reaches the nose through the eustachian tube
be difficult to identify in this situation. A low thresh- and may result in either anterior or posterior rhin-
old of suspicion and early lumbar puncture will orrhea. If a tympanic membrane perforation is pres-
allow early identification and rapid resolution with ent at the time of operation in the middle or
the institution of appropriate intravenous anti- posterior fossa or occurs in the postoperative period,
biotics.43 CSF otorrhea may occur. Initial treatment of CSF
Cerebrospinal fluid leaks can occur at any time leak consists of head elevation and either lumbar
after the operation, but the risk is greatest in the first puncture or placement of an indwelling lumbar
10 days. In high-risk procedures, CSF lumbar drains spinal drain. If these conservative measures are
may be placed at the time of operation to keep unsuccessful, then surgical exploration and reclosure
intracranial pressures low and decrease tension on of the wound are necessary.
Surgery of the Skull Base 537
Injury to any of the vascular structures (ie, clicks through an external auditory canal insert.
carotid artery) or neural structures (ie, cranial Since recordings are generally obtained with a nee-
nerves) is possible and must be dealt with intraoper- dle electrode on the promontory, the responses are
atively if the structure has been interrupted and post- more robust, require fewer trials, and ideally
operatively if there are significant sequelae. In the require less time between the operative maneuver
lateral and posterior approaches, altered function of and the change in the observed waveform. Direct
the seventh cranial nerve is a frequent postoperative eighth nerve monitoring records nerve impulses
problem. Transection of the nerve intraoperatively traveling in the auditory nerve. The electrode is
requires immediate primary repair or cable grafting, placed on the nerve proximal to the operative site
if possible. In this case, delayed and incomplete so that any alteration in the physiologic status of
recovery would be expected. If the continuity is the peripheral part of the auditory system will be
maintained, but injury occurs secondary to stretch- immediately detected.44
ing or contusion, recovery generally occurs, but time
and completeness are variable. Risk to the cornea, Surgical Approaches Because of the complexity
which results from incomplete eye closure, is the of the skull base and the diversity of the possible
most important issue. For expected transient weak- abnormalities, many surgical approaches have been
nesses, local eye care such as use of lubricants is all developed. They are continually being modified, and
that is generally needed. For longer periods of altered new ones are being described.45,46
function or permanent paralysis, procedures such as
upper eyelid gold weight implantation, lower eyelid CRANIOFACIAL APPROACH. For lesions that involve the
ectropion repair, or tarsorrhaphy are frequently indi- roof of the ethmoid sinuses or the superior nasal
cated for adequate corneal protection. In cases of per- vault (cribriform area), visualization from above
manent paralysis, nerve grafting, twelfth to seventh (cranially) and below (facially) can be obtained
end-to-side (jump graft) or end-to-end grafting, or through a craniofacial approach. The most common
muscle transposition (ie, temporalis) may be useful lesions include olfactory neuroblastoma and eth-
for rehabilitation of the entire face. moid sinus cancer.
The approach from above is initiated with a
Intraoperative Monitoring Preservation of neu- bicoronal incision originating anterior and supe-
ral structures is a crucial part of skull base surgery. rior to the auricles bilaterally followed by flap ele-
Although there is no substitute for surgical knowl- vation over the forehead (Figure 25–11). An
edge, neural monitoring is a useful adjunct. The anterior craniotomy exposes the frontal sinus,
motor nerve integrity can be followed by monitoring which is completely removed, and the frontal lobes
EMG activity in the appropriate muscles. Increased that are gently elevated, necessitating transection of
activity will be seen as the nerve is manipulated. The the olfactory nerves. This allows visualization of
nerve of interest can also be electrically stimulated in the floor of the anterior cranial fossa, including the
the operative field to verify its identity. The seventh roofs of the orbits and cribriform plate area.
nerve is probably the most commonly and easily Visualization can be obtained back to the area over
monitored motor nerve. the anterior portion of a fully pneumatized sphe-
In the hearing preservation approaches in noid sinus. The cribriform plate and various
acoustic neuroma surgery, auditory function can be amounts of bone can be resected. Ideally, the
monitored in several ways. Most commonly, con- tumors are extradural, although dura (and even
tinuous ABR can be elicited. This has the advan- brain parenchyma) can be resected.
tage of being readily available and easy to set up but The approach from below is more variable but
the disadvantage of requiring many averaged trials generally involves at least an ethmoidectomy. Most
to detect an alteration. This can translate into a sig- commonly, a lateral rhinotomy incision is used to
nificant delay between the occurrence of a com- allow a generous view of the nasal vault and associ-
promising action and the detection of the change ated paranasal sinuses. If necessary, the ethmoidec-
in the ABR. The recording of an electro- tomy can be combined with maxillectomy or orbital
cochleogram during a procedure is frequently used. exenteration. Reconstruction and closure vary,
As in ABR, stimulation is with repeated auditory depending on the resection performed. At the com-
538 Ballenger’s Otorhinolaryngology
pletion of the procedure, dural repair can be accom- procedures, the external auditory canal is removed,
plished with temporalis fascia, fascia lata, or a local and the lateral canal skin is closed on itself. The
pericranial flap. In the most limited resections, the facial nerve is skeletonized in the mastoid and mid-
anterior cranial bone flap is replaced, and the upper dle ear and then completely mobilized. It is retracted
and lower incisions are closed primarily. For more anteriorly to allow direct visualization of the more
extensive resections, local or distant flaps may be
required to reconstruct the defect, and/or surgical
prostheses may be necessary.
medial structures (Figure 25–14). Having done this, jugular bulb, and upper portion of the internal jugu-
the remaining infralabyrinthine bone is removed to lar vein are resected with the tumor. The operation
allow access to the tumor, the entire sigmoid may be continued intracranially in the same sitting
sinus/jugular bulb/internal jugular vein, and the or in a second stage for larger tumors. In glomus
internal carotid artery anteromedial to the jugular jugulare tumor operations, major blood loss is usu-
vein. Removal of the tumor is then generally possi- ally encountered, although it is usually markedly
ble. In glomus jugulare tumors, the sigmoid sinus, decreased with preoperative embolization.
In most situations, the wound can be closed MIDDLE CRANIAL FOSSA APPROACH. The middle cra-
primarily. In more extensive resections, abdominal nial fossa procedure approaches the IAC from above,
fat grafting, local tissue flaps such as temporalis and here the labyrinth can be preserved in an
muscle, or free vascularized grafts may be necessary. attempt to conserve hearing. This procedure is com-
monly used in the resection of acoustic neuromas
INTERNAL AUDITORY CANAL/POSTERIOR FOSSA and for vestibular neurectomy. In the IAC, the
APPROACHES. These surgical approaches overall are vestibular portions of the eighth nerve are distinct
the most commonly used and are designed to allow from the cochlear division, and, at least theoretically,
exposure of the IAC, the CPA, and the petrous apex. the vestibular nerve can be sectioned more precisely.
The middle cranial fossa, translabyrinthine, and ret- In acoustic neuroma surgery, the middle cranial
rosigmoid approaches can all be used for resection fossa approach is used when two main criteria are
of acoustic neuromas (Figure 25–15). The middle fulfilled: the tumors are completely within the IAC
cranial fossa and retrosigmoid approaches are classi- (intracanalicular) and the patient has preoperative
fied as hearing preserved, and in many instances, the hearing that is good enough to justify a procedure
cochlear division of the eighth nerve can be pre- that is somewhat more complex than the other
served, allowing at least the possibility of hearing approaches.
postoperatively. In the translabyrinthine approach, This procedure can also be used to access the
the vestibular portion of the labyrinth is intention- area medial to the IAC (petrous apex) for lesions
ally removed. Although this allows better visualiza- such as cholesterol granulomas. For larger temporal
tion of the seventh nerve and the IAC, any residual lobe encephaloceles, visualization through the mid-
hearing is predictably and completely lost. Each has dle cranial fossa approach is necessary to bring the
its advantages and indications. brain back into the intracranial cavity and to cover
FIGURE 25–15. Diagram of the three main approaches to tumors of the cerebellopontine angel (CPA). The
translabyrinthine approach gives the surgeon the best exposure but sacrifices hearing. The middle fossa offers the least
exposure and thus is useful only for intracranial tumors in patients in whom hearing preservation will be attempted.
The retrosigmoid approach gives good exposure of the CPA but offers the least number of landmarks for identifica-
tion of the facial nerve. We reserve it for small tumors of the CPA in patients in whom hearing preservation is worth-
while. Reproduced with permission from Monsell EM, McElveen JT, Hitselberger WE, House WF. Surgical approaches
to the human cochlear nuclear complex. Am J Otol 1987;8:450–5.
Surgery of the Skull Base 541
the bony defect adequately (generally with a bone ally), which lie on each side of the IAC, must not be
flap). Additionally, this approach is used for explo- violated or hearing will be lost.
ration of the geniculate and labyrinthine portion of In vestibular neurectomy, the superior and
the seventh nerve in cases of temporal bone trauma inferior vestibular nerves are identified in the IAC
and for bony decompression for Bell’s palsy. and transected. For seventh nerve decompression,
With the surgeon at the head of the table, the exposure of the geniculate ganglion and labyrinthine
patient is placed in a supine position with the head portion of the seventh nerve with opening of the
turned so the involved side is up. Although different nerve sheath is completed. In acoustic neuroma
incisions have been used, the simplest is a vertical resection, the tumor is carefully removed from the
incision extending from a point in the preauricular IAC, with care being taken to preserve the seventh
area 1 cm anterior to the auricle directly superiorly nerve and the cochlear branch of the eighth cranial
for 6 to 8 cm. The incision is carried down to the nerve.
bone. Fascia and/or a muscle plug are used to close
A 3 × 3 cm bone flap is created in the underly- the dural defect, and the retracted temporal lobe is
ing bone and is removed to expose the dura overly- placed back in its anatomic position. The bone flap
ing the temporal lobe. The temporal lobe is elevated is replaced, and the incision is carefully closed.
off the floor of the middle cranial fossa until the
foramen spinosum and middle meningeal artery are RETROSIGMOID APPROACH. In the retrosigmoid ap-
seen anteriorly, the greater superior petrosal nerve is proach, the CPA is approached directly, and the IAC
seen anteromedially, and the superior petrosal sinus can be approached posteriorly. Because this
is seen posteriorly (Figure 25–16). The pertinent approach allows a generous view of the CPA, it is
surface of the temporal bone can now be visualized. useful in a variety of conditions and is used most
The arcuate eminence (the bony elevation over the frequently for CPA tumor resection, vestibular
superior semicircular canal) and the greater superfi- neurectomy, and microvascular cranial nerve
cial petrosal nerve are the most common overt land- decompression. Because this is a hearing preserva-
marks. From these, the facial nerve and the IAC can tion approach, it is used in situations in which serv-
be identified once drilling has begun. The superior iceable hearing is present and the tumor is
semicircular canal (laterally) and the cochlea (medi- extracanalicular but is less than 2 cm. However, for
B
542 Ballenger’s Otorhinolaryngology
intracanalicular tumors, the middle cranial fossa tigo in Meniere’s disease is generally reported to be
approach is more appropriate. In tumors greater greater than 90% regardless of the approach
than 2 cm, hearing preservation is unlikely, so the used.47,48 Cerebellopontine angle tumors such as
translabyrinthine approach is used. acoustic neuromas and meningiomas can be
First, a curvilinear incision is made 4 cm pos- resected through this approach.
terior to the auricle to create an anteriorly based flap On completion of the procedure, the dura is
(Figure 25–17). The bone of the mastoid and occip- closed in a watertight fashion. If this is not possible,
ital area is exposed. A bone square is created with the an abdominal fat graft is laid over the closure to seal
sigmoid sinus defining the anterior limit and the the dural defect. Although some surgeons drill away
transverse sinus defining the superior limit. Removal the bone of the entire cranial defect, we prefer to
of the bone plug exposes the dura overlying the cere- preserve the bone square and replace it at the com-
bellum. The dura is incised 5 to 10 mm posterior to pletion of the procedure. The skin is closed in the
the sigmoid sinus and inferior to the transverse usual manner.
sinus. The cerebellum is retracted posteriorly to
expose the CPA. In acoustic neuroma resection, the TRANSLABYRINTHINE APPROACH. The translabyrinthine
posterior lip of the IAC must be drilled away to approach allows a generous view of the IAC, CPA,
allow visualization of the intracanalicular portion of and petrous apex, if necessary. This approach is gen-
the tumor. erally used in patients with poor hearing as any
Since the fifth to eleventh nerves can be read- remaining hearing will be predictably and totally lost.
ily viewed, microvascular decompression of the fifth Less brain retraction is required than in the
(for trigeminal neuralgia), seventh (for hemifacial middle cranial fossa or the retrosigmoid approach,
spasm), or eighth (for tinnitus or disabling posi- and unlike the retrosigmoid approach, the facial
tional vertigo) nerves can be readily accomplished nerve can be identified prior to tumor identifica-
by gently placing a strip of Teflon felt between the tion/removal. This approach is used in essentially all
offending blood vessel and the nerve to prevent the acoustic neuromas that are larger than 2 cm or in
irritating contact. Vestibular neurectomy is per- any patient with poor hearing regardless of the
formed by identifying the longitudinal septum tumor size. Tumors greater than 4 to 5 cm may
between the vestibular and the cochlear portions of require this approach combined with the retrosig-
the eighth nerve and transecting the upper (vestibu- moid approach for complete resection (Figure
lar) half. With vestibular neurectomy, control of ver- 25–18).
A
B
Surgery of the Skull Base 543
With the patient in the supine position and the medially and anteriorly. In the transcochlear
head rotated away from the side of interest, a postau- approach, drilling is continued after a complete mas-
ricular incision is made 2 to 3 cm behind the postau- toidectomy and labyrinthectomy.50 The facial nerve
ricular sulcus (Figure 25–19). The mastoid bone is is skeletonized and mobilized posteriorly from the
completely exposed, and a drill is used to remove stylomastoid foramen to the geniculate ganglion.
completely the bone of the mastoid. The sigmoid The cochlea is then completely exenterated and the
sinus, posterior fossa dura, and middle cranial fossa internal carotid artery skeletonized, allowing a gen-
are completely decompressed. The vertical portion erous view of the internal carotid artery, petrous
of the facial nerve is identified and left with a thin apex, clivus, sixth and twelfth nerves, and the basilar
bony covering. The fossa incudus is clearly identi- and vertebral arteries, if necessary. A more extended
fied, and the incus is removed so that the middle ear view can be obtained through the transotic
space may be viewed and carefully packed at the end approach, with the tympanic membrane, malleus,
of the procedure. A labyrinthectomy is completed, incus, and posterior external auditory canal wall
and as drilling continues medially, the IAC is removed in addition to skeletonization and mobi-
exposed. The dura of the posterior fossa and IAC is lization of the seventh nerve and exenteration of the
opened, and the IAC and CPA are viewed. In the cochlea.51 In the modified transotic approach, the sev-
fundus (lateral) portion of the IAC, a vertical crest of enth nerve is left in the fallopian canal, decreasing
bone (Bill’s bar) is present and is a useful landmark the risk to it.52
since the facial nerve is anterior and the superior
vestibular nerve is posterior. After completion of the APPROACHES TO THE TEMPORAL BONE. A large amount
procedure, the middle ear space is carefully packed of skull base pathology occurs within the temporal
with small pieces of temporalis muscle, the aditus is bone. Frequently, there are specific approaches avail-
covered with compressed bone pate and bone wax, able that are generally simpler than the intracranial
and the remainder of the surgical defect is filled with procedures.
fat obtained from the abdomen.49 The incision is Tympanotomy is performed through the exter-
meticulously closed, and a mastoid dressing is nal auditory canal and allows exposure of the meso-
placed. tympanum. Frequently, glomus tympanicum and
In selected situations, the translabyrinthine congenital cholesteatoma are limited enough to be
approach can be “extended” to allow better access removed through this approach. Mastoidectomy
33. Arriaga MA, Lo WW, Brackmann DE. Magnetic res- for acoustic schwannomas. J Neurosurg 1996;85:
onance angiography of synchronous bilateral 1013–9.
carotid body paragangliomas and bilateral vagal 43. Wiet RJ, Teixido M, Liang JG. Complications in
paragangliomas. Ann Otol Rhinol Laryngol 1992: acoustic neuroma surgery. Otolaryngol Clin North
101:955–7. Am 1992;25:389–412.
34. Stewart K, Kountakis S, Chang CY, Jahrsdoerfer RA. 44. Wiet RJ, Liang JG, Teixido MT. Electrocochleogra-
Magnetic resonance angiography in the evaluation phy and direct nerve monitoring during vestibular
of glomus tympanicum tumors. Am J Otolaryngol neurectomy. In: Wiet RJ, editor. Intraoperative
1997:18;116–20. auditory monitoring. Alexandria (VA): American
35. Gacek RR. Evaluation and management of the tem- Academy of Otolaryngol Head and Neck Surgery
poral bone arachnoid granulations. Arch Otolaryn- Foundation; 1992.
gol Head Neck Surg 1992;118:327–32. 45. Sekhar S. Tumors of the cranial base. Diagnosis and
36. Møller AR, Jannetta PJ. On the origin of synkinesis treatment. Mount Kisco (NY): Futura Publishing; 1987.
in hemifacial spasm: results of intracranial record- 46. Jackler RK, Brackmann DE. Neurotology. St. Louis:
ings. J Neurosurg 1984;61:569–76. Mosby; 1994.
37. Lunsford LD, Linskey ME. Stereotatic radiosurgery 47. Glasscock ME, Kveton JF, Christiansen SG. Middle
in the treatment of patients with acoustic tumors. fossa vestibular neurectomy: an update. Otolaryngol
Otolaryngol Clin North Am 1992;25:471–91. Head Neck Surg 1984;92:216–20.
38. Leskell L. A note on the treatment of acoustic 48. Monsell E, Wiet RJ, Young NM, Kazan RP. Surgical
tumors. Acta Chir Scand 1971;137:763–5. treatment of vertigo with retrolabyrinthine vestibu-
39. Kamerer DB, Lunsford LD, Moller M. Gamma knife: lar neurectomy. Laryngoscope 1988;98:835–9.
an alternative treatment for acoustic neuromas. Ann 49. Wiet RJ, Mamikoglu B, Hoistad D, Battista R. A tech-
Otol Rhinol Laryngol 1988;97:61–5. nique to prevent cerebrospinal fluid leakage after
40. Flinkinger JC, Lunsford LD, Linskey ME, et al. translabyrinthine approach. Laryngoscope 2000;110:
Gamma knife radiosurgery for acoustic tumors: 1234–6.
multivariate analysis of four year results. Radiother 50. House WF, Hitselberger WE. The transcochlear
Oncol 1993;27:91–8. approach to the skull base. Arch Otolaryngol 1976;
41. Maire JP, Floquet A, Darrouzet V, et al. Fractionated 102:334–42.
radiation therapy in the treatment of stage III and IV 51. Jenkins HA, Fisch U. The transotic approach to
cerebellopontine angle neuromas: preliminary results resection of difficult acoustic tumors of the cerebel-
in 20 cases. Int J Radiat Oncol Biol Phys 1992;23: lopontine angle. Am J Otol 1980;2:70–6.
147–52. 52. Gantz BJ, Fisch U. Modified transotic approach to
42. Mendenhall WM, Friedman WA, Buatti JM, Bova FJ. the cerebellopontine angle. Arch Otolaryngol 1983;
Preliminary results of linear accelerator radiosurgery 109:252–6.
CHAPTER 26
ANATOMY OF THE NOSE AND gently rounded, convex, vertically oriented depres-
PARANASAL SINUSES sion in the skin of the upper lip, extends upward
from the center of the upper lip to the base of the
EXTERNAL ASPECTS OF THE NOSE membranous columella. On either side of the col-
umella are the skin-lined nares, bounded by the
From the tip or apex, the nose slopes upward and lower lateral (alar) cartilages above, the floor of the
slightly posteriorly to reach the forehead at a junc- nose below, and the columella medially. Just within
tion marked by a slight depression termed the the naris is a slight dilation, the nasal vestibule, lined
nasion (or radix nasi). Above each eye there are by skin containing coarse hair or vibrissae and seba-
slightly projecting bony arches and between the ceous and sweat glands.
arches a slightly flattened area known as the glabella. The two nasal bones together with the two
The rhinion is found at the lower end of the suture upper and lower lateral cartilages form the external
between the two nasal bones. framework of the nose (Figures 26–1 and 26–2).
The membranous columella lies between the The caudal margins of the upper lateral cartilages
two nares and extends posteriorly from the nasal usually overlie the upper margins of the lower lat-
apex to the center of the upper lip. The philtrum, a eral cartilages, and by elevating the tip of the nose,
Medial crus
alar c. Lateral crus
alar cart.
Ant. Nares
nasal spine
Intermaxillary
suture
547
548 Ballenger’s Otorhinolaryngology
A B C
Glabella
Nasion
Nasal Bone
Rhinion
Upper lateral
cartilage
Septal cartilage Septal
cartilage
Lower lateral Alar
FIGURE 26–2. A, Lateral profile cartilage cartilage
of the nose. B, Coronal section of Tip
the nose. C, Lateral view of nasal Ala
cartilages. Naris
this margin can be demonstrated within the nose. the ethmoid bone and anteriorly by the septal
The junction is called the limen nasi or nasal valve (quadrilateral) cartilage, premaxilla, and membra-
area; it is the narrowest part of the nasal airway and nous columella. Inferiorly, it is formed by the crests
accounts for almost half of the total airflow resist- of the vomer, maxillary, and palatine bones and pos-
ance. At times, the medial margins of the lower lat- teriorly by the sphenoidal crest (Figure 26–3).
eral cartilages may lie close to but separate from the
septum and thus provide less support for the nasal
dorsum. Lying lateral to the two alar cartilages in NASAL CAVITIES: NOSE
the soft tissues of the nose are frequently found one The palatal processes of the maxilla and horizontal
or more unattached, small, functionless sesamoid processes of the palate bones form the floor of the
cartilages. nose. The roof of the nose is formed by alar carti-
The horseshoe-shaped lower lateral cartilage lages, the nasal bones, the nasal processes of the
provides the framework of the naris. Its weak medial frontal bones, and the bodies of the ethmoid and
crus, together with its fellow from the other side, is sphenoid bones. The cribriform plate (lamina
incorporated into the substance of the columella. cribrosa) forms the major portion of the roof of the
In the bony skull, the pear-shaped opening to nasal lumen. The inner surfaces of the maxillae, the
the nose is the pyriform aperature, and in the mid- lacrimal bones, the superior and middle turbinates,
line of the inferior border, a midline prominence, the inferior turbinate, and the medial pterygoid
the anterior nasal spine, is located. The superior and make up the lateral wall.
lateral margins of the pyriform aperature are formed The three scroll-like, pitted turbinate bones, or
by the nasal bones and the frontal processes of the the conchae, on each side of the nose divide the nasal
maxillae, and the base or floor by the alveolar lumen into meatus. The space between the inferior
processes of the maxillae. turbinate and floor of the nose is the inferior mea-
There are two sets of alar muscles: the dilators tus, the space between the inferior and middle
(dilator naris, m. procerus, caput angulare) and con- turbinates is the middle meatus, and the space above
strictors (m. nasalis and depressor septi). They all the middle turbinate is the superior meatus. Occa-
receive innervation from cranial nerve VII. sionally, there is a supreme turbinate. The middle
and superior turbinates are extensions of the eth-
moid bones, whereas the inferior turbinate is a sep-
NASAL SEPTUM
arate bone attached by its superior border to the
The nasal septum is a midline structure derived lateral nasal wall. At the anterior ends of the middle
from several bony and cartilaginous sources: superi- and inferior turbinates, a low cuboidal or squamous
orly and posteriorly by the perpendicular plate of cell epithelium is found.
Anatomy and Physiology of the Nose and Paranasal Sinuses 549
Perpendicular
plate of
ethmoid bone
Quadrilateral
cartilage
Upper
lateral
cartilage
Lower
lateral Vomer
cartilage
Nasal crest
of palatine
Columella bone
FIGURE 26–3. The nasal sep-
Premaxilla tum.
Posteriorly, the surfaces of both middle and cells may open above the ethmoid bulla, and the
inferior turbinates are covered with pseudostratified frontonasal duct may have a separate opening. Addi-
ciliated columnar (respiratory) epithelium. The tional details of endoscopic anatomy of the nose are
epithelial stroma of the middle turbinate contains given in Chapter 34.
many glands. The large, tortuous, valveless, anasto-
mosing veins, called sinusoids, are found mainly in Inferior Meatus The inferior meatus lies below
the middle and inferior turbinates. By the degree of the inferior turbinate. On its lateral surface, 3 to 5
fluid contained in the sinusoids, they can influence cm beyond the naris, is found the orifice of the duct
the size of the nasal airway and, in effect, are capac- from the lacrimal gland. The floor of the meatus is
itance structures. They respond to neural, mechani- congruent with the roof of the mouth.
cal, thermal, physiologic, and chemical stimuli.
Nares The anterior nares are formed medially,
Superior Meatus The superior meatus (also called superiorly, and laterally by the lower lateral cartilages
the ethmoid fissure) is a slit-like space above the and the floor by the upper lip. Each naris measures
middle turbinate and is situated between the nasal about 1.5 × 1.0 cm, whereas the choanae are 2.5 × 1.5
septum and the ethmoid bone (Figure 26–4). The cm. Just within the naris is a skin-lined enlargement,
posterior ethmoid cells open into the central portion the nasal vestibule. The thin skin here contains
of this meatus. Above and posterior to the superior coarse hair (the vibrissae) and sebaceous and sweat
turbinate is the sphenoid recess, into which the glands. The choanae are formed by the horizontal
sphenoid sinus opens. plate of the palatine bone inferiorly, the vomer
medially, the vaginal process of the spenoid bone
Middle Meatus This meatus lies between the mid- superiorly, and the medial pterygoid plate laterally.
dle and inferior turbinates. It contains the orifices of
the frontal and maxillary sinuses and also the anterior
ethmoid cells. Hidden by the anterior half of the over-
PARANASAL SINUSES
hanging middle turbinate is a deep crescentic groove, There are four paired paranasal sinuses: the maxil-
the infundibulum. The crescent-shaped opening is lary, ethmoid, sphenoid, and frontal. In health, each
called the hiatus semilunaris. The inferior medial wall is filled with air and communicates with the nasal
of the infundibulum forms a shelf-like ledge known lumen through an ostium. The bony ostium is
as the uncinate process and above the ledge a hemi- slightly larger than the aperature in the mucous
spheric prominence termed the ethmoid bulla. membrane. Each sinus is lined by a relatively thin,
The frontal, maxillary, and anterior ethmoid ciliated mucous membrane whose cilia beat the
sinuses open into the infundibulum. Some ethmoid overlying blanket of mucus toward the sinus ostium
550 Ballenger’s Otorhinolaryngology
Anterior ethmoidal
cells
Upper portion of
nasal cavities
Posterior ethmoidal
cells
Sphenoid cells
to join the mucous blanket in the nose. The cilia in followed by a final period from ages 7 to 17 to 18
the sinal mucous membrane become more numer- years. Much of the growth is an invasion into the
ous as the ostium is approached. alveolar process following eruption of permanent
For clinical purposes, the sinuses are divided dentition.
into two groups, anterior and posterior, depending The maxillary sinus (also called the antrum of
on their location in reference to the line of attach- Highmore) occupies the body of the maxilla. The
ment of the middle turbinate to the lateral wall of sinus is generally pyramidal in shape, with its base
the nose. The anterior group consisting of the formed by the lateral wall of the nasal cavity and its
frontal, maxillary, and anterior ethmoid cells open apex directed toward the zygomatic process. Its
into or near the infundibulum. The posterior group, roof separates the sinus from the orbit. The floor is
made up of the posterior ethmoid cells and the formed by the alveolar process of the maxilla and
sphenoid sinuses, opens above the middle turbinate. the hard palate. In children, the sinus floor lies at or
above the level of the floor of the nasal interior,
Maxillary Sinus The growth of this sinus, the whereas in the adult, the sinus floor may lie 5 to 10
largest of the four, is biphasic (Table 26–1). The mm below. The anterior wall corresponds with the
first period occurs during the first 3 years of life canine fossa and separates the sinus from the
cheek. The posterior wall lies against the contents Ethmoid Sinus At birth, usually three or four cells
of the infratemporal space and pterygomaxillary of the ethmoid sinus are present and, along with the
fossa. maxillary sinus, are the only sinus cavities that are
The antrum communicates with the large enough to be of clinical importance (Table
infundibulum through an ostium located in the 26–2). The cells lie either in front of and below
upper anterior part of the medial wall of the sinus. (anterior ethmoid cells) or posterior and above
In 10 to 30%, an additional (accessory) ostium is (posterior ethmoid cells) the attachment of the mid-
present. The bony orifice is larger than the membra- dle turbinate to the lateral nasal wall. They lie on
nous one. The ostium serves as an entry conduit for either side of the superior halves of the nasal cavities
most nerves and blood vessels. and are separated from the orbits by the laminae
The apices of the second upper bicuspid and papyraceae (Figures 26–5 and 26–6).
first and second molar teeth are located in close The anterior ethmoid cells open into the
relation to the floor of the sinus and may be sepa- infundibulum of the middle meatus and the poste-
rated only by mucous membrane, thus permitting rior cells into the superior meatus. The middle
easy spread of a dental infection into the sinus. turbinate may be the site of an ethmoid cell, a con-
The superior wall or roof is usually traversed in its cha bullosa, which can obstruct free sinus drainage
central portion by the infraorbital nerve that may, but is usually asymptomatic. There are many varia-
at times, be protected only by a thin plate of bone. tions of pneumatization of the ethmoid cells.
Crista galli
Ethmoid sinuses
Orbit
Zygoma
Middle and
Maxillary Inferior turbinates
sinus
Agar nasi cells are the most anterior of the At this time, it slowly invades the frontal bone and
anterior ethmoid cells and are located anterior to the has much diversity of shape. The frontonasal duct
anterosuperior attachment of the middle turbinate. enters the nose near the upper portion of the
They lie in close proximity to the frontal recess and infundibulum. The anterior wall of the sinus is com-
can occasionally obstruct the nasofrontal duct. The posed of diploic bone, and the posterior wall is com-
anterior ethmoid cells frequently extend into the posed of a compact, bony plate.
uncinate process and may invade the lumen of the
frontal sinus as a frontal bulla or invade the body of Sphenoid Sinus Pneumatization of the sphenoid
sphenoid bone. bone occurs during middle childhood, proceeding
Haller cells are ethmoid cells that may obstruct rapidly after 7 years of age to its final form at 12 to
maxillary ventilation in the region of the sinus 15 years (Table 26–4). Each sinus communicates
ostium. They occur in about 10% of the population with the sphenoethmoidal recess of the superior
and may be without symptoms. Onodi cells are pos- nasal meatus by means of a small aperature of 0.5 to
terior ethmoid cells that can extend laterally or supe- 4 mm. The bony ostium is usually larger than the
riorly toward the nearby sphenoid sinus and lie near membranous and, for gravity drainage, is disadvan-
the optic nerve as well. tageously located 10 to 20 mm above the sinus floor.
Several vital structures lie closely adjacent to
Frontal Sinus The frontal sinus can rarely be the sinus: the optic nerve and the hypophysis above,
imaged before the second year of life (Table 26–3). the pons posteriorly and external and lateral to the
Inferior
Middle
meatus
meatus
Inferior
turbinate Orifice of
Nasolacrimal
auditory tube
duct
Anatomy and Physiology of the Nose and Paranasal Sinuses 553
sinus, the cavernous sinus, the superior orbital fis- FUNCTION OF THE PARANASAL SINUSES
sure, the carotid artery, and several cranial nerves.
Prevailing theories of the function of the sinuses are
The nerve of the pterygoid canal (vidian nerve) may
numerous, but none are generally accepted. They
encroach on the sinus floor.
include lightening the skull, a vocal resonating box,
Ostiomeatal Unit The ostiomeatal unit refers to increased olfaction, humidification of the inspired
the relationship between the middle meatus and air, and assistance in regulation of intranasal pres-
anterior group of sinuses, particularly the anterior sure.
ethmoid cells (Figure 26–7). If there is an It has been proposed that the sinuses provide a
anatomic deformity (eg, concha bullosa) or a dis- source of environmentally uncontaminated mucus
ease process that brings two mucosal surfaces into that is delivered to the midportions of the middle
direct contact, local ciliary stasis occurs, and likely and superior meatus and dilutes the contamination
infection of one or more paranasal sinuses may be of the mucus more directly exposured to the incom-
inaugurated. This pathogenesis is further des- ing air.
cribed in Chapter 34.
PTERYGOPALATINE FOSSA
This space, an elongated triangular area with apex
laterally, lies between the rounded posterior border
of the maxillary sinus and the pterygoid process. It is
bounded medially by the perpendicular plate of the
palatal bone and superiorly by the undersurface of
the sphenoid bone.
Just medial to the sphenopalatine foramen, an
opening in the perpendicular plate of the palatal
bone opposite the posterior end of the middle
turbinate, is the sphenoethmoid recess. Through the
foramen, vessels and nerves pass to the nasal cavity.
The pterygopalatine (sphenopalatine) ganglion is
located just lateral to the foramen.
Also communicating with the pterygopalatine
space are the foramen rotundum and the pterygo-
maxillary and inferior orbital fissures. A wire passed
up the greater or lesser palatine canals enters the fossa
from below. Within the fossa are also found the sec-
ond division of the fifth cranial nerve, the third divi-
sion of the internal maxillary artery, and the vidian
FIGURE 26–7. Concept of the ostiomeatal unit nerve. Infection into the pterygopalatine space may
(shaded). (Courtesy of Dr. David W. Kennedy.) spread from the molar teeth. Entrance for drainage
554 Ballenger’s Otorhinolaryngology
can be made through the alveobuccal sulcus above the the anterior and posterior ethmoid and infra-
third molar tooth or through a Caldwell-Luc opera- trochlear branches. The anterior ethmoid nerve
tion with removal of the posterior wall of the antrum passes over the anterior end of the cribriform plate
and direct exposure into the pterygopalatine fossa. (Figures 26–8 and 26–9) and enters with the anterior
ethmoid artery by way of the anterior ethmoid fora-
men, dividing into medial and lateral branches.
NASAL MUCOUS MEMBRANE The medial branch passes forward and down-
The skin within the nasal vestibule is a tough, kera- ward on the nasal septum and the lateral branch a
tinized, squamous cell epithelium containing coarse similar part of the lateral wall. An external branch
hairs (the vibrissae) and sebaceous and sweat glands. exits at the distal end of the nasal bone to reach the
As the turbinates are approached, the epithelium external surface of the nose. The posterior ethmoid
blends first into a cuboidal cell type and then into crosses the cribriform plate to enter the nose with
the respiratory type. As the nasopharynx is reached, the artery through the posterior ethmoid foramen
the respiratory type blends to a moist, nonkera- to the nasal septum as well as the olfactory region.
tinized, squamous cell mucous membrane similar to Branches from the maxillary division give rise
that in the oral cavity. The nasal mucous membrane to the posterior superior nasal nerves that enter the
is further considered later in this chapter. nose by way of the sphenopalatine foramen and pass
The mucosa of the paranasal sinuses contains over the anterior face of the sphenoid bone to reach
pseudostratified ciliated columnar to cuboidal cell the nasal septum as the nasopalatine nerve (n. of
epithelium, is thin, and contains a few glands. The Cotunnius) and finally reach the incisive canal. Lat-
basement membrane is thin. Cilia, somewhat more erally, a branch, the posterior inferior, passes down-
abundant near the sinus ostia, propel the overlying ward and forward to distribute on the middle and
blanket of mucus through the ostium, where it joins inferior conchae.
that in the nose.1 The autonomic innervation of the nose con-
sists of parasympathetic and sympathetic fibers.
The former originates in the superior salivary
NERVE SUPPLY OF THE NOSE nucleus and travels via the nervus intermedius to
The nerve supply of the nose (olfaction is consid- the geniculate ganglion, where it joins with the
ered in Chapter 27) consists mainly of ophthalmic greater superficial petrosal nerve. As this nerve
and maxillary divisions of cranial nerve V. The for- leaves the temporal bone, it is joined by the deep
mer gives rise to the nasociliary nerve, dividing into petrosal nerve to form the nerve of the pterygoid
Olfactory bulb
Sphenopalatine
ganglion
Anatomy and Physiology of the Nose and Paranasal Sinuses 555
AIR CONDITIONING
The air is heated (or cooled) by radiation from the
mucosal blood vessels. Humidification occurs by
evaporation from the mucous blanket. That this is
an efficient mechanism is attested to by the fact that,
in the nasopharynx, the inspired air is near normal
body temperature and the relative humidity is near
100%. The mucosal blood vessels lie in two layers of
more or less parallel rows. The more superficial layer
sends capillaries into the epithelium, and the capil-
laries of the deeper layer near the basement mem-
brane are fenestrated to facilitate fluid movement.
The flow of blood is from posterior to anterior,
opposite to the flow of inspired air and mucus. The
mechanism of a “counter current” adds to the effi-
ciency of the system.
The nasal mucous membrane is cooler by vary-
ing amounts than the expired air; thus, some con-
densation on and warming of the membrane occur FIGURE 26–11. Diagram of the ultrastructural arrange-
—a so-called regenerative effect. ment of ciliary tubules at various levels.
558 Ballenger’s Otorhinolaryngology
the center of the axoneme, creating the characteris- At the base of the cilium, the two central
tic “9 plus 2” pattern (Figure 26–11). microtubules terminate, and each of the peripheral
At the tip of the cilium is a dense cap or crown doublets continues downward to enter the basal
from which three to seven “claws,” 25 to 35 nm long, body as a triplet with a subfiber, C, added.
project. Below the cell membrane and the axoneme
is a short, cylindrical basal body, and below this, the Ciliary Beat The to-and-fro movement of the cil-
tubules (with a third added to form a triplet) seem ium is termed the ciliary beat (Figure 26–12). The
to extend into the apical cytoplasm of the cell as a forward beat is the more forceful, effective stroke in
“rootlet.” They converge into a cone-shaped form which the cilium is fully extended, and the claws at
and acquire periodic striations. This structure, the the tip penetrate the top layer of mucus bordering on
basal foot, curves in the direction of the effective cil- the luminal surface and propel the mucus forward.
iary beat. The recovery stroke is less forceful and slower, and
The basal foot has a cross-striated appearance the shaft curls back on itself so that it does not reach
resembling that of collagen fibers. In addition, other the overlying flakes of mucus. Beating is metachro-
fine microtubules, which appear to be branched, nous and occurs 1,000 or more times per minute.
attach to adjacent basal bodies, to each other, and The motion of the cilium is caused by the slid-
ultimately to the junctional complex of the cell, con- ing of one tubule against an adjacent one, thus cre-
stituting the terminal web. ating a shearing force that induces the bending. The
Looking top-downward on the outer ring of nature of the “nervous” connection between adja-
doublets, each is composed of two juxtaposed cent cilia is not clear; perhaps the “touch” of one cil-
microtubules—a slightly more centrally located ium against the adjacent cilium is enough to initiate
subfiber, A, and a slightly more peripherally located the coordinated, metachronous movement. Energy
subfiber, B (see Figure 26–11). Two regularly for this work is derived from the adenosine triphos-
arranged arms extend from A toward B. They are phate found in the dynein arms. The “spokes” seem
composed of adenosine triphosphate and are called to detach and reattach several times during the
dynein arms. Also present are links attaching each bending process. The axis of motion of the cilium is
subfiber A to B of the adjacent doublet. They are defined by a line perpendicular to a plane connect-
believed to be of an elastic material called nexin. ing the central pair of tubules.
Extending centrally from A to the central pair are In health, particles resting on the mucous blan-
radial spokes. ket are moved by active cilia at 3 to 255 mm per
minute, with an average of about 6 mm per minute. In health, the pH is slightly acid. Its approximate
Apparent health exists, however, with speeds at some composition is 2.5 to 3% glycoprotein, 1 to 2% salts,
variance from this average. Dryness of the mucosa is and 95% water. Immunoglobins comprise about 70%
quickly detrimental to ciliary activity. Other factors of the protein content. Mucus is found throughout
known to influence clearance speeds are the relative the nose (except the vestibule), paranasal sinuses,
humidity and the pH of the fluids. β2-Adrenergic middle ear, eustachian tube, and bronchial tree (and
agonists accelerate the wave frequency, whereas α2- extending into the alveoli in the form of surfactant).
adrenergic activity retards the movement. The beating of the underlying cilia propels the blan-
Numerous structural abnormalities of the ket of mucus, along with trapped or dissolved mate-
axonemal tubules have been found (Figure 26–13). rial, in a more or less continuous movement toward
Either a dye or saccharin can be used to meas- the pharyngeal end of the esophagus.
ure the movement of material resting on the Enveloping the shafts of the mucosal cilia is the
mucous blanket of the nose. Dye or saccharin is thicker, less viscid, and deeper periciliary layer, and
placed on the anterior aspect of the nasal mucosa above this, interfacing with the luminal surface, is
and the time until the color of the dye is seen in the the more viscid layer of mucus riding on the pericil-
pharynx or the taste is reported by the subject is iary fluid below. The mucus on the luminal surface
recorded. The use of tagged particles, developed by may take the form of flakes. Soluble and insoluble
Quinlan et al, involves placing an anion exchange matter caught in the mucus and on the mucous
resin particle about 0.5 mm in diameter tagged flakes are carried posteriorly by the movement of the
with a technetium 99m ion on the anterior nasal mucous blanket to the upper end of the esophagus.
ciliated mucosa, and its clearance can be followed
accurately with a gamma camera or multicolli-
mated detectors.6
MUCOCILIARY TRANSPORT
The mucociliary transport or clearance system is
really two systems working in concert with one
MUCOUS BLANKET another. Its motive force is dependent on the actively
The bilayered mucous blanket, produced mostly by beating cilia reaching the flakes of mucus at the
the serous and goblet glands, is a 12 to 15 µm luminal surface and propelling the flakes and sur-
thick, sticky, tenacious, adhesive sheet consisting rounding mucus posteriorly to the esophagus. The
of an upper, more tenacious mucus riding on the mechanism by which the deeper periciliary, less vis-
tips of the ciliary shafts and a deeper, thinner peri- cid fluid, with its dissolved contaminants and likely
ciliary layer.7 The blanket functions as a lubricant, viruses, also moves posteriorly is less well under-
protects against desiccation, and traps particulate stood. More needs to be learned about the rheology
matter and soluble gases. It amounts to 1 to 2 L and the effects of various viscoelastic properties, as
per day. well as the thickness of the mucous blanket under
varying conditions (Figure 26–14) and its relation to 5. Hasegawa M, Kern EB. The human nasal cycle. Mayo
health and the cleansing function of the nose. Clin Proc 1977;52:28–34.
Although most bacteria seem to impede the 6. Quinlan MF, Salman SD, Swift DL, et al. Measure-
metachronous ciliary cycle and efficient transport ment of mucociliary function in man. Ann Rev
system little or not at all, Bordetella pertussis, Respir Dis 1969;99:13–23.
Mycoplasma pneumoniae, and Pseudomonas aerugi- 7. Proctor DF. The mucociliary system. In: Proctor DF,
nosa, among others, do so. Some respiratory viruses Anerson IB, editors. The nose. New York: Elsevier
and bacteria, notably influenza virus, rhinovirus, Biomedical Press; 1982.
adenovirus, herpes simplex virus, and respiratory 8. Grossman M. Clinical measurement of mucociliary
syncytial virus, seem to impede mucociliary trans- clearance. In: Otolayrngology. Vol 2. Baltimore: Lip-
port by altering either the axonemal ultrastructure pincott; 1994.
or the viscoelastic properties of the mucous blanket8
(see Figure 26–13). The relationship of healthy
SUGGESTED READING
mucociliary activity to disease is discussed further in
Chapter 33. Alberti PW. Applied surgical anatomy of the maxillary
sinus. Otolaryngol Clin North Am 1976;9:3–20.
Hollishead W. Anatomy for surgeons. Vol 1. Head and
REFERENCES neck. 2nd ed. New York: Harper and Row; 1968.
1. Baroody F, Naclerio RM. A review of the anatomy and Lang J. Clinical anatomy of the nose, nasal cavity, and
physiology of the nose. Alexandria (VA): American paranasal sinuses. New York: Thieme; 1989.
Academy of Otolaryngology Head Neck Surgery; 1990. Libersa C, Laude M, Libersa J. The pneumatization of the
2. Courtiss EH, Gargan TJ, Courtiss GB. Nasal physiol- accessory sinuses of the nasal fossae during growth.
ogy. Ann Plast Surg 1984;11:214–223. Anat Clin 1981;2:265.
3. Proetz AW. Essays on the applied physiology of the Peele J. Unusual anatomical variations of the sphenoid
nose. St. Louis: Annals Publishing Co.; 1941. sinus. Laryngoscope 1957;67:208.
4. Lund VJ. Objective assessment of nasal obstruction. Schaeffer J. The clinical anatomy and development of the
Otolaryngol Clin North Am 1989;22:279–90. paranasal sinuses. Pa Med J 1936;39:395.
CHAPTER 27
The chemical senses are important to humans as they nial nerve I (CN I)* and lines the cribriform plate
determine the flavor of foods and beverages and pro- and sectors of the superior turbinate, middle
vide a sensitive and early means for detecting dan- turbinate, and septum. Although it reportedly com-
gerous environmental situations, including the prises ~ 2 cm2 of the upper recesses of each nasal
presence of fire, spoiled food, and leaking natural gas. chamber, it is not a homogenous structure, at least in
Unfortunately, taste and smell are typically ignored the adult, as metaplastic islands of respiratory-like
by otolaryngologists, even though (1) the steward- epithelium accumulate within its borders beginning
ship of these senses falls within the purview of their early in life, presumably as a result of insults from
specialty; (2) some otolaryngologic operative proce- viruses, bacterial agents, and toxins.1 On the basis of
dures compromise the functioning of these senses; immunohistochemical and anatomic criteria,2 at
(3) alterations in chemosensory function can be an least six major classes of cells can be identified in this
early sign of a number of diseases, including neuroepithelium: bipolar sensory receptor cells, sup-
Alzheimer’s disease (AD) and idiopathic Parkinson’s porting or sustentacular cells, microvillar cells, Bow-
disease (PD); and (4) losses or distortions of man’s gland and duct cells, globose basal cells, and
chemosensation are of considerable personal and horizontal basal cells. The ~ 6 million receptor cells
practical significance to the patient. The latter should are derived embryologically from the olfactory pla-
not be underestimated and is particularly acute for code and thus are of central nervous system (CNS)
patients whose lifestyle, livelihood, or immediate origin. The cilia of these cells, which extend into the
safety depends on smelling and tasting (eg, cooks, mucus of the nasal lumen, harbor the seven-domain
firemen, homemakers, plumbers, professional food transmembrane olfactory receptors. The axons of
and beverage tasters, employees of natural gas works, these cells ultimately unite into bundles of 50 or so
chemists, and numerous industrial workers). “fila” ensheathed by glial cells that traverse the crib-
This chapter provides an overview of the riform plate to form the outermost layer of the
anatomy and physiology of the smell and taste sys- olfactory bulb. The sustentacular cells insulate the
tems, describes basic chemosensory pathology, and receptor cells from one another and extend
discusses up-to-date means for quantitatively assess- microvilli, rather than cilia, into the mucus. These
ing, managing, and treating disorders of these gen- cells contribute to the mucus of the region and may
erally neglected sensory systems. be involved to some degree in deactivating odorants
and xenobiotic agents. The function of the ~ 600,000
THE OLFACTORY SYSTEM microvillar cells located at the epithelial surface is
unknown. Although earlier workers reported that an
ANATOMY AND PHYSIOLOGY axon-like process projects from these cells to the
Olfactory Neuroepithelium The olfactory neu- olfactory bulb,3 more recent studies have been
roepithelium contains the olfactory receptors of cra- unable to confirm such a projection.4 Bowman’s
*It should be noted that humans possess elements of two other intranasal neural systems in addition to CN I: the nervus
terminalis or terminal nerve (CN O) and the trigeminal nerve (CN V). CN O, known for its high gonadotropin-releasing
hormone content, is apparently unresponsive to volatile chemicals. Chemically induced CN V sensations include cool-
ness, sharpness, and warmth. Although a rudimentary vomeronasal organ is present on each side of the base of the nasal
septum in most persons, this organ is nonfunctional. Despite reports of chemically induced local potentials within this
structure, it has no neural connection with the central nervous system, and no accessory olfactory bulb exists in humans.
561
562 Ballenger’s Otorhinolaryngology
glands are a major source of the mucus in the olfac- granule cell (Figure 27–2). The receptor cell axons
tory region, whereas the globose and horizontal basal of the olfactory nerve layer enter the glomeruli
cells are the progenitor cells of the other cell types2 within the second layer of the bulb, where they
(Figure 27–1). synapse with the dendrites of the mitral and tufted
cells within the spherical glomeruli. These second-
Olfactory Bulb and Olfactory Cortex The first order cells, in turn, send collaterals that synapse
processing station in the olfactory system, the olfac- within the periglomerular and external plexiform
tory bulb, is located directly over the cribriform layers, resulting in “reverberating” circuits in which
plate. Its neural components are arranged in six con- negative and positive feedback occur. Indeed, mitral
centric layers: the olfactory nerve, glomerular, exter- cells modulate their own output by activating gran-
nal plexiform, mitral cell, internal plexiform, and ule cells (which are inhibitory to them). Whereas the
olfactory bulbs of younger persons have thousands
of glomeruli arranged in single or double layers
within the glomerular layer, older persons typically
have far fewer numbers of glomeruli, reflecting the
decrease in olfactory receptor cell numbers within
the epithelium. After the age of 80 years, such struc-
tures are nearly absent.5,6
The mitral and tufted cell axons project ipsilat-
erally to the primary olfactory cortex via the olfac-
tory tract without an intervening thalamic synapse.
The primary olfactory cortex is comprised of the
anterior olfactory nucleus (AON), piriform cortex,
olfactory tubercle, entorhinal area, periamygdaloid
cortex, and corticomedial amygdala. Some projec-
tions occur, via the anterior commissure, from
pyramidal cells of the AON to contralateral elements
of the primary olfactory cortex. A number of pro-
jections from primary to secondary (ie, orbito-
frontal) cortex are direct, whereas others relay within
the thalamus. Recent functional imaging studies
have found that odors reliably and significantly acti-
vate, in a concentration-dependent manner, pos-
terolateral areas of the cerebellum, whereas sniffing
alone tends to activate mainly anterior central cere-
bellar regions.7 The cerebellar activity may reflect the
circuits involved in modulating sniff size relative to
the intensity of an odor or other movement-related
behaviors.
FIGURE 27–1. Low-power electron micrograph (origi- Olfactory Transduction Humans can detect and
nal magnification × 670) of a longitudinal section discriminate among thousands of airborne odor-
through a biopsy specimen of human olfactory mucosa ants. Ten to 15% of the incoming air stream is
taken from the nasal septum. Four cell types are indi- shunted toward the olfactory cleft during inhalation
cated: ciliated olfactory receptors (c), microvillar cells (Figure 27–3). Some of the odorant molecules
(m), supporting cells (s), and basal cells (b). The arrows within this deflected air stream move from the air to
point to ciliated olfactory knobs of the bipolar receptor the largely aqueous phase of the olfactory mucus,
cells. d = degenerating cells; bs = base of the supporting where they diffuse or are actively transported via
cells; lp = lamina propria; n = nerve bundle; bg = Bow- “odorant binding proteins” to the olfactory recep-
man’s gland. Courtesy of DT Moran. tors. Receptor activation then leads to transduction
Olfaction and Gustation 563
FIGURE 27–2. Diagram of major layers and types of olfactory bulb neurons in the mammalian olfactory bulb, as based
on Golgi-stained material. Main layers are indicated on the left as follows: ONL = olfactory nerve layer; GL = glomeru-
lar layer; EPL = external plexiform layer; MBL = mitral cell body layer; IPL = internal plexiform layer; GRL = granule
cell layer; ON = olfactory nerves; PGb = periglomerular cells with biglomerular dendrites; PGm = periglomerular cell
with monoglomerular dendrites; SAe = short axon cell with extraglomerular dendrites; M = mitral cell; M/Td = dis-
placed mitral or deep tufted cell; Tm = middle tufted cell; Ts = superficial tufted cell; Gm = granule cell with cell body
in mitral cell body layer; Gd = granule cell with cell body in deep layers; SAc = short axon cell of Cajal; SAg = short
axon cell of Golgi; C = centrifugal fibers; AON = fibers from anterior olfactory nucleus; AC = fibers from anterior com-
missure; LOT = lateral olfactory tract. Reproduced with permission from Shepherd GM.8 Copyright © 1972, Ameri-
can Physiological Society.
cascades that produce action potentials within the pattern across the activated receptors or glomeruli
olfactory receptor neurons. that serves as the proximal code for odorant quality.
Most olfactory receptors are representatives The stimulatory guanine nucleotide-binding
of a large (~ 1,000) multigene family of G protein– protein, Golf, is activated by most olfactory receptor
coupled seven-transmembrane receptors.9 Each proteins.11 In turn, Golf induces production of the
olfactory receptor neuron seems to express only one second messenger cyclic adenosine monophosphate
type of receptor, and neurons expressing the same by activating the enzyme adenyl cyclase. Cyclic
gene appear randomly distributed within a few seg- adenosine monophosphate then diffuses through
regated strip-like “spatial zones” of the neuroepithe- the cytoplasm, producing cellular depolarization by
lium, at least in the rodent. Each receptor binds a opening cyclic nucleotide–gated ionic channels and
number of odorant molecules, although not all Ca2+-dependent Cl– or K+ channels. Cyclic guanosine
odorant molecules activate all receptors. Since the monophosphate is also activated by some odorants.
olfactory neurons that express a given receptor gene It appears, among other things, to modulate the sen-
project to the same glomeruli of the olfactory bulb,10 sitivity of olfactory receptor neurons during adapta-
the glomeruli can be considered functional units. tion.12 G proteins other than Golf (eg, Gi2 and Go) are
Data from a variety of sources suggest that it is the present in olfactory receptor cells and aid in axonal
564 Ballenger’s Otorhinolaryngology
signal propagation, axon sorting, target innervation, lucination); and olfactory agnosia: inability to recog-
and other such processes.14 nize an odor sensation even though olfactory pro-
cessing, language, and general intellectual functions
Receptor Cell Regeneration The olfactory neu- are essentially intact, as in some stroke patients.
roepithelium has the ability to regenerate, although in Olfactory dysfunction can be either bilateral
cases in which significant damage to the basement (binasal) or unilateral (uninasal), although, most
membrane has occurred, regeneration is nonexistent commonly, such dysfunction is bilateral. Although
or incomplete. Although, under normal circum- presbyosmia is sometimes used to describe smell loss
stances, relatively continuous neurogenesis occurs owing to aging, this term is less specific than those
within basal segments of the epithelium, many recep- noted above (ie, it does not distinguish between
tor cells are relatively long lived and appear to be anosmia and hyposmia) and is laden, by definition,
replaced only after they are damaged.15 Receptor cell with the notion that it is age per se that is causing the
death, as well as replenishment from progenitor cells, age-related deficit.
is determined by both endogenous and exogenous
factors.16 For example, differentiated neurons send
regulatory signals that program the numbers of new CLINICAL EVALUATION OF OLFACTORY
neurons that need to be produced by the stem cells to FUNCTION
maintain equilibrium in the cell population.17 Apop-
Three steps are involved in assessing a patient with
totic cell death occurs in cells representing all stages of
chemosensory dysfunction: (1) obtaining a detailed
regeneration, implying that biochemical regulation of
clinical history, (2) testing olfactory function quan-
neuronal numbers occurs at multiple stages of the
titatively, and (3) physically examining the head and
neuronal lineage.18
neck.19,20
or ruled out. Questions regarding epistaxis, dis- time (including those resulting from therapeutic
charge (clear, purulent or bloody), nasal obstruction, interventions), (4) detect malingering, and (5)
allergies, and somatic symptoms, including obtain an objective basis for determining compensa-
headache or irritation, may have localizing value. A tion for disability. In the past, many physicians have
review of the history of tobacco, alcohol, or recre- tested olfaction by simply asking the patient to iden-
ational drug use may also provide clues to etiology tify several crude odorants, such as licorice, coffee
(eg, chronic alcoholism or Wernicke-Korsakoff syn- grounds, or tobacco, placed under the nose. Unfor-
drome). A detailed assessment of the medications tunately, such qualitative testing can lead to false
being used prior to and during the onset of the dys- positives (eg, patients have difficulty identifying
function is important as many common medica- odors without response alternatives), lacks reliabil-
tions (eg, antihypertensive and antilipid agents, ity, has no normative reference, and is easily faked by
antibiotics) can produce smell or taste disturbances. malingerers.
Importantly, medication-induced deficits may take During the last two decades, a number of stan-
some time to appear, so simply because a patient has dardized and practical psychophysical tests have
been taking a drug for some time does not rule out been developed.21 The most widely used test is the
its possible etiologic involvement. Likewise, some 40-item University of Pennsylvania Smell Identifica-
medication-induced alterations do not disappear tion Test (UPSIT; commercially known as the Smell
immediately on drug cessation. Identification TestTM; Figure 27–4).22 This reliable
Specifics concerning the nature, timing of (test–retest r = .94) test employs microencapsulated
onset, and duration and pattern of fluctuations, if (“scratch and sniff ”) odorants and is available in
any, of the patient’s chemosensory symptoms should English-, French-, German-, and Spanish-language
be obtained. For example, sudden olfactory loss sug- versions. It can be self-administered in 10 to 15 min-
gests the possibility of head trauma, infection, utes in the waiting room by most patients and scored
ischemia, or a psychogenic condition. Gradual loss in less than a minute by nonmedical personnel. In
can reflect the development of degenerative addition to providing a percentile rank of a patient’s
processes, progressive obstructive lesions or tumors performance relative to age- and sex-matched con-
within the olfactory receptor region or more central trols, an absolute determination of normosmia, mild
neural structures. Intermittent loss can be indicative microsmia, moderate microsmia, severe microsmia,
of an intranasal inflammatory process.20 anosmia, or probable malingering can be made.
A family history of smell dysfunction may sug- In some cases, unilateral testing is warranted,
gest a genetic basis. Delayed puberty in association although usually olfactory problems are bilateral. To
with anosmia (with or without midline craniofacial assess olfaction unilaterally, the naris contralateral to
abnormalities, deafness, and renal anomalies) sug- the tested side should be occluded without distorting
gests the possibility of Kallmann’s syndrome or some the nasal valve region. This can be easily accom-
variant thereof. Subtle signs of central tumors, plished by sealing the contralateral naris using a
dementia, parkinsonism, and seizure activity (eg, piece of MicrofoamTM tape (3M Corporation, Min-
automatisms, occurrence of blackouts, auras, and neapolis, Minnesota) cut to fit the naris borders
déjà vu perceptions) should be sought in both the (Figure 27–5). The patient is instructed to sniff the
history and the physical examination. stimulus normally and to exhale through the mouth.
Such occlusion not only prevents air from entering
Quantitative Olfactory Testing Many patients are the olfactory cleft from the contralateral naris
inaccurate in describing their chemosensory func- (orthonasal stimulation), it also prevents active
tion; some are unaware of a chemosensory deficit, movement of odor-laden air into the occluded side
whereas others overstate the nature of their problem. from the nasopharynx on exhalation (retronasal
Hence, one should employ modern means for quan- stimulation).
titatively assessing olfactory function in the office The measurement of olfactory event-related
setting. Reliable quantitative testing is needed to (1) potentials (OERPs) is available in only a few special-
verify the validity of the patient’s complaint, (2) ized centers. In essence, synchronized brain elec-
characterize the exact nature and degree of the prob- troencephalographic (EEG) activity induced by
lem, (3) accurately monitor changes in function over repeated pulsatile presentations of an odorant is iso-
566 Ballenger’s Otorhinolaryngology
lated from overall EEG activity. Averaging of reflect the topographic distribution of specific olfac-
responses from repetitive stimulation increases the tory receptors in combination with the relatively few
signal-to-noise ratio. Although OERPs are relatively odorants used or the presence of metaplasia of res-
sensitive and useful in detecting malingering, they piratory-like epithelium within the olfactory epithe-
are presently unable to localize where in the olfac- lium.
tory pathway an anomaly exists, unlike their visual
and auditory counterparts. Unfortunately, OERP Physical Examination, Laboratory Tests, and
testing requires specialized and expensive equipment Medical Imaging Careful otolaryngologic and
capable of delivering odorant pulses with rapid rise neurologic assessment is warranted in patients com-
times (~ 30 to 40 ms) to the olfactory neuroepithe- plaining of olfactory dysfunction.19,20 Visual field and
lium within a background of continuously flowing acuity tests, as well as optic disk examinations,
warmed and humidified air without inducing con- should be performed to determine whether intracra-
founding somatosensory sensations.23 nial mass lesions that produce increased intracranial
The electro-olfactogram (EOG) is another pressure, papilledema, and optic atrophy are present
electrophysiologic measure of the olfactory system.24 (eg, Foster Kennedy syndrome, which consists of
This surface potential, detected via an electrode ipsilateral anosmia, ipsilateral optic atrophy, and
placed on the surface of the olfactory neuroepithe- contralateral papilledema owing to a meningioma of
lium, reflects summated generator potentials mainly the ipsilateral optic nerve). With nasal endoscopy,
from olfactory receptor neurons. The recording of employing both flexible and rigid endoscopes, spe-
the EOG is, from a practical perspective, often more cific attention should be paid to the olfactory meatal
difficult than that of the OERP, and far fewer area. The nasal secretions should be carefully evalu-
patients are amenable to such recording. The place- ated, as well as the color, swelling, surface texture,
ment of the recording electrode is under endoscopic inflammation, erosion, ulceration, and atrophy of
guidance, but since local anesthesia must be avoided, the nasal mucosa. Mucopus below the eustachian
the placement of the electrode can be quite unpleas- tube orifice suggests involvement of the osteomeatal
ant, and sneezing and mucous discharge are com- complex, whereas mucopus above this orifice sug-
mon. Importantly, even after the electrode has been gests posterior ethmoid and/or sphenoid sinus dis-
placed within the region of the olfactory epithelium, ease. Masses, polyps, and adhesions of the turbinates
it cannot be recorded in many subjects. This may to the septum may all compromise airflow to the
Olfaction and Gustation 567
the statistical likelihood of malingering. Malingering elements of the olfactory system can be simultane-
is also suspected if the patient reports smell loss in ously present or occur in stages. Thus, chronic rhi-
the presence of a clear OERP, although olfactory nosinusitis can produce damage to the olfactory
agnosia in such cases cannot be ruled out. neuroepithelium in addition to blocking airflow, and
It is noteworthy that malingering is sometimes altered neuroepithelium function can, over time,
discovered in head injury patients by their scores on lead to degeneration within the olfactory bulb, a
forced-choice taste tests, rather than their scores on central structure.
forced-choice smell tests, since bona fide smell loss There are numerous causes of olfactory distur-
is, in fact, present (negating the ability to avoid cor- bance (Table 27–1). Most cases of chronic anosmia
rect answers on the olfactory element of the exami- or hyposmia are attributable to previous upper res-
nation). Such malingering implies relatively normal piratory infections, head trauma, and nasal and
taste function and reflects the patient’s naive attempt paranasal sinus disease, reflecting long-lasting or
to embellish the “taste loss” that, in fact, results from permanent damage to the olfactory neuroepithe-
lack of retronasal stimulation of the olfactory recep- lium.27 Other causes include intranasal neoplasms
tors. (eg, inverting papillomas, hemangiomas, and esthe-
Evidence for a general tendency to malinger sioneuroblastomas), intracranial tumors or lesions
can also be obtained using neuropsychological tests (eg, olfactory groove meningiomas, frontal lobe
specifically designed for this purpose, for example, gliomas), neurologic diseases (eg, AD, idiopathic PD,
tests sensitive to head trauma patients trying to feign multiple sclerosis [MS], schizophrenia), exposure to
memory disturbances. Among those that are widely airborne toxins (including cigarette smoke), iatro-
used is Rey’s Memory Test (RMT), also known as genic interventions (eg, septoplasty, rhinoplasty, tur-
Rey’s 3 × 5 Test, and the Rey 15-item Memory Test.26 binectomy, radiation therapy, medications), epilepsy,
The rationale behind this test is that malingerers psychiatric disorders, and various endocrine and
typically fail at a memory task that all but the most metabolic disorders.† The more common disorders
developmentally disabled or severely brain-injured or entities associated with smell loss are described in
persons perform easily. detail later in this section.
Most dysosmias reflect dynamic changes in the
olfactory epithelium and remit over time.27,28 Many
CAUSES OF OLFACTORY DYSFUNCTION anosmic patients report that prior to onset of their
Olfactory dysfunction can result from three general anosmia, they experienced a period of weeks or
causes: (a) conductive or transport impairments from months when dysosmia was present. Usually, some
nasal passage obstruction (eg, by chronic rhinosi- smell function is present during the period of dysos-
nusitis, polyposis, excessive mucus secretion, etc), mia. In rare instances, dysosmias present as aura-like
(b) sensorineural impairment from injury to the hallucinations presumably associated with central
olfactory neuroepithelium (eg, by viruses, airborne (eg, temporal lobe) dysfunction. In many such cases,
toxins, etc), and (c) central olfactory neural impair- no seizure activity can be documented, and no evi-
ment from injury to CNS structures (eg, tumors, dence of CNS lesions or tumors is apparent.
masses impinging on the olfactory tract, etc). These Nonetheless, low doses of anticonvulsant medica-
categories, however, are not mutually exclusive. For tion may be effective in mitigating the frequency and
example, both blockage of airflow to the receptors severity of some of these dysosmias. Dysosmias can
and damage to the receptors and/or more central also occur in a number of neurologic or psychiatric
†It has long been known that exogenous agents, including a number of neurotropic viruses, can enter the CNS from
the nasal cavity via the olfactory nerve cells and that cauterization of the olfactory neuroepithelium can protect against
infection from viruses instilled either intranasal or systemically.29,30 In fact, otolaryngologists in the late 1930s prophy-
lactically sprayed the noses of schoolchildren with zinc sulfate during poliomyelitis outbreaks.31 The “olfactory vector
hypothesis” has been proposed as an explanation for both the olfactory loss and the cause of several common neuro-
logic diseases.32–35
Olfaction and Gustation 569
TABLE 27–1. Agents, Diseases, Drugs, Interventions, and Other Etiologic Categories Associated in the
Medical or Toxicologic Literature with Olfactory Dysfunction.*
Neurologic Nutritional/Metabolic
Amyotrophic lateral sclerosis Abetalipoproteinemia
Alzheimer’s disease Chronic alcoholism
Cerebral abscess (especially frontal or ethmoidal Chronic renal failure
regions) Cirrhosis of liver
Down syndrome Gout
Familial dysautonomia Protein calorie malnutition
Guam amyotrophic lateral sclerosis/Parkinson’s Total parenteral nutrition without adequate
disease/dementia replacement
Head trauma Trace metal deficiencies
Huntington’s disease Copper
Hydrocephalus Zinc
Korsakoff ’s psychosis Whipple’s disease
Migraine Vitamin deficiency
Meningitis A
Multiple sclerosis B6
Myasthenia gravis B12
Paget’s disease
Psychiatric
Parkinson’s disease
Anorexia nervosa (severe stage)
Refsum’s disease
Attention-deficit disorder
Restless legs syndrome
Depressive disorders
Syphilis
Hysteria
Syringomyelia
Malingering
Temporal lobe epilepsy
Olfactory reference syndrome
Hamartomas
Schizophrenia
Mesial temporal sclerosis
Seasonal affective disorder
Scars/previous infarcts
Vascular insufficiency/anoxia Pulmonary
Small multiple cerebrovascular accidents Chronic obstructive pulmonary disease
Subclavian steal syndrome
Transient ischemic attacks
disturbances, which are usually diagnosed on other In contrast to cases of anosmia, hyposmia, and
grounds (eg, psychosis, MS). Infrequently, dysosmia dysosmia, cases of hyperosmia are rare. Although
may be owing to the perception of foul odors pro- untreated adrenal cortical insufficiency has been
duced by the body, such as those from purulent nasal reported to produce hyperosmia in humans, this
secretions in sinusitis or from exhalations in halito- finding has yet to be confirmed, and no evidence for
sis or uremia. Other disorders that may present as hypersensitivity following adrenalectomy has been
dysosmia include trimethylaminuria (fish odor found in animal studies.37 There have been sugges-
syndrome) and cat odor syndrome, a pediatric neu- tions of hyperosmia in syndromes such as multiple
rologic disorder associated with a ß-methylcrotonyl- chemical sensitivity, but the limited data available
CoA carboxylase deficiency. Such rare disorders also fail to support this notion.38 Hyperosmia
usually exist in the presence of a normally function- reportedly occurs in some cases of epilepsy during
ing olfactory system. the interictal period, although most patients with
572 Ballenger’s Otorhinolaryngology
long-term epilepsy and intractable seizure activity, become fractured in some cases, such fractures are
such as candidates for temporal lobe resection, are not a prerequisite for smell loss.40 In a recent study
hyposmic.39 of 268 patients evaluated at the University of Penn-
sylvania Smell and Taste Center who had experi-
Upper Respiratory Infections Upper respiratory enced head trauma, 66.8% had anosmia and 20.5%
system viruses (eg, influenza, colds) are the most hyposmia. Of 66 patients retested 1 month to 13
common cause of permanent smell loss in adult- years later, only 3, none of whom initially had anos-
hood.27 Factors that predispose individuals to virus- mia, regained normal olfactory function. Dysosmia
induced smell dysfunction and the mechanisms prevalence decreased from 41.1 to 15.4% over post-
underlying it remain unclear, although direct insult trauma periods averaging several years.40
to an already compromised neuroepithelium is most Even though the loss of smell following head
likely, and, in rare cases, central structures may also trauma is usually immediate, this is not always the
become involved. If neural damage is present, topi- case, and it may take the patient a while to recognize
cal or systemic corticosteroid treatment is ineffec- the presence of the loss. In some cases, delayed loss
tive. Reduced numbers of olfactory receptor cells reflects delayed receptor cell death. Rodent research
and other epithelial abnormalities are commonly shows that intracranial hemorrhage and ischemia
found in biopsies taken from the olfactory epithelia can lead to degeneration of the olfactory epithelium
of patients with postviral anosmia or hyposmia. without transection of the olfactory nerves.42
Head Trauma Smell loss or distortion occurs in Nasal and Sinus Disease It is now apparent that
~ 15% of patients with significant head trauma but the olfactory loss associated with nasal or sinus dis-
can be present even in mild cases in which rapid ease is not solely caused by decreased conduction of
acceleration/deceleration of the brain has occurred airflow to the olfactory receptors. Although medical
(coup contra coup injury) (Figure 27–6). In general, (eg, administration of topical or systemic corticos-
the severity of trauma is roughly correlated with the teroids) or surgical (e.g., excision of polyps) treat-
degree of loss. Occipital blows tend to produce more ment can improve olfactory function in some cases,
frequent and more severe olfactory deficits than return to normal levels is not the norm.43 In the case
frontal blows.40 The physiologic mechanisms of rhinosinusitis, for example, factors other than, or
involved include shearing of the olfactory fila and in addition to, nasal airflow blockage are responsible
contusions of the olfactory bulb and frontal and for the loss. Chronic inflammation is, in fact, likely
temporal poles.41 Although the cribriform plate may toxic to olfactory neurons. Hence, many cases of rhi-
nosinusitis have a significant sensorineural compo- and, possibly in some cases, even general immunity
nent. The severity of histopathology within the and defensive responses to illnesses.50,51 About one
olfactory epithelium of chronic rhinosinusitis half of the population between 65 and 80 years of
patients is correlated with the degree of smell loss, as age experiences significant decrements in the ability
measured by the UPSIT.44 Olfactory biopsies from to smell. Over the age of 80, this figure rises to nearly
patients with nasal disease are less likely to yield 75%. This is in marked contrast to persons under
olfactory epithelial tissue than biopsies from con- the age of 65 years, of whom only 1 to 2% suffers
trols.45 The same is true for anosmic versus from major difficulty smelling.49
nonanosmic rhinosinusitis patients.46 Despite the association with age, smell loss in
the later years should not be attributed simply to
Central Nervous System Neoplasms Olfactory age, per se, as often an accumulation of damage over
disturbances can arise from tumors impinging on the years is the culprit, and a single event, such as a
the olfactory bulbs or tracts, such as frontal lobe bad cold, can be the precipitating factor. In general,
gliomas, olfactory groove meningiomas, and supra- the age-related changes in smell function reflect
sellar ridge meningiomas arising from the dura decrements in both olfactory receptors and the
mater of the cribriform plate, as well as from tumors number of olfactory bulb glomeruli.6 Interestingly,
on the floor of the third ventricle, pituitary tumors recent data suggest that age-related closure of crib-
extending above the sella turcica, and tumors in the riform plate foramina by ossification is common in
temporal lobe or uncinate convolution.19 Foster skulls from older persons.52 Whether other age-
Kennedy syndrome can result from tumors imping- related factors increase the susceptibility of the
ing on the bulb or tract.47 Pseudo Foster Kennedy epithelium to damage from exogenous agents is not
syndrome has been found in patients with increased clear.
intracranial pressure who had previous unilateral
optic atrophy.48 Neurodegenerative and Other Neurologic Dis-
eases An exciting chapter in the study of olfaction
Aging Age-related smell loss is well documented has been the discovery that a number of neurologic
and occurs in most older people, including those disorders are commonly accompanied by olfactory
who are healthy and taking no medications (Figure deficits, including AD, idiopathic PD, Huntington’s
27–7).49 Such loss clearly impacts on the quality of disease, alcoholic Korsakoff ’s syndrome, Pick’s dis-
life of the elderly, influencing nutrition, appetite, ease, the parkinsonism dementia complex of Guam,
amyotrophic lateral sclerosis, schizophrenia, and poral lobe and (2) drugs that alter cholinergic func-
MS.32,53–55 Indeed, olfactory dysfunction appears to tion alter the ability to smell. For example, the
be the first clinical sign of AD and idiopathic PD.56,57 cholinesterase inhibitor physostigmine improves
Although usually considered a neurodevelopmental odor discrimination performance, at least in rats,62
disorder, smell loss is present in patients with schiz- whereas scopolamine, a muscarinic cholinergic
ophrenia and appears to be correlated with disease antagonist, reportedly decreases olfactory sensitivity
duration, suggesting a possible degenerative compo- in humans.63
nent to this disorder in olfaction-related pathways.55 In idiopathic PD, bilateral olfactory deficits
It has recently been shown that patients with schiz- occur early on in the disease, such as at the onset of
ophrenia have much smaller olfactory bulbs and hemiparkinsonism, and occur at a higher frequency
tracts than those of matched controls.58 than some cardinal signs of this disorder (eg,
Several studies provide data suggesting that tremor).57 The olfactory impairment is unrelated to
smell testing is useful in identifying persons at risk for use of antiparkinsonian medications, duration of ill-
later significant cognitive decline or AD. Graves et al ness, and severity of the symptoms and signs, such as
administered a 12-item abbreviated version of the tremor, rigidity, bradykinesia, or gait disturbance.64
UPSIT (termed the Brief-Smell Identification TestTM Since smell loss is absent or infrequent in a number
or B-SIT) and several cognitive tests to 1,985 Japanese of other neurologic disorders that exhibit similar
American people around the age of 60 and then read- motoric signs, smell testing can aid in differential
ministered these tests to 1,604 of these people 2 years diagnosis in some cases.32 For example, patients with
later.59 Sixty-nine percent of the follow-up partici- essential tremor, progressive supranuclear palsy,
pants were genotyped for apolipoprotein E (apoE). multiple system atrophy, and parkinsonism induced
Low B-SIT scores in the presence of one or more by the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-
APOE-epsilon 4 alleles were associated with a very tetrahydropyridine exhibit little or no olfactory dys-
high risk of subsequent cognitive decline, and the B- function.33 It is of interest that familial PD is also
SIT identified persons who later came to exhibit cog- associated with olfactory impairment that occurs
nitive decline better than a global cognitive test did. independently of the parkinsonian phenotype.65
More recently, the UPSIT was administered by It has generally been assumed that olfactory
Devanand et al to 90 outpatients with mild cognitive function in MS is normal since the axons of the pri-
impairment and to matched healthy controls at 6- mary olfactory receptors are unmyelinated. How-
month intervals over a 5-year period.60 Patients with ever, myelin is present in other segments of the
mild cognitive impairment had lower UPSIT scores olfactory pathway, and we have recently shown that,
than did controls. Most importantly, patients with at any one time, about a third of MS patients exhibit
low UPSIT scores (< 34) were more likely to develop some degree of smell loss.66 Furthermore, we have
AD than the other patients. Low UPSIT scores, com- found that the degree of olfactory loss is directly
bined with lack of awareness of olfactory deficits on related to the number of MRI-determined plaques
the part of the patients, predicted the time to devel- in central brain regions associated with olfactory
opment of AD. UPSIT scores from 30 to 35 showed processing (eg, inferior middle temporal lobe and
moderate to strong sensitivity and specificity for periorbital frontal cortex) (Figure 27–8).54,66 Indeed,
diagnosis of AD at follow-up. a seemingly one-to-one longitudinal association is
The underlying cause for the olfactory deficit present between UPSIT scores and changes in
of AD is not yet clear, even though AD is associated plaque load over time (Figure 27–9),67 implying that
with loss of neurons in the anterior olfactory olfactory function waxes and wanes as the plaque
nucleus, olfactory bulb, and layer II of the entorhinal numbers increase and decrease. In effect, knowledge
cortex.32,61 Disproportionate numbers of neurofibril- of a patient’s UPSIT score accurately predicts the
lary plaques and tangles are found within limbic plaque load in the olfaction-related regions and vice
brain regions that receive olfactory bulb projections. versa.
Central cholinergic deficits may also be involved
since (1) individuals with no history of cognitive loss Exposure to Neurotoxic Agents A number of
who are in the early histopathologic stages of AD environmental and industrial chemicals have been
exhibit a cholinergic deficit within the inferior tem- linked to olfactory dysfunction, including acrylates,
Olfaction and Gustation 575
removal). Of the surgical approaches, intranasal the esophagus.72 The majority of taste buds are
ablation or stripping of tissue from the olfactory found on the lingual surface within the protruding
epithelium on the affected side is more conservative papillae. Of the four types of papillae—fungiform,
and less invasive than removal of the olfactory bulb foliate, circumvallate, and filiform—only the first
and/or tract via a craniotomy.71 Should the dysosmia three harbor taste buds. Taste buds are continually
reappear after intranasal intervention, additional or bathed in secretions from the salivary glands and
repeat ablations can be performed. In the majority nearby lingual glands. Ebner’s glands discharge into
of cases, demonstrable smell loss does not accom- the troughs surrounding the vallate papillae, and lin-
pany the dysosmic condition, reiterating the require- gual glands empty into the long fissures between the
ment of at least some degree of olfactory system folds of the foliate papillae on the posterior aspect of
function for the dysosmic expression. the margin of the tongue. The saliva contains not
Discontinuance, dose changes, or substitution only proteins such as amylase (which initiates starch
of other modes of therapy can be effective for some breakdown of foodstuffs) but also growth factors
medications that induce distortions of olfaction. important for wound healing and the maintenance
Although there are advocates for zinc and vitamin of taste buds. Indeed, removal of the submandibular
therapies, there is no compelling evidence that these and sublingual salivary glands in rats leads to taste
therapies work, except in rare cases in which frank bud loss that can be prevented by supplying epider-
zinc or vitamin deficiencies are present. mal growth factor in the drinking water.73
The human tongue contains, on average,
THE GUSTATORY SYSTEM around 4,600 taste buds.72 Each bud is comprised of
50 to 150 thin epithelial cells arranged much like the
ANATOMY AND PHYSIOLOGY segments of an orange or grapefruit (Figure 27–10).
Such sensations as sweet, sour, bitter and salty, as The opening to the bud is termed the taste pore, and
well as possibly “metallic” (iron salts), “umami” the excavation below the pore is termed the taste pit.
(monosodium glutamate, disodium guanylate, dis- Several types of cells are found within the taste bud,
odium inosinate), and “chalky” (calcium salts), are including cells that project microvilli into the taste
mediated via the taste buds of the gustatory system. pit and basal cells from which other cell types arise.
Unlike olfaction, taste sensations are carried by sev- On the basis of granule density in their apical
eral cranial nerves (ie, CN VII, IX, X), as discussed in regions, light cells, dark cells, and intermediate cells
detail below. Because of this fact, complete loss of can be identified within each bud.74 Like the cells of
taste function is rare from peripheral insults or the olfactory neuroepithelium, taste bud cells have
trauma (since all nerves would have to be involved) the propensity to replace themselves periodically,
and is more likely owing to systemic or central with the time course for at least some of this
causes. Intraoral CN V free nerve endings are also “turnover” being between 2 and 3 weeks.75
stimulated by some foods and beverages (eg, car-
bonated or spicy foods), contributing to the overall Gustatory Neural Transduction A tastant must
gestalt of flavor. Hence, a piece of milk chocolate in be in solution to enter the taste pore. Hence, placing
the mouth is not only sweet but has texture and tem- sugar or salt crystals on a dry lingual surface does
perature. The sensation of “chocolate,” however, is not immediately lead to sweet or salty sensations, a
dependent on retronasal stimulation of the olfactory common mistake made by some practitioners in
receptors. Unfortunately, as noted earlier in this attempting to assess taste function. After entering
chapter, many patients and their physicians fail to the taste pore, the tastant initiates the transduction
distinguish between “taste” sensations mediated by process via one of two mechanisms: (1) activating
the taste buds from CN I–mediated “taste” sensa- receptors coupled to G proteins that, in turn, activate
tions (eg, strawberry, chocolate, meat sauce, etc). second-messenger systems (a process that probably
occurs with sweet and bitter-tasting stimuli), and (2)
Taste Buds The goblet-shaped taste buds are dis- directly gating apical ion channels on the microvil-
tributed over the dorsal surface of the tongue, mar- lae within the taste bud pit (a process that probably
gin of the tongue, base of the tongue, soft palate, occurs with sour and salty tasting stimuli). Gust-
pharynx, larynx, epiglottis, uvula, and first third of ducin, a specialized G protein specialized for taste
578 Ballenger’s Otorhinolaryngology
reception, has been identified in taste receptor cells veyed by two respective branches of the facial nerve
of fungiform, foliate, and circumvallate papillae.77 (CN VII): the chorda tympani nerve and the greater
Taste threshold sensitivity is directly related to petrosal nerve via the lesser palatine nerve. Cranial
the number of taste papillae and hence taste buds nerve VII also supplies the salivary and lacrimal
that are actively stimulated.78 Furthermore, taste glands, the mucous membranes of the oral and nasal
thresholds are inversely correlated with stimulus cavities, the muscles of facial expression, and the
duration.79 Interestingly, there are agents, when stapedius muscle. Cranial nerve VII taste fibers,
swished in the mouth, that selectively alter the qual- whose cell bodies are located within the geniculate
ity of taste perceptions. For example, miraculin, a ganglion, share a common path with the lingual
glycoprotein from the berry of the African shrub nerve (CN V3) proximal to the tongue (see Figure
Syncepalum dilcificum, temporarily changes most 27–11).
sour-like sensations to sweet sensations. Gymnemic All circumvallate and most, if not all, foliate
acid, an extract from the leaves of the Indian plant taste buds within the posterior one-third of the
Gymnema sylvestre, can mitigate the perception of tongue are innervated by the lingual-tonsillar
sweet sensation (and the corresponding electrophys- branch of the glossopharyngeal nerve (CN IX). The
iologic activity) without significantly changing the taste buds in the region of the nasopharynx are sup-
perception of the other taste qualities.80 plied by the pharyngeal branch of this nerve. The
nerve cell bodies of these gustatory afferent fibers are
Taste Afferent Nerves Different taste buds are found within the petrous ganglion immediately out-
innervated by different cranial nerves, depending on side the jugular foramen, where the fibers eventually
the region of the oral cavity in which they are pass to enter the cranium. Cranial nerve IX also
located. Unlike CN I, such nerves are mixed motor innervates the stylopharyngeus muscle, the parotid
and sensory nerves that transmit multiple forms of gland, the baroreceptors of the carotid sinus, and the
information. An understanding of this fact can be pharyngeal mucous membrane.
important when clinical syndromes that involve The taste buds on the epiglottis, aryepiglottal
taste dysfunction are considered. The nerve fibers folds, and esophagus are innervated by the vagus
from each of the taste nerves enter the brainstem nerve (CN X) via the internal portion of its superior
and synapse within the nucleus of the tractus soli- laryngeal branch.82 Nontaste sensory functions are
tarius (NTS), which extends from the rosterolateral mediated by this nerve from the external ear, exter-
medulla caudally along the ventral border of the nal auditory canal, external surface of the tympanic
vestibular nuclei (Figure 27–11).81 membrane, and vocal cords. Cranial nerve X also
Taste sensations from the taste buds of the mediates (1) visceral sensation from the larynx and
fungiform papillae on the anterior two-thirds of the the gut; (2) motor function to the smooth muscle of
tongue and the taste buds of the soft palate are con- the pharynx, larynx, and viscera; and (3) motor
Olfaction and Gustation 579
function to all striated muscles of the pharynx, lar- within the insula and perisylvian regions, including
ynx, and palate except the stylopharyngeus (CN IX) the frontal operculum, superior temporal gyrus
and tensor veli palatini (CN V3). Afferent fibers from (opercular part), and inferior sectors of the pre- and
the superior laryngeal nerve project via their cell postcentral gyrus.87,88 A secondary cortical taste
bodies in the inferior nodose ganglion. region is present within the caudomedial/caudolat-
eral orbitofrontal cortex, several millimeters anterior
Central Gustatory Regions: Functional Anatomy to the primary taste cortex.81
The first central relay station of the taste system is The specific role of the gustatory cortical
the NTS.82 The afferents from CN VII, IX, and X regions in the processing of taste information is not
synapse, respectively, within the NTS in descending clear. These regions contain multimodal neurons
(and overlapping) order. Cells from the NTS also responsive to touch and temperature, as well as
make reflexive connections, via the reticular forma- taste.89 Some structures within the right hemisphere
tion, with cranial motor nuclei that control such seem to play a more important role in taste percep-
taste-related behaviors as chewing, licking, saliva- tion than their left-hemisphere counterparts. For
tion, swallowing, and preabsorptive insulin release, example, citric acid presented to the whole mouth
as well as the muscles of facial expression.83 The increases regional cerebral blood flow more in the
major gustatory projections from the NST, however, right than in the left anteromedial temporal lobe and
are the tertiary ones that ultimately lead to activa- more in the right than in the left caudomedial
tion of cortical gustatory structures. These occur via orbitofrontal cortex, although bilateral activation is
the thalamic taste nucleus (TTN) in primates, that observed in the caudolateral orbitofrontal cortex.90
is, the parvicellular division of the ventropostero- Also, patients who have had right anterior temporal
medial thalamic nucleus.84 From the TTN, fibers lobe resection for intractable seizure activity have
project to the primary taste cortex deep in the pari- higher citric acid recognition thresholds than both
etal operculum and adjacent parainsular cortex.85 controls and left anterior temporal lobe resection
Positron emission tomography and fMRI studies patients. There is some evidence, however, that
have found taste stimulus–induced activation largely handedness may need to be controlled in such stud-
580 Ballenger’s Otorhinolaryngology
ies. Thus, whereas fMRI data suggest that the supe- Most patients are unaware of regional taste
rior part of the insula is activated by tastants simi- deficits. In fact, most patients can sustain loss of taste
larly in left- and right-handed subjects, this is not sensation on one half of the anterior part of the
the case for the inferior parts of the insulae, where tongue following unilateral sectioning of the chorda
the left is relatively more activated in right-handed tympani in middle ear surgery without noticing the
subjects and the right is relatively more activated in problem. Such lack of awareness stems, in part, from
left-handed subjects.87 the redundancy of the multiple taste nerves, as well
as compensatory mechanisms.
CLASSIFICATION OF GUSTATORY DISORDERS
Gustatory disorders can be classified in a manner CLINICAL EVALUATION OF GUSTATORY
similar to olfactory disorders: ageusia: inability to FUNCTION
detect qualitative gustatory sensations from all (total History A history similar to that described earlier
ageusia) or some (partial ageusia) tastants; hypogeu- for patients complaining of olfactory disturbance
sia: decreased sensitivity to tastants; dysgeusia: dis- should be obtained from patients complaining of
tortion in the perception of a normal taste (ie, an gustatory disturbance. Specific consideration as to
unpleasant taste induced by a stimulus that is nor- the type of stimuli that can or cannot be detected by
mally associated with pleasant sensations) or the the patient is essential to distinguish between
presence of a taste in the absence of a stimulus retronasal CN I flavor loss and true taste bud–medi-
(sometimes termed phantogeusia); gustatory ated gustatory loss. One should specifically inquire
agnosia: inability to recognize a taste sensation, even as to whether the patient can detect the saltiness of
though gustatory processing, language, and general potato chips, pretzels, or salted nuts; the sourness of
intellectual functions are essentially intact. Some vinegar, pickles, or lemons; the sweetness of sugar,
patients complain of oral sensations of burning or soda, cookies, or ice cream; and the bitterness of cof-
numbness, which may or may not have their genesis fee, beer, or tonic water. If the patient indicates that
in gustatory afferents, for example, burning mouth there is a problem in such detection, the possibility
syndrome in which the sensation of “burning” occurs of a true taste bud–mediated dysfunction exists.
within the mouth without obvious physical cause. Previous or current problems with salivation,
Total ageusia is rare and, when present, is usually chewing, swallowing, oral pain or burning, dryness
produced by central (eg, ischemic) events since regen- of the mouth, periodontal disease, speech articula-
eration of taste buds can occur, and peripheral dam- tion, bruxism, or foul breath odor should be ascer-
age would have to involve multiple pathways to tained. Inquiry as to diet, oral habits, stomach
induce taste loss. Thus, whereas 433 of 585 patients problems, and possible problems with acid reflux is
(74%) studied at the University of Pennsylvania Smell relevant, given that acid reflux into the oral cavity
and Taste Center who exhibited olfactory loss com- can irritate or damage taste buds. Recent dental
plained of both smell and taste disturbance, less than work or exposure to radiation should be noted. Doc-
4% had verifiable whole-mouth gustatory dysfunc- umentation of hearing or balance problems should
tion, and even that was limited.27 Regional deficits are be made since past or current ear infections or sur-
much more common. For example, in one study, sen- gery can result in altered chorda tympani function
sitivity to three concentrations of NaCl was measured and produce taste loss or distortions. A careful
on the tongue tip and 3 cm posterior to the tongue tip assessment of medication use is critical. As described
in 12 young (20 to 29 years of age) and 12 elderly (70 in detail later in this chapter, many drugs, including
to 79 years of age) subjects. On average, the young lipid-reducing agents, antibiotics, and antihyperten-
subjects were more sensitive to NaCl on the tongue tip sives, can produce significant distortions or other
than on the more posterior stimulation site and alterations in taste function.
exhibited, at both tongue loci, an increase in detec-
tion performance as the stimulus concentration Physical Examination A thorough head and neck
increased. The elderly subjects, who would be examination is essential for ascertaining the poten-
expected to exhibit, at worse, moderate deficits on tial cause of a gustatory disorder.20 Nongustatory
whole-mouth testing, performed at chance levels.91 deficits in CN VII, IX, and X can shed light on
Olfaction and Gustation 581
whether gustatory dysfunction may be present (eg, made on left and right anterior (CN VII) and poste-
abnormal facial motion, swallowing, salivation, gag rior (CN IX) tongue regions, 16 trials (4 tastants ×
reflex, voice production). Changes in epithelial color 4 tongue regions) would be needed to present a sin-
or signs of scarring, inflammation, or atrophy of lin- gle stimulus for each quality. Since multiple stimuli
gual papillae should be noted. Neoplastic lesions are required to produce reliable responses, the num-
deep in the tongue’s musculature should be ruled ber of trials increases considerably.
out by palpation. Specific attention to the condition In a regional chemical test used at our center, a
of the teeth and gums is important since exudates single suprathreshold concentration of each of four
produced by gingivitis may produce or contribute to stimuli (sucrose, citric acid, sodium chloride, and
dysgeusic symptoms. An inspection of the nature caffeine) is employed. The stimuli have been equated
and integrity of the fillings, bridges, and other den- for perceived intensity (using a magnitude matching
tal work should also be made (eg, dissimilar metals procedure) and are presented at the same volume
can induce small electrical currents that, in turn, (15 µL from an Eppendorff pipette; Brinkman
produce abnormal oral sensations). In cases for Instruments, Westbury, New York) and kinematic
which an explanation of the taste problem is not viscosity (1.53 mm2/s2 using tasteless cellulose gum).
clear, neuroimaging to rule out CNS tumors or Equating viscosity eliminates context effects and tac-
lesions should be performed. tile cues and increases control of solution spread
In some instances, it may be useful to evaluate when placed on the tongue in microliter quantities.
biopsies of circumvallate or fungiform papillae to The stimuli are presented six times to each tongue
determine the presence of pathology. The tongue region, resulting in a test consisting of 96 stimulus
can also be stained with a dark food dye and can be trials and 96 rinses. Testing time is between 1 and 11⁄2
photographed under high illumination and low- hours. The task of the subject is to report the pres-
power magnification to allow for counting or better ence of a sweet, sour, bitter, or salty sensation using
visualizing selected classes of papillae. In general, a forced-choice procedure with these four alterna-
there is a high correlation between the number of tives available and to rate the perceived intensity of
fungiform papillae and the number of taste buds.78 the stimulus on a standardized rating scale with log-
arithmic visual properties.
Quantitative Gustatory Testing Quantitative A more practical approach to taste testing is to
taste testing is rarely performed in the clinic, largely employ an electrogustometer, a device that presents
because of issues of practicality (eg, time and brief µA currents to small regions of the tongue for
expense of presenting and preparing limited shelf- known durations (Figure 27–12).93 No stimulus
life taste stimuli). Although a number of whole- preparation or rinsing is required. Electrogustomet-
mouth taste tests have been described in the ric thresholds can be obtained easily, although their
literature,92 regional taste testing is needed to estab- relationship to chemical thresholds is still not clear,
lish the function of each of the nerves innervating and extreme care must be taken to apply the stimu-
multiple taste bud fields. As noted above, whole- lator to the same region of the tongue on each trial
mouth tests are insensitive to even complete dys- as considerable regional variation in sensitivity is
function of one or several of the nerves that present. At low current ranges, electrogustometry
innervate the tongue. has been demonstrated to activate only taste affer-
Regional taste testing can be made using either ents, not trigeminal (CN V) afferents. Unfortunately,
chemical or electrical stimuli. The former requires sound normative data based on forced-choice test-
applying known concentrations of liquid stimuli (eg, ing paradigms are still generally lacking for such
sucrose, citric acid, caffeine, and sodium chloride as devices.
prototypical representatives of sweet, sour, bitter,
and salty taste qualities) to the tongue or oral cavity Imaging Studies Imaging studies of the gustatory
(in some cases in comparison with blank trials), pathways can be useful in explaining the gustatory
rinsing the stimuli off between trials, and expecto- symptoms of some patients. In addition to detecting
rating after each presentation. Such testing can be large central lesions and tumors, modern MRI tech-
quite time consuming. For example, if responsive- niques can detect discrete lesions (eg, infarcts)
ness to each of the four basic taste qualities is to be within brain structures that correlate both with
582 Ballenger’s Otorhinolaryngology
patient complaints and with the results of sensory as being less intense. In conjunction with the loss
testing. As noted in detail in the next section, MRI- seen with the sense of smell, decrements in taste
determined infarcts in the pons have been repeat- function can be harmful to some of the elderly, lead-
edly associated with ageusia and dysgeusia.94,95 ing to anorexia, weight loss, malnutrition, impaired
immunity, and worsening of a medical illness.50,97 As
noted earlier, whole-mouth testing reveals moderate
CAUSES OF GUSTATORY DYSFUNCTION degrees of age-related taste loss, whereas regional
Although central or systemic factors are the most taste testing reveals marked age-related decre-
likely causes of ageusia, local factors can significantly ments.91
alter taste perception. Proximal mechanisms include
(1) the release of foul-tasting materials from oral Bell’s Palsy Bell’s palsy is the most frequent cause
medical conditions (eg, gingivitis, sialadenitis); (2) of facial nerve damage. Usually of viral origin (eg,
problems in movement of tastants to the taste buds herpes simplex), this disease affects both sexes of all
(eg, damage to taste pores from a burn); (3) damage ages. This disorder typically begins with pain in or
to the taste buds proper, as from caustic or allergic behind the ipsilateral ear, followed by symptoms of
reactions to toxins or oral products; (4) damage to unilateral facial weakness over the course of a few
taste nerves (eg, postviral Bell’s palsy, dental or sur- days (maximum paralysis within 48 to 72 hours).
gical procedures); and (5) CNS damage (eg, from Hyperacusis occurs in many cases owing to a weak-
tumors, epilepsy, infarcts). One cause of dysgeusia ening of the stapedius muscle. Although commonly
can be the use of different metals in the mouth that accompanied by ipsilateral taste loss over the ante-
set up subtle electrical currents within the oral cav- rior two-thirds of the tongue, patients are often
ity. The more common causes of taste disorders are unaware of the taste problem without formal testing.
discussed below. There is a suggestion that return of taste function by
2 weeks after onset is a positive prognostic indicator
Aging Although whole-mouth taste acuity for complete and relatively rapid recovery from
declines with age, the perceptual decrease is not as facial paresis, whereas longer-lasting taste impair-
marked as that seen for olfaction.96 Compared with ment is associated with poor prognosis. The taste-
younger persons, the elderly tend to perceive tastes salivary reflex arc, which extends from the taste
Olfaction and Gustation 583
nerves via the NST to the parasympathetic fibers tralateral dysgeusia has been observed in patients
innervating the salivary glands, can also be compro- with lateralized infarcts of the thalamus and in
mised in this disorder. patients with infarcts in the corona radiata (reflect-
Herpes zoster oticus, termed Ramsay Hunt ing the crossed taste pathways at this level of the
syndrome, results from active infection of the genic- nervous system).101 Unilateral lesions above the
ulate ganglion and involves pain and vesicles in the brainstem do not usually cause complete loss of
external auditory canal or soft palate. Bartoshuk and function because of the multiple areas involved in
Miller described a patient with Ramsay Hunt syn- processing taste information.
drome that involved both CN V and CN IX on the Gustatory problems can arise from damage to
left side.98 Intensity ratings were obtained for each the brainstem structures related to taste, often in
of the four taste qualities at regular intervals across conjunction with impairment of other cranial
a nearly 600-day period for the front, back, and nerves or long tracts. Regions susceptible to damage
palate regions. About 3 months after the herpes include the NTS and the pontine tegmentum, which
attack, the entire left side of the patient was devoid involves both gustatory lemnisci. Hemiageusia from
of taste function. After 400 days, all taste qualities an ipsilateral MS plaque at the midpontine tegmen-
were perceived on the left rear and palate regions, tum has been reported.94 Similarly, ageusia to all
but only sweetness could be perceived on the left taste qualities on the right side of the tongue was
front. Full taste recovery of the anterior part of the noted in a patient who had a small hemorrhage in
tongue was not present even by the end of the nearly the right tegmentum of the middle pons.102 Recently,
600-day-long testing period. three cases of ipsilateral hemiageusia owing to focal
ischemic lesions in the brainstem have been
Burning Mouth Syndrome In some cases, burn- described.103
ing mouth syndrome, also called glossodynia or An example of unilateral hypogeusia resulting
glossalgia, is associated with salty or bitter dysgeu- from a brainstem infarct is shown in Figure 27–13.
sias. This poorly understood syndrome is character- In this case, ischemic activity is evident in a region of
ized by idiopathic intense “burning” pain within the the upper medulla near the right NTS (note that, in
mouth without obvious physical cause. To what this image, the patient’s right side is on the left of
extent this disorder is mediated via gustatory or CN the picture, and the left side is on the right of the
V afferents is not known. The burning sensation picture). This individual complained of dysgeusia on
typically begins by late morning and continues the right side of the tongue and evidenced on testing
throughout the day.99 Suggested causes include (1) a decrement in the ability to discern sweet, sour, bit-
diabetes mellitus (possibly predisposing to oral can- ter, and salty sensations that was greater on the right
didiasis); (2) nutritional or hormone deficiencies than on the left. Both CN VII and CN IX seemed to
(eg, iron, folic acid, B vitamins, estrogen, zinc); (3) be involved.
denture allergy (including reactions to amalgam fill-
ings); (4) mechanical irritation from dentures or Head and Neck Trauma Trauma-related taste loss
oral devices; (5) parafunctional habits of the mouth is much less common than trauma-related smell
(eg, tongue thrusting, teeth grinding, jaw clenching); loss, with fewer than 1% of persons with major head
(6) tongue ischemia as a result of temporal arteritis; injury exhibiting ageusia to sweet, sour, salty, or bit-
(7) oral candidiasis; (8) periodontal disease; (9) ter taste qualities.27,104 Nonetheless, taste loss, as well
reflux esophagitis; and (10) geographic tongue.100 as dysgeusia, can occur in some types of head
Anxiety and depression are common in the popula- trauma. For example, basilar temporal bone frac-
tion with burning mouth syndrome. tures and other injuries that impinge on the middle
ear have the potential for impairing chorda tympani
Central Lesions and Tumors Taste dysfunction nerve–mediated taste function unilaterally, as well as
has been attributed to a variety of tumors and other for altering salivary secretion. Traumatic injury to
lesions, including acoustic neuromas, tumors of the the lingual nerve in and around the mouth and
hypophysis with marked extrasellar growth, facial tongue can also occur in some trauma cases. This
nerve schwannomas extending into the middle cra- nerve, a branch of the mandibular division of CN
nial fossa, and cerebellopontine angle lesions. Con- V3, is the most proximal pathway to the tongue for
584 Ballenger’s Otorhinolaryngology
FIGURE 27–13. Left, Axial T2-weighted (2500/90) magnetic resonance scan through the upper brainstem reveals a
hyperintensive infarct (4 × 3 mm) in the right side of the medulla (arrow A). Note also the large infarct (15 × 8 mm)
inside the white matter of the left side of the cerebellum (arrow B). Right, Taste identification scores showing relative
decrement on the right side of the tongue. From a 65-year-old-woman with a history of ministrokes who developed a
persistent salty/metallic dysgeusia and soreness on the right side of the tongue following a severe 2-day bout of eme-
sis accompanied by marked dehydration and increased blood pressure but unaccompanied by fever. Reproduced with
permission from Doty RL. Copright © 2001, Richard L. Doty.
general somatic sensation (touch) and special vis- goscopy,107–109 reflecting the close proximity of the
ceral sensation of taste (owing to concurrent chorda lingual branch of this nerve to the muscle layer of
tympani fibers). the palatine tonsillar fossa.110 Surgical treatment for
Trauma-induced damage to the auriculotem- snoring (eg, uvulopalatoplasty),111 as well as surgery-
poral nerve can produce a rare clinical syndrome of related procedures such as endotracheal intubation
post-traumatic gustatory neuralgia, characterized by (causing injury to the lingual nerve)112 and the
paroxysmal, lancinating facial pain in the cutaneous employment of a laryngeal mask,113 has been associ-
distribution of the auriculotemporal nerve follow- ated with taste loss or alteration.
ing gustatory stimulation.105,106 This condition, The chorda tympani nerve is at particular risk
which can also be caused by viruses and by iatro- from surgical procedures that involve the middle ear,
genic trauma (eg, that induced by parotid gland sur- given its course between the malleus and the incus.
gery, temporomandibular joint surgery, carotid The nerve is often stretched or sectioned during
endarterectomy, orthognathic surgery, and onco- tympanoplasty, mastoidectomy, and stapedectomy,
logic surgery), produces episodic, transient, electric in some cases producing long-lasting symptoms.
shock-like pain in the preauricular region of the Bull, for example, found that 78% of patients with
affected side.105 Taste-mediated post-traumatic bilateral section and 32% of patients with unilateral
sweating and flushing in this same region are known section of the chorda tympani had persistent adverse
as Frey’s syndrome. Although usually provoked by gustatory symptoms.114
taste stimuli, there is suggestion that such responses A recent study evaluated gustatory function in
can be provoked, in some cases, by the smell of food 17 patients before third molar surgery and at 1 and
or even emotional excitement.105 7 months after surgery.115 On average, an ~15%
reduction of perceived intensity was observed 1
Iatrogenic Surgical Damage Numerous surgical month after surgery for NaCl, citric acid, and qui-
interventions can induce taste dysfunction. The nine hydrochloride. The taste quality of NaCl was
glossopharyngeal nerve is susceptible to damage identified correctly less often after than before third
during tonsillectomy, bronchoscopy, or laryn- molar extraction. Citric acid intensity perception
Olfaction and Gustation 585
had not recovered at 6 months after the surgery. (which normally provide trophic factors that main-
These data suggest that not only do gustatory deficits tain the integrity of the taste bud). The xerostomia
commonly occur after third molar extraction, they secondary to salivary gland damage can influence
also can persist for at least 6 months after surgery food transport, protection from bacterial invasion,
and seem to be associated with the depth of and salivary proteins potentially involved in taste
impaction. transduction119 and can aid in the promotion of
opportunistic oral infections (eg, oral candidiasis).120
Medications Medications produce taste distur- Although typically idiosyncratic and transient, some
bances more frequently than olfactory disturbances. taste aversions can be long lasting and can produce
Such side effects can be very debilitating and, in rare generalized anorexia and cachexia. A means for mit-
instances, have contributed to extreme weight loss igating such aversions is to have the patient consume
and even suicide. Among offending agents are a novel food immediately before the first course of
antiproliferative drugs, lipid-reducing drugs, antihy- chemo- or radiotherapy. This simple maneuver
pertensive agents, diuretics, antifungal agents, somehow focuses the aversion primarily on the novel
antirheumatic drugs, antibiotics, and drugs with food and interferes with the formation of condi-
sulfhydryl groups, such as penicillamine and capto- tioned aversions to preferred dietary items.121
pril.36,116 Onset of taste dysfunction following the use
of some agents can take weeks or even months. For Other Causes Among other reported causes of
example, in a well-controlled study of 87 patients taste dysfunction are hypothyroidism, renal disease,
experiencing taste loss as a result of the antifungal liver disease, myasthenia gravis, Guillain-Barré syn-
agent terbinafine, the average time period from the drome, numerous neoplasms, and familial dysau-
first intake of the drug and the experience of taste tonomia (a genetic disorder with lack of taste buds
loss was 35 days. In most cases, recovery after drug and papillae). Idiopathic dysgeusia has been associ-
cessation took several months.117 ated with blood transfusions.122 Complaints of taste
Taste function is reportedly altered by repetitive loss or distortion are reported in many carcinomas
use of some oral topical agents, including hydrogen and mass lesions. For instance, whereas squamous
peroxide or corticosteroids. Some medications (eg, cell carcinoma of the mucous membranes of the
anticholinergics, antidepressants, antihistamines) upper aerodigestive tract can interfere with taste by
reduce glandular secretion, causing hyperviscous direct destruction of receptors, mass lesions along
saliva, a condition that, in time, can result in lessened the course of CN VII, IX, and X may cause impair-
taste acuity. It is noteworthy that approximately one- ment through neural compression. Carcinoma-
fourth of all cardiac medicines (including antilipemic related malnutrition may also lead to ageusia.
agents, adrenergic blockers, angiotensin-converting
A persistent and unpleasant sweet dysgeusia
enzyme inhibitors, angiotensin II antagonists, cal-
was recently described in three patients with small
cium channel blockers, vasodilators, anticoagulants,
cell carcinoma of the lung.123 The dysgeusia was the
antiarrhymics, and various diuretics) are listed in the
presenting symptom in all three cases, and hypona-
Physicians’ Desk Reference as having potential side
tremia secondary to the syndrome of inappropriate
effects of “altered taste,” “bad taste,” “bitter taste,” or
secretion of antidiuretic hormone was present in
“metallic taste.”
each case. Resolution of the dysgeusia paralleled an
Radiation Therapy Radiotherapy for head and increase in serum sodium concentration after water
neck cancer can induce taste loss and dysgeusia, sali- restriction alone. The close association between the
vary dysfunction, and conditioned taste aversions. dysgeusia and the low serum sodium concentration
Such problems can significantly alter quality of life suggests that hyponatremia is the causative factor,
and, on occasion, appetite to the degree that nutri- rather than the carcinoma, antiduretic hormone,
tion is compromised. Symptoms usually begin early medications, or chemotherapy.
in the course of treatment, and post-treatment recov- Gustatory symptoms have been reported in
ery can take months and, in rare instances, years.118 association with epileptic seizures. Examples of taste
The cause of such disturbances can be quite varied, sensations that have been reported in such cases
including direct radiation-induced damage to taste include “peculiar,”“rotten,”“sweet,”“like a cigarette,”
cells and buds, salivary glands, and taste nerve fibers “like rotten apples,” and “like vomitus.”39 Some of
586 Ballenger’s Otorhinolaryngology
these “tastes,” however, likely represent smell sensa- employing alternative medications, or by changing
tions that are miscategorized as tastes by both the drug dosage. It should be kept in mind, however, that
patients and their physicians. a number of pharmacologic agents appear to induce
Selective taste nerve damage or alterations may long-term alterations in taste that may take months
produce some forms of hypergeusia and dysgeusia. to disappear after drug discontinuance.
For example, one study found that anesthetizing a Since most patients with burning mouth syn-
single chorda tympani nerve reportedly increases the drome are postmenopausal, dysgeusias associated
perceived intensity of bitter substances, such as qui- with this disorder may, in some cases, respond to
nine, applied to taste fields innervated by the con- estrogen replacement therapy. Topical capsaicin may
tralateral glossopharyngeal nerve.124 In contrast, also be helpful in some cases. Given that burning
perceived intensity of NaCl applied to an area inner- mouth syndrome is often associated with anxiety
vated by the ipsilateral glossopharyngeal nerve and depression, tricyclic antidepressants (eg,
appeared decreased. When both chorda tympani amitriptyline, desipramine, nortriptyline) and ben-
nerves were anesthetized, the taste of quinine is zodiazepines appear, in selected instances, to have
intensified, and the taste of NaCl was diminished in some therapeutic efficacy.127
areas innervated by the glossopharyngeal nerve on
both sides of the tongue. In about 40% of the sub-
jects, a phantom taste, usually localized to the poste-
CONCLUSIONS
rior part of the tongue contralateral to the Disorders of the chemical senses of taste and smell
anesthesized area, appeared in the absence of stimu- are relatively common, particularly in the elderly, and
lation. This phantom taste was eliminated when the can result from a broad array of causes. Such causes
region of origin was anesthetized. These authors range from simple irritation of the receptive elements
suggest that such phantoms arise because of release to serious neurologic disorders, including AD and
of inhibition normally present between the central idiopathic PD. In this chapter, a succinct overview of
projection areas of the different taste nerves. the anatomy and physiology of the chemical senses,
as well as of the primary causes of chemosensory dys-
function, has been provided. Approaches to therapy
TREATMENT OF TASTE DYSFUNCTION have been discussed, with an emphasis on the need
As with other sensory systems, prognosis in cases of for quantitative psychophysical evaluation of patients
taste dysfunction is likely inversely related to the before initiating surgical or medical interventions.
degree of neural or structural damage, although clin- Clearly, a number of disorders of the chemical senses
ically such damage can rarely be assessed. Fortu- can be approached with optimism as long as the
nately, the taste nerves and buds appear to be physician establishes the exact nature of the problem
relatively resilient, as many cases of taste loss or dis- and is aware of the available avenues of treatment
tortion spontaneously resolve over time.28 In some and objective assessments of efficacy.
dysgeusic cases, antifungal and antibiotic treatments
have been reported to be useful, although double-
blind studies of the efficacy of such treatments are ACKNOWLEDGMENT
lacking, and some of these agents themselves can
This work was supported in part by Grants PO1
produce taste disturbance. Chlorhexidine employed
DC 00161, RO1 DC 04278, RO1 DC 02974, and
in a mouthwash has been suggested as having possi-
RO1 AG 27496 from the National Institutes of
ble efficacy for some salty or bitter dysgeusias, possi-
Health, Bethesda, Maryland (R. L. Doty, principal
bly as a result of its strong positive charge.125 In the
investigator).
case of neural damage from viruses or other agents,
presumably the damaged taste afferents regenerate.
Thyroxine replacement therapy reportedly brings
back taste sensitivity to normal levels in cases of taste
REFERENCES
loss secondary to hypothyroidism.126 Taste disorders 1. Nakashima T, Kimmelman CP, Snow JB. Structure of
caused by medications can, in some instances, be human fetal and adult olfactory neuroepithelium.
reversed by discontinuing the offending drug, by Arch Otolaryngol 1984;110:641–6.
Olfaction and Gustation 587
2. Huard JM, Youngentob SL, Goldstein BL, et al. Adult 17. Calof AL, Rim PC, Askins KJ, et al. Factors regulat-
olfactory epithelium contains multipotent progeni- ing neurogenesis and programmed cell death in
tors that give rise to neurons and non-neural cells. J mouse olfactory epithelium. Ann N Y Acad Sci
Comp Neurol 1998;400:469–86. 1998;30:226–9.
3. Rowley JC, Moran DT, Jafek BW. Peroxidase back- 18. Holcomb JD, Mumm JS, Calof AL. Apoptosis in the
fills suggest the mammalian olfactory epithelium neuronal lineage of the mouse olfactory epithelium:
contains a second morphologically distinct class of regulation in vivo and in vitro. Dev Biol 1995;
bipolar sensory neuron: the olfactory microvillar 172:307–23.
cell. Brain Res 1989;502:387–400. 19. Doty RL, Snow JB. Olfaction. In: Goldman JL, editor.
4. Carr VM, Farbman AI, Colletti LM, Morgan JI. Iden- The principles and practice of rhinology. New York:
tification of a new non-neuronal cell type in rat Wiley; 1987. p. 761–84.
olfactory epithelium. Neuroscience 1991;45:433–49. 20. Bromley SM. Smell and taste disorders: a primary
5. Smith CG. Age incident of atrophy of olfactory care approach. Am Fam Physician 2000;61:427–36.
nerves in man. J Comp Neurol 1942;77:589–94. 21. Doty RL. Olfaction. Ann Rev Psychol 2001;52:423–52.
6. Meisami E, Mikhail L, Baim D, Bhatnagar KP. 22. Doty RL. The Smell Identification TestTM adminis-
Human olfactory bulb: aging of glomeruli and tration manual. 3rd ed. Haddon Heights (NJ): Sen-
mitral cells and a search for the accessory olfactory sonics, Inc.; 1995. p. 1–57.
bulb. Ann N Y Acad Sci 1998;855:708–15. 23. Doty RL, Kobal G. Current trends in the measure-
7. Sobel N, Prabhakaran V, Desmond JE, et al. Sniffing ment of olfactory function. In: Doty RL, editor.
and smelling: separate subsystems in the human Handbook of olfaction and gustation. New York:
olfactory cortex. Nature 1998;392:282–6. Marcel Dekker; 1995. p. 191–225.
8. Shepherd GM. Synaptic organization of the mam- 24. Ottoson D. Analysis of the electrical activity of the
malian olfactory bulb. Physiol Rev 1972;52: 864–917. olfactory epithelium. Acta Physiol Scand 1956;35:
9. Buck L, Axel R. A novel multigene family may 1–83.
encode odorant receptors: a molecular basis for odor 25. Doty RL, Shaman P, Dann M. Development of the
recognition. Cell 1991;65:175–87. University of Pennsylvania Smell Identification Test:
10. Ngai J, Chess A, Dowling MM, et al. Coding of olfac- a standardized microencapsulated test of olfactory
tory information: topography of odorant receptor function. Physiol Behav 1984;32:489–502.
expression in the catfish olfactory epithelium. Cell 26. Lezak MD. Neuropsychological assessment. 3rd ed.
1993;72:667–80. New York: Oxford University Press; 1995.
11. Jones DT, Reed RR. Golf: an olfactory neuron-specific 27. Deems DA, Doty RL, Settle RG, et al. Smell and taste
G protein involved in odorant signal transduction. disorders, a study of 750 patients from the University
Science 1989;244:790–5. of Pennsylvania Smell and Taste Center. Arch Oto-
12. Leinders-Zufall T, Shepherd GM, Zufall F. Modula- laryngol Head Neck Surg 1991;117:519–28.
tion by cyclic GMP of the odour sensitivity of verte- 28. Deems DA, Yen DM, Kreshak A, Doty RL. Sponta-
brate olfactory receptor cells. Proc R Soc Lond B Biol neous resolution of dysgeusia. Arch Otolaryngol
Sci 1996;263:803–11. Head Neck Surg 1996;122:961–3.
13. Swift DL, Procter DF. Access of air to the respiratory 29. Clark WEL. Anatomical investigation into the routes
tract. In: Brau JD, Procter DF, Reid LM, editors. Res- by which infections may pass from the nasal cavities
piratory defense mechanisms. New York: Marcel into the brain. Rep Pub Health Med Sub No 54
Dekker; 1977. p. 63–93. 1929;1–27.
14. Wekesa KS, Anholt RRH. Differential expression of 30. Armstrong C, Harrison WT. Prevention of
G proteins in the mouse olfactory system. Brain Res intranasally-inoculated poliomyelitis of monkeys by
1999;837:117–26. instillation of alum into the nostrils. Public Health
15. Hinds JW, Hinds PL, McNelly NA. An autoradi- Rep 1935;22:725–30.
ographic study of the mouse olfactory epithelium: 31. Tisdall FF, Brown A, Defries RD, et al. Nasal spraying
evidence for long-lived receptors. Anat Rec 1984; as preventive of poliomyelitis. Can J Public Health
210:375–83. 1937;28:431–4.
16. Mackay-Sim A, Kittel PW. On the life span of olfac- 32. Doty RL. Olfactory dysfunction in neurogenera-
tory receptor neurons. Eur J Neurosci 1990;3:209–15. tive disorders. In: Getchell TV, Doty RL, Barto-
588 Ballenger’s Otorhinolaryngology
shuk LM, Snow JB, editors. Smell and taste in 47. Watnick RL, Trobe JA. Bilateral optic nerve com-
health and disease. New York: Raven Press; 1991. pression as a mechanism for the Foster Kennedy syn-
p. 735–51. drome. Ophthalmology 1989;96:1793–8.
33. Doty RL, Singh A, Tetrude J, Langston JW. Lack of 48. Schatz NJ, Smith JL. Non-tumor causes of the Foster
olfactory dysfunction in MPTP-induced parkinson- Kennedy syndrome. J Neurosurg 1967;27:37–44.
ism. Ann Neurol 1992;32:97–100. 49. Doty RL, Shaman P, Applebaum SL, et al. Smell
34. Roberts E. Alzheimer’s disease may begin in the nose identification ability: changes with age. Science
and may be caused by aluminosilicates. Neurobiol 1984;226:1441–3.
Aging 1986;7:561–7. 50. Mattes RD, Cowart BJ. Dietary assessment of
35. Ferreyra-Moyano H, Barragan E. The olfactory sys- patients with chemosensory disorders. J Am Diet
tem and Alzheimer’s disease. Int J Neurosci Assoc 1994;94:50–6.
1989;49:157–97. 51. Schiffman SS. Taste and smell losses in normal aging
36. Doty RL, Bartoshuk LM, Snow JB. Causes of olfac- and disease. JAMA 1997;278:1357–62.
tory and gustatory disorders. In: Getchell TV, Doty 52. Kalmey JK, Thewissen JG, Dluzen DE. Age-related
RL, Bartoshuk LM, Snow JB, editors. Smell and taste size reduction of foramina in the cribriform plate.
in health and disease. New York: Raven Press; 1991. Anat Rec 1998;251:326–9.
p. 449–61. 53. Mesholam RI, Moberg PJ, Mahr RN, Doty RL. Olfac-
37. Doty RL, Risser JM, Brosvic GM. Influence of tion in neurodegenerative disease: a meta-analysis of
adrenalectomy on the odor detection performance olfactory functioning in Alzheimer’s and Parkinson’s
of rats. Physiol Behav 1991; 49:1273–7. diseases. Arch Neurol 1998;55:84–90.
38. Doty RL, Deems DA, Frye RE, et al. Olfactory 54. Doty RL, Li C, Mannon LJ, Yousem DM. Olfactory
sensitivity, nasal resistance, and autonomic function dysfunction in multiple sclerosis: relation to plaque
in patients with multiple chemical sensitivities. Arch load in inferior frontal and temporal lobes. Ann N Y
Otolaryngol Head Neck Surg 1988;114:1422–7. Acad Sci 1998;855:781–6.
39. West SE, Doty RL. Influence of epilepsy and tempo- 55. Moberg PJ, Doty RL, Turetsky BI, et al. Olfactory
ral lobe resection on olfactory function. Epilepsia identification deficits in schizophrenia: correlation
1995;36:531–42. with duration of illness. Am J Psychiatry 1997;
40. Doty RL, Yousem DM, Pham LT, et al. Olfactory dys- 154:1016–8.
function in patients with head trauma. Arch Neurol 56. Doty RL, Reyes PF, Gregor T. Presence of both odor
1997;54:1131–40. identification and detection deficits in Alzheimer’s
41. Yousem DM, Geckle RJ, Bilker WB, et al. Post- disease. Brain Res Bull 1987;18:597–600.
traumatic olfactory dysfunction: MR and clinical 57. Doty RL, Deems DA, Stellar S. Olfactory dysfunction
evaluation. AJNR Am J Neuroradiol 1996;17:1171–9. in parkinsonism: a general deficit unrelated to neu-
42. Nakashima T, Kimmelman CP, Snow JB. Progressive rologic signs, disease stage, or disease duration. Neu-
olfactory degeneration due to ischemia. Surg Forum rology 1988;38:1237–44.
1983;34:566–8. 58. Turetsky BI, Moberg PJ, Yousem DM, et al. Reduced
43. Doty RL, Mishra A. Olfaction and its alteration by olfactory bulb volume in patients with schizophrenia.
nasal obstruction, rhinitis, and rhinosinusitis. Laryn- Am J Psychiatry 2000;157:828–30.
goscope 2001;111:409–23. 59. Graves AB, Bowen JD, Rajaram L, et al. Impaired
44. Kern RC. Chronic sinusitis and anosmia: pathologic olfaction as a marker for cognitive decline: interac-
changes in the olfactory mucosa. Laryngoscope tion with apolipoprotein E epsilon4 status. Neurol-
2000;110:1071–7. ogy 1999;53:1480–7.
45. Feron F, Perry C, McGrath JJ, Mackay S. New tech- 60. Devanand DP, Michaels-Marston KS, Liu X, et al.
niques for biopsy and culture of human olfactory Olfactory deficits in patients with mild cognitive
epithelial neurons. Arch Otolaryngol Head Neck impairment predict Alzheimer’s disease at follow-
Surg 1998;124:861–6. up. Am J Psychiatry 2000;157:1399–405.
46. Lee SH, Lim HH, Lee HM, et al. Olfactory mucosal 61. Gomez-Isla T, Price JL, McKeel DW, et al. Profound
findings in patients with persistent anosmia after loss of layer II entorhinal cortex neurons occurs in
endoscopic sinus surgery. Ann Otol Rhinol Laryngol very mild Alzheimer’s disease. J Neurosci 1996;16:
2000;109:720–5. 4491–500.
Olfaction and Gustation 589
62. Doty RL, Bagla R, Kim N. Physostigmine enhances 78. Doty RL, Bagla R, Mogensen M, Mirza N. NaCl
performance on an odor mixture discrimination thresholds: relationship to anterior tongue locus,
test. Physiol Behav 1999;65:801–4. area of stimulation, and number of fungiform papil-
63. Serby M, Flicker C, Rypma B, et al. Scopolamine and lae. Physiol Behav 2001;72:373–8.
olfactory function. Biol Psychiatry 1990;28:79–82. 79. Bagla R, Klasky B, Doty RL. Influence of stimulus
64. Doty RL, Stern MB, Pfeiffer C, et al. Bilateral olfac- duration on a regional measure of NaCl taste sensi-
tory dysfunction in early stage treated and untreated tivity. Chem Senses 1997;22:171–5.
idiopathic Parkinson’s disease. J Neurol Neurosurg 80. Kurihara K, Kurihara Y, Beidler LM. Isolation and
Psychiatry 1992;55:138–42. mechanism of taste modifiers; taste modifying pro-
65. Markopoulou K, Larsen KW, Wszolek EK, et al. tein and gymnemic acids. In: Pfaffman C, editor.
Olfactory dysfunction in familial parkinsonism. Olfaction and taste. New York: Rockefeller Univer-
Neurology 1997;49:1262–7. sity Press; 1969. p. 450–62.
66. Doty RL, Li C, Mannon LJ, Yousem DM. Olfactory 81. Rolls ET. Central taste anatomy and neurophysiol-
dysfunction in multiple sclerosis. N Engl J Med ogy. In: Doty RL, editor. Handbook of olfaction and
1997;336:1918–9. gustation. New York: Marcel Dekker; 1995. p. 549–73.
67. Doty RL, Li C, Mannon LJ, Yousem DM. Olfactory 82. Brodal A. Neurological anatomy. New York: Oxford
dysfunction in multiple sclerosis: relation to longi- University Press; 1981.
tudinal changes in plaque numbers in central olfac- 83. Smith DV, Shipley MT. Anatomy and physiology of
tory structures. Neurology 1999;53:880–2. taste and smell. J Head Trauma Rehabil 1992;7:1–14.
68. Doty RL, Hastings L. Neurotoxic exposure and olfac- 84. Beckstead RM, Morse JR, Norgren R. The nucleus of
tory impairment. Clin Occup Environ Med 2001; the solitary tract in the monkey: projections to the
1:1–29. thalamus and brain stem nuclei. J Comp Neurol
69. Frye RE, Schwartz BS, Doty RL. Dose-related effects 1980;190:259–82.
of cigarette smoking on olfactory function. JAMA 85. Pritchard TC, Hamilton RB, Morse JR, Norgren R.
1990;263:1233–6. Projections of thalamic gustatory and lingual areas
70. Chitanondh H. Stereotaxic amygdalotomy in the in the monkey, Macaca fascicularis. J Comp Neurol
treatment of olfactory seizures and psychiatric dis- 1986;244:213–28.
orders with olfactory hallucination. Confin Neurol 86. Netter FH. The CIBA collection of medical illustra-
1966;27:181–96. tions. Vol 1. Nervous system. New York: Ciba Phar-
71. Leopold DA, Schwob JE, Youngentob SL, et al. Suc- maceutical Corporation; 1964.
cessful treatment of phantosmia with preservation 87. Cerf B, Lebihan D, Van De Moortele PF, et al. Func-
of olfaction. Arch Otolaryngol Head Neck Surg tional lateralization of human gustatory cortex
1991;117:1402–6. related to handedness disclosed by fMRI study. Ann
72. Miller IJ. Anatomy of the peripheral taste system. In: N Y Acad Sci 1998;855:575–8.
Doty RL, editor. Handbook of olfaction and gusta- 88. Faurion A, Cerf B, Le BD, Pillias AM. fMRI study of
tion. New York: Marcel Dekker; 1995. p. 521–47. taste cortical areas in humans. Ann N Y Acad Sci
73. Morris-Witman J, Sego R, Brinkley L, Dolce C. The 1998;855:535–45.
effects of sialoadenectomy and exogenous EGF on 89. Pritchard TC. The primate gustatory system. In:
taste bud morphology and maintenance. Chem Getchell TV, Doty RL, Bartoshuk LM, Snow JB, edi-
Senses 2000;25:9–19. tors. Smell and taste in health and disease. New York:
74. Farbman AI. Renewal of taste bud cells in rat circum- Raven Press; 1991. p. 109–25.
vallate papillae. Cell Tissue Kinet 1980;13:349–57. 90. Small DM, Jones-Gotman M, Zatorre RJ, et al. A role
75. Beidler LM, Smallman RL. Renewal of cells within for the right anterior temporal lobe in taste quality
taste buds. J Cell Biol 1965;27:263–72. recognition. J Neurosci 1997;17:5136–42.
76. Shepherd GM. Neurobiology. 2nd ed. New York: 91. Matsuda T, Doty RL. Regional taste sensitivity
Oxford University Press; 1994. to NaCl: relationship to subject age, tongue locus
77. Takami S, Getchell TV, McLaughlin SK, et al. Human and area of stimulation. Chem Senses 1995;20:
taste cells express the G protein alpha-gustducin and 283–90.
neuron-specific enolase. Brain Res Mol Brain Res 92. Frank ME, Hettinger TP, Clive JM. Current trends
1994;22:193–203. in measuring taste. In: Doty RL, editor. Handbook
590 Ballenger’s Otorhinolaryngology
of olfaction and gustation. New York: Marcel 106. Helcer M, Schnarch A, Benoliel R, Sharav Y.
Dekker; 1995. p. 669–88. Trigeminal neuralgic-type pain and vascular-type
93. Frank ME, Smith DV. Electrogustometry: a simple headache due to gustatory stimulus. Headache
way to test taste. In: Getchell TV, Doty RL, Bar- 1998;38:129–31.
toshuk LM, Snow JB, editors. Smell and taste in 107. Ohtuka K, Tomita H, Yamauchi Y, Kitagoh H.
health and disease. New York: Raven Press; 1991. p. [Taste disturbance after tonsillectomy] [Japanese].
503–14. Nippon Jibiinkoka Gakkai Kaiho 1994;97:1079–88.
94. Combarros O, Sanchez-Juan P, Berciano J, De 108. Donati F, Pfammatter JP, Mauderli M, Vassella F.
Pablos C. Hemiageusia from an ipsilateral multi- Neurologische Komplikationen nach Tonsillek-
ple sclerosis plaque at the midpontine teg- tomie. Schweiz Med Wochenschr 1991;121:1612–7.
mentum. J Neurol Neurosurg Psychiatry 2000; 109. Arnhold-Schneider M, Bernemann D. Uber die
68:796. Haufigkeit von Geschmacksstorungen nach Ton-
95. Fujikane M, Nakazawa M, Ogasawara M, et al. sillektomie. HNO 1987;35:195–8.
[Unilateral gustatory disturbance by pontine 110. Ohtsuka K, Tomita H, Murakami G. [Anatomical
infarction] [Japanese]. Rinsho Shinkeigaku study of the tonsillar bed: the topographical rela-
1998;38:342–3. tionship between the palatine tonsil and the lin-
96. Weiffenbach JM. Taste and smell perception in gual branch of the glossopharyngeal nerve]
aging. Gerodontology 1984;3:137–46. [Japanese]. Nippon Jibiinkoka Gakkai Kaiho 1994;
97. Schiffman SS. Taste and smell losses in normal 97:1481–93.
aging and disease. JAMA 1997;278:1357–62. 111. Walker RP, Gopalsami C. Laser-assisted uvu-
98. Bartoshuk LM, Miller IJ Jr. Taste perception, taste lopalatoplasty: postoperative complications.
bud distribution, and spatial relationships. In: Laryngoscope 1996;106:834–8.
Getchell TV, Doty RL, Bartoshuk LM, Snow JB, 112. Evers KA, Eindhoven GB, Wierda JM. Transient
editors. Smell and taste in health and disease. New nerve damage following intubation for trans-sphe-
York: Raven Press; 1991. p. 205–33. noidal hypophysectomy. Can J Anaesth 1999;46:
99. Gorsky M, Silverman SJ, Chinn H. Clinical charac- 1143–5.
teristics and management outcome in the burning 113. Ostergaard M, Kristensen BB, Mogensen TS.
mouth syndrome. An open study of 130 patients. [Reduced sense of taste as a complication of the
Oral Surg Oral Med Oral Pathol Oral Radiol laryngeal mask use] [Danish]. Ugeskr Laeger 1997;
Endod 1991;72:192–5. 159:6835–6.
100. Tourne LP, Fricton JR. Burning mouth syndrome. 114. Bull TR. Taste and the chorda tympani. J Laryngol
Critical review and proposed clinical management. Otol 1965;79:479–93.
Oral Surg Oral Med Oral Pathol Oral Radiol 115. Shafer DM, Frank ME, Gent JF, Fischer ME. Gusta-
Endod 1992;74:158–67. tory function after third molar extraction. Oral
101. Fujikane M, Itoh M, Nakazawa M, et al. [Cerebral Surg Oral Med Oral Pathol Oral Radiol Endod
infarction accompanied by dysgeusia—a clinical 1999;87:419–28.
study on the gustatory pathway in the CNS] 116. Ackerman BH, Kasbekar N. Disturbances of taste
[Japanese]. Rinsho Shinkeigaku 1999;39:771–4. and smell induced by drugs. Pharmacotherapy
102. Kojima Y, Hirano T. [A case of gustatory distur- 1997;17:482–96.
bance caused by ipsilateral pontine hemor- 117. Stricker BH, Van RM, Sturkenboom MC, Otter-
rhage] [Japanese]. Rinsho Shinkeigaku 1999;39: vanger JP. Taste loss to terbinafine: a case-control
979–81. study of potential risk factors. Br J Clin Pharmacol
103. Lee BC, Hwang SH, Rison R, Chang GY. Central 1996;42:313–8.
pathway of taste: clinical and MRI study. Eur Neu- 118. Bartoshuk LM. Chemosensory alterations and can-
rol 1998;39:200–3. cer therapies. NCI Monogr 1990;179–84.
104. Sumner D. Post-traumatic ageusia. Brain 1967; 119. Della Fera MA, Mott AE, Frank ME. Iatrogenic
90:187–202. causes of taste disorders: radiation therapy, surgery,
105. Scrivani SJ, Keith DA, Kulich R, et al. Posttraumatic and medication. In: Doty RL, editor. Handbook of
gustatory neuralgia: a clinical model of trigeminal olfaction and gustation. New York: Marcel Dekker;
neuropathic pain. J Orofac Pain 1998;12:287–92. 1995. p. 785–91.
Olfaction and Gustation 591
120. Conger AD. Loss and recovery of taste acuity in 124. Yanagisawa K, Bartoshuk LM, Catalanotto FA, et al.
patients irradiated to the oral cavity. Radiat Res Anesthesia of the chorda tympani nerve and taste
1973;53:338–47. phantoms. Physiol Behav 1998;63:329–35.
121. Chambers KC, Bernstein IL. Conditioned flavor aver- 125. Helms JA, Della-Fera MA, Mott AE, Frank ME.
sions. In: Doty RL, editor. Handbook of olfaction and Effects of chlorhexidine on human taste percep-
gustation. New York: Marcel Dekker; 1995. p. 745–73. tion. Arch Oral Biol 1995;40:913–20.
122. Erick M. Idiopathic dysgeusia associated with 126. Mattes RD, Kare MR. Gustatory sequelae of ali-
blood transfusion: a case report [letter]. J Am Diet mentary disorders. Dig Dis 1986;4:129–38.
Assoc 1996;96:450. 127. Grushka M, Epstein J, Mott A. An open-label,
123. Panayiotou H, Small SC, Hunter JH, Culpepper dose escalation pilot study of the effect of clon-
RM. Sweet taste (dysgeusia). The first symptom of azepam in burning mouth syndrome. Oral Surg
hyponatremia in small cell carcinoma of the lung. Oral Med Oral Pathol Oral Radiol Endod 1998;
Arch Intern Med 1995;155:1325–8. 86:557–61.
CHAPTER 28
Immunology, the study of the immune system, grew tem can distinguish between antigens that are very
out of the common observation that human beings similar, such as between two proteins that differ in
who recover from certain infectious diseases are only a single amino acid or between two optical iso-
thereafter immune to the disease, that is, they rarely mers of the same molecule.1
develop the same disease again. Immunity is highly This chapter specifically addresses two broad
specific: an individual who recovers from measles is classes of immune responses: antibody response and
protected against the measles virus but not against cell-mediated immune responses. Antibody responses
other common viruses, such as mumps or chicken- involve the production of antibodies, which are pro-
pox. Such specificity is a fundamental characteristic teins called immunoglobulins (Igs). The antibodies
of immune responses. In other vertebrate systems, circulate in the bloodstream and permeate the other
cells such as macrophages and neutrophils also play body fluids, where they bind specifically to the for-
an important role in defending vertebrates against eign antigen that induced them. Binding by antibody
infection, but they are only one part of a much inactivates viruses and bacteria and bacterial toxins
more complex and sophisticated defense strategy. by blocking their ability to bind to receptors on host
This chapter is devoted to the specific immune cells. Antibody binding also marks invading micro-
response. organisms for destruction, either by making it easier
Many of the responses of the human immune for a phagocytic cell to ingest them or by activating
system initiate the destruction and elimination of a system of blood proteins, collectively called com-
invading microorganisms and any toxic molecules plement, which kills the invaders. The complement
produced by them. Because these immune reactions system is addressed in this chapter as well.
are destructive, it is essential that they be made only Cell-mediated immune responses, the second
in response to molecules that are foreign to the host class of immune responses, involve the production
and not to those of the host itself, resulting in of specialized cells, which react with foreign antigens
autoimmunity. This ability to distinguish foreign on the surface of other host cells. The reacting cell,
molecules from self-molecules, in general, is another for example, can kill a virus-infected host cell that
fundamental feature of the human immune system. has viral antigens on its surface, thereby eliminating
Occasionally, it fails to make this distinction and the infected cell before the virus has replicated. In
reacts destructively against the host’s own molecules; other cases, the reacting cell secretes chemical sig-
such autoimmune diseases can be fatal. nals that activate macrophages to destroy the invad-
Although the immune system evolved to pro- ing microorganisms. The main challenge in
tect vertebrates from infection by microorganisms immunology has been to understand how the
and larger parasites, most of what we know about immune system specifically recognizes and reacts
immunity has come from the studies of the aggressively to a virtually unlimited number of dif-
responses of laboratory animals to injections of ferent foreign macromolecules but avoids reacting
noninfectious substances, such as foreign proteins against the tens of thousands of different self-
and polysaccharides. Almost any macromolecule, as macromolecules made by host cells. Thus, initially
long as it is foreign to the recipient, can induce an in this chapter, the functional and structural features
immune response; any substance capable of eliciting of antibodies that enable them to recognize and
an immune response is referred to as an antigen destroy extracellular antigens are considered. After
(antibody generator). Remarkably, the immune sys- discussing how this antibody diversity is generated,
592
Cellular Biology of the Immune System 593
this chapter then considers the special features of About 40 years ago, it was discovered that the two
cell-mediated immune responses that are crucial in major classes of immune responses are mediated by
the defense against intracellular microorganisms. different classes of lymphocytes: T cells, which
Wherever possible, the fundamental principles of develop in the thymus and are responsible for cell-
immunobiology are applied to diseases of the mid- mediated immunity, and B cells, which in mammals
dle ear and sinuses and particular reference is made develop in the adult bone marrow or the fetal liver
to immunobiology of the tonsils and adenoids. and produce antibodies.3 This dichotomy of the
Finally, an overview of three classes of soluble medi- lymphoid system was initially demonstrated in ani-
ators of inflammation is discussed using the nasal mals with experimentally induced immune defi-
polyp as a model of chronic inflammation. ciencies. These studies on immune-deficient
animals demonstrated that individuals deficient in
T cells were unable to make cell-mediated immune
CELLULAR BASIS OF IMMUNITY responses and had somewhat impaired antibody
THE HUMAN IMMUNE RESPONSE IS responses. We now know that there are two main
classes of T cells; helper T cells and cytotoxic T
COMPOSED OF TRILLIONS OF LYMPHOCYTES cells.4 Helper T cells enhance the response of other
The cells responsible for immune specificity belong white blood cells, and some of these T cells help B
to a class of white blood cells known as lymphocytes.2 cells to make antibody responses. Cytotoxic T cells,
They are found in large numbers in the blood and by contrast, kill infected cells; because they are
the lymph and in specialized lymphoid organs such involved directly in defense against infection, unlike
as the thymus, bone marrow, lymph nodes, spleen, helper cells, they, together with B cells, are some-
appendix, tonsils, and adenoids (Figure 28–1). times referred to as effector cells.
There are approximately 2 × 1012 lymphocytes
in the human body, which make the immune sys- LYMPHOCYTES DEVELOP IN PRIMARY
tem comparable in cell mass to the liver or brain.
LYMPHOID ORGANS AND REACT WITH FOREIGN
ANTIGENS IN SECONDARY LYMPHOID ORGANS
It is now known that lymphocytes develop from
pluripotent hemopoietic stem cells, which give rise to
all of the blood cells, including red blood cells, white
blood cells, and platelets.5 These stem cells are
located primarily in the liver in fetuses and in the
bone marrow of adults. T cells develop in the thy-
mus from precursor cells that migrate in from the
hemopoietic tissues via the blood in mammals (Fig-
ure 28–2). B cells develop from stem cells in the
hemopoietic tissues themselves. Because they are
sites in which lymphocytes develop from precursor
cells, the thymus and the bone marrow are referred
to as primary lymphoid organs. Other lymphocytes,
however, mature and migrate via the blood to the
FIGURE 28–1. Human lymphoid organs. Lymphocytes secondary peripheral lymphoid organs such as the
develop in the thymus and bone marrow, which are lymph nodes, spleen, and epithelium-associated
therefore referred to as primary (or central) lymphoid lymphoid tissue found in the gastrointestinal tract,
organs. The newly formed lymphocytes migrate from respiratory tract, skin, tonsils, and adenoids. It is
these primary regions to secondary (or peripheral) lym- chiefly in the secondary lymphoid organs that T and
phoid organs, where they can react with antigen. Only B cells react with incoming foreign antigens. The
some of the secondary lymphoid organs are shown; bone marrow in mammals continues to generate
many lymphocytes, for example, are found in the skin large numbers of new B cells, approximately 5 ×
and lungs. 107/day in the mouse throughout life.6
594 Ballenger’s Otorhinolaryngology
Hemopoietic Secondary
FIGURE 28–2. The develop- Tissue Thymus Lymphoid Organs
ment of T and B cells. The pri-
mary lymphoid organs are where
lymphocytes develop from pre- T Cell Cell-
Mediated
cursor cells. The bursa of Fabri- Immune
Thymus Response
cius (birds only) is the lymphoid Bone Marrow Lymphocyte Antigen
Hemopoietic
organ for B-cell development, Lymphocyte (Mammals)
Stem Cells Antibody
whereas in mammals, the bone Response
B Cell
marrow is the predominant pre-
s)
cursor of B cells. T cells in sec- (Bird (Bird
ondary lymphoid organs are s)
Bursa Lymphocyte
primarily involved in cell-medi-
ated immune response, whereas
Bursa of
B cells are primarily involved in Fabricius
antibody responses. (Birds Only)
Cell-surface markers make it possible to distin- antigens in a highly specific way, for example, by
guish and separate T and B cells. T and B cells making antibodies that react specifically with the
become morphologically distinguishable only after antigen and induce their production. How this
they have been stimulated by antigen. Both are acti- immune system produces such diversity of specific
vated by antigens to proliferate and mature further. antibodies led to the emergence of the theory in the
Activated B cells develop into antibody-secreting 1950s that came to be known as the clonal selection
cells, the most mature of which are plasma cells that theory.9 According to this theory, each animal first
are filled with an extensive rough endoplasmic retic- randomly generates a vast diversity of lymphocytes,
ulum. In contrast, activated T cells contain very little and then those cells that react against the foreign
endoplasmic reticulum and do not secrete antibod- antigens that the animal actually encounters are
ies, although they do secrete a variety of mediators specifically selected for action. The theory is based
called lymphokines, interleukins (ILs), or cytokines. on the proposition that during development, each
Since both T and B cells occur in all secondary lym- lymphocyte becomes committed to react with a par-
phoid organs, it has been necessary to find ways to ticular antigen before ever being exposed to it. Each
distinguish and separate the two cell types and their cell expresses this commitment in the form of cell-
various subtypes to study their individual properties. surface receptor proteins that specifically fit the anti-
Fortunately, there are many differences in the plasma gen. The binding of antigen to the receptors activates
membrane proteins of the different types of lym- the cell, causing it to proliferate and mature. There-
phocytes that can serve as distinguishing markers. fore, a foreign antigen selectively stimulates those
Antibodies that react with the Thy-1 protein, for cells that express complementary antigen-specific
example, which is found on T cells but not on B cells receptors and are thus already committed to respond
in mice, are widely used to remove or purify T cells to it. This is what makes the immune response anti-
from a mixed population of mouse lymphocytes.7 gen specific.
Similarly, antibodies against CD4 and CD8 proteins, The term “clonal” in clonal selection arises
which are discussed later, are widely used to distin- from the postulate that the immune system is com-
guish and separate helper T cells and cytotoxic T posed of millions of different families, or clones of
cells, respectively, in both mice and humans.8 cells, each consisting of T or B cells descended from
a common ancestor. Each ancestral cell is already
THE IMMUNE SYSTEM WORKS BY CLONAL committed to make one particular antigen-specific
receptor protein, and all cells in a clone have the
SELECTION same antigen specificity. It is now known that the
The most remarkable feature of the immune system antigen-specific receptors on both T and B cells are
is that it can respond to millions of different foreign encoded by genes that are assembled from a series of
Cellular Biology of the Immune System 595
gene segments by a unique form of genetic recom- phocytes in the crypts.11 However, in the germinal
bination that occurs early in the cell’s development, centers of the tonsil or adenoids, B cells may present
beginning before it has encountered antigen. antigen to helper T cells.12 This will be discussed in
Most antigens stimulate many different lym- a further section of this chapter.
phocyte clones. Those parts of an antigen that com- The majority of T and B lymphocytes contin-
bine with the antigen-binding site on the antibody uously recirculate between the blood and the sec-
molecule or on a lymphocyte receptor are called ondary lymphoid tissue. In a lymph node, for
antigenic determinants or epitopes.10 Most antigens example, lymphocytes leave the bloodstream,
have a variety of antigenic determinants that stimu- squeezing out between specialized endothelial cells,
late the production of antibodies or T-cell responses. so-called high endothelial venules; after percolating
Some determinants are more antigenic than others, through the node, they accumulate in small lym-
so the reaction to them may dominate the overall phatic vessels that leave the node and connect with
response. Such determinants are said to be immun- other lymphatic vessels that pass through other
odominant. Even an antigen that activates many lymph nodes downstream and finally pass into a
clones will stimulate only a tiny fraction of the total large vessel called the thoracic duct, which carries
lymphocyte population. To ensure that these few them back to the blood. Lymphocyte recirculation
lymphocytes are exposed to the antigen, antigens are depends on specific interactions between the lym-
generally collected by specialized antigen-presenting phocyte cell surface and the surface of specialized
cells in secondary lymphoid organs, through which T endothelial cells lining small veins of the secondary
and B cells continuously circulate. Antigens that lymphoid organs; because their endothelial cells are
enter through the gut are trapped by gut-associated unusually tall, they are called postcapillary high
lymphoid tissue, those that enter through the skin endothelial venules (Figure 28–3). These migrations
or respiratory tract are retained locally and/or are are guided by various homing receptors on lympho-
transported via the lymph to local lymph nodes, and cytes and by the ligands for these receptors (often
those that enter the blood are filtered out in the called counter-receptors) on endothelial cells.13 Both
spleen. The antigen-presenting cells of the tonsil, receptors and counter-receptors have been identified
also called M cells, are in the crypts and present anti- by monoclonal antibodies that bind to the surface of
gen to T lymphocytes and subsequently to B lym- either lymphocytes or the specialized high endothe-
Basal
Lamina
High Endothelial
Cell of Postcapillary
Venule
FIGURE 28–3. Migration of a lymphocyte out of the bloodstream into a lymph node. A circulating lymphocyte
adheres weakly to the surface of the specialized high endothelial cells in a postcapillary venule in a lymph node. This
initial adhesion, mediated by E-selectin on the lymphocyte surface, is sufficiently weak that it enables the lymphocyte
to roll along the surface of the endothelial cells. The lymphocyte rapidly activates a stronger adhesion system medi-
ated by an integrin, which enables the cell to stop rolling and migrate out of the venule between the endothelial cells.
596 Ballenger’s Otorhinolaryngology
lial cells and inhibit the ability of the lymphocytes migration of activated lymphocytes and other white
both to bind the endothelial cells and tissue sections blood cells into sites of inflammation is largely
of secondary lymphoid organs and allows them to mediated by other combinations of selectins and
recirculate in vivo. Lymphocyte migration into integrins. For example, in nasal polyps, there is an
lymph nodes, for example, depends on the cell adhe- up-regulation of eosinophils because of the integrin
sion protein called E-selectin, which belongs to the VLA-4 (very late activation antigen 4), which is
selectin family of cell-surface selectins, which are increased on the surface of eosinophils, and a
glycoproteins.14 This homing receptor, which is pres- counter-receptor on the small blood vessels of
ent on most lymphocytes, binds to a specific sugar venules in the nasal polyp called VCAM-1 (vascular
group on a highly glycosylated, mucin-like counter- cell adhesion molecule). Very late activation antigen
receptor that is expressed exclusively on the surface 4 and VCAM-1 are receptor and counter-receptor
of high endothelial cells lining postcapillary venules and account for the significant increase of
and lymph nodes. E-selectin binding causes the lym- eosinophils in nasal polyps.17
phocytes to adhere weakly to the endothelial cells The immune system, like the nervous system,
and to roll slowly along their surface. The rolling can remember. This is why we develop lifelong
continues until another, much stronger adhesion immunity to many common viral diseases after our
system is activated. This strong adhesion, which is initial exposure to the virus, and this is why immu-
mediated by a member of the integrin family of cell nization works. If an animal is injected once with
adhesion molecules on the lymphocyte surface, antigen A, its immune response, either antibody or
allows the lymphocytes to stop rolling and crawl out cell mediated, will appear after a lag period of several
of the blood vessel into the lymph node.15 days, rise rapidly and exponentially, and then more
Other homing receptors on lymphocytes are gradually fall again. This is characteristic of a pri-
found to be responsible for the subsequent segrega- mary immune response occurring on an animal’s first
tion of T and B cells into distinct areas of the lymph exposure to an antigen. If some weeks, months, or
node. For example, B cells are primarily restricted to even years are allowed to pass and the animal is re-
the follicle and mantle zone of the tonsil and ade- injected with another antigen A, it would usually
noids, and T cells are primarily located between the produce a secondary immune response, which is very
secondary follicles and in the reticular epithelium of different from the primary immune response. The
these organs.16 Once they are activated by antigen, lag period is shorter, and the response is greater.
most lymphocytes lose many of their homing recep- These differences indicate that the animal has
tors and acquire new ones: instead of migrating “remembered” its first exposure to antigen A. There-
though lymphoid organs, they migrate through the fore, the secondary response reflects antigen-specific
nonlymphoid tissues to sites of inflammation. The immunologic memory for antigen A (Figure 28–4).
phocyte (clonal deletion) or functionally inactivating antigen-binding site. The antibodies made by a
cells and leaving them alive (clonal anergy). Toler- newly formed B cell are not secreted. Instead, they
ance to self-antigens sometimes breaks down, caus- are inserted into the plasma membrane, where they
ing T or B cells or both to react against their own serve as a receptor for antigen. Each B cell has
tissue antigens. Myasthenia gravis is an example of approximately 105 such antibody molecules in its
such an autoimmune disease.19 Affected individuals plasma membrane.22 Each of these antibody mole-
make antibodies against the acetylcholine receptors cules is noncovalently associated with an invariant
on their own skeletal muscle cells; the antibodies set of transmembrane polypeptide chains that are
interfere with the normal functioning of the recep- involved in passing signals to the cell interior when
tors so that such patients become weak and can die the extracellular binding site of the antigen is occu-
because they cannot breathe. pied by antigen. Each B cell produces a single species
In summary, the immune system evolved to of antibody with a unique antigen-binding site.
defend vertebrates against infection. It is composed When a virgin or memory B cell is activated by anti-
of millions of lymphocyte clones. The lymphocyte gen, it proliferates and matures to become an anti-
in each clone shares a unique cell-surface receptor body-secreting cell (plasma cell). The activated cells
that enables it to bind to a particular antigenic deter- make and secrete large amounts of soluble rather
minant consisting of a specific arrangement of than membrane-bound antibody, which has the
atoms on a part of a molecule. There are two classes same unique antigen-binding site as the cell-surface
of lymphocytes: B cells, which are produced in the antibody that served earlier as the antigen receptor.23
bone marrow and make antibodies, and T cells, Plasma cells seem to have committed so much of
which are produced in the thymus and make cell- their protein synthesizing machinery to making
mediated immune responses. Beginning early in antibody that they are incapable of further growth
lymphocyte development, many lymphocytes that and division, and most die after several days.
would react against antigenic determinants on self-
macromolecules are eliminated or inactivated; as a
result, the immune system normally reacts only to
ANTIBODIES HAVE TWO IDENTICAL ANTIGEN-
foreign antigens. The binding of a foreign antigen to BINDING SITES
a lymphocyte initiates a process by the cell that helps The simplest antibodies are Y-shaped molecules
to eliminate the antigen. As part of the response, with two identical antigen-binding sites, one at the
some lymphocytes proliferate and mature into tip of each arm of the Y (Figure 28–6). Because of
memory cells that are able to respond more readily
to antigen than do virgin cells. Thus, the next time Antigen-Binding Sites
the same antigen is encountered, the immune
response to it is much faster and stronger. The
remainder of this chapter discusses the structure
and property of antibodies that are the result of
B-cell maturation and the development of T-cell
immunity.
ANTIBODIES
Synthesized exclusively by B cells, antibodies are pro- Tail
duced in millions of forms, each with a different Region
amino acid sequence and a different binding site for 5 nm
antigen.20 Collectively, these antibodies are called Igs.
They are among the most abundant protein compo-
nents in the blood, constituting about 20% of the FIGURE 28–6. A simple representation of an antibody
total plasma protein by weight.21 All antibody mole- molecule. Note that its two antigen-binding sites are
cules made by an individual B cell have the same identical.
Cellular Biology of the Immune System 599
their two antigen-binding sites, they are said to be antigen-binding site, and both light and heavy
bivalent. As long as an antigen has three or more chains usually cooperate to form the antigen-bind-
antigenic determinants, bivalent antibody molecules ing surface (Figure 28–8, A). There are five classes of
can cross-link it into a large lattice, which can be heavy chains, each with different biologic properties.
rapidly phagocytosed and degraded by macrophages In higher vertebrates, there are five classes of anti-
(Figure 28–7).24 The efficiency of antigen binding bodies, IgA, IgD, IgE, IgG, and IgM, each with its
and cross-linking is greatly increased by a flexible own class of heavy chain, α, δ, ε, γ, and µ, respec-
hinge region in antibodies, which allows the distance tively.26 Immunoglobulin A molecules have α chains,
between the two antigen-binding sites to vary. IgG molecules have γ chains, and so on. In addition,
The protective effect of antibodies is not due there are a number of subclasses of IgG and IgA; for
simply to their ability to bind antigen. They engage example, there are four human IgG subclasses (IgG1,
in a variety of activities that are mediated by the tail IgG2, IgG3, and IgG4), having γ1, γ2, γ3, and γ4
of the Y-shaped molecule. This part of the molecule heavy chains, respectively.27 The various heavy
determines what will happen to the antigen once it chains impart a distinctive confirmation to the hinge
is bound to the antibody. One of several different and tail regions of the body and give each class (and
tailed regions can confer on the antibody different subclass) characteristic properties.
functional properties such as the ability to activate Immunoglobulin M, which has a µ heavy chain,
complement or to bind to phagocytic cells. The basic is always the first class of antibody produced by
structural unit of an antibody molecule consists of developing B cells, although many of these cells
four polypeptide chains; two identical light (L) eventually switch to making other classes of anti-
chains, each containing about 220 amino acids, and body, which are discussed below. The immediate
two identical heavy (H) chains, each usually contain- precursor of the B cell, called a pre-B cell, initially
ing about 440 amino acids.25 The four chains are makes µ chains, which associate with non–light-
held together by a combination of noncovalent and chain polypeptides, often referred to as surrogate
covalent disulfide bonds. The molecules are com- light chains, which insert into the plasma membrane.
posed of two identical halves, each with the same As the synthesis of bona fide light chains increases,
FIGURE 28–7. Antibody–antigen interactions. Because antibodies have two identical antigen-binding sites, they can
cross-link antigens. The types of antibody-antigen complexes that form depend on the number of antigenic determi-
nants on the antigen. Here a single species of antibody (a monoclonal antibody) is shown binding to antigens con-
taining one, two, or three copies of a single type of antigenic determinant. Antigens with two antigenic determinants
can form small cyclic complexes or linear chains with antibody, whereas antigens with three or more antigenic deter-
minants can form large three-dimensional lattices that readily precipitate out of solution. Most antigens have many
different antigenic determinants, and the different antibodies that recognize these different determinants can cooper-
ate in cross-linking the antigen.
600 Ballenger’s Otorhinolaryngology
these combine with the µ chains, displacing the sur- antigen to the Fab regions of the secreted pentameric
rogate light chains, to form a four-chain IgM mole- IgM molecule induces the Fc regions to bind to and
cule (with two µ chains and two light chains), which thereby activate the first component of the comple-
inserts into the plasma membrane. The cell now has ment system.30 When the antigen is on the surface of
cell-surface receptors with which it can bind anti- an invading microorganism, the resulting activation
gen, and, at this point, it is called a virgin B cell. of complement unleashes a biochemical attack that
Many virgin B cells soon start to produce cell-sur- kills the microorganism. Unlike IgM, IgD molecules
face IgD molecules as well, with the same antigen- are rarely secreted by an activated B cell, and their
binding site as the IgM molecules. Finally, it is to be functions (other than receptors for antigen) are
noted that IgM, IgD surface-positive B cells are unknown.
found in the mantle zone in the palatine tonsil and The major class of Ig in the blood is IgG, which
nasopharyngeal tonsil.28 is produced in large quantities during secondary
Immunoglobulin M is not only the first class of immune responses.31 Besides activating the comple-
antibody to appear on the surface of the developing ment system, the Fc region of an IgG molecule binds
B cell, it is also the major class secreted into the blood to specific receptors on macrophages and neu-
in the early stages of a primary antibody response. In trophils. Largely by means of such Fc receptors, these
its secreted form, IgM is a pentamer composed of five phagocytic cells bind, ingest, and destroy infecting
four-chain units and thus has a total of 10 antigen- microorganisms that have become coated with the
binding sites. Each pentamer contains one copy of IgG antibodies produced in response to the infection
another polypeptide chain called a J chain (joining (Figure 28–9).
chain).29 The J chain is produced by IgM-secreting Immunoglobulin G molecules are the only
cells and is covalently inserted between two adjacent antibodies that can pass from mother to fetus via the
tails (Fc regions) (Figure 28–8, B). The binding of placenta. Immunoglobulin G is also secreted into the
Macrophage or α Heavy
Chains
Neutrophil Phagocytosis
Light
Chain
Secretory
Component
J Chain
Extracellular
Fluid
Epithelial Cell
Lumen
lgA Dimer
Secretory
Component
Transcytosis
Membrane-Bound
Fc receptor
FIGURE 28–11. The mechanism of transport of a dimeric immunoglobulin (Ig)A molecule across an epithelial cell.
The IgA molecule, as a J chain–containing dimer, binds to a specialized transmembrane Fc receptor protein on the non-
luminal surface of the secretory epithelial cell. The surface of the receptor-IgA complexes are ingested by receptor-
mediated endocytosis, transferred across the epithelial cell cytoplasm in vesicles, and then secreted into the lumen of
the opposite side of the cell by exocytosis. When exposed to the lumen, the part of the Fc receptor protein that is bound
to the IgA dimer (the secretory component) is cleaved from its transmembrane tail, thereby releasing the antibody in
the form shown in Figure 28–10.
tations of such allergic reactions as hay fever, ANTIBODIES RECRUIT COMPLEMENT TO HELP
asthma, and hives. Mast cells also secrete factors that FIGHT BACTERIAL INFECTIONS
attract and activate a special class of white blood
cells called eosinophils, which can kill various types Complement, so called because it complements and
of parasites, especially if the parasites are coated with amplifies the action of antibody, is one of the prin-
IgE or IgA antibodies. The properties of the various cipal means by which antibodies defend vertebrates
classes of antibodies in humans are summarized in against most bacterial infections. Individuals with a
Table 28–1. deficiency in one of the central complement com-
ponents (called C3) are subject to repeated bacterial
infections, just as are individuals deficient in anti-
ANTIBODIES CAN HAVE EITHER OR LIGHT
bodies themselves. The complement system consists
CHAINS BUT NOT BOTH of at least 20 interacting soluble proteins that are
In addition to the five classes of heavy chains, higher made mainly by the liver and circulate in the blood
vertebrates have two types of light chains, κ and λ, and extracellular fluid.35 Most are inactive until they
either of which may be associated with any of the are triggered by an immune response or, more
heavy chains.34 An individual-antibody molecule directly, by an invading microorganism itself. The
always consists of identical light chains and identical ultimate consequence of complement activation is
heavy chains; therefore, its two antigen-binding sites the assembly of the so-called late complement com-
are always identical. This symmetry is crucial for the ponents into large protein complexes, called mem-
cross-linking function of secreted antibodies. Con- brane attack complexes, that form holes in the
sequently, an Ig molecule may have either κ or λ membrane of a microorganism and thereby destroy
light chains but not both. No difference in the bio- the microorganism.36
logic function of these two types of light chains has Because one of its main functions is to attack
yet been identified. the membrane of microbial cells, the activation of
Cellular Biology of the Immune System 603
Ig = immunoglobulin.
complement is focused on the microbial cell mem- ally leading to the formation of membrane attack
brane, where it is triggered either by antibody bound complexes. In this way, complement activation is
to the microorganism or by microbial envelope confined largely to the particular cell surface where
polysaccharides, both of which activate the early
complement components. There are two sets of early
components belonging to two distinct pathways of
complement activation: the classic pathway and the
alternative pathway. The early components of both
pathways act locally to activate C3, which is the piv-
otal component of complement, whose cleavage
leads not only to the assembly of membrane attack
complexes but also to the recruitment of various
white blood cells, particularly neutrophils (Figure
28–12).
The early components and C3 are proenzymes
that are activated sequentially by a limited prote-
olytic cleavage: the cleavage of each proenzyme in
the sequence activates the component to generate a
serine protease, which cleaves the next proenzyme in
the sequence, and so on. Since each activated
enzyme cleaves many molecules of the next proen-
zyme in the chain, the activation of the early com-
ponents consists of an amplifying proteolytic cascade.
Thus, each molecule activated at the beginning of FIGURE 28–12. The principal stages in complement
the sequence leads to the production of many acti- activation by the classic and alternative pathways. In both
vated components, including many membrane pathways, the reactions of complement activation usu-
attack complexes. ally take place on the surface of an invading microbe,
Many of these cleavages liberate a small pep- such as a bacterium. C1–C9 and factors B and D are the
tide fragment and thereby expose a membrane- reacting components of the complement system; various
binding site on the large fragment, which binds other components regulate the system. The early compo-
tightly to the target cell membrane and helps to nents are shown with thin arrows, whereas the late com-
carry out the next reaction in the sequence, eventu- ponents are shown with broad arrows.
604 Ballenger’s Otorhinolaryngology
it began. The larger fragment of C3 is called C3b. It binding or cleaving certain components once they
binds covalently to the surface of a target cell. There have been activated by proteolytic cleavage.37 Sec-
it not only acts as a protease to catalyze the subse- ond, many of the activated components in the cas-
quent steps in the complement cascade but also is cade are unstable; unless they bind immediately to
recognized by specific receptor proteins on an appropriate component in the chain or nearby
macrophages and neutrophils that enhance the abil- membrane, they rapidly become inactive. The
ity of these cells to phagocytose the target cell. The assembly of the late complement components to
smaller fragment of C3, C3a, acts independently as a form a membrane attack complex is illustrated in
diffusable signal that promotes an inflammatory Figure 28–13.
response by encouraging white blood cells to In summary, a typical antibody molecule is a
migrate into the site of the infection. Y-shaped protein with two individual antigen-bind-
The classic pathway is usually activated by clus- ing sites at the tips of the Y (the Fab regions), and
ters of IgG or IgM antibodies bound to antigens on binding sites for complement components and/or
the surface of a microorganism. The alternative various cell-surface receptors are on the tail of the Y
pathway, in contrast, is activated by polysaccharides (the Fc region). Antibodies defend humans against
in the cell envelopes of the microorganisms even in infection by inactivating viruses and bacterial toxins
the absence of antibodies. The alternative pathway and by recruiting the complement system in various
therefore provides a first line of defense against cells to kill and ingest invading microorganisms.
infection before an immune response can be Multiple studies performed in our laboratory have
mounted and also amplifies the effects of the classic shown that IgG is the principal Ig involved in
pathway once an immune response has begun. defense against acute bacterial infections of the mid-
The self-amplifying destructive properties of dle ear and sinuses.38 On the other hand, IgA is the
the complement cascade make it essential that key principal Ig covering the nasopharyngeal mucus and
activated components be rapidly inactivated after in preventing adherence of potentially pathogenic
they are generated to ensure that the attack does not microorganisms.39
spread to nearby normal host cells. Deactivation is Each B-cell clone makes antibody molecules
achieved in at least two ways. First, specific inhibitor with a unique antigen-binding site. Initially, the
proteins in the blood terminate the cascade by either molecules are inserted into the plasma membrane,
Plasma Membrane
Transmembrane
Aqueous Channel
Cytosol
FIGURE 28–13. Assembly of the late complement components to form a membrane attack complex. When C3b is pro-
duced by either the classic or alternative pathway, it is mobilized on the membrane, where it causes the cleavage of a
complement protein called C5 to produce C5a and C5b. C5b remains loosely bound to C3b (not shown) and rapidly
assembles with C6 and C7 to form C5,6,7, which then binds firmly via C7 to the membrane, as illustrated. This com-
plex adds one molecule of C8 to form C5,6,7,8. The binding of a molecule of C9 to C5,6,7,8 induces a confirmational
change in the C9 that exposes a hydrophobic region and causes the C9 to insert into the lipid bilayer of the target cell
next to C8. This starts a chain reaction in which the altered C9 binds a second molecule of C9, which undergoes a con-
firmational change and inserts into the bilayer, where it combines with another molecule of C9, and so on. In this way,
a large transmembrane channel or pore is formed by a chain of C9 molecules.
Cellular Biology of the Immune System 605
where they serve as receptors for antigen. Antigen most part, restricted to three small hypervariable
binding to these receptors activates the B cells (usu- regions in each chain.43 The remaining part of the
ally with the aid of helper T cells) to multiply and variable region, known as the framework regions, is
mature into either memory cells or antibody-secret- relatively constant. These findings led to the predic-
ing cells, which secrete antibodies with the same tion that only 5 to 10 amino acids in each hyper-
unique antigen-binding site as the membrane- variable region form an antigen-binding site. This
bound antibodies. These B-cell clones are found in prediction has since been confirmed by x-ray dif-
the tonsils and adenoids, and these two lymphoep- fraction studies of antibody molecules. In agreement
ithelial structures represent primarily B-cell tissues with the size of the antigen-binding site of an anti-
that are primarily responsible for a first line of body molecule, the antigenic determinant that is
defense against invading viruses and other microor- specifically recognized by an antibody is generally
ganisms, possibly as well as food antigens.40 comparatively small; it can consist of fewer than 25
Each antibody molecule is composed of two amino acid residues on the surface of the globular
identical heavy chains and two identical light chains. protein and can be as small as a dinitrophenol
Typically, parts of both the heavy and light chains group.44
form the antigen-binding sites.41 There are five Both light and heavy chains are made up of
classes of antibodies (IgA, IgD, IgE, IgG, and IgM), repeating segments, each about 110 amino acids and
each with a distinctive heavy chain (α, δ, ε, γ, and µ, each containing one intrachain disulfide bind, that
respectively). The heavy chains also form the Fc fold independently to form compact functional
region of the antibody, which determines what other units or domains. As shown in Figure 28–14, a light
proteins will bind to the antibody and therefore
what biologic properties the antibody class has.
Either type of light chain (κ or λ) can be associated
with any class of heavy chain, but the type of light
chain does not seem to influence the properties of
the antibody.
The complement system cooperates with anti-
bodies to defend vertebrates against infection.42 The
early components are proenzymes that circulate in
the blood and are sequentially activated in an ampli-
fying series of limited proteolytic reactions. The
most important complement component is the C3
protein, which is activated by proteolytic cleavage
and binds to the membrane of the microbial cell,
where it helps to initiate the local assembly of the
late complement components and to induce the
phagocytosis of the microbial cell. The late compo-
nents form large membrane attack complexes in the FIGURE 28–14. Immunoglobulin (Ig) domains. The
microbial cell membrane and thereby kill the invad- light and heavy chains in an Ig molecule are each folded
ing microorganism. Two final subjects on antibodies into repeating domains that are similar to one another.
need to be discussed; the fine structure of antibod- The variable domains of the light and heavy chains (VL
ies and antibody diversity. and VH) make up the antigen-binding sites, whereas the
constant domains of the heavy chains (mainly CH2 and
LIGHT AND HEAVY CHAINS EACH CONTAIN CH3) determine the other biologic properties of the mol-
THREE HYPERVARIABLE REGIONS THAT ecule. The heavy chains of IgM and IgE antibodies have
an extra constant domain (CH4). Hydrophobic interac-
TOGETHER FORM THE ANTIGEN-BINDING SITE tions between domains on adjacent Ig chains play an
Scrutiny of the amino acid sequences of a variety of important part in holding the chains together in the Ig
Ig chains shows that the variability in the variable molecule: CL binds to CH1, for example, and the CH3
regions of both the light and heavy chains is, for the domains bind to each other.
606 Ballenger’s Otorhinolaryngology
chain consists of one variable (VL) and one constant remarkably economical way by joining separate gene
(CL) domain, whereas most heavy chains consist of a segments together before they are transcribed.
variable domain (VH) and three constant domains Antibodies are produced from three pools of
(CH1, CH2, CH3).45 The µ and ε chains each have one gene segments, encoding κ light chains, λ light
variable and four constant domains. The variable chains, and heavy chains, respectively.48 In each
domains are responsible for antigen binding, pool, separate gene segments that code for different
whereas the constant domains of the heavy chains parts of the variable regions of light and heavy
excluding CH1 form the Fc region that determines chains are brought together by site-specific recom-
the other biologic properties of the antibody. The bination during B-cell differentiation. The light
similarity between their domains suggests that Ig chain pools contain one or more constant (C) gene
chains arose during evolution by a series of gene segments and sets of variable (V) and joining (J)
duplications, beginning with the primordial gene segments. The heavy chain pool contains a set of C
cloning for a similar 110 amino acid domain of gene segments and sets of V, diversity (D), and J
unknown function. This hypothesis is supported by gene segments. To make an antibody molecule, a VL
the finding that each domain of the constant region gene segment is recombined with a JL gene segment
of the heavy chain is encoded by a separate coding to produce a DNA sequence coding for the V region
sequence (exon).46 The amino acid sequence varia- of the light chain, and a VH gene segment is com-
tion in the variable regions of both light and heavy bined with a D and a JH gene segment to produce a
chains is for the most part confined to several small DNA sequence coding for the V region for the heavy
hypervariable regions; they form protruding surface chain. Each of the assembled gene segments is then
loops that come together to form the antigen-bind- cotranscribed with the appropriate C-region
ing site. sequence to produce a messenger ribonucleic acid
molecule that codes for the complete polypeptide
chain. By variously combining gene segments that
GENERATION OF ANTIBODY DIVERSITY code for VL and VH regions, mammals can make
Finally, a brief comment of antibody diversity is thousands of different light chains and thousands
necessary to complete our discussion of the B-cell of different heavy chains. Since the antigen-binding
repertoire and antibody function as part of the site is formed where VL and VH come together in the
humoral immune system. It is estimated that even final antibody, the heavy and light chains can pair to
in the absence of antigen stimulation, a human form antibodies with millions of different antigen-
makes at least 1015 different antibody molecules, its binding sites. This number is enormously increased
preimmune antibody repertoire.47 Antibodies are by the loss and gain of nucleotides at the site of
proteins, and proteins are encoded by genes. Anti- gene-segment joining, as well as by somatic muta-
body diversity, therefore, poses a special genetic tions that occur with very high frequency in the
problem: how can an animal make more antibodies assembled V-region coding sequences following
than there are genes in its genome? (The human antigen stimulation.
genome, for example, is thought to contain fewer All B cells initially make IgM antibodies. Later,
than 105 genes.) This problem is not quite as formi- some make antibodies of other classes but with the
dable as it might first appear. Because the variable same antigen-binding site as the original IgM anti-
regions of both the light and heavy chains con- bodies. Such class switching allows the same anti-
tribute to an antigen-binding site, an animal with gen-binding sites to be distributed among antibodies
1,000 genes encoding light chains and 1,000 genes with varied biologic properties. In regard to the ton-
encoding heavy chains could combine their prod- sils and adenoids, such B class switching has been
ucts in 1,000 × 1,000 ways to make 106 different well documented. The mantle zone of the secondary
antigen-binding sites, assuming that any light chain follicles possesses primarily IgD and IgM. The follic-
can combine with any heavy chain to make an anti- ular areas of the tonsils and adenoids possess IgM,
gen-binding site. Nonetheless, the mammalian IgA, and IgG. The reticular epithelium possesses
immune system has evolved unique genetic mecha- mainly IgG followed by IgA, IgM, and IgD. Finally,
nisms that enable it to generate an almost unlimited only approximately 2% of the tonsillar lymphocytes
number of different light and heavy chains in a are mature plasma cells that secrete Igs.49
Cellular Biology of the Immune System 607
Thus, in summary, foreign protein molecules nal domains of the α chain, which are farthest from
are presented to the T-cell receptor only in the con- the membrane, bind antigen and contain the poly-
text of their association with self-MHC molecules. In morphic (variable) amino acids that are recognized
a sense, this is a form of physiologic autoimmunity in by T cells in transplantation reactions. Like class I
that a foreign molecule can be recognized by a T cell MHC molecules, class II MHC molecules are het-
only when it is combined with a self-MHC molecule. erodimers with two conserved Ig-like domains close
to the membrane and two antigen-binding polymor-
phic (variable) amino-terminal domains farthest
THERE ARE TWO PRINCIPAL CLASSES OF from the membrane. In these molecules, however,
MHC MOLECULES both chains (α and β) are encoded within the MHC,
Class I and class II MHC proteins have very similar and both span the membrane. The presence of Ig-
overall structures, as shown in Figure 28–16. They are like domains in class I and class II proteins suggests
both transmembrane heterodimers whose extracel- that MHC molecules and antibodies have a common
lular amino-terminal domains bind antigen for pres- evolutionary history. The locations of the genes that
entation to T cells. Each class I MHC gene encodes a encode class I and class II MHC proteins in mice and
single transmembrane polypeptide chain (called α), humans are shown in Figure 28–17.61
most of which is folded into three extracellular glob-
ular domains (α1, α2, α3). Each α chain is noncova- CLASS I AND CLASS II MHC MOLECULES
lently associated with a small extracellular protein
called 2-microglobulin, which does not span the
HAVE DIFFERENT FUNCTIONS
membrane and is encoded by a gene that does not lie Class I MHC molecules are expressed on virtually all
in the MHC cluster.60 β2-Microglobulin and the α3 nucleated cells, presumably because cytotoxic T cells
domain, which are closest to the membrane, are both must be able to focus on any cell in the body that
homologous to an Ig domain. The two amino-termi- happens to become infected with an intracellular
α Chain β Chain
Microglobulin
Extracellular
Space
Plasma
Membrane
Cytosol
FIGURE 28–16. Class I and class II major histocompatibility complex (MHC) proteins. On the left, the α chain of the
class I molecule has three extracellular domains, αl, α2, and α3, encoded by separate exons. It is noncovalently associ-
ated with a smaller polypeptide chain, β2-microglobulin, which is not encoded within the MHC. The α3 domain and
β2-microglobulin are immunoglobulin (Ig)-like. Whereas β2-microglobulin is invariant, the α chain is extremely poly-
morphic, mainly in the α1 and α2 domains. On the right in class II MHC molecules, both chains are polymorphic (β
more than α), mainly in the α1 and β1 domains; the α2 and β2 domains are Ig-like. Thus, there are striking similarities
between class I and class II MHC proteins. In both, the two outermost domains interact to form a groove that binds
foreign antigen and presents it to T cells. All of the chains are glycosylated except for β2-microglobulin.
610 Ballenger’s Otorhinolaryngology
H-2 Complex
Mouse
Chromosome 17
Centromere
Human
Chromosome 6
HLA Complex
FIGURE 28–17. The H-2 and human leukocyte antigen (HLA) gene complexes. This simplified schematic drawing
shows the location of the genetic loci that encode the transmembrane subunits of class I and class II major histocom-
patibility complex (MHC) proteins. There are three types of class I proteins (H-2K, H-2D, and H-2L in the mouse,
and HLA-A, HLA-B, and HLA-C in the human). There are two class II MHC loci in the mouse, H-2A and H-2E, and
more than three in humans, of which only three are shown, HLA-DP, HLA-DQ, and HLA-DR. Each class II locus
encodes at least one α chain and at least one β chain, but some encode more than one α or β chain.
microbe such as a virus. Class II molecules, in con- morphic part of the appropriate class of MHC mol-
trast, are normally confined to specialized cells, such ecule. CD4 and CD8 proteins act as MHC-binding
as B cells, macrophages, and other antigen-present- coreceptors on helper and cytotoxic T cells, respec-
ing cells that take up foreign antigens from the extra- tively.62 The affinity of T-cell receptors for peptide-
cellular fluid and interact with helper T cells (Figure MHC complexes on the target cell is usually too low
28–18). The principal features of the two classes of to mediate a functional interaction between the two
MHC proteins are summarized in Table 28–2. cells. Accessory receptors are normally required to
It is important that cytotoxic T cells focus their help stabilize the interaction by increasing the over-
attack on cells that make foreign antigens, whereas all strength of the cell-to-cell adhesion; when they
helper T cells focus their help on cells that take up also have a direct role in activating the T cell by gen-
foreign antigens from the extracellular fluid. The erating their own intercellular signals, they are called
former type of target cell is a menace, but the latter coreceptors. Unlike T-cell receptors or MHC mole-
type is essential for the body’s immune defenses. The cules, the accessory receptors do not bind antigen
immune system must be able to dispose of extracel- and are invariant and nonpolymorphic. The most
lular foreign antigens as many bacteria multiply out- important and best understood of the coreceptors
side cells, and some secrete protein toxins, such as on T cells are the CD4 and CD8 proteins, both of
tetanus toxin and botulinum toxin, that can be which are single-pass transmembrane proteins with
lethal. Helper T cells help eliminate such pathogens, extracellular Ig-like domains. Like T-cell receptors,
both by helping B cells make antibodies against they recognize MHC proteins, but unlike T-cell
microbes and their toxins and by activating receptors, they bind to nonvariable parts of the pro-
macrophages to destroy ingested microbes. tein, far away from the peptide-binding groove. CD4
To ensure that there is no misdirection of cyto- is expressed on helper T cells and binds to class II
toxic and helper functions, each of the two major MHC molecules, whereas CD8 is expressed on cyto-
classes of T cells, in addition to the antigen receptor toxic T cells and binds to class I MHC molecules
that recognizes a peptide-MHC complex, also (Figure 28–19). The CD4 and CD8 proteins are not
expresses a coreceptor that recognizes a nonpoly- only required to increase the strength of cell-to-cell
Cellular Biology of the Immune System 611
T-Cell Receptor
Class I Fragment Class II Fragment
MHC of Foreign MHC of Foreign
Protein Protein Protein Protein
Infected Antigen-
Target Cell Presenting Cell
FIGURE 28–18. Cytotoxic and helper T cells recognize different major histocompatibility complex (MHC) molecules.
Cytotoxic T cells recognize foreign antigens in association with class I MHC proteins on the surface of any infected host
cell, whereas helper T cells recognize foreign antigens in association with class II MHC proteins on the surface of an anti-
gen-presenting cell, such as a macrophage or a B cell. The foreign antigen bound to a class I MHC molecule is synthe-
sized within the target cell, whereas the foreign antigen bound to a class II MHC molecule has been taken up by the cell
by endocytosis and processed before it is presented on the cell surface. In transplantation reactions as well, helper T cells
react against foreign class II MHC proteins, whereas cytotoxic T cells react against foreign class I MHC proteins.
adhesion and to help activate the T cell, they are also human immunodeficiency virus, allowing the virus
needed for T-cell development; if the genes that to infect helper T cells.
encode CD4 and CD8 are inactivated by targeted
genetic recombination, then either helper T cells or
cytotoxic T cells, respectively, do not develop. Ironi-
CYTOTOXIC T CELLS
cally, CD4 also functions as a receptor for the Cytotoxic T cells recognize fragments of viral pro-
acquired immune deficiency syndrome (AIDS) teins on the surface of virus-infected cells. As men-
Class I MHC the endoplasmic reticulum (ER). Once inside ER, the
CD8 Protein
Protein peptides bind to MHC molecules that they encounter
there and are then carried to the cell surface with
them. When T cells are activated by antigen, they
secrete various signaling protein molecules, including
interferon-gamma (IFN-γ), which greatly enhances
antiviral responses.64 The IFN-γ induces the expres-
sion of many genes within the MHC chromosomal
T-Cell Receptor Infected Cell
region, including those in class I and class II MHC
proteins, the two specialized proteasome subunits,
Polymorphic Nonpolymorphic and the two subunits of the peptide pump located in
Part Part the ER. Thus, all of the machinery required for pre-
senting viral antigens to cytotoxic T cells is coordi-
nately called into action by IFN-γ, creating a positive
feedback that amplifies the immune response and
culminates in the death of the infected cell.
Once a cytotoxic T cell recognizes a viral peptide
bound to a class I MHC molecule on the surface of a
target cell, its job is to destroy the cell before the virus
that gave rise to the peptide can produce new viral
CD4 Protein Antigen-Presenting particles that can escape from the infected cell. The
Cell mechanism by which cytotoxic T cells kill their targets
Class II MHC Protein is not known. They seem to employ at least two strate-
gies, both of which are thought to operate by induc-
FIGURE 28–19. CD4 and CD8 coreceptors on the sur- ing the target cell to undergo programmed cell death
face of T cells. Note that these proteins bind to the non- (also called apoptosis).65 In one strategy, binding to a
variable part of the same major histocompability target cell stimulates the cytotoxic T cells to release a
complex (MHC) molecule that the T-cell receptor has pore-forming protein called perforin, which is homol-
engaged, so that they are bought together with T-cell ogous to the complement component C9 and poly-
receptors during the cell activation process. Antibodies merizes in the target cell plasma membrane to form
against CD4 and CD8 are widely used to distinguish transmembrane channels.66 Perforin is stored in secre-
helper and cytotoxic T cells, respectively. tory vesicles and is released by local exocytosis at the
point of contact with the target cell. The secretory
tioned above, T cells of any individual that recognize vesicle also contains serine proteases and other pro-
a specific antigen will do so only when that antigen is teins, which are also thought to play a part in killing
associated with the allelic forms of MHC molecules the target cell, perhaps by entering the target cell
expressed by that individual, a phenomenon known through the perforin channels and inducing pro-
as MHC restriction. It has been shown that cytotoxic grammed cell death. The second strategy, by contrast,
T cells, when activated by, for example, influenza involves the cytotoxic T cell activating a receptor on
virus, specifically recognize internal proteins of that the surface of the target cell, thereby signaling the tar-
virus that would not be accessible in the intact virus get cell to undergo programmed cell death.67
particle. Subsequent evidence has suggested that the
T cells have recognized degraded fragments of the HELPER T CELLS AND T-CELL
internal viral proteins. Because a T cell can recognize
tiny amounts of antigen (only a few hundred mole-
ACTIVATION
cules), only a small fraction of the fragments gener- Unlike cytotoxic T cells, helper T cells do not act
ated from viral proteins has to get to the cell surface directly to kill infected cells or to eliminate microor-
to attract an attack by a cytotoxic T cell.63 Proteins ganisms. Instead, they stimulate macrophages to be
destined for the cell surface usually begin their jour- more effective in destroying pathogens, and, most
ney by crossing from the cytosol into the lumen of importantly, they help other types of lymphocytes to
Cellular Biology of the Immune System 613
respond to antigen. Helper T cells recognize frag- The initial activation of a T cell usually occurs when
ments of endocytosed foreign protein antigens in it recognizes foreign peptide bound to an MHC
association with class II MHC proteins. molecule on the surface of an antigen target cell. For
Like the viral antigens presented to cytotoxic T a helper T cell, the appropriate target is an antigen-
cells, the antigen presented to helper T cells on anti- presenting cell.
gen-presenting cells is degraded fragments of foreign Antigen-presenting cells are derived from the
protein that are bound to class II MHC molecules in bone marrow and comprise a heterogeneous set of
much the same way that virus-derived peptides are cells, including interdigitating dendritic cells in lym-
bound to class I MHC molecules. But both the source phoid organs and Langerhans’ cells in skin, as well as
of the peptide fragments presented and the route the B cells and macrophages that will subsequently
they take to find the MHC molecules are different be the target of T-cell help. Together with thymus
from those of peptide fragments presented by the epithelial cells, which have a special role in T-cell
class I MHC molecules to cytotoxic T cells. Rather development and activate T cells in some mammals,
than being derived from foreign proteins synthesized these specialized antigen-presenting cells are the
inside the target cell, the peptides presented to helper only cell types that normally express class II MHC
T cells are derived from extracellular microbes or molecules. In addition to class II MHC molecules,
their products, which have been ingested by antigen- antigen-presenting cells also express a second cell-
presenting cells and degraded in the acidic environ- surface molecule, called B7, that plays a crucial part
ment of endosomes.68 These peptides do not have to in activating T cells.
be pumped across the membrane because they do
not originate in the cytosol; they are generated in the TWO SIMULTANEOUS SIGNALS ARE REQUIRED
compartment that is topographically equivalent to
FOR HELPER T-CELL ACTIVATION
the extracellular space. They never enter the lumen of
the ER, where the class II MHC molecules are syn- To activate a helper T cell, an antigen-presenting cell
thesized and assembled, but instead bind to pre- must provide at least two signals. Signal 1 has already
assembled class II heterodimers in a late endosomal been discussed; it is provided by a foreign peptide
compartment. Once the peptide binds, the class II bound to a class II MHC molecule on the surface of
MHC molecule alters its confirmation, trapping the the presenting cell that activates the T-cell receptor
peptide in the binding groove for presentation at the complex. Depending on the type of helper T cell, a
cell surface to helper T cells. signal 2 is provided by either a secreted chemical sig-
Most of the class I and class II MHC molecules nal such as IL-1, or by the plasma membrane–bound
on the surface of the target cell have peptides derived signaling molecule B7 on the surface of the antigen-
from self-proteins in their binding groove: for class presenting cell. B7 is recognized by a coreceptor pro-
I molecules, fragments of degraded cytosolic and tein called CD28, which is present on the surface of
nuclear proteins; for class II molecules, fragments of the helper T cell and is a member of the Ig superfam-
degraded membrane and serum proteins that pass ily.69 If helper T cells receive both signals, they are acti-
through the endosome-lysosome system. Only a vated to proliferate and secrete a variety of cytokines.
small fraction of the class II MHC molecules on the In contrast, if they receive signal 1 without signal 2,
surface of an antigen-presenting cell will have for- they are altered so that they can no longer be activated
eign peptides bound to them. This, however, suffices even when they receive both signals. This has been
to initiate an immune response because only a few suggested to be one mechanism whereby T cells
hundred such molecules are required to activate a become tolerant. Some accessory proteins present on
helper T cell, just as only a few hundred peptide– the surface of T cells are summarized in Table 28–3.
class I MHC complexes on a target cell are required
to activate a cytotoxic T cell. HELPER T CELLS, ONCE ACTIVATED, STIMULATE
Just as a B cell must be activated to proliferate
THEMSELVES AND OTHER T CELLS TO
and differentiate into an antibody-secreting cell
before it can function, so, too, must a T cell be acti- PROLIFERATE BY SECRETING INTERLEUKIN-2
vated to proliferate and differentiate before it can kill The combined action of signal 1 and signal 2 pro-
an infected target cell or help a macrophage or B cell. vokes helper T-cell proliferation by a curiously indi-
614 Ballenger’s Otorhinolaryngology
]
CD3 Ig — Helps transduce signal when
δ chain = 20,000 Ig All T cells antigen-MHC complex
ε chain = 20,000 Ig binds to T-cell receptors
ζ chain = 16,000 —
CD4 55,000 Ig Helper T cells Class II MHC Promotes adhesion to
antigen-presenting cells
and to B cells; signals T cell
CD8 70,000 (homodimer Ig Many helper and Class I MHC Promotes adhesion to infected
or heterodimer) cytotoxic T cells target cells; signals T cell
CD28 80,000 (homodimer) Ig Cytotoxic T cells B7 Provides signal 2 to some
T cells
LFA-1 a1 chain = 190,000 Integrin Most white blood ICAM-1 Promotes cell-to-cell adhesion
b2 chain = 95,000 cells, including
T cells
rect mechanism. It causes the T cells to stimulate secreted signals. Once activated, the helper T cell can
their own proliferation by simultaneously secreting help activate a B cell that specifically displays the
a growth factor called IL-2 and the synthesized cell- same complex of foreign antigen and class II MHC
surface receptors that bind it. The binding of IL-2 to protein on its surface. The display of antigen on the
these IL-2 receptors then directly stimulates the T B-cell surface reflects the selectivity with which it
cells to proliferate.70 By this autocrine mechanism, takes up foreign molecules from the extracellular
helper T cells can continue to proliferate after they fluid. The specific membrane-bound antibodies on
have left the surface of the antigen-presenting cell the surface of the B cell are ingested and then
(Figure 28–20). The helper T cell can also stimulate degraded and recycled to the cell surface in the form
the proliferation of any other nearby T cells, includ- of peptides bound to class II MHC proteins. Thus,
ing cytotoxic T cells, which have first been induced the helper cell activates those B cells that make mem-
by antigen to express IL-2 receptors. Because the brane-bound antibodies that specifically recognize
expression of IL-2 receptors is strictly dependent on the antigen that initially activated the T cell. In sec-
antigen stimulation, however, IL-2 causes the prolif- ondary antibody responses, memory B cells them-
eration of only T cells that have encountered that selves may act as antigen-presenting cells and activate
specific antigen. helper T cells, as well as be the subsequent targets of
the helper T cells. The mutually reinforcing actions of
HELPER T CELLS ARE REQUIRED FOR MOST B T and B cells lead to an immune response that is both
intense and highly selective. The membrane-bound
CELLS TO RESPOND TO ANTIGEN signaling molecule is a transmembrane protein called
Although there are some antigens, including micro- CD40 ligand, which is expressed on the surface of
bial polysaccharides, that can stimulate B cells to pro- activated, but not resting, helper T cells. It is recog-
liferate and differentiate into antibody-secreting cells nized by the CD40 transmembrane protein on the B
without T-cell help, the activation of B cells by helper cell.71 The interaction between CD40 ligand and
T cells is mediated by both membrane-bound and CD40 is required for helper T cells to activate B cells
Cellular Biology of the Immune System 615
Antigen-Presenting Cell
IL-2
Signal
T-Cell IL-2 Receptor
Receptor
Activation
Proliferation
Antigen Signal
Fragment
Resting Helper Activated Helper
T Cell T Cell
FIGURE 28–20. The stimulation of T-cell proliferation by interleukin (IL)-2. Signals 1 and 2 activate the helper T cells
to make IL-2 receptors and to secrete IL-2. The binding of IL-2 to its receptors stimulates the cell to grow and divide.
When the antigen is eliminated, the T cells eventually stop producing IL-2 and IL-2 receptors, so cell proliferation stops.
Some helper T cells do not make IL-2; their proliferation, like that of cytotoxic cells, is stimulated by IL-2 made by
neighboring helper T cells (signals 1 and 2 are discussed in the text).
to proliferate and mature into memory and anti- maturation and promotes the switching to IgE and
body-secreting cells. This interaction is critical for T- IgG1 antibody production: if the IL-4 gene is inac-
cell help: individuals whose T cells lack the CD40 tivated by targeted recombination in a mouse, the
ligand because of the mutation in the gene encoding mouse is unable to make IgE and makes very little
the protein can make only IgM antibodies and are IgG1.
severely immune deficient, being susceptible to the Thus, most B cells, like T cells, require multiple
same infections that affect AIDS patients, whose signals for activation, one provided by antigen bind-
helper T cells have been destroyed. ing to the membrane-bound Ig molecules and the
Secreted signals from the T cells provide addi- others provided by the helper T cells; as in the case
tional help by activating B cells to proliferate, of T cells, if a B cell receives the first signal only, it
mature, and, in some cases, switch the class anti- may be functionally inactivated. The comparison of
body they produce. Interleukin-4 is one such sig- the signals required to activate helper T cell and a B
nal. 72 It stimulates B-cell proliferation and cell are outlined schematically in Figure 28–21.
SOME HELPER T CELLS HELP ACTIVATE In summary, helper T cells help activate B cells
CYTOTOXIC T CELLS AND MACROPHAGES BY and macrophages. They are themselves initially acti-
vated when they recognize peptide fragments
SECRETING INTERLEUKINS derived from foreign extracellular proteins that are
There are at least two functionally distinct subclasses endocytosed by specialized antigen-presenting cells.
of helper T cells that can be distinguished by the The ingested proteins are degraded in endosomes,
cytokines that they secrete. TH1 cells secrete IL-2 and and some of the resulting peptide fragments bind to
IFN-γ and are concerned mainly with helping cyto- class II MHC molecules, forming complexes that are
toxic T cells and macrophages.73 TH2 cells secrete IL- carried to the cell surface, where the helper T cells
4 and IL-5 and are concerned mainly with helping B recognize them. The activation of the helper T cell
cells and eosinophils.74 The properties of some ILs requires at least two signals: signal 1 is provided by
are outlined in Table 28–4. The antigen-triggered the MHC-peptide complex, whereas signal 2 is pro-
secretion of ILs underlies the familiar tuberculin skin vided by either the B7 protein on the surface of an
test. If tuberculin is injected into the skin of an indi- antigen-presenting cell or a signal secreted by this
vidual who had been immunized against tuberculo- cell. Once activated, helper T cells stimulate their
sis, a characteristic immune response occurs in the own proliferation by secreting IL-2 and activate their
skin. It is initiated at the site of injection by the secre- target cells by a combination of membrane-bound
tion of ILs by memory helper T cells that react to the and secreting signaling molecules. Developing T
tuberculin. The ILs attract macrophages and lym- cells that recognize peptides in association with self-
phocytes into the site, thereby causing the character- MHC molecules are positively selected in the thy-
istic swelling of a positive reaction to tuberculin. mus, whereas developing T cells that react strongly
Another important effect of IFN-γ is to induce with self-peptides bound to self-MHC molecules are
the expression of class II MHC proteins on the sur- eliminated in the thymus. Thus, those immature T
face of some cells such as endothelial cells that do cells that will be capable of recognizing foreign pep-
not normally express them, thereby enabling these tides presented by self-MHC molecules are selected
cells to present antigen to helper T cells.75 to survive, whereas the remainder, which would be
of no use to the animal, die. Thus, MHC restriction as integrins that are heterodimeric proteins that pro-
is a required property of the immune system that mote cell to cell-surface interaction and counter-
emerges as T cells develop in the thymus. Positive receptors on the surface of endothelial cells of blood
selection still leaves a large problem to be solved. If vessels is emphasized because the cell-to-cell inter-
developing T cells with receptors that recognize self- action is responsible for the migration of inflamma-
peptides associated with self-MHC molecules were tory cells into the tissue following an immune
to mature in the thymus and migrate to peripheral response.76 A great deal of molecular biologic infor-
lymphoid tissues, they would wreak havoc. A sec- mation has accumulated on the pathogenesis of
ond, negative selection process in the thymus is nasal polyposis. It appears that eosinophils and lym-
required to avoid this disaster. A fundamental fea- phocytes are the predominant inflammatory cell in
ture of the immune system is that it can distinguish nasal polyp tissue. The events leading up to the
self from nonself and normally does not react extravasation of eosinophils into the lamina propria
against self-molecules. This state of immunologic of nasal polyps are regulated by the proinflamma-
self-tolerance is acquired mainly during T-cell devel- tory cytokines, tumor necrosis factor alpha (TNF-α)
opment. It is not enough, therefore, for the thymus and IL-1β.77 These cytokines up-regulate VLA-4 on
to select for T cells that recognize self-MHC mole- the surface of eosinophils and VCAM-1 on the sur-
cules; it must also select against T cells that recognize face of the endothelial cells of blood vessels. 78
self-MHC molecules complex with self-peptides. In Chemokines such as RANTES (regulated upon acti-
other words, it must pick out for survival just those vation, normal T cell expressed and secreted) and
T cells that would be capable of recognizing self- eotaxin are responsible for the movement of
MHC molecules complexed with foreign peptides, eosinophils into the lamina propria of the nasal
even though these peptides are not present in the polyp.79 The release of major basic protein from
developing thymus. Thus, the required goal can be eosinophils has an effect on alteration of the epithe-
achieved by (1) ensuring the death of T cells that lial architecture and on the sodium and chloride flux
bind strongly to the peptide-MHC complexes in the into and out of the apical epithelial cell of the tis-
thymus while (2) promoting the survival of those sue.80 Therefore, it is incumbent on the student of
that bind weakly and (3) permitting the death of chronic inflammation to understand how the
those that do not bind at all. Process 2 is the positive immune process, which has been thoroughly dis-
selection that has been discussed above. Process 1 is cussed in this chapter, can effect the inflammatory
called negative selection. response. Therefore, to conclude this chapter on the
In summary, the T-cell repertoire is shaped immune response and its effect on inflammation, a
mainly by a combination of positive and negative brief review of cytokines, integrins, and endothelial
selection processes that operate during T-cell devel- cell receptors is undertaken.
opment in the thymus. These processes ensure that
only T cells with potentially useful receptors survive
and mature, whereas the others undergo pro-
CYTOKINES
grammed cell death: T cells that will be able to rec- Cytokines are a group of signaling molecules
ognize foreign peptide complex with self-MHC involved in communication between cells, including
molecules are positively selected, whereas T cells that those of the immune system.81 Cytokine-mediated
react strongly with self-peptide complex with self- events occur during the initiation and effector stages
MHC molecules are eliminated. of immune responses and the development of
hematopoietic cells. Within the last decade, there has
THE IMMUNE SYSTEM AND THE been an explosion of knowledge of cytokine and
cytokine receptor structures and genes along with a
INFLAMMATORY RESPONSE clarification of the roles of individual cytokines. This
The final part of this chapter briefly reviews certain section focuses on two proinflammatory cytokines,
surface molecules that are up-regulated in inflam- namely TNF-α and IL-1β. However, there are over
matory tissues with specific emphasis on nasal poly- 20 cytokines that have been identified, as well as
posis as a model of chronic inflammation. A their receptors.82 A schematic overview of the role of
knowledge of these inflammatory cytokines as well various cytokines on TH1- and TH2-dependent
618 Ballenger’s Otorhinolaryngology
immune reactions is summarized in Figure 28–22. weight of 17 kDa. It has a vast array of biologic activ-
Tumor necrosis factor α can be derived from ities that include promoting bone resorption by
macrophages, T cells, thymocytes, B cells, and natu- osteoclasts, stimulation of T-cell production,
ral killer cells. The target of TNF-α may be tumor enhancement of B-cell proliferation and Ig secre-
cells, transformed cell lines, fibroblasts, macro- tion, the activation of vascular endothelial cells,
phages, osteoclasts, neutrophils, adipocytes, increasing eosinophilic toxicity for parasites, and the
eosinophils, endothelial cells, chondrocytes, and stimulation and proliferation of fibroblasts, among
hepatocytes. Tumor necrosis factor α is known to be other activities. It is apparent that many of the bio-
made by activated macrophage and other cells and logic activities of TNF-α are important in both
to have wide-ranging proinflammatory effects. It is immunity and inflammation. They act in a very
purified from natural sources and has a molecular wide range of cellular targets and cause enormous
T Cell
TH2
FIGURE 28–22. Diagram of the effect of multiple irritants on the epithelial cell in the lateral wall of the nose. Bacte-
ria, virus, air pollution, allergy, or fungus can have an effect of up-regulating various cytokines such as granulocyte-
macrophage colony stimulating factor (GM-CSF), interleukin (IL)-8, or tumor necrosis factor (TNF)-α directly by
changing the genetic potential of the respiratory epithelial cell. These cytokines can mobilize from the microvascula-
ture of the nasal polyp various inflammatory cells including neutrophils, macrophages, mast cells, and, particularly,
eosinophils. Tumor necrosis factor-α and IL-1β that may be released by the stimulated epithelial cells can up-regulate
very late activation antigen-4 and vascular cell adhesion molecule (VCAM)-1 that are receptors on eosinophils and
counter-receptors on endothelial cells, respectively, and, in this way, specifically direct eosinophils into the tissue of the
nasal polyp. Finally, interferon (IFN)-γ may be released by the epithelial cell and produce intercellular adhesion mol-
ecule (ICAM)-1 on the epithelial cell, which is a receptor for the rhinovirus as well as for neutrophils. The five stimu-
lators of the epithelial cell as seen at the top of the figure can also induce human leukocyte antigen (HLA)-DR on the
basolateral surface of the cell. This class II antigen can, in turn, up-regulate the immune response for both TH1 and
TH2 lymphocytes, with the final outcome of the production of the typical cytokines for the TH1 lymphocytes (IFN-γ
and IL-2) and for the TH2 lymphocyte (IL-4 and IL-5), which, in turn, can up-regulate the eosinophilia in the nasal
polyp. It is thus suggested that the lateral wall of the nose, either by mucosal contacts or more likely by specific aero-
dynamic airflow, can allow various stimulants to activate the epithelial or constitutive cells of the lateral wall of the nose
to produce a heightened inflammatory response in a genetically predisposed individual for the development of nasal
polyposis.
Cellular Biology of the Immune System 619
numbers of cellular changes. For the purposes of this tions. In continuing our explanation of the role of
discussion, TNF-α, along with IL-1β, which is dis- the eosinophil in nasal polyps, the VLA family of
cussed briefly below, has the effect of increasing the integrins is of most importance. Very late activation
surface receptors on eosinophils, particularly VLA-4, antigen 4 is also the α4, β1 heterodimer on the sur-
and of up-regulating VCAM-1 on the endothelial face of eosinophils. Beta-1 integrins are essentially
cells of blood vessels of nasal polyps. involved in cell–extracellular matrix interactions and
Interleukin-1β is produced by macrophages, β2 subfamily in leukocyte–leukocyte and leuko-
endothelial cells, T and B cells, fibroblasts, epithelial cyte–endothelial cell communications. The soluble
cells, and osteoblasts. The cellular target for IL-1β α4, β1 fusion protein exhibits divalent cation-
includes thymocytes, neutrophils, hepatocytes, dependent binding to VCAM-1. Furthermore, anti-
chondrocytes, muscle cells, endothelial cells, epider- VLA-4 monoclonal antibodies can inhibit eosinophil
mal cells, osteocytes, macrophages, T and B cells, and infiltration in the allergic conjunctivitis model of the
fibroblasts. The biologic activities of IL-1β parallel guinea pig, suggesting that specific monoclonal anti-
those of TNF-α. In regard to chronic inflammation, bodies directed against specific integrins or adhesion
IL-1β also has a powerful effect on the up-regulation cell molecules might be the future for the treatment
of VLA-4 on eosinophils and VCAM-1 on nasal of nasal polyposis. Because VLA-4 is up-regulated on
polyp vascular endothelial cells. It is emphasized that the surface of eosinophils in chronic inflammation, it
both of these cytokines (TNF-α and IL-1β) can be would be interesting to consider the role of antago-
synthesized by constitutive cells of the nasal mucosa, nists to VLA-4, also known as integrin α4, β1. The
including the epithelial cells and the endothelial most advanced in this endeavor is a humanized anti-
cells. Thus, any kind of irritation caused by inflam- α4 antibody, which is in phase 2 clinical trials for
matory mediators or external environmental irri- multiple sclerosis. The first reported small-molecule
tants can stimulate the constitutive cells of the nasal VLA-4 antagonist to advance to clinical trials is cur-
mucosa to produce proinflammatory cytokines, rently in phase 1 as an aerosol for treating asthma.
which, in turn, cause a whole array of inflammatory Thus, the future of the treatment of many chronic
effects in the lateral wall of the nose in the develop- inflammatory diseases, as mentioned above, may be
ment of nasal polyposis. It is to be emphasized that the purification and clinical use of antagonists of var-
the cellular immunology as described in this chapter ious integrins that are up-regulated on the surface of
following stimulation of helper T cells, cytotoxic inflammatory cells.
cells, and B cells will give rise to the synthesis of
cytokines that produce chronic inflammation. Vascular cell adhesion molecule 1 Lymphocytes
migrate from the blood across endothelial cells to
reach foreign substances sequestered in peripheral
INTEGRINS lymphoid organs and inflammatory sites. This
The integrins are the major family of cell-surface migration is inhibited by anti-VCAM-1 or anti-α4
receptors that mediate adhesion to the extracellular integrin, suggesting that VCAM-1 adhesion is
matrix and sometimes cell-to-cell adhesive interac- required for migration. Studies suggest that endothe-
tions.83 These integrin-mediated adhesive interac- lial cells not only are a scaffold for lymphocyte adhe-
tions are involved in the regulation of many cellular sion but also play an active role in promoting
functions, including embryonic development, tumor lymphocyte migration. In addition to lymphocyte
cell growth and metastasis, prolonged cell death, migration, there is abundant evidence to suggest that
homeostasis, inflammation, immune reaction, and TNF-α is a cytokine implicated in the pathogenesis
bone resorption, among other phenomena. Integrins of numerous chronic and acute inflammatory condi-
are composed of α and β transmembrane subunits tions. Furthermore, TNF-α is an effective inducer of
selected from 16 alpha and 8 beta subunits that het- eosinophil accumulation in vivo, and this response
erodimerize to produce more than 20 different recep- appears to be dependent on an interaction between
tors that bind specific ligands. Integrins link to α4 integrins and VCAM-1. Thus, it appears that the
intracellular cytoskeletal complexes and bundles of proinflammatory cytokines are capable of up-regu-
actin filaments. There are many intracellular signal- lating integrins on the surface of eosinophils, partic-
ing pathways activated by integrin-ligand interac- ularly VLA-4, and that this integrin has a specific
620 Ballenger’s Otorhinolaryngology
predilection to adhere to VCAM-1 on the surface of tory cells into sites of the upper respiratory tract. For
vascular endothelial cells. The final phase of the otolaryngologist, knowledge of these cytokines,
eosinophilic migration into the nasal polyp stroma is integrins, and chemokines will be necessary in the
ultimately dependent on the chemokines. future. Although the antibiotic era is still with us,
eradicating chronic inflammatory disease such as
Chemokines The relatively recent appreciation of nasal polyposis, chronic sinusitis, and chronic otitis
a new class of cytokines, the chemokines, has done media with antibiotics probably cannot be accom-
much to enhance our understanding of the extracel- plished. Our knowledge of the molecular biology of
lular signals involved in the movement of various the inflammatory response will require knowledge
populations of white blood cells.84 Investigation of of the biology of the immune system and the inflam-
the molecular underpinnings of chemokine func- matory mediators that are released by immune cells
tion and their involvement in inflammatory such as T cells, B cells, macrophages, fibroblasts, and
processes of all kinds is beginning to yield informa- other cells. It may very well be that the future of clin-
tion about the mechanisms of pathogenesis of a ical medicine will be an understanding of the molec-
number of conditions, as well as provide hope for ular nature of these proteins and glycoproteins
new therapeutic insights. Chemokines share struc- released by the immune cells as well as inflamma-
tural similarities, including four conserved cystine tory cells and to counteract their activity with spe-
residues that form disulfide bonds in the tertiary cific monoclonal antibodies directed against either
structures. Traditionally, the chemokines superfam- the cytokine itself or the receptor for the cytokine
ily has been divided into two subgroups: C-X-C on tissue cells. Ultimately, this will be the future of
(where X is any amino acid) and C-C according to otolaryngology as well as medicine in general.
whether an intervening residue spaces the first two
cysteines in the motif. This structural distinction has
been shown to delineate a general, although not
absolute, distinction in the biologic properties of REFERENCES
these molecules: most C-X-C cytokines are 1. Verdoliva A, Ruvo M, Cassani G, Fassina G. Topo-
chemoattractants for neutrophils but not mono- logical mimicry of cross-reacting enantiomeric pep-
cytes, whereas C-C chemokines appear to attract tide antigens. J Biol Chem 1995;270:30422–7.
monocytes but not neutrophils. There are probably 2. Gowans JL, McGregor DD. The immunological
more structural distinctions that can be made that activities of lymphocytes. Prog Allergy 1965;9:1–78.
may illuminate chemokine function. However, for 3. Greaves MF, Owen JJT, Raff MC. T and B lympho-
our purposes, there are two major chemokines of the cytes: origins, properties and roles in immune
C-C family known as RANTES and eotaxin. responses. Amsterdam: Excerpta Medica; 1973.
Eosinophils are the predominant cell type 4. Thomas Y, Rogozinski L, Chess L. Relationship
recruited in inflammatory reactions in response not between human T cell functional heterogeneity and
only to allergen challenge but also to the up-regula- human T cell surface molecules. Immunol Rev
tion of specific cytokines that are related to TH2 1983;74:113–28.
lymphocytes. The data from many studies suggest 5. Frasca D, Guidi F, Barattini P, Doria G. Haemopoi-
that RANTES and eotaxin induce eosinophil etic reconstitution after sublethal irradiation: com-
transepithelial migration with great potency and parison of the effects of different haemopoietic
efficacy. It is interesting to note that activation of the cytokines on murine lymphocytes and bone marrow
endothelial cells by either TNF-α or IL-1β promotes cells. Br J Haematol 1999;106:317–24.
migration of eosinophils from the vasculature in 6. Grossi CE, Velardi A, Cooper MD. Postnatal liver
conjunction with RANTES and eotaxin. hemopoiesis in mice: generation of pre-B cells, gran-
ulocytes and erythrocytes in discreet colonies. J
Immunol 1985;135:2203–11.
SUMMARY
7. Liu CP, Auberbach R. Ontogeny of murine T cells:
The immune response through both T cells and B thymus-regulated development of T cell receptor-
cells can release a cascade of cytokines that are bearing cells derived from embryonic yoke sack. Eur
responsible for the specific migration of inflamma- J Immunol 1991;21:1849–55.
Cellular Biology of the Immune System 621
8. Yen CJ, Lin Sl, Huang KT, Lin RH. Age-associated 21. Nisonoff A, Hopper JE, Spring SD. The antibody
changes in interferon-gamma and interleukin-4 molecule. New York: Academic Press; 1975.
secretion by purified human CD4+ and CD8+ T 22. Reth M. Antigen receptors on B lymphocytes. Annu
cells. J Biomed Sci 2000;7:317–21. Rev Immunol 1992;10:97–122.
9. Ada GL, Nossal G. The clonal selection theory. Sci 23. DeFranco AL. Structure and function of the B cell
Am 1987;257:62–9. antigen receptor. Annu Rev Cell Biol 1993;9:
10. Siiman O, Burshteyn A. Cell surface receptor-anti- 377–410 .
body association constants and enumeration of 24. Ohno S. The origin of immunoglobulins and T-cell
receptor sites for monoclonal antibodies. Cytometry receptors is likely to be the cell death sensor of
2000;40:316–26. macrophages. Res Immunol 1996;147:247–52.
11. Claeys S, Cuvelier C, Quatacker J, Van Cauwenberg P. 25. Edelman GM. The structure and function of anti-
Ultrastructural investigation of M-cells and lym- bodies. Sci Am 1970;223:34–42.
phoepithelial contacts in nasopharyngeal associated 26. Porter RR. Structural studies of immunoglobulins.
lymphoid tissue (NALT). Acta Otolaryngol Suppl Science 1973;180:713–6.
(Stockh) 1996;523:40–2. 27. Kabat EA. Structural concepts in immunology and
12. Bernstein JM, Gorfien J, Brandtzaeg P. The immuno- immunochemistry. 2nd ed. New York: Holt, Rine-
biology of the tonsils and adenoids. In: Ogra PL, hart and Winston; 1976.
Lamm ME, McGhee JR, et al, editors. Mucosal 28. Brandtzaeg P, Farstad IN. The human mucosal B-cell
immunology. 2nd ed. San Diego: Academic Press; system. In: Ogra PL, et al, editors. Mucosal immunology,
1999. p. 1339–62. 2nd ed. San Diego: Academic Press; 1999. p. 439–68.
13. Reinherz EL, Schlossman SF. The differentiation and 29. Koshland ME. The coming of age of the im-
function of human lymphocytes. Cell 1980;19:821–7. munoglobulin J chain. Annu Rev Immunol 1985;
14. Whyte A, Licence ST, Robinson MK, VanderLienden 3:425–54.
K. Lymphocyte subsets and adhesion molecules in 30. Muller-Eberhard HJ. Molecular organization and
cutaneous inflammation induced by inflammatory function of the complement system. Annu Rev
antagonists: correlation between E-selectin and Biochem 1988;57:321–48.
gamma delta CtR+ lymphocytes. Lab Invest 31. Burton DR, Woof JM. Human antibody effector
1996;75:439–49. function. Adv Immunol 1992;51:1–84.
15. Butcher EC, Williams M, Youngman K, et al. Lym- 32. Kraehenbuhl JP, Neutra MR. Transepithelial trans-
phocyte trafficking and regional immunity. Adv port and mucosal defense. II: secretion of IgA.
Immunol 1999;72:209–53. Trends Cell Biol 1992;2:170–4.
16. Bernstein JM. The immunobiology of the tonsils and 33. Metzger H. The receptor with high affinity for IgE.
adenoids. In: Johnson J, Blitzer A, Ossoff R, Thomas Immunol Rev 1992;125:37–48.
JR, editors. Instructional courses. St. Louis: Mosby 34. VanderKeyl H, Gellad ZF, Owen JA. Disparity in the
Yearbook; 1990. p. 3–20. kinetics of onset of hypermutation in immunoglob-
17. Jia GQ, Gonzalo JA, Hidlalgo A, et al. Selective ulin heavy and light chains. Immunol Cell Biol
eosinophil transendothelial migration triggered by 2000;78:224–37.
eotaxin via modulation of Mac-1/ICAM-1 and VLA- 35. Reid KB. Structure-function relationships of the
4/VCAM-1 interactions. Int Immunol 1999;11:1–10. complement components. Immunol Today 1989;10:
18. Harris DE, Cairns L, Rosen FS, Borel Y. A natural 177–80.
model of immunological tolerance. Tolerance to 36. Tomlinson S. Complement defense mechanisms.
murine C5 is mediated by T cells, and antigen is Curr Opin Immunol 1993;5:83–9.
required to maintain unresponsiveness. J Exp Med 37. Reid KB. Activation and control of the complement
1982;156:567–84. system. Essays Biochem 1986;22:27–68.
19. Lindstrom J. Immunobiology of myasthenia gravis, 38. Bernstein JM, Faden HS, Loos BG, et al. Recurrent
experimental autoimmune myasthenia gravis, and otitis media with non-typable Haemophilus influen-
Lambert-Eaton syndrome. Annu Rev Immunol zae: the role of serum bactericidal antibody. Int J
1985;3:109–32. Pediatr Otorhinolaryngol 1992;23:1–13.
20. Davies DR, Metzger R. Structural basis of antibody 39. Bernstein JM, Reddy MS, Scannapieco FA, et al. The
function. Annu Rev Immunol 1983;1:87–118. microbial ecology and immunology of the adenoid:
622 Ballenger’s Otorhinolaryngology
implications for otitis media. Ann N Y Acad Sci 54. Davis MM. T cell receptor gene diversity and selec-
1997;830:19–31. tion. Annu Rev Biochem 1990;59:475–96.
40. Bernstein JM, Scheerer R, Shoenfeld E, Albini B. 55. Swain SL, Bradley LM, Croft M, et al. Helper T-cell
The distribution of immunocompetent cells in the subset: phenotype, function and the role of lym-
compartments of the palatine tonsils in bacterial phokines in regulating their development. Immunol
and viral infections of the upper respiratory tract. Rev 1991;123:115–44.
Acta Otolaryngol Suppl (Stockh) 1988;454: 56. Rammensee H, Falk K, Rotzschke O. MHC mole-
153–62. cules as peptide receptors. Curr Opin Immunol
41. Capra JD, Edmundson AB. The antibody combining 1993;5:35–44.
site. Sci Am 1977;236:50–9. 57. Auffray C, Strominger JL. Molecular genetics of the
42. Tomlinson S. Complement defense mechanisms. human histocompatibility complex. Adv Hum Genet
Curr Opin Immunol 1993;5:83–9. 1987;15:197–247.
43. Wu TT, Kabat EA. An analysis of the sequences of 58. Moller G, editor. Molecular genetics of class I and
the variable regions of Bence Jones proteins and class II MHC antigens. Immunol Rev 1985;43:84,
myeloma light chains and their implications for 85.
antibody complementarity. J Exp Med 1970;132: 59. Matsumura M, Fremont DH, Peterson PA, Wilson
211–50. IA. Emerging principles for the recognition of pep-
44. Davies DR, Padlan EA, Sheriff S. Antibody-antigen tide antigens by MHC class I molecules. Science
complexes. Annu Rev Biochem 1991;59:439–73. 1992;257:927–34.
45. Sakano H, Rogers JH, Huppi JK, et al. Domains and 60. Johnson DR, Mook-Kanamori B. Dependence of ele-
a hinge region of an immunoglobulin heavy chain vated human leukocyte antigen class I molecule
encoded in separate DNA segments. Nature expression on increased heavy chain-light chain
1979;277:627–33. (beta 2-microglobulin) transporter associated with
46. Fitzsimmons SP, Rotz BT, Shapiro MA. Asymmetric antigen processing, tapasin, and peptide. J Biol
contribution to Ig repertoire diversity by V kappa Chem 2000;275:16643–9.
exons: differences in the utilization of the V kappa 61. Bach FH, Sacks DH. Transplantation immunology.
10 exons. J Immunol 1998;161:290–300. N Engl J Med 1987;317:489–92.
47. Leder P. The genetics of antibody diversity. Sci Am 62. Janeway CA. The T cell receptor as a multi-compo-
1982;246:72–83. nent signaling machine: CD4/CD8 co-receptors and
48. Hozumi N, Tonegawa S. Evidence for somatic CD45 and T cell activation. Annu Rev Immunol
rearrangement of immunoglobulin genes coding for 1992;10:645–74.
variable and constant regions. Proc Natl Acad Sci 63. Townsend AR. Recognition of influenza virus pro-
U S A 1976;73:3628–32. teins by cytotoxic T lymphocytes. Immunol Res
49. Nadal DE, Soh N, Schlapfer E, et al. Distribution 1987;6:80–100.
characteristics of immunoglobulin-secreting cells in 64. De Maeyer E, De Maeyer-Guignar J. Interferon-γ.
the adenoids. Relationship to age and disease. Int J Curr Opin Immunol 1992;4:321–6.
Pediatr Otorhinolaryngol 1992;24:121–30. 65. Yagita H, Nakata M, Kawasaki A, et al. Role of per-
50. Disis ML, Schiffman K, Gooley TA, et al. Delayed- forin in lymphocyte-mediated cytolysis. Adv
type hypersensitivity response is a predictor of Immunol 1992;51:215–42.
peripheral blood T cell immunity after HER-2/new 66. Kawasaki A, Shinkai Y, Yagita H, Okumura K.
peptide immunization. Clin Cancer Res 2000;6: Expression of perforin in murine natural killer cells
1347–50. and cytotoxic T lymphocytes in vivo. Eur J Immunol
51. Rothenberg EV. Stepwise specification of lympho- 1992;22:1215–9.
cyte development lineages. Curr Opin Genet Dev 67. Koyama AH, Fukumori T, Fujita M, et al. Physiolog-
2000;10:370–9. ical significance of apoptosis in animal virus infec-
52. Kupfer A, Singer SJ. Cell biology of cytotoxic and tion. Microb Infect 2000;2:1111–7.
helper T-cell function. Annu Rev Immunol 1989; 68. Tangri S, Brossay L, Burdin N, et al. Presentation of
7:309–37. peptide antigens by mouse CD1 requires endosomal
53. Marrack P, Kappler J. The T cell receptor. Science localization and protein antigen processing. Proc
1987;238:1073–9. Natl Acad Sci U S A 1998;95:14314–9.
Cellular Biology of the Immune System 623
69. Schwartz RH. Co-stimulation of T lymphocytes: the Synergistic effects of interleukin-4 or interleukin-13
role of CD28, CTLA-4 and B7/BB1 in interleukin-2 and tumor necrosis factor-α on eosinophil activa-
production and immunotherapy. Cell 1992;71: tion in vitro. Am J Respir Cell Mol Biol 1999;20:
1065–8. 474–80.
70. Taniguchi T, Minami Y. The IL-2/IL-2 receptor sys- 78. Bocchino V, Bertoreli G, D’Ippolito R, et al. The
tem: a current overview. Cell 1993;73:5–8. increased number of very late activation antigen-4-
71. Noelle RJ, Ledbetter JA, Aruffo A. CD40 and its lig- positive cells correlates with eosinophils and severity
and, an essential ligand-receptor pair for thymus of disease in the induced sputum of asthmatic
dependent B-cell activation. Immunol Today 1992; patients. J Allergy Clin Immunol 2000;105:65–70.
13:431–3. 79. Lee CH, Lee KS, Rhee CS, et al. Distribution of
72. Moller G, editor. IL-4 and IL-5: biology and genetics. RANTES and interleukin-5 in allergic nasal mucosal
Immunol Rev 1988;105:102–22. nasal polyps. Ann Otol Rhinol Laryngol
73. Bar-Or RL. Feedback mechanisms between T helpers 1999;108:594–8.
cells and macrophages in the determination of the 80. Jacoby DB, Ueki IF, Widdicombe JH, et al. Effect of
immune response. Math Biosci 2000;163:353–8. human eosinophil major basic protein on ion trans-
74. Jinquan T, Quan S, Jacobi HH, et al. Cutting edge: port in dog tracheal epithelium. Am Rev Respir Dis
expression of the NF of activated T cells in 1988;137:13–6.
eosinophils: regulation by IL4 and IL5. J Immunol 81. Kronenwett R, Martin S, Haas R. The role of
1999;163:21–4. cytokines and adhesion molecules for mobilization
75. Sgagias MK, Nieroda C, Yannelli JR, et al. Upregula- of peripheral blood stem cells. Stem Cells 2000;
tion of DF3, in association with ICAM-1 and MHC 18:320–30.
class II by interferon-γ in short-term human mam- 82. Hamblin AS. Cytokines and cytokine receptors.
mary carcinoma cell cultures. Can Biother Radio London: IRL Press, Oxford University in association
Pharm 1996;11:177–85. with the British Society for Immunology; 1993.
76. Jahnsen FL, Haraldsen G, Aanesen JP, et al. 83. Lustig L, Denduchis B. Integrins: a family of cell
Eosinophil infiltration is related to increased expres- adhesion receptors. Medicina 1993;53:357–63.
sion of vascular cell adhesion molecule-1 in nasal 84. Schall TJ, Bacon KB. Chemokines, leukocyte traf-
polyps. Am J Respir Cell Mol Biol 1995;12:624–32. ficking and inflammation. Curr Opin Immunol
77. Luttmann W, Matthiesen T, Mattys H, Virchow JC. 1994;6:865–73.
CHAPTER 29
Acquired immune deficiency syndrome (AIDS) has sub-Saharan Africa and Southern and Southeast Asia.
emerged as one of the most extraordinary diseases in Less than 3% of the HIV infected worldwide reside in
human history. We have seen the unfolding of a North America. Since the start of the epidemic, more
medical mystery in which an apparently new disease than 12 million persons have died of AIDS-related
has appeared, first reported in the United States in complications worldwide. Of the 16,000 new cases of
1981, and has since become a major worldwide epi- HIV infection that are estimated to occur each day
demic. Acquired immune deficiency syndrome is worldwide, more than 40% are among women, more
caused by human immunodeficiency virus (HIV). than 50% are among 15 to 24 year olds, and 10% are
Human immunodeficiency virus infection of among children less than 14 years old.4
macrophages, monocytes, and CD4 (helper) T lym- Human immunodeficiency virus transmission
phocytes leads to a cell-mediated immune deficiency occurs by unprotected heterosexual or homosexual
that predisposes to a constellation of opportunistic sexual contact, use of HIV-infected contaminated
infections and malignancies.1,2 needles, infusion of contaminated blood and blood
More than 1,200,000 cases of AIDS have been products, or from mother to child in utero, perina-
reported in the United States since 1981, and as tally or through breast-feeding. The patterns of
many as 900,000 Americans are estimated to be liv- transmission vary from country to country.1,5 In
ing with HIV infection. The epidemic is growing sub-Saharan Africa and Southern and Southeast
most rapidly among minority populations and is a Asia, heterosexual transmission is the predominant
leading killer of African American males. According mode of transmission, although intravenous drug
to the US Centers for Disease Control and Preven- use is a major factor in India and parts of Southeast
tion (CDC), the prevalence of AIDS is six times Asia. In Northern Europe, homosexual transmission
higher in African Americans and three times higher is most common, whereas intravenous drug use is
in Hispanics than among whites.3 the major risk factor in Southern Europe, particu-
Acquired immune deficiency syndrome has larly Spain and Italy. In the United States, homosex-
had a significant impact on the practice of otolaryn- uals were the major risk group at the outset of the
gology. The fact that many patients originally pre- epidemic, but over the past several years, the rate of
sented with physical findings in the head and neck increase in new cases has been greatest among
region, especially during the 1980s, required a high women, heterosexuals, and minorities.
level of vigilance for detecting these findings as man- There are significant racial and socioeconomic
ifestations of HIV infection. Implementation of differences in the distribution of HIV/AIDS cases
measures for handling instruments in the office and among the various risk groups. Whites predominate
operating room emerged as part of the universal among homosexuals with HIV, whereas African
precautions that were promulgated as a way of con- Americans and Hispanics are disproportionately
trolling spread of the infection. represented among HIV positives, with injection-
drug use as a risk factor. Poverty has been shown to
be independently associated with higher rates of
EPIDEMIOLOGY HIV/AIDS, and racial minorities are disproportion-
To date, an estimated 36 million persons are living ately represented among those living below the
worldwide with HIV/AIDS. Of these, most reside in poverty line.
624
Acquired Immune Deficiency Syndrome 625
gp120
Lipid
gp41 RNA Membrane
p24
p17
viral core contains four proteins: the p24 capsid pro- second DNA strand, complementary to the first, is
tein, the p17 matrix protein, and the p6 and p7 synthesized. Viral encoded integrase enzyme then
nucleocapsid proteins. The core also contains two mediates the incorporation of the double-stranded
copies of single-stranded ribonucleic acid (RNA) DNA into the host genome. Transcription of RNA
and three viral enzymes: reverse transcriptase, inte- from this proviral DNA provides the coding for viral
grase, and protease. polyproteins, which are cleaved by viral proteins to
Human immunodeficiency virus infects cells produce the structural proteins and enzymes, which
by binding to a combination of cell-surface recep- are eventually incorporated into progeny virus,
tors. The CD4 receptor is a high-affinity target for which bud off the infected cell.
binding by glycoprotein 120, which is necessary but
not sufficient for binding of the virion to the cell.
CD4 receptors are expressed on T lymphocytes,
CLINICAL COURSE
macrophages, and, to a lesser extent, a variety of The median time from infection with HIV to the
somatic cells. Some strains of HIV preferentially development of AIDS-related symptoms among
infect CD4 (helper) T lymphocytes, whereas others untreated patients is approximately 10 years, with a
preferentially infect macrophages. This preference or wide variation in time to progression. Approxi-
tropism is mediated by the differential expression of mately 10% of HIV-infected persons progress to
chemokine receptors on T cells and macrophages. AIDS within the first 2 to 3 years following infec-
Human immunodeficiency virus strains trophic for tion. In contrast, 5 to 10% of patients are so-called
activated T lymphocytes bind by the CD4 receptor nonprogressors, having stable CD4 cell counts after
and CXCR4 chemokine coreceptor. Macrophage 15 or more years of follow-up. Factors that deter-
tropic strains bind by the CD4 receptor and the mine the rate of progression of untreated disease
CCR5 chemokine receptor. include patient age (more rapid progression over age
After binding to the cell receptors, the HIV 40 years), genetic differences, the virulence of the
envelope fuses to the cell membrane, and the virus is infecting strain, the viral load that is directly pro-
internalized (Figure 29–2). Viral replication begins portional to the rate of decline of the CD4 lympho-
with the viral enzyme reverse transcriptase mediat- cyte count, and co-infection with other microbes
ing the synthesis of deoxyribonucleic acid (DNA) (eg, hepatitis C). The onset of clinical disease is
complementary to the viral RNA genome. This related to the decline in immune competence as
DNA-RNA heteroduplex then dissociates, and then a CD4 lymphocytes are depleted.1–3 The most signifi-
Acquired Immune Deficiency Syndrome 627
Cellular DNA
Unintegrated
Circular DNA
Unintegrated
Integrated Linear DNA
Proviral DNA
Reverse
Transcriptase Genomic CD4 Molecule
Genomic RNA RNA
mRNA gp120
Budding HIV
Protein synthesis,
Mature HIV Viron processing and assembly
FIGURE 29–2. Human immunodeficiency virus (HIV) life cycle: on the right side of the diagram, the glycoprotein (gp)
120 has tropism for the CD4 molecule. The HIV genomic ribonucleic acid (RNA) is uncoated and enters the cell. The
genomic RNA is transcribed by the reverse transcription enzyme to double-stranded deoxyribonucleic acid (DNA).
The DNA translocates to the nucleus, where it becomes integrated into the cellular DNA by the enzyme integrase as a
provirus. It can remain dormant for years or be activated to transcribe messenger and genomic RNA of the virus. The
virus is assembled at the periphery and buds off as a mature HIV variant. mRNA = messenger ribonucleic acid.
Adapted from Fauci AS. The human immunodeficiency virus: infectivity and pathogenesis. Science 1988;239:617.
cant complications, that is, opportunistic infections in the general population is high. Even in developed
and malignancies, occur after reduction of CD4 cell countries, where background levels of TB are low,
below 200/mm3. HIV has caused increased rates and atypical presen-
tations of TB. Widespread use of effective prophy-
laxis against such agents as Pneumocystis carinii and
OPPORTUNISTIC INFECTIONS MAC has reduced the risk of these infections in
Opportunistic infections have remained the proxi- developed countries.
mate cause of death for nearly all AIDS patients.
Advances in prophylaxis have decreased the inci-
dence of Pneumocystis, Toxoplasma, Mycobacterium
ANTIRETROVIRAL THERAPY
avium-intracellulare complex (MAC), Cryptococcus, Recommendations regarding the use of antiviral
and other opportunistic infections and consequently drugs in HIV are in flux. When and what to initiate,
their contribution to morbidity and mortality.1 when to change regimens, and how to minimize the
Patterns of specific opportunistic infections development of resistance and cross-resistance are
vary geographically, among risk groups, and as a continually being re-evaluated. Clearly, monother-
result of medical interventions. In the United States apy results in resistance and loss of efficacy as a
and Europe, over 90% of AIDS patients with result of the huge viral burden, short viral half-life,
Kaposi’s sarcoma are homosexual or bisexual men, and propensity to mutate.
probably because they are co-infected with human Viral loads are critical in determining the effi-
herpesvirus 8, a newly identified viral cofactor (with cacy of regimens; the goal is to make all viral loads
HIV) for Kaposi’s sarcoma. Toxoplasmosis and undetectable because high loads drive CD4 loss and
tuberculosis (TB) are more common in tropical ultimate immune suppression. The current recom-
areas, where the prevalence of latent infections with mendation is to initiate a three-drug regimen in
Toxoplasma gondii and Mycobacterium tuberculosis patients with a detectable viral load of over 5,000 to
628 Ballenger’s Otorhinolaryngology
10,000 HIV RNA copies per milliliter, regardless of HIV reverse transcriptase enzyme competitively and
CD4 count. This regimen offers sustained viral sup- act as a chain terminator of DNA synthesis. Non-
pression compared with double- and single-drug nucleoside reverse transcriptase inhibitors directly
regimens. bind to the reverse transcriptase enzyme at sites sep-
Triple combinations containing a protease arate from the nucleoside-binding site. In general,
inhibitor are considered the most potent of all regi- viral resistance to these drugs occurs quickly, and
mens. The difficulty with multidrug therapy is that they should not be used as monotherapy except in
the patient may not fully comply because of the specific cases.
number of pills and adverse effects. Even minimal Protease inhibitors are the most potent class
noncompliance causes drug resistance and loss of of antiviral drugs; they target the viral proteinase
efficacy. When changing a failing regimen, two new enzyme. Inhibition of viral protease prevents cleav-
drugs (preferably three new drugs) should be age of an important structural polyprotein that
started. All regimens must be individualized, and, results in noninfectious viral particles. Primary and
occasionally, when patients are unable to comply accessory mutations of the gene encoding the viral
with the rigors of three drugs, double therapy is proteinase lead to cross-resistance between this
preferable to no therapy. The classes of anti-HIV class of drugs. The only well-studied dual-protease
drugs include reverse transcriptase inhibitors regimen is ritonavir and saquinavir, which has
(nucleoside and non-nucleoside) and protease demonstrated significant, sustained viral load
inhibitors (Table 29–1).9 reduction and CD4 gain. Some in vitro data suggest
Nucleoside reverse transcriptase inhibitors are that saquinavir and indinavir are antagonists.
phosphorylated to active metabolites that compete Other combinations of multiple protease inhibitors
for incorporation into viral DNA. They inhibit the are under study. The protease inhibitors are metab-
*Cost to the pharmacist for 30 days’ treatment, based on wholesale price (AWP) listings, June 1999 in US dollars.
Adapted from Abramowicz M.9
Acquired Immune Deficiency Syndrome 629
olized through cytochrome P-450, and all con- common in HIV patients and is probably a reflec-
comitant drugs should be reviewed for potential tion of the higher incidence of viral infections.
interactions.
SKIN
OTORHINOLARYNGOLOGIC Dermatologic involvement in the head and neck
MANIFESTATIONS also occurs quite commonly.12 Seborrheic dermati-
tis presents with erythema and scaling of the skin
Patients who are HIV positive can acquire otorhino-
of the forehead and the malar area, although it may
laryngologic diseases similar to those experienced
be more generalized. Treatment is with topical
by patients without HIV infection. However, the
corticosteroids and topical antifungal agents.
patient may experience unusual presentations and
Eosinophilic folliculitis or “itchy bump disease”
recurrent or refractory disease. The evaluation and
presents as an intensely pruritic papular rash,
treatment of patients with HIV-related head and
which can occur on the head and neck but more
neck disease frequently require an interdisciplinary
approach, including the input of the infectious dis- commonly involves the upper back, upper chest,
eases specialist, oncologist, ophthalmologist, derma- and proximal limbs. The treatment of this condi-
tologist, dentist, and oral surgeon. tion of unknown cause is difficult. Topical or sys-
temic corticosteroids, phototherapy, and high-dose
itraconazole have all been demonstrated to provide
EAR relief for some patients.
Acute bacterial or serous otitis media is frequently Skin diseases owing to virus include der-
encountered among HIV-infected individuals. 10 matomal varicella-zoster (shingles), herpes simplex,
Patients present with aural fullness, hearing loss, and molluscum contagiosum. Herpes zoster is fre-
and, occasionally, otorrhea. The clinical response quently an early indication of underlying HIV infec-
to appropriate therapy with antibiotics and decon- tion. In patients with well-preserved immune
gestants is in part dependent on the patient’s function, the natural history of the infection is sim-
underlying immune status. Patients with well-pre- ilar to that of non–HIV-positive persons. The
served cell-mediated immune function as meas- painful vesicular/pustular lesions usually remain
ured by the CD4 cell count are more likely to localized to a single dermatome. The time course
respond normally, whereas those with impaired from initial presentation as a papule to crusting and
immunity more frequently experience refractory healing is 2 to 3 weeks. In patients with significant
or recurrent disease requiring tympanostomy tube immune deficiency, the risk of dissemination is
placement. increased, and the duration of acute illness may be
Otitis externa is caused by the same bacterial prolonged. Complications of herpes zoster include
pathogens as in the non–HIV-positive population.11 Ramsay Hunt syndrome (facial palsy owing to facial
Unusual conditions, which may involve the auricle, nerve involvement); ophthalmic involvement
pinna, and external auditory canal, are Kaposi’s sar- including keratitis, iritis, uveitis or retinitis caused
coma, molluscum contagiosum, herpes simplex by involvement of the ophthalmic division of the
virus (HSV), varicella-zoster virus, and seborrheic trigeminal nerve; and postherpetic neuralgia, which
dermatitis. Diagnosis of these conditions is usually may cause prolonged or permanent dysesthesias.
clinical, and treatment is specific to the etiology. The diagnosis of shingles is made clinically in most
Sensorineural hearing loss can occur in up to cases. Definitive diagnosis by Tzanck preparation of
69% of AIDS patients; cytomegalovirus (CMV) is vesicular fluid demonstrating multinucleated giant
often implicated because CMV inclusion-bearing cells or culture of the fluid is rarely necessary. Treat-
cells can sometimes be found in cranial nerve VIII in ment is indicated for all patients with immune defi-
the internal auditory canal, in the cochlea, or in ciency to hasten crusting and healing, reduce
vestibular endolymphatic epithelium. Other causes infectivity, and prevent dissemination. Early treat-
of the hearing loss may include primary cochlear ment, that is, within 24 to 48 hours after the onset of
effects of the HIV virus, ototoxic drugs, or demyeli- rash, with systemic antiviral agents has been shown
nation in the auditory tract.12 Facial paralysis is to decrease the risk of postherpetic neuralgia. Recur-
630 Ballenger’s Otorhinolaryngology
rences of shingles are uncommon, and thus routine testing may be useful to identify allergens that can
use of chronic suppressive therapy, is not indicated. be avoided. Desensitization shots are generally
Herpes simplex presents with characteristic avoided, however, owing to the perceived risks of
pruritic or painful papules of the vermilion border of CD4 cell activation that may lead to increased HIV
the lip. Over a period of 7 to 10 days, the lesions replication.
progress through vesicular, pustular, crusting, and
ulcerative stages before spontaneously healing. In
patients with advanced cell-mediated immune
ORAL CAVITY AND OROPHARYNX
deficiency, the ulcerative lesions may persist and Oral candidiasis is one of the most common head
extend widely unless treated with systemic antiviral and neck problems encountered in HIV-infected
agents. Recurrences of orolabial herpes are com- patients. It may present with tender, erythematous
mon, but chronic suppression should be limited to mucosa of the tongue, palate, and other mucosal
those patients who have demonstrated a pattern of surfaces or with white plaques or pseudomem-
frequent recurrences. branes, which can be readily scraped to reveal an
erythematous base. Diagnosis is usually made clini-
cally. A microbiologic diagnosis can be made with
NOSE KOH smear and/or culture of the exudate. Treat-
Externally, herpex simplex can often be seen involv- ment with topical agents such as nystatin swish or
ing the nasal vestibule.12 The infection presents as a clotrimazole troches is usually effective for oral dis-
chronic nonhealing inflammatory process that ease. With more extensive disease or esophageal
extends onto the septum, the nasal alae, and, ulti- involvement associated with odynophagia and dys-
mately, the upper lip and face. Again, early culture phagia, systemic therapy with an absorbable agent
for diagnosis and treatment with appropriate antivi- such as ketoconazole, fluconazole, or itraconazole is
ral agents will show substantial improvement. indicated.
Chronic rhinitis with nasal crusting and dry- Angular cheilitis presents as erythema and fis-
ness is particularly common among patients with sures at the corner of the mouth and may be caused
HIV infection. Although no specific treatment has by Candida species, herpes simplex, or vitamin
been routinely successful, administration of guaife- deficiency. Angular cheilitis responds to specific
nesin (1,200 mg twice daily) and humidification are therapy.
useful. There are multiple causes for oral ulcerations
Sinusitis occurs with increasing frequency as including HSV, CMV, and aphthous ulcers. The
the CD4 cell count decreases. The bacteriology of small, painful, clustered ulcers caused by herpes sim-
acute sinusitis in patients with a CD4 cell count plex can occur on any mucosal surface and are usu-
above 200/mm 3 is similar to that in non-HIV ally self-limited. Treatment with systemic acyclovir,
patients. Treatment for these patients is directed valacyclovir, or famciclovir is indicated for nonre-
against Streptococcus pneumoniae and Haemophilus solving ulcers, extensive ulceration, and chronic
influenzae. In patients with more severe immune suppression of frequent recurrences.
deficiency, microorganisms such as Pseudomonas Cytomegalovirus ulcers are generally fewer in
aeruginosa, Staphylococcus aureus, fungal patho- number and larger in diameter than herpes simplex
gens, and other opportunists become more impor- or aphthous ulcers. They are usually associated with
tant. Empiric broad-spectrum antibiotic therapy is systemic CMV infection in patients with profound
indicated in those patients with more advanced cell-mediated immune deficiency (CD4 < 50 cells/
immune deficiency.13 Paranasal sinus puncture may mm3). Diagnosis is by biopsy and culture of the
be necessary for accurate microbiologic diagnosis ulcer. Treatment is with systemic antiviral therapy,
in a patient who fails empiric therapy. and ganciclovir, foscarnet, or cidofovir is always
Allergic rhinitis has been shown to occur sec- indicated. Because of the high rate of recurrence,
ondary to eosinophilia and an increase in long-term suppressive therapy is required unless
immunoglobulin E levels from HIV.12 Treatment immune function improves with use of highly anti-
with topical nasal corticosteroids and second-gen- retroviral therapy. Antiviral therapy for CMV can
eration antihistamines alleviates symptoms. Allergy be safely withdrawn when patients have stable
Acquired Immune Deficiency Syndrome 631
(> 6 months) immune reconstitution with CD4 infections (histoplasmosis, coccidiomycosis, asper-
counts above 100 cells/mm3. gillosis, and candidiasis) have been described in the
Recurrent aphthous ulcers are common in larynx of HIV-infected patients.14 Diagnosis is often
persons with HIV infection at all stages of disease. made after laryngoscopy with biopsies and cultures.
The lesions range in size from 1 to 2 mm shallow
ulcerations on mucosal surfaces to giant oral ulcers
as large as 2 to 3 cm. Diagnosis is usually clinical,
ESOPHAGUS
but biopsy and cultures may be indicated in some The esophagus is a common target in patients with
patients to exclude HSV, CMV, or lymphoma. Treat- HIV disease, with odynophagia and/or dysphagia
ment with topical corticosteroids or in more exten- being the most frequent presenting complaints.
sive, posterior pharyngeal, or esophageal disease Candida is the most common cause of these symp-
with systemic corticosteroids is usually effective in toms. Esophageal candidiasis is usually but not
decreasing pain and promoting healing. Cautery invariably associated with oral candidiasis. Other
with silver nitrate can provide immediate pain relief causes include HSV, CMV, and aphthous ulcera-
and speed healing. Thalidomide has recently been tions. The diagnosis of Candida esophagitis can be
approved for use in treating aphthous ulcers. reliably inferred by the presence of oral thrush and
Good oral hygiene and regular dental care are odynophagia/dysphagia. An empiric trial of therapy
important in patients with HIV. Gingivitis and peri- with systemic antifungal agents is indicated. If the
odontal disease are more prevalent in HIV patients, symptoms fail to improve within several days, endo-
particularly with advanced disease. Linear gingival scopic evaluation is indicated to exclude viral or
erythema occurs with or without significant plaque aphthous esophagitis or other less common condi-
accumulation. Periodontal disease occurs in up to tions, including severe reflux esophagitis, Kaposi’s
50% of patients with advanced HIV disease. The sarcoma, lymphoma, and tubercular and MAC
periodontal disease may be severe with resultant hal- esophagitis. Endoscopic biopsy and cultures provide
itosis, regression of the gingivae, and loosening and definitive diagnosis. Therapy is directed at the spe-
loss of the teeth. Therapy must be aggressive and cific cause.
includes débridement, topical antiseptics, and sys-
temic antibiotics.
The Epstein-Barr virus is the etiologic agent of
NECK
a unique oral finding in patients with HIV, hairy Lymphadenopathy of the head and neck is most
leukoplakia. This condition consists of white patches commonly reactive secondary to HIV itself. Gener-
usually involving the lateral borders of the tongue. It alized lymphadenopathy is a finding in acute retro-
often manifests early in the course of HIV disease viral infection and is associated with fever and other
and may be the initial clue to underlying HIV infec- systemic symptoms. Patients in the chronic phase of
tion. The diagnosis is clinical. Unlike candidiasis, the HIV infection may be asymptomatic, with the
white plaques cannot be scraped from the mucosa. exception of progressive generalized lymphadenopa-
Treatment is not indicated except for cosmetic rea- thy. This reactive lymphadenopathy is generally
sons. Oral and topical acyclovir have been shown to symmetric and does not require biopsy for confir-
cause regression of leukoplakia, although recurrence mation of its benign nature. Other conditions that
is invariable. may present with lymphadenopathy of the head and
Warts on mucosal surfaces caused by human neck include malignancies such as lymphoma,
papillomavirus can present as plaque-like or verru- Kaposi’s sarcoma, squamous cell carcinoma, and a
cous lesions. The diagnosis is usually clinical with variety of infections, including those owing to
biopsy confirmation. Treatment is local excision/ Mycobacterium tuberculosis, MAC, S. aureus, cat-
ablation. scratch disease, and Treponema pallidum. In these
instances, lymphadenopathy is commonly asymmet-
ric and associated with other findings such as fever,
LARYNX weight loss, cutaneous findings (Kaposi’s sarcoma,
The larynx is an often difficult area to evaluate and impetigo), or oropharyngeal disease (lymphoma,
accurately diagnose. Viral (HSV, CMV) and fungal squamous cell carcinoma).
632 Ballenger’s Otorhinolaryngology
Upper respiratory infection (URI) is one of the most common colds are caused by rhinoviruses of the
common ailments for which patients seek medical family Picornaviridae, of which there are more than
care. The importance of understanding the causes of 100 serotypes. Makela and coworkers, using viral
these infections is evident. This chapter is divided culture and polymerase chain reaction (PCR) tech-
into five sections. The first reviews pathogens of niques, detected rhinoviruses in approximately half
URIs according to anatomic sites. The following sec- of 200 young adults with common colds over a 10-
tions cover those viral, bacterial, fungal, and miscel- month period.2 Rhinovirus infections occur year
laneous infections that are of special interest or round, with peaks in the early spring and fall months
importance. in the temperate zones and during the rainy periods
in the tropics. Coronaviruses account for about 10%
of infections. At least two serotypes cause URIs, and
CAUSES BY ANATOMIC SITE re-infections are common. Parainfluenza viruses and
The pathogens principally responsible for URIs are the respiratory syncytial virus are members of the
listed by anatomic site in Table 30–1. This listing is Paramyxoviridae family. They are primarily known
not intended to be exhaustive but is limited to causes as causes of lower respiratory tract infections but
that are predominant for each site. also account for a proportion of common colds. Re-
infections occur throughout life. Influenza viruses
usually produce a primary influenza-like illness.
COMMON COLD However, subsequent infections with the same or a
The common cold is an acute, self-limited viral dis- similar serotype may result in common cold symp-
ease characterized by rhinorrhea and nasal conges- toms. Adenoviruses are an important cause of upper
tion, sometimes accompanied by throat irritation, and lower respiratory tract infections, including the
fever, and malaise. Symptoms generally begin 1 to 2 common cold. Specific serotypes are associated with
days after the onset of viral infection and peak at 2 pharyngoconjunctival fever and epidemic kerato-
to 4 days. Cough is associated with approximately conjunctivitis. Adenoviruses are also important
30% of colds and typically does not become the causes of pharyngitis and pneumonia, especially in
most bothersome symptom until the fourth or fifth military recruits.
day of illness, when nasal symptoms decrease. The Most of the information regarding the patho-
average incidence of the common cold in preschool genesis of the common cold is derived from studies
children is five to seven per year. The incidence of experimentally induced rhinovirus infections.
decreases with age and averages two to three per year The rhinovirus is a nonenveloped 30 nm ribonucleic
by adulthood.1 Infection is spread by direct contact acid (RNA) virus characterized by a single positive
with virus-contaminated respiratory secretions. stranded genome not only acting as a template for
Inoculation occurs at the nasal mucosa and, per- RNA synthesis but also encoding for a single
haps, the conjunctiva. polypeptide necessary for viral replication. After
More than 200 viruses have been associated inoculation, the virus invades the host by binding to
with the common cold. The most important come the intracellular adhesion receptor molecule 1
from the six viral families listed in Table 30–1. Most (ICAM-1) receptors of the basal epithelial cells,
633
634 Ballenger’s Otorhinolaryngology
mainly located in the ICAM-1-rich area of the ade- gen-specific B-cell proliferation. Tumor necrosis fac-
noid.3 After attachment, the entire virus is translo- tor alpha (TNF-α) stimulates T and B lymphocytes
cated across the epithelial cell membrane and and activates endothelial cells to express viral adhe-
uncoated to release viral RNA into the cytoplasm for sion molecules and to release further cytokines.3
replication. Translation of the entire genome leads Bradykinin, a known potent inflammatory media-
to a large polyprotein that, when cleaved, results in tor, causes vasodilatation, increases vascular perme-
newly formed viral proteins. These newly formed ability, and stimulates pain and glandular secretions
proteins (RNA) can aggregate and eventually be via neuronal reflexes.
released when the host cell disintegrates. After intra- The similarity between the clinical manifesta-
cellular invasion and replication, the rhinovirus tions of allergic rhinitis and the common cold has
infection spreads intranasally and to the pharynx. prompted attempts to establish the role of histamine
Typical for rhinovirus infections are the isolated in the common cold. Several studies have reported
scattered foci of infected epithelium between large no increase in histamine in nasal secretions during
areas of normal epithelium. In contrast to other rhinovirus infection. Prostaglandin D2, another
common cold viruses such as influenza and aden- mediator derived from mast cells, cannot be detected
oviruses, the epithelium does not show any striking in the nasal secretions of subjects infected with rhi-
damage or cytopathic alterations during a rhi- novirus. Nasal biopsy studies show no change in
novirus infection.3 mast cell numbers or mast cell degranulation. These
The mechanism(s) by which rhinovirus infec- studies suggest that it is unlikely that histamine or
tion of epithelial cells in the upper airway causes the other mast cell mediators make an important con-
symptoms of the common cold is incompletely tribution to the pathogenesis of rhinovirus colds.
understood. The original concept that symptoms The current concepts of the pathogenesis of
resulted from destruction of nasal epithelium has symptoms in rhinovirus infection may one day allow
not been supported by biopsies, which have shown the development of methods to block or dampen the
no striking damage or cytopathic alteration other host response. It may be that such an approach
than an increased number of polymorphonuclear would allow the host to become immune to the
neutrophils in the submucosa and epithelium. It infecting virus without the accompanying sympto-
appears that the viral infection per se does not pro- matic illness.4
duce symptoms; rather, it is the host response to the
viral infection that is responsible for the symptoms.
A rhinovirus infection of the epithelium
PHARYNGITIS
evokes the synthesis and release of mediators and In most cases of acute pharyngitis, particularly mild
cytokines, which result in a cascade of the inflam- cases, it is not possible to determine a specific micro-
matory reactions held responsible for common cold biologic cause on clinical grounds alone. In a study
symptoms. Vasodilatation, increased vascular per- of pharyngitis in adults, clinical findings such as
meability, cellular infiltration, and the release of var- fever, lymphadenopathy, and exudate correlated
ious mediators characterize this response. One imperfectly with microbiologic findings.5
cytokine, interleukin-8 (IL-8), is a strong chemoat- About 70% of acute sore throats are caused by
tractant for neutrophils. Interleukin-8 is also capable viruses. Most of these occur as part of common cold
of activating the recruited neutrophils, resulting in or influenza syndromes. The most common viral
the release of their cytotoxic granule content. agents are rhinovirus, coronavirus, adenovirus, and
Another cytokine, IL-6, stimulates B-lymphocyte influenza and parainfluenza viruses.6 Other associ-
differentiation into plasma cells, with resultant pro- ated viruses include respiratory syncytial virus, her-
duction of immunoglobulins. Interleukin-6 also pes simplex virus (types 1 and 2), coxsackievirus,
induces acute-phase proteins, such as C-reactive Epstein-Barr virus, cytomegalovirus (CMV), and
protein, and mediates T-cell activation, growth, and human immunodeficiency virus (HIV).
differentiation. Interferon-gamma (IFN-γ), another Adenoviruses are common agents of acute
cytokine, stimulates macrophage accumulation, acti- pharyngitis and cause a major share of pharyngitis
vation, and cytokine production. In addition, it in military recruits. Sore throat is severe and may be
stimulates natural killer (NK) cell function and anti- accompanied by cough, hoarseness, and substernal
636 Ballenger’s Otorhinolaryngology
pain. Fever, chills, malaise, myalgias, and headache common bacterial cause of acute pharyngitis. Inci-
are generally present. Adenoviruses are also the dence is age related. In one study of school-aged
cause of pharyngoconjunctival fever, a syndrome children, GABHS accounted for 40% of cases of
characterized by fever, pharyngitis, and follicular pharyngitist.6 A prospective study of symptomatic
conjunctivitis. Community epidemics of this infec- adults patients found 10% with culture-proven
tion most often center around contaminated public GABHS pharyngitis.8 Although GABHS pharyngitis
swimming pools. was previously thought rare in infants, a more recent
Herpangina is a vesicular and ulcerative study found a 25% incidence of GABHS in children
pharyngitis caused by coxsackieviruses or, less fre- less than 3 years old.9 As mentioned, attempts to cor-
quently, echoviruses. It is seen primarily in children relate clinical findings with the presence of GABHS
3 to 10 years old or, less commonly, in adolescents in acute pharyngitis have shown imperfect results.
and young adults. Outbreaks are most common in Features suggestive of GABHS, however, include
the summer and fall. Onset is heralded by fever, pharyngeal exudate, dysphagia, headache, painful
which is followed by the development of small (1 to cervical lymphadenitis, fever, and the absence of
2 mm) mucosal vesicles and ulcers. Over 2 to 3 days, cough, coryza, and hoarseness. Diagnosis may be
these enlarge to 3 to 4 mm and are surrounded by confirmed by rapid antigen tests and/or throat cul-
erythematous rings. Lesions are most commonly ture. Timely diagnosis is important to prevent sup-
noted on the anterior tonsillar pillars, as well as the purative or nonsuppurative complications of
soft palate, tonsils, pharyngeal walls, and posterior GABHS infection. These complications are dis-
aspects of the buccal mucosa. Uninvolved areas of cussed later in this chapter.
the pharynx appear normal or are only slightly ery- The role of groups B, C, and G streptococci in
thematous. Fever and sore throat are sometimes the pathogenesis of symptomatic pharyngitis is
accompanied by constitutional symptoms, including uncertain. These non–group A streptococci may be
anorexia and abdominal pain, which can mimic responsible for a small portion of pharyngitis but are
appendicitis. Most cases of herpangina are mild and not associated with the nonsuppurative complica-
resolve without complications in 3 to 6 days. tions seen in GABHS.
Herpes simplex viruses (types 1 and 2) can Vincent’s angina is an acute oropharyngeal
cause acute pharyngitis indistinguishable from that ulcerative condition caused by a combination of
caused by other respiratory viruses. More typically, anaerobic gram-negative and fusobacterial microor-
vesicles and shallow ulcers accompany an infection. ganisms. Fusobacterium necrophorum, Treponema
Herpes simplex virus is to be suspected when palatal vincentii, Peptococcus, Bacteroides, and other anaero-
or pharyngeal ulcers are accompanied by gingivos- bic microorganisms have been identified. Poor oral
tomatitis. Chronic herpetic lesions can occur in hygiene, fatigue, stress, malnutrition, and endocrine
immunocompromised patients and are character- or metabolic disturbances are predisposing factors.
ized by progressively large, shallow, painful ulcers. Infection typically manifests as unilateral pseudo-
Infectious mononucleosis most often presents membranous tonsillar ulceration with pain, fetid
with fever, pharyngotonsillitis, fatigue, and cervical breath, and cervical lymphadenopathy. Acute necro-
lymphadenopathy. The illness is caused predomi- tizing ulcerative gingivitis (ANUG), or “trench
nantly by the Epstein-Barr virus (EBV). Cyto- mouth,” is a similar ulcerative process of the gingiva.
megalovirus is an occasional cause of infectious Penicillin and metronidazole are effective in the
mononucleosis-like disease. In such cases, pharyngi- treatment of Vincent’s angina and ANUG.
tis and cervical lymphadenopathy may be mild or Neisseria gonorrhoeae should be considered as
absent. These two viruses are addressed in more a cause of pharyngitis in sexually active patients,
detail later in this chapter. especially those with known orogenital contact. In a
Primary infection with HIV may cause an study of adults with gonorrhea, gonococcal pharyn-
acute febrile pharyngitis.7 Fever, sore throat, and gitis was found in 20% of homosexual men, 10% of
varying constitutional symptoms precede onset of women, and 3% of heterosexual men. About 50% of
lymphadenopathy by about a week. infected individuals were asymptomatic, although
Group A β-hemolytic streptococcus (GABHS), odynophagia, low-grade fever, and erythema may
also known as Streptococcus pyogenes, is the most occur. Gonococcal pharyngitis may occur without
Etiology of Infectious Diseases of the Upper Respiratory Tract 637
associated urethritis and may serve as a source of after a prodromal period of coryza and low-grade
disseminated disease.10 fever lasting for 12 to 72 hours, spreads to the respi-
ratory epithelium of the larynx, trachea, and
bronchi.
ACUTE SUPRAGLOTTITIS (EPIGLOTTITIS) Parainfluenza viruses (types 1, 2, and 3) are the
Acute supraglottitis is cellulitis of supraglottic struc- most frequent etiologic agents, accounting for
tures including the epiglottis and aryepiglottic folds. almost 75% of isolated viral agents.14 Influenza A
Edema progresses rapidly and may result in airway virus, respiratory syncytial virus, adenoviruses,
obstruction. enteroviruses, and rhinoviruses are less commonly
Formerly, Haemophilus influenzae type b (Hib) isolated. Rarely, Mycoplasma pneumoniae has been
was the etiologic agent in almost all cases of supra- isolated from children with croup. Bacterial agents
glottitis in children. However, with the advent of the such as S. pneumoniae, S. aureus, and Moraxella
Hib vaccine, the rates of disease caused by this catarrhalis have been associated with croup. They
microorganism have dramatically decreased.11 likely represent superinfection of a preceding viral
Although H. influenzae is still identified in areas disease.
where the vaccine is available, group A streptococcus
has been more frequently recovered in more recent
studies.11,12 When caused by group A streptococcus,
SINUSITIS
supraglottitis was seen in an older age at onset The microbiology of sinusitis varies according to the
(mean 6.2 years) and associated with slower recov- chronicity of the infection, as well as the age and
ery, greater involvement of the aryepiglottic folds, underlying condition of the patient. Accurate cul-
and negative blood cultures. This differs from the ture requires aspiration or irrigation because of the
presentation of Hib supraglottitis, which includes presence of resident microflora in the nasal cavity
younger age, involvement of the epiglottis, faster and nasopharynx.
recovery, and positive blood cultures.11 Other causes Acute community-acquired sinusitis in adults
of acute supraglottitis in children are uncommon is most frequently associated with S. pneumoniae
and include Staphylococcus aureus, other strepto- and nontypable H. influenzae. In children, to these
cocci, H. influenzae non-type b, and H. parainfluen- pathogens may be added M. catarrhalis.15 Anaerobic
zae. Immunocompromised patients are more likely bacteria are recovered in about 5 to 10% of cases of
to have these and other, more unusual pathogens. acute sinusitis in adults, usually in the presence of
Acute supraglottitis is increasingly recognized dental disease. Anaerobes are rarely recovered from
in adults. In most cases, no causative microorganism cases of acute sinusitis in children, presumably
is found, either by blood or throat culture. Using because of the relative absence of odontogenic infec-
serology, PCR, and blood culture to investigate their tions in the young. Staphylococcus aureus is an
series of adult epiglottitis patients, Trollfors and uncommon cause of acute sinusitis, found in only
coworkers found Hib in about 25% and Streptococ- about 3% of cases. In contrast, S. aureus, α-
cus pneumoniae in 20% of patients.13 No pathogen hemolytic streptococci, and S. pneumoniae were
was identified in 43% of patients. Other pathogenic reported as the predominant pathogens of isolated
bacteria have been cultured from adult patients with sphenoid sinusitis. Although this may reflect
supraglottitis, including H. parainfluenzae, S. aureus, increased contamination by resident nasal flora,
and group A streptococci. antimicrobial coverage for S. aureus is prudent in
patients with acute sphenoid sinusitis. Viral URIs
ACUTE LARYNGOTRACHEOBRONCHITIS undoubtedly play an important role in predisposing
a patient to acute sinusitis; however, viruses, includ-
(CROUP) ing rhinoviruses, adenoviruses, and influenzae and
Acute laryngotracheobronchitis, or croup, produces parainfluenzae viruses, are isolated in only 15 to
inflammation of the subglottic areas that result in 20% of antral aspirates taken from patients with
stridor and respiratory distress. Most patients are acute sinusitis.
children between the ages of 3 months and 3 years. In studies of chronic sinusitis, the most com-
The viral infection begins in the nasopharynx and, mon microorganisms identified were those seen in
638 Ballenger’s Otorhinolaryngology
acute sinusitis plus S. aureus, coagulase-negative pneumoniae and an overall increase in β-lactamase-
Staphylococcus, and anaerobic bacteria. Infection is producing H. influenzae and M. catarrhalis. Blue-
often polymicrobial, and anaerobic bacteria play a stone and colleagues also studied the bacteriology of
far greater role in both adults and children than in 34 adults with AOM. Streptococcus pneumoniae
acute sinusitis.16 Such anaerobes include Bacteroides, (21%) and H. influenzae (26%) were again the most
Peptostreptococcus, and Fusobacterium. Staphylococ- frequently isolated microorganisms. This study con-
cal species, including S. aureus, are also far more fre- firmed the importance of H. influenzae beyond the
quently encountered in chronic sinusitis, as are age of preschool children.19
α-hemolytic streptococci. Streptococcus pneumoniae is more likely than
Nosocomial sinusitis, such as that seen follow- H. influenzae or M. catarrhalis to cause a more severe
ing prolonged nasotracheal intubation, is commonly and persistent AOM. In the absence of therapy, S.
polymicrobial and has a high incidence of S. aureus, pneumoniae tends to persist longer than these other
anaerobes, and gram-negative bacteria such as microorganisms. Also, there is an increased likeli-
Pseudomonas aeruginosa, Escherichia coli, Klebsiella hood of finding S. pneumoniae in AOM less respon-
pneumoniae, Proteus mirabilis, and Enterobacter sive to antibiotic therapy. Acute otitis media caused
species.17 by S. pneumoniae is less likely to require a preceding
In cystic fibrosis patients with acute sinusitis, P. viral infection and more likely to induce a greater
aeruginosa and H. influenzae were the most fre- inflammatory response.22
quently isolated pathogens.18 Viruses play a significant role in the pathogen-
esis of AOM. Clinical experience shows that AOM
usually occurs concurrently with, or immediately
OTITIS MEDIA after, a viral URI. Also, the seasonal rates of AOM
Otitis media is the most common illness diagnosed parallel that of viral URI. Several studies have
by pediatricians. Acute otitis media (AOM) is a sup- demonstrated the effect of viral URIs in inducing
purative infection of the middle ear with a relatively eustachian tube dysfunction. The pathogenesis by
rapid onset. Recurrent otitis media refers to episodes which viral URIs turn into AOM or facilitate bacte-
of repeated AOM separated by a month or more. rial AOM is not yet clear. Heikkinen noted that in
Chronic otitis media includes the diagnoses of otitis vitro studies have shown an increase in levels of
media with effusion, as well as chronic suppurative inflammatory mediators (bradykinin, IL-1, IL-6, IL-
otitis media with and without cholesteatoma. 8, leukotriene C4, and TNF) in nasopharyngeal
In children with AOM, S. pneumoniae, H. secretions in response to a viral infection. Intranasal
influenzae, and M. catarrhalis are the microorgan- challenge of these mediators has been shown to pro-
isms most frequently isolated after tympanocentesis voke eustachian tube dysfunction in adult volun-
and culture of middle ear fluid (MEF). Several stud- teers. Respiratory viruses have also been shown to
ies have demonstrated that S. pneumoniae causes have a suppressive effect on polymorphonuclear and
about 35% of AOM episodes, nontypable H. influen- cell-mediated immune function, presumably increas-
zae 25%, and M. catarrhalis 15%.19,20 Most AOM ing the host’s susceptibilty to bacterial infections.23
associated with H. influenzae is caused by nonty- Fainstein et al have shown that experimentally
pable strains. In about 10% of H. influenzae infec- induced influenza virus infection increases the
tions, the otitis is caused by type b. Such type b adherence of S. pneumoniae and H. influenzae to
infections may have a higher incidence of concomi- pharyngeal epithelial cell.24
tant bacteremia or meningitis and should be pre- Viral culture and antigen detection techniques
ventable by immunization. Staphylococcus aureus, have allowed demonstration of viruses or viral anti-
other streptococci, and P. aeruginosa were found in gens in the MEF of about 20% of children with
less than 3% of AOM. Chlamydia pneumoniae, AOM. Respiratory syncytial virus, influenza viruses,
which is susceptible only to macrolides and tetracy- parainfluenza viruses, rhinovirus, and adenovirus
clines, was isolated in 8% in one study of young chil- are most commonly identified. In about two-thirds
dren.21 The most notable recent trends in the of the cases, bacteria were also identified, indicating
bacteriology of AOM have been the rise in the pro- a mixed infection. Virus as the only pathogen in
portion of patients infected with drug-resistant S. MEF has been detected in 6% of AOM cases.24
Etiology of Infectious Diseases of the Upper Respiratory Tract 639
Recently, studies using the more sensitive PCR tech- (DNA) virus. Two strains have been identified in
nique have detected RNA genomic sequences in humans. Epstein-Barr is ubiquitous, infecting
about 50% of MEF in AOM. Heikkinen et al noted more than 90% of the world’s population. In less
that respiratory syncytial virus is especially capable industrialized societies, nearly all inhabitants are
of causing inflammation in the middle ear, as well as infected during childhood, when symptoms of
facilitating subsequent bacterial infection.25 Vaccina- infection are mild. In the United States, western
tion against influenza A has been shown to reduce Europe, and other industrialized countries, infec-
the incidence of bacterial AOM in children during tion may be delayed until adolescence or young
an expected influenza epidemic. It is to be expected adulthood and may manifest as infectious mono-
that effective vaccines against the major viral nucleosis because of the reaction of a more mature
pathogens predisposing to AOM, especially RSV, will immune system.
reduce the incidence of AOM in children.23 Infection by EBV is largely limited to epithelial
Neonatal otitis media is most frequently asso- cells of the pharynx and to B lymphocytes. The sur-
ciated with microorganisms similar to those seen in face receptor for the virus on these cells is the CD21
infants; however, gram-negative enteric microorgan- molecule, which is also the receptor for the CD3
isms and S. aureus are more frequently identified component of complement. Primary infection is ini-
than in older children.26 tiated in the oropharyngeal epithelium, where repli-
The bacteriology of recurrent otitis media in cation, host cell lysis, and release of virions take
children with episodes separated by a month or place. Adjacent B lymphocytes are infected and dis-
more is essentially that of AOM. seminate the virus to local and distant lymphoid tis-
In their 10-year review, Bluestone and associ- sues and to other epithelial cells, including the
ates studied the bacteriology of otitis media with nasopharynx and salivary glands. Within B lympho-
effusion in children.19 Haemophilus influenzae cytes, the virus establishes a latent infection. The
(15%), M. catarrhalis (10%), and S. pneumoniae DNA genome circularizes to form an episome, or
(7%) were most frequently isolated. Other strepto- extrachromosomal element, in the nucleus of the
cocci, S. aureus, and P. aeruginosa were isolated in cell. Transformation of the infected B lymphocyte
less than 3% of cases. No growth was found in 30%. causes them to become “immortalized,” which is to
This and other reports refute previous assumptions say that they acquire the ability to proliferate indef-
that MEF in otitis media with effusion is sterile. initely. Such resting memory B cells are thought to
Chronic suppurative otitis media is defined by be the site of persistence, or latent infection, of EBV
the presence of chronic infection in the middle ear within the body.30 The host’s immune system
and discharge through a tympanic membrane per- responds to infection first with NK cells, then with
foration or patent pressure equalization tube. Mas- human leukocyte antigen (HLA) class I restricted
toiditis is invariably present. Bacteria isolated are cytotoxic and suppressor T lymphocytes and by
seldom those seen in an initial AOM. Polymicrobial antibody-producing anti-EBV B lymphocytes. The
infections are common. Pseudomonas aeruginosa is NK and T lymphocytes appear in the peripheral
most commonly isolated, and S. aureus is seen more blood as “atypical lymphocytes.” Cytokines released
frequently than in AOM.27 Anaerobes, including from these cells are largely responsible for the clini-
anaerobic gram-positive cocci, Bacteroides species, cal manifestations of primary EBV infection. In
and Fusobacterium, are present in 50% of cases.28 In infants and small children, these immune responses
chronic suppurative otitis media with cholestea- are weak, and symptoms of infection are mild. The
toma, P. aeruginosa, S. aureus, and anaerobes again immune systems of adolescents and young adults
predominate.29 respond more vigorously and cause the symptoms
of infectious mononucleosis.
Epstein-Barr virus is the predominant cause of
SPECIFIC VIRUSES infectious mononucleosis, which is characterized by
fever, fatigue, pharyngitis, and lymphadenopathy.
EPSTEIN-BARR VIRUS Splenomegaly, mild hepatitis, and cerebritis may also
Epstein-Barr virus, a member of the herpesvirus occur. Uncommon manifestations include jaundice,
family, is a double-stranded deoxyribonucleic acid pneumonitis, blood dyscrasias, and central nervous
640 Ballenger’s Otorhinolaryngology
system syndromes. The diagnosis is suggested by the blood transfusion or solid organ transplantation; or
clinical features. Abnormal laboratory findings by transplacental transfer to a fetus. Ductal epithelial
include the presence of atypical lymphocytes in the cells of the major salivary glands and proximal renal
peripheral blood, elevation of hepatic enzymes, and tubules are especially involved by primary infection.
the presence of positive heterophil antibodies (the Once acquired, the virus infects nucleated blood
“Monospot” or Paul-Bunnell test). Heterophil anti- cells and spreads systemically. After primary infec-
bodies are immunoglobulin (Ig)M antibodies that tion, CMV generally remains in an asymptomatic
bind to red blood cells from nonhuman species such latent state, but immunosuppression may result in
as sheep or horses. Many rapid test kits for their reactivation and disease.
detection are commercially available. The percent- In infants and children, CMV infection gener-
age of patients with acute EBV infection who have ally causes few symptoms. In young adults, however,
heterophil antibodies in their serum increases rela- CMV can produce a mononucleosis syndrome with
tive to the time since onset of symptoms. The per- fever, fatigue, pharyngitis, lymphadenopathy, and rel-
centage is also higher in patients over 4 years of age. ative lymphocytosis. It is estimated that 20% of infec-
In one study of young adults, 69% tested positive for tious mononucleosis is caused by acute CMV
heterophil antibodies by 1 week and 80% by 3 weeks infection. Pharyngitis, lymphadenopathy, and
after the onset of symptoms. A pediatric study found splenomegaly are less common and severe than in
fewer than 50% of children under age 4 to have any cases caused by EBV. Patients with CMV mononucle-
detectable heterophil antibodies at any time.31 osis will show a relative lymphocytosis but will have a
Epstein-Barr virus is closely linked to nonker- negative heterophil antibody (Paul-Bunnell) test.
atinizing nasopharyngeal carcinoma and to Burkitt’s Primary or reactivated CMV infections com-
lymphoma, a tumor of B lymphocytes limited monly cause disease in immunosuppressed hosts,
largely to children in tropical Africa and New such as persons with HIV infection or those who
Guinea. Epstein-Barr virus genomes are also found have undergone bone marrow or solid organ trans-
in about one-third of the non-Hodgkin’s B-cell lym- plantation. Cytomegalovirus itself may adversely
phoma found in patients with acquired immune affect the immune system, causing suppression of
deficiency syndrome (AIDS). NK-cell and T-lymphocyte function. Clinical fea-
Oral hairy leukoplakia is common in patients tures in immunosuppressed patients include
with HIV and represents infection by EBV of epithe- encephalitis, chorioretinitis, hepatitis, pneumonitis,
lial cells. It consists of white lesions with a hairy or colitis, and esophagitis. Cytomegalovirus has also
corrugated appearance located on the lateral surface been identified as a cause of oral ulcers in immuno-
of the tongue. Epstein-Barr virus replication is evi- suppressed patients. Diagnosis in these cases in
dent only in the upper layers of the epithelium. based on tissue biopsy, which demonstrates the
characteristic histologic findings of intranuclear
CMV inclusions surrounded by clear halos (“owl
CYTOMEGALOVIRUS eyes”), as well as clusters of intracytoplasmic inclu-
Cytomegalovirus, the largest member of the her- sions seen with periodic acid–Schiff or Gomori’s
pesvirus family, consists of a core of double- methenamine silver techniques.
stranded DNA genome surrounded by a protein Cytomegalovirus is among the most common
coat. The virus is ubiquitous, and serologic evidence viral pathogens causing congenital abnormalities.
suggests that up to 80% of adults have been infected. Fetal involvement follows a primary CMV infection
Most primary infections in immunocompetent per- of a woman lacking antibody to the virus during
sons are asymptomatic. An upsurge in interest in pregnancy. Clinical features include mental retarda-
CMV has resulted from an appreciation of its role as tion, hearing loss, jaundice, chorioretinitis, micro-
an opportunistic pathogen in immunocompromised cephaly, and pneumonitis, among others.
patients, including those with HIV infection.
The details of pathogenesis in CMV infection
are less well understood than for EBV. Infection may
HUMAN IMMUNODEFICIENCY VIRUS
be acquired by contact with the saliva, sputum, Human immunodeficiency virus is a retrovirus. It is
urine, or genital fluid of infected persons; through able to convert its own single-stranded RNA to dou-
Etiology of Infectious Diseases of the Upper Respiratory Tract 641
ble-stranded DNA for incorporation into a host cell described.35 Patients with HIV with CD4 counts less
genome. The principal targets are T helper (CD4) than 200 cells/mm3 are more susceptible to unusual
cells, which are central to the function of cell-medi- pathogens. Infections with P. aeruginosa are more
ated immunity. Impairment of these cells renders a frequent. Other pathogens reported include CMV,
patient susceptible to a variety of opportunistic Pneumocystis carinii, Acanthamoeba castellanii, and
infections and unusual malignant diseases. Legionella pneumophila. Patients with AIDS are at
Human immunodeficiency virus attaches to increased risk for invasive fungal sinusitis.
CD4 receptors and enters T-helper cell lymphocytes. Aspergillus fumigatus has been most frequently
The single-stranded RNA is converted by the reported. Other fungal pathogens have included
enzyme reverse transcriptase into double-stranded Pseudallescheria boydii, Candida albicans, Cryptococ-
DNA. The viral DNA is incorporated into the host cus neoformans, Rhizopus arrhizus, and mucormyco-
cell genome. A latent phase follows that corresponds sis, among others.36
to clinically quiescent infection. Activation and viral Studies have suggested that children with HIV
replication lead to cell death and the destruction of infection have an increased incidence of otitis
large numbers of CD4 cells. It is possible that acti- media. Moreover, those HIV-infected children with
vation is speeded by the presence of DNA viruses a deteriorating immune system, as indicated by a
such as herpes simplex virus and CMV. The presence decline in the CD4 count, are at greater risk for
or absence of opportunistic infections corresponds recurrent or chronic disease than those who retain
with the patient’s CD4 count. A normal count is an intact immune system.37 Causative microorgan-
700 to 1,200 cells/mm3. CD4 counts below 200 isms do not seem to differ from those found in
cells/mm3 are associated with increased susceptibil- immunocompetent hosts. Streptococcus pneumo-
ity to opportunistic infections. Such patients benefit niae, H. influenzae, and M. catarrhalis predominate.
from antibiotic prophylaxis. Unusual pathogens, however, should be suspected
Humoral immunity is adversely affected by when a patient has a severely depressed immune
HIV as well. Immunoglobulin G2 and IgG4 subclass system or responds poorly to standard antibiotic
deficiencies predispose patients to recurrent therapy.
sinopulmonary infections. Patients with HIV may Adult HIV-infected patients appear to have
also develop elevated IgE levels, which may be an increased incidence of serous otitis media. This
responsible for an increased incidence of allergic may be partly attributable to poor eustachian tube
rhinitis. function. The eustachian tube may be affected by
The reported prevalence of sinusitis in HIV adenoidal hypertrophy, nasopharyngeal tumors such
patients varies widely, although clinicians generally as Kaposi’s sarcoma and non-Hodgkin’s lymphoma,
agree that the incidence is higher than in immuno- or allergic rhinitis prompted by increased IgE levels.
competent patients. Retrospective studies have esti- Pneumocystis carinii is a common cause of pneumo-
mated the prevalence of disease at 10 to 20%. Two nia in AIDS patients. Although extrapulmonary
prospective studies placed the incidence at 30 to infections are rare, several reports have described
68%.32 Several reports suggest that the incidence of otitic involvement. Patients present with aural dis-
sinus disease increases with progressive immunode- charge and the presence of a polyp in the middle ear
fiency, as measured by declining CD4 counts.33,34 In or external auditory canal. Several patients have had
addition, IgE levels increase in many HIV-infected no history of prior P. carinii pneumonia. Diagnosis is
patients with disease progression. Such immune dys- made by biopsy of the polyp and demonstration of
function, with the resultant increase in allergic dis- pneumocystis on Gomori’s methenamine silver stain.
ease, may predispose HIV-infected patients to These aural infections have responded well to
recurrent rhinosinusitis. The prevalence of specific trimethoprim-sulfamethoxazole. Other unusual
pathogens in sinusitis of those HIV-infected patients pathogens have caused otitis media or mastoiditis,
with a CD4 count of greater than 200 cells/mm3 is including A. fumigatus, Candida albicans, and
similar to that of non–HIV-infected patients. In Mycobacterium tuberculosis. Chronic otitis media,
acute sinusitis, S. pneumoniae and H. influenzae are cholesteatoma, and intracranial complications of oti-
most frequently recovered. In chronic sinusitis, S. tis media do not appear to occur more often in the
aureus, anaerobic bacteria, and P. aeruginosa are also HIV-infected population than in other patients.38
642 Ballenger’s Otorhinolaryngology
Oral candidiasis is a common feature of HIV protein strains of GABHS that cause pharyngitis are
infection and is often the first finding of the disease. generally distinct from those causing impetigo or
Candidal infections are considered in more detail pyoderma. M proteins inhibit phagocytosis of
later in this chapter. As noted earlier, oral hairy GABHS by host leukocytes in the absence of type-
leukoplakia is thought to be caused by EBV. The specific antibodies and therefore play an important
lesion is most frequently located on the lateral sur- role in the virulence of these microorganisms.42
face of the tongue and has a white corrugated or fil- Group A β-hemolytic streptococcus secretes
iform appearance. Epstein-Barr virus replication is certain toxins and enzymes that have clinical effects
evident only in the upper layer of the epithelium. or cause antibodies to be produced that may be used
Herpes simplex viral infections are more common for serologic identification. Streptolysins O and S
in HIV-infected patients. Lesions are generally more induce lysis of host cell membanes, including red
severe, numerous, and persistent than in immuno- blood cells. Streptolysin O is antigenic and is the
competent patients. Herpes labialis is frequent and basis of the antistreptolysin O (ASO) antibody assay,
may extend onto the face to form a giant herpetic the most widely used of the many streptococcal anti-
lesion. body tests. Pyogenic (also called erythrogenic) exo-
Opportunistic infections of the larynx must be toxins are produced by some serotypes of GABHS.
considered in HIV-infected patients with hoarseness Three exotoxins have been identified: streptococcal
or stridor. Candidiasis is the most common cause. pyogenic exotoxin A (SPE A), SPE B, and SPE C.
Laryngeal candidiasis is most often part of a more These exotoxins are thought to be in part responsi-
widespread infection involving the oral cavity or ble for the clinical manifestations of scarlet fever and
esophagus. Absence of candidiasis in these sites, of streptococcal toxic shock-like syndrome (TSLS).
however, does not exclude laryngeal infection. The The leading role of GABHS as a cause of
vocal folds are most frequently involved. Candidal pharyngitis is discussed earlier in this chapter. The
infection of the epiglottis is much less common but greater significance of these microorganisms lies in
is capable of causing stridor and airway compro- their capacity to cause complications. These compli-
mise, especially in children.39,40 Laryngeal infections cations may be broadly separated into three cate-
caused by CMV and Cryptococcus neoformans, gories: suppurative, toxin mediated, and non-
among others, have been described in HIV-infected suppurative.
patients. A series of five HIV-infected patients with Suppurative complications of GABHS include
supraglottitis was reported by Rothstein and associ- peritonsillar abscess, retropharyngeal abscess, sup-
ates.41 A pale, floppy epiglottis with supraglottic purative cervical lymphadenitis, sinusitis, otitis
edema, cervical lymphadenopathy, normal to low media, and mastoiditis. Group A β-hemolytic strep-
white blood cell count without a shift to the left, and tococcus is a prominent cause of peritonsillar and
rapidly progressive airway obstruction comprised retropharyngeal abscesses. Similarly, GABHS and S.
the typical presentation. No unusual pathogens were aureus are the most important causes of suppurative
recovered from epiglottic cultures in these patients. cervical lymphadenitis. In contrast, GABHS plays a
The most common pathogens were S. pneumoniae minor role in the pathogenesis of sinusitis, otitis
and S. aureus. Conservative medical management media, and mastoiditis.
was not successful. Patients required airway inter- Toxin-mediated complications of GABHS
vention with appropriate antibiotic therapy. pharyngitis include scarlet fever and streptococcal
TSLS. Both are thought to be associated with the
release of streptococcal pyogenic exotoxins by cer-
SPECIFIC BACTERIA tain M protein serotypes. In the 1980s, an increase in
GROUP A -HEMOLYTIC STREPTOCOCCUS the incidence and severity of scarlet fever, as well as
the emergence of TSLS, suggested an increase in the
(STREPTOCOCCUS PYOGENES) number of virulent GABHS strains capable of pro-
Group A β-hemolytic streptococcus, or S. pyogenes, ducing pyogenic exotoxins. Serotypes M-1 and M-3,
is a chain-forming, gram-positive coccus. More than in particular, were found to be associated with
80 serotypes have been recognized based on a series TSLS.43 Investigators have postulated that manifesta-
of distinct surface proteins, the M proteins. The M tions of scarlet fever, including the characteristic
Etiology of Infectious Diseases of the Upper Respiratory Tract 643
rash, are attributable to host hypersensitivity to these resulting in inflammation of the renal glomeruli.
pyogenic exotoxins. Acute glomerulonephritis may follow either pharyn-
Initial manifestations of scarlet fever include gitis or cutaneous infections caused by GABHS. A
sore throat, fever, and constitutional symptoms such limited number of strains are “nephritogenic.” M-12
as vomiting, headache, and malaise. The characteris- is the M protein serotype most frequently related to
tic rash follows 12 to 48 hours later, beginning on pharyngitis-associated nephritis.42 The pathogenesis
the trunk before quickly becoming generalized. The of AGN is unclear. Antibodies to antigens of nephri-
rash appears diffusely erythematous with fine red togenic streptococci may cross-react with struc-
papules. It blanches on pressure, may become turally similar renal antigens, producing injury.
petechial, and fades in 2 to 5 days, leaving a fine Alternatively, inflammation may result from deposi-
desquamation. Skin folds, such as the groin and tion of streptococcal antigen-antibody complexes
axilla, are most intensely involved. The face is within the kidney. Acute glomerulonephritis associ-
flushed, with circumoral pallor. Enlargement and ated with GABHS pharyngitis occurs most fre-
erythema of the papillae of the dorsal tongue pro- quently in school-aged children. The latent period
duce a characteristic “strawberry tongue.” following pharyngitis averages 10 days. Clinical fea-
In the late 1980s, reports emerged of GABHS tures include fever, moderate edema, hypertension,
infections associated with hypotension, progressive and azotemia. Mild cases may have few symptoms.
multisystem organ failure, and other features sug- The urine is smoky or brown in color with a high
gestive of a toxin-mediated disorder. Because of a specific gravity, proteinuria, and hemoglobinuria.
partial resemblance to staphylococcal toxic shock Microscopic examination reveals red blood cells,
syndrome, the new disorder was named streptococ- white blood cells, and hyaline, granular, or red blood
cal TSLS. The syndrome occurs most often in cell casts. Other laboratory findings include a mild
healthy adults. Most patients have a severe soft tissue normocytic normochromic anemia, prolonged ery-
focus of infection, such as necrotizing fasciitis throcyte sedimentation rate (ESR), decreases in C3
and/or myositis; however, 10 to 20% of cases have complement, and elevations of the blood urea nitro-
been associated with pharyngitis.43 The syndrome gen and serum creatinine. Unlike in ARF, recur-
most typically consists of hypotension, fever, rash, rences are rare. The long-term prognosis in children
desquamation, and multisystem organ failure, which is excellent, with few cases leading to residual renal
is out of proportion to the extent of local signs and disease. Prognosis in adults is more guarded.
symptoms. Bacteremia is present in about half of the Acute rheumatic fever is a nonsuppurative
cases. In a reported series of 50 patients, the mortal- complication of GABHS characterized by inflamma-
ity rate was 24%. Group A β-hemolytic streptococ- tory lesions of the heart, joints, subcutaneous tissues,
cus isolated from patients with TSLS appears to and central nervous system. Pyodermic infections are
come from a limited group of M protein serotypes. not associated with ARF. The disease has become
M-1 and M-3 strains, in particular, have been asso- uncommon in more prosperous areas of the world,
ciated with TSLS. Streptococcal pyogenic exotoxin A although local outbreaks thought to be caused by
stimulates production of TNF by peripheral mono- highly rheumatogenic strains of GABHS are period-
cytes in vitro. A cytokine, IL-1β, is thought to con- ically reported. In poorer regions, ARF remains
tribute to the pathophysiology of shock and tissue prevalent and accounts for a large proportion of car-
injury. Treatment of streptococcal TSLS involves diac disease in children and young adults.44 The
support of failing organ systems, appropriate antibi- pathogenesis of ARF is poorly understood. Current
otics, and, if present, aggressive surgical débridement evidence supports an immune mechanism. Humor-
of necrotizing fasciitis or myositis. and cell-mediated immune re- sponses to rheumato-
Nonsuppurative complications of GABHS genic antigens of GABHS are thought to cross-react
pharyngitis include poststreptococcal glomeru- mistakenly with structurally similar antigens in host
lonephritis and acute rheumatic fever (ARF). The tissues. Pathologic findings of ARF include inflam-
pathogenesis of these conditions is unclear, but each matory lesions of connective tissues in the heart,
is suspected to be immune mediated. joints, blood vessels, and subcutaneous tissues. A
Poststreptococcal acute glomerulonephritis unique feature, seen mainly in the heart, is the
(AGN) is a delayed, nonsuppurative complication Aschoff ’s nodule, a granuloma that results from
644 Ballenger’s Otorhinolaryngology
injury to collagen. Cardiac findings also include peri- Humans are the only known reservoir for C.
carditis, myocarditis, and/or endocarditis. Valvular diphtheriae. Transmission occurs via contact with
involvement begins as edema and inflammation of respiratory secretions or exudate from infected skin
the leaflets and chorda tendinae. With healing, the lesions. The virulence of C. diphtheriae results from
valves may become thickened and deformed, the the action of a potent exotoxin capable of inhibiting
chordae shortened, and the valve commissures fused. intracellular protein synthesis. After host cell uptake,
These changes result in valvular stenosis or insuffi- the exotoxin catalyzes inactivation of the transfer
ciency. The mitral valve is affected in 75 to 80% of RNA translocase elongation factor 2. Loss of this
cases, the aortic valve in 30%, and the tricuspid and enzyme prevents the interaction of messenger RNA
pulmonary valves in under 5%. Acute rheumatic and transfer RNA, stopping further addition of
fever occurs most often in children 5 to 15 years of amino acids to developing polypeptide chains. Local
age; it is rare before age 4 or after age 40. Symptoms action of the exotoxin in the upper respiratory tract
and signs usually commence 1 to 3 weeks after the induces a characteristic pseudomembrane comprised
streptococcal pharyngitis. No single symptom, sign, of fibrin, leukocytes, erythrocytes, dead respiratory
or laboratory test is diagnostic of the disease. The cells, and microorganisms. Systemically, the exotoxin
Jones criteria, most recently updated in 1992, remain has a predilection for the heart (myocarditis), nerves
useful in making the diagnosis.45 If supported by evi- (demyelination), and kidneys (tubular necrosis).
dence of preceding group A streptococcal infection, Some strains of C. diphtheriae do not produce exo-
the presence of two major manifestations, or one toxin. Such strains will not produce severe systemic
major and two minor manifestations, a high proba- symptoms or the characteristic pseudomembrane.
bility of ARF is indicated. Supporting evidence The posterior structures of the mouth and the
includes a positive throat culture, positive rapid proximal parts of the pharynx are the most common
streptococcal antigen test, or an elevated or rising sites for respiratory tract diphtheria. Onset is abrupt
streptococcal antibody titer. Major manifestations and involves sore throat, malaise, and low-grade
include carditis, polyarthritis, chorea, erythema mar- fever. Initial erythema usually progresses to develop-
ginatum, and subcutaneous nodules. Minor manifes- ment of an adherent pseudomembrane typically on
tations include clinical findings such as arthralgia or one or both tonsils with extension to the soft palate,
fever, laboratory findings such as an elevated ESR or oropharynx, and nasopharynx. Its color may vary
C-reactive protein, and a prolonged PR interval on from creamy to grayish green. The pseudomem-
an electrocardiogram. Treatment of ARF includes the brane is surrounded by a deep red border, and
use of salicylates and corticosteroids to quiet inflam- attempts at removal result in bleeding. Cervical
mation. Neither agent prevents the development of lymph nodes are usually enlarged, and severely ill
rheumatic heart disease, the only long-term sequelae patients may have a bull-neck appearance. Non–exo-
of ARF. Rheumatic patients are at extremely high risk toxin-producing strains of C. diphtheriae will not
of developing recurrent ARF after streptococcal produce a pseudomembrane. Infections produced
infections and require antibiotic prophylaxis. by such strains may closely resemble streptococcal
pharyngitis.
Laryngeal and tracheobronchial involvement
CORYNEBACTERIUM DIPHTHERIAE usually results from direct spread from the pharynx,
The corynebacteria are nonmotile, pleomorphic, although the disease may occasionally begin there.
unencapsulated, gram-positive bacilli. Diphtheria is Symptoms include hoarseness, respiratory distress,
caused by toxin-producing strains of Corynebac- and a brassy cough. If the presence of a laryngeal
terium diphtheriae or, occasionally, the related or tracheal membrane is found on laryngoscopy,
microorganism Corynbacterium ulcerans. The infec- consideration must be given to early endotracheal
tion is now rare in countries with immunization intubation or tracheostomy to forestall airway
programs but remains widespread elsewhere. In obstruction, especially in children.
1990, an epidemic centered in the former Soviet Nasal diphtheria initially causes purulent or
Union demonstrated the potential for resurgence of serosanguinous nasal discharge. Patients with
this disease should efforts to maintain high levels of chronic nasal diphtheria may act as carriers of the
immunity in a population lapse. disease.
Etiology of Infectious Diseases of the Upper Respiratory Tract 645
Diphtheria exotoxin has its most striking progresses through three stages. The catarrhal stage
effects on the heart and nervous system. Clinically is manifested by prolonged purulent rhinorrhea,
significant myocarditis occurs in 7 to 20% of respi- crusting, and nasal obstruction. Diagnosis in this
ratory tract diphtheria cases. Neuropathy can stage is difficult because of the nonspecific findings.
involve cranial nerves IX and X, causing palatal or In the granulomatous stage, multiple nodules form
pharyngeal paralysis with resultant regurgitation of and coalesce to form bluish-red or pale, rubbery
swallowed fluids through the nose. granulomas.46 Most cases are diagnosed in this stage.
Diphtheria must be suspected in any unimmu- Severe cases can progress to local destruction and
nized patient with a severe, rapidly spreading pha- cosmetic deformity. Broadening of the nasal dorsum
ryngeal exudate. Diagnosis is confirmed by culture produces the characteristic Hebra nose. The final
on Loeffler’s or Tindale’s medium. Because routine fibrotic stage causes cicatrix formation. Nasal or
methods of throat culture do not promote the isola- nasopharyngeal stenosis is common. Stenosis of the
tion and identification of C. diphtheriae, the labora- larynx or trachea can cause life-threatening airway
tory must be alerted to use selective media when the obstruction. Diagnosis of rhinoscleroma is made by
disease is suspected. Toxin production is demon- clinical findings and biopsy. Histologic findings
strated by immunodiffusion on solid culture media include granulomatous inflammation and the pres-
(Elek test), by monoclonal enzyme immunoassay for ence of Mikulicz’s cells and Russell’s bodies. These
toxin (EIA), or by PCR testing of the isolate’s DNA, findings are most characteristic of the granuloma-
using primers for the tox gene. tous stage, in which K. rhinoscleromatis is most eas-
Treatment of diphtheria involves the use of ily isolated. Mikulicz’s cells are “foamy histiocytes”
antitoxin and antibiotics and protection of a com- caused by gram-negative bacteria in the cytoplasm
promised airway. Diphtheria antitoxin only neutral- of macrophages. Russell’s bodies are eosinophilic
izes the exotoxin before its entry into cells, so it is structures within the cytoplasm of plasma cells. In
critical that it be administered as soon as a pre- advanced cases, fibrosis may obscure characteristic
sumptive diagnosis has been made, without awaiting findings. Treatment of rhinoscleroma is with pro-
diagnostic confirmation. Penicillin and erythromy- longed antibiotics. The most commonly used antibi-
cin are the antibiotics of choice. By eradicating the otics are tetracycline (2 g/day), ciprofloxacin (1
pathogen, they end local disease, further production g/day), and streptomycin (1 g/day). The criteria for
of exotoxin, and transmission of disease. cessation of therapy are clinical improvement and
repeated negative tissue culture. Surgical débride-
KLEBSIELLA RHINOSCLEROMATIS ment may be indicated to alleviate airway obstruc-
tion. Laryngeal dilatation, endoscopic resection, or
(RHINOSCLEROMA, SCLEROMA) tracheostomy may be required for laryngeal stenosis.
Klebsiella rhinoscleromatis (K. pneumoniae, sub-
species rhinoscleromatis) is a capsulated gram-
negative coccobacillus that causes a chronic
MYCOBACTERIUM TUBERCULOSIS
granulomatous disease of the upper respiratory Mycobacterium tuberculosis, an acid-fast bacillus, is a
tract. It is endemic to tropical and subtropical areas cause of infection throughout the upper respiratory
of Africa, Central and South America, and Asia. tract. Its incidence has again increased with the
Most European cases are reported from Eastern advent of AIDS. Two sites of special interest are the
Europe. In temperate zones, cases are generally larynx and middle ear.
imported from endemic areas. Poor hygiene, Tuberculosis is the most common cause of
crowded living, and malnutrition are predisposing granulomatous disease of the larynx. It is usually,
factors. Females are more frequently affected than but not invariably, associated with active pulmonary
males. The disease tends to present in the second and disease. Spread from the lung to larynx is largely
third decades of life. The nose is almost always ascribed to direct inoculation by bacilli-laden spu-
involved. Less commonly, the paranasal sinuses, tum, but hematogenous and lymphatic spread from
lacrimal sacs, pharynx, larynx, and trachea are pulmonary foci is recognized as well. Symptoms of
affected. Nasal lesions often begin at the mucocuta- laryngeal tuberculosis may include hoarseness,
neous junction of the vestibule. The disease usually odynophagia, dysphagia, and referred otalgia. Exam-
646 Ballenger’s Otorhinolaryngology
ination may show edema, submucosal nodules, and facial nerve paralysis, subperiosteal abscess, persist-
shallow ulcerations. Lesions may progress to deeper ent postauricular fistula, labyrinthitis, or extension
ulceration, perichondritis, and arytenoid fixation. of the infection into the central nervous system.
The posterior part of the larynx is most commonly Cortical mastoidectomy may disclose thick granula-
involved, although any portion of the larynx may be tion tissue and possible bony necrosis. Tym-
involved.47 Laryngeal tuberculosis may mimic carci- panoplasty or ossicular reconstruction should be
noma or chronic laryngitis. Syphilis, mycotic infec- delayed until the infection has been controlled.
tions, sarcoidosis, and Wegener’s granulomatosis
must also be considered. A chest radiograph is help-
ful in suggesting the diagnosis if active pulmonary
MYCOBACTERIUM LEPRAE
disease is present. A sputum smear may show acid- Mycobacterium leprae is a gram-positive, acid-fast
fast bacilli. The diagnosis may be confirmed by bacillus. It prefers an ambient temperature of less
biopsy. Laryngeal tuberculosis responds well to than 37°C and, as a result, has a predilection for
antitubercular chemotherapy. Fibrotic changes skin, peripheral nerves, and the upper aerodigestive
from advance disease may require surgical recon- tract. Leprosy presents in three general forms. In the
struction. lepromatous form, the patient is unable to generate
Tuberculous otitis media may result from an effective immune response to M. leprae because
either hematogenous spread from pulmonary foci of a selective unresponsiveness of T lymphocytes.
or from direct inoculation by bacilli-laden sputum This form of leprosy tends to be the most wide-
refluxed through the eustachian tube. Otorrhea spread and destructive. Most upper aerodigestive
may be scant or profuse. Although the disorder is tract leprosy is of the lepromatous form. In the
often painless, many patients experience otalgia. tuberculoid form, the host has a normal T-cell
Granulation tissue and occasionally polyps are seen response. Tuberculoid form lesions are generally less
in the middle ear. Conductive hearing loss may widespread. They consist of plaques and macules
result from effusion, mucosal thickening, tympanic with sharp, raised borders. An intermediate third
membrane perforation, or ossicular destruction. form of leprosy is the borderline form, which reflects
Classically, tympanic membrane perforations have a partial reduction in immune response.
been described as initial small multiple perforations The nose is by far the most frequently involved
that coalesce to a near-total perforation. More recent site in the upper aerodigestive tract. Approximately
studies show that simple perforations are more com- 95% of patients with lepromatous leprosy have nasal
mon, however. Denudation and destruction of the involvement. Lesions begin as a pale, nodular,
ossicular chain are common. Facial nerve paralysis is plaque-like thickening of the nasal mucosa.
more common in aural tuberculosis than in otitis Untreated lesions can progress to ulceration, septal
media caused by other bacteria. Tuberculous otitis perforation, and saddle-nose deformity. Symptoms
media can also cause mastoiditis, which, in turn, include rhinitis, obstruction, crusting, and bleeding.
may progress to subperiosteal abscess and a draining The anterior end of the inferior turbinate is the site
fistula. Other complications may include labyrinthi- most likely to give a positive biopsy.
tis, meningitis, and osteomyelitis of the petrous The larynx is less commonly involved. Involve-
pyramid. The diagnosis of aural tuberculosis is best ment nearly always begins at the tip of the epiglot-
made by biopsy of granulation tissue or polyps. His- tis. Mucosal thickening is followed by granuloma
tologic presence of caseating granulomata and acid- formation and ulceration. Symptoms may include
fast bacilli confirms the diagnosis. Smear and culture hoarseness and pain. Laryngeal leprosy can closely
of aural discharge are unreliable because the bacilli mimic carcinoma. Untreated lesions may progress
can be demonstrated in only a minority of patients. to fibrosis and airway obstruction, requiring
Chest radiograph abnormalities suggestive of pul- tracheostomy.
monary disease are present in only 50% of patients Mycobacterium leprae has never been cultured
with aural tuberculosis. in vitro. Diagnosis is most reliably made by tissue
Treatment of aural tuberculosis consists of smear or biopsy, which may show granulomatous
long-standing antitubercular chemotherapy. Surgi- changes and the presence of bacilli. Rifampin, dap-
cal intervention may be indicated in the presence of sone, and clofazimine are the most widely used
Etiology of Infectious Diseases of the Upper Respiratory Tract 647
antileprosy drugs. Treatment is generally with the resection.49 The duration of penicillin therapy will
standard World Health Organization regimen.48 vary from 2 to 18 months. Concomitant hyperbaric
oxygen treatment in severe cases should be consid-
ered as well.
ACTINOMYCES
Actinomycosis is caused by anaerobic gram-posi-
tive bacterium of the family Actinomycetaceae. The SPECIFIC FUNGAL INFECTIONS
filamentous, branching appearance of these oral CANDIDIASIS
saprophytes on microscopy caused their initial
misidentification as fungi. Actinomyces israelii is Candida albicans is the most frequent of several
the microorganism most frequently incriminated species that cause candidiasis. It is a dimorphic fun-
in human disease. These inhabitants of the normal gus with both yeast and hyphal forms. Candida albi-
oral flora take advantage of infection, trauma, or cans is a commensal of the oral cavity and pharynx.
surgical injury to penetrate mucosa and invade Infection usually only follows changes in the local
adjacent tissue. Cervicofacial infections commonly bacterial flora, mucosal integrity, or host immunity.
follow dental infections or manipulations. Such Local factors that may predispose patients to can-
infections most commonly affect otherwise didiasis include xerostomia and dentures. Systemic
healthy individuals. factors are numerous and include prolonged antibi-
The clinical manifestations of cervicofacial otic use, diabetes mellitus, immunocompromised
actinomycosis may vary from an indolent infection states (eg, HIV, cytotoxic therapy), pernicious ane-
to a more rapidly progressive, tender, fluctuant mia, and hematologic malignant diseases.
swelling resembling a typical pyogenic infection.49 Oral candidiasis (“thrush”) can vary greatly in
Most cases, however, present as a chronic infection appearance. Zegarelli has described several vari-
with few systemic symptoms. A typical presentation ants.51 The pseudomembranous variant resembles
shows a slowly progressive, mildly tender induration white milk curds overlying an erythematous base.
of the neck, buccal, and mandibular regions. Infec- The erythematous variant appears flat, irregular, and
tion spreads without regard to tissue planes. Pro- dusky red. When candidiasis occurs beneath den-
gression leads to formation of a hard, board-like tures, it is flat and red and extends up to but not
lesion (“lumpy jaw”), suppuration, draining fistulae, beyond the denture border. A hyperplastic variant
and the presence of “sulfur granules” (white-yellow resembling lichen planus manifests as a true leuko-
granules of bacterial filaments, 1 to 5 mm in diame- plakia without pseudomembrane or erythematous
ter) in exudates or tissues. Overlying skin can be base. Oral candidiasis is often asymptomatic but
dark red to purple, and associated cutaneous sinus may also cause a “burning” pain. Candidiasis may
tracts remain chronic, with little tendency to heal. also be responsible for median rhomboid glossitis, as
Osseous involvement of the mandible occurs in 15% well as some cases of angular cheilitis.
of cases. Candidiasis less commonly infects the larynx
A diagnosis of actinomycosis is based on the and pharynx. When involved, the larynx is covered
clinical presentation, positive culturing of the by a thick, white exudate. Hoarseness is the most
microorganism, and observation of sulfur granules common symptom, followed by pharyngeal pain.
or acid-fast–negative pleomorphic filaments in exu- Severe cases may proceed to airway obstruction and
date or tissue sections.50 Anaerobic culturing must laryngeal scarring. Diagnosis is best made by direct
be meticulous to obtain growth. Even with proper laryngoscopy and biopsy.
precautions, actinomycosis is identified from culture
in fewer than 50% of cases. Fine-needle aspiration
has been shown to be useful in obtaining specimens
ASPERGILLOSIS
for histologic examination and culture. The Aspergillus species are ubiquitous saprophytic
Treatment of cervicofacial actinomycosis con- fungi found in soil and decaying organic material.
sists of prolonged antibiotics and surgical débride- Aspergillus fumigatus and Aspergillus flavus are the
ment. Although sensitive to penicillin, nearly all most common of many species to cause disease.
cases require surgical drainage, curettage, or lesion Hyphae show regular septa with frequent acute
648 Ballenger’s Otorhinolaryngology
branching. Aspergillus infections are distributed alternating high- and low-density signals and may
worldwide, although chronic disease is especially also be useful in determining the extent of the dis-
prevalent in the Sudan and Saudi Arabia. Infection is ease. Often the proper diagnosis is suggested only at
acquired by the inhalation of spores. The lungs, surgery, with discovery of mucus-covered, inspis-
nose, and paranasal sinuses are the most commonly sated, cheesy material typical of fungal sinusitis.
affected sites. Diagnosis is confirmed by histology and culture.
Aspergillus is the most common cause of fun- Treatment of acute invasive and chronic invasive
gal sinusitis. The maxillary and ethmoid sinuses are forms requires surgical drainage, débridement, and
most frequently involved. Conditions that obstruct the use of systemic antifungal agents. Treatment for
sinus drainage such as allergic rhinitis, nasal polyps, a fungus ball requires only surgical removal and aer-
and chronic bacterial sinusitis may predispose ation of the involved sinus. Systemic antifungal
patients to fungal sinusitis. Infections take one of agents are not required. Allergic fungal sinusitis is
four forms. Acute invasive fungal sinusitis occurs treated by surgical débridement and aeration of the
primarily in immunocompromised patients. Vascu- involved sinus followed by the use of systemic and
lar invasion by hyphae with resultant thrombosis topical intranasal corticosteroids. Recurrence is
and necrosis may cause a fulminant course resem- common and may be heralded by rising serum total
bling craniofacial mucormycosis. Erosion into the IgE levels. Specific immunotherapy with multiple
orbits, cranium, palate, and skin is common. relevant fungal and nonfungal antigens has reduced
Chronic invasive fungal sinusitis occurs more fre- the necessity for corticosteroid therapy, while pre-
quently in immunocompetent patients. Progression venting recurrence of the disease and the need for
of the infection is generally slow, with mild early repeat surgery.52
signs and symptoms. Extension into the orbit or
cranium may produce proptosis, ophthalmoplegia,
and headache. The third form of fungal sinusitis is
PHAEOHYPHOMYCOSES (DEMATIACEOUS FUNGI)
the “fungus ball.” This is a tangle of fungal hyphae Dematiaceous fungi are defined by the presence of
within a sinus cavity but without invasion of sinus melanin in the walls of their hyphae or spores. These
mucosa. The maxillary sinus is most commonly fungi are increasingly recognized as causes of fungal
involved. A fourth form of fungal sinusitis is allergic sinusitis previously ascribed to Aspergillus species.
fungal sinusitis (AFS). Most patients with AFS are The list of dematiaceous fungi causing sinusitis is
immunocompetent and present with features of rapidly expanding and currently includes Drechslera,
refractory sinusitis and nasal polyposis. Many also Bipolaris, Exserohilum, Curvularia, Alternaria, and
have a history of atopy or asthma. The pathogenesis Cladosporium species. Signs and symptoms are
of AFS is incompletely understood, but evidence essentially indistinguishable from those of chronic
supports a Gell and Coombs type I (IgE-mediated) indolent Aspergillus sinusitis. These fungi are also
immune response to fungal antigens. Type III and common causes of AFS. Diagnosis and treatment are
IV immune responses may also be involved. The similar to that of aspergillosis.
pathologic hallmark of AFS is “allergic mucin,” con-
sisting of eosinophils, Charcot-Leyden crystals, and
scattered fungal hyphae. Although AFS is not
MUCORMYCOSIS
thought to be invasive, bony erosion is seen on com- Mucormycosis (zygomycosis) is an infection caused
puted tomographic (CT) scans in 20% of reported by fungi of the Mucoraceae family, which includes
cases. Laboratory abnormalities include eosino- Rhizopus, Mucor, and Absidia species. Nearly all cases
philia, elevated total serum IgE, and elevated IgE occur in patients with diabetes mellitus or who are
radioallergosorbent test (RAST) titers to specific otherwise immunocompromised. These fungi are
fungi. The diagnosis of AFS is confirmed by demon- found in soil and decaying organic matter. When
stration of allergic mucin and culture of the fungus. examined microscopically, their hyphae are broad (7
The presence of Aspergillus or other fungi must to 20 µm), with few septa and irregular 90-degree
be suspected in cases of sinusitis that do not respond branching.
to the usual medical treatment. Computed tomo- Craniofacial (rhino-orbital-cerebral) mucor-
graphic scans may show a characteristic pattern of mycosis usually originates in the nose or sinuses.
Etiology of Infectious Diseases of the Upper Respiratory Tract 649
Vascular invasion by hyphae leads to thrombosis An oral azole, particularly itraconazole, may be used
with resultant ischemic infarction and necrosis. This for milder infections or suppressive therapy.
accounts for the potentially rapid erosion and spread
of this infection into the orbit, cranium, palate, or
face. Patients with nasal involvement present with
BLASTOMYCOSIS
purulent or serosanguinous drainage, ulceration, or Blastomyces dermatitidis is a dimorphic fungus that
necrosis. The lateral nasal wall and turbinates are the grows in a mycelial form at room temperature and as
most frequent site of initial involvement. Edema and a budding yeast at body temperature. Blastomycosis
erythema are followed by cyanosis and black necro- is most prevalent in the eastern portion of North
sis. Orbital extension may cause periorbital swelling, America and over a wide area of Africa. Infection is
proptosis, and ophthalmoplegia. Cranial involve- thought to be acquired by the inhalation of spores.
ment may cause cranial neuropathies, focal neuro- Dissemination occurs by hematogenous seeding
logic deficits, and coma. Anesthesia of an involved from primary pulmonary foci and, when present, is
area may provide an early clue to the presence of most frequent in the skin, bone, and genitourinary
mucormycosis.53 tract. Skin lesions are most commonly located on
Prompt diagnosis requires a high index of sus- the face, extremities, scalp, and neck. The appearance
picion and is confirmed by biopsy. Frozen sections of these lesions may vary. Most begin as papules
may speed diagnosis. A CT scan delineates the extent that, over a course of weeks or months, progress to
of the infection. Treatment requires a prolonged relatively painless ulcerative or verrucous lesions.
course of amphotericin B, as well as aggressive sur- Long-standing lesions may show central healing
gical débridement of all nonviable tissue. Antifungal with extensive fibrosis. Subcutaneous abscesses and
azoles are ineffective. The underlying condition draining sinuses may also be present.
must be corrected if possible. Involvement of the nose, sinuses, larynx, or
mouth may cause well-circumscribed, indurated
lesions of the mucosa. As in skin involvement, these
HISTOPLASMOSIS lesions are relatively painless, may be ulcerative or
Histoplasma capsulatum is a dimorphic fungus that verrucous, and may closely mimic squamous cell
exists in a mycelial form in the soil and a budding carcinoma in appearance. Biopsy shows pseudoep-
yeast form at body temperature. It is found through- itheliomatous hyperplasia of the mucosa with
out the world and in the United States is especially microabscesses, granulomas, and the presence of
prevalent in the Mississippi and Ohio River valleys. fungi. Treatment involves the use of systemic anti-
The disease is acquired by inhalation of airborne fungal agents. Many patients with indolent head and
conidia, often during contact with soil contaminated neck manifestations of blastomycosis can be treated
by avian or bat feces. An increased incidence has with a prolonged course of oral itraconazole.54 Intra-
been seen in patients with AIDS. venous amphotericin B is used in more severe
Disseminated histoplasmosis occurs most fre- infections.
quently in patients with impaired cell-mediated
immunity. In such patients, lesions of the upper
aerodigestive tract are most often seen. The larynx is
CRYPTOCOCCOSIS
most commonly involved, with preference for the Cryptococcus neoformans, a yeast with a thick poly-
anterior part of the larynx and epiglottis. Symptoms saccharide capsule, is saprophytic and distributed
include sore throat, hoarseness, and dysphagia. worldwide. A common natural source is avian drop-
Other sites of involvement include the tongue, pings. Many patients with cryptococcosis are
palate, buccal mucosa, and pharynx. Lesions may immunosuppressed. Acquired immune deficiency
appear nodular or ulcerative and may mimic carci- syndrome is now the most important predisposing
noma, syphilis, tuberculosis, or any other granulo- factor. Cryptococcosis occurs in about 8% of AIDS
matous lesion. Biopsy is a reliable method of patients and is a commonly recognized cause of life-
diagnosis. It shows a granulomatous response with threatening infection. The fungus is acquired by
budding yeast cells. Amphotericin B is the drug of inhalation, with primary pulmonary infection fol-
choice for severe, refractory, or relapsing infections. lowed by hematogenous spread. The next most com-
650 Ballenger’s Otorhinolaryngology
mon site of involvement is the central nervous sys- ity, nose, pharynx, and larynx are involved in
tem. Other frequently involved sites include the approximately half of all cases. In a smaller number
bones and skin. The upper respiratory tract is rarely of cases, the fungus may be directly inoculated into
involved. Laryngeal lesions have been described as the mucosa by chewing or cleaning of the teeth with
edematous, exudative, or verrucous. Diagnosis is plant fragments. Pulmonary infection is found in the
made by biopsy, which shows pseudoepithelioma- majority of symptomatic patients. Dyspnea, hemop-
tous hyperplasia, granulomatous changes, and the tysis, and chest pain may occur. Lymphadenitis and
presence of encapsulated fungi. The antifungal hepatosplenomegaly are also common.
azoles and amphotericin B are used for treatment. Lesions of the mucosa of the oral cavity, nose,
pharynx, and larynx are painful and manifest as
well-defined areas of hyperemic granulation tissue
COCCIDIOIDOMYCOSIS and ulceration. Enlargement of lymph nodes drain-
Coccidioides immitis is a dimorphic fungus, growing ing these lesions may be present. Clinical manifesta-
in mycelial form in the soil and as thick-walled tions include hoarseness, odynophagia, sore throat,
endospore-forming spherules at body temperature. and dyspnea. Destruction of underlying cartilages
Coccidioidomycosis is endemic to desert and semi- may lead to nasal collapse. Cutaneous involvement
arid portions of the southwestern United States and may be present, with areas of the face around the
northern Mexico, as well as scattered areas of Cen- mouth and nose most frequently involved.
tral and South America. Diagnosis is made by the results of smear, cul-
Infection is acquired by the inhalation of ture, and biopsy. Serologic tests may be helpful. Biopsy
spores. Most symptomatic patients develop only a demonstrates pseudoepitheliomatous hyperplasia
mild to moderate flu-like illness that resolves spon- with intraepithelial abscesses, granulomatous changes,
taneously. A few patients develop a severe pul- and the presence of fungi. Treatment is with antifun-
monary illness that may include hematogenous gal azoles, amphotericin B, and sulfonamides.56
dissemination. Immunocompromised hosts are
especially at risk. The most frequent sites of spread
are to the skin, bones, and meninges. In the upper CONIDIOBOLOMYCOSIS
respiratory tract, the larynx is most frequently Conidiobolus coronatus is present in soil and decay-
involved.55 Lesions may involve any area of the lar- ing organic matter and is endemic to tropical
ynx and may appear nodular or ulcerative. Biopsy regions of Africa and America. This chronic gran-
shows granulomatous changes. Fungal staining ulomatous infection begins in the nasal submucosa
shows the characteristic spherules filled with before extending to the contiguous facial skin.
endospores. Antifungal azoles may be effective in Nasal symptoms may include obstruction, rhinor-
indolent disseminated disease, but amphotericin B rhea, and epistaxis. Infection may slowly spread
is required for severe infections. bilaterally to the skin of the nose, upper lip, and
cheeks or to the paranasal sinuses, orbits, and phar-
PARACOCCIDIOIDOMYCOSIS ynx. The skin remains intact but turns shiny and
erythematous. Diagnosis is suggested by the clinical
Paracoccidioides brasiliensis is a dimorphic fungus picture and is confirmed by potassium hydroxide
found in mycelial form at cooler temperatures and smear, culture, and biopsy. Treatment is with anti-
in yeast form at body temperature. Paracoccid- fungal agents, although long-term results have been
iodomycosis is endemic to those areas of Latin disappointing.
America with hot, humid summers and dry, tem-
perate winters. The greatest number of cases are
from Brazil, although the disease has been reported MISCELLANEOUS INFECTIONS
from Mexico to Argentina. The fungus is a sapro-
phyte found in soil and decaying organic matter.
LEISHMANIASES
Infection is acquired through the respiratory tract. The leishmaniases are caused by species of the pro-
Hematogenous spread may then occur to other areas tozoan genus Leishmania. These parasites are trans-
of the body. The mucous membranes of the oral cav- mitted from animal hosts to humans by sandflies.
Etiology of Infectious Diseases of the Upper Respiratory Tract 651
The disease is endemic to Central and South Amer- Because its mature stage consisted of large, thick-
ica, South Asia, the Middle East, Africa, and the walled, spherical structures containing smaller
shores of the Mediterranean. Leishmania are obligate daughter cells (endospores), it was thought to be a
intracellular parasites that primarily inhabit fungus. Recent studies, however, by amplifying and
macrophages. Expression of the disease can vary and sequencing a portion of the R. seeberi 18S riboso-
depends on the species of parasite and on the mal DNA subunit, have demonstrated it to be phy-
immune status of the human host. Three major clin- logenetically related to a group of fish parasites
ical forms of the disease are recognized: visceral, referred to as the Dermocystidium, rosette agent,
cutaneous, and mucosal. Ichthyophonus, and Psorospermium (DRIPs) clade.
Visceral leishmaniasis, also known as kala-azar, These novel aquatic Protistan parasites are near the
reflects parasitic infection of the spleen, liver, bone animal-fungal divergence.58
marrow, and lymph nodes. Fever and weight loss Rhinosporidiosis is endemic to South Asia and
are followed by hepatomegaly and massive is occasionally seen in tropical Africa and America. It
splenomegaly. Uncommonly, the mucosa of the is most frequently contracted by immersion in con-
upper respiratory tract is involved. Untreated taminated water. Rhinosporidiosis is a chronic
patients with kala-azar may die of hepatic failure. inflammatory disease that most frequently involves
Cutaneous leishmaniasis typically progresses the nasal mucosa. The conjunctiva, oral cavity, and
from small papules and nodules to ulcerative lesions, larynx are less commonly involved. In the nose, the
with a central depression and raised, indurated bor- disease typically manifests as a friable, painless, poly-
der. Healing may be accompanied by considerable poid growth. Nasal obstruction and bleeding are the
scarring. The external nose is frequently involved. most common symptoms. Histologic findings include
Cutaneous lesions of the nose may extend to the skin chronic inflammatory changes and the presence of
of the vestibule but do not ordinarily involve nasal sporangia. Surgical excision is the preferred treat-
mucosa. ment. No effective medical treatment as yet exists.
Mucosal (mucocutaneous) leishmaniasis is the
least common form of the disease. It occurs as a
sequela of the cutaneous form of the disease and REFERENCES
appears when the initial skin lesions have healed.
The nasal mucosa is most frequently involved. Sep- 1. Turner RB. The common cold. Pediatr Ann 1998;
tal perforation is common, and nasal deformity may 27:790–5.
result. Advanced lesions may extend onto the exter- 2. Makela MJ, Puhakka T, Ruuskanen O, et al. Viruses
nal nose, lip, and palate. Mucosal lesions of the oral and bacteria in the etiology of the common cold. J
cavity and larynx have also been described. Clin Microbiol 1998;36:539–42.
The diagnosis of leishmaniasis can be made 3. Van Kempen M, Bachert C, Van Cauwenberge P. An
directly by identification of the intracellular update on the pathophysiology of rhinovirus upper
amastigote in stained histologic sections of tissue or respiratory tract infections. Rhinology 1999;37:
by culture of the promastigote from biopsy. Indirect 97–103.
diagnosis can be made by serologic tests (enzyme- 4. Hendley JO. Editorial comment: the host response,
linked immunosorbent assay, direct agglutination, not the virus, causes the symptoms of the common
others), PCR testing, or monoclonal antibody stain- cold. Clin Infect Dis 1998;26:847–8.
ing of tissue smears.57 5. Huovinen P, Lahtonen R, Zeigler T, et al. Pharyngi-
Pentavalent antimony in the form of sodium tis in adults: the presence and coexistence of viruses
stibogluconate is the most widespread treatment for and bacterial organisms. Ann Intern Med 1989;
leishmaniasis. Amphotericin B, pentamidine, and 110:612–6.
paromomycin are alternate therapies. 6. McMillan JA, Sandstrom C, Weiner LB, et al. Viral
and bacterial organism asssociated with acute
pharyngitis in a school-aged population. J Pediatr
RHINOSPORIDIOSIS 1986;109:747–52.
The etiologic agent of rhinosporidiosis, Rhi- 7. Kessler HA, Blaauw B, Spear J, et al. Diagnosis of
nosporidium seeberi, has been difficult to classify. human immunodeficiency virus infection in sero-
652 Ballenger’s Otorhinolaryngology
negative homosexuals presenting with an acute viral 26. Berman SA, Balkany TJ, Simmons MA. Otitis media
syndrome. JAMA 1987;258:1196–9. in infants less than 12 weeks of age: differing bacte-
8. Komaroff AL, Pass TM, Aronson MD, et al. The pre- riology among in-patients and out-patients. J Pedi-
diction of streptococcal pharyngitis in adults. J Gen atr 1978;93:453–4.
Intern Med 1986;1:1–7. 27. Kenna MA, Bluestone CD, Reilly JS, Lusk RP. Med-
9. Schwartz RH, Hayden GF, Wientzen R. Children less ical management of chronic otitis media without
than three years old with pharyngitis. Are group A cholesteatoma. Laryngoscope 1986;96:146–51.
really that common? Clin Pediatr 1986;25:185–8. 28. Wald ER. Anaerobes in otitis media and sinusitis.
10. Hutt DM, Judson FN. Epidemiology and treatment Ann Otol Rhinol Laryngol 1991;154:14–6.
of oropharyngeal gonorrhea. Ann Intern Med 1986; 29. Brook I. Aerobic and anaerobic bacteriology of
104:655–8. cholesteotoma. Laryngoscope 1981;91:250–3.
11. Wenger JK. Supraglottitis and group A streptococ- 30. Cohen JI. Epstein-Barr virus infection. N Engl J Med
cus. Pediatr Infect Dis J 1997;16:1005–7. 2000;343:481–92.
12. Gorelick MH, Baker MD. Epiglottitis in children, 31. Godshall SE, Kirchner JT. Infectious mononucleosis:
1979 through 1992. Effects of Haemophilus influen- complexities of a common syndrome. Postgrad Med
zae type b immunization. Arch Pediatr Adolesc Med 2000;107:175–9.
1994;148:47–50. 32. Rubin JS, Honigberg R. Sinusitis in patients with the
13. Trollfors B, Nylen O, Carenfelt C, et al. Aetiology of acquired immunodeficiency syndrome. Ear Nose
acute epiglottitis in adults. Scand J Infect Dis 1998; Throat J 1990;69:460–3.
30:49–51. 33. Armstrong M, McArthur JC, Zinreich SJ. Radi-
14. Kaditis AG, Wald ER. Viral croup: current diagnosis ographic imaging of sinusitis in HIV infection. Oto-
and treatment. Pediatr Infect Dis J 1998;17:827–34. laryngol Head Neck Surg 1993;108:36–43.
15. Wald ER. Sinusitis. Pediatr Ann 1998;27:811–8. 34. Thompson C, et al. Etiology of acute sinusitis in HIV
16. Hamilos DL. Chronic sinusitis. J Allergy Clin Im- infection [abstract]. Int Conf AIDS 1993;9:51.
munol 2000;106:213–27. 35. Tami TA, Wawrose SF. Diseases of the nose and
17. Brook I. Microbiology of nosocomial sinusitis in paranasal sinuses in the human immunodefiency
mechanically ventilated children. Arch Otolaryngol virus-infected population. Otolaryngol Clin North
Head Neck Surg 1998;124:35–8. Am 1992;25:1199.
18. Shapiro ED, Milmoe GJ, Wald ER, et al. Bacteriology 36. Hunt SM, Miyamoto RC, Cornelius RS, Tami TA.
of the maxillary sinuses in patients with cystic fibro- Invasive fungal sinusitis in the acquired immunode-
sis. J Infect Dis 1982;146:589–93. ficiency syndrome. Otolaryngol Clin North Am
19. Bluestone CD, Stephenson JS, Martin LM. Ten-year 2000;33:335–47.
review of otitis media pathogens. Pediatr Infect Dis 37. Barnett ED, Klein JO, Pelton SI, Luginbuhl LM. Otitis
J 1992;11:S7–11. media in children born to immunodeficiency virus-
20. Pelton SI. Otoscopy for the diagnosis of otitis media. infected mothers. Pediatr Infect Dis J 1992;11:360–4.
Pediatr Infect Dis J 1998;17:540–3. 38. Lalwani AK, Sooy CD. Otologic and neurotologic
21. Block SL. Causative pathogens, antibotic resistance manifestations of acquired immunodeficiency syn-
and therapeutic considerations in acute otitis media. drome. Otolaryngol Clin North Am 1992:25:1183.
Pediatr Infect Dis J 1997;16:449–56. 39. Marelli RA, Biddinger PW, Gluckman JL. Cyto-
22. Musher D, Dagan R. Is the pneumococcus the one megalovirus infection of the larynx in the acquired
and only in acute otitis media? Pediatr Infect Dis J immunodeficiency syndrome. Otolaryngol Head
2000;19:399–400. Neck Surg 1992;106:296–301.
23. Heikkinen T. Role of viruses in the pathogenesis of 40. Browning DG, Schwartz DA, Jurado RL. Cryptococ-
acute otitis media. Pediatr Infect Dis J 2000;19:S17–23. cosis of the larynx in a patient with AIDS. South
24. Fainstein V, Musher DM, Cate TR. Bacterial adher- Med J 1992;85:762–4.
ence to pharyngeal cells during viral infection. J 41. Rothstein SG, Persky MS, Edelman BA, et al. Epiglot-
Infect Dis 1980;141:172–6. titis in AIDS patients. An unusual cause of fungal
25. Heikkinen T, Thint M Chonmaitree T. Prevalence of laryngitis. Laryngoscope 1989;99:389–92.
various respiratory viruses in the middle ear during 42. Cunningham MA. Pathogenesis of group A strepto-
acute otitis media. N Engl J Med 1999;340:260–4. coccal infections. Clin Microbiol Rev 2000;13:470.
Etiology of Infectious Diseases of the Upper Respiratory Tract 653
43. Shulman ST. Complications of streptococcal 52. Mabry RL, Mabry CS. Allergic fungal sinusitis: the
pharyngitis. Pediatr Infect Dis J 1994;13:S70–4. role of immunotherapy. Otolaryngol Clin North Am
44. Wood TF, Potter MA, Jonasson O. Streptococcal 2000;33:433–40.
toxic shock-like syndrome. The importance of sur- 53. Ferguson BJ. Mucormycosis of the nose and paranasal
gical intervention. Ann Surg 1993;217:109–14. sinuses. Otolaryngol Clin North Am 2000;33:349–65.
45. Special Writing Group of the American Heart Asso- 54. Hanson JM, Spector G, El-Mofty SK. Laryngeal blas-
ciation. Guidelines for the diagnosis of rheumatic tomycosis: a commonly missed diagnosis. Ann Otol
fever: Jones criteria, 1992 update. JAMA 1992;268: Rhinol Laryngol 2000;109:281–6.
2069. 55. Boyle JO, Coulthard SW, Mandel RM. Laryngeal
46. Hart CA, Rao SK. Rhinoscleroma. J Med Microbiol involvement in disseminated coccidioidomycosis.
2000;49:395–6. Arch Otolaryngol Head Neck Surg 1991;117:433–8.
47. Kandiloris DC, et al. Laryngeal tuberculosis at the 56. Sant’Anna GD, Mauri M, Arrarte JL, Camargo H.
end of the 20th century. J Laryngol Otol 1997;111: Laryngeal manifestations of paracoccidioidomycosis
619. (South American blatomycosis). Arch Otolaryngol
48. Jacobson RR, Krahenbuhl JL. Leprosy. Lancet 1999; Head Neck Surg 1999;125:1375–8.
353:655–60. 57. Lohuis PJ, Lipovsky MM, Hoepelman AI, et al. Leish-
49. Miller M, Haddad AJ. Cervicofacial actinomycosis. mania braziliensis presenting as a granulomatous
Oral Surg Oral Med Oral Pathol Oral Radiol Endod lesion of the nasal septum mucosa. J Laryngol Otol
1998;85:496–508. 1997;111:973–5.
50. Nagler R, Peled M, Laufer D. Cervicofacial actino- 58. Herr RA, Ajello L, Taylor JW, et al. Phylogenetic
mycosis: a diagnostic challenge. Oral Surg Oral Med analysis of Rhinosporidium seeberi’s 18S small-sub-
Oral Pathol Oral Radiol Endod 1997;83:652–6. unit ribosomal DNA groups this pathogen among
51. Zegarelli DJ. Fungal infections of the oral cavity. members of the protoctistan Mesomycetozoa clade. J
Otolaryngol Clin North Am 1993;26:1069–89. Clin Microbiol 1999;37:2750–4.
CHAPTER 31
The development of computed tomography (CT) Zero is arbitrarily chosen to represent water.
and magnetic resonance imaging (MRI) has been The numbering system –500 to +500 used on the
regarded as the most important contribution to original scanners is referred to as old Hounsfield
diagnostic medical imaging techniques since Roent- units.2 The numbering system, –1,000 or less to
gen discovered the x-ray in 1895. Computers were +1000 or more, is referred to now as Hounsfield
first used in nuclear medicine in the 1960s, but it units (HU). In this system, air is black (dense air,
was the introduction of CT in 1971, an invention of –1,000 HU) and bone is white (dense bone,
Godfrey N. Hounsfield, who won the Nobel Prize +1,000 HU). Fat absorbs the x-ray less than water
for his pioneering research, that accelerated interest and more than air; therefore, its CT numbers will be
in the application of computers to the broader negative, usually between –50 and –140 HU. The CT
aspects of radiology. Like CT, MRI has proven to be number of circulating blood is +40 to +50; con-
a major breakthrough in diagnostic medical imag- gealed blood, +50 to +80; calcium, +80 to +500;
ing. Based on the pioneering work of Paul Lauter- muscle, +30 to +40; cerebrospinal fluid (CSF), +5 to
bur in the early 1970s,1 MRI, with its continued +12; bone, +100 to +1000; and air, –100 to –1000.
refinement, is considered to be the most important The viewing devices (console) provided with
medical imaging advance of the century. CT scanners usually have a set number of gray scales
(eg, 50, 100, 150, 300, 1,000, or more). The range of
CT numbers covered by these gray scales (the con-
COMPUTED TOMOGRAPHY trast) is adjustable (eg, window-width control) (Fig-
The technique of CT employs a narrow highly colli- ure 31–1).2 The location of the center of the gray
mated rotating (scanning) x-ray beam that is used to scale also is adjustable (window-level control) (see
irradiate the patient from numerous projections. Figure 31–1). This manipulation of window width
Detectors with high detection efficiency, located on (image contrast) and window level (mean level; see
the other side, opposite to the source of the beam, Figure 31–1) by the CT radiologist at the console
register the amount of radiation that has passed gives the most effective diagnostic information,
through the part of the body.2 The data collected are ensuring that the diagnostic sensitivity is limited by
processed by a computer, which, by solving thou- the recorded image and not the observer’s eye. A
sands of equations instantaneously, produces a true window width of 80 units with the level of 35 exam-
tomographic section.2,3 The reconstruction of the ines values ranging from +75 to –5 (see Figure
subject cross-section resides in the computer as a 31–1). With the window level = L = +35 and window
series of digital numbers, usually referred to as “CT width = W = +80 setting, values higher than +75 will
numbers.”2 These numbers are related to the linear be white, those lower than –5 will be black, and those
x-ray attenuation of the material in the volume ele- between +75 and –5 will be shades of gray (see Fig-
ment (voxel) at the location of interest.2 ure 31–1).
654
Imaging of Nasal Cavities, etc, and Base of the Skull 655
using the interaction of magnetic fields, generated domly oriented magnetic dipoles respond to the force
the first two-dimensional MRI.1 This depicted the of the field by trying to line up in the direction of the
proton density and the spin-lattice relaxation time field (see Figure 31–2). In the magnetic field, there-
(T1) distribution (see section of MR phenomenon) fore, there is a net (sum) magnetization produced
in two 1 mm tubes of water.1 Subsequently, numer- parallel to and in the same direction as the applied
ous NMR techniques have been developed generat- field (see Figure 31–2). The magnetic behavior of the
ing data from a point, line, plane, or multiple planes entire population of nuclei can be defined as a macro-
within a volume and from the entire volume.12 scopic or bulk magnetization vector or moment (M)
(see Figure 31–2), which represents the net effect of all
of the magnetic moments of the nuclei of a given
MAGNETIC RESONANCE nuclear species in the sample.
PHENOMENON In the absence of an external magnetic field, the
net magnetization is, of course, zero owing to random
ELEMENTARY PHYSICS orientation of nuclei. When the external magnetic
In discussing x-rays and their effects on atoms, we are field Bo (see Figure 31–2) is imposed on the sample,
concerned with their extranuclear structure, that is, however, the nuclear dipoles become orientated par-
the arrangement of planetary (orbital) electrons, out- allel to the applied field, and the net magnetization
side the nucleus. In MR phenomenon, we are con- (spin vector, M) (see Figure 31–2) yields a finite equi-
cerned with nuclear structures of atoms, that is, the librium that will point in a direction parallel to the
nucleons (“nucleon” is the generic term for a proton external magnetic field Bo (see Figure 31–2). This
or neutron). The existence of nuclear spin and nuclear direction conventionally defines the longitudinal (Z)
angular momentum, the entity essential to the MR axis (see Figure 31–2). By convention, the spin system
phenomenon, was first suggested by the Austrian is presented in a cartesian coordinate system (X, Y, Z),
physicist Wolfgang Pauli in 1924 when he observed with the Z-axis parallel with the direction of the exter-
the behavior of light in a magnetic field.4 Since then, nal magnetic field Bo. (see Figure 31–2).
it has been verified that atomic nuclei have an angu-
lar momentum arising from their inherent property
of rotation or spin. Pairs of protons or neutrons, how-
PRECESSION MOTION
ever, align in such a way that their spins cancel out, Let us focus particular attention on the nuclei of the
and a net spin (net rotation) will therefore exist for a hydrogen atoms, protons, which, from the standpoint
nucleus only when it contains an odd (unpaired) pro- of the MR phenomenon, are particularly favorable
ton, an odd neutron, or both.13 Since protons carry a nuclei. The hydrogen atom is now referred to as a pro-
positive charge, the nuclei have an associated electric ton. Each proton can be regarded as a small, freely
charge distribution; therefore, the spin generates a suspended bar magnet spinning rapidly about its
current flowing about the spin axis, which, in turn, magnetic axis. If a group of protons are placed in a
generates a small magnetic field. Each nucleon of static magnetic field of particular strength (Bo), the
nonzero spin has an inherent magnetic field (mag- magnetic moment of each proton experiences a cou-
netic dipoles) and a magnetic moment (a magnetic ple (from the north and south pole), a force or torque
moment is a vector quality represented by an arrow, tending to turn its magnetic moment (M) parallel to
which describes the magnetic field’s strength and the static magnetic field (see Figure 31–2). Because it
direction), or dipole, associated with it that can be spins, the proton responds to this couple by rotation
thought of as behaving like a tiny spinning bar mag- about the line of force (like a gyroscope precessing
net with north and south poles (Figure 31–2). There- about the gravitational force); therefore, its axis is
fore, these tiny spinning magnets can interact with the tilted and begins to precess (rotate) about the direc-
electromagnetic field.12–14 In a sample of materials, the tion of the magnetic field in a movement known as
nuclear magnets (magnetic moments or dipoles) will “precessing” (see Figure 31–2). The precessional
be pointing in random directions,12–14 and the result motion traces a cone in a manner analogous to the
of many nuclei in a random arrangement is that there wobbling of a toy top as it spins and tries to orient
is no net magnetization (one cancels the other) in any itself in the earth’s gravitational field. The frequency
direction (see Figure 31–2). However, if the nuclei are of the precessional motion given by the famous theo-
placed in an external static magnetic field, the ran- rem of Larmor and the Larmor equation, ω (omega)
Imaging of Nasal Cavities, etc, and Base of the Skull 657
FIGURE 31–2. Nuclei of odd number of neutrons, protons, or both, such as hydrogen (proton), have a net spin or
“nuclear angular momentum.” Each spinning nucleus generates a magnetic field and hence a magnetic moment that
is a vectoral quantity with both direction and magnitude (1a). Nuclear magnets of the nuclei with spin will be point-
ing in random directions. Therefore, there is no net magnetization in any direction. If the nuclei are placed in an exter-
nal static magnetic field Bo (1b), the randomly oriented magnetic moments line up in the direction of field at a state
of equilibrium. The magnetic behavior of the entire population of nuclei is defined as a macroscopic or bulk magne-
tization vector M (1b). When a proton is placed in a magnetic field Bo (1c), it experiences a couple (from the north
and south poles), tending to turn its magnetic moment parallel to the field. Because it spins, the proton responds to
this force like a gyroscope, and its axis of the magnetic moment vector M wobbles or precesses about the direction of
the magnetic field Bo (1c). The frequency (ω) of this precessional motion is unique for each nuclear magnetic sensi-
tive element and is given by the famous theorem of Larmor (ω = γ × Bo). By convention, the spin system is presented
in a cartesian coordinate system (X, Y, Z) with the Z-axis parallel with the external magnet field Bo. When the spin sys-
tem (M) is placed in an external magnetic field (Bo), besides the creation of precession, another phenomenon, a reso-
nance condition, is produced in which the nuclei can absorb energy at sharply defined frequency (Larmor frequency)
from an electromagnetic pulse (wave) and re-emit the energy as electromagnetic radiation of the same frequency after
the incident beam has been turned off. Let us wind a coil around a nuclear magnetic sensitive specimen and place it
inside a magnet (with north, N, and south, S, poles), as shown in 1d, and supply it with radiofrequency (RF) current
at Larmor frequency. A short pulse of each resonant RF current can be arranged to tip the net magnetization vector
(M) through 90 degrees in the X-Y plane (1d) that is perpendicular to Bo. This is called 90-degree pulse. The magne-
tization M now continues to rotate in the X-Y plane at the same frequency and induces a voltage (current) in a receiver
coil (antenna) in the X-Y plane. If the pulse is then turned off, the excited spin system (the nuclei) returns to its state
of equilibrium and loses the excess energy. The vector (M) continues to rotate freely in the X-Y plane, causing the
induced current (signal) in the antenna to fade. This decaying signal is called the “free induction decay” (FID), which
can be amplified, detected, and displayed on an oscilloscope or fed into a computer to provide pictorial information.
The return of the excited spin system to the state of equilibrium, the so-called relaxation, is characterized by two sam-
ple-related time constants. T1 (spin-lattice relaxation time) is the time constant required for the net magnetization (M)
to return from the X-Y plane to its equilibrium along the Z-axis. T2 (spin-spin relaxation time or transverse relaxation
time) is the time constant of the decay of FID.
658 Ballenger’s Otorhinolaryngology
= γ (gamma) × B0, states that the frequency of the pre- “Z” direction at a state of equilibrium “rest” (see Fig-
cessional motion (ω) is proportional to the couple ure 31–2). At equilibrium, the nuclei possess their
and therefore to the strength of the applied static lower energy level. When an electromagnetic radia-
external magnetic field (B0) and the constant of pro- tion (RF) or RF pulse (wave) is used at a sharply des-
portionality gamma, the so-called gyromagnetic ignated frequency (Larmor frequency) because of
property (or ratio) of the specific nucleus.4 The equa- resonant condition, some of the nuclei can absorb
tion shows that as the magnetic field changes, so does energy from the RF pulse, become excited (attain
the nuclear precessional rate of motion (angular fre- higher energy level), and change the direction of their
quency ω or Larmor frequency). This is an important magnetic moments. When the RF pulse is turned off,
point in MRI because it enables us to locate the ori- the excited nuclei relax and return to their original
gin of the MR signal and to pinpoint spatially the orientation (equilibrium, lower energy level), losing
source of each frequency (ω). the excess energy by emitting electromagnetic radia-
tion (the source of the MR signal) of the same fre-
quency as the applied RF pulse by transferring energy
NUCLEAR MAGNETIC RESONANCE to surrounding (lattice) molecules. This process is
Resonance is a physical phenomenon that permits called “relaxation” and is characterized by two sam-
the transfer of energy from an object, particle, or sys- ple-related relaxation time constants: the longitudi-
tem vibrating mechanically or electronically to nal (spin-lattice) relaxation time (T1) and the
another similar object, particle, or system, causing transverse (spin-spin) relaxation time (T2). When the
the latter to vibrate at the same frequency. When a RF pulse of specific frequency (Larmor frequency) is
substance containing nuclei of nonzero spin is placed applied, it affects the NMR-sensitive nuclei in two
in a magnetic field, a resonance condition is pro- ways: (1) the RF pulse excites the nuclei and makes
duced, which means that there will be a strong inter- them move into a higher energy level, and (2) the net
action or resonant effect.4,15 The nuclei can then magnetization vector (M) (see Figure 31–2) will pre-
absorb energy at a sharply defined frequency from cess along the direction of the main field (Z axis)
electromagnetic radiation and re-emit the energy as with an ever-increasing angle depending on the
electromagnetic radiation of the same frequency after intensity and duration of the RF pulses (Figure
the incident beam has been turned off.4,13–15 Either 31–3). The magnetization vector (M) will conse-
the absorption or the re-emission can be measured. quently spiral down toward the X-Y plane (90-degree
To secure this resonant effect, the applied electro- pulse) and then continue to rotate in the X-Y plane
magnetic radiation (pulse) from the radiofrequency (see Figure 31–3). The magnetization vector M can
(RF) generator (see Figure 31–2) must have the same be considered as having a component, Mz (longitudi-
frequency as the Larmor precession frequency (natu- nal magnetization), along the z-axis (see Figures 31–2
ral resonant frequency) of the sample (ie, it has to be and 31–3) and a component, Mxy (transverse magne-
resonant). Hence, the name “nuclear magnetic reso- tization), in the x-y plane perpendicular to the field
nance” has been designated for the phenomenon. In axis (Z) (see Figure 31–3). At equilibrium, the “lon-
short, the precession is a resonance effect, and if a gitudinal magnetization” Mz is equal to the net mag-
system has a natural resonance (frequency resonance, netization M, and the “transverse magnetization” Mxy
frequency of oscillation), energy needs can most effi- is zero (see Figure 31–3). After RF excitation, the pre-
ciently be imparted at the resonance frequency. For cessional angle (see Figures 31–2 and 31–3) contin-
example, at the field strength of 1.5 tesla (1 tesla = ues to increase as long as the RF pulse is applied (see
10,000 gauss), a pulse at 63.87 megahertz (MHz) will Figure 31–3). The precessional or Larmor frequency
excite hydrogen (protons), whereas a pulse at 25.86 (cycles per second), however, remains constant, being
MHz will excite phosphorus nuclei.4 fixed by the inherent properties of the nuclei and the
strength of the static magnetic field, Bo. After the
excitation of the RF pulse, Mz decreases and Mxy
RELAXATION PHENOMENON AND TIMES increases (see Figures 31–2 and 31–3). The RF
As mentioned earlier, in the presence of a static mag- needed to tip the vector (M) through an angle of 15
netic field, Bo, nuclei with nonzero spin orient them- degrees is described as a 15-degree pulse. Pulses of 90
selves with the magnetic field lines that point in the and 180 degrees cause corresponding increases in the
Imaging of Nasal Cavities, etc, and Base of the Skull 659
T1 RELAXATION TIME
The T1 relaxation time represents the time constant
required for the net magnetization vector (M) to
FIGURE 31–3. The precessing net magnetization vector return to its equilibrium after it has been perturbed
(M) can be considered as having a component, Mz, along by the RF pulse. In other words, T1 is the time that
the axis of the main field (Bo) and a component, Mxy, in a characterizes the recovery of the net magnetization
plane perpendicular to the field axis such as the x-y plane (M), after it is perturbed, to its equilibrium state in
(top image). At equilibrium, the net magnetization is the field direction (see Figures 31–2 and 31–3). The
aligned with the main field so that Mz has its maximum alignment of nuclei is not instantaneous but rather
(Mz = M) and Mxy has its minimum (zero) magnitude. grows exponentially, increasing to approximately
After a 90-degree pulse, the Mxy has its maximum and Mz 63% of its final value within a period equal to the
its minimum (zero) magnitude. Following application of time constant (T1). It will reach 95% of the final
a radiofrequency (RF) pulse, the net magnetization vector value at a time equal to three times the constant.
M, will precess at an ever-increasing angle to the main field Therefore, in reality, T1 is the time that characterizes
direction (bottom image), with the precession occurring at the recovery (return of excited spin to equilibrium)
the inherent or natural Larmor frequency. If the RF pulse of 63% of nuclear magnetization. T1 is called “spin-
is long enough or strong enough, the net magnetization lattice relaxation” because the thermal equilibrium
vector (M) spirals down toward the X-Y plane (bottom state, hot state (excited spin) to cold state (spin at
image). When the RF pulse is turned off, the spin system rest or equilibrium), is reached through an exchange
will relax, and the excess energy is released as decaying sig- of energy with its molecular environment or lattice.
nal (free induction decay) with a time constant T2. The T2 The alternative term, “longitudinal relaxation time,”
relaxation time for most tumors is longer than that for is used to reflect the fact that T1 characterizes the
normal tissue. In other words, the nuclear magnetic reso- behavior of the Mz component of the magnetic vec-
nance signal of the tumor (lower decaying pulse) decays tor (M) (see Figure 31–3) when magnetization
longer than the normal tissue (upper decaying pulse). reverts to its equilibrium orientation in the direction
of the applied field (Z) (see Figure 31–3). Basically,
precessional angle.13 After a 90-degree pulse, the vec- T1 is a measure of how fast energy can be transferred
tor (M) will be in the x-y plane, and when the nuclei from the spinning nuclei to their surrounding envi-
are flipped through 180 degrees, the net magnetiza- ronment or lattice by random collision between
660 Ballenger’s Otorhinolaryngology
molecules or the rate at which thermal equilibrium netic field contribution from neighboring nuclei is
is restored after being disturbed. more effective, and the resonant frequency is there-
fore different (rapid phase difference and loss of
coherence) for each nucleus; this makes T2 short.
T2 RELAXATION TIME Solids, on the other hand, have fixed atoms and mol-
As mentioned, the NMR signal picked up after an RF ecules that maintain local field variation (spin–spin
pulse is known as FID. The signal is proportional to or dipole–dipole interaction), which result in a rapid
the magnetization in the sample and would be pro- loss of coherence and a very short T2. Relaxation
duced continuously if the individual nuclear spins times are affected by viscosity, temperature, and the
were able to maintain their coherence (synchroniza- presence of dissolved ions and molecules.14
tion) with no shifting of their relative phases.14 The
FID signal, however, decays because of spin-spin NUCLEAR MAGNETIC RESONANCE
(“dipole-dipole”) interaction (magnetic interaction
of neighboring nuclei) and the inhomogeneity of the
SPECTROSCOPY AND CHEMICAL SHIFT
static magnetic field Bo, both causing fluctuation in Nuclear magnetic resonance spectroscopy is a plot of
local magnetization with resultant fluctuation (any signal intensity versus resonance frequency. The
error) in precessional frequency (around Larmor fre- appearance of NMR spectra depends on the density
quency) of the individual proton. This causes the res- and molecular environment surrounding a nucleus.
onance of protons within the sample to lose The presence of neighboring atoms and the “shielding
synchronization and their vectors to develop a phase currents” that are associated with the distribution of
difference. The signal decays exponentially in time, electrons around adjacent atoms slightly modifies the
with a time constant characterized by the T2 (see Fig- strength of local magnetic fields at particular nuclei
ure 31–3). Basically, T2 is the time taken for the trans- and hence modifies the resonance frequency12–14,16 so
verse magnetization, Mxy, to decrease by 63% of its that the details of molecular structure change the
original value. In a period three times as long as this, NMR frequency of a nucleus in that molecule. The
the transverse magnetization will almost have disap- extent of this field change depends on the electronic
peared. In short, T2 relaxation time is the time taken environment of the observed nucleus; consequently,
for the decay of FID or MR signal to decrease by 63% identical nuclides have slightly different resonance fre-
of its original intensity value. quencies (lines) if they are residing in different chem-
For water, T1 and T2 are several seconds, the ical structures (environments). For example, the
precise value depending on the purity of the water. resonant frequency of a hydrogen proton within a
For cellular water, T1 and T2 are shorter. T1 is shorter water molecule differs slightly from that of a hydro-
in liquids (seconds) than in solids (minutes). In gen proton within a fat molecule, and the resonant
solids and/or in a sample of materials at low tem- frequency of a 31P nucleus bound in an adenosine
peratures, where the atoms and molecules move triphosphate (ATP) molecule varies slightly from that
about very little, transfer of thermal energy is slow; of a 31P nucleus within a phosphocreatine molecule.
therefore, T1 can last for hours.13 T1 is short in liquids These small but specific displacements or shifts in fre-
because of the mobility of the atoms and molecules quency produce separate absorption peaks in a spec-
and the consequent rapid transfer of thermal energy. trum (chemical shift), which are “fingerprints” of the
For protons in pure water, T1 and T2 are molecular conformations and directly aid in the
approximately equal.13 T2 is short in solids determination of chemical structures.13–18 The chem-
(microseconds) and long in fluids. In pure fluids, ical shift is measured and listed in parts per million
because of rapid motion of the atoms and molecules with respect to the signal from a reference such as a
(random process), the magnetic field contribution signal of tetramethylsilane. The chemical shift is of
from neighboring nuclei averages zero, and only the paramount importance in analytic chemistry since it
main magnetic field determines the resonant fre- allows the assignment of different signals (lines) in an
quency. In this case, T2 is very long. If the nuclei find NMR spectrum to corresponding substances or
themselves in impure liquids where molecules attach molecular groups. For example, the proton spectrum
to proteins and have low translational and rotational of acetic acid CH3-COOH provides two lines. One
speeds, this averaging random process of the mag- line represents the three protons (hydrogen) of the
Imaging of Nasal Cavities, etc, and Base of the Skull 661
methyl group and another line the carboxyl proton. to become transverse magnetization Mxy (see Figures
The three protons of the methyl group have an iden- 31–2 and 31–3). Therefore, the longitudinal compo-
tical electronic environment, so their signal appears nent of magnetization Mz is zero. The longitudinal
as a single resonance line. In 31P spectra of muscle component of magnetization will recover exponen-
tissue, the signal of phosphocreatine is used as a ref- tially with a time constant of T1. Rapid repetition of
erence signal. The 31P spectrum of a muscle typically pulses (irradiation of sample) would not allow much
shows five signals that are related to inorganic phos- recovery of magnetization, and little signal would be
phate, phosphocreatine, and the three phosphorus detected after each successive 90-degree exciting
atoms of ATP (alpha, beta, and gamma). pulse. Thus, a certain time (repetition time = TR) is
Currently, NMR spectroscopy is one of the introduced between successive RF pulses. As the TR
most powerful tools used in chemical analysis.13 The increases, the signal and imaging time increase. After
combined MRI, in vivo spectroscopy, has become a RF pulse, as discussed earlier, the FID signal decays
routine procedure to provide morphologic as well as exponentially in time with a time constant T2. The
noninvasive biochemical “noninvasive biopsy” infor- interval between application of the RF pulse and
mation of internal structures of human tissues.16–18 reception of a signal or spin echo is called echo time
or time of echo (TE). As TE increases, signal
CLINICAL USE OF T1-WEIGHTED, PROTON- decreases (see Figure 31–3), and contrast between tis-
sues of different values of T2 changes. If the signal is
WEIGHTED, AND T2-WEIGHTED MAGNETIC
obtained immediately after RF excitation, it will not
RESONANCE IMAGING undergo any T2 decay; therefore, although it is a
Magnetic resonance scanners produce images that strong signal, it has no T2 dependence. If, instead, the
represent one or more of NMR parameters. These signal is obtained sometime after RF excitation, the
are (1) hydrogen (proton) density (also called spin available signal, although weaker, has an exponential
density), (2) the state of motion of hydrogen, (3) the dependence on T2. Strong signals (proton-weighted
tissue relaxation times T1 and T2, and (4) chemical [PW] and T1-weighted [T1W] images) yield better
shift. All forms of unprocessed MR signals depend signal-to-noise levels or ratios and, therefore, better
on nuclear spin density. spatial resolution. With better optical resolution,
The ability to rotate net magnetization (M) anatomy is better appreciated. However, in the image,
(see Figures 31–2 and 31–3) from the direction of the differences owing to T2 relaxation time (T2-
the static magnetic field (Bo) into some other orien- weighted [T2W] image) contribute to contrast reso-
tation by applying an RF pulse is fundamental to lution with better pathologic details to the extent that
MR spectroscopy and imaging techniques because it T2 often contributes to tissue characterization.
provides a flexible method for investigating relax-
ation processes and other phenomena.14 By choosing
SPIN-ECHO PULSE SEQUENCE
an appropriate pulse sequence, the intensity of an
MR image can be made to reflect one or more of The spin-echo (SE) pulse sequence is the most com-
several NMR parameters inherent to the tissue being monly used technique to acquire MR images. T1-
examined.13,14 Although the proton density, chemical weighted MR images can be obtained using the SE
makeup, T1 and T2, and motion represent intrinsic pulse sequence with a short TR of 400 to 1,000 ms
tissue properties, the transition of these parameters and a short TE of 20 to 25 ms. The SE pulse
onto the MR image is also dependent on the partic- sequence of long TR (1,000 to 3,000 or more ms)
ulars of the imaging technique used to form that and short TE (20 to 40 ms) provides proton density
image. This subject has been described by many (PW) MR images. Long TR (1,000 to 3,000 or more
authors in several articles.19,20 ms) and long TE (40 to 120 or more ms) provide the
The 90- and 180-degree pulses are used for T2W MR images.
NMR techniques.14 In forming an MR image, the RF
pulse must be applied repeatedly. After each 90-
INVERSION RECOVERY PULSE SEQUENCE
degree pulse, the magnetization of the sample is
reduced to zero as this rotates the longitudinal mag- Various pulse patterns that emphasize different
netization vector (M) into the transverse (x-y) plane aspects of the evoked NMR signal can be exploited to
662 Ballenger’s Otorhinolaryngology
alter the contrast of MR images.13 In an “inversion delineation. It is often used with fat suppression
recovery” (IR) pulse sequence, a 180-degree (invert- T1W MR technique in the head and neck or where
ing) pulse, followed by a 90-degree (read) pulse, must the lesion may be obscured within high-intensity fat.
be applied repetitively for signal averaging pur- The gadolinium T1W pulse sequence is the best
poses.12,17 Because of application of a 180-degree pulse to evaluate intracranial extension of head and neck
and the fact that magnetization must be allowed to lesions. Gadolinium also enhances normal struc-
recover after the 180-degree inverting pulse, the IR tures, including mucosa, lymphoid tissue, extraocu-
sequence is slower than SE in data collection. lar muscles, and slow-flowing blood in veins.
The viewing devices (console) provided with
MR scanners, like CT scanners, have a set number of
FLUID-ATTENUATED INVERSION RECOVERY gray scales that can be used to adjust the contrast.
Fluid-attenuated inversion recovery (FLAIR) is used The MR parameters (TR, TE) and pulse sequences
to suppress the high CSF signal in T2W MR images (SE, IR), the strength of the magnet (eg, 1.5 tesla),
so that pathology adjacent to CSF is seen more and the time and number of images in each series of
clearly. This is a powerful pulse sequence to detect pulse sequences are recorded on the screen and
demyelinating disease, subarachnoid hemorrhage, reflected on each frame of hard-copy MR films.
leptomeningeal pathology, and most of intracranial Therefore, a simple method for beginners is to look
pathology. for TR and TE to recognize the T1W, PW, and T2W
images. A short TR (less than 1,000 ms) and a short
TE (20 to 25 ms) is a T1W image (Figure 31–4). A
USE OF GADOLINIUM CONTRAST MATERIAL long TR (more than 1,000 ms) and a short TE (20 to
Gadolinium, a rare earth element, is used in con- 40 ms) is a PW image, and a long TR (1,000 ms or
junction with T1W pulse sequences. With a standard more) and long TE (more than 40 ms) is a T2W
dose of 1 mmol/kg, it has little effect on T2W MR image (Figure 31–5). T1-weighted and PW images
images. The use of gadolinium-diethylenetriamine provide better anatomic details, and T2W images are
pentaacetic acid contrast material improves lesion best for pathologic details.
A B
FIGURE 31–5. Inverted papilloma. Proton-weighted (PW) (2000/02, TR/TE) (A) and T2-weighted (T2W) (2000/80,
TR/TE) (B) magnetic resonance (MR) images showing a large inverted papilloma (P). Notice the hyperintensity of the
tumor on the T2W MR image. Extension of the tumor in the left maxillary sinus is better demonstrated on T2W scan.
Fluid (F) in the sinus has an intermediate signal on PW and a hyperintense signal on T2W MR scans.
MAGNETIC RESONANCE ANGIOGRAPHY AND conventional invasive angiography, without the use
VENOGRAPHY of ionizing radiation or iodinated contrast materials
(Figure 31–6, A and B). On standard SE pulse
Magnetic resonance angiography (MRA) and venog- sequences, rapidly moving blood will usually yield a
raphy (MRV) are noninvasive techniques used to signal void (dark) regardless of the orientation of the
depict blood vessels in a projective format similar to plane of the image. Therefore, MRA must employ
A B
FIGURE 31–6. A, Magentic resonance venogram: two-dimensional time-of-flight coronal venography shows normal
venous structures. S = superior sagittal sinus; Ts = transverse sinus; ss = sigmoid sinus; jb = jugular bulb; jv = inter-
nal jugular vein. B, Sagittal magnetic resonance venogram shows normal venous structures. S = superior sagittal sinus;
T = torcula herophili; Ts = transverse sinus; ss = sigmoid sinus; jb = jugular bulb.
664 Ballenger’s Otorhinolaryngology
certain RF pulse sequences to produce signal from tumor, evaluating for carotid or vertebral dissection,
flowing blood. In MRA, the appearance of flowing and assessing the draining veins of arterial venous
blood depends on two main flow-related effects: malformations. Two-dimensional TOF MRV can be
time-of-flight (TOF) and phase contrast (PC). used to evaluate suspected intracranial venous
Technical advances, such as the development of thrombosis; however, thrombus may appear bright
the two-dimensional and three-dimensional gradi- (as a result of the short T1 of methemoglobin) and
ent-echo (GRE) pulse sequences (Figure 31–7), led can be confused for a patent venous sinus, resulting
to more widespread use of MRA and MRV. These in a false-negative examination.21
noninvasive techniques of studying blood flow not
only permit the evaluation of the vascular anatomy STANDARD FILM RADIOGRAPHY VERSUS
of the head and neck but also provide information
COMPUTED TOMOGRAPHY AND MAGNETIC
on flow direction, velocity, and blood vessel patency.
Both TOF and PC MRA can be obtained as a series RESONANCE IMAGING
of two-dimensional images or as a three-dimen- The modern diagnostic radiology department is
sional data set. This leads to the logical terminology equipped with a variety of medical imaging systems.
of two-dimensional TOF, three-dimensional TOF, Each has advantages and limitations. Plain film radi-
two-dimensional PC, and three-dimensional PC for ography is simple, fast, and inexpensive and pro-
the two fundamental approaches to vascular MRI duces sharp images of high-contrast structures (air,
techniques. fluid, bone) (Figures 31–8 to 31–15); however, high-
Clinical application best suited for two-dimen- contrast objects can obscure low-contrast objects,
sional TOF MRA includes mapping dural venous and the presence of overlying objects can sometimes
sinuses, evaluating the vascular structures of the be misleading.
neck for evidence of thrombosis or invasion by
TOMOGRAPHY
The conventional radiographic films and screens are
inherently nonuniform (less sensitive than the com-
puter) and would limit subject-contrast discrimina-
tion (resolution) to possibly 3 to 5%, which is greater
than the range for some soft tissue. Because of these
limitations, standard tomography such as polyto-
mography is no longer used if a CT unit is available.
Computed tomography and MRI allow the
reconstruction of tissue contrast in true cross-sec-
tions (ie, without being influenced by nearby or dis-
tant tissues in the section), with excellent tissue-
contrast discrimination (resolution).2 Both modali-
ties, and in particular MRI, provide the best
anatomic cross-sectional imaging technology avail-
able to date. The new-generation high-resolution
scanner, with a smaller pixel (picture element), the
combination of thin section (1 to 1.5 mm) and
extended bone range possibility (expansion of the
HU scale up to 4,000 units, ie, +3,000 to –1,000),
FIGURE 31–7. Schwannoma of the jugular fossa extend- provides clear definition and differentiation of soft
ing into the neck. A GRASS (gradient-recalled acquisi- tissue structures while also providing superior bone
tion in the steady state) image shows the hyperintense detail to complex motion tomography (Figures
internal carotid artery (i), internal jugular vein (j), verte- 31–16 to 31–18). Dynamic CT provides excellent
bral artery (arrow), and hyperintense mass (M) within definition of vascular structures and can differenti-
the right jugular vein. ate vascular tumors such as chemodectomas from
Imaging of Nasal Cavities, etc, and Base of the Skull 665
FIGURE 31–8. A, Waters’ view showing maxillary sinuses (S), frontal sinuses (F), nasal cavities (N), body of the zygoma
(Z), orbits (O), inferior orbital rim (arrowheads), floor of the orbit (curved arrow), temporal line (crossed arrows), zygo-
matic arch (curved hollow arrow), and petrous pyramid (P). B, Waters’ view shows blow-out fracture (depressed floor) of
the left orbit (arrows) with associated air-fluid level (hollow arrow). Note soft tissue swelling of the eyelid and cheek. F =
frontal sinus; N = nasal cavity; O = orbit; S = maxillary sinus; Z = zygoma. Arrowheads point to the inferior orbital rim,
the curved arrow points to the normal floor of the right orbit, and short arrows refer to the innominate line. C, Caldwell’s
view showing the maxillary (M), ethmoid (E), and frontal (F) sinuses. Notice orbits (O), inferior orbital rim (short
arrows), orbital floor (hollow arrows), lamina papyracea (crossed arrows), and innominate lines (curved arrows).
less vascular lesions such as neurogenic tumors (Fig- on CT scanning (see Figure 31–17). The technical
ure 31–19).22–24 factors of various pulse sequences to obtain an MR
image, in addition to physical and biochemical
composition of the sample, play a significant role in
MAGNETIC RESONANCE IMAGING tissue contrast in MR images. Water, such as in vit-
One of the advantages of MRI is the ability to reous cavity (see Figure 31–17, B), has long T1 and
obtain transverse (axial) and direct coronal, sagittal, T 2 relaxation times and would appear as
and oblique images without needing to change the hypointense (dark) in T1W and PW (proton-den-
position of the patient. The contrast relationships sity) (see Figure 31–17, B) images and as hyperin-
of different tissues on MRI are much different than tense (bright) in T2W MR scans. The lens has an
666 Ballenger’s Otorhinolaryngology
FIGURE 31–14. Epiglottitis and angioedema. A, Lateral neck film, showing marked enlargement of the epiglottis
(arrows). Notice marked thickening of the aryepiglottic folds. B, Lateral neck in another patient with angioedema show-
ing thickening of the epiglottis (E), aryepiglottic folds (small arrows), arytenoid region (A), pre-epiglottic space (PE),
and base of the tongue (BO). The large arrow points to the cricoid cartilage. C, Lateral neck of the same patient as in B,
showing marked resolution of the edema. There is now slight retropharyngeal soft tissue thickening (edema) (arrows).
FIGURE 31–16. A, Direct sagittal computed tomographic (CT) scan of the midline head, showing the hard palate
(arrow), sphenoid sinus (S), clivus (C), ethmoid air cells (E), and craniocervical junction. B, Sagittal CT scan showing
mucosal thickening of the maxillary sinus (short arrows), pterygomaxillary fissure (hollow arrow), pterygoid plate (P),
pterygopalatine fossa and inferior orbital fissure (curved arrow), carotid canal (C), jugular fossa (J), internal auditory
canal (long arrow), and mandible (M).
FIGURE 31–17. A, Normal ethmoid: axial computed tomographic (CT) scan through the plane of optic nerves, show-
ing the nasal bone (1), nasal process of the maxilla (2), lacrimal bone (3), periorbital fat (4), globe (5), lamina
papyracea (6), medial rectus muscle (7), optic nerve (8), zygomatic process of the frontal bone (9), lateral rectus mus-
cle (10), temporal fossa (11), temporal line (curved arrow), cranial opening of the optic canal (12), anterior clinoid
process (13), and posterior clinoid process (14). Note ethmoid (E) and sphenoid (S) sinuses and retroglobar fat (F).
Two of the “triple lines” seen in the submentovertical projection (see Figure 31–10), the orbital line (posterior wall of
the orbit) (open arrow) and middle cranial fossa line (arrows), are seen. B, Proton-weighted axial magnetic resonance
scan showing optic nerves, optic chiasm (long white arrow), hypothalamus (short black arrows), brainstem (B), and
cerebral aqueduct (arrowhead). Note visualization of the intracanalicular segment of the optic nerve (curved white
arrow) that is hardly seen in the CT scan. Notice that in this proton-weighted image, the water in the vitreous cavity
and cerebrospinal fluid in the lateral ventricles (curved black arrows) are hypointense and fat in the retrobulbar space
and is hyperintense in the subcutaneous space. The blood vessels are hypointense (hollow arrows).
670 Ballenger’s Otorhinolaryngology
FIGURE 31–19. A, Glomus vagale tumor. Incremental dynamic computed tomographic (CT) scan with the first sec-
tion obtained at the level of the tongue and extending superiorly (with automatic table incrementation) to the level of
the superior alveolar ridge in this patient with a large right neck mass. Notice sequential enhancement of the external
(a) and internal (b) carotid arteries and the internal jugular vein (c). A rounded enhancing mass is recognized on sec-
tions 5 and 6 (arrows), which show a prominent feeding vessel (see B). B, Glomus vagale tumor. Dynamic CT scan per-
formed at the level of the right neck mass in the same patient in A. Note intense enhancement of a paravertebral mass
(m) in the second section and rapid washout of contrast in the remainder of the sections. The glomus tumors often
behave like an arteriovenous malformation in CT dynamic study. Note the large artery (most likely the ascending pha-
ryngeal artery) (arrow) feeding this tumor. Note also the marked atrophy of the right side of the tongue in this patient
with twelfth nerve palsy caused by superior extension of the tumor into the posterior cranial fossa and with associated
destruction of the hypoglossal canal. Reproduced with permission from Mafee MF et al.24
Imaging of Nasal Cavities, etc, and Base of the Skull 671
T2W MR scans. Chronic blood would appear hyper- sinuses are too small to be seen, and the frontal
intense on T1W, PW, and T2W MR scans. Dense cal- sinuses develop later from the anterior ethmoid air
cifications would appear hypointense on T1W, PW, cells. Ethmoid and maxillary sinuses are the only
and T2W MR scans, and proteinaceous fluid such as sinuses that are large enough at birth to be seen on
a thick mucosal secretion and exudate would appear imaging studies (CT, MRI) and to be clinically sig-
hyperintense on T1W, PW, and T2W MR scans. nificant in rhinosinusitis. The framework of the
Highly proteinaceous fluid may appear hypointense external nose is composed of bones and hyaline car-
on T2W MR images. Inspissated mucus may appear tilages. Its bony framework consists of the nasal
very hypointense on T2W MR scans. bones, the frontal processes of the maxillae, and the
nasal part of the frontal bone. The posterior nasal
apertures or choanae are two oval openings, each
POSITRON EMISSION TOMOGRAPHY measuring about 2.5 cm in the vertical and 1.25 cm
Positron emission tomography (PET) using 2-18F- in the transverse direction. The choanae are best
fluoro-2-deoxy-D-glucose (FDG) has come to play a evaluated on axial CT and MRI scans (Figure
definite role in head and neck oncology.28 Positron 31–20). The roof, floor, and medial (septal) and lat-
emission tomography depends on the altered meta- eral walls of each half of the nasal cavity can be best
bolic activity of the tumoral tissue, of which evaluated on coronal CT and MR scans (Figure
increased glycolysis is a hallmark. 2-18F-fluoro-2- 31–21). The roof of the nasal cavity is narrow from
deoxy-D-glucose, a glucose analog, is trapped prefer- side to side. The lateral wall of the nasal cavity is very
entially within tumor cells with increased glycolysis, irregular owing to the presence of nasal conchae.
allowing for their detection. As a metabolic imaging The nasal conchae are best evaluated on coronal CT
modality, FDG-PET has been shown to have a sig- scans, projecting downward and slightly medially,
nificant impact in the diagnosis and management of each forming the roof of a passage or meatus (infe-
head and neck malignancies. It is a powerful tool in rior, middle, and superior), which communicates
the assessment of recurrence of malignancies and freely with the nasal cavity (see Figure 31–21). The
seems to be more effective and reliable than inferior concha is an independent thin bone that
anatomic imaging techniques for the evaluation of articulates with the nasal surface of the maxilla and
head and neck tumors. the perpendicular plate of the palatine bone. The
A B
FIGURE 31–21. A, Coronal computed tomographic (CT) scan, same patient as in Figure 31–20, shows the inferior
turbinate (1), middle turbinate (2), nasolacrimal ducts (N), uncinate process (long black arrow), Haller cell (hollow
arrow), agger nasi cell (A), lateral lamella (long white arrow), fovea ethmoidalis (double white arrows), and canal for the
ethmoidal artery (curved arrow). B, Coronal CT scan, same patient as in A, shows the bulla (B), Haller cells (H), and
maxillary ostia (arrows), opening into the infundibulum.
inferior meatus receives the orifice of the naso- A). The superior concha is a small curved lamina
lacrimal canal (see Figure 31–21, A). The middle and that lies above and behind the middle concha. The
superior conchae are bony projections from the superior meatus receives the opening of the poste-
medial surface of the ethmoidal labyrinth (see Fig- rior ethmoidal air cells (Figure 31–22). A narrow inter-
ure 31-21, A). The middle concha extends backward val, the sphenoethmoidal recess (see Figure 31–22),
to articulate with the perpendicular plate of the separates the superior concha from the anterior sur-
palatine bone. The middle meatus receives the open- face of the body of the sphenoid, through which the
ing of the anterior and middle ethmoid air cells, sphenoidal sinus opens into the nasal cavity (see Fig-
frontal sinuses, and maxillary sinuses (Figure 31–21, ure 31–22). A fourth concha (concha suprema) is
A B
FIGURE 31–22. A, Sagittal computed tomographic (CT) scan shows the uncinate process of the ethmoid (arrows),
infundibulum (broken line), bulla (B), basal lamella (hollow arrow), posterior ethmoid sinus (Pe), sphenoid sinus (S),
and middle (2) and inferior (1) turbinates. B, Sagittal CT scan shows the inferior turbinate (1), middle turbinate (2),
uncinate process (small straight arrow), agger nasi cell (A), frontal recess (large straight arrow), basal lamella (hollow
arrow), posterior ethmoid sinus (pe), sphenoid sinus (S), and sphenoid sinus ostium (curved arrow).
Imaging of Nasal Cavities, etc, and Base of the Skull 673
often present on the medial surface of the ethmoidal to the presence of fat. The air is seen as a dark image
labyrinth above and behind the posterior end of the on both CT (low electron density) and MR (low pro-
superior concha. Immediately behind the superior ton density) images (see Figure 31–17).
meatus, the sphenopalatine foramen, which opens The ethmoid sinuses are positioned between
into the pterygopalatine fossa, pierces the lateral wall the orbits and comprise approximately 10 to 12 cells
of the nasal cavity. It transmits the sphenopalatine within the labyrinth of the ethmoid bone. The fine
artery, nasopalatine artery, and the nasopalatine and bone septa of the ethmoid labyrinth, the lamina
superior nasal nerves from the pterygopalatine fossa. papyracea, olfactory groove, cribriform plate and its
lateral lamella, fovea ethmoidalis, canals for eth-
Maxillary Sinuses Maxillary sinuses begin to moidal arteries, and maxillofacial bony structures
develop around the sixty-fifth day of gestation. The will be best imaged by extended-bone window high-
size of the sinus at birth is about 6 to 8 cm3. Air can resolution CT (Figures 31–18, 31–22, and 31–23).29,30
be seen on CT scans within the maxillary sinuses at The anatomic landmarks of the ethmoid bone and
or a few days after birth. Rapid expansion occurs ostiomeatal unit, such as the uncinate process,
from 7 to 18 years, related to eruption of the perma- infundibulum, middle meatus-ethmoid complex,
nent teeth. They are the largest accessory air sinuses ethmoid bullae, middle turbinate, and cribriform
of the nose, and when fully developed, they occupy plate (as well as the ostium of the maxillary
the body of the maxilla, and each is approximately sinuses), are best evaluated on coronal as well as axial
15 mL in volume (see Figures 31–20 and 31–21). and reformatted sagittal CT images (see Figures
The natural opening of the sinus is high above the 31–20 and 31–21).31–34 Just anterior to the superior
floor and poorly placed for natural drainage. The attachment of the middle turbinate and anterior to
middle meatus is of such a shape that pus running the frontal recess (frontonasal duct) are the agger
down from the frontal sinus or the anterior eth- (ridge) nasi (a rudimentary turbinate) and agger nasi
moidal sinuses is directed by the hiatus semilunaris cells (see Figure 31–22). The agger nasi cells can
into the opening of the maxillary sinus, which may, invade the lacrimal bone or the ascending process of
in some cases, act as a secondary reservoir for pus the maxilla. Just posterior and inferior to the agger
discharged from these sinuses. Accessory ostia are nasi cells lies the ethmoidal uncinate process, a thin
present in 15 to 40% of cases, usually in the mem- curved bar of bone from the lateral side of the eth-
branous medial sinus wall. moidal labyrinth that forms a portion of the lateral
nasal wall. It projects downward and backward and is
Ethmoid Sinuses Ethmoid cells begin to develop subject to considerable variation in size. It ranges in
around the third to fourth month of fetal life, and height from 1 to 4 mm and is 14 to 22 mm long.31
there may be a few cells (four to five cells) present at Anteriorly, it articulates with the lacrimal bone and
birth. At birth, the size of the anterior ethmoid cells ethmoidal process of the inferior nasal concha (see
is approximately 5 mm high, 2 mm long, and 2 mm Figure 31–21). The superior edge of this process is
wide. The size of the posterior cells is 5 mm high, 4 free and forms the medial boundary of the hiatus
mm long, and 2 mm wide. By the age of 12 years, the semilunaris (see Figure 31–23). The ethmoidal
ethmoid air cells have almost reached their adult size infundibulum is a trough-shaped cavity (cleft) that is
(see Figure 31–22). below the bulla ethmoidalis and above and lateral to
Because fat, fluid, and bone are natural contrast the uncinate process. The infundibulum is best visu-
material, the orbit is the ideal structure for a highly alized on coronal CT scans (see Figure 31–21). In
detailed CT and MRI scan. A scan taken through the more than 50%, the infundibulum continues superi-
orbits shows the relationship of the ethmoid sinuses, orly as the frontonasal duct into the frontal sinus.32
sphenoid sinuses, pituitary fossa, cavernous sinuses, The basal (ground) lamella, which separates the ante-
and temporal lobes with the orbit (see Figure 31–17). rior and posterior air cells, can best be evaluated on
The cortical bones, which appear hyperdense on CT axial as well as coronal CT scans. An air space (cleft)
images (see Figure 31–17, A), are seen on MR as is usually found between the basal lamella and the
hypointense images because of little MR signal from bulla, which may extend superiorly to the bulla. This
them (see Figure 31–17, B). The bone marrow is called the sinus lateralis. This sinus lateralis, unlike
appears on T1W MRI as a hyperintense image owing the other anterior ethmoidal air cells that open into
674 Ballenger’s Otorhinolaryngology
A B
FIGURE 31–23. Normal base of the skull. A, High-resolution axial computed tomographic (CT) scan at the level of the
clivus (11), using the extended-bone CT range technique showing the ethmoidal labyrinth (E), sphenoid sinus (S), pos-
terior wall of the orbit (arrowheads), foramen ovale (1), foramen spinosum (2), air in the eustachian tube (3), jugular
fossae (4), mastoid air cells (5), foramen magnum (6), hypoglossal canal (7), vertical portion of the facial nerve canal
(8), lateral extension of the right jugular fossa (9), and mandibular condyle (10). B, Coronal CT scan shows the ante-
rior clinoid (small straight arrow), superior orbital fissure (curved arrow), greater wing of the sphenoid (large arrow),
foramen rotundum (R), intersphenoid septum (arrowhead), inferior orbital fissure (hollow arrow), and optic canal (O).
the infundibulum, may communicate with the terior ethmoidal air cells, encroaching into the sphe-
frontal recess or open directly and independently noid sinus. (7) An asymmetric intersphenoid septum
into the middle meatus. Certainly, individual struc- or septae are important because the posterior exten-
tural differences in ethmoidal and ostiomeatal com- sion of this partition usually marks the location of
plexes and other paranasal sinuses are to be expected, the internal carotid artery groove (sulcus), which at
and the reader ought not be discouraged should cer- times may be dehiscent, resulting in bulging of the
tain illustrations in the literature fail to be identical internal carotid artery into the sphenoid sinus. Other
with the images he or she will review for any indi- anatomic variations include deviation of the nasal
vidual patient. Certain anatomic variations are septum, paradoxical middle turbinate, uncinate
observed more commonly, and these are as follows: process pneumatization (bulla), pneumatized supe-
(1) concha bullosa, a pneumatized middle turbinate; rior turbinate, pneumatized cristal galli, congenital
(2) low position of the fovea ethmoidalis and dehis- dehiscence or post-traumatic deformity of the
cence of the lateral lamella of the cribriform plate; medial wall or floor of the orbit, and exposed inferior
(3) bulging of the optic canal into the posterior eth- orbital nerve within the maxillary sinus.
moidal complex; and (4) deviation of the uncinate
process. The superior edge of the uncinate process Frontal Sinuses Developmentally, the frontal sinus
may elevate medially to obstruct the middle meatus begins during the fourth month of fetal life in the
and, more importantly, may deviate laterally to region of the frontal recess. At birth, it is indistin-
obstruct the infundibulum. Marked lateral deviation guishable from the anterior ethmoid cells. Postnatal
(commonly seen in patients with a hypoplastic max- growth is slow. It is visible after the first or second year
illary sinus) or even fusion of the uncinate process to of life and is well developed by 7 to 8 years. Its size
the medial orbital wall may endanger the orbit. (5) increases until the late teens. Each frontal sinus drains
Haller cells are ethmoidal air cells extending along into the middle meatus of the nasal cavity via the
the medial floor of the orbit (infraorbital ethmoid air frontonasal duct, best visualized on sagittal CT scans
cells) (see Figure 31–21, B). (6) Onodi cells are pos- (see Figure 31–22). This communication between the
Imaging of Nasal Cavities, etc, and Base of the Skull 675
frontal sinus and nasal cavity is not strictly a duct but axial and coronal sections have established CT as
an internal channel positioned between the sinus and the method of choice in the staging of maxillofacial
the anterior part of the middle meatus, referred to as neoplasms and the evaluation of chronic and com-
the frontal recess. The natural ostium of the frontal plicated inflammatory processes of the paranasal
sinus can be found at the superior-anterior end of the sinuses and face.32–34 Magnetic resonance imaging has
infundibulum. When the frontal recess air cells and been used to evaluate maxillofacial anatomy as well
agger nasi cells in this area are carefully removed, the as pathology. Familiarity with CT dictates that the
ostium will come into view. MR evaluation complements and does not substitute
for the CT evaluation. Magnetic resonance imaging is
Sphenoid Sinuses Developmentally, the sphenoid superior to CT for evaluation of the extent of soft tis-
sinuses begin during the third fetal month as evagi- sue involvement and intracranial invasion by
nations of mucosa of the nasal cavity. At birth, the sinonasal tumors. A detailed discussion of the vari-
sinuses remain small and are little more than evagi- ous pathologic entities of the paranasal sinuses and
nations of the sphenoethmoid recess. After the fifth nasal cavity is limited by the scope of this chapter,
year, invasion of the sphenoid bone is more rapid, although certain conditions will be described to illus-
and by the age of 7, the sinus extends posteriorly to trate the role of CT and MRI in the evaluation of
the level of the sella turcica. Further enlargement patients with paranasal sinus and nasal diseases.
occurs after puberty. The pneumatization of sphe- Conventional plain films still can be used to
noid bone may be extensive. The sinuses may extend provide the screening studies in various pathologic
posteriorly to the clivus, anteriorly to the tuberculum conditions of the sinuses and in particular in max-
sella and planum sphenoidale, and out into the ante- illofacial trauma and give orientation and direction
rior clinoids (see Figures 31–22 and 31–23). Lateral to further examinations using CT.33,34 Developmen-
extension results in pneumatization of the base of the tal anomalies, such as a palatomaxillary cleft, are
pterygoid processes as well as part of the greater wing more clearly seen using CT (Figure 31–24). The
of the sphenoid. Each sinus drains into the nasal cav- appearance of lesions of the paranasal sinuses and
ity. The sphenoidal ostium drains into the superior face on CT scans usually does not provide sufficient
meatus in the sphenoethmoidal recess, above the evidence for a specific histologic diagnosis; however,
superior concha, well above the floor of the sinus. On cystic (Figure 31–25), cartilaginous, and osseous
average, the ostium measures 2 × 3 mm and lies 10
tumors are an exception (Figure 31–26). Fibrous
mm above the floor of the sinus.
dysplasia (FD) also frequently shows characteristic
Use of Computed Tomographic Scan for Com-
puter-Aided Endoscopic Surgery Functional
endoscopic sinus surgery has become a frequently
performed operation in patients with chronic rhi-
nosinusitis.35,36 A preoperative CT scan is obtained in
all patients according to the protocol of the specific
system used. The CT protocol requires contiguous,
1 to 3 mm-thick, nonoverlapping, axial sections.
Images are transferred to the computer-aided sur-
gery system by means of an optical disk or storage
tape. The CT scan is performed using fiducials;
therefore, correlation of the patient’s anatomy with
corresponding points on the CT images is accom-
plished by the registration process.
FIGURE 31–28. Ethmoid periostitis and subperiosteal phlegmon. Note soft tissue replacement of air in the left eth-
moid labyrinth with thickening of the trabeculae. The left lamina papyracea is thickened and in some areas dehiscent.
These findings are indicative of periostitis. Note soft tissue swelling (not yet leading to necrosis and abscess formation)
in the left periorbita (arrowheads), resulting in displacement of the left medial rectus muscle (1). Notice proptosis of
the left eye and marked periorbital edema and inflammation anterior to the orbital septum (arrow).
abscess, and ophthalmic vein thrombophlebitis (Fig- Periostitis and osteomyelitis of the frontal bone
ure 31–30).37–41 Should the infection spread from the can complicate frontal sinusitis.37 An infection of the
sinuses into the cranial cavity, one or more of the fol- frontal sinus severe enough to involve the orbit may
lowing complications may ensue: cavernous sinus also extend through the posterior plate of the frontal
thrombosis, meningitis, epidural (see Figure 31–30), sinus to involve the anterior cranial fossa (see Figure
subdural, or brain abscesses.37–41 Intracranial compli- 31–30).37 Orbital complications that result from
cations are better evaluated by MRI than CT scanning sphenoid sinusitis can best be evaluated with CT and
(Figure 31–31). MRI scans (see Figure 31–31).
FIGURE 31–30. A, A computed tomographic (CT) scan showing increased density of the ethmoid labyrinth and bilat-
eral retro-orbital soft tissue inflammation (cellulitis) (A and B). Note also a low-density image involving the left upper
eyelid (C). The eyelid lesion (C) was drained, and 3 mL of pus were removed. Hollow arrowhead points to the supe-
rior ophthalmic vein, and the arrow points to the retroseptal granulation tissue. B, Postcontrast semicoronal CT scan
of the same patient in A showing enhancing soft tissue densities (polyps and hyperplastic mucosa) involving the max-
illary and ethmoid sinuses. Notice the polyp in the right nasal cavity (7) and periorbital cellulitis involving the right
orbit (A). 1 = medial rectus muscle; 2 = optic nerve; 3 = inferior rectus muscle; 4 = lateral rectus muscle; 5 = superior
rectus muscle; 6 = superior oblique muscle. C, A CT scan of the same patient in A and B showing increased density of
the frontal sinuses with erosion of the posterior table of the left frontal sinus (arrows). D, Postcontrast CT scan obtained
5 mm superior to C, showing enhancement along the exposed and displaced dura (arrows).
Chronic inflammatory disease is often associ- asymptomatic unless they are associated with bleed-
ated with sclerosis of the walls of the sinuses and ing. Fungus ball is seen as an area of increased den-
ethmoidal trabeculae41 (Figures 31–32 and 31–33). sity and calcification within the center of an involved
Fungi, particularly Aspergillus, may be considered sinus. Allergic fungal sinusitis can slowly expand and
possible causative agents. Fungal sinusitis can be erode into surrounding structures. Atopy, asthma,
divided into several categories: fungus ball forma- and chronic illness requiring multiple courses of
tion, allergic fungal sinusitis, and acute and chronic antibiotics are characteristic of this infection.43 Nei-
sinusitis. “Fungal ball” refers to a saprophytic colo- ther fungus ball formation nor allergic fungal sinusi-
nization of a cavity by fungus hyphae without inva- tis has been associated with diabetes.43
sion of adjacent tissue. It usually occurs in the lung Polyposis of the paranasal sinuses and nasal
(typically in a parenchymal cavity or an ectatic cavity (Figure 31–34) and mucocele of the maxillary
bronchus), the paranasal sinuses, nasal and auricular (Figure 31–35), frontoethmoid (Figure 31–36), and
cavities, or the urinary tract.42 Aspergillus is most sphenoid sinuses (Figure 31–37) are best evaluated
commonly involved in the formation of fungus balls, by CT and MRI scans.29,33,44,45 Mucoceles and benign
although they may occasionally be caused by Can- tumors tend to expand the area of origin by virtue of
dida, Sporothrix, or Penicillium or by bacteria, their slow growth.29,44 The gradual pressure, atrophy,
namely Nocardia.42 Fungus balls are generally and erosion of the bone by the enlarging soft tissue
Imaging of Nasal Cavities, etc, and Base of the Skull 679
A B
FIGURE 31–39. Squamous cell carcinoma of the sinonasal cavities. A, Axial proton-weighted magnetic resonance
(MR) scan showing a large mass (arrows) involving the left nasal cavity and ethmoid complex. Note mucosal secretion
(S) in the left posterior ethmoid sinus and left sphenoid sinus. B, Coronal T1-weighted MR scan, showing a large mass
(arrows). Note mucosal secretion (S) in the ethmoid air cells.
tumors or inflammatory conditions are best demon- CT scanning. Orbital findings in trauma are well
strated by MRI. documented.51 The fracture fragments and foreign
bodies projecting into the orbit and fat and muscle
Trauma Conventional plain film examination can herniation projecting into the ethmoid or maxillary
be used for radiologic diagnosis of the isolated max- sinuses are readily identified together with any
illofacial fracture.51 In complex maxillofacial trauma, hematoma and/or pneumo-orbit (Figure 31–43).
CT provides the most cost-effective imaging modal- Computed tomography is the procedure of choice
ity.51 Current-generation spiral CT scanners provide for evaluation of the position of the Silastic implant
excellent bone detail. The orbit is superbly suited to for the repair of orbital floor fracture. The fracture
of the lamina papyracea, which is difficult to image
conventionally, can be imaged using axial and coro-
nal sections.
The intracranial and intraorbital extension of
complex maxillofacial fractures, shattering craniofa-
cial fractures, and medial and lateral orbital wall and
orbital apex fractures can be imaged using CT scan-
ning in a manner not previously possible.51 The axial
dimension of posterior maxillary, alveolar, and
pterygoid plate fractures and the posterior exten-
sions of the Le Fort group of fractures are particu-
larly suited to axial CT imaging (Figure 31–44).30
Displacement and rotation of the malar bone and
bone fragments in tripod fractures can best be
demonstrated with axial CT (Figure 31–45). Sphe-
FIGURE 31–40. Carcinoma of the nasal cavity. Postcon- noid sinus fractures can be evaluated using axial and
trast coronal computed tomographic scan showing a particularly direct coronal section and sagittal refor-
large tumor in the left nasal cavity (1) extending into the matted images. The coronal CT sections should be
left maxillary sinus (2) and left ethmoid sinus (3). Note taken only in the injured patient who is physically
destruction of the medial wall of the left maxillary sinus stable and is without cervical spine injury. In a
and partial destruction of the maxilloethmoidal plate. sphenoid sinus fracture, opacification of the sinus
Imaging of Nasal Cavities, etc, and Base of the Skull 683
FIGURE 31–41. A, Carcinoma of the right maxillary sinus. Postcontrast axial computed tomographic (CT) scan show-
ing a large mass involving the right maxillary sinus (1) and extending into the right nasal cavity. There is erosion of
the anterior wall of the maxillary antrum (arrows). Note destruction of the posterior wall of the right maxillary sinus
and extension of the tumor into the right infratemporal fossa (2). Note the tumor in the right pterygopalatine fossa
with partial erosion in the pterygoid portion of the right sphenoid bone (arrow). B, Rhabdomyosarcoma; axial CT scan
shows a large mass in the right ethmoid sinus (black arrows) with extension into the right orbit (white arrows). Note
extension of the tumor in the superior portion of the right maxillary sinus (hollow arrow) with tumor seen in the ptery-
gopalatine fossa (curved arrow). C, Esthesioneuroblastoma; axial CT scan shows a mass in the left ethmoid sinus
(arrows) with opacity of the sphenoid sinuses. D, Coronal CT scan of the same patient as in C showing markedly
enhanced mass (arrows) in the anterior cranial fossa caused by extension of the tumor along the cribriform plate into
the cranium.
Continued on next page
684 Ballenger’s Otorhinolaryngology
FIGURE 31–41 continued. E, Adenocarcinoma of the nasal cavity and ethmoid sinus. T1-weighted sagittal magnetic res-
onance (MR) scan shows a large tumor (T) within the nasal cavity and ethmoid cells. Note the hyperintensity of the
retained secretion in the sphenoid sinus (S). F, T2-weighted sagittal MR scan of the same patient as in E. The tumor (T)
appears hyperintense. The retained fluid remains hyperintense within the sphenoid sinus (S).
with blood or CSF can be readily recognized with a Cerebrospinal Fluid Leak and Pneumocephalus
CT scan. In trauma patients, the recognition of free air within
Three-dimensional reconstruction of CT the cranial cavity and cisternal and ventricular system
images is a well-established imaging modality that is the result of a dural and subarachnoid tear. This
has been investigated in various clinical settings. can occur at any number of sites: the posterior wall
Perhaps one of its most useful applications is in of the frontal sinus, the roof of the ethmoid
trauma. Rotational abnormalities are better appre- labyrinth, the cribriform plate, the walls of the sphe-
ciated on three-dimensional images (see Figure noid sinus, the middle and posterior cranial fossae,
31–45). and beyond. Localization of the fracture site and
FIGURE 31–42. A, Osteogenic sarcoma computed tomographic (CT) scan showing a large maxillary tumor with irreg-
ular islands of bone formation (arrows) and with marked bone destruction. Notice invasion of the floor of the orbit (hol-
low arrow). B, Giant cell tumor of the sphenoid bone; axial CT scan shows a destructive tumor of the sphenoid bone (black
arrows) with extension into the posterior ethmoid cells. Notice destruction of the clivus (white arrow) and exposed dura.
Imaging of Nasal Cavities, etc, and Base of the Skull 685
bone fragments in axial and, if possible, direct coro- roof is attached to the base of the skull at the clivus
nal display, using thin sections (1.5 to 3 mm) in crit- and slopes downward to become the posterior pha-
ical areas is mandatory. Contrast examination with ryngeal wall, which overlies the atlas and its related
intrathecal, water-soluble, iodinated contrast mate- ligaments and muscles. The inner surface of the pha-
rial is not indicated at this stage since most acute CSF ryngeal musculature (pharyngeal constrictor mus-
leaks will close spontaneously or with operative frac- cle) is lined by the pharyngobasilar fascia. The
ture reduction alone.30 In persistent CSF leaks, all pharyngobasilar fascia, or pharyngeal aponeurosis,
such fistulae should undergo CT cisternography encircles the space between the upper border of the
(Figure 31–46).52,53 The examination must be carried superior constrictor muscle and the skull base. The
out during a period of active CSF rhinorrhea or otor- eustachian tube opens into the nasopharynx by
rhea for effective imaging results.52,53 Other examina- piercing the pharyngobasilar fascia. The most
tions, such as a radionuclide CSF scan, may not be prominent anatomic landmark on the lateral wall of
needed.30 When the leak is large, MRI may be suffi- nasopharynx on each side is the cartilaginous medial
cient to make the correct diagnosis. Aggressive end of the eustachian tube (torus tubarius) (Figures
arachnoid granulations, causing CSF leak, may be 31–47 and 31–48). Between the torus and the poste-
detected by MR following IV administration of rior wall is the fossa of Rosenmüller, a cleft-like
gadolinium contrast material. There will be local space whose apex reaches the anterior margin of the
enhancement at the site of arachnoid granulation. carotid canal (see Figures 31–47 and 31–48).54,55
Computed tomography and MR examinations of
Nasopharynx The nasopharynx is a cuboidal the nasopharynx delineate the air-containing cavity of
structure whose anterior limits are the choanae. The the nasopharynx, the mucosal surfaces, and the deep
686 Ballenger’s Otorhinolaryngology
FIGURE 31–45. A, Malar fracture. Axial computed tomographic (CT) scan showing fractures involving the inferior
orbital rim and the left malar bone, which extend along the left zygomaticomaxillary suture (small arrow). Notice frac-
ture of the left zygomatic arch, fracture of the posterior wall of the left maxillary sinus (open arrowhead), and bone
fragments within the left maxillary antrum with associated left antral submucosal hematoma. B, Malar fracture. Three-
dimensional image reformation from regular CT scans showing the fractures and displacement of the malar bone.
compartments. The relationship between the medial and perhaps more accurate diagnosis. Specifically,
pterygoid fascia, representing the medial wall of the tumors that arise in the prestyloid PPS are most
masticator space, and the fascia of the tensor veli often of salivary gland origin.56 We have seen neuro-
palatini, representing the medial wall of the presty- genic tumors and hemangiopericytoma in the
loid PPS, allows better preoperative differentiation prestyloid PPS. Tumors that arise in the masticator
space are unlikely to be of salivary gland origin.
Tumors that arise in the poststyloid PPS are most
often of neurogenic or chemoreceptor (paragan-
glion) origin. The fat content of the PPS allows one
to identify it as hypodense (dark) on CT scan (see
Figure 31–47, A) and hyperintense (bright) on T1W
and PW MR images (see Figure 31–47, B).
Squamous cell carcinomas account for 80% of
nasopharyngeal cancers. The remaining nasopha-
ryngeal tumors will prove to be lymphomas (includ-
ing plasmacytoma and Burkitt’s lymphoma),
chloroma, chordoma, and a variety of rare condi-
tions, including adenocarcinomas, melanoma, rhab-
domyosarcoma, schwannoma, lipoma, liposarcoma,
Kaposi’s sarcoma, and metastasis. Magnetic reso-
nance imaging and CT scans of the nasopharynx are
FIGURE 31–46. Cerebrospinal fluid rhinorrhea. Coronal indispensable in patients with clinically diagnosed
computed tomographic scan after intrathecal injection of nasopharyngeal disease in whom information con-
metrizamide showing contrast-enhanced subarachnoid cerning the extent of disease is necessary (Figures
space of the anterior cranial fossa (upper arrow) just 31–49 through 31–53) and in those patients in
above the crista galli. Note the fracture of the left cribri- whom a search is being made for an unknown pri-
form plate (lower arrow) and the presence of metrizamide mary tumor of the head and neck (see Figure
(high density) within the ethmoid labyrinth and the air 31–51). Hypertrophied and normal lymphoid tissue
metrizamide fluid level in the left maxillary sinus. is seen commonly within the nasopharynx.54 Ade-
688 Ballenger’s Otorhinolaryngology
FIGURE 31–47. Normal nasopharynx, maxillary sinus, and infratemporal fossa. A, Axial computed tomographic scan
through the midportion of the maxillary sinuses (M) and upper part of the odontoid process (13) showing the nasal
septum, inferior turbinate (1), nasopharynx (NP), temporalis muscle (2), coronoid process (3), zygoma (4), masseter
muscle (5), parotid gland (6), styloid process (7), longus capitis muscle (8), torus tubarius (9), tensor veli palatini mus-
cle (10), lateral pterygoid plate (11), and lateral pterygoid muscle (12). The density seen behind the torus is mainly
caused by the levator veli palatini muscle. The tensor veli palatini is rarely seen as a distinct muscle bundle. Part of the
density seen medial to the lateral pterygoid plate is caused by the tensor veli palatini muscle (10). Medial to the deep
lobes of the parotid glands (6), the symmetric low-density parapharyngeal spaces are seen. Posterior to the styloid
process are seen the densities of the petrostyloid neurovascular structures. B, Axial proton-weighted magnetic reso-
nance scan showing the quadratus labii superioris muscle (open arrow), obicularis oculi and zygomaticus muscles
(white and black arrows), angular vein (white arrow), zygomatic bone (Z), maxillary antrum (*), nasal turbinate (N),
masseter muscle (M), pterygoid muscles (P), mandible (curved arrow), retromandibular vein (arrowhead), vertebral
artery (white and black arrows), longus colli muscle (L), external (e) and internal (I) carotid arteries, internal jugular
vein (J), and temporalis muscle (T).
noidal tissue is usually symmetric and has a lobu- cial planes. In children, rhabdomyosarcoma of the
lated pattern. Benign lymphoid tumor of the nasopharynx as well as lymphoepithelioma (see Fig-
nasopharynx is limited to the mucosa and is smooth ure 31–52) and lymphoma should always be included
in outline. Any extension into the deeper plane with in differential diagnosis of a nasopharyngeal mass.
obliteration of the facial planes should be considered Lymphoepitheliomas or the so-called Schmincke
evidence of a more aggressive lesion54,55 (Figures tumors refer to undifferentiated nonkeratinizing
31–49, 31–50, 31–54, and 31–55). Extension of the tumors that have numerous lymphocytes. These
nasopharyngeal carcinoma into the nasal cavity (see tumors can be seen in young adults and children (see
Figure 31–49), infratemporal fossa, orbit, and cra- Figure 31–52). We have seen them in children as
nial cavity is best demonstrated by contrast- young as 5 to 12 years of age. A dynamic CT or a
enhanced CT examination or MRI.55 Naso- dynamic MR study should be used to differentiate
pharyngeal carcinomas and, in particular, lym- lesions such as juvenile angiofibroma (see Figure
phoepitheliomas are infiltrative. Lymphomas, which 31–54) and for any nasopharyngeal hypervascular
are the second most common malignant nasopha- lesion such as extension of the glomus tumor along
ryngeal tumors, are bulky and often respect the fas- the eustachian tube into the nasopharynx (see Figure
Imaging of Nasal Cavities, etc, and Base of the Skull 689
FIGURE 31–48. A, Normal nasopharynx. Axial computed tomographic (CT) scan through the midnasopharynx (NP)
with the patient instructed to blow against a closed mouth. Note the torus tubarius (arrowhead) and extension of air
into the eustachian tube (e) (anterior to tori) and Rosenmüller’s fossae (r) (posterior to tori). Note enhancement of
the retrostyloid vascular structures (internal jugular vein) (curved arrow) after intravenous iodine-contrast infusion.
The upper part of the parotid gland is seen posterior to the mandible (m) and anterior to the mastoid process (ma).
s = styloid process; c = mandibular condyle. B, Semicoronal CT section of the nasopharynx showing the clivus (1),
longus capitis muscle (2), torus tubarius (3), lateral (4) and medial (5) pterygoid muscles, soft palate (6), mandible (7),
masseter muscle (8), and parotid gland (9). Note the eustachian tube opening (lower arrow) just inferior to the tori (3)
and superior extension of Rosenmüller fossa (upper arrow).
31–55) and hypervascular metastases such as meta- Benign lesions of the nasopharynx such as
static hypernephroma and thyroid carcinoma. inflammatory processes (Figure 31–56), Tornwaldt’s
cyst, parapharyngeal cyst, polyps, papillomas, juve-
nile angiofibromas, neuromas, fibromas, and lipo-
mas are all well suited for MRI and CT.54,55
ORBITS
Because fat, fluid, and bone are natural contrast
material, the orbits are the ideal structures for highly
detailed CT and MRI scans. Scans taken through the
orbits show the relationship of the ethmoid sinuses,
sphenoid sinuses, pituitary fossa, cavernous sinuses,
and temporal lobes with the orbits (see Figure
31–17). The cortical bones, which appear hyper-
dense on CT images (see Figure 31–17), are seen on
MR as hypointense images (see Figure 31–17). The
bone marrow appears on T1W scans as hyperintense
owing to the presence of fat. The air is seen as a dark
image on both CT and MRI scans. The optic nerves
FIGURE 31–49. Nasopharyngeal carcinoma. Axial com- within the orbits can be visualized with both CT and
puted tomographic scan of the nasopharynx showing a MRI. The intracanalicular portion of the optic nerve
large soft tissue tumor (T) occupying the left side of the is best seen on MRI (see Figure 31–17). The lateral
nasopharyx and extending into the left nasal cavity. orbital wall separates the orbit from the middle cra-
690 Ballenger’s Otorhinolaryngology
FIGURE 31–56. Scleroma of the nasopharynx. Proton-weighted (A) and T2-weighted (B) axial magnetic resonance
scans show a mass (M) in the nasopharynx.
Imaging of Nasal Cavities, etc, and Base of the Skull 693
The horizontal limb is the inferior orbital fissure, palatine) fossa is a small, pyramidal space at the
which is shown best in coronal and axial CT sections angle of the junction of the inferior orbital fissure
(see Figure 31–23), and the vertical limb is the ptery- and pterygomaxillary fissure at the apex of the orbit
gomaxillary fissure, which is formed by the diver- (see Figure 31–16, B). It is bound by the infratem-
gence of the maxilla from the pterygoid process of poral (posterior) surface of the maxilla, the vertical
the sphenoid and is shown best in sagittal (see Fig- plate of the palatine bone, and the base of the ptery-
ure 31–16, B) and horizontal (axial) CT and MRI goid process (see Figure 31–16, B). It communicates
images. The pterygomaxillary fissure connects the with the nasal cavity by the sphenopalatine foramen,
infratemporal fossa with the pterygopalatine fossa with the infratemporal fossa by the pterygomaxillary
(see Figure 31–16, B) and transmits the terminal fissure, and with the orbit by the inferior orbital
part of the internal maxillary artery and veins.55,56 fissure. The sphenopalatine foramen transmits
The pterygopalatine (sphenomaxillary or spheno- the sphenopalatine vessels and the superior nasal
FIGURE 31–57. All magnetic resonance images (A to E) are proton density 2000/20 of the same normal subject. A,
This section passes through the lower part of the alveolar process of the maxilla and upper part of the ramus of the
mandible (white arrow) and shows the following structures: quadratus labii superioris (1), buccinator (2), masseter (3),
and internal pterygoid (4) muscles; parotid gland (5); rectus capitis anterior (6), longus capitis (7), rectus capitis lat-
eralis (8), digastric (9), splenius capitis (sc), and superior constrictor (small white and black arrows) muscles; pharynx (P);
soft palate (S); parapharyngeal space (ps); pharyngeal vein (black arrowhead); retromandibular vein (black arrow-
heads); external (e) and internal (I) carotid arteries; internal jugular vein (J); pharyngopalatinus muscle (large white
arrows); hard palate (H); and platysma muscle (white and black arrowheads). Note part of the levator veli palatini mus-
cle (curved white arrow). B, This section is 3 mm superior to A and passes through the midportion of the alveolar process
of the maxilla, upper end of the coronoid process of the mandible, and mastoid portion of the temporal bone (8). The
following structures are seen: quadratus labii superioris (1), buccinator (2), and masseter (3) muscles; parotid gland (4);
medial (5) and lateral (6) pterygoid and temporalis (7) muscles; mastoid process (8); rectus capitis anterior (9), longus
capitis (L), splenius capitis (sc), levator veli palatini (white arrows), and pharyngopalatinus (small black arrows) muscles;
nasopharynx (P); buccopharyngeal space (white arrow); buccal fat (BF); and platysma muscle (black arrows).
Continued on next page
694 Ballenger’s Otorhinolaryngology
and nasopalatine nerves. Five foramina open into ures 31–47, 31–48, and 31–57). The temporalis is a
the pterygopalatine fossa, including the foramen broad, radiating muscle, arising from the whole of
rotundum, pterygoid (vidian) canal, and spheno- the temporal fossa.55,56 It passes inferiorly deep to the
palatine foramen, which, in turn, lead to the ptery- zygomatic arch and inserts into the medial surface,
gopalatine canal (see Figures 31–16, B, and 31–23). apex and anterior border of the coronoid process,
The fourth foramen, the pharyngeal canal, which and anterior aspect of the ramus of the mandible
transmits the pharyngeal nerve and artery, is a (see Figures 31–48 and 31–57).55,56 The temporalis
potential communication between the nasopharynx muscle is seen anterolateral to the lateral pterygoid
and the fossa. The fifth foramen, the pterygopalatine muscle and pterygoid process as it inserts on the
canal, is placed inferiorly at the junction of the ante- coronoid process. Symmetric, low-density, fascial-
rior and posterior walls and leads into the greater fatty planes are seen on CT scans between the lateral
palatine canal. The pterygopalatine canal transmits pterygoid and infratemporal muscles. They are con-
the palatine vessels and nerves, serving as a potential tinuous with the symmetric fat pad just anterior to
communication with the oral cavity. The fossa con- the infratemporal muscles and posterior to the pos-
tains the maxillary nerve, pterygopalatine ganglion, terior wall of the maxillary sinus. Obliteration of
and terminal part of the internal maxillary artery.55,56 these fascial-fatty planes is usually indicative of
Many of the superficial and deep muscles of the face extension of a neoplastic or inflammatory process
are imaged on CT and MRI scans at the level of the into them (Figure 31–58).
infratemporal fossa and nasopharynx (see Figures
31–47 and 31–48). The lateral pterygoid muscle is a
short, thick muscle, somewhat conical in shape,
PARAPHARYNGEAL SPACE
which extends almost horizontally between the The PPS is an irregular, predominantly fat-filled
infratemporal fossa and the condyle of the mandible space within the suprahyoid neck (see Figures 31–47,
(see Figure 31–47). It has its origins in the lateral 31–48, and 31–57). Various synonyms for PPS have
surface of the lateral pterygoid plate and lateral sur- been used, including lateral PPS, pharyngomastica-
face of the greater wing of the sphenoid bone and tory space, pterygopharyngeal space, and pharyngo-
inserts into the articular disk of the temporo- maxillary space. The PPS is subdivided into the
mandibular joint and the condyle of the mandible prestyloid and retrostyloid compartments. Fascia
(see Figures 31–47 and 31–48).55,56 The main mass of that extends from the styloid process to the tensor
the medial pterygoid muscle lies deep and inferior to veli palatini muscle crosses posteriorly in the PPS fat
the lateral pterygoid muscle (see Figures 31–47 and and separates the PPS into those two spaces. The
31–48) and arises from the medial surface of the lat- carotid sheath is considered anatomically to be the
eral pterygoid plate, palatine bone, and maxilla and posterior compartment of the PPS. Infection and
inserts into the angle and ramus of the mandible both benign and malignant tumors of the infratem-
(see Figure 31–48).55,56 In axial CT and MRI sections poral fossa (Figure 31–58) and PPS are manifested
taken at the level of the low nasopharynx and soft by obliteration or distortion of the normal soft tissue
palate, the medial pterygoid muscle occupies a posi- planes and/or by a mass effect.56,57 Tumors and
tion on the inside of the ramus of the mandible, sim- inflammatory processes in these areas are difficult to
ilar to that of the masseter on the outside (see Figure assess clinically (Figures 31–59, 31–60, and 31–61).
31–57). Both pterygoid muscles can be visualized in However, they are identified readily by MRI and CT.
a coronal section taken at the level of the infratem- Tumors of the PPS are rare, accounting for only 0.5%
poral fossa (see Figure 31–48, B). The masseter is a of head and neck neoplasms.55 Neuromas of the
thick, somewhat quadrilateral muscle that arises vagus, trigeminal, sympathetic chain (Figures 31–62
from the zygomatic process of the maxilla and the and 31–63, A) and hypoglossal nerves and neurofi-
zygomatic arch and inserts into the angle and lateral bromas that arise within the PPS present as rounded
surface of the ramus and the lateral surface of the masses bulging into the nasopharynx.55,56 The benign
coronoid process of the mandible.55,56 In axial and nature of the tumor is often predicted by an evalua-
coronal sections, the masseter is seen as a thick, tion of CT and MRI scans, which show mass effect
somewhat quadrilateral muscle, anterior and infe- but not obliteration or invasion of the fascial planes
rior to the parotid gland, occupying a position on (see Figure 31–59). Eighty percent of PPS tumors are
the outside of the ramus of the mandible (see Fig- benign, and 20% are malignant. The most common
696 Ballenger’s Otorhinolaryngology
FIGURE 31–58. A, Mucormycosis. Semicoronal computed tomographic (CT) scan showing a soft tissue density in the
left nasal cavity (2) and left sphenoid sinus, with bone destruction along the superior aspect of the lateral wall of the
left nasal cavity and soft tissue infiltration along the inferior orbital fissure (iof) and into the apex of the left orbit along
the superior orbital fissure (sof) (compare with the density of the right inferior and superior orbital fissures). There
is also involvement of the left infratemporal fossa (3) with an irregularity of the bone of the left middle cranial fossa
(arrows) caused by osteomyelitis. B, Mucormycosis. Postcontrast axial CT scan of the same patient in A showing soft
tissue density in the left sphenoid sinus (1) and left nasal cavity, with extension into the left infratemporal fossa caus-
ing obliteration of the deep fascial plane (white and black arrows). Compare with the normal right infratemporal fossa
(2). Note also involvement of the posterior portion of the left maxillary sinus as compared with the right side (arrow).
primary tumors are salivary gland neoplasms that common tumors of poststyloid PPS. Unlike presty-
originate from the deep lobe of the parotid gland or loid PPS masses, these retrostyloid PPS masses result
from ectopic minor salivary gland tissue. These in displacement of the internal carotid artery anteri-
tumors are located in the prestyloid PPS. On CT and orly (Figures 31–62, 31–63, and 31–64). Tumors of
MRI, these tumors displace the internal carotid the mandible are usually confined to the bone; how-
artery posteriorly (Figures 31–59, 31–60, and 31–61). ever, extension deep into the adjacent infratemporal
Neurogenic tumors and paragangliomas are the most fossa may occur. Extension of the nasal, maxillary,
FIGURE 31–59. Pleomorphic adenoma. Proton-weighted (A) and T2-weighted (B) axial magnetic resonance scans
show a well-defined mass (M) involving the left parotid gland.
Imaging of Nasal Cavities, etc, and Base of the Skull 697
FIGURE 31–62. A, Paranasopharyngeal neurofibroma. Axial computed tomographic (CT) scan in a patient with a 12-
year history of recurrent right serous otitis media showing a large, smoothly marginated mass (arrows) in the right
parapharyngeal region that is protruding into the nasopharynx. Note the normal Rosenmüller’s fossa on the left (2)
and its obliteration on the right. Note also expansion of the pterygoid fossa without bone destruction as well as dis-
tortion of the right pterygoid muscle, all of which indicate the benign and slow-growing nature of the lesion. 1 = left
lateral pterygoid muscle. B, Parapharyngeal neurofibroma. Axial CT scan of the same patient in A following extended
transantral removal of the right parapharyngeal tumor. The superficial landmarks of the right side of the nasophar-
ynx (effaced in A) are symmetric with those on the left and appear normal in this CT scan. Notice extension of air in
the right Rosenmüller’s fossa (2) and right eustachian tube and the symmetric appearance of lateral pterygoid mus-
cles (1) and parapharyngeal spaces. Note postsurgical changes of the maxillary sinus (arrow).
Imaging of Nasal Cavities, etc, and Base of the Skull 699
A C
B D
FIGURE 31–63. A, Parapharyngeal schwannoma. T1-weighted sagittal magnetic resonance scan shows a large mass
(large arrows), resulting in anterior displacement of the internal carotid artery (hollow arrows). B, T2-weighted axial
magnetic resonance (MR) scan of the same patient in A shows marked hyperintensity of the tumor (T). i = internal
carotid artery; j = internal jugular vein. C, Coronal MR scan of the same patient in A and B shows the tumor (T) and
laterally displaced carotid artery (arrows). D, Two-dimensional time-of-flight magnetic resonance angiogram showing
laterally displaced common (C), internal (straight arrow), and external (curved arrow) carotid arteries. Note the left ver-
tebral artery (hollow arrow), right common carotid artery (arrowhead), and right vertebral artery (curved hollow arrow).
brain do not affect the skull base. Primary osseous droma, chondromyxoid tumor chondrosarcoma,
lesions of the skull base include congenital osteogenic sarcoma, lymphoma including plasmacy-
cholesteatoma (epidermoid) (see Figure 31–66), toma, Langerhans’ histiocytosis, hemangiopericy-
cholesterol granuloma (hematic cyst) (Figure toma, aggressive fibromatosis, and metastasis.
31–68), osteoma, osteoid osteoma, osteoblastoma, Metastatic lesions are most commonly from primary
osteoclastoma (giant cell tumor), intraosseous tumors of the lung, breast, prostate, thyroid, and
hemangioma, fibrous dysplasia, chordoma, chon- kidney; leukemia; and neuroblastoma (children).
700 Ballenger’s Otorhinolaryngology
FIGURE 31–64. Carotid body tumor. A, Proton-weighted axial magnetic resonance (MR) scan shows a large mass (M)
displacing the internal carotid artery (arrow) toward the parapharyngeal space. Note prominent vessels within the mass
(arrowheads). 1 = posterior belly of the digastric muscle; 2 = parotid gland. B, Sagittal T1-weighted MR scan showing
the carotid body tumor mass (M). Note marked anterior displacement of the internal carotid artery (I) and serpigi-
nous low-density vascular structures within the mass. C, T2-weighted coronal MR scan showing a hyperintense mass
(M) with several tortuous low-density images representing prominent vessels within the mass. The location of the mass
as seen in sagittal and coronal MR scans is high, raising the possibility of a glomus vagale rather than a carotid body
tumor. D, A dynamic GRASS (gradient-recalled acquisition in the steady state) axial MR image showing the tumor (M).
Note the hyperintensity of the arteries and veins in this section. e = external carotid artery; I = internal carotid artery;
J = internal jugular vein; v = vertebral artery. Note the retromandibular veins (large arrow) and displaced left internal
carotid artery (small arrow). Reproduced with permission from Mafee MF et al.5
The extracranial lesions commonly affecting the bone (Figure 31–69); hemangiopericytoma; juvenile
skull base include carcinoma of the nasopharynx; angiofibroma; neurogenic tumors; and metastatic
tumors and infections of the sinonasal cavities (see retropharyngeal and skull base nodal deposits.
Figure 31–40); necrotizing otitis externa, glomus Tumors and inflammatory lesions of the
complex tumors, and carcinoma of the temporal paranasal sinuses, orbits, or nasal cavities, which
Imaging of Nasal Cavities, etc, and Base of the Skull 701
A B
medium (see Figure 31–66).58–60 Although choles- intense to brain on T2W MR images. Cholesterol
teatomas may not be differentiated from cholesterol granulomas, however, appear as a hyperintense
granulomas on CT scans, they often can be easily dif- image on both T1W and T2W MR scans (see Figure
ferentiated by MRI. On T1W images, epidermoid 31–68, B). Cholesterol granulomas may be homoge-
cysts (cholesteatomas) are seen as a hypointense or neous or heterogeneous. The heterogeneity of signal
isointense image relative to brain and appear hyper- is usually owing to hemosiderin debris.60 Primary
Imaging of Nasal Cavities, etc, and Base of the Skull 703
C
704 Ballenger’s Otorhinolaryngology
A C
D E
FIGURE 31–71. A, Coronal computed tomographic scan showing a soft-tissue mass (m) in the region of the right
enlarged and eroded jugular fossa. Note extension of the tumor along the carotid sheath down to the level of the soft
palate (curved arrows). B, Coronal T1-weighted magnetic resonance (MR) scan shows a large mass in the left jugular
fossa (arrows). C, Coronal post–gadolinium-diethylenetriamine pentaacetic acid T1-weighted MR scan shows marked
enhancement of the lesion (arrows). D, Standard angiogram shows marked vascularity of the tumor (arrows). E,
Postembolization angiogram shows a marked decrease in tumor vascularity. At surgery, the tumor was completely
resected, and the patient recovered with no neurologic deficit. (Courtesy of Arvind Kumar, MD, University of Illinois
at Chicago Medical Center.)
706 Ballenger’s Otorhinolaryngology
REFERENCES 17. Mafee MF. Magnetic resonance imaging and its sim-
plifications for ophthalmology. In: Reinecke RD, edi-
1. Lauterbur PC. Image formation by induced local tor. Ophthalmology annual. New York: Raven Press.
interactions: examples employing nuclear magnetic 1989. p. 193–264.
resonance. Nature 1973;242:190–1. 18. Mafee MF. MRI and in-vivo proton H-1 spec-
2. McCullough EC. Basic physics of x-ray computed troscopy of the lesions of the globe. Semin Ultra-
tomography. In: Krobkin M, Newton TH, editors. sound CT MRI 1988;9.
Computed tomography. St. Louis: CV Mosby; 1977. 19. Smith SL. Nuclear magnetic resonance imaging.
3. Hounsfield GN. Picture quality of computed tomog- Anal Chem 1985;57:597–608.
raphy. AJR Am J Roentgenol 1976;127:3–9. 20. Wehrli FW, Macfall JR, Newton TH. Parameters
4. Mafee MF, Rasouli F, Spigos DG, et al. Magnetic res- determining the appearance of NMR images. In:
onance imaging in the diagnosis of nonsquamous Newton TH, Potts DV, editors. Modern neuroradiol-
tumors of the head and neck. Otolaryngol Clin ogy. Vol II. San Anselmo (CA): Clavadel Press; 1983.
North Am 1986;19:523–36. 21. Pisaneschi MJ, Mafee MF, Samii M. Applications of
5. Mafee MF, Compos M, Raju S, et al. Head and neck, magnetic resonance angiography in head and neck
high field magnetic resonance imaging versus com- pathology. Otolaryngol Clin North Am 1995;28:
puted tomography. Otolaryngol Clin North Am 543–61.
1988;21:513–46. 22. Mafee MF. Dynamic CT and its application to oto-
6. Mafee MF, Valvassori GE, Kumar A, et al. Tumors and laryngology-head and neck surgery. J Otolaryngol
tumor-like conditions of the middle ear and mastoid: 1982;11:307–18.
role of CT and MRI: an analysis of 100 cases. Oto- 23. Shugar MA, Mafee MF. Diagnosis of carotid body
laryngol Clin North Am 1988;21:349–75. tumors by dynamic computerized tomography.
7. Gorter CJ. Paramagnetic relaxation. Physica 1936;3: Head Neck Surg 1982;4:518–21.
503. 24. Mafee MF, Valvassori GE, Shugar MA, et al. High
8. Rabi I, et al. A new method of measuring paramag- resolution and dynamic sequential computed
netic moment. Physiol Rev 1938;53:318. tomography. Use in the evaluation of glomus com-
9. Gorter CJ, Broer LJF. Negative results of an attempt plex tumors. Arch Otolaryngol 1983;109:691–6.
to observe nuclear magnetic resonance in solids. 25. Damadian R, Zaner K, Hor D, Dimaio T. Human
Physica 1942;9:591. tumors by NMR. Physiol Chem Phys 1973;5: 381– 402.
10. Bloch F, et al. Nuclear induction. Physiol Rev 1946; 26. Mafee MF, Peyman GA, Grisolano JE, et al. Malig-
69:127. nant uveal melanoma and simulating lesions: MR
11. Purcell EM, Torrey HG, Pound RV. Resonance imaging evaluation. Radiology 1986;160:773–80.
absorption by nuclear magnetic moments in a solid. 27. Mafee MF, Peyman GA, Peace JH, et al. Magnetic
Physiol Rev 1946;69:37. resonance imaging in the evaluation and differenti-
12. Rosen BR, Brady TS. Principles of nuclear magnetic ation of uveal melanoma. Ophthalmology 1987;94:
resonance for medical application. Semin Nucl Med 341–8.
1983;13:308–18. 28. Chisin R, McCapinlac HA. The indications of FDG-
13. Pykett IL, Newhouse JH, Buonanno FS, et al. Princi- PET in neck oncology. Radiol Clin North Am 2000;
ples of nuclear magnetic resonance imaging. Radiol- 38:999–1012.
ogy 1982;143:157–68. 29. Hesselink JR, New PF, Davis KR, et al. Computerized
14. Gore JC, Emery EW, Orr JS, et al. Special articles. tomography of the paranasal sinuses and face: parts
Medical nuclear magnetic resonance imaging. I. I and II. J Comput Assist Tomogr 1978;2:559–76.
Physical principles. Invest Radiol 1981;16:269–74. 30. Noyek AM, Kassel EE, Gruss JS, et al. Sophisticated
15. Hawkes RC, Holland GN, Moore WS, et al. Nuclear CT and complex maxillofacial trauma. Laryngo-
magnetic resonance imaging: an overview. Radiog- scope 1982;92:1–17.
raphy 1980;551:253–5. 31. Mafee MF, Chow JM, Meyers R. Functional endo-
16. Luyten PR, den Hollander JA, et al. Observation of scopic sinus surgery: anatomy, CT screening, indica-
metabolites in the human brain by MR spectroscopy. tions, and complications. Am J Radiol 1993;160:
Radiology 1986;161:795–8. 735–44.
Imaging of Nasal Cavities, etc, and Base of the Skull 707
32. Chow JM, Mafee MF. Radiologic assessment pre- 48. Mafee MF, Pai E, Philip B. Rhabdomyosarcoma of
operative to endoscopic sinus surgery. Otolaryngol the orbit: evaluation with MR imaging and CT.
Clin North Am 1989;22:691–701. Radiol Clin North Am 1998;36:1215–27.
33. Mafee MF. Modern imaging of paranasal sinuses and 49. Wenig BM, Mafee MF, Ghosh L. Fibro-osseous,
the role of limited sinus computerized tomography; osseous, and cartilaginous lesions of the orbit and
consideration of time, cost and radiation. Ear Nose paraorbital region: correlative clinicopathologic and
Throat J 1994;8:532–46. radiographic features, including the diagnostic role
34. Mafee MF. Imaging methods for sinusitis. JAMA of CT and MR imaging. Radiol Clin North Am
1993;269:2808. 1998;36:1241–59.
35. Amon JB. Computer-aided endoscopic sinus sur- 50. Chernak ES, Rodriquez-Antunez A, Jelden GL, et al.
gery. Laryngoscope 1998;108:949–61. The use of computed tomography for radiation
36. Loehrl TA, Toohill RJ, Smith TL. Use of computer- therapy treatment planning. Radiology 1975;117:
aided surgery for frontal sinus ventilation. Laryngo- 613–4.
scope 2000;110:1962–7. 51. Som PM, Brandwein M. Sinonasal cavities: inflam-
37. Hawkins DB, Clark RW. Orbital involvement in matory diseases, tumors, fractures, and postopera-
acute sinusitis. Lessons from 24 childhood patients. tive findings. In: Som PM, Curtin HD, editors. Head
Clin Pediatr 1977;16:464–71. and neck imaging. 3rd ed. St. Louis: CV Mosby:
38. Mafee MF. Imaging of the orbit. In: Valvassori GE, 1996. p. 51–276.
Mafee MF, Carter BL, editors. Imaging of the head 52. Drayer BP, Wilkins RH, Boehnke M, et al. Cere-
and neck. New York: Georg Thieme Verlag; 1995. p. brospinal fluid rhinorrhea demonstrated by metriza-
158–215. mide cisternography. AJR Am J Roentgenol 1977;
39. Eustis HS, Mafee MF, Walton C, Mondorca J. MR 129:149–51.
imaging and CT of orbital injections and complica- 53. Manelfe C, Cellerier P, Sobel D, et al. Cerebrospinal
tions in acute rhinosinusitis. Radiol Clin North Am fluid rhinorrhea: evaluation with metrizamide cis-
1998;36:1165–83. ternography. AJR Am J Roentgenol 1982;138:471–6.
40. Dobben GD, Philip B, Mafee MF, et al. Orbital sub- 54. Mancuso AA, Bohman L, Hanafee WN, Maxwell D.
periosteal hematoma, cholesterol granuloma and Computed tomography of the nasopharynx: normal
infection: evaluation with MR imaging and CT. and variants of normal. Radiology 1980;137:
Radiol Clin North Am 1998;36:1185–200. 113–21.
41. Mafee MF, Carter BL. Nasal cavity and paranasal 55. Mafee MF. Nasopharynx, parapharyngeal space and
sinuses. In: Valvassori GE, Mafee MF, Carter BL, edi- base of skull. In: Valvassori GE, Mafee MF, Carter BL,
tors. Imaging of the head and neck. New York: Georg editors. Imaging of the head and neck. New York:
Thieme Verlag; 1995. p. 248–328. Georg Thieme Verlag; 1995. p. 332–63.
42. Gori F, Nesi G, Pedemonte E. Aspergillus fungus balls 56. Curtin HD. Separation of the masticator space from
on the mitral valve. N Engl J Med 2001;344:310–1. the parapharyngeal space. Radiology 1987;163:
43. Brown RB, Lau SK. Case 3-2001, the New England 195–204.
Journal of Medicine. N Engl J Med 2001;344:286–93. 57. Som PM, Braun IF, Shapiro MD, et al. Tumors of the
44. Som PM, Shugar JM. The classification of ethmoid parapharyngeal space and upper neck: MR imaging
mucoceles. J Comput Assist Tomogr 1980;4: characteristics. Radiology 1987;104:823–9.
199–203. 58. Mafee MF, Valvassori GE, Dobben GD. Role of radi-
45. Mafee MF. Nonepithelial tumors of the paranasal ology in surgery of the ear and skull base. Otolaryn-
sinuses and nasal cavity: role of CT and MR imag- gol Clin North Am 1982;15:723–54.
ing. Radiol Clin North Am 1993;31:75–90. 59. Mafee MF, Aimi K, Valvassori GE. Computed
46. Weber R, Draf W, Kratzch B, et al. Modern concepts tomography in the diagnosis of primary tumors of
of frontal sinus surgery. Laryngoscope 2001;111: the temporal bone. Laryngoscope 1984;94:1423–30.
137–46. 60. Mafee MF, Kumar A, Heffner DK. Epidermoid cyst
47. Chow JM, Leonetti JP, Mafee MF. Epithelial tumors (cholesteatoma) and cholesterol granuloma of the
of the paranasal sinuses and nasal cavity. Radiol Clin temporal bone and epidermoid cysts affecting the
North Am 1993;31:61–75. brain. Neuroimag Clin North Am 1994;3:561–78.
CHAPTER 32
Allergic Rhinitis
Jayant M. Pinto, MD, Robert M. Naclerio, MD
Allergic rhinitis, the most common of all atopic dis- asymptomatic to symptomatic asthmatic patients.9,10
eases, is an important public health problem. It Similarly, skin test–positive subjects who lack clini-
affects up to 20% of the adult population in the cal symptoms of allergic rhinitis may be converted
United States.1 It is the sixth most prevalent chronic into symptomatic patients by exposure to environ-
condition in the United States, and its prevalence is mental pollutants. Another purported role for pol-
increasing.2 In an otolaryngologist’s practice, the lution is that of an adjuvant in the development of
prevalence of allergic rhinitis in patients coming to immunoglobulin (Ig)E antibodies, which are central
the office exceeds that of the general population to the allergic reactions.11 Studies in both animals
and is in the range of 50%. Although it is a benign and humans suggest that diesel exhaust particles
chronic disease of the upper airway, quality-of-life enhance IgE production by a variety of mecha-
studies demonstrate that allergic rhinitis causes sig- nisms.12 Evidence against the role of outdoor pollu-
nificant impairment of function, exceeding that of tants comes from a German study comparing the
heart disease and asthma.3,4 In the United States, the prevalence of rhinitis and asthma in genetically sim-
public health impact is significant, with approxi- ilar populations in a West and an East German city.13
mately $1.5 billion spent annually on office visits Despite higher levels of SO2 and particulate matter
and medications. Diminished functional capacity in the air in the East German city, the incidence of
owing to allergic rhinitis alone causes the loss of 3.5 rhinitis and asthma was considerably lower than in
million work days and 2 million school days each the comparison city in West Germany.
year.5 These numbers are augmented when one con- Another potential explanation for the appar-
siders related disorders such as asthma and sinusitis, ent increased prevalence of allergic rhinitis involves
which are thought to be affected by allergic rhinitis. the role of indoor allergens. Evaluation of specific
Evidence supporting an increase in the inci- IgE antibodies suggests that increased rates of sen-
dence of allergic rhinitis comes from studies of sitization occur more frequently to common indoor
Swedish military conscripts, with skin testing used to allergens such as dust mites and household pets
document the existence of atopy.6 The prevalence of than to outdoor allergens such as grass pollens. This
allergic rhinitis was 4.4% in this 18-year-old Swedish study suggested that “Western”-style housing with
population in 1971 and increased to 8.1% by 1981. better weatherproofing and decreased ventilation
Similar trends have been observed in studies per- may be increasing the indoor allergen burden, lead-
formed in the 1990s.7,8 The cause of the increasing ing to an increased rate of sensitization.14 In sup-
prevalence of allergic rhinitis is not clear. Because port of this notion is a study of allergen avoidance
the increase has occurred within a decade, it does in children of atopic parents.15 Compared with a
not represent a genetic shift in the population. Pol- control group, reduction of allergen load in the first
lution may play a role by increasing nasal respon- 2 years of life led to a lower than expected incidence
siveness to environmental allergens. Common of allergic rhinitis at the age of 2 years. Indeed, the
outdoor pollutants include sulfur dioxide (SO2), prevalence in the former East Germany increased
nitrogen dioxide (NO2), and ozone, whereas indoor sharply during the years after reunification with the
pollutants include sidestream cigarette smoke. Expo- former West Germany, suggesting that factors asso-
sure to high levels of SO2, NO2, and ozone leads to ciated with a Western affluent lifestyle may play a
bronchial hyperresponsiveness and potentiates the role in the development of allergic disease. 8
pulmonary response to allergen, perhaps converting Although untested, proposed risk factors included
708
Allergic Rhinitis 709
exposure to automobile exhaust, indoor heating Symptoms of allergic rhinitis can begin at any
and ventilation systems, indoor allergens, smaller age but are most frequently first reported in adoles-
family size, and a relatively higher socioeconomic cence or young adulthood.27 Rates of prevalence are
status. Several other determinants have been identi- similar for males and females, and no racial or eth-
fied, including breast-feeding, month of birth, and nic variations are reported.28 The incidence of devel-
age of entry to day nursery. oping an allergic diathesis is higher in children
Another hypothesis is that a decrease in infec- whose parents suffer from allergic rhinitis. If one
tions in early childhood may affect the development parent has allergies, the chances of the child’s having
of atopic diseases. This hypothesis is based on rhinitis are 29% and increase to 47% when both par-
observations that show a higher prevalence of aller- ents have the disease.29 The rate of loss of allergic
gic diseases in individuals brought up in smaller rhinitis symptoms has been estimated to be about
and more affluent families, particularly in children 10%, which occurs in patients with the mildest form
and young adults in developed nations. The of the disease.30
increase of allergic diseases is associated with cer- A genetic component to allergic diseases,
tain socioeconomic conditions found in these coun- including asthma, allergic rhinitis, and others, has
tries. One common effect of these conditions is the long been suggested. Several investigators have con-
decreasing prevalence of childhood infections that ducted genome-wide screens in a variety of popula-
are assumed to have a protective effect for the devel- tions in the search for susceptibility genes involved
opment of allergy. This decreasing prevalence of in allergic diseases, primarily asthma.31–35 These
early childhood infections can be explained by a atopic diseases may be linked by common mecha-
lowered risk of exposure to infectious agents early nisms.36 A number of chromosomal regions show
in life as a result of increased immunization, evidence for linkage in multiple populations for
improved sanitary conditions, and smaller family asthma- and atopy-related phenotypes.37 Positional
size.16–25 cloning efforts are under way in these regions. Het-
A skew in the balance between T-cell subpop- erogeneity of phenotype, gene environment interac-
ulations from (normal) T helper 1 (TH1)-cell tion, complexity of molecular mechanisms, an
responses toward (atopic) TH2-cell responses, unknown mode of inheritance, and the possibility
including increased production of IgE, may be of small effects of a number of genes have compli-
caused by decreasing exposure to infectious agents. cated these approaches. To date, no loci have been
In support of the hygiene theory are studies demon- conclusively identified for association with allergic
strating an inverse relationship between the fre- rhinitis. However, positive associations of certain
quency of allergic disorders and childhood HLA (human leukocyte–associated antigens, also
infection.16–18,25 Additional evidence comes from known as major histocompatibility complex
studies in which children attending day care have [MHC]; for more information, see Chapter 28) alle-
been shown to develop more infections than those les with dust and mite allergens have been
who do not. A study of 1,035 children in Tucson, reported.38 This remains an area of intense interest
Arizona, showed that exposure to other children at and will likely accelerate with the recent completion
day care was protective against the development of of the first draft sequence of the human genome.
asthma and frequent wheezing in childhood.25 Chil- Part of the clinical importance of allergic rhini-
dren with more exposure to other children were less tis lies in its association with complications related
likely to have wheezing after age 6 through age 13 to chronic nasal obstruction. Total nasal obstruction,
years, although they wheezed more in the first 2 regardless of cause, can result in sleep disturbances.
years of life. The mechanism of these phenomena is Whether interference with sleep or the effects of sys-
not known. However, signals to the developing temically released mediators contribute to the
immune system provided by infections may cause fatigue associated with the disease is unknown. Evi-
alterations in the functional responses of lympho- dence for a systemic role has been outlined.39 Aller-
cytes.26 For example, the absence of a driving signal gic rhinitis is the third most common cause of
toward a TH1 response may allow the development hyposmia.40 Sinusitis often occurs in conjunction
of TH2 responses, resulting in a more atopic pheno- with allergic rhinitis. For example, the prevalence of
type later in life (Figure 32–1).26 abnormal sinus radiograph studies is greater in
710 Ballenger’s Otorhinolaryngology
patients with perennial allergic rhinitis compared in 80% of asthmatic subjects, and 40% of allergic
with those with seasonal disease and approaches rhinitic patients have asthma, suggesting a close link
50%.41 Whether nasal polyps result from allergic between the two diseases.
rhinitis remains an open question. Settipane and
Chafee, in an allergy practice setting, found that
2.1% of patients with allergic rhinitis had nasal PATHOPHYSIOLOGY
polyps.42 Although this is higher than the 0.3% inci-
dence of nasal polyposis reported for the general
IMMUNOGLOBULIN E
population in the 1980 American Health Survey, it is The distinguishing characteristic of allergic rhinitis
less than the 12.5% incidence noted by Settipane is the involvement of IgE. In an individual with a
and Chafee in nonallergic asthmatic patients.42 susceptibility for developing allergic disease, an ini-
The contribution of allergic rhinitis to middle tial contact with allergen leads to the production of
ear disease is debated. Studies by Friedman and col- specific IgE molecules, a process termed sensitiza-
leagues suggest that an induced allergic reaction can tion. This begins when macrophages and other
cause eustachian tube dysfunction.43 Moreover, aller- antigen-presenting cells process the allergen before
gic mediators have been found in the middle ear presenting it to T-helper cells, which then interact
fluid of patients with otitis media with effusion.44 with B lymphocytes, leading to their differentiation
Expression of TH2 cytokines and inflammatory cells into IgE-producing plasma cells, a process involving
has been documented in the middle ear mucosa of interleukin (IL)-4 and IL-13 and accessory mole-
allergic patients.45 Other data provide less support cules such as CD40. These newly formed IgE mole-
for a significant role of allergic rhinitis in the patho- cules bind to high-affinity receptors principally
physiology of otitis media.46 Allergic rhinitis occurs located on mast cells and basophils and to low-affin-
Allergic Rhinitis 711
ity receptors located on eosinophils, monocytes, and For ascertaining the importance of any media-
platelets. The high-affinity IgE receptors on mast tor in the pathophysiology of allergic rhinitis, three
cells mediate the initial allergic response. In the nasal criteria should be satisfied: (1) the mediator should
mucosa of allergic subjects, mast cells are usually be present during the allergic reaction, (2) instilling
found within the mucosal connective tissue stroma, the mediator in the nasal cavity should mimic part
in the vicinity of blood vessels and glandular struc- of the pathophysiology and symptoms of the dis-
tures.47 Seasonal exposure increases the number of ease, and (3) a mediator antagonist must partially or
mast cells located close to the surface in the nasal totally attenuate disease expression. To establish the
epithelium without affecting their overall number, importance of different mediators in allergic rhini-
suggesting that these cells migrate from the deeper tis, several investigators have attempted to satisfy one
to the more superficial layers of the nasal mucosa or more of these criteria.
during the pollen season.47 Recent studies demon- Multiple mediators have been recovered at
strating epsilon germline gene transcripts in biopsy increased levels in nasal secretions after allergen chal-
specimens obtained from asymptomatic patients lenge, and these include histamine,52 kinins,53 plasma
with seasonal allergic rhinitis and exposed to aller- and glandular kallikrein,54,55 mast cell tryptase,56
gen ex vivo suggest that production of IgE may PGD2,53 leukotriene C4 (LTC4),57 leukotriene B4
occur, at least in part, locally within the nasal (LTB4),58 and major basic protein (MBP)59 (Figure
mucosa.48 This elevates the importance of local tar- 32–2). Furthermore, several of these mediators have
geting of therapeutic interventions.49 been used to challenge the nasal mucosa and observe
resultant responses. Histamine provocation, for
example, produces rhinorrhea, congestion, pruritus,
EARLY RESPONSE and sneezing by stimulating receptors on sensory
In a sensitized individual, another encounter with nerves and blood vessels.60 Instillation of serotonin
the same allergen provokes an immediate (early) produces sneezing,61 whereas PGD262 and kinins63 all
allergic reaction. Within seconds of entering the produce nasal congestion.64 The other approach to
nasal cavity, antigens interact with specific IgE mol- establishing the importance of a mediator involves
ecules on the surface of mast cells. Cross-linking of the use of antagonists; the best example is H1 anti-
two adjacent IgE molecules by antigen initiates a histamines: the clinical utility of H1 receptor antago-
sequence of intracellular events resulting in mast nists serves to demonstrate the importance of this
cell degranulation and the subsequent release of inflammatory mediator.
preformed and newly generated mediators into the Whereas mast cell degranulation and the
nasal milieu. The preformed mediators are stored released inflammatory mediators mimic most of the
within granules in the cytoplasm and include hista- symptoms of allergic disease, the short duration of
mine, tryptase, heparin, and chondroitin sulfate. these events, as opposed to the prolonged symptoms
The newly generated mediators are synthesized of clinical disease, suggests that additional inflam-
from the phospholipids of the cell membrane sub- matory processes are probably important in clinical
sequent to mast cell activation. These mediators disease. Furthermore, increased responsiveness and
include platelet activating factor (PAF), prosta- mucosal cellular changes that accompany chronic
glandins (PGs), and leukotrienes. Evidence suggests allergen exposure cannot be explained by this mech-
that mast cells produce ILs by IgE mechanisms, and anism alone. Many of these phenomena relate to the
these, unlike the lipid and granule mediators, cellular infiltration that is a hallmark of the inflam-
require hours to be synthesized and released.50,51 matory response.65
Released mediators can also initiate extracellular
events that generate additional mediators; for exam-
ple, the generation of kinins depends, in part, on the
LATE RESPONSE
transudation of precursor proteins, kininogens, Various techniques of experimental nasal allergen
from the plasma that increase as a result of the provocation, in addition to being useful for an
action of histamine on vascular H1 receptors. Other understanding of the early response, assist investiga-
non–mast cell mediators are also associated with tors in understanding subsequent inflammatory
this early response to antigen. events. Following challenge, there is an increase in
712 Ballenger’s Otorhinolaryngology
FIGURE 32–3. Pathophysiology of allergic rhinitis. On the left side of the schematic, sensitization to allergen is
depicted and involves the production of specific immunoglobulin (Ig) E antibodies to certain allergens. On subsequent
exposure to the allergen, depicted on the right, there is cross-linking of specific IgE receptors with resultant degranu-
lation of mast cells and the release of inflammatory mediators. Subsequent to the early reaction, inflammatory cells
infiltrate the nasal mucosa, and the late-phase response develops. This is accompanied by a state of increased reactiv-
ity that renders the nasal mucosa more responsive to subsequent exposure to allergen (priming) or other stimuli
(hyperreactivity). Finally, natural allergic disease might resolve or lead to complications such as sinus infections or oti-
tis media. Reproduced with permission from Naclerio RM. Allergic rhinitis. N Engl J Med 1991;325:860–9.
reported a significant seasonal increase in total important in the recruitment of inflammatory cells
MBP+ and activated eosinophils in the submucosa from the intravascular compartment into tissue
of allergic patients when compared with presea- sites of allergic inflammation are intercellular adhe-
sonal biopsies or biopsies from nonallergic control sion molecule 1 (ICAM-1), which is constitutively
subjects.79 expressed in the nasal mucosa, and E-selectin, which
is modestly up-regulated 24 hours after allergen
provocation.80 Intercellular adhesion molecule 1, a
ADHESION MOLECULES ligand for the ß2 integrin molecules leukocyte
Studies have also demonstrated increases in function-associated antigen-1 and membrane attach
endothelial adhesion molecules, namely, vascular complex-1, which are present on the surface of
cell adhesion molecule 1 (VCAM-1) in nasal biop- leukocytes, mediates the attachment of all classes of
sies obtained from allergic subjects 24 hours after leukocytes to endothelial cells,82 and E-selectin binds
nasal allergen challenge.80 This molecule is expressed to sialyl Lewis X expressed on the surface of leuko-
on the surface of vascular endothelial cells and inter- cytes.85 The expression of adhesion molecules has
acts with a counterligand, very late activation anti- also been studied by Montefort and colleagues, who
gen 4 (VLA-4), which is present on the surface of compared the expression of endothelial cell adhe-
several leukocytes including lymphocytes, mono- sion molecules in nasal biopsies from subjects with
cytes, eosinophils, and basophils but not neu- perennial allergic rhinitis and normal control
trophils.81,82 The VLA-4/VCAM-1 adhesion pathway subjects. These investigators found enhanced expres-
has been suggested as a mechanism for specific sion of ICAM-1 and VCAM-1, but not E-selectin, in
eosinophil, as opposed to neutrophil, migration the mucosa of allergic subjects.86 Intercellular adhe-
from the circulation into allergic inflammatory sion molecule expression has been shown to be
sites.81,83,84 Other adhesion molecules thought to be suppressed by H1 antihistamines.
714 Ballenger’s Otorhinolaryngology
siveness to histamine was reversible. Other studies as gasoline odors, reported by patients during their
showed a positive correlation between the number of allergy season.
eosinophils 24 hours after antigen challenge and the
magnitude of the responsiveness to histamine, and
this hyperresponsiveness was inhibited by pretreat-
NEURAL REFLEXES
ment with topical corticosteriods.99,100 Neural reflexes are thought to be involved in the
Majchel and colleagues examined the effect of pathophysiology of allergic rhinitis. Sneezing and
seasonal exposure on nasal responsiveness to hista- itching seen during the early response to allergen
mine by challenging allergic subjects with histamine provocation involve the nervous system. Konno and
before, at the peak of, near the end of, and 2 weeks Togawa and others demonstrated the importance of
after the ragweed pollen season.101 These investiga- neural reflexes in patients with allergic rhinitis by
tors observed a significant increase in symptoms at showing that stimulating one nasal cavity with his-
the peak of the pollen season that returned to base- tamine led to bilateral nasal secretions.107 Unilateral
line with the disappearance of pollen. The increase intranasal challenge with antigen in subjects with
above baseline at the peak of the season was not sig- allergic rhinitis led to an increase in sneezes, rhinor-
nificant for any of the parameters measured. How- rhea, nasal secretions, histamine, nasal airway resist-
ever, they suggested that increased reactivity to ance,108 and PGD2109,110 on the side of challenge.
histamine with seasonal exposure appears to repre- Contralateral to the challenge, rhinorrhea and secre-
sent a change in baseline rather than an increased tion weights increased significantly, as did PGD2.110
sensitivity to histamine itself. This change in baseline The contralateral secretory response was rich in the
reactivity was inhibited in subjects who were receiv- glandular markers lactoferrin and lysozyme109 and
ing immunotherapy. was inhibited by atropine, an anticholinergic agent,
Similar studies demonstrate nasal hyperre- suggesting that the efferent limb was cholinergically
sponsiveness to the cholinomimetic agonist metha- mediated.108 The muscarinic receptors that mediate
choline.102 Klementsson and colleagues measured the actions of acetylcholine in the human nasal
the volume of nasal secretions after intranasal mucosa are of both the M1 and M3 receptor subtypes
administration of 6 mg of methacholine before and and coexist at high densities in submucosal glands.111
after antigen challenge of allergic subjects out of Immunohistochemical studies have established
allergy season and observed significant increases in the presence of several neuropeptides in addition to
methacholine-induced secretions at 2, 4, 6, 8, 10, sympathetic and parasympathetic nerves and their
and 24 hours after antigen challenge, compared transmitters in the nasal mucosa. These neuropep-
with baseline. 103 Although eosinophils in nasal tides are secreted by unmyelinated nociceptive C
secretions increased significantly after antigen fibers (tachykinins, calcitonin gene-related protein
challenge, no correlation was seen between their [CGRP], neurokinin A [NKA], and gastrin-releasing
numbers and the increase in nonspecific hyper- peptide), parasympathetic nerve endings (vasoac-
responsiveness to methacholine. These workers also tive intestinal protein [VIP], peptide histidine
showed that premedication with two different H1 methionine), and sympathetic nerve endings (neu-
antihistamines (terfenadine and cetirizine) resulted ropeptide Y). Substance P (SP), a member of the
in inhibition of both the acute allergic response tachykinin family, is often found as a cotransmitter
and the allergen-induced increase in responsiveness with NKA and CGRP and has been found in high
to methacholine without affecting eosinophil density in arterial vessels and, to some extent, in
influx after antigen.104 This observation was con- veins, gland acini, and the epithelium of the nasal
firmed by Baroody et al for the H1 antihistamine mucosa.112 In addition to the identification of these
terfenadine and extended to the antihistamine lora- neuropeptides in the nasal mucosa, Okamoto et al
tidine.105 In contrast, corticosteroids, given topi- showed that incubation of nasal biopsy specimens
cally or orally, have dramatic inhibitory effects on of perennial rhinitics and nonallergic rhinitics with
cellular infiltration and both specific and nonspe- SP or mite allergen resulted in significant increases
cific hyperresponsiveness. 99,100,106 An important in mRNA for IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6,
consequence of nonspecific hyperactivity is the tumor necrosis factor-α, and interferon-γ in speci-
increased symptoms on exposure to irritants, such mens from allergic subjects but not nonallergic con-
716 Ballenger’s Otorhinolaryngology
trols.113 In nasal challenge studies in allergic subjects, underlying factor in 40 to 67% of patients with
Mosimann and colleagues showed that levels of SP, chronic sinusitis.121 Complementing the above data
CGRP, and VIP all increased significantly immedi- that allergic rhinitis occurs frequently in patients
ately after antigen challenge, with significant but with chronic sinusitis are data showing a high preva-
modest increases in SP during the late response.114 lence of sinus disease in patients with allergic rhini-
These experiments suggest that neuropeptides are tis. Sinus radiographs are abnormal in more than
released in vivo in man after allergen challenge and 50% of adults and children with perennial allergic
might be partly responsible for symptoms of the rhinitis.122,123 In contrast, Enberg reported a low
allergic reaction. Repetitive application of capsaicin, incidence of sinus abnormalities in patients with
the essence of chili peppers, depletes sensory nerves perennial nonallergic rhinitis.124 Magnetic resonance
of their content of SP and CGRP and initiates both imaging scans demonstrate increased evidence of
central and axonal reflexes. Unlike its effects in sinus mucosal abnormalities during major pollinat-
rodents, the capsaicin-induced nasal secretory ing seasons.125 A study of subjects with ragweed
response in humans is primarily glandular and not rhinitis during the pollen season showed that 60% of
attributable to increased vascular permeability.115 In the subjects had sinus mucosal abnormalities on
support of its proinflammatory effects, capsaicin computed tomography (CT).126 Multiple mecha-
nasal challenge caused significant increases in neu- nisms are postulated to explain these relationships.
trophils, eosinophils, and mononuclear cells from In one recent study of subjects with seasonal allergic
the prechallenge baseline, with no difference rhinitis outside their season, the nose was challenged
between rhinitic and normal subjects.116 Further- with allergen, and nasal and ipsilateral maxillary
more, capsaicin desensitization reduced nasal symp- sinus responses were monitored by use of lavage.
toms recorded for 24 hours after allergen challenge, There was a late increase in total cell count (the per-
and this reduction persisted for up to 2 months.117 centage of eosinophils and total eosinophils within
Therefore, several experimental findings high- the sinus cavity in the allergen-challenged subjects)
light the importance of neurogenic control of the but not in the control experiments. There were sig-
allergic response. These include the presence of nificantly more total cells after allergen challenge
nasonasal reflexes after nasal antigen provocation, compared with the control group as well as a higher
the presence of neuropeptides in nasal tissues and number of total eosinophils.127 This study highlights
their recovery in nasal secretions after antigen chal- the fact that important relationships exist between
lenge, the ability of these peptides to produce symp- the nose and sinus in the response to allergen, pos-
toms and inflammatory responses similar to those sibly through regional or central neural reflexes.
obtained after exposure to antigen, and the clinical There are important relationships between the
efficacy of capsaicin, which depletes the stores of nose and other organs in the pathophysiology of
these substances. allergic rhinitis. A relationship between pulmonary
disease such as asthma and allergic rhinitis has long
been observed. Allergic rhinitis and asthma often
RELATIONSHIPS WITH RELATED ORGANS coexist. Allergic rhinitis can lessen the severity of
Multiple lines of evidence support the observation asthma,128 and treatment of allergic rhinitis by
that allergic rhinitis and sinusitis are closely associ- intranasal corticosteroids can improve the symptoms
ated disease entities, although controlled studies of of asthma and reduce bronchial hyperresponsive-
the incidence of rhinosinusitis in patients with aller- ness.129 Treatment with orally inhaled corticosteroids
gic rhinitis have not been conducted. Benninger, in not only prevented development of increased bron-
a study of outpatients in an otolaryngology practice, chial hyperresponsiveness to methacholine but also
found that 54% of those with chronic sinusitis also reduced nasal symptoms, eosinophils from nasal
had allergic rhinitis.118 Grove and Farrior described brushings, markers of eosinophil activation in nasal
a 50% incidence of positive skin tests in patients lavage fluid, and peripheral blood eosinophilia.130
undergoing sinus surgery, whereas Friedman A recent study by Braunstahl and colleagues
reported an incidence of atopy in 94% of patients demonstrated that segmental provocation with aller-
undergoing sphenoethmoidectomies.119,120 Van gen in the lungs produced allergic inflammation
Dishoeck and Franssen described allergy as an in the nose in atopic patients.131 Another study
Allergic Rhinitis 717
examined the ability of the nose to condition cold, fies the allergic reaction by both central and periph-
dry air. Assanasen et al demonstrated that asthmat- eral reflexes that result in changes at sites distant from
ics have a reduced ability to warm and humidify those of antigen deposition. All of these changes
cold, dry air as compared with normal subjects; sub- lower the threshold of mucosal responsiveness and
jects with seasonal allergic rhinitis also had a amplify it to a variety of specific and nonspecific
reduced ability to condition air, with possibly stimuli, making allergic individuals more responsive
adverse implications for the lower airways.132 Patho- than nonallergic individuals to stimuli to which they
physiologic connections between the nose and lungs are exposed in daily life (see Figure 32–3).
are still not entirely understood and remain an active
topic of investigation. The above data, however, sup-
port the presence of important physiologic and
ALLERGENS
pathophysiologic connections between contiguous Allergens are foreign substances capable of provok-
areas of the respiratory tract. ing an IgE-mediated response. Most allergens are
Nasal inflammation with an allergic or infec- between 5 and 20 µm in diameter, a size that permits
tious cause may be a factor involved in the develop- their complete removal by the nose. They are pro-
ment of otitis media. Studies of the pathogenesis of teins with molecular weights between 10 and 40 kD.
otitis media have identified interactions among No distinguishing surface characteristics appear to
infection, allergic reactions, and eustachian tube differentiate allergens from nonantigenic substances.
dysfunction.133 In the presence of allergic rhinitis, Allergens are often categorized into indoor and
treatment may improve symptom resolution and outdoor types. In general, outdoor allergens are
therapeutic response. The inflammation found in responsible for seasonal allergic rhinitis, whereas
allergic rhinitis is thought to promote eustachian indoor allergens usually cause perennial rhinitis. Pol-
tube dysfunction and support the development of lens causing allergy in temperate climates are released
otitis through mediators and cytokines. This into the air from plants, trees, weeds, and grasses and
remains an area of ongoing investigation. are carried over great distances. Thus, cutting down
trees around a suburban home in an effort to reduce
the amount of pollen has little effect. About 75% of
SUMMARY OF PATHOPHYSIOLOGY patients with seasonal allergens have symptoms
The pathophysiology of allergic rhinitis can be sum- caused by ragweed, 40% by grasses, and 5% by trees
marized as follows: After sensitization of the nasal alone. Approximately 25% have allergies to both
mucosa to a certain allergen, subsequent exposure grass and ragweed, and 5% have allergies to all three
leads to cross-linking of specific IgE receptors on pollens.27 Trees clearly have geographic variations; for
mast cells and their resultant degranulation, with the example, Western red cedar is limited to the North-
release of a host of inflammatory mediators that are west. Grasses are diverse and include timothy grass,
responsible for allergic nasal symptoms (see Figure often used for feeding horses; Kentucky bluegrass,
32–3). Proinflammatory substances produced by widely used in lawn grass mixtures; orchard grass; rye
other inflammatory cells are also generated after grass; and English plantain. Common short ragweed
antigen exposure, most prominent among which are is found throughout North America, with the excep-
eosinophil products and cytokines. Cytokines are tion of Newfoundland, and is conspicuously absent
thought to be generated, in part, by lymphocytes, from the European continent.
which are found in abundance in both resting and Pollination, and hence the allergy season,
stimulated nasal mucosa. Recent evidence also points occurs in a predictable annual pattern for different
to an important role for mast cells in the storage and regions of the country.134 The pattern, however,
probable production and secretion of cytokines. varies throughout the country. In the Northeast,
Cytokines can up-regulate adhesion molecules on the trees pollinate in mid-March to late April, grasses
vascular endothelium and possibly marginating follow in May and June, and ragweed flowers from
leukocytes, leading to the migration of these cells into mid-August until the first frost. In the South, tree
tissues. Other cytokines also promote chemotaxis blooming begins in early February. In contrast to the
and survival of recruited inflammatory cells. Another sharply demarcated grass season that occurs in the
important player is the nervous system, which ampli- North, in the South, grasses may pollinate from
718 Ballenger’s Otorhinolaryngology
March through September, and in some areas, polli- Cat dander is “sticky,” and children with cats can
nation may be a year-round process. The pattern in carry enough to school to cause symptoms in cat-
the central United States resembles the patterns seen allergic children who have no cats in their homes.136
on the east coast. In the California lowlands, grass The cockroach is an important source of aller-
pollen is present from early March through Novem- gen in inner-city populations. Both the American
ber, and trees and short ragweed are present as in (Periplaneta americana) and German cockroach
other regions. In the Northwest coastal region, trees (Blattella germanica) have been identified as impor-
and grass pollen are present, but the region is rag- tant allergens in asthma. Allergenicity occurs to body
weed free. In the traditionally arid Southwest, previ- parts and to feces. Molds, although less well studied,
ously a haven for allergy sufferers, increased are sources of allergens, particularly in warm, humid
urbanization and irrigation have contributed to environments. They tend to be found inside older
increasing the pollen load. Humans tend to bring homes in areas of decreased ventilation or increased
their allergens with them. dampness. Although a phenomenal variety of molds
The most frequent perennial allergens are ani- exists, Alternaria and Cladosporium are principally
mal danders, dust mites, cockroaches, and molds. responsible for symptoms owing to outdoor expo-
Dust mites are microscopic, eight-legged organisms sure, and Aspergillus and Penicillium are most preva-
of the genus Dermatophagoides, including D. lent indoors.
pteronyssinus, D. farinae, and Euroglyphus maynei. The patient’s work environment may also be a
They are the major allergens in “house dust.” Dust source of allergens. Symptoms occurring only at
mites are found throughout the world, with the work and subsiding on weekends may reflect an
exception of extremely dry climates such as northern occupational disorder. At risk are flour handlers,
Sweden, central Canada, and areas at elevations workers in paint and plastic industries, woodwork-
above 10,000 feet. These mites feed on human ers, fish and shellfish processors, and animal han-
epithelial scales and thrive in warm, humid environ- dlers. Unfortunately, few specific tests exist for the
ments (60 to 70% relative humidity, temperature 65 diagnosis of these disorders.
to 80°F). Bedding provides an ideal environment for Allergic reactions to natural rubber latex have
proliferation of dust mites. Other sites for mite accu- increased, especially in health care workers who have
mulation are upholstered furniture, carpets, and high exposure by direct skin contact and inhalation
stuffed toys. Dust mite feces, the source of the aller- of latex particles from powdered gloves. This prob-
gen, are relatively large particles that remain airborne lem is being addressed by studies on improving
for short periods, unlike outdoor pollen. When an diagnostic methods for latex allergy and evaluating
individual sits on a bed, the particles become air- strategies for prevention.
borne and are inhaled. Because these particles are
large, they settle from the air rapidly, and air filtra-
tion systems cannot effectively remove them. Lower- CLINICAL PRESENTATION
ing the indoor relative humidity to less than 50%
during the summer months has a profound effect on
HISTORY
the mite population and the antigen load throughout Antigen exposure causes itching within seconds, which
the year,135 suggesting a role for dehumidifiers even in is soon followed by sneezing. Rhinorrhea ensues, and
homes with central air conditioning. within about 15 minutes, nasal congestion peaks.
Animal danders are an important source of Besides nasal symptoms, patients often complain
indoor allergens. Cat and dog danders are the most about ocular pruritus, tearing, pharyngeal itching,
frequent, but mice, guinea pigs, and horses can all be throat clearing, cough, and ear popping. Other com-
responsible for allergic symptoms. Laboratory work- monly reported symptoms include postnasal drip,
ers can become allergic to animals at work. In most increased lacrimation, dry cough, red eyes, headaches
cases, the allergen is found in secretions. In cats, Fel d (pressure) over the paranasal sinus areas, and loss of
I is the principal allergen secreted in cat saliva. It dries smell or taste. These symptoms are nonspecific and
on fur and is spread to furniture, bedding, and car- have significant clinical overlap with other disorders.
pets. When these reservoirs are disturbed, the aller- Itching of mucous membranes and repetitive sneez-
gen becomes airborne and can provoke symptoms. ing, however, are the symptoms most suggestive of
Allergic Rhinitis 719
allergic disease. The relative importance of each symp- tribute to nasal congestion through interference with
tom may vary among individuals, but nasal conges- the adrenergic mechanism. Tricyclic antidepressants
tion tends to be the most bothersome, although each may produce dryness of the nasal mucosa by virtue
symptom is usually present, at least to some degree. of their anticholinergic effects. Angiotensin-convert-
When obtaining the history, the physician ing enzyme inhibitors can produce a chronic cough.
should attempt to link exposure to allergens tempo- Birth control pills can cause nasal congestion, and
rally with the occurrence of symptoms. This tempo- topical eyedrops can also induce nasal symptoms.
ral correlation is the hallmark of allergic rhinitis.
Patients with seasonal allergies complain of recur-
rent symptoms only at specific times of each year
EXAMINATION
that coincide with pollination periods. In contrast, a Attentive history taking and physical examination,
history of year-round symptoms may indicate sensi- combined with appropriate diagnostic tests, are
tivity to a perennial allergen or multiple seasonal required for establishing the correct diagnosis
allergens. Symptoms immediately following expo- because allergic rhinitis shares features of other nasal
sure to a potential source of allergen, such as a cat, disease entities. The classic description of allergic
strongly suggest an allergy to that source. Exposures facies includes mouth breathing, allergic “shiners”
to perennial allergens tend to be accentuated in win- (resulting from periorbital venous stasis from
ter in colder climates, when ventilation is reduced. chronic nasal obstruction), and a transverse supratip
Symptoms occurring only at work or during the nasal crease from long-term rubbing of the nose
workweek and subsiding on weekends may reflect an upward to relieve itching. These classic presentations
occupationally related disorder. The presence of occur especially often in children, but absence of
domestic pets (including birds) and whether these these signs does not exclude the disease.
sleep in the patient’s room must be determined. Physical examination must be complete. Ocu-
Additional considerations in history taking lar examination may demonstrate injection of the
include the response to prior therapy and evidence conjunctiva or swelling of the eyelids. Examination
of complications. Related effects of the pathophysi- of the nose begins with observing the external
ology must be addressed. For example, nasal appearance for gross deformities such as a deviation
obstruction may lead to mouth breathing. In chil- suggesting previous trauma or expansion of the
dren, this may be manifested as adenoid facies, with nasal bridge suggestive of nasal polyps. A nasal
a high palatal arch and abnormal dental develop- speculum permits evaluation of the anterior third of
ment. In adults, nasal obstruction may contribute to the internal nasal architecture and the character of
snoring and sleep-disordered breathing. Obstruc- the nasal mucosa. Structural anomalies providing an
tion of sinus ostia may predispose to sinusitis. anatomic basis for obstruction or recurrent infec-
Eustachian tube dysfunction may occur,137 but this tions such as septal deviations or spurs should be
has not been shown to lead to an increased incidence sought. The character and consistency of nasal secre-
of otitis media with effusion.138,139 tions should be noted. These can vary from thin and
A general medical history remains important. clear to thick and whitish. The nasal mucosa may
The medical history may document systemic disor- be swollen and pale-bluish, although these signs are
ders that affect the nose, such as hypothyroidism. not pathognomonic of the disease, as previously
Pregnancy can produce nasal congestion and may thought. The examination of allergic individuals
require modification of treatment strategies. The often appears normal, and the primary importance
presence of pulmonary disease such as asthma of the physical examination is to rule out other
should be sought. Indeed, a significant percentage of causes of or contributors to the symptoms.
patients with allergic rhinitis have asthma. Between 5 Decongestion of swollen nasal mucosa with a
and 10% of asthmatic subjects may have intolerance topical decongestant improves visualization and
to aspirin and nonsteroidal anti-inflammatory drugs. allows the differentiation of reversible from irre-
A family history of allergic rhinitis increases the versible changes. Combining the vasoconstrictor
chances of the patient’s having an allergic disorder. with a topical anesthetic allows complete examina-
Nasal symptoms might also be caused by intake of tion with an endoscope. The choanae and the
medications such as beta blockers, which may con- nasopharynx can be visualized in this manner. The
720 Ballenger’s Otorhinolaryngology
region of the middle meatus should also be exam- Skin testing often begins with puncture testing,
ined carefully because secretions there might be sug- which provides low-dose allergen exposure. A small
gestive of acute or chronic sinusitis. Nasal polyps drop of concentrated allergen is placed on the skin
that were not visualized by anterior rhinoscopy may (usually on the volar surface of the forearm or the
be seen during a careful endoscopic examination. back), and a minute quantity is introduced into the
Nasal polyps are infrequent in allergic rhinitis dermis with a sharp object. Positive responses occur
(< 2%) but are found in up to 20% of patients with within 10 to 15 minutes and produce a characteris-
cystic fibrosis.42 The presence of nasal polyps in chil- tic raised central area of induration (wheal), with a
dren suggests the diagnosis of cystic fibrosis because surrounding zone of erythema (flare). The response
polyps are rarely found in this age group. These chil- is graded in comparison with a positive histamine or
dren should undergo sweat or genetic testing. codeine response, and a negative control with the
diluent for the allergen extracts is also included to
control for nonspecific reactivity to the vehicle. The
DIAGNOSIS positive control ensures that the patient can mount
The identification of allergen(s) responsible for the a cutaneous reaction to histamine, and the absence
patient’s symptoms is important both for establishing of a reaction can unmask interference by medica-
the diagnosis and for the institution of avoidance meas- tions, decreased skin reactivity, or technical prob-
ures. Symptoms occurring in temporal relation to aller- lems with the procedure. Skin testing is valid in
gen exposure suggest sensitization but are not infants and young children, but the criteria for a
diagnostic. Sensitization implies the presence of ele- positive reaction need to be adjusted because the
vated levels of IgE directed against a specific allergen reactions are smaller.142 Measurement of serum-
and can be demonstrated by a wheal and flare response specific IgE levels is also valid in this younger age
to skin testing with allergen extracts or by measuring group.143 It is important, however, to test with only
the level of antigen-specific IgE antibodies in the relevant antigens. Infants are more likely to be aller-
serum. However, individuals can show evidence of sen- gic to foods, and children are more likely to be aller-
sitization by a positive skin test or elevated specific anti- gic to perennial rather than seasonal allergens.
body levels in the serum without having evidence of Negative puncture tests are usually confirmed
clinical disease. This emphasizes the importance of by intradermal tests, which are more sensitive. In an
obtaining a good history in the evaluation of patients intradermal test, a small (0.01 to 0.05 mL) quantity
with suspected allergic disorders. In patients with a of dilute allergen is injected into the superficial der-
positive history, the magnitude of skin responses often mis, and the same wheal and flare responses are
corresponds to the severity of symptoms. observed and graded in comparison with a positive
histamine or codeine control. Because antihista-
mines can interfere with the results of skin testing,
SKIN TESTING most H1 receptor antagonists are withheld for 2 days
Skin testing furnishes an excellent in vivo method to before skin testing. Tricyclic antidepressants sup-
demonstrate sensitivity to a given allergen. This test press responses for several weeks, as can tranquiliz-
evaluates the presence of specific IgE antibodies on ers and antiemetics of the phenothiazine class
skin mast cells, the reactivity of these cells, and the through intrinsic anti-H1 activity. Short-term oral
reaction of the end-organ to released mediators. Its corticosteroid treatment has no effect on skin test
advantages include greater sensitivity, the rapidity reactivity but may have an inhibitory effect if the
with which results can be obtained, and low cost. agent is taken for long periods. Testing with extracts
Like all diagnostic tests, skin testing also has disad- that are standardized (ragweed, grass pollens) is
vantages, which include the inability to perform the more reliable than for nonstandardized antigens
test in patients with dermatologic problems such as such as foods and chemicals.
dermatographism and extensive eczema, poor toler-
ance of many children for multiple needle pricks, the IN VITRO IMMUNOGLOBULIN E
inhibitory effect of certain ingested drugs such as
antihistamines on skin test reactivity,140,141 the need
MEASUREMENTS
to maintain the potency of the allergen extracts, and Drawing blood for the measurement of specific IgE
the possibility of systemic reactions. can circumvent some of the disadvantages of skin
Allergic Rhinitis 721
testing. False-positive results may occur if patients when the predominant symptom is nasal obstruc-
have elevated IgE levels in their sera because of non- tion. Sinus disease often complicates perennial aller-
specific binding. Therefore, although IgE levels alone gic rhinitis and may be a consideration in the
are of limited usefulness in the diagnosis of allergic differential diagnosis. In the past, sinus plain films
rhinitis, and because elevated levels can also exist in were used, but CT is now standard for evaluation of
patients with nonallergic conditions, these levels must the presence and extent of sinus abnormalities. The
be obtained in conjunction with a determination of common association of upper and lower airway dis-
specific IgE levels. False-negative results may also ease makes tests of pulmonary functions useful
occur from inhibition by IgG antibodies with similar adjuvants. This statement applies to such diverse dis-
affinities as in patients receiving immunotherapy. orders as cystic fibrosis, asthma, and bronchopul-
Data from clinical studies comparing the results of monary aspergillosis.
skin testing and in vitro tests for specific IgE determi-
nation (the radioallergosorbent assay or RAST) in
allergic subjects suggest a good correlation between THERAPY
the two,144 with a higher sensitivity for skin testing.145
Therefore, both determinations of specific IgE levels
ENVIRONMENTAL MODIFICATIONS
and skin testing are useful in the diagnosis of allergic The most potent treatments cannot eliminate symp-
disorders, but their results should always be inter- toms in the face of an overwhelming allergen load.
preted in the context of clinical symptoms. The dis- Complete avoidance of the allergen(s) to which the
advantages of this form of allergy testing include cost, patient is sensitive eliminates symptoms of the dis-
slightly lower sensitivity, and the time delay between ease. Thus, measures aimed at reducing the allergen
drawing the blood and obtaining the results. load from the patient’s environment are effective in
reducing symptoms. Although many methods of
environmental control (removal of a pet, restriction
OTHER DIAGNOSTIC TESTS of activities, home renovations) are difficult to exe-
Peripheral eosinophilia, although nonspecific, may cute, particularly with children, simple measures can
indicate the presence of other atopic diseases. Nasal be very effective. In seasonal allergic rhinitis, patients
cytologic examination allows the identification of can reduce exposure by keeping windows closed on
eosinophils and other inflammatory cells in nasal days when pollen counts are high and limiting phys-
secretions and may be helpful in differentiating an ical activity outdoors in the early morning and
infectious from an allergic cause during a clinical evening when pollen counts peak. Air conditioning
exacerbation of symptoms. In normal individuals, can help, and the addition of special filters can pre-
smears show the presence of epithelial cells, includ- vent pollen grains and mold spores from entering
ing some ciliated and goblet cells, with few the home. Pollen counts are often given during daily
eosinophils, neutrophils, basophils, or bacteria. In weather reports, and the previous day’s pollen
subjects with an infection, neutrophils increase in counts are the best predictor of the next day’s
nasal secretions, and in symptomatic allergic sub- counts. Rain, however, profoundly reduces the levels
jects, the percentage of eosinophils increases. A value of outdoor pollens.
greater than 10% is suggestive of allergic dis- Measures to reduce exposure to dust mites
ease.146–150 Eosinophils, however, may also be present concentrate on bedding.152 These include replacing
in the absence of IgE-mediated disease. Approxi- feather pillows and bedspreads with synthetic ones
mately 25% of patients with chronic rhinitis and that can be washed in hot water (hotter than 130°F)
negative skin tests demonstrate eosinophilia on nasal and covering mattresses with commercially available
cytologic study, and this entity is known as the non- plastic covers (< 10 µm). Removing carpets and fre-
allergic rhinitis with eosinophilia syndrome quent vacuuming also help. Where carpets cannot
(NARES). Regardless of the cause, the presence of be removed, acaricidal products can directly kill
eosinophilia usually implies a favorable clinical mites. Stuffed toys can be placed in the freezer for 2
response to corticosteroid therapy.151 days to reduce the number of dust mites.
Soft tissue radiography of the neck can evalu- In subjects with allergies to animal dander,
ate adenoid size, a major consideration in the differ- removal of a domestic pet is the best step. Reduction
ential diagnosis of rhinitis in children, especially in the allergen load after pet removal may take up to
722 Ballenger’s Otorhinolaryngology
6 months, however; thus, symptoms may persist. Fur- rationale for the large number of H1 antagonists
thermore, complete removal of a pet may be difficult, in clinical use.
but eliminating the animal from the bedroom, where H1 antihistamines have been classified as first-
we spend an average of 8 hours per day, is a helpful generation, or sedating, and second-generation, or
alternative. In the case of cats, regular washing of the nonsedating, antihistamines. The first generation of
animal may help decrease the allergen load.153 antihistamines is effective, but they have some unde-
Humidifiers must be cleaned regularly to avoid sirable side effects because of their lack of selectivity
becoming a source of mold allergens, which thrive in and subsequent nonspecific stimulation of other
moist environments. The humidity should not receptors. Among these side effects are sedation,
exceed 40 to 45% because higher levels encourage anticholinergic effects, functional and performance
the growth of dust mites and molds. The use of impairment, and gastrointestinal distress. When
high-efficiency particulate air (HEPA) filters and of applied topically, some act as local anesthetics. The
electrostatic filters effectively removes particulates most important of the side effects is sedation, which
larger than 1 µm in diameter. Particles, however, is reported in approximately 20% of patients. 156
must be airborne for removal, such as pollens, Objective studies of performance have documented
whereas heavy particles that settle from the air rap- the problem. The correlation with the subjective
idly, such as dust mites, are not eliminated by these reporting of sedation was weak, however, and the
measures.154 High-efficiency particulate air filters are problem appeared more significant than previously
preferred to electrostatic ones as they filter out par- believed; that is, a larger number of subjects devel-
ticulate matter without generating ozone, an irritant. oped impaired performance compared with the
General household changes may also be helpful. number reporting sedation. Furthermore, impaired
Repair of any plumbing or drainage problem areas in performance can persist after the subjective feeling
the house must be undertaken to eliminate mold. of somnolence dissipates—hence, the importance of
Decontamination of surfaces contaminated with warning patients who are taking these medications
mold by use of diluted bleach and elimination of not to perform some tasks such as operating heavy
soiled organic materials is useful. Appropriate pack- machinery or driving. Although some side effects
aging of garbage and pesticide application are neces- may be useful, such as the use of diphenhydramine
sary to eliminate cockroaches. Use of well-fitting, for treating insomnia, they are usually a nuisance
semirigid masks when vacuuming offers useful pro- and limit compliance. In one study, diphenhy-
tection from airborne allergens such as dust mites.155 dramine caused worse impairment to driving than
consuming alcohol to the level of being legally
drunk.157 In this study, performance after a second-
PHARMACOLOGIC THERAPY generation agent was similar to that after a placebo.
Second-generation antihistamines are less
ANTIHISTAMINES lipophilic than first-generation H1 antihistamines
Three receptors exist for histamine. H1 receptors and do not penetrate the blood-brain barrier. There-
are found on blood vessels, on sensory nerves, on fore, they produce no more somnolence than does
smooth muscles of the respiratory and digestive placebo. Their greater receptor selectivity also
tracts, and in the central nervous system. Stimula- reduces the incidence of anticholinergic side effects.
tion leads to vasodilatation, increased vascular In addition to antagonizing histamine at the H1
permeability, sneezing, pruritus, glandular secre- receptor, some antihistamines, such as azatadine, of
tion, and increased intestinal motility. H2 recep- the piperidine class, and terfenadine, a nonsedating
tors have a distribution similar to that of H 1 antihistamine, inhibit histamine release after
receptors but are principally involved in the regu- intranasal antigen challenge.158,159 Treatment with
lation of gastric acid secretion. H3 receptors are some antihistamines also reduces the production of
located principally in the brain and seem to be leukotrienes and kinins, which are mediators with
involved in the regulation of histamine synthesis proinflammatory effects,159,160 as well as the allergen-
and release. The contribution of histamine to the induced increased responsiveness to metha-
early allergic response, largely mediated by the H1 choline.104 Another anti-inflammatory property of
receptor, has long been recognized and is the antihistamines is a reduction of soluble ICAM-1 lev-
Allergic Rhinitis 723
els in nasal secretions, a property demonstrated by are most effective in treating sneezing, nasal and ocu-
both loratidine and cetirizine.161 lar pruritus, and rhinorrhea associated with allergic
Oral antihistamines are readily absorbed. Their rhinitis but have little or no effect on nasal congestion.
onset of action is rapid, usually within 60 minutes, Thus, they are often combined with an oral deconges-
and maximum benefit occurs within hours.160 tant. Generic first-generation H1 blockers are con-
Metabolism of most antihistamines occurs prima- siderably less expensive than their nonsedating
rily through the hepatic cytochrome P-450 system. counterparts. Some clinicians have tried to circumvent
Drugs that interfere with this system, such as anti- the sedation caused by first-generation antihistamines
fungal agents, can lead to the accumulation of anti- by directing that they be taken before bedtime, when
histamines to toxic levels. One exception is somnolence is not a problem. The next day, prolonged
cetirizine, which is primarily excreted in the urine tissue levels provide continued efficacy without the
and does not depend on the cytochrome P-450 sys- undesirable side effect of drowsiness.169 Some studies,
tem. The clinical effectiveness of antihistamines however, suggest that performance is impaired despite
exceeds the duration of measurable serum levels. the lack of drowsiness. It is therefore important to
This phenomenon may be attributable to the pres- warn patients receiving these drugs about their effect
ence of active metabolites. Another explanation for on daily activities, such as driving or operating heavy
the prolonged efficacy of H1 receptor antagonists machinery. Patients who lack medical insurance or
beyond their measurable serum levels relates to formulary coverage often use first-generation agents
extended tissue levels. despite their significant side effects. This poses consid-
In the United States, four common second- erable public health concerns, given recent studies
generation antihistamines are in clinical use: azelas- demonstrating the marked performance impairment
tine, cetirizine, fexofenadine, and loratidine.162 associated with their use. Unfortunately, the nonsedat-
Azelastine, a phthalazinone derivative, is an ing antihistamines are more expensive than the tradi-
intranasal preparation with efficacy comparable to tional antihistamines.
that of other antihistamines. Although it does not
cause somnolence, azelastine may cause a sensation
of altered taste immediately after use.163 Cardiac
DECONGESTANTS
arrhythmias, fatal ventricular tachycardia, or pro- Decongestants exert their effect through stimulation
longation of the QT interval associated with con- of α1- or α2-adrenergic receptors. These receptors
comitant administration of agents that interfere are present on resistance vessels, where they control
with the cytochrome P-450 system have been blood flow, and on capacitance vessels, where they
reported with two older second-generation antihis- control blood volume. In capacitance vessels, α2
tamines, terfenadine and astemizole. These agents receptors outnumber α1 receptors.170 In resting con-
are no longer available in the United States. Fexofe- ditions, sympathetic nervous activity regulates nasal
nadine, a metabolite of terfenadine, does not possess patency by maintaining the sinusoids contracted to
these cardiac risks. Second-generation agents have approximately half maximal capacity. The resting
been shown to be effective. Both cetirizine and fex- state is affected by the nasal cycle, a periodic, recip-
ofenadine have been demonstrated to improve qual- rocal alteration of nasal cavity congestion and
ity of life, as measured by generic and disease- decongestion that affects about 80% of normal indi-
specific tools.164,165 They cause little or no somno- viduals. Increased sympathetic stimulation, such as
lence, do not affect performance, and have no anti- occurs during exercise, reduces nasal congestion.
cholinergic effects.166 Azelastine and fexofenadine Oral decongestants exert their effects directly
are approved for children older than 12 years, lorati- and by stimulating norepinephrine release. The two
dine may be used in children age 6 or older, and cet- major decongestants are pseudoephedrine and
irizine may be used in children as young as 2 years.167 phenylpropanolamine, which can be prescribed sep-
All antihistamines are effective in the treatment arately or in combination with antihistamines. Use
of allergic rhinitis and differ principally in their side of phenylpropanolamine in diet medication has
effects, duration of action, and cost. In equipotent been associated with rare hemorrhagic stroke and
doses, they are equally effective in suppressing hista- has been withdrawn from the US market. Because
mine-induced skin wheals.168 H1 receptor antagonists oral decongestants also stimulate adrenergic recep-
724 Ballenger’s Otorhinolaryngology
tors other than those in the nasal vasculature, over- of mediator release during both early- and late-phase
dosage has been associated with hypertensive crisis. reactions after antigen challenge, along with a signifi-
When given in prescribed doses, however, they do cant inhibition of the influx of basophils, eosinophils,
not induce hypertension in normotensive patients, neutrophils, and mononuclear cells in nasal secre-
nor do they alter the pharmacologic control of sta- tions.174,175 Treatment with intranasal corticosteroids
ble hypertensive patients. Current recommendations also reduced the antigen-induced hyperresponsive-
suggest that decongestants should not be used in ness of the nasal mucosa to subsequent antigen174 and
patients with uncontrolled hypertension, in those histamine provocation.100 Intranasal corticosteroid
with severe coronary artery disease, or in patients administration also leads to a reduction in inflamma-
receiving monoamine oxidase inhibitors. Deconges- tory cells and TH2-type cytokines within the nasal
tants should be prescribed with caution in patients mucosa.92 For example, treatment with fluticasone
with diabetes, hyperthyroidism, closed-angle glau- inhibits the allergen-induced increase in IL-4, IL-13,
coma, coronary artery disease, cardiac insufficiency, eotaxin, and MCP-4 mRNA. In addition, intranasal
prostatic hypertrophy, or urinary retention.171 Their corticosteroids increase the level of TH1-type
major side effect is insomnia, which occurs in cytokines such as interferon-γ and IL-12, which can
approximately 25% of patients. suppress the transcription of IL-4.92 These beneficial
Topical decongestants are effective in reducing anti-inflammatory effects of intranasal corticosteroids
nasal congestion, regardless of the cause, and these support the findings in several placebo-controlled
include catecholamines (such as phenylephrine) and clinical trials of a variety of these agents that demon-
imidazoline derivatives (such as xylometazoline or strated their efficacy in the reduction of nasal symp-
oxymetazoline). Prolonged use can bring about rhini- toms in both seasonal176 and perennial177 allergic
tis medicamentosa, which is characterized by reduced rhinitis. Corticosteroid-induced cellular modifica-
duration of action and rebound nasal congestion after tions require several hours to appear, and this might
cessation of therapy. Because this phenomenon can explain why their onset of action was gauged in days,
appear even after a short period, use of these agents although more recent studies show that fluticasone
should be limited to a few days. These agents are best affects symptoms within 12 hours.
reserved for patients in whom nasal congestion is so Topical corticosteroids effectively suppress the
severe that it precludes the use of other topical prepa- response to allergen provocation. In contrast to sys-
rations such as intranasal corticosteroids or more temic corticosteroids, pretreatment with topical cor-
restful sleep is required during acute exacerbations of ticosteroids reduces the acute nasal response to
disease. Seizures have occurred in children given these allergen challenge, as shown by a reduction in symp-
medications intranasally. toms and in levels of recovered inflammatory medi-
ators in nasal secretions (Figure 32–4).174 Treatment
with topical corticosteroids also reduces symptoms,
TOPICAL INTRANASAL CORTICOSTEROIDS the levels of mediators, and cellular infiltration dur-
Topical intranasal glucocorticosteroids are potent ing the late-phase reaction to allergen challenge and
medications for the treatment of allergic rhinitis. the priming response to antigen (see Figure
These agents profoundly reduce multiple aspects of 32–4).70,174 These agents also inhibit hyperrespon-
the inflammatory response to allergen. Corticos- siveness to nonantigenic stimuli such as histamine.99
teroids penetrate the interior of the cell, where they Topical corticosteroids also prevent the increase in
are bound by a glucocorticoid receptor in the cyto- mast cells and inflammatory cells seen during sea-
plasm. The glucocorticoid-receptor complex then sonal exposure to allergen.147 Furthermore, they also
penetrates the nucleus, where it inhibits the synthesis resulted in suppression of the seasonal increase in
of the proinflammatory cytokines IL-1, -2, -3, -5, and specific IgE antibodies during the ragweed season.178
-6; interferon-γ; tumor necrosis factor-α; and GM- A direct vasoconstrictor effect of topical glucocorti-
CSF172 and induces the synthesis of other anti-inflam- costeroids, found in the skin, does not occur on the
matory substances such as vasocortin and lipocortin. nasal mucosa.179
These agents reduce eosinophil survival and function Currently, topical forms of corticosteroids
induced by IL-1, -3, and -5.173,174 Treatment with include flunisolide, beclomethasone dipropionate,
intranasal flunisolide resulted in significant inhibition triamcinolone, budesonide, mometasone, and fluti-
Allergic Rhinitis 725
but some of these patients had also received systemic In comparative trials, topical corticosteroids
corticosteroids.191 An Australian study suggested a were more potent in relieving nasal symptoms than
significant increase in cataract formation associated cromolyn200 or antihistamines.201,202 Previously, the
with prolonged use of these medications, but the addition of antihistamines to intranasal corticos-
effect was small and not much greater than not wear- teroids was thought to benefit ocular symptoms and
ing sunglasses.192 In a more recent study in the United add more rapid onset of effectiveness at the initia-
Kingdom, the use of intranasal corticosteroids was tion of treatment, although a meta-analysis showed
not associated with an increased risk of cataracts.193 A antihistamines and topical corticosteroids to have
reduction in bone growth in children has concerned equivalent effects on ocular symptoms.203 In a study
pediatricians.194 This problem has been studied best comparing intranasal corticosteroids with immuno-
in asthmatic children, and the majority of studies therapy, budesonide was found to be superior to
suggest no effect and are confounded by the effect of Pollinex-R (Bencard Allergy Service, Weston, Ontario,
asthma itself on growth in these patients.195 There- Canada). Pollinex-R is not a standard, accepted form
fore, for long-term use, a topical corticosteroid with of immunotherapy, however, and further investiga-
low bioavailability, administered in the lowest dose tion is warranted in that regard.204
necessary to provide relief of symptoms, seems advis-
able and safe. A recent placebo-controlled clinical
study has shown that treatment of children with
SYSTEMIC CORTICOSTEROIDS
perennial allergic rhinitis with beclomethasone Clinical practice confirms the impression that oral
dipropionate caused a reduction in growth velocity corticosteroids reduce symptoms during seasonal
compared with the effect of placebo.196 This effect allergies, but this has not been documented in
was observed in the absence of laboratory evidence of placebo-controlled trials.205 These agents are usually
hypothalamic-pituitary-adrenal axis suppression, administered to patients during severe exacerbations
suggesting that growth velocity may be a more sensi- of allergic symptoms when total nasal obstruction
tive indicator of systemic corticosteroid exposure prevents the introduction of a topical intranasal cor-
than assessment of the hypothalmic-pituitary axis in ticosteroid. Furthermore, these agents are used suc-
pediatric patients. On the other hand, treatment of cessfully in combination with antibiotics for
children with perennial allergic rhinitis with treatment of sinus infections complicating allergic
mometasone furoate for a year did not result in any exacerbations. Depot injections of corticosteroids
growth retardation or hypothalamic-pituitary-adre- have efficacy comparable with short-term oral pred-
nal axis suppression compared to placebo.197 The nisone therapy and enjoy some popularity in
long-term effects of the reduction in growth velocity, Europe, including Scandinavia.206 Corticosteroid
including the final impact on adult height and the injections into the turbinates are also perceived as
ability to catch up in growth after discontinuation of clinically effective but have rarely been used in North
treatment, have not been adequately studied. Recent America since the advent of intranasal corticos-
recommendations state that the growth of pediatric teroids and because of a small associated risk of
patients receiving intranasal corticosteroids should blindness.207 Although this complication can be
be monitored regularly (every 3 to 6 months) with an minimized by use of a corticosteroid with small par-
accurate instrument (stadiometer) by trained staff in ticle size, the need to take this infrequent risk in lieu
a consistent way. Furthermore, it seems wise to use of alternative successful therapies has led to a decline
the newer agents with the lower systemic bioavail- in the popularity of this form of treatment.
ability such as mometasone and fluticasone for the
treatment of children. These agents have been
approved by the US Food and Drug Administration
CROMOLYN SODIUM
(FDA) starting at the ages of 3 (mometasone) and 4 Cromolyn is available over the counter as a 4% solu-
years (fluticasone), with the recommended dose tion for intranasal use and has been shown to be clin-
being half that used for adults. Mometasone and flu- ically effective in the treatment of allergic rhinitis. It
ticasone are poorly absorbed from the gastrointesti- exerts a protective effect on the allergic response
nal tract, with the remaining fraction of absorbed when given four to six times daily beginning before
drug rapidly metabolized by the liver.198,199 the development of symptoms.208 Although it was
Allergic Rhinitis 727
initially thought to prevent mast cell degranulation, tive in patients who do not tolerate intranasal
the exact mechanism of action of this agent is corticosteroids.
unknown. Its effectiveness approximates that of anti-
histamines,209 but the need for frequent dosing limits
compliance. Like antihistamines, cromolyn is more
OPHTHALMIC PREPARATIONS
helpful for sneezing, rhinorrhea, and nasal itching Treatment of ocular symptoms of allergy employs a
than for nasal congestion.210 Its safety profile, how- regimen of medications similar to those used for
ever, makes it an attractive treatment, especially in nasal manifestations. After avoidance, pharma-
children and pregnant women. When effective, the cotherapy includes the use of topical decongestants,
potency of this agent parallels that of antihistamines antihistamines, mast cell–stabilizing agents, and anti-
but is less than that of intranasal corticosteroids. inflammatory preparations.217 Topical decongestants
such as phenylephrine and tetrahydrozoline decrease
vascular congestion and eyelid edema through α-
ANTICHOLINERGIC AGENTS adrenergic receptors. Several over-the-counter topi-
Ipratropium bromide is the only anticholinergic cal antihistamines are available, some in combination
agent available for topical use in the United States. with a decongestant. Recently, second-generation
Anticholinergic agents inhibit parasympathetic topical antihistamines have become available. Levo-
stimulation of glandular secretion by competing for cabastine is a long-lasting topical antihistamine with
muscarinic receptors on glands. They are highly a rapid onset of action that has been shown to be
effective in reducing rhinorrhea but have no effect effective.218 Azelastine has recently been approved for
on the other symptoms of allergic rhinitis.211,212 The the treatment of allergic conjunctivitis.219 Emedastine
clinical benefit of anticholinergic agents is prima- and olopatadine are also new topical agents that have
rily limited to the treatment of patients with rhini- also been shown to be effective.220,221 Ophthalmic for-
tis in whom rhinorrhea is the predominant mulations of ketotifen fumarate, pemirolast potas-
complaint. This could occur in a variety of nasal sium, and nedocromil sodium, agents with mast
conditions such as allergic and nonallergic rhinitis, cell–stabilizing agents and other properties, have
as well as the rhinorrhea precipitated by exposure to recently been approved by the FDA for use in adults
cold, windy environments, often referred to as and children with itching of the eyes owing to aller-
“skiers’ nose.”213 The dosage should be titrated to gic conjunctivitis. Ketorolac, a nonsteroidal anti-
avoid excessive drying of the nasal mucosa and epis- inflammatory agent, diminishes ocular itching and
taxis, which are the most frequent side effects. This hyperemia and is the only agent in this class
agent serves as a useful adjuvant therapy with topi- approved by the FDA for treatment of allergic con-
cal corticosteroids and antihistamines for control of junctivitis.222 Mild topical corticosteroids can be used
rhinorrhea. in patients who continue to have symptoms despite
treatment with the aforementioned agents, but these
can cause local complications. Rapidly inactivated
LEUKOTRIENE MODIFIERS topical corticosteroids are under investigation for use
Among the numerous mediators released into the in this disease. Although a number of new drugs are
nose on antigen challenge, leukotrienes have been now in use, there are few randomized, placebo-con-
shown to contribute to nasal congestion in allergic trolled trials comparing the efficacy of these agents.
rhinitis.57,58 Symptoms of allergic rhinitis have been
shown to be reduced by two clinically available
leukotriene modifiers, zafirlukast and mon-
IMMUNOTHERAPY
telukast.214,215 These drugs, although not currently The exact mode by which immunotherapy achieves
indicated in the primary treatment of allergic rhini- efficacy remains to be fully elucidated.223 Studies show
tis, may be useful in the treatment of patients with that this treatment induces a state of specific T-cell
allergic rhinitis and concomitant asthma. The com- tolerance with a subsequent reduction in mediator
bination of a leukotriene modifier with an antihis- release and tissue inflammation.224 Immunotherapy
tamine increases the efficacy of both medications.216 produces several immune modifications in the
This combination can be considered as an alterna- peripheral blood and nasal mucosa that probably
728 Ballenger’s Otorhinolaryngology
contribute to its efficacy.225,226 Treatment causes a rise allergens, dust mites, and some animal danders,
in serum-specific IgG antibodies, a suppression in the treatment with molds is less reliable. Immunother-
usual seasonal rise in specific IgE antibodies with a apy with too many allergens is impractical, and usu-
decline over years, and an increase in IgA and IgG ally treatment with no more than 6 to 10 allergens is
antibodies in nasal secretions.227,228 It reduces in vitro attempted. Enzymes from some allergens can
lymphocyte responsiveness to antigen229 and destroy other extracts, reducing the expected
decreases IL-2 release by inflammatory cells.230 In potency of the treatment.233 Furthermore, combin-
experimental models of nasal provocation, immuno- ing allergens of different clinical sensitivities may
therapy reduces both early and late responses to rag- interfere with reaching adequate maintenance doses
weed antigen challenge, cellular influx into nasal for all allergens. Patients who are taking beta block-
secretions, and priming.231 During the allergy season, ers should not receive immunotherapy because, if
immunotherapy leads to an inhibition of eosinophil anaphylaxis occurs, they cannot be resuscitated.
migration into nasal secretions232 and a reduction in Immunotherapy of symptomatic asthmatic patients
nonspecific hyperreactivity to histamine.233 A ran- should be administered with extreme caution
domized, double-blind, placebo-controlled trial of the because these patients have the greatest morbidity.
discontinuation of immunotherapy for grass-pollen Immunotherapy should not be started in pregnant
allergy showed a sustained reduction in the late skin women because of the risk of anaphylaxis and the
response and associated CD3+ T-cell infiltration and resultant effect of hypotension on the fetus.
IL-4 mRNA expression.234 These results suggest that Improvement of symptoms may begin as soon
long-term changes occur in immune function as a as 12 weeks, but an optimal effect usually takes 1
result of immunotherapy, possibly owing to a switch year to attain.233 Effectiveness of immunotherapy
from TH2 to TH1 responses. requires administration of sufficient amounts of
Indications for immunotherapy have not been allergen. For ragweed, this has been shown to be
established by experimental studies but rather have between 6 and 12 µg of Amb a 1 (the major antigen
evolved over years of clinical experience.233 The in ragweed) per injection. The effect is antigen spe-
primary indication is symptoms not adequately con- cific; thus, selection of relevant antigens for treat-
trolled by avoidance measures and pharmacother- ment is paramount. Patients who do not achieve
apy. Patients with perennial symptoms may prefer symptomatic improvement after 1 year of im-
immunotherapy to yearlong daily medication. In munotherapy should have it discontinued. No infor-
making their selection, patients must be advised that mation is available on the length of time over which
immunotherapy offers control of symptoms but is effective immunotherapy should be pursued, but
slow in onset and, unlike pharmacotherapy, is effec- most physicians treat for 2 to 5 years.
tive only for the allergens for which the patient is Allergen injections should be administered
treated. Whether years of successful therapy cure the under the supervision of a qualified medical practi-
disease after discontinuation of immunotherapy is tioner, and patients should be observed for at least 30
an important but unanswered question. However, minutes after every injection. Local reactions at the
one study suggested that improvement in rhinitis site of injection are frequent with effective dosages
symptoms persists for several years after the end of and require no therapy. Repeated strong reactions (ie,
treatment.234 greater than 4 cm in diameter) persisting for 24
Immunotherapy begins with low-dose injec- hours should lead to consideration of dose reduction.
tions of allergen extracts and builds to a mainte- Proper resuscitative equipment should be present
nance dose. Injections usually begin at weekly because anaphylactic reactions can occur at any time
intervals and are then reduced in frequency when during treatment, even in patients receiving mainte-
maintenance doses are reached. The choice of aller- nance dosages. Factors that seem to contribute to
gens for treatment must be made after a careful diag- increased complications, including fatalities, seem to
nostic workup so that the probability of treatment be labile, corticosteroid-dependent asthma that has
being started with extracts from all of the allergens required prior hospitalizations, high sensitivity to
responsible for symptoms is increased. Treatment allergen (as demonstrated by serum-specific IgE tests
should not be given if skin or serum testing cannot or skin test), and a history of prior systemic reac-
confirm evidence of an IgE-mediated mechanism. tions.235 Therefore, although death from immuno-
Whereas excellent relief can be expected with pollen therapy is uncommon (the risk is estimated at one
Allergic Rhinitis 729
fatality for every 2 million injections), special pre- elite athletes, preventive therapy must be initiated so
cautions need to be taken with asthma, and a waiting that effects on peak performance can be avoided.242
period of at least 20 minutes after administration of The Olympic Committee bans pseudoephedrine-
the injection is recommended for all patients, with containing agents. Similarly, care must be taken in
longer intervals (30 minutes) appropriate for high- the treatment of elderly patients with respect to side
risk patients.236 Concern over mortality has led to effects, clearance, and drug interactions. Treatment
decreased use in the United Kingdom. of rhinitis during pregnancy poses special problems.
Rhinitis and nasal congestion frequently occur dur-
ing pregnancy (30%) and are related to hormonal
FUTURE THERAPIES changes.243,244 Pregnant patients require careful con-
As the molecular dissection of the complex immuno- sideration in the choice of therapy. Ideally, no med-
logic pathophysiology of allergic rhinitis has devel- ication should be used, particularly during the first
oped, new targets are surfacing for pharmacologic trimester. Avoidance measures should be imple-
development. Perhaps the most obvious target is IgE, mented first. If symptoms of rhinitis interfere with
given its central role in allergic rhinitis. An antihuman maternal well-being, pharmacologic management is
IgE antibody (rhuMAb-E25) showed promise in early considered.245 The patient must be advised that no
trials237,238; a phase 3 trial suggested that this therapy drug can be considered absolutely safe because most
may have potential.239 A third generation of antihist- drugs cross the placenta and can be measured in
amines is in phase 2 and phase 3 clinical trials (deslo- fetal blood.
ratadine and norastemizole). Development of drugs The American College of Obstetricians and
combining antihistamines and antileukotriene agents Gynecologists (ACOG) and the American College
is under way. Perhaps most exciting are advances in of Allergy, Asthma and Immunology (ACAAI) make
cytokine biology. Drugs targeting several cytokines the following recommendations. Pseudoephedrine
known to play a role in the inflammatory process are has been recommended as the decongestant to be
being developed and tested. These include mono- used in pregnancy, even though studies show an asso-
clonal antibodies to IL-4, IL-13, and IL-5; monoclonal ciation with a rare birth defect, gastroschisis.246 There-
antibodies to the receptors of IL-4 and IL-13; and sol- fore, the recommendation remains to avoid oral
uble IL-4 and IL-13 receptors.240 Classes of investiga- decongestants during the first trimester.247 Chlor-
tional agents that target other molecules thought to be pheniramine and tripelennamine have been recom-
important in the inflammatory processes of allergic mended as the antihistamines of choice for use in
rhinitis include tryptase inhibitors, phosphodi- pregnancy, based on animal and human studies. Ani-
esterase-4 inhibitors, chemokine inhibitors, and adhe- mal studies have been reassuring for cetirizine and
sion receptor antagonists.240 loratidine but not for azelastine or fexofenadine. In
A perhaps more elegant therapeutic strategy patients who do not tolerate chlorpheniramine and
would be to effect long-lasting changes in immune tripelennamine and who fail other therapies, use of
responses away from an allergic phenotype. Such a cetirizine and loratidine could be considered.247
strategy might alter the natural course of disease and Sodium cromoglycate is a safe drug during pregnancy
allow discontinuation of medication. This type of and should be considered in the treatment of allergic
immunotherapy may involve immunization with rhinitis before corticosteroids. No data exist on the
allergen, modified allergen, peptides of allergen, or teratogenicity of intranasal corticosteroids in
complementary deoxyribonucleic acid (cDNA) of humans,170 although they are thought to be safe and
allergen, with adjuvants, including immunostimula- effective.248 They are widely used during gestation,
tory DNA sequences, cytokines, and bacterial prod- given their effectiveness in allergic disease and the lack
ucts.241 These therapies will require further study but of systemic effects. Studies on inhaled corticosteroids
ultimately may prove useful in expanding the arma- and pregnancy would suggest that beclomethasone
mentarium against allergic rhinitis. and budesonide would be the agents to be initiated.
Because the available intranasal corticosteroids do not
vary in efficacy or safety and lack systemic side effects,
SPECIAL CONSIDERATIONS one may consider continuing treatment with these
Several patient populations require careful attention agents in a patient who has well-controlled disease
in the treatment of allergic rhinitis. In the case of prior to pregnancy and who continues to require
730 Ballenger’s Otorhinolaryngology
treatment.247 Newer forms of intranasal corticos- teroids are initially given at the dose recommended
teroids with lower bioavailability may be a more pru- in the Physicians’ Desk Reference. Patients should be
dent choice. Leukotriene modifiers show adverse seen 2 weeks after initiation of therapy for monitor-
effects in animals and cannot be recommended in ing for the development of local side effects. Super-
pregnancy. Maintenance immunotherapy may be ficial septal erosions can occur secondary to trauma
safely continued during pregnancy in patients who from the nozzle, and the application technique
are not prone to systemic reactions. Because of the should be carefully reviewed with these patients. The
increased risk of systemic reactions, immunotherapy dosage is adjusted depending on the response: if a
should not be initiated during pregnancy. patient is doing better but continues to have break-
through symptoms, the frequency of administration
TOWARD A RATIONAL CHOICE OF is increased; if excellent control is achieved, the fre-
quency or the dose should be reduced.
THERAPY Furthermore, periods of exacerbations can be
Prevention remains the mainstay of treatment of predicted, based on a patient’s pattern of allergies;
allergic rhinitis (Figure 32–5). If allergen exposure therefore, the medication dosage can be varied
can be reduced, this should be part of long-term accordingly. Ocular symptoms may be minimally
management. Short-term avoidance does not result controlled by intranasal corticosteroids; thus, adding
in an instant resolution of symptoms and is rarely an ophthalmic preparation or an oral antihistamine
completely achievable. may be necessary.
Pharmacotherapy provides the fastest relief. In children, the long-term use of certain topi-
Antihistamines begin to take effect within 1 hour cal corticosteroids is approved in patients as young
and traditionally constitute the first line of interven- as age 3 years or older. For most topical cortico-
tion. They are excellent for the treatment of sneezing steroids, it is recommended to reduce the dose by
and watery rhinorrhea. When cost is not an issue, half in young children. Because of the slight possi-
nonsedating antihistamines should always be pre- bility that intranasal corticosteroids could interfere
scribed. To minimize cost, one can administer a with growth, these medications should always be
long-acting, sedating antihistamine around bedtime given in the lowest effective dose. Growth should be
and allow its efficacy to persist into the next day carefully and regularly monitored. Treatment with
without its sedative side effect, although adverse cen- topical corticosteroids requires patient education.
tral nervous system effects may still occur. Decon- The physician must often reassure patients as to the
gestants can be added to antihistamines in fixed safety of intranasal corticosteroids compared with
combinations or as separate agents for relief of nasal oral preparations.
congestion. Cromolyn sodium is an alternative to Initiation of immunotherapy depends on
antihistamines as an initial treatment, but the need patient preference and the response to pharma-
for frequent dosing, with the resultant reduction in cotherapy. Immunotherapy has not been shown to
compliance, should be kept in mind. Leukotriene be more effective than intranasal corticosteroids.
modifiers may be used for effects against congestion Surgical management of nasal obstruction is
in asthmatic or refractory cases and may be used in presented in Chapter 33. Major septal deviations
combination with antihistamines in patients who do should be corrected because they may interfere with
not tolerate other therapies. the delivery of intranasal medications. Less severe
When antihistamines and/or decongestants are obstructions should be corrected only if symptoms
insufficient in relieving symptoms, topical corticos- persist after adequate control of the allergic symp-
teroids should be recommended. These have been toms. Similarly, turbinate reduction by means of
shown to be equally effective as antihistamines even submucous resection, vaporization with the laser,
when used on an as needed basis. They are highly electrocautery, or radiofrequency ablation may be
effective in reducing all of the nasal symptoms of adjuvant procedures in patients with allergic rhinitis
allergic rhinitis, including congestion. They are but more often find use in the management of non-
nonsedating, have few side effects, and are well tol- allergic rhinitis (see Chapter 33). Functional endo-
erated by patients. The daily cost of treatment with scopic sinus surgery, presented in Chapter 34, can be
nasal corticosteroids is less than that of the daily use used for the treatment of chronic rhinosinusitis,
of nonsedating antihistamines. Topical corticos- which frequently complicates perennial rhinitis.249
Allergic Rhinitis 731
lenge with antigen of allergic subjects. Am Rev number, asthma, hay fever, and eczema. Arch Dis
Respir Dis 1990;142:594–601. Child 1998;79:328–33.
10. Molfino NA, Slutsky AS, Zamel N. The effect of air 25. Ball TM, Castro-Rodriguez JA, Griffith KA, et al. Sib-
pollution on allergic bronchial responsiveness. Clin lings, day-care attendance, and the risk of asthma
Exp Allergy 1992;22:667–72. and wheezing during childhood. N Engl J Med
11. Matsumura Y. The effects of ozone, nitrogen dioxide, 2000;343:538–43.
and sulfur dioxide on the experimentally induced 26. Martinez FD. Maturation of immune responses at
allergic respiratory disorders in guinea pigs 1. The the beginning of asthma. J Allergy Clin Immunol
effect of sensitization with albumin through the air- 1999;103:355–61.
way. Am Rev Respir Dis 1970;102:430–7. 27. Evans RI. Epidemiology and natural history of
12. Nel AE, Diaz Sanchez D, Ng D, et al. Enhancement of asthma, allergic rhinitis, and atopic dermatitis.
allergic inflammation by the interaction between In: Middleton EJ, Reed CE, Ellis EF, et al, editors.
diesel exhaust particles and the immune system. J Allergy: principles and practice. 4th ed. St. Louis:
Allergy Clin Immunol 1998;102(Pt 1):539–54. Mosby-Year Book; 1993.
13. von Mutius E, Martinez FD, Fritzsch C, et al. Prevalence 28. Malmberg H. Symptoms of chronic and allergic
of asthma and atopy in two areas of West and East Ger- rhinitis and occurrence of nasal secretion granulo-
many. Am J Respir Crit Care Med 1994;149:358–64. cytes in university students, children and infants.
14. Magnussen H, Jörres R, Nowak D. Effect of air pol- Allergy 1979;34:389–94.
lution on the prevalence of asthma and allergy: les- 29. Zeiger RS. Development and prevention of allergic
sons from the German reunification. Thorax disease in childhood. In: Middleton EJ, Reed CE, Ellis
1993;48:879–81. EF, et al, editors. Allergy: principles and practice. 4th
15. Hide DW, Matthews S, Matthews L, et al. Effect of ed. St. Louis: Mosby-Year Book; 1993. p. 1137–72.
allergen avoidance in infancy on allergic manifesta- 30. Aberg N, Engstrom I. Natural history of allergic dis-
tions at age two years. J Allergy Clin Immunol eases in children. Acta Paediatr Scand 1990;79:
1994;93:842–6. 206–11.
16. Shaheen SO, Aaby P, Hall AJ, et al. Measles and atopy 31. The Collaborative Study on the Genetics of Asthma
in Guinea-Bissau. Lancet 1996;347:1792–6. (CSGA). A genome-wide search for asthma suscep-
17. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. tibility loci in ethnically diverse populations. Nat
The inverse association between tuberculin re- Genet 1997;15:389–92.
sponses and atopic disorders. Science 1997;275:77–9. 32. Daniels SE, Bhattacharrya S, James A, et al. A
18. Matricardi PM, Rosmini F, Ferrigno L, et al. Cross genome-wide search for quantitative trait loci
sectional, retrospective study of prevalence of atopy underlying asthma. Nature 1996;383:247–50.
among Italian military students with antibodies 33. Dizier MH. Genome screen for asthma and related
against hepatitis A virus. BMJ 1997;314:999–1003. phenotypes in the French EGEA study. Am J Respir
19. von Mutius E, Martinez FD, Fritzsch C, et al. Skin Crit Care Med 2000;162:1812–8.
test reactivity and number of siblings. BMJ 1994; 34. Ober C, Tsalenko A, Parry R, Cox NJ. A second-gen-
308:692–5. eration genome wide screen for asthma-susceptibil-
20. Strachan DP, Harkins LS, Johnston IDA, Anderson ity alleles in a founder population. Am J Hum Genet
HR. Childhood antecedents of allergic sensitization 2000;67:1154–6.
in young British adults. J Allergy Clin Immunol 35. Wjst M. Specific IgE—one gene fits all? German
1997;99:6–12. Asthma Genetics Group. Clin Exp Allergy 1999;29
21. Strachan DP. Hay fever, hygiene, and household size. Suppl 4:5–10.
BMJ 1989;299:1259–60. 36. Barnes KC. Evidence for common genetic elements
22. Strachan, DP, Taylor EM, Carpenter RG. Family in allergic disease. J Allergy Clin Immunol 2000;
structure, neonatal infection, and hay fever in ado- 106(5 Suppl):S192–200.
lescence. Arch Dis Child 1996;74:422–6. 37. Ober C, Moffatt MF. Contributing factors to the
23. Rona RJ, Duran-Tauleria E, Chinn S. Family size, pathobiology. The genetics of asthma. Clin Chest
atopic disorders in parents, asthma in children, and Med 2000;21:245–61.
ethnicity. J Allergy Clin Immunol 1997;99:454–60. 38. Blumenthal JB, Blumenthal MN. Immunogenetics of
24. Ponsonby AL, Couper D, Dwyer T, Carmichael A. allergy and asthma. Immunol Allergy Clin North
Cross sectional study of the relation between sibling Am 1996;16:517–35.
Allergic Rhinitis 733
39. Togias AG. Systemic immunologic and inflamma- gen challenge of allergic individuals. J Clin Invest
tory aspects of allergic rhinitis. J Allergy Clin 1985;76:191–7.
Immunol 2000;106(5 Suppl):S247–50. 54. Baumgarten CR, Nichols RC, Naclerio RM, et al.
40. Church JA, Bauer H, Bellanti JA, et al. Hyposmia Plasma kallikrein during experimentally induced
associated with atopy. Ann Allergy 1978;40:105–9. allergic rhinitis: role in kinin formation and contri-
41. Binder E, Holopainen E, Malmberg K, Salo OP. Clin- bution of TAME-esterase activity. J Immunol
ical findings in patients with allergic rhinitis. Rhi- 1986;137:977–82.
nology 1984;22:255–60. 55. Baumgarten CR, Nichols RC, Naclerio RM, Proud D.
42. Settipane GA, Chafee FH. Nasal polyps in asthma Concentration of glandular kallikrein in human nasal
and rhinitis. A review of 6,037 patients. J Allergy secretions increase during experimentally induced
Clin Immunol 1977;59:17–21. allergic rhinitis. J Immunol 1986;137:1323–8.
43. Friedman RA, Doyle WJ, Casselbrant ML, et al. 56. Castells M, Schwartz LB. Tryptase levels in nasal-
Immunologic-mediated eustachian tube obstruc- lavage fluid is an indicator of the immediate allergic
tion: a double-blind crossover study. J Allergy Clin reaction. J Allergy Clin Immunol 1988;82:348–55.
Immunol 1983;71:442–7. 57. Creticos PS, Peters SP, Adkinson NF, et al. Peptide
44. Hurst DS, Amin K, Seveus L, Venge P. Mast cells and leukotriene release after antigen challenge in
tryptase in the middle ear of children with otitis patients sensitive to ragweed. N Engl J Med 1984;
media with effusion. Int J Pediatr Otorhinolaryngol 310:1626–30.
1999;49 Suppl 1:S315–9. 58. Peters SP, Freeland HS, Kelly SJ, et al. Is leukotriene
45. Wright ED, Hurst D, Miotto D, et al. Increased B4 an important mediator in human IgE-mediated
expression of major basic protein (MBP) and inter- allergic reactions? Am Rev Respir Dis 1987;135(6 Pt
leukin-5 (IL-5) in middle ear biopsy specimens 2):S42–5.
from atopic patients with persistent otitis media 59. Bascom R, Pipkorn U, Proud D, et al. Major basic
with effusion. Otolaryngol Head Neck Surg 2000; protein and eosinophil-derived neurotoxin concen-
123:533–8. trations in nasal-lavage fluid after antigen challenge:
46. Bernstein JM, Lee J, Conboy K, et al. Role of IgE effect of systemic corticosteroids and relationship to
mediated hypersensitivity in recurrent otitis media eosinophil influx. J Allergy Clin Immunol 1989;84:
with effusion. Am J Otol 1983;5:66–9. 338–46.
47. Enerbäck L, Pipkorn U, Olofsson A. Intraepithelial 60. Togias AG, Lykens K, Kagey-Sabotka A, et al. Studies
migration of mucosal mast cells in hay fever: ultra- on the relationship between sensitivity to cold dry
structural observations. Int Arch Allergy Appl air, hyperosmolar solutions and histamine in the
Immunol 1986;81:289–97. adult nose. Am Rev Respir Dis 1990;141:1428.
48. Cameron L, Hamid Q, Wright E, et al. Local synthe- 61. Tønnesen P, Mygind N. Nasal challenge with sero-
sis of epsilon germline gene transcripts, IL-4, and IL- tonin and histamine in normal persons. Allergy
13 in allergic nasal mucosa after ex vivo allergen 1985;40:350–3.
exposure. J Allergy Clin Immunol 2000;106(1 Pt 1): 62. Karim SM, Adaikian PG, Kunaratnam N. Effect of
46–52. topical prostaglandins on nasal patency in man.
49. Durham SR, Smurthwaite L, Gould HJ. Local IgE Prostaglandins 1978;15:457–62.
production. Am J Rhinol 2000;14:305–7. 63. Bisgaard H, Olsson P, Bende M. Effect of leukotriene
50. Plaut M, Pierce JH, Watson CJ, et al. Mast cell lines D4 on nasal mucosal blood flow, nasal airway resist-
produce lymphokines in response to cross-linkage of ance and nasal secretions in humans. Clin Allergy
Fc epsilon RI or to calcium ionophores. Nature 1986;16:289–97.
1989;339:64–7. 64. Proud D, Reynolds CJ, Lacapra S, et al. Nasal provo-
51. Bradding P, Feather IH, Howarth PH, et al. Inter- cation with bradykinin induces symptoms of rhinitis
leukin 4 is localized to and released by human mast and a sore throat. Am Rev Respir Dis 1988;137:613–6.
cells. J Exp Med 1992;176:1381–6. 65. Doyle WJ, Boehm S, Skoner DP. Physiologic
52. Naclerio RM, Meier HL, Kagey-Sobotka A, et al. responses to intranasal dose-response challenges
Mediator release after airway challenge with antigen. with histamine, metacholine, bradykinin, and
Am Rev Respir Dis 1983;128:597–602. prostaglandin in adult volunteers with and without
53. Baumgarten CR, Togias AG, Naclerio RM, et al. nasal allergy. J Allergy Clin Immunol 1990;86:
Influx of kininogens into nasal secretions after anti- 924–35.
734 Ballenger’s Otorhinolaryngology
66. Gleich GJ. The late phase of the immunoglobulin E- 80. Lee BJ, Naclerio RM, Bochner BS, et al. Nasal chal-
mediated reaction: a link between anaphylaxis and lenge with allergen upregulates the local expression
common allergic disease? J Allergy Clin Immunol of vascular endothelial adhesion molecules. J Allergy
1982;70:160–9. Clin Immunol 1994;94(6 Pt 1):1006–16.
67. Naclerio RM, Proud D, Togias AG, et al. Inflamma- 81. Walsh GM, Mermod JJ, Hartnell A, et al. Human
tory mediators in late antigen-induced rhinitis. N eosinophil, but not neutrophil, adherence to IL-1
Engl J Med 1985;313:65–70. stimulated human umbilical vascular endothelial
68. Iliopoulos O, Proud D, Adkinson NF, et al. Relation- cells is alpha 4 beta 1 (very late antigen-4) depend-
ship between the early, late, and rechallenge reaction ent. J Immunol 1991;146:3419–23.
to nasal challenge with antigen: observations on the 82. Lobb RR. Integrin-immunoglobulin superfamily inter-
role of inflammatory mediators and cells. J Allergy actions in endothelial-leukocyte adhesion. In: Harlan
Clin Immunol 1990;86:851–61. JM, Liu DY, editors. Adhesion: its role in inflammatory
69. Taylor G, Shivalkar PR. ‘Arthus-type’ reactivity in the disease. New York: WH Freeman; 1992. p. 1–15.
nasal airways and skin in pollen sensitive subjects. 83. Schleimer RP, Sterbinsky SA, Kaiser J, et al. IL-4
Clin Allergy 1971;1:407–14. induces adherence of human eosinophils and
70. Bascom R, Wachs M, Naclerio RM, et al. Basophil basophils but not neutrophils to endothelium. Asso-
influx occurs after nasal antigen challenge: effects of ciation with expression of VCAM-1. J Immunol
topical corticosteroid pretreatment. J Allergy Clin 1992;148:1086–92.
Immunol 1988;81:580–9. 84. Bochner BS, Luscinskas FW, Gimbrone MA, et al.
71. Lim-Mombay M, Baroody FM, Taylor R, Naclerio Adhesion of human basophils, eosinophils, and neu-
RM. Mucosal cellular changes after nasal antigen chal- trophils to interleukin1-activated human vascular
lenge [abstract]. J Allergy Clin Immunol 1993;89:205. endothelial cells: contributions of endothelial cell
72. Varney VA, Jacobson MR, Sudderick RM, et al. adhesion molecules. J Exp Med 1991;173:1553–7.
Immunohistology of the nasal mucosa following 85. Phillips ML, Nudelman E, Gaeta FC, et al. ELAM-1
allergen-induced rhinitis. Identification of activated mediates cell adhesion by recognition of carbohy-
T lymphocytes, eosinophils, and neutrophils. Am drate ligand, sialyl-Lex. Science 1990;250:1130–2.
Rev Respir Dis 1992;146:170–6. 86. Montefort S, Feather IH, Wilson SJ, et al. The expres-
73. Bryan WTK, Bryan MP. Significance of mast cells in sion of leukocyte-endothelial adhesion molecules is
nasal secretions. Trans Am Acad Ophthalmol Oto- increased in perennial allergic rhinitis. Am J Respir
laryngol 1959;63:613. Cell Mol Biol 1992;7:393–8.
74. Okuda M, Otsuka H. Basophilic cells in allergic nasal 87. Robinson DS. Interleukin-5, eosinophils and bronchial
secretions. Arch Otorhinolaryngol 1977;214:283–9. hyperreactivity. Clin Exp Allergy 1993;23:1–3.
75. Okuda M, Kawabori S, Otsuka H. Electron micro- 88. Altman LC, Ayars GH, Baker C, Luchtel DL. Cytokines
scope study of basophilic cells in allergic nasal secre- and eosinophil-derived cationic proteins upregulate
tions. Arch Otorhinolaryngol 1978;221:215–20. intercellular adhesion molecule-1 on human nasal
76. Hastie R, Heroy JH, Levy DA. Basophil leukocytes epithelial cells. J Allergy Clin Immunol 1993;92:
and mast cells in human nasal secretions and scrap- 527–36.
ings studied by light microscopy. Lab Invest 89. Holgate S. Mediator and cytokine mechanisms in
1979;40:554–61. asthma. Thorax 1993;48:103–9.
77. Okuda M, Otsuka H, Kawabori S. Basophil leuko- 90. Durham SR, Ying S, Varney VA, et al. Cytokine mes-
cytes and mast cells in the nose. Eur J Respir Dis senger RNA expression for IL-3, IL-4, IL-5, and
1983;64 Suppl 128:7–15. granulocyte/macrophage-colony-stimulating factor
78. Otsuka H, Denburg J, Dolovich J, et al. Heterogene- in the nasal mucosa after local allergen provocation:
ity of metachromatic cells in the human nose: sig- relationship to tissue eosinophilia. J Immunol
nificance of mucosal mast cells. J Allergy Clin 1992;148:2390–4.
Immunol 1985;76:695–702. 91. Alam R, Sim TC, Hilsmeier K, Grant JA. Develop-
79. Bentley AM, Jacobson MR, Cumberworth V, et al. ment of a new technique for recovery of cytokines
Immunohistology of the nasal mucosa in seasonal from inflammatory sites in situ. J Immunol Meth-
allergic rhinitis: increases in activated eosinophils ods 1992;155:25–9.
and epithelial mast cells. J Allergy Clin Immunol 92. Christodoulopoulos P, Cameron L, Durham S,
1992;89:877–83. Hamid Q. Molecular pathology of allergic disease.
Allergic Rhinitis 735
II: upper airway disease. J Allergy Clin Immunol relationship to eosinophil influx. J Allergy Clin
2000;105:211–23. Immunol 1990;86:466–72.
93. Hanazawa T, Antuni JD, Kharitonov SA, Barnes PJ. 105. Baroody FM, Lim MC, Proud D, et al. Effects of
Intranasal administration of eotaxin increases nasal loratadine and terfenadine on the induced nasal
eosinophils and nitric oxide in patients with allergic allergic reaction. Arch Otolaryngol Head Neck Surg
rhinitis. J Allergy Clin Immunol 2000;105:58–64. 1996;122:309–16.
94. Sim TC, Reece LM, Hilsmeier KA, et al. Secretion 106. Klementsson H, Svensson C, Andersson M, et al.
of chemokines and other cytokines in allergen- Eosinophils, secretory responsiveness and glucocorti-
induced nasal responses: inhibition by topical coid-induced effects on the nasal mucosa during a
steroid treatment. Am J Respir Crit Care Med weak pollen season. Clin Exp Allergy 1991;21:705–10.
1995;152:927–33. 107. Konno A, Togawa K. Role of the vidian nerve in nasal
95. Bradding P, Feather IH, Wilson S, et al. Immunolo- allergy. Ann Otol Rhinol Laryngol 1979;88:258–66.
calization of cytokines in the nasal mucosa of nor- 108. Baroody FM, Ford S, Lichtenstein LM, et al. Physi-
mal and perennial rhinitic subjects. The mast cell ologic responses and histamine release after nasal
as a source of IL-4, IL-5, and IL-6 in human aller- antigen challenge. Effect of atropine. Am J Respir
gic mucosal inflammation. J Immunol 1993;151: Crit Care Med 1994;149:1457–65.
3853–65. 109. Raphael GD, Igarashi Y, White MV, Kaliner MA.
96. Kuna P, Alam R, Ruta U, Gorski P. RANTES induces The pathophysiology of rhinitis. V. Sources of pro-
nasal mucosal inflammation rich in eosinophils, tein in allergen-induced nasal secretions. J Allergy
basophils and lymphocytes in vivo. Am J Respir Clin Immunol 1991;88:33–42.
Crit Care Med 1998;157:873–9. 110. Wagenmann M, Baroody FM, Desrosiers M, et al.
97. Connell JT. Quantitative intranasal pollen chal- Unilateral nasal allergen challenge leads to bilateral
lenges. 3. The priming effect in allergic rhinitis. J release of prostaglandin D2. Clin Exp Allergy
Allergy 1969;43:33–44. 1996;26:371–8.
98. Walden SM, Proud D, Lichtenstein LM, et al. Anti- 111. Okayama M, Mullol J, Baraniuk JN, et al. Muscarinic
gen-provoked increase in histamine reactivity. receptor subtypes in human nasal mucosa: character-
Observations on mechanisms. Am Rev Respir Dis ization, autoradiographic localization, and function in
1991;144:642–8. vitro. Am J Respir Cell Mol Biol 1993;8:176–87.
99. Andersson M, Andersson P, Pipkorn U. Allergen- 112. Baraniuk JN, Lundgren JD, Okayama M, et al. Sub-
induced specific and non-specific nasal reactions: stance P and neurokinin A in human nasal mucosa.
reciprocal relationship and inhibition by topical Am J Respir Cell Mol Biol 1991;4:228–36.
glucocorticosteroids. Acta Otolaryngol (Stockh) 113. Okamoto Y, Shirotori K, Kudo K, et al. Cytokine
1989;107:270–7. expression after the topical administration of sub-
100. Baroody FM, Cruz AA, Lichtenstein LM, et al. stance P to human nasal mucosa. The role of sub-
Intranasal beclomethasone inhibits antigen- stance P in nasal allergy. J Immunol 1993;151:4391–8.
induced nasal hyperresponsiveness to histamine. J 114. Mosimann BL, White MV, Hohman RJ, et al. Sub-
Allergy Clin Immunol 1992;90:373–6. stance P, calcitonin gene-related peptide, and
101. Majchel AM, Proud D, Freidhoff L, et al. The nasal vasoactive intestinal peptide increase in nasal secre-
response to histamine challenge: effect of the pollen tions after allergen challenge in atopic patients. J
season and immunotherapy. J Allergy Clin Immunol Allergy Clin Immunol 1993;92:95–104.
1992;90:85–91. 115. Philip G, Baroody FM, Proud D, et al. The human
102. Druce HM, Wright RH, Kossoff D, Kaliner MA. nasal response to capsaicin. J Allergy Clin Immunol
Cholinergic nasal hyperreactivity in atopic subjects. 1994;94:1035–45.
J Allergy Clin Immunol 1985;76:445–52. 116. Philip G, Sanico AM, Togias A. Inflammatory cel-
103. Klementsson H, Andersson M, Baumgarten CR, et lular influx follows capsaicin nasal challenge. Am J
al. Changes in nonspecific nasal reactivity and Respir Crit Care Med 1996;153:1222–9.
eosinophil influx and activation after allergen chal- 117. Stjarne P, Rinder J, Heden-Blomquist E, et al. Cap-
lenge. Clin Exp Allergy 1990;20:539–47. saicin desensitization of the nasal mucosa reduces
104. Klementsson H, Andersson M, Pipkorn U. Aller- symptoms upon allergen challenge in patients with
gen-induced increase in nonspecific nasal reactivity allergic rhinitis. Acta Otolaryngol (Stockh) 1998;
is blocked by antihistamines without a clear-cut 118:235–9.
736 Ballenger’s Otorhinolaryngology
118. Benninger M. Rhinitis, sinusitis and their relation- 134. Solomon WR. Aerobiology and inhalant allergens:
ships to allergies. Am J Rhinol 1992;6:37–43. pollens and fungi. In: Middleton EJ, Reed CE, Ellis
119. Grove R, Farrior J. Chronic hyperplastic sinusitis in EF, et al, editors. Allergy: principles and practice.
allergic patients. A bacteriologic study of two hun- 4th ed. St. Louis: Mosby-Year Book; 1993. p. 469–528.
dred operative cases. J Allergy 1990;11:271–6. 135. Arlian LG, Neal JS, Morgan MS, et al. Reducing rel-
120. Friedman W. Surgery for chronic hyperplastic rhi- ative humidity is a practical way to control dust
nosinusitis. Laryngoscope 1975;85:199–201. mites and their allergens in homes in temperate cli-
121. van Dishoeck H, Franssen M. The incidence and mates. J Allergy Clin Immunol 2001;107:99–104.
correlation of allergy and chronic maxillary sinusi- 136. Almqvist C, Larsson PH, Egmar AC, et al. School as
tis. Pract Otolaryngol 1957;19:502–6. a risk environment for children allergic to cats and
122. Rachelefsky G, Goldberg M, Kutz R, et al. Sinus dis- a site for transfer of cat allergen to homes. J Allergy
ease in children with respiratory allergy. J Allergy Clin Immunol 1999;103:1012–7.
Clin Immunol 1978;61:310–4. 137. Skoner DP, Doyle WJ, Boehm S, Fireman P. Prim-
123. Shapiro G. Role of allergy in sinusitis. Pediatr Infect ing of the nose and eustachian tube during natural
Dis 1985;4:555–8. pollen season. Am J Rhinol 1989;3:53.
124. Enberg R. Perennial nonallergic rhinitis: a retro- 138. Reisman RE, Bernstein JM. Allergy and secretory
spective review. Ann Allergy 1989;63:513–6. otitis media: clinical and immunologic studies.
125. Conner BL, Roach ES, Laster WS, Georgitis JW. Pediatr Clin North Am 1975;22:251–7.
Magnetic resonance imaging of the paranasal 139. Van Cauwenberge P. Secretoire otitis media: een
sinuses: frequency and type of abnormalities. Ann epidemiologische, klinische en experimentale stuie.
Allergy 1989;62:457–60. Ghent, Belgium: Facultent Geneeskunde 1988.
126. Naclerio RM, DeTineo ML, Baroody FM. Ragweed 140. Long WF, Taylor RJ, Wagner CJ, et al. Skin test sup-
allergic rhinitis and the paranasal sinuses: a com- pression by antihistamines and the development of
puted tomographic study. Arch Otolaryngol Head subsensitivity. J Allergy Clin Immunol 1985;76: 113–7.
Neck Surg 1997;123:193–6. 141. Bousquet J, Michel FB. In vivo methods for the study
127. Baroody FM, DeTineo M, Haney L, et al. Influx of of allergy: skin tests. In: Middleton EJ, Reed CE, Ellis
eosinophils into the maxillary sinus after nasal EF, et al, editors. Allergy: principles and practice. 4th
challenge with allergen. J Allergy Clin Immunol ed. St. Louis: Mosby-Year Book; 1993. p. 573–94.
2000;105 Suppl:S70. 142. Menardo JL, Bousquet J, Rodiere M, et al. Skin test
128. Vignola AM, Chanez P, Godard P, Bousquet J. Rela- reactivity in infancy. J Allergy Clin Immunol
tionships between rhinitis and asthma. Allergy 1985;75:646–51.
1998;53:833–9. 143. Ownby DR. Allergy testing: in vivo versus in vitro.
129. Corren JAD, Adinoff AD, Buchmeier AD, Irvin CG. Pediatr Clin North Am 1988;35:995–1008.
Nasal beclomethasone prevents the seasonal 144. Norman P. Correlations of RAST with in vivo and
increase in bronchial hyperresponsiveness in in vitro assays. In: Evans R, editor. Advances in
patients with allergic rhinitis and asthma. J Allergy diagnosis of allergy, RAST. Miami (FL): Symposia
Clin Immunol 1992;90:250–6. Specialists; 1975. p. 45–56.
130. Greiff L, Andersson M, Svensson C, et al. Effects of 145. Berg TLO, Johansson SGO. Allergy diagnosis with
orally inhaled budesonide in seasonal allergic radioallergosorbent test: a comparison with the
rhinitis. Eur Respir J 1998;11:1268–73. results of skin and provocation tests in an unse-
131. Braunstahl GJ, Kleinjan A, Overbeek SE, et al. Seg- lected group of children with asthma and hay fever.
mental bronchial provocation induces nasal J Allergy Clin Immunol 1974;54:209.
inflammation in allergic rhinitis patients. Am J 146. Bickmore J. Nasal cytology in allergy and infection.
Respir Crit Care Med 2000;161:2051–7. ORL Allergy 1978;40:39.
132. Assanasen PA, Baroody FM, Naureckas E, et al. The 147. Meltzer E, Orgel H, Bronsky E, et al. A dose rang-
nasal passages of asthmatic subjects have a ing study of fluticasone propionate aqueous nasal
decreased ability to warm and humidify inspired spray for seasonal allergic rhinitis assessed by
air. Am J Respir Crit Care Med 2001;164:1640–46. symptoms, rhinomanometry and nasal cytology. J
133. Fireman P. Otitis media and eustachian tube dys- Allergy Clin Immunol 1990;86:221–30.
function: connection to allergic rhinitis. J Allergy 148. Lans D, Alfano N, Rocklin R. Nasal eosinophilia in
Clin Immunol 1997;99 Suppl:S787–97. allergic and non-allergic rhinitis: usefulness of the
Allergic Rhinitis 737
nasal smear in the diagnosis of allergic rhinitis. H1-blockers in seasonal allergic rhinitis. Allergy
Allergy Proc 1989;10:275–80. 1997;52:1022–5.
149. Miller RE, Paradise JL, Friday GA, et al. The nasal 162. Virant FS. Allergic rhinitis. Immunol Allergy Clin
smear for eosinophils. Its value in children with North Am 2000;20:265–83.
seasonal allergic rhinitis. Am J Dis Child 1982; 163. LaForce C, Dockhorn RJ, Prenner BM, et al. Safety
136:1009–11. and efficacy of azelastine nasal spray (Astelin NS) for
150. Meltzer E, Orgel HA, Jalowayski A. Cytology. In: seasonal allergic rhinitis: a 4-week comparative mul-
Naclerio RM, Mygind NM, editors. Allergic and ticenter trial. Ann Allergy Asthma Immunol 1996;
non-allergic rhinitis: clinical aspects. Copenhagen: 76:181–8.
Munksgaard; 1993. p. 66–81. 164. Bousquet J, Duchateau J, Pignat JC, et al. Improve-
151. Mullarkey MF, Hill JS, Webb DR. Allergic and non- ment of quality of life by treatment with cetirizine
allergic rhinitis: their characterization with atten- in patients with perennial allergic rhinitis as deter-
tion to the meaning of nasal eosinophilia. J Allergy mined by a French version of the SF-36 question-
Clin Immunol 1980;65:122–6. naire. J Allergy Clin Immunol 1996;98:309–16.
152. Kniest FM, Young E, Van Praag MC, et al. Clinical 165. Meltzer EO, Casale TB, Nathan RA, Thompson AK.
evaluation of a double-blind dust-mite avoidance Once-daily fexofenadine HCl improves quality of
trial with mite-allergic rhinitic patients. Clin Exp life and reduces work and activity impairment in
Allergy 1991;21:39–47. patients with seasonal allergic rhinitis. Ann Allergy
153. De Blay F, Chapman MD, Platts-Mills TA. Airborne Asthma Immunol 1999;83:311–7.
cat allergen (Fel d I). Environmental control with 166. Corren J. Allergic rhinitis: treating the adult. J
cat in situ. Am Rev Respir Dis 1991;143:1334–9. Allergy Clin Immunol 2000;105:S610–5.
154. Reisman RE, Mauriello PM, Davis GB, et al. A 167. Fireman P. Therapeutic approaches to treating
double blind study of the effectiveness of a high- allergic rhinitis: treating the child. J Allergy Clin
efficiency particulate air (HEPA) filter in the treat- Immunol 2000;105:S616–21.
ment of patients with perennial allergic rhinitis 168. Simons FE, McMillan JL, Simons KJ. A double-blind,
and asthma. J Allergy Clin Immunol 1990;85: single dose, cross over comparison of cetirizine, terfe-
1050–7. nadine, loratadine, astemizole, and chlorpheniramine
155. Platts-Mills TAE, Chapman MD. Dust mites: versus placebo: suppressive effects on histamine-
immunology, allergic disease, and environmental induced wheal and flares during 24 hours in normal
control. J Allergy Clin Immunol 1987;80:755–75. subjects. J Allergy Clin Immunol 1990;86:540–7.
156. Drovin MA. H1 antihistamines: perspective on the 169. Majchel AM, Proud D, Kagey-Sobotka A, et al.
use of conventional and new agents. Ann Allergy Evaluation of a bedtime dose of a combination
1985;55:797. antihistamine/analgesic/decongestant product on
157. Weiler JM, Bloomfield JR, Woodworth GG, et al. antigen challenge the next morning. Laryngoscope
Effects of fexofenadine, diphenhydramine, and 1992;102:330–4.
alcohol on driving performance. A randomized, 170. Lacroix J. Adrenergic and non-adrenergic mecha-
placebo-controlled trial in the Iowa driving simu- nisms in the sympathetic vascular control of the nasal
lator. Ann Intern Med 2000;132:354–63. mucosa. Acta Physiol Scand 1989; Suppl 581:1–63.
158. Togias AG, Naclerio RM, Warner J, et al. Demon- 171. Compendium of pharmaceuticals and specialties.
stration of inhibition of mediator release from 29th ed. Toronto: CK Productions; 1994.
human mast cells by azatadine base. In vivo and in 172. Schleimer R. Glucocorticosteroids: their mecha-
vitro evaluation. JAMA 1986;255:225–9. nisms of activation and use in allergic diseases. In:
159. Naclerio RM, Kagey-Sobotka A, Lichtenstein LM, Middleton EJ, Reed CE, Ellis EF, et al, editors.
et al. Terfenadine, an H1 antihistamine, inhibits his- Allergy: principles and practice. 4th ed. St. Louis:
tamine release in vivo in the human. Am Rev Respir Mosby-Year Book; 1993. p. 893–925.
Dis 1990;142:167–71. 173. Cox G, Ohtoshi T, Vancheri C, et al. Promotion of
160. Naclerio RM, Proud D, Kagey-Sobotka A, et al. The eosinophil survival by human bronchial epithelial
effect of cetirizine on early allergic response. Laryn- cells and its modulation by steroids. Am J Respir
goscope 1989;99:596–9. Cell Mol Biol 1991;4:525–31.
161. Campbell A, Chanal I, Czarlewski W, et al. Reduc- 174. Pipkorn U, Proud D, Lichtenstein LM, et al. Inhibi-
tion of soluble ICAM-1 levels in nasal secretion by tion of mediator release in allergic rhinitis by pre-
738 Ballenger’s Otorhinolaryngology
treatment with topical glucocorticosteroids. N Engl 187. Orgel HA, Meltzer EO, Bierman CW, et al. Intranasal
J Med 1987;316:1506–10. fluorocortin butyl in patients with perennial rhinitis:
175. Bascom R, Wachs M, Naclerio RM, et al. Basophil a 12-month efficacy and safety study including nasal
influx occurs after nasal antigen challenge: effects biopsy. J Allergy Clin Immunol 1991;88:257–64.
of topical corticosteroid pretreatment. J Allergy 188. Klemi PJ, Virolainen E, Puhakka H. The effect of
Clin Immunol 1988;81:580–9. intranasal beclomethasone dipropionate on the
176. Ratner PH, Paull BR, Findlay SR, et al. Fluticasone nasal mucosa. Rhinology 1980;18:19–24.
propionate given once daily is as effective for sea- 189. Sorensen H, Mygind N, Pedersen C, Prytz S. Long
sonal allergic rhinitis as beclomethasone dipropi- term treatment of nasal polyps with beclometha-
onate given twice daily. J Allergy Clin Immunol sone dipropionate aerosol. III. Morphological stud-
1992;90:285–91. ies and conclusions. Acta Otolaryngol (Stockh)
177. van As A, Bronsky EA, Dockhorn RJ, et al. Once daily 1976;82:260–2.
fluticasone propionate is as effective for perennial 190. Norman PS, Winkerwerder WL, Agbayon BF,
allergic rhinitis as twice daily beclomethasone dipro- Migeon CJ. Adrenal function during the use of dex-
pionate. J Allergy Clin Immunol 1993;91:1146–54. amethasone aerosols in the treatment of ragweed
178. Naclerio RM, Adkinson NF, Creticos PS, et al. hay fever. J Allergy 1967;40:57–61.
Intranasal steroids inhibit seasonal increases in rag- 191. Frauenfelder F, Myer S. Posterior subcapsular
weed-specific immunoglobulin E antibodies. J cataracts associated with nasal or inhalational
Allergy Clin Immunol 1993;92:717–21. steroids. Am J Ophthalmol 1990;109:489.
179. Bende M, Lindqvist N, Pipkorn U. Effect of topical 192. Cumming RG, Mitchell P, Leeder SR. Use of
glucocorticoid, budesonide, on nasal mucosal inhaled corticosteroids and the risk of cataracts. N
blood flow as measured with 133Xe wash-out tech- Engl J Med 1997;337:8–14.
nique. Allergy 1983;38:461–4. 193. Derby L, Maier WC. Risk of cataract among users
180. Juniper EF, Guyatt GH, O’Byrne PM, Viveiros M. of intranasal corticosteroids. J Allergy Clin Immu-
Aqueous beclomethasone dipropionate nasal spray: nol 2000;105:912–6.
regular versus “as required” use in the treatment of 194. Wolthers OD, Pedersen S. Growth of asthmatic
seasonal allergic rhinitis. J Allergy Clin Immunol children during treatment with budesonide: a dou-
1990;86:380–6. ble blind trial. BMJ 1991;303:163–5.
181. Juniper EF, Guyatt GH, Archer B, Ferrie PJ. Aque- 195. Agertoft L, Pedersen S. Effect of long-term treatment
ous beclomethasone diproprionate in the treat- with inhaled budesonide on adult height in children
ment of ragweed pollen-induced rhinitis: further with asthma. N Engl J Med 2000;343:1064–9.
exploration of “as needed” use. J Allergy Clin 196. Skoner DP, Rachelefsky GS, Meltzer EO, et al.
Immunol 1993;92:66–72. Detection of growth suppression in children during
182. Jen A, Baroody F, deTineo M, et al. PRN use of treatment with intranasal beclomethasone dipropi-
Flonase reduces symptoms of ragweed rhinitis. J onate. Pediatrics 2000;105:E23.
Allergy Clin Immunol 2000;105:732–8. 197. Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence
183. Baroody FM, deTineo M, Kaszuba SM, et al. Supe- of growth retardation in children with perennial
riority of an intranasal corticosteroid compared to allergic rhinitis after one year of treatment with
an oral antihistamine in the as needed treatment of mometasone furoate aqueous nasal spray. Pedi-
seasonal allergic rhinitis. J Allergy Clin Immunol atrics 2000;105:E22.
2001;107 Suppl:S312. 198. Wiseman LR, Benfield P. Intranasal fluticasone pro-
184. Naclerio RM, Mygind N. Intranasal steroids. In: prionate: a reappraisal of its pharmacology and
Naclerio RM, Mygind N, editors. Allergic and non- clinical efficacy in the treatment of rhinitis. Drugs
allergic rhinitis: clinical aspects. Copenhagen: 1997;53:885–907.
Munksgaard; 1993. p. 114–22. 199. Onrust SV, Lamb HM. Mometasone furoate: a
185. Soderberg-Warner M. Nasal septal perforation review of its intranasal use in allergic rhinitis.
associated with topical corticosteroid therapy. J Drugs 1998;56:725–45.
Pediatr 1984;105:840–1. 200. Rhuno J, Denburg J, Dolovich J. Intranasal
186. Sahay JN, Ibrahim NB, Chatterjee SS, et al. Long- nedocromil sodium in the treatment of ragweed
term study of flunisolide treatment in perennial allergic rhinitis. J Allergy Clin Immunol 1998;81:570.
rhinitis with special reference to nasal mucosal his- 201. Beswick KB, Kenyon GS, Cherry JR. A comparative
tology and morphology. Clin Allergy 1980;10:451–7. study of beclomethasone dipropionate aqueous
Allergic Rhinitis 739
A wide range of acute and chronic conditions may perspective, the nose is rarely affected in isolation,
affect the nose, either arising locally or occurring as and the majority of conditions impact on the adja-
part of systemic disease. These may be broadly cent paranasal sinuses to a greater or lesser extent.
divided into allergic and nonallergic, with the latter Thus, there has been agreement on the term “rhi-
divided into infectious and noninfectious (Table nosinusitis” in a number of international consensus
33–1). This chapter considers some of the infectious documents1,2 as primarily relating to infection
conditions, the nonallergic, noninfectious diseases, although, in reality, probably applicable to most dis-
and a number of other conditions that enter into the ease processes in this region. Similarly, the upper and
differential diagnosis of patients presenting with lower respiratory tract should be considered as one
nasal symptoms. From an anatomic and physiologic organ, with many conditions manifesting themselves
in both areas, sometimes in subtly different ways (eg,
TABLE 33–1. Classification of Nose and Sinus asthma and nasal polyps).
Disorders
Allergic INVESTIGATION
Nonallergic A considerable number of tests and procedures are
Infectious now available for the investigation of sinonasal dis-
Viral ease (Table 33–2). However, not all are routinely
Bacterial available or indeed applicable to each individual
Fungal patient, and their selection will depend on clinical
Parasitic indicators and local factors.
Protozoal
Noninfectious
Idiopathic HISTORY AND EXAMINATION
Occupational/environmental In practical terms, the nose has a limited repertoire
Hormonal of responses in any given condition, that is, nasal
Drug induced congestion, discharge, sneezing, itching, and epis-
Food taxis with associated symptoms of headache and/or
Emotional facial pain. However, a careful history will usually
Atrophic suggest the diagnosis. A thorough general medical
Nonallergic rhinitis with eosinophilia history should be followed by questions specific to
Gastroesophageal reflux rhinologic symptoms including information on
Differential diagnosis environmental and occupational factors and family
Polyps history. The frequency, duration, and severity of
Mechanical factors symptoms should also be discussed, and a visual
Tumors analog score can be used to semiquantify severity by
Granulomas simply asking the patients to mark on a 10 cm line
Cerebrospinal rhinorrhea where they feel they lie for a particular symptom
during the last week.3 This method can be repeated
Adapted from Lund VJ et al.1 on each subsequent visit, with the patients acting as
741
742 Ballenger’s Otorhinolaryngology
TABLE 33–2. Diagnostic Techniques choanal atresia. Hyposmia and anosmia are most
often associated with nasal polyps or more severe
History disease such as Wegener’s granulomatosis or sar-
General otolaryngologic examination coidosis. Secondary symptoms related to blockage of
the airways include frequent sore throats, dryness of
Allergy tests
the mouth and oropharynx, a nasal quality to the
Skin tests
voice, and snoring. A full drug history may also give
Total serum IgE
a clue to the source of the problem. Symptoms spe-
Serum-specific IgE
cific to particular conditions are discussed in the rel-
Endoscopy evant sections.
Rigid Examination of the nose should be performed
Flexible in all cases of rhinologic complaint and should
Nasal smear include anterior rhinoscopy using a nasal speculum
Cytology and head light and rigid endoscopy combined with
flexible nasoendoscopy in selected cases to ensure a
Nasal swab
full evaluation of the nasal cavity and nasopharynx.
Bacteriology
The quantity and quality of secretion should
Radiology be noted, both the viscosity and color, and speci-
Plain sinus radiography mens may be taken for a nasal smear. Similarly,
Computed tomography under endoscopic control, a swab may be taken from
Magnetic resonance imaging the middle meatus, which provides a reasonable cor-
Chest radiography relation with the bacteriology of the dependent
Mucociliary function sinuses.4
Nasomucociliary clearance The appearance of the mucosa is rarely altered
Ciliary beat frequency in a way that is pathognomonic for a particular dis-
Electron microscopy ease. However, it is usually reddened in acute infec-
Nitric oxide measurement tions and overuse of topical medications, whereas a
typical allergic mucosa appears pale and swollen. In
Nasal airway assessment granulomatous conditions such as Wegener’s and
Nasal inspiratory peak flow sarcoidosis, the mucosa is generally reddened, fri-
Rhinomanometry (anterior and posterior) able, and associated with crusting and evidence of
Acoustic rhinometry previous epistaxis. A careful examination of the
Olfaction nasal cavity should reveal polyps, tumor, foreign
Threshold testing bodies, or septal deflections, although it is impor-
“Scratch and sniff ” tests tant that the unwary examine beyond the deflection
Blood tests wherever possible as secondary pathology may be
Full blood count and white cell differential present and go unnoticed. The presence of a septal
Erythrocyte sedimentation rate perforation should raise the possibility of cocaine
Thyroid function tests abuse, previous surgery, or one of the systemic
Antineutrophil cytoplasmic antibody granulomatous diseases, although most often it is
Immunoglobulins and IgG subclasses “idiopathic,” resulting from minor or repeated
Antibody response to immunization with protein trauma.
and carbohydrate antigens Physical examination should not be confined
to the nose alone and should be accompanied by a
Adapted from Lund VJ et al.1 full otolaryngoloic examination including posterior
rhinoscopy, indirect laryngoscopy, and palpation of
the neck in selected cases. It should also be remem-
their own controls. Consistent obstruction on the bered that many conditions affecting the nose and
same side suggests a polyp, structural problem, or, sinuses also affect the lower respiratory tract, and
more rarely, a tumor or even a congenital unilateral this may be revealed by appropriate examination.
Acute and Chronic Nasal Disorders 743
(For allergy testing, see Chapter 32, and for imaging, The level is commensurately elevated in the presence
see Chapter 31.) of inflammation.
ability of viruses for mutation, has so far confounded makes it unlikely that there is preexisting immunity,
attempts at prophylactic immunization. Most young and, as a consequence, most individuals are suscepti-
adults suffer from two to three colds each year, and it ble most of the time. The virus is normally trans-
is estimated that 0.5 to 2% of these become bacteri- ported into the nose by direct contact with the fingers
ally infected. Predisposing factors such as climatic rather than by airborne contamination, and once the
and environmental changes, fatigue, and stress have virus gains access to the respiratory epithelium, it will
all been implicated, but the huge variety of viruses produce ciliary stasis and damage to the cilia. The
746 Ballenger’s Otorhinolaryngology
BACTERIAL INFECTIONS
Folliculitis and Vestibulitis Specific bacterial
infections can occur in the nasal vestibule when
Staphylococcus aureus invades a pilosebaceous follicle
to produce an extremely painful, indurated area.
This will spontaneously burst and discharge its
purulent contents after 4 to 5 days. The condition is
extemely painful as the vestibular skin is tightly
FIGURE 33–1. Coronal computed tomographic scan bound to the underlying cartilages, providing little
showing massive nasal polyposis with expansion of the room for swelling. Local cleaning and systemic
nasal cavity and ethmoid complexes in a patient with cys- antibiotics, which should include floxacillin, should
tic fibrosis. be given, taking into account problems of local bac-
terial resistance. If the abscess is localized and fluc-
condition is characterized by edema, increased secre- tuant, it may be incised, but the condition should
tion, and desquamation of respiratory epithelium. always be treated seriously as it is associated with the
Clinically, after 1 to 3 days incubation, a prodromal potential complication of cavernous sinus thrombo-
or “dry” phase follows. The subject feels unwell and sis by retrograde spread of infection along the angu-
shivery with a headache, muscle aches, and loss of lar and superior ophthalmic veins.
appetite, while the nose feels irritated and sneezing The cavernous sinus lies on either side of the
occurs. The catarrhal phase follows after a few hours sphenoid bone. It is broken up by trabeculae into
accompanied by profuse watery secretion, nasal many venous cavernous spaces through which the
obstruction, a reduced sense of smell, and an increase third, fourth, and first two divisions of the fifth cranial
in constitutional symptoms. The infection then nerve, sixth cranial nerve, and internal carotid artery
enters a mucous phase in which symptoms improve pass. It is connected by an extensive valveless venous
or may continue after 5 days owing to secondary bac- system to the nose, adjacent face, nasopharynx, phar-
terial infection with a progressively mucopurulent ynx, orbit, and paranasal sinuses, allowing retrograde
discharge. Other areas of the upper respiratory tract spread of infection from any of these areas. The con-
may be affected including the pharynx, middle ear, dition carries a serious morbidity, often with bilateral
and tonsils. blindness and mortality. It is a complication predom-
From a practical point of view, little can be inantly of the young, with two-thirds being under 20
done other than symptomatic relief with deconges- years.16 The patient will complain of headache and
tants and antipyretics, although recent studies have painful paresthesia in the distribution of the trigemi-
suggested that a combination of oral chlorpheni- nal nerve, following which other cranial nerves related
ramine and intranasal ipratropium bromide may be to the cavernous sinus become involved, affecting
effective in reducing symptoms if taken early in the extraocular movement and resulting in ophthalmo-
prodromal phase. Antibiotics should be reserved for plegia. The sudden development of bilateral orbital
secondary bacterial infection. signs should alert the clinician to this complication.
Influenza, in its many forms, constitutes a more Prior to antibiotics, cavernous sinus thrombosis car-
specific and potentially serious viral upper respira- ried a 50% mortality, which nevertheless still stands at
tory tract infection, resulting in pandemics with sig- a significant 10 to 27%.17 Computed tomography and
Acute and Chronic Nasal Disorders 747
magnetic resonance imaging confirm the diagnosis, health and living conditions. The disease classically
and high-dose broad-spectrum systemic antibiotic has three phases: rhinitic, infiltrative, and nodular,
therapy should be given, together with anticoagula- finally resulting in adhesions, stenosis, and atresia.
tion in selected cases. The large red tumor-like masses of the nodular phase
The increase of asymptomatic carriage of are characterized histologically by the presence of
methicillin-resistant S. aureus (MRSA) in the nasal Mikulicz’s cells, large cells with clear cytoplasm con-
vestibule is a source of considerable concern as it is taining the bacilli, and by Russell’s bodies, which are
implicated in nosocomial infection, with serious plasma cells with eosinophilic staining cytoplasm
consequences for debilitated patients. Despite vigor- and prominent nuclei. Large doses of streptomycin
ous eradication programs, the incidence of MRSA and tetracycline over 4 to 6 weeks are needed until
appears to be increasing worldwide. two consecutive biopsies are negative. Topical acri-
A mild form of nonspecific infective vestibuli- flavine solution has also been used.
tis is often encountered, producing mild irritation, In leprosy caused by the acid-fast Mycobac-
small fissures, or pustules. The application of white terium leprae, two forms in the nose are recognized:
petroleum jelly or antibiotic ointments such as tuberculoid and lepromatous. The microorganism
chlortetracycline hydrochloride 3% may be used. may enter via the nose, transferred by a fingernail;
incubation can take up to 10 years. In tuberculoid lep-
Erysipelas and Other Specific Infections rosy, solitary lesions occur as small anesthetic patches,
Erysipelas is an acute beta-hemolytic streptococcus whereas in lepromatous leprosy, a diffuse infiltration
infection of the skin and soft tissue of the head and of the skin, mucous membranes, and nerves is found,
neck following a cut or surgical incision. The onset producing nodular thickening particularly in the
is usually abrupt, with fever, redness, tenderness, and region of the anterior inferior turbinate. The septum
induration of the involved skin. On the face, the is progressively involved, leading to perforation of the
infection frequently displays a butterfly pattern cartilage and a typical nasal deformity of collapse and
across the nose, adjacent cheeks, and upper lip. The stenosis. Dapsone is still the treatment most generally
infection generally responds well to penicillin or used worldwide, although increasing resistance has
erythromycin and should be distinguished from cel- led to newer agents and combinations with rifampin
lulitis, which is a more generalized deep infection of and clofazimine.
the skin and subcutaneous tissues also caused by In tuberculosis, the nose may be involved sec-
Staphylococcus or Streptococcus. ondary to pulmonary involvement, with nodular or
A variety of other specific infections may occur ulcerative lesions usually found on the anterior part
in this region including diphtheria, rhinosceleroma, of the cartilaginous septum, on the inferior tur-
leprosy, tuberculosis, and syphilis. binate, or in the choanae. The lesions show the usual
In diphtheria, caused by Corynebacterium diph- appearances of caseating epithelioid granulomas
theriae, the nose may be affected primarily or sec- together with the presence of acid-alcohol-fast
ondarily to infections of the oropharynx. The false bacilli. The condition responds to standard systemic
membrane associated with the condition is made of antituberculosis therapy together with topical saline
fibrin, neutrophils, necrotic epithelium, and the douching. Lupus vulgaris is a chronic indolent form
bacillae. Removal of the membrane leaves a bleeding of tuberculosis, producing the classic “apple jelly”
surface. Treatment is with parenteral penicillin, with nodules at the mucocutaneous junction of the
the antitoxin reserved for acute cases. A carrier state vestibule.
can occur after contact, and the individual may need In syphilis caused by Treponema pallidum, the
to be isolated until nose swabs are negative. nose may be affected in the primary, secondary, or
In rhinoscleroma, a chronic inflammatory con- tertiary phases as well as in its congenital form. A
dition is characterized by large, deforming masses primary chancre can occur on the external nose or
distending the nasal cavity. The condition, ascribed vestibule around 3 to 4 weeks after contact and then
to Klebsiella rhinoscleromatis, was once found in Cen- disappears spontaneously within 6 to 10 weeks.
tral and Eastern Europe but now occurs in Central Smears taken at this time may reveal the Treponema,
and South America, Africa, the Middle East, and although the serology can be negative in the early
India, where it is associated with a poor standard of stages. Secondary syphilis appears around 6 to 10
748 Ballenger’s Otorhinolaryngology
weeks after infection and may produce no more than anterior rhinorrhea, and postnasal discharge, some-
simple catarrhal rhinitis, although a serologic diag- times with sneezing. There is no characteristic sea-
nosis can be made during this phase. Tertiary sonal variation, and ocular symptoms are almost
syphilis is associated with a gumma that appears as always missing. Skin prick tests are negative or do
a firm, reddened nodule invading the mucous mem- not correlate with the symptoms (ie, may be positive
brane, periosteum, and bone and often producing to grass pollen).
tenderness over the bridge of the nose, posterior sep- Therapy may encompass avoidance of obvi-
tal perforations, and nasal collapse. Serology is pos- ous triggers, but most patients require medication,
itive in 90% of these patients. Congenital syphilis the mainstays of which are topical corticosteroids
may manifest itself with “snuffles” a few weeks after that are safe for long-term use. If watery rhinor-
birth or as a latent form occurring at puberty, with rhea is the most significant or only symptom, a
the characteristic nasal saddling, dental abnormali- topical anticholinergic agent such as ipratropium
ties, and sensorineural hearing loss. The condition bromide may be helpful. Topical decongestants are
must be distinguished from other granulomatous best avoided because of their side effects in the long
diseases and should be treated with standard antibi- term (sic), and although oral decongestants are
otics such as penicillin. For more information on popular, their effect is variable and not without
infections, see Chapter 30. cardiovascular and central nervous system effects.
Topical capsaicin has been investigated for
intractable nonallergic rhinitis22 as it produces a
NONALLERGIC, NONINFECTIOUS short-term neuronal defunctionalization, but the
RHINITIS effects are short-lived and are accompanied by an
unpleasant burning sensation, so its role remains
IDIOPATHIC (VASOMOTOR) RHINITIS undetermined.
The term “idiopathic rhinitis” relates to any inflam- Surgery has a limited role to play. Vidian
mation of the nose the cause of which is unknown. neurectomy has had a vogue but has largely been
It is the diagnosis of exclusion as underlying abandoned as the effects are unpredictable and at
causative or contributory factors can often be found best short-lived. Correction of septal deformity
if carefully sought. Patients are generally manifesting and/or turbinate hypertrophy is occasionally indi-
an upper respiratory hyperresponsiveness or reactiv- cated if medication fails.
ity, which is simply an exaggeration of normal
defense mechanisms to nonspecific environmental
triggers such as changes in temperature and humid-
OCCUPATIONAL/ENVIRONMENTAL RHINITIS
ity or exposure to irritants (eg, cigarette smoke or Airborne agents present in the workplace may affect
strong odors). An extreme example of a normal the upper respiratory tract, producing either an
physiologic response can be seen in “skier’s nose” in allergic reaction or a nonallergic hyperresponsive-
reaction to cold, dry air.18 The commonly used term ness. Chemicals such as acid anhydrides, platinum
“vasomotor rhinitis” is less satisfactory as it suggests salts, glues, and solvents, as well as dusts from grain
a known pathophysiologic mechanism for the con- and wood, may act as irritants.23 Considerable con-
dition that is far from proven.1 troversy now surrounds the adverse effects of envi-
Cigarette smoke is known to affect mucociliary ronmental pollutants such as ozone, sulfur dioxide,
clearance19 and has been shown to cause an nitric dioxide, particulate matter, volatile organic
eosinophilic inflammation in the nasal mucosa of compounds, and formaldehyde. Some contradictory
nonatopic children.20 Challenge of smoke-sensitive evidence needs to be clarified by carefully con-
individuals produces rhinorrhea and obstruction, structed epidemiologic studies that may ultimately
and in smokers, eye irritation and hyposmia are support present concerns.
more common than in nonsmokers. It has also been A careful history will usually indicate the cause,
shown that the more people smoke, the more they confirmed by improvement once the patient is
experience the symptoms of chronic rhinitis.21 removed from the suspected irritant. However, there
In nonallergic, noninfectious rhinitis, symp- may be a reluctance to complain if a worker’s job is
toms vary in intensity but consist of nasal blockage, jeopardized, and chronic exposure may produce
Acute and Chronic Nasal Disorders 749
However, if there are no contraindications, an initial copious crusts often bleed when they detach and
short course of oral prednisolone (30 mg/day for 5 may extend into the nasopharynx, producing an
days) may be necessary.1 unpleasant choking sensation and snorting. The
nose paradoxically feels blocked, owing to the drying
FOOD-INDUCED RHINITIS effect in the abnormally patent airway.
Having eliminated other possible underlying
Food can produce nasal symptoms in a variety of conditions by appropriate hematology and imaging,
ways. Although allergy to food is a rare cause of iso- local treatment with saline or alkaline douching,
lated rhinitis, hypersensitivity may result in reaction emollients and lubricants such as 25% glucose and
to the foods themselves or to colorants and preserv- glycerine drops, and regular decrusting may suffice.
atives.34 Alcoholic beverages can produce physiologic Antibiotics directed at Klebsiella are rarely successful
vasodilatation with associated nasal blockage as well in the long term, although the fluoroquinolones and
as allergic and nonallergic reactions to their many metronidazole have been used. A wide range of sur-
components. gical procedures have been suggested, largely aimed
Gustatory rhinorrhea may result from spicy at reduction of the size of the cavity, all with limited
hot foods, probably owing to the capsaicin content success. Closure of the nostrils with small skin flaps,
of red pepper. This substance is known to stimulate as advocated by Young,36 can be helpful, but relapse
sensory nerves, inducing release of neuropeptides often occurs on reopening. It was suggested that
such as tachykinins.22 reduction of airflow inhibited growth of the
microorganisms, but this is unproven.
EMOTION
Sexual arousal and stress are known to have an effect NONALLERGIC RHINITIS WITH EOSINOPHILIA/
on the nose—hence “honeymoon rhinitis,” probably EOSINOPHILIC RHINITIS SYNDROME
owing to autonomic stimulation, although thera- Nonallergic rhinitis with eosinophilia syndrome
peutic intervention is rarely sought. (NARES) was described 20 years ago, although its
existence as a separate entity is disputed. It should
ATROPHIC RHINITIS probably be regarded as a subgroup of idiopathic
rhinitis characterized by nasal eosinophilia and
Primary atrophic rhinitis has been attributed to infec- perennial symptoms of sneezing, itching, rhinorrhea,
tion, most notably to Klebsiella ozaenae35 (from the blockage, and sometimes hyposmia in the absence of
word “ozaena” meaning “stench”), but may also relate demonstrable allergy. It is possible that it represents
to environmental factors and general health. The con- an early stage of aspirin sensitivity and may be asso-
dition is characterized by progressive atrophy of the ciated with asthma and nasal polyposis. Intranasal
mucosa with loss of the turbinate bone and resulting corticosteroids are the mainstay of medical treatment
in a capacious cavity full of foul-smelling crust. This combined with surgery for the polyps.37
should be distinguished from secondary atrophy fol-
lowing excessive surgery, trauma, radiotherapy, and
chronic granulomatous conditions. GASTROESOPHAGEAL REFLUX
Primary atrophic rhinitis has become less Reflux is increasingly thought to play a role in non-
common in countries where social conditions and allergic rhinitis, particularly in children.38
health have generally improved. It affects both sides
of the nose, occurs after puberty, and is more com-
mon in women. Because of this, an endocrine
MECHANICAL NASAL OBSTRUCTION
imbalance has been postulated as a cause, whereas A common nasal complaint is one of nasal blockage,
others believe it has an autoimmune basis, possibly congestion, or obstruction. This may arise for a vari-
initiated by a virus or owing to vitamin or iron ety of reasons, be it a genuine mechanical obstruc-
deficiencies. tion to airflow, a response to autonomic or sensory
The most unpleasant symptom is the foul changes in the nose, inflammation within the
smell, of which the patient is often unaware. The osteomeatal complex, allergic changes, or even a per-
Acute and Chronic Nasal Disorders 751
ception paradoxically in the presence of a patent or Treatment Septal manipulation is only of value in
overpatent airway. It is important to investigate this neonates when trauma has occurred during delivery.
complaint carefully to elucidate the cause since in Septoplasty or submucous resection have been
the past there has been a tendency to offer surgery described to correct septal deviation. The distinction
for the septum and/or turbinates without consider- between these two techniques relates primarily to
ation or treatment of other contributory factors, the approach, and in practice, most surgeons per-
inevitably compromising a successful symptomatic form a combination of the two. The anterior
outcome. approach used for septoplasty via a transfixion inci-
sion gives excellent access to the whole septum,
whereas the lateral approach used for submucous
SEPTAL DEVIATION resection denies access to the caudal septum. Theo-
Causes Septal deformity can be congenital or retically, there is also a difference in the amount of
acquired, although it should be recognized that a cartilage resected, but in practice, this will vary from
completely straight septum is the exception rather individual to individual.
than the rule. This may be attributable to prenatal or
perinatal factors, in utero or during delivery. A true
COMPLICATIONS
dislocation of the septum is rare; more often, a hor-
izontal fracture above the maxillary crest occurs, Septal Hematoma The septal cartilage relies on
which can be relocated immediately. Small the perichondrium and overlying mucosa for its
microfractures may go unnoticed, presenting in later blood supply. A hematoma may form between the
life, or be exacerbated by falls during the “toddler” cartilage and the perichondrium or between the
stage that may go unnoticed. In adolescents and perichondrium and the septal mucosa (Figure
young adults, sports injuries, assault, and traffic acci- 33–2). In the former case, the blood supply to the
dents may all have their impact. cartilage will be damaged, and unless the hematoma
is drained, cartilage death may ensue. This situation
Effects Any part of the nasal internal and external is further exacerbated by secondary infection leading
structure may be damaged, leading to deflections
and deformities of the cartilages and bones. The
effects may not be immediately obvious to the indi-
vidual until infection or allergy intervenes. With age,
loss of tensile strength in collagen may lead to col-
lapse of the nasal valve region, uncovering preexist-
ing nasal asymmetry. The sensation of nasal
obstruction may alternate with the nasal cycle or be
apparent when lying on that side. Disordered airflow
may result in crusting and epistaxis on the deflected
area. “As goes the septum, so goes the nose” correctly
indicates that septal deviation can be associated with
cosmetic deformity of the bridge and columella.
(For nasal reconstruction, see Chapter 38.)
Assessment of the external and internal nose,
including anterior rhinoscopy and rigid endoscopy,
is important to assess the septal position, spurs, and
turbinates and exclude other pathology, particularly
in the middle meatus and nasopharynx. Instillation
of a topical decongestant may help determine the
degree of mucosal swelling, particularly of the ante- FIGURE 33–2. Coronal computed tomographic scan
rior part of the nasal septum and inferior turbinates. showing expansion of the anterior part of the nasal sep-
Where available, objective measures of airway can be tum in a septal hematoma with opacification of the ante-
helpful. rior ethmoid cells.
752 Ballenger’s Otorhinolaryngology
body temperature. Cases of toxic shock syndrome controlled prospective trial has been performed to
have been described as a result of nasal packing. The determine which of the many techniques is superior
condition is caused by the toxin produced by a in the short or long term, choice devolves to per-
Staphylococcus that, when absorbed, produces sonal preference, and all may be accompanied by
headache, myalgia, nausea, and vomiting secondary hemorrhage and crusting:
to the pyrexia. Tachycardia, hypertension, hypoten-
• Lateral outfracture. Single or multiple fractures of
sion, and erythema of the skin are followed some-
the inferior turbinate bone can be done with or
time later by desquamation of the skin of the hands.
Toxic shock must be dealt with promptly and defin- without a submucous incision. The turbinate is
itively. Cultures for S. aureus must be taken, a β-lac- pushed closer to the medial wall of the maxilla and
tamase-resistant antistaphylococcal antibiotic given may even be pressed into the maxilla (antrocon-
systemically, and all packs and stitches removed. chopexy), but the long-term results are debatable
as the turbinate may resume its original position
and the procedure does not deal with any soft tis-
TURBINATE ENLARGEMENT sue swelling or its cause.
Causes The inferior turbinates and, to a lesser • Submucous diathermy. This has been popular since
extent, the adjacent septum and middle turbinates the early 1900s. A pointed electrode, insulated
have a complex submucosal structure, composed of except for the terminal 3 to 5 mm, is introduced
vascular sinusoids under autonomic control. Under into the anterior end of the inferior turbinate and
normal physiologic conditions, the inferior passed along the whole length. The probe is then
turbinates change in size with the nasal cycle withdrawn slowly, over 20 seconds, and the proce-
throughout the day. This may be overridden by a dure is repeated at two or three points. Hemor-
number of factors, such as exercise, posture, emo- rhage and adhesions can occur, and the patient
tion, environmental temperature, and humidity. should be warned that there will be blockage
Generally, one is unaware of these changes unless owing to reactionary swelling for some weeks after
one side of the nose is narrower. A compensatory the surgery.
hypertrophy of the inferior turbinate is often seen • Linear electrocautery. This is done with a red-hot
on the wider side. A wide range of pathologic wire electrode to produce a thermal burn or a
processes including allergy, inflammation, and infec- high-frequency coagulating current using a ball-
tion can produce symptomatic swelling of the tip electrode. The technique enjoyed some popu-
turbinates. larity in the past but has largely been replaced by
more precise laser therapy.
Effects Resistance to airflow primarily occurs in • Turbinectomy. Partial or subtotal removal of the
the valve region at the anterior end of the inferior turbinate offers a permanent solution to hypertro-
turbinates. To a lesser extent, the middle turbinate phy. The attachment of the inferior turbinate pre-
changes, obstructing the middle meatus and abut- cludes genuine total turbinectomy unless a portion
ting the septum. of the lateral nasal wall is removed. Apart from the
occasional mulberry enlargement of the posterior
Treatment Medical Although topical deconges- end of the inferior turbinate, it should be remem-
tant sprays can significantly shrink the mucosa, bered that the anterior end of the turbinate offers
long-term use will lead to rebound congestion and the greatest resistance to airflow. As with all inferior
rhinitis medicamentosa. Topical nasal corticos- turbinate surgery, patients must be warned about
teroids, by contrast, can be used over long periods of
postoperative hemorrhage, which can be profuse. A
time for most forms of perennial rhin(osinus)itis.
secondary hemorrhage rate of 8% is quoted in the
SURGICAL Surgery should be considered only after literature, which will be severe in 1%.
careful evaluation of the cause of the patient’s symp- • Submucous resection. Dissection of the mucope-
toms and after failure of adequate medication. Most riosteum of the turbinate is described in the orig-
of the techniques can be performed under local or inal literature, although is difficult to perform in
general anesthesia and using head-light, microscope, practice owing to the irregularities of the bone. It
or endoscopic visualization.39 As no randomized is best achieved by taking off an anterior sliver and
754 Ballenger’s Otorhinolaryngology
then nibbling back the exposed bone so that the picion as one may have the first opportunity to
mucosal edges fall together. make the diagnosis.
• Laser turbinectomy. A variety of cutting and coag-
ulating lasers have been used to “cauterize” and
reduce the inferior turbinate, including carbon
SARCOIDOSIS
dioxide, argon, KTP and neodymium:YAG lasers. Cause and Effects Sarcoidosis is a systemic condi-
A cross-hatching of the mucosa is thought to opti- tion of unknown cause characterized by noncaseating
mize shrinkage while preserving mucosa. epithelioid granulomas. It rarely occurs in isolation
• Cryosurgery with liquid nitrogen. This was popular in the upper respiratory tract, usually being found in
in the past but has largely been superseded by association with lower respiratory involvement. The
other techniques. condition has a predilection for certain geographic
• Intraturbinal corticosteroid injection. Enthusiasm areas such as the rural southeast United States and
for intraturbinal corticosteroid injection dimin- Scandinavia and certain ethnic groups such as West
ished after reports of temporary and permanent Indians and is more common in women.
blindness appeared. These may have occurred Nasal symptoms include obstruction, mucop-
owing to retrograde flow of particulate matter into urulent blood-stained discharge, and crusting.40
the ophthalmic circulation, possibly associated There may be associated sinus infection, septal per-
with inadequate vasoconstriction. foration with saddling of the nasal bridge, and vio-
laceous lesions of lupus pernio on the nasal skin.
The mucosa is inflamed with crust and old blood,
FOREIGN BODIES and a “strawberry skin” effect may be seen of the yel-
Types and Effects A wide range of objects includ- lowish granulomas against the reddened lining.
ing metal, plastic, organic materials, and live insects Diagnosis includes erythrocyte sedimentation
find their way into the nose, either accidentally or rate, serum calcium, and angiotensin-converting
deliberately, with size being the only limiting factor. enzyme, although there is no one absolute test for
The result is a unilateral chronic purulent nasal dis- this condition. The Kveim test, which was hitherto
charge, which in a young child should be attributed the most accurate, has been withdrawn in the United
to a foreign body until proved otherwise. If the for- Kingdom owing to concerns over slow viruses. Radi-
eign material has been present for some time, it may ology of the chest is mandatory, and plain radi-
form the nidus for deposition of calcium and mag- ographs may show punched-out erosion of the nasal
nesium salts, producing a rhinolith that is usually bones similar to that seen in dactylitis (Figure 33–4).
radiopaque. Nasal biopsy can be useful when mucosal change is
GRANULOMATOUS CONDITIONS
A range of systemic conditions, including granulo-
mas, vasculitides, connective tissue disorders such
as systemic lupus erythematosus, relapsing poly-
chondritis, eosinophilic angiocentric fibrosis, and
skin conditions such as pemphigus, pemphigoid, FIGURE 33–4. Coronal computed tomographic scan
and scleroderma can all manifest in the nose. Con- showing osteitis of the nasal bones in a patient with sar-
sequently, one should have a low threshold of sus- coidosis.
Acute and Chronic Nasal Disorders 755
present but is positive in only 7% when the nose unknown cause. An autoimmune basis or infection
appears normal.40 The condition must be distin- has been suggested but remains unproven.41 It was
guished from other granulomatous diseases such as originally described affecting the upper and lower res-
tuberculosis, leprosy, berylliosis, Wegener’s granulo- piratory tracts, together with a focal glomeru-
matosis, and acquired immune deficiency syndrome lonephritis, which rapidly led to renal failure and
(AIDS). death. It is now known to affect any part of the body
ab initio and to have a variable natural history, pro-
Treatment Local treatment with saline douche gressing inexorably in some individuals over a few
and topical corticosteroids is helpful, and the nose weeks or months or to a more insidious limited form
may improve with systemic treatment that usually in others that may continue for some years before
includes oral corticosteroids and a variety of cyto- affecting other organs. Whether all of the latter ulti-
toxic agents. Surgery, except for sinus infection, mately progress to the full-blown disease is unknown.
should be avoided as this can exacerbate collapse of Patients often present with a short history of
the nose. progressive malaise, pyrexia, weight loss, and a dis-
proportionate feeling of “unwellnesss” in compari-
WEGENER’S GRANULOMATOSIS son with what are often fairly nonspecific findings.
In the nose, the swollen, inflamed mucosa produces
Cause and Effects This systemic condition charac- blockage and blood-stained crusting. There may be
terized by granulomas and vasculitis is also of destruction of the septum with a characteristic
implosion of the nasal bridge (Figure 33–5). The
nasopharynx, ears, mouth, larynx, trachea, cranial
nerves, and orbit may all be involved.
Diagnosis of the condition relied in the past on
clinical acumen supported by a high erythrocyte
sedimentation rate, C-reactive protein, and evidence
of pulmonary and renal damage. The advent of the
C-ANCA (antineutrophil cytoplasmic antigen)
greatly assisted diagnosis, being highly specific and
sensitive for the condition. However, a negative C-
ANCA does not absolutely exclude the condition,
particularly in the limited form and/or when oral
corticosteroids have been given. Computed tomog-
raphy of the nose and paranasal sinuses may show
some midline destruction and often shows opacifi-
cation of the sinuses (Figure 33–6). This may be
attributable to active granulomatous infiltration,
burnt-out disease with fibrotic change, or secondary
infection. Unfortunately, biopsy is not diagnostic, at
best being described as “consistent with” Wegener’s
granulomatosis, but is helpful to exclude other
pathology such as T-cell lymphoma.
RHINOPHYMA
In rhinophyma, a disfiguring enlargement of the
nose develops owing to an overgrowth of sebaceous
tissue. Tissue overgrowth begins at the tip of the
nose and progresses to involve the ala nasi and the
columella and is associated with a florid discol-
oration. The affected tissue may be pared down
FIGURE 33–7. An endoscopic view of nasal lesions in using a knife, electrodissection, or laser therapy, pro-
hereditary hemorrhagic telangiectasia. ducing good cosmetic results.
758 Ballenger’s Otorhinolaryngology
12. Doty RL, Shaman P, Dann M. Development of the 27. Girgis IH, Yassin A, Hamdy H, Moris M. Estimation
University of Pennsylvania Smell Identification Test: of effect of drugs on the nasal circulation. J Laryngol
a standardized microencapsulated test of olfactory Otol 1974;88:1163–8.
function. Physiol Behav 1984;32:489–502. 28. Bauer GE, Hull RD, Stokes GS, Raftos J. The
13. Simmen D, Briner HR, Hess K. Screeningtest des reversibility of side effects of guanethidine therapy.
Geruchssinnes mit Riechdisketten. Laryngorhin- Med J Aust 1973;1:930–3.
ootologie 1998;77:1–6. 29. Proud D, Naclerio RM, Meyers DA, et al. Effects of a
14. Kobal G, Hummel T, Sekinger B, et al. “Sniffin’ single-dose pretreatment with captopril on the
sticks”: screening of olfactory performance. Rhinol- immediate response to nasal challenge with allergen.
ogy 1996;344:222–6 Int Arch Allergy Appl Immunol 1990;93:165–70.
15. Gwaltney JM, Phillips CD, Miller RD, et al. Com- 30. Schwartz RH, Estroff T, Fairbanks DN, Hoffmann
puter tomographic study of the common cold. N NG. Nasal symptoms associated with cocaine abuse
Engl J Med 1994;330:25–30. during adolescence. Arch Otolaryngol Head Neck
16. Shahin J, Gullane PJ, Dayal VS. Orbital complica- Surg 1989;115:63–4.
tions of acute sinusitis. J Otolaryngol 1987;16:23–7. 31. Dax EM. Drug dependence in the differential diag-
17. Lund VJ. Complications of sinusitis. In: Scott- nosis of allergic respiratory disease. Ann Allergy
Brown’s otolaryngology. Vol 4. Rhinology. London: 1990;64:261–3.
Butterworth Heineman; 1997. p. 1–11. 32. Graf P. Rhinitis medicamentosa: aspects of patho-
18. Silvers WS. The skier’s nose: a model of cold- physiology and treatment. Allergy 1997;52(40
induced rhinorrhea. Ann Allergy 1991;67:32–6. Suppl):28–34.
19. Bascom R, Kesavanatha J, Fitzgerald TK, et al. Side- 33. Scadding GK. Rhinitis medicamentosa [editorial].
stream tobacco smoke exposure acutely alters Clin Exp Allergy 1995;25:391–4.
human nasal mucociliary clearance. Environ Health 34. Bousquet J, Metcalfe D, Warner J. Food allergy. Report
Perspect 1995;103:1026–30. of the Codex alimentarius. ACI Int 1997;9:10–21.
20. Vinke JG, KleinJan A, Severijnen LW, Fokkens WJ. 35. Henriksen S, Gundersen W. The aetiology of ozaena.
Passive smoking causes an “allergic” cell infiltrate in Acta Pathol Microbiol Scand 1959;47:380–6.
the nasal mucosa of non-atopic children. Int J Pedi- 36. Young A. Closure of the nostrils in atrophic rhinitis.
atr Otorhinolaryngol 1999;51:73–81. J Laryngol Otol 1967;81:515–24.
21. Annesi-Maesano I, Oryszczyn MP, Neukirch F, 37. Blom HM, Godthelp T, Fokkens WJ, et al. The effect
Kauffmann F. Relationship of upper airway disease of nasal steroid aqueous spray on nasal complaint
to tobacco smoking and allergic markers: a cohort scores and cellular infiltrates in the nasal mucosa of
study of men followed up for 5 years. Int Arch patients with nonallergic, noninfectious perennial
Allergy Immunol 1997;114:193–201. rhinitis. J Allergy Clin Immunol 1997;100(6
22. Lacroix JS, Buvelot JM, Polla BS, Lundberg JM. Pt 1):739–47.
Improvement of symptoms of nonallergic chronic 38. Euler AR. Upper respiratory tract complications of
rhinitis by local treatment with capsaicin. Clin Exp gastroesophageal reflux in adult and pediatric-age
Allergy 1991;21:595–600. patients. Dig Dis 1998;16:111–7.
23. Schiffman SS, Nagle HT. Effect of environmental 39. Lund VJ. Surgery of the inferior turbinate. Fac Plast
pollutants on taste and smell. Otolaryngol Head Surg 1986;3:227–80.
Neck Surg 1992;106:693–700. 40. Wilson R, Lund VJ, Sweatman M, et al. Upper respi-
24. Ellegard E, Karlsson G. Nasal congestion during ratory tract involvement in sarcoidosis and its man-
pregnancy. Clin Otolaryngol 1999;24:307–11. agement. Eur J Respir Med 1988;1:269–72.
25. Schatz M. Special considerations for the pregnant 41. Lund VJ, Cambridge G. Immunological aspects of
woman and senior citizen with airway disease. J Wegener’s granulomatosis. In: Veldman JE, Passali D,
Allergy Clin Immunol 1998;101(Suppl 2 Pt 2): Lim DJ, editors. New frontiers in immunology. Ams-
S373–8. terdam: Kugler Publications; 2000. p. 195–207.
26. Mazzotta P, Loebstein R, Koren G. Treating allergic 42. Lund VJ, Howard J. A treatment algorithm for the
rhinitis in pregnancy. Safety considerations. Drug management of epistaxis in hereditary haemor-
Saf 1999;20:361–75. rhagic telangiectasia. Am J Rhinol 1999;13:319–22.
CHAPTER 34
760
Sinusitis and Polyposis 761
cases, it is edema secondary to inflammation that patient to acute sinusitis. Chronic illness, such as
constricts the small sinus openings in a reversible diabetes, or malnutrition, metabolic derangement,
fashion. This may result from a viral upper respira- chemotherapy, or long-term corticosteroid therapy
tory infection, allergy, environmental irritants, or will similarly increase the tendency to develop acute
barotrauma. Irreversible blockage caused by fixed sinusitis. The intensive care unit setting is particu-
anatomy may contribute to the problem or be the larly conducive to the development of a nosocomial
sole etiologic agent. Examples of anatomic obstruc- sinusitis owing to the presence of critical illness in
tion would include septal deviations, polyps, nasal conjunction with nasotracheal and/or nasogastric
tumors, foreign bodies, or postsurgical synechiae. tubes, which cause mechanical obstruction of sinus
Additionally, sinus disease is often related to a host drainage. Although fluid and mucosal thickening in
of anatomic variants such as Haller’s cells, agger nasi the sinuses is common, acute sinusitis is rarely the
cells, concha bullosa, and paradoxical middle sole or main cause of fever or sepsis in this patient
turbinate, although this relation has not been defin- population.8 Antral puncture is only indicated in the
itively supported by randomized, controlled studies. presence of an endoscopic examination that reveals
Whatever the cause, once the ostium becomes purulence.9 Immunocompromised patients with
occluded, a local hypoxia develops in the sinus cav- HIV infection or other severe immune deficiencies
ity, and sinus secretions accumulate. This combina- are prone to sinus infection with unusual pathogens
tion of low-oxygen tension and a rich culture such as fungi and atypical mycobacteria. Bone mar-
medium of secretions allows exponential bacterial row transplant patients are another group with a
growth to occur within the sinus. high incidence of acute sinusitis and a propensity
A normal sinus is generally considered to be a toward developing life-threatening invasive fungal
sterile environment. Bacteria that find their way into sinusitis.
the sinus are rapidly eliminated by the action of cil-
iated columnar epithelial cells moving a layer of vis- Classification Sinusitis is a clinical diagnosis,
cous secretions created by epithelial goblet cells and based largely on history and physical examination
submucosal glands. Abnormalities of the cilia them- findings. In 1997, the Rhinosinusitis Task Force of
selves, or of the double-layered mucus blanket the American Academy of Otolaryngology-Head
within which the cilia beat, may hinder bacterial and Neck Surgery (AAO-HNS) attempted to create
removal. Ciliary function may be defective second- a uniform diagnostic paradigm for sinusitis by
ary to underlying disease states such as primary cil- organizing common sinonasal symptoms and signs
iary dyskinesia or Kartagener’s syndrome or to into major and minor factors.10 The presence of two
injury by environmental irritants or surgical trauma. or more major factors, or one major and two minor
In animal models of sinusitis, bacterial products and factors, is considered suggestive of sinusitis. These
endogenous mediators of inflammation disrupt signs and symptoms of sinusitis are discussed in the
epithelial cilary activity.7 The quality of the mucus in diagnosis section of this chapter. The Task Force
the sinuses is of critical importance in the effective- defined five categories of adult rhinosinusitis in their
ness of ciliary clearance. In cystic fibrosis and severe report. These categories are based on duration, his-
dehydration, for example, the viscosity and elasticity tory, and physical examination. They do not take
of the mucus are increased by alterations in water into account radiologic findings. Table 34–2 shows a
and electrolyte transport. Additionally, increased list of major and minor factors associated with the
production of mucus, which can occur in response diagnosis of rhinosinusitis that are used in this clas-
to airborne irritants, allergens, cold air exposure, or sification scheme. The first category is “acute,” which
viral upper respiratory infections, also may exceed is defined, in part, as having a duration of less than
the rate of mucociliary clearance. Any of these situ- or equal to 4 weeks. The patient’s history must
ations will lead to the accumulation of mucus in the include either two or more major factors or one
sinuses, with poor removal of bacteria and the cre- major and one minor factor. If the patient has nasal
ation of a favorable environment for bacterial purulence on endoscopy, the presence of a strong
growth. history is not necessary. Acute rhinosinusitis should
Any systemic disease leading to an immuno- be considered if patient symptoms worsen after 5
compromised state will potentially predispose a days or if symptoms persist for more than 10 days.
762 Ballenger’s Otorhinolaryngology
TABLE 34–2. Major and Minor Factors Associated to diagnose. Another important distinction is that the
with the Diagnosis of Rhinosinusitis underlying process in chronic sinusitis is not neces-
sarily infectious and is often a self-perpetuating
Major factors inflammatory process. The exact nature of the
Facial pain/pressure* mucosal dysregulation is unknown but in some cases
Facial congestion/fullness can be recalcitrant to all medical and surgical thera-
Nasal obstruction/blockage pies currently available. Many times, the only effective
Nasal discharge/purulence/discolored postnasal treatment is systemic corticosteroids, which provide
discharge short-term control of symptoms at the risk of serious
Hyposmia/anosmia complications related to their use.
Purulence in nasal cavity on examination Whereas acute sinusitis is histologically an
Fever (acute rhinosinusitis only)† exudative process characterized by neutrophilic infil-
Minor factors tration and necrosis, chronic sinusitis is a prolifera-
Headache tive process remarkable for thickening of the mucosa
Fever (in nonacute cases) and lamina propria. The predominant infiltrative cell
Halitosis in chronic sinusitis is the eosinophil, both in the
Fatigue allergic and the nonallergic patient. There is evidence
Dental pain that potent eosinophil-attracting chemokines are
Cough produced in the sinus mucosa, elaborated by a vari-
Ear pain/pressure/fullness ety of cell types under the stimulation of cytokines
produced largely by T cells.11 An increase in the lev-
*Facial pain/pressure alone does not constitute a suggestive els of interleukin-4 and -5 in the sinonasal tract pro-
history for rhinosinusitis in the absence of another major motes the continued proliferation and prolonged life
symptom or sign. span of eosinophils.12 A number of other proinflam-
†Fever in acute sinusitis alone does not constitute a strongly matory cytokines are up-regulated and participate in
suggestive history for acute sinusitis in the absence of the process of directing lymphocyte and granulocyte
another major symptom or sign.
traffic, while causing further production of cytokines
in an autocrine fashion. Degranulation of eosino-
The next category is “subacute,” which is defined by phils releases a number of destructive enzymes that
a duration of 4 to 12 weeks. “Recurrent acute” is damage the epithelium. This disrupts the normal
defined as four or more episodes of rhinosinusitis barrier function and the mucociliary activity of the
per year with complete resolution between episodes. mucosa, allowing bacteria and fungi to colonize the
sinus cavities. The damage to the epithelium irritates
sensory nerve endings, causing pain and stimulating
CHRONIC RHINOSINUSITIS changes in mucus secretion and endothelial perme-
Rhinosinusitis lasting longer than 12 weeks is classi- ability via reflex pathways. Corticosteroids disrupt
fied as chronic. If the symptoms worsen periodically this vicious cycle by interfering with the transcrip-
and then return to baseline with treatment, the AAO- tion of many cytokines at the nuclear level. Without
HNS Task Force separately categorizes this as acute these mediators in the sinus mucosa, the inflamma-
exacerbations of chronic rhinosinusitis. The patho- tory process is halted, and there is a return to more
physiology of chronic sinusitis shares many similar normal function. However, for reasons that remain
features with acute sinusitis, but with some important poorly understood, the reversal of inflammation is
differences. The predisposing conditions for chronic often temporary and recurs once the corticosteroids
disease parallel those for acute infections in terms of are withdrawn.
environmental, systemic, and local host factors. How-
ever, in addition, multiple episodes of acute sinusitis
themselves may cause scarring and mucosal dysfunc-
FUNGAL RHINOSINUSITIS
tion that lead to chronic sinus infections. Symptoms Some forms of sinusitis are caused by fungal
in chronic sinusitis are usually more insidious than in microorganisms within the sinonasal tract. The fun-
an acute situation and therefore may be more difficult gal infection can be either invasive or noninvasive.
Sinusitis and Polyposis 763
One noninvasive form is a fungal ball growing sistence, recurrence, and a poor prognosis. However,
within a sinus cavity. The invasive forms can present the presence or absence of a granulomatous histol-
in either an indolent, chronic form or a fulminant, ogy is not apparent in the clinical presentation and
acute form. The latter frequently occurs in immuno- does not currently alter treatment.
suppressed patients, such as diabetics in ketoacido- In addition to fungal balls, the other noninva-
sis, transplant recipients, HIV-infected individuals, sive form of fungal sinusitis is an entity known as
and patients undergoing chemotherapy. Without allergic fungal rhinosinusitis (AFRS). It is the most
control of the underlying immunosuppression, the common form of fungal sinus disease, although the
process is rapidly progressive and may extend into pathogenesis remains poorly understood. The diag-
the orbits and intracranial space despite aggressive nosis of AFRS depends on five criteria: (1) type I
surgical and medical management. The disease is hypersensivity, (2) nasal polyposis, (3) characteristic
uniformly fatal if the immune failure cannot be cor- computed tomographic (CT) scan appearance
rected. Even if the underlying condition is con- (hyperdense material in the sinus cavity), (4) posi-
trolled, significant morbidity and mortality may tive fungal stain or culture, and (5) no evidence of
result based on the ultimate extent of the disease. In tissue invasion.15 The disease is also characterized by
contrast, chronic invasive sinusitis tends to occur in increased total IgE, antigen-specific IgE, and periph-
immunocompetent hosts and generally advances eral eosinophil count. Allergic fungal rhinosinusitis
very slowly. Vascular invasion in the chronic form is is often unilateral and can cause bony erosion with
minimal or nonexistent. The microorganisms orbital or intracranial extension (Figure 34–2). At
involved in fulminant fungal sinusitis are varied, but surgery, there is typically thick, brown-green mucus
the Mucoraceae family (most often Rhizopus oryzae) that has been called “peanut butter”-like. Histologi-
and Aspergillus species are most frequent (Figure cally, this mucus contains eosinophils in sheets,
34–1, A and B). A number of fungal microorganisms Charcot-Leyden crystals, and fungal hyphae. The
have been reported as pathogens in chronic invasive critical element that separates AFRS from chronic
disease, with Aspergillus being the most typical. eosinophilic rhinosinusitis is the presence of allergy
Mucor, Alternaria, Curvularia, Bipolaris, Candida, to fungus.16 Allergic fungal rhinosinusitis is not
Drechslera, Sporothrix schenckii, and Pseudallescheria caused by the abnormal presence of fungus in the
boydii (which is unresponsive to amphotericin B) nose but rather an abnormal response to nonpatho-
have specifically been cultured.13 A further classifica- genic fungi that exist in the environment. It has been
tion of chronic invasive fungal sinusitis was pro- shown by Ponikau et al that fungi are ubiquitous and
posed by deShazo et al based on histopathology.14 can be isolated out of every nose, given sufficiently
The form of the disease that lacks a granulomatous sensitive culture techniques.17 A wide range of fun-
response has been associated with a high rate of per- gal species have been implicated in allergic fungal
A B
FIGURE 34–1. A, Hematoxylin and eosin stain of Aspergillus. B, Hematoxylin and eosin stain of Mucor.
764 Ballenger’s Otorhinolaryngology
POLYPOSIS
DIAGNOSIS
ETIOLOGY The typical complaints associated with polyposis are
Nasal polyposis is a prevalent condition that is said nasal congestion, rhinorrhea, and olfactory dysfunc-
to affect between 1 and 4% of the general US popu- tion. A thorough nasal endoscopic examination is
lation.18 Based on autopsy studies, the true incidence
of polyps may be much greater, although most
polyps are small and presumably asymptomatic. The
etiology of nasal polyps is largely unknown and has
long been a topic of debate. Although historically
many have believed polyps to be a manifestation of
allergy, in part because of the histologic prominence
of eosinophils, epidemiologic evidence for this is
lacking. The incidence of allergy is not higher in
patients with nasal polyps than in the population as
a whole, nor do polyp patients have elevated rates of
positive allergy skin tests.19 Nasal polyps are associ-
ated with a number of systemic diseases including
aspirin intolerance, intrinsic asthma, primary ciliary
dyskinesia, and cystic fibrosis. They are frequently
observed in chronic rhinosinusitis, including allergic
rhinosinusitis, and other chronic sinonasal inflam-
matory states. Overall, the mechanisms behind
polyp formation are believed to be multifactorial. FIGURE 34–3. Polyp in the left middle meatus.
Sinusitis and Polyposis 765
necessary for all patients with polyp disease to assess of nasal tumors and differentiating tumor from sec-
the gross appearance and sites of origin. When eval- ondary mucosal disease and retained secretions.
uating a patient with nasal polyps, the differential These radiologic studies should be obtained prior to
diagnosis of nasal masses should be entertained, performing a biopsy of any unusual nasal mass.
including the possibility of systemic disease. For
example, the finding of nasal polyps in children
should elicit consideration of cystic fibrosis or ciliary
MANAGEMENT
dyskinesia. Unilateral polyps should raise concern for The most important element in the treatment of
allergic fungal sinusitis or inverted papilloma. nasal polyposis is medical therapy with cortico-
Sinonasal neoplasms may display a similar endo- steroids. Both oral corticosteroids and topical nasal
scopic appearance to polyps; thus, consideration corticosteroids are effective in shrinking polyps and
should be given to the possibility of carcinoma, sar- controlling their recurrence. Topical corticosteroids
coma, angiofibroma, meningioma, or esthesioneu- are first-line therapy that should be employed prior
roblastoma in certain patients. A single, unilateral to considering surgical intervention. Unless there is a
polyp originating high in the nasal cavity or with a contraindication, a trial of a tapering course of oral
stalk that is not clearly visible may represent an corticosteroids is also frequently used prior to surgi-
encephalocele or meningocele. Visible pulsations on cal resection. Should surgery eventually become nec-
endoscopy and enlargement of the mass with ipsilat- essary, topical corticosteroids and occasionally oral
eral internal jugular vein compression (Furstenberg’s corticosteroids may be needed for long-term mainte-
sign) help to confirm the diagnosis. As a rule, if the nance. A variety of topical nasal corticosteroid prepa-
intranasal mass does not have the characteristic rations are available today with similar efficacy in
appearance of a polyp, is unilateral, bleeds easily, or reducing polyps. They differ primarily in the propel-
has a stalk that is not clearly identified, imaging stud- lant and additives rather than in the active ingredi-
ies are indicated before proceeding with management ents. However, these factors may make one brand
(Figure 34–4). High-resolution CT may reveal bony more acceptable than another to a given patient.
dehiscences or erosion. Magnetic resonance imaging Head positioning is important during intranasal cor-
(MRI) is confirmatory of meningoencephalocele and ticosteroid use to direct the medication in contact
is advisable when evaluating an area of skull base ero- with the polypoid mucosa. Since most recurrent
sion adjacent to an opacified sinus. Magnetic reso- polyps after surgery occur in the frontal recess, the
nance imaging is also useful for identifying the extent head-inverted position is necessary to obtain the
maximal benefit in the localized area of disease.
The use of oral corticosteroids in polyposis and
sinusitis is somewhat controversial because of the
myriad side effects and complications associated with
them. However, the effectiveness of oral corticos-
teroids is remarkable, sometimes with even a short
taper. In some patients, recurrence of nasal polyps
can be prevented with very low doses given for pro-
longed periods of time. The dose of corticosteroids
prescribed is dependent on the extent of disease. Typ-
ically, for moderate to severe polyposis, the upper end
of the taper is 30 to 40 mg of prednisone per day for
3 to 4 days. A similar dose is used preoperatively to
maximize shrinkage of the polyps and to reduce the
mucosal reactivity and vascularity. Also, since asthma
is a comorbid condition in many patients with
FIGURE 34–4. Coronal computed tomographic scan polyps, the corticosteroids help to stabilize bronchial
showing a meningocele in the right ethmoid. The hyperreactivity preoperatively. Antibiotics are often
appearance of encephaloceles and meningoceles may used along with corticosteroids in treatment for
mimic that of nasal polyps in some patients. polyps occurring secondary to an infectious chronic
766 Ballenger’s Otorhinolaryngology
sinusitis. Most patients with nasal polyps have some leads to early extension of infections that are not
concurrent sinusitis at the time of presentation, and treated adequately or in the setting of impaired host
this is likely to be an exacerbating factor. Aggressive immunity. Most orbital complications occur in
treatment of the underlying sinusitis will lead to young children, but those in older children and
more rapid resolution of inflammatory polyps. adults are typically more severe and necessitate sur-
Surgery for polyps is indicated when medical gery. Ethmoiditis most commonly leads to orbital
management fails to give symptomatic improvement involvement, followed by infections of the maxillary,
or if complications develop. Also, in those polyp frontal, and sphenoid sinuses. Infections of the eth-
patients with asthma, surgical intervention may be moid can directly erode the thin lamina papyracea or
considered when repeated sinus infections are caus- extend through suture lines or foramina into the
ing a worsening of the lower airway disease. The orbit. The other mechanism of spread is hematoge-
operative technique of polyp removal is the same as nously via retrograde thrombophlebitis of valveless
other endoscopic sinus surgery and is described in veins. Chandler et al described a classification scheme
detail later in this chapter. Powered instrumentation for orbital complications of sinusitis in 1970.21 The
using a microdébrider is particularly useful in polyp first stage, preseptal periorbital cellulitis, consists of
surgery because it is rapid and spares the mucosa, eyelid swelling anterior to the orbital septum without
while the continuous suction allows excellent visual- involvement of the orbital contents (Figure 34–5, A
ization to be maintained in the face of bleeding. The and B). When the orbital soft tissue becomes
postoperative monitoring of the sinus cavities is involved, the result is orbital cellulitis, a diffuse
absolutely critical for the success of sinus surgery. process of inflammation without abscess formation.
Recurring disease should be addressed early in an Patients with this complication are generally prop-
office setting by débriding small polyps under topi- totic, with some degree of ophthalmoplegia and
cal anesthesia. Although complete resolution of chemosis. When pus accumulates between the bone
mucosal abnormalities is rare, continued medical and the orbital periosteum, the result is a subpe-
management and vigilance in follow-up make revi- riosteal abscess (Figure 34–5, C and D). This will dis-
sion surgery unnecessary in the vast majority of place the orbit inferolaterally and may cause some
patients. Successful treatment ultimately depends on proptosis. Unrecognized or untreated, the process
a commitment by both the patient and the physician can expand to cause extraocular muscle impairment,
to an intensive postoperative course, which may be chemosis, and loss of visual acuity. Pus within the
quite prolonged and involve multiple débridements. orbital tissue is an orbital abscess and can be intra-
conal or extraconal. In either case, marked proptosis,
limitation of extraocular movement, and visual loss
COMPLICATIONS OF are commonly observed when an orbital abscess is
present. Finally, the most serious complication is cav-
RHINOSINUSITIS ernous sinus thrombosis. This may result from exten-
The complications of sinusitis can be divided sion of ethmoid or sphenoid sinusitis directly or via
broadly into those involving the orbits and those thrombophlebitis of the ophthalmic vein. Here,
that involve the intracranial space. In the antibiotic proptosis, chemosis, ophthalmoplegia, and decreas-
era, such complications have become less common- ing visual acuity are the rule. In the early stages, fever,
place, but they still have the potential for serious headache, periorbital edema, or photophobia may
morbidity or even mortality. Awareness and early herald the onset of cavernous sinus thrombosis. Once
recognition of complications are necessary to mini- it occurs, the process can extend to the opposite side,
mize adverse sequelae. Fortunately, improved diag- and bilateral findings are considered a diagnostic
nostic modalities and advances in medical and hallmark. Cranial neuropathies of nerves II to VI are
surgical techniques have significantly reduced the seen, and pituitary insufficiency may occur. From the
risk of blindness or life-threatening intracranial cavernous sinuses, the infection can spread rapidly
infections. through the dural sinuses, causing a range of
Orbital complications of sinusitis occur intracranial complications.
because the orbit is bounded by the sinuses inferi- Intravenous antibiotics are the mainstay of
orly, superiorly, and medially. This close proximity medical therapy and may be combined with topical
Sinusitis and Polyposis 767
C
A
FIGURE 34–5. A, Preseptal cellulitis secondary to ethmoid sinusitis. B, A computed tomographic (CT) scan of child
with a preseptal cellulitis. Large arrow points to swelling in the preseptal compartment; small arrows point to con-
comitant ethmoid and maxillary sinusitis. C, Right subperiosteal abscess causing ophthalmoplegia, proptosis, and
chemosis. D, A CT scan of a right subperiosteal abscess. Arrow points to the abscess adjacent to the medial rectus mus-
cle. Note swelling of the medial rectus muscle.
resonance imaging is an excellent complementary lumbar puncture results other than a high opening
study when intracranial extension needs to be eval- pressure. Headache and low-grade fever are com-
uated. Serial CT scans may be used to monitor the mon findings, and only when the abscess becomes
progress of medical management and to help deter- enlarged do effects of increased intracranial pres-
mine if surgery is needed. sure become evident. Epidural abscesses can extend
The decision to proceed to surgery is made by rupturing into the subdural space to create an
based on a number of factors and is individualized empyema. Because of the barrier function of the
to the particular patient. Certainly, progressive arachnoid, subdural infections do not necessarily
visual loss demands aggressive management and progress to meningitis. However, as the empyema
drainage of the source of infection. Medical ther- spreads from anterior to posterior, inflammation of
apy is typically not effective once an abscess devel- the leptomeninges will occur, resulting in signifi-
ops, and so surgical incision and drainage are cant edema. This edema can lead to increased
required at that point. Often the extent of the infec- intracranial pressure and eventually cortical
tion is unclear, even with radiologic imaging, and ischemia. Early signs include headache, fever, and
the decision should be based on the clinical picture. leukocytosis, whereas later findings may be much
Surgical intervention should be considered when more severe such as hemiparesis, hemiplegia, or
there is disease progression after 24 hours of antibi- seizures. When the intracranial pressure becomes
otics or no improvement after 2 to 3 days of ther- high enough, bradycardia, hypotension, and
apy. Ideally, surgery involves approaching both the decreased mental status will ensue. Unless treated,
orbital complication and underlying sinusitis transtentorial herniation can follow, causing death.
simultaneously. Endoscopic approaches will gener- Brain abscesses in the frontal lobe can also begin
ally be used to approach the sinuses and can even insidiously and then progress rapidly to fatal her-
be employed in experienced hands to drain eth- niation. Abscesses in this location are frequently
moid subperiosteal abscesses. The classic technique neurologically silent except for subtle mood or per-
for managing orbital complications is the external sonality changes. If the abscess becomes large
ethmoidectomy approach. Frontal sinus trephina- enough, or if the surrounding edema is extensive,
tion may also be employed for acute frontal sinusi- symptoms of increased intracranial pressure may
tis. These techniques are described in detail later in become evident. Rupture of the abscess into the
this chapter. ventricles will quickly lead to death.
Intracranial complications of sinusitis occur When intracranial complications are suspected,
less frequently than orbital complications but are the study of choice is a CT scan of the brain and
potentially life threatening if not recognized and sinuses with and without contrast. Magnetic reso-
treated. Most intracranial infections arise from the nance imaging is a more sensitive tool in the early
frontal sinus, although extension from the other stages of intracranial infection and can demonstrate
sinuses is possible. The most frequent route of enhancement of the dura in meningitis. Magnetic
spread is retrograde thrombophlebitis via the resonance imaging is also excellent for showing dural
diploic veins of Breschet in the posterior table of the sinus thrombosis. Lumbar puncture may be helpful
frontal sinus. These valveless veins communicate in making the diagnosis but needs to be performed
directly with dural veins and empty into the sagittal with caution in the setting of a potentially increased
sinus. The types of complications that may develop intracranial pressure. Lumbar puncture is generally
include osteomyelitis of the frontal bone, meningi- nondiagnostic in abscesses and subdural empyema
tis, epidural abscess, subdural empyema, and intra- but will clearly indicate meningitis if it is present.
cerebral abscess. Pott’s puffy tumor is a well- The mainstay of therapy for suspected intracra-
circumscribed swelling of the forehead caused by nial complications is intravenous antibiotics capable
anterior extension of frontal sinusitis. The edema of of crossing the blood-brain barrier. If cultures can be
the skin and soft tissue overlies a collection of pus obtained from the affected sinuses, this will guide
under the periosteum of the anterior table of the specific antibiotic choice. A neurosurgical consulta-
frontal sinus. tion is sought when a procedure may be necessary to
Abscesses in the epidural space often do not drain an intracranial collection. Since these compli-
give localizing findings and do not give abnormal cations often cause seizures, input from a neurologist
Sinusitis and Polyposis 769
may be helpful in determining appropriate anticon- in its identification. Particularly in acute sinusitis,
vulsant medications. Corticosteroids are usually not pain over the maxillary or frontal regions can be a
used during an active infectious process; however, prominent feature in the patient’s history. Maxillary
they are sometimes employed to reduce severe brain sinus pain may also be referred to the upper teeth
edema. Surgery should be directed at the involved and palate. Ethmoid sinusitis classically causes pain
sinuses as well as the intracranial process unless the between or behind the eyes. Sphenoid sinus inflam-
patient’s condition limits operative time, in which mation or infection tends to cause more insidious
case, the neurosurgical procedure takes precedence. pain that may be referred to the occipital, vertex, or
Epidural abscesses are drained via bur holes without bitemporal regions of the skull. Of course, there are
violating the dura. Subdural empyema can be many other causes of headache and dental pain
approached with either bur holes or a craniotomy. other than sinusitis; thus, facial or head pain is not a
The morbidity from subdural empyema is high with specific finding. Also, pain is a less common finding
either technique, and the mortality is between 12 and once sinusitis becomes chronic, except when there is
18%.22 Brain abscesses actually have a lower mortal- an acute exacerbation. Similarly, acute sinusitis is
ity, although the morbidity remains high. These col- sometimes associated with systemic symptoms such
lections can be either serially aspirated or excised, as malaise, fever, and lethargy, whereas chronic
based largely on the accessibility of the lesion and the sinusitis typically is not. A common symptom seen
stability of the patient. in chronic disease more often than in the acute situ-
ation is olfactory loss. Sore throat and cough may be
present in either case. As discussed earlier, the Rhi-
DIAGNOSIS OF RHINOSINUSITIS nosinusitis Task Force of the AAO-HNS has identi-
fied major and minor symptoms associated with
HISTORY rhinosinusitis that can be helpful in making the
The diagnosis of rhinosinusitis is made difficult by diagnosis (see Table 34–2).
the similarity in symptomatology with allergic rhini- It is important in the history to elicit any
tis and acute viral rhinitis. In rhinosinusitis, the symptoms related to orbital or intracranial exten-
most common complaints are nasal obstruction and sion of the infection. Mild periorbital swelling is not
nasal congestion. These sensations likely result from uncommon in frontal, ethmoid, or maxillary sinusi-
the thickening of the sinus and nasal mucosa, along tis. This swelling is often worse in the morning and
with reactive swelling of the inferior and middle improves over the course of the day. However, mas-
turbinates. Postnasal discharge is also a common sive periorbital edema, orbital pain, diplopia, or
symptom reported by sinusitis patients. These change in vision may signal the presence of an
symptoms, which largely reflect inflammation of the orbital complication. Change in mental status or
nasal cavities, are present in allergies and colds as meningeal signs can herald an intracranial process
well as sinusitis. One factor that may help in the dif- related to ethmoid, frontal, or sphenoid sinusitis.
ferentiation is the duration and timing of symptoms.
Allergic rhinitis often has a seasonal component and
is associated temporally with exposure to known
PHYSICAL EXAMINATION
allergens. Upper respiratory tract infections usually The external findings in sinusitis may be limited and
last less than 10 days or are at least on their way nonspecific. Periorbital, forehead, or cheek swelling
toward resolution by then. Both allergic rhinitis and is sometimes apparent, and there may also be asso-
colds can trigger rhinosinusitis and may therefore be ciated tenderness to palpation or percussion in these
present in the history prior to onset of sinus symp- regions. The oral cavity and oropharynx should be
toms. It is estimated that 0.5 to 2% of upper respi- examined for dental pathology and for the presence
ratory tract viral infections go on to cause sinusitis.23 of postnasal discharge. Anterior rhinoscopy can
A history of a “cold” that lasts longer than 10 days, reveal mucosal hyperemia and edema of the septum
especially with green nasal discharge, is suspicious and inferior turbinate. It may be possible to discern
for sinusitis. mucopurulent discharge in this manner, although
Facial pain, pressure, or fullness can be a more the site of origin is not likely to be visualized. Trans-
localizing symptom of sinus disease that may help illumination of the maxillary and frontal sinuses is
770 Ballenger’s Otorhinolaryngology
clearly demonstrate dural inflammation that would obliteration from retained mucosa, secretions, and
not be appreciable by CT and shows the communi- infection. The disadvantage of MRI is mainly that
cation of encephaloceles with the intracranial space. bony anatomy is not seen with this technique, mak-
In invasive fungal sinusitis, MRI can reveal vascular ing it useless as a surgical map. Also, to a greater
abnormalities that represent fungal infiltration of extent than even CT, mucosal disease on MRI is dif-
neurovascular structures, sometimes allowing the ficult to interpret because of the high sensitivity and
process to be detected early when it is more treat- the presence of abnormalities in many asympto-
able. In the setting of orbital complications of sinusi- matic people.
tis or sinus surgery, CT is generally the better study,
unless intracranial complications are suspected as
well. Another use of MRI is to evaluate symptoms
STAGING SYSTEMS FOR RHINOSINUSITIS
referable to the frontal sinus after it has been surgi- In addition to the establishment of diagnostic crite-
cally obliterated and cannot be monitored endo- ria for rhinosinusitis, there have been several efforts
scopically. Whereas CT merely shows opacification in the last decade to formulate a standardized stag-
of the sinus, MRI can differentiate fat used in the ing system to be applied across individuals and used
A C
B
772 Ballenger’s Otorhinolaryngology
to follow the course of the disease. These staging sys- must be strongly entertained. Unique issues in chil-
tems have attempted to identify parameters of the dren that may play a causative role in the pathogen-
history, physical examination, and sinus CT scan esis of sinusitis include adenoid hypertrophy and
with prognostic significance. Most rely heavily on gastroesophageal reflux disease. There is good evi-
CT findings such as mucosal thickness, anatomic dence that removal of large, obstructive adenoids is
abnormalities, and the location of involved sinuses beneficial for chronic pediatric sinusitis. However,
because these are relatively objective criteria that are removal of nonhypertrophied adenoids is contro-
readily quantifiable. Unfortunately, the radiographic versial for this indication. Antireflux therapy for
appearance can be misleading when viewed as an sinusitis is also somewhat controversial in the
isolated snapshot in time and generally cannot iden- absence of other overt manifestations. The mainstay
tify the underlying pathophysiology. Better staging of the medical treatment of pediatric rhinosinusitis
information can be obtained by incorporating nasal is antibiotic therapy directed against the typical
endoscopy and intraoperative findings into the par- sinus pathogens. This is discussed further in the next
adigm. The modified Lund-Mackay System is the section as it pertains also to the adult disease.
staging system for rhinosinusitis currently recom-
mended by the AAO-HNS.25 This system includes
patient symptoms as well as scores derived from TREATMENT
radiographic, demographic, endoscopic, and opera-
tive findings. Since it is comprehensive and relatively
MEDICAL THERAPY
simple to use, the modified Lund-Mackay System Acute Rhinosinusitis Once the diagnosis of acute
may help to unify the various staging techniques that sinusitis is ensured, the goal of therapy is to prevent
have been described in the literature. Future modifi- disease progression and the possibility of serious
cations may involve the inclusion of any biochemi- sequelae. Without treatment, acute sinusitis is often
cal or molecular markers that are demonstrated to self-limiting, with approximately 40% resolving
have prognostic significance in rhinosinusitis. spontaneously.26 However, prompt treatment is
believed to hasten the resolution of tissue edema and
bacterial contamination, restoring ostial patency and
PEDIATRIC RHINOSINUSITIS sinus ventilation before permanent mucosal damage
Pediatric sinus disease is gaining increasing recog- occurs. There is no debate that antibiotics should be
nition in terms of its prevalence and economic instituted for all cases of acute sinusitis. In three of
impact. As in adults, the diagnosis of rhinosinusitis four randomized trials reviewed by Hueston et al,
in children is made largely on clinical grounds and the use of antibiotics was supported by a more rapid
is similarly difficult to distinguish from viral upper resolution of symptoms.27 Historically, there has
respiratory tract infections. The principal com- been a dramatic reduction in the incidence of com-
plaints in pediatric sinus disease are nasal con- plications secondary to sinusitis since the introduc-
gestion, cough, and purulent rhinorrhea. Unfortu- tion of antibiotics.
nately, a good history and physical examination may The selection of first-line antibiotics for acute
be unobtainable, especially in very young children. sinusitis is directed by the knowledge of the most
Usually, an otoscope is the most effective instru- common pathogens. Typically, patients will be seen
ment to examine the nose of a young child. To the initially by their primary care physician and treated
extent possible, attention should be directed toward with inexpensive agents such as amoxicillin or
viewing the region of the middle meatus to look for trimethoprim-sulfamethoxazole (TMP-SMX). The
purulence. Radiologic studies such as CT may be effectiveness of these agents is hampered by emerging
helpful where the physical examination is limited, patterns of resistance in many geographic areas, how-
although the same problems of interpretation exist ever. Resistance to TMP, by Streptococcus pneumoniae
as do in adults. The pathophysiology of sinus disease in particular, has increased in recent years and has
in children mirrors that of the adult population, been reported to be greater than to penicillin. For
with anatomic, local, and host factors playing amoxicillin, recent in vitro evidence suggests that
important parts. In a child with nasal polyps and current doses may be inadequate, although clinical
recurrent sinusitis, the diagnosis of cystic fibrosis trials at higher doses have not been completed.28 In
Sinusitis and Polyposis 773
general, these first-line agents should not be used important to maintain appropriate follow-up to
when resistant microorganisms are suspected. ensure that the complete course of antibiotics is taken.
The choice of a second-line antibiotic is A good guideline is a 10- to 14-day course of therapy,
dependent on a number of variables including which can be lengthened for persistent symptoms.
patient allergies, dosing schedule, proven efficacy,
physician experience, and the patient’s previous ANCILLARY THERAPY. A variety of therapeutic meas-
response history, as well as resistance patterns in the ures can augment the effectiveness of antibiotics in
community. β-Lactam cephalosporins have long the treatment of acute sinusitis. The goal of these
been the most common second-line agents, interventions is to restore proper nasal function
although macrolides and fluoroquinolones have through improvement in ciliary function and reduc-
recently been increasing in popularity. The use of tion of mucosal edema. Many simple, inexpensive
penicillin, erythromycin, cephalexin, cefixime, and supportive measures are effective because they help
tetracycline is condemned for their limited spectrum to clear crusts and thick mucus. Examples include
of activity. In addition, first-generation cepha- nasal saline sprays, humidifiers (warm or cool),
losporins have poor Haemophilus influenzae cover- steam, hot soup, or tea. Mucolytic agents such as
age and should be used cautiously. The most guaifenesin also are useful because they lead to thin-
relevant pharmacokinetic parameter of β-lactam ning of the mucus, which promotes clearance and
antibiotics is the time above minimal inhibitory prevents stasis.29 Systemic and topical decongestants
concentration, which has been shown to correlate act on α-adrenergic receptors to cause vasoconstric-
with efficacy. In this regard, cefprozil, cefuroxime, tion and reduction of edema and are therefore
and cefpodoxime are the most consistently reliable appropriate to relieve nasal obstruction, re-establish
agents of this class against penicillin-sensitive and ostial patency, and ventilate the sinuses. Topical
intermediately penicillin-resistant strains. These decongestants have minimal systemic side effects
antibiotics are effective in twice-daily dosing and and are rapid in onset. However, use of these agents
have an adequate spectrum of activity. For β-lacta- for longer than 3 consecutive days can result in
mase-producing strains of H. influenzae or rebound congestion and rhinitis medicamentosa.
Moraxella catarrhalis, the use of amoxicillin-clavu- Systemic decongestants can be used for longer peri-
lanate may be indicated. In this case, a separate pre- ods of time but may be associated with insomnia,
scription for amoxicillin alone must be written to hyperactivity, cardiac stimulation, worsening of
give a double dose of that drug without increasing hypertension, and negative interactions with con-
the clavulanate dose. It should be noted that clavan- current medications. For these reasons, systemic
ulate has no effect on resistant S. pneumoniae decongestants should be prescribed with caution in
microorganisms because their mechanism of resist- some patient groups. The use of decongestants in
ance is different. The newer macrolides such as conjunction with antibiotics has been shown to be
azithromycin and clarithromicin may be acceptable more effective than antibiotics alone.
second-line agents, especially in penicillin-allergic Antihistamines have been used empirically in
patients, although pneumococcal resistance to these patients with sinusitis and allergy, although no
agents is on the rise. Any microorganism that is studies show a clearly beneficial role for these med-
resistant to erythromycin will also be resistant to ications. In the setting of acute infectious sinusitis,
these newer agents. Finally, the newer fluoro- first-generation antihistamines may actually be
quinolones such as levofloxacin, moxifloxacin, and counterproductive because of their anticholinergic
gatifloxacin are good second-line agents for patients side effects of mucosal dryness, crusting, and
with activity against S. pneumoniae. However, as has increased mucus viscosity. The newer second-
been observed with other classes of antibiotics, generation antihistamines cause less of these unde-
resistance will develop if these drugs are used inap- sirable changes and therefore may be suitable in
propriately; thus, they are recommended only for cases of sinusitis in which allergy plays an impor-
moderate-to-severe infections or treatment failures. tant role. Topical nasal corticosteroids are also excel-
Once antibiotics have been instituted, the dura- lent for the management of allergic rhinosinusistis
tion of therapy is controversial. Symptoms should but have no proven value in the treatment of acute
begin to improve within 48 to 72 hours, and it is infectious sinusitis. Systemic corticosteroids are
774 Ballenger’s Otorhinolaryngology
potent anti-inflammatory agents that are effective greater difficulty in unoperated patients using
in the treatment of allergic disease as well as other indwelling catheters into the maxillary sinuses. There
inflammatory conditions of the nose. Because cor- is some evidence to suggest a role for this strategy in
ticosteroids reduce tissue edema and inhibit inflam- chronic sinus disease failing systemic antibiotic ther-
matory mediator production, they almost certainly apy. As compared to acute sinusitis, the mechanisms
are beneficial in the treatment of acute sinusitis. of chronic rhinosinusitis are more obscure and seem
However, a number of potential complications are to involve many factors other than infection. In fact,
associated with corticosteroid use, including hypo- much of the infectious component of chronic disease
thalamic-pituitary-adrenal axis suppression, gastric may be secondary to the compromise of the normal
ulcers, psychiatric changes, sleep disturbances, and mucosal barrier mechanisms by long-term inflam-
exacerbation of diabetes, as well as long-term mation. In the future, new therapies may target ele-
sequelae such as osteoporosis, weight gain, ocular ments of the ongoing inflammatory response in an
problems, and hypertension. For these reasons, the attempt to allow healing to occur and restore normal
use of corticosteroids is not widely accepted for mucosal function.
acute sinusitis. In general, the risk of adverse side
effects when corticosteroids are used conservatively
over short, tapered doses is minimal; therefore, SURGICAL THERAPY
these drugs are reasonable adjunctive therapy for Endoscopic sinus surgery More than 100 years
acute sinusitis treated primarily with antibiotics. have passed since the first nasal endoscopy was per-
formed by Hirschmann, who used a modified cysto-
Chronic Rhinosinusitis In chronic sinusitis, the scope. Since then, major advances in optics,
microorganisms primarily involved are coagulase- biomechanics, and radiographic imaging have
positive and coagulase-negative species of Staphylo- allowed evaluation and treatment of paranasal sinus
coccus and Streptococcus. Antibiotic therapy should disorders with greater precision.
therefore be directed at these pathogens, although Naumann recognized the relationship between
resistance is a constant problem. The use of antibi- the middle meatal-anterior ethmoid complex,
otics with activity against anaerobes is controversial termed the ostiomeatal unit (Figure 34–8), and the
since some studies show these microorganisms to be
of minor importance; however, these agents can be
used alone or in combination with other antibiotics
when anaerobes are identified in sinus fluid. The
duration of antibiotic therapy in chronic sinusitis is
not clearly defined but is typically on the order of 4
to 8 weeks. The goals of ancillary therapy for chronic
sinus disease are similar to those in the acute situa-
tion; however, there are some important differences.
When an underlying condition such as allergy, poly-
posis, fungal infection, or systemic disease is present,
the treatment must first be directed toward control-
ling these processes. In the case of allergic rhinosi-
nusitis, management with antihistamines, topical
nasal corticosteroids, and immunotherapy will be of
more value than it would in an acute infection. Like-
wise, systemic corticosteroids are indispensable for
the treatment of polyps and sinus inflammation
caused by systemic granulomatous or autoimmune
diseases. In patients with chronic sinusitis who have
undergone previous sinus surgery, there is access for FIGURE 34–8. The ostiomeatal unit (shaded). Obstruc-
direct irrigation of the sinus cavities with topical tion of this area leads to disease within the maxillary and
antibiotic solutions. This can also be performed with frontal sinuses.
Sinusitis and Polyposis 775
A B
FIGURE 34–10. A, Microdébrider used for powered dissection in endoscopic sinus surgery. B, Intraoperative endo-
scopic view of a microdébrider being used to remove nasal polyps.
son, microdébriders and manually operated forceps ANESTHESIA The operation can be performed
serve complementary roles and are generally used under local or general anesthesia. Local anesthesia
concurrently in FESS procedures. with intravenous sedation may be preferable because
Another significant advance in endoscopic sensory information remains intact along the peri-
sinus surgery has been the development of com- orbita and skull base. Allowing the patient to listen
puter-assisted image-guided technology. Accurate to favorite music during surgery reduces the amount
three-dimensional CT reconstruction with real-time of anxiolytics necessary during the procedure. On
intraoperative computer guidance has become the other hand, general anesthesia is preferable for
widely available in recent years. There are several patients who are very anxious about being awake
devices available today that use either electromag- and for those who become disinhibited under seda-
netic or infrared tracking and are relatively user tion. There has been a general tendency toward per-
friendly. With some systems, the patient must forming more endoscopic sinus surgery under
undergo a preoperative CT wearing a specially fitted general anesthesia in recent years. One reason for
headpiece that is worn again in the operating room. this is that the meticulous nature of mucosa-pre-
The computer uses the headpiece to determine head serving sinus surgery has increased the length of the
position and correlate this with the preoperative CT. procedure to the point that it may be difficult for
In other systems, anatomic landmarks are selected patients to remain still comfortably. Also, the advent
from the CT scan and identified on the patient in of image-guided surgery has made it necessary for
the operating room, instead of making use of a the patient to wear a tight-fitting headpiece, which is
headpiece. Probes and instruments are then tracked not tolerable for long periods of time. It is reason-
with an infrared or electromagnetic system to deter- able to present the advantages and disadvantages of
mine their position continuously. The surgeon views both anesthetic approaches to patients and let them
the sinus CT in multiple planes on the monitor, with decide which they prefer preoperatively. Patients
the instrument tip position displayed in real time electing local anesthesia must be informed that they
(Figure 34–11). The accuracy of the system is on the will be put to sleep if they cannot tolerate being
order of 2 mm currently, although the technology is awake for the duration of the procedure or if they
constantly undergoing refinement and improve- become disinhibited with sedation.
ment. Overall, image-guided surgery is helpful in all Before the patient enters the operating suite,
sinus cases but especially valuable for difficult revi- oxymetazoline hydrochloride nasal spray is used for
sion cases with few landmarks or where unusual or initial mucosal shrinking. The nasal mucosa is then
distorted anatomy is present. further decongested and anesthetized, one side at a
Sinusitis and Polyposis 777
time, with 150 mg of topical cocaine followed by PROCEDURE The surgeon should be comfortable
injections of 1% lidocaine with 1:100,000 epineph- and relaxed during the dissection. The preoperative
rine at the sphenopalatine neurovascular bundle CT scan should be readily available in the operating
(Figure 34–12). Septal abrasions should be avoided; room for repeated viewing. The surgeon must per-
otherwise, visualization becomes difficult from form a meticulous dissection with adequate visuali-
repeated soiling of the telescope. In addition, the zation if complications are to be avoided.
sphenopalatine ganglion is anesthetized through the To begin, an infundibulotomy is made using a
nose or through the greater palatine foramen. Allow- sickle knife along the anterior and inferior edges of
ing at least 10 minutes for maximal vasoconstriction the uncinate process. The uncinate is grasped with
decreases bleeding. The second side of the nose is Blakesley forceps and removed, taking care not to
anesthetized when surgery on the first side is near strip mucosa from the lateral nasal wall. Gentle
completion. medial displacement of the uncinate during the
infundibulotomy helps define the line of the inci- endoscope medial to the middle turbinate usually
sion. If possible, the location of the maxillary sinus brings the free edge of the superior turbinate in
ostium is noted along with any accessory ostia. view. The sphenoid sinus can also be entered by
Extent of surgery is based on the preoperative assess- amputating the inferior aspect of the superior
ment; however, for purposes of instruction, a turbinate. Care must be taken not to remove this
description of a sphenoethmoidectomy with frontal turbinate completely because olfactory neuroepithe-
sinusotomy and antrostomy follows. lium could be injured. Absolutely no blind tissue
The bulla ethmoidalis is entered and removed. removal is performed within the sphenoid because
The medial orbital wall should be identified as early this may lead to optic nerve or carotid artery injury.
as possible during the dissection. Every attempt at At this point, the dissection is continued ante-
preserving the mucosa along the medial orbital wall riorly along the skull base, with care not to injure the
is made to improve and hasten postoperative heal- anterior and posterior ethmoid arteries. The mucosa
ing. The posterior ethmoid is entered through the along the skull base is also preserved. The frontal
inferior and medial area of the basal lamella. The recess is dissected only if required because manipu-
skull base is most easily identified within the poste- lation of this region can lead to stenosis of the
rior ethmoidectomy and serves as the superior frontal ostium. In addition, frontal recess surgery
boundary for the dissection. The safest way to increases the requirement for postoperative care.
remove bony partitions within the ethmoid is to feel Operating within the frontal recess is the most
behind the partitions with up-biting forceps prior to challenging segment of the operation. Changing to
removal (Figure 34–13). This technique assists in the 30- or 45-degree endoscope is helpful for dis-
avoiding orbital or intracranial penetration. secting this area. The dome of the ethmoid should
The sphenoid ostium is located and, if neces- be identified and followed anteriorly as the skull
sary, widened beginning inferiorly and medially. The base ascends. The skull base represents the posterior
ostium is usually a few millimeters from the pos- limit of dissection in this area. All motions should be
teroinferior edge of the superior turbinate. The free made away from the skull base in an anterior direc-
edge of the superior turbinate may be difficult to tion. Anteromedial ethmoid cells and agger cells can
appreciate when working in the ethmoid sinus but be removed with a frontal recess curette. Eicken
can be palpated medially. Alternatively, placing an curved suction is helpful in this area. The size of the
frontal ostium should be recorded for postoperative
reference.
Finally, attention is turned toward the maxil-
lary sinus ostium. The 30-degree telescope is usually
required to identify the natural ostium of the maxil-
lary sinus. If necessary, the ostium is enlarged poste-
riorly and inferiorly. Beginning from within the
ostium, the mucosa of the posterior fontanelle is
split and then removed with the aid of a back-biting
instrument. The remaining uncinate is removed at
this time to prevent postoperative scarring in this
area.
At the conclusion of the operation, an expand-
able sponge covered with a water-soluble antibacter-
ial ointment is placed lateral to the middle turbinate.
Additional packing is rarely required. Most patients
are released the day of surgery and return to the
clinic on the first postoperative day for removal of
the sponge.
FIGURE 34–13. Blakesley forceps are used to palpate POSTOPERATIVE CARE The overall success of FESS is
behind bony partitions before removal. in large part attributable to appropriate postopera-
Sinusitis and Polyposis 779
tive care. The goal during this period is to promote postoperative débridement and sinus cavity revi-
mucosal generation within the sinus cavities. To sion. Local anesthetic injection may be necessary to
facilitate this generation, sinus cavities are examined allow the patient to tolerate the intranasal manip-
and cleaned of blood, fibrin clots, and crusts at reg- ulation comfortably. Endoscopic surveillance and
ular intervals following surgery. Endoscopes should proactive treatment of residual disease eliminate
be used, as opposed to blind manipulation, to pre- the need for most revision surgery and lead to
vent injury to healthy mucosa and for directed long-term success.
débridement. This is especially true for the frontal
recess. Open Sinus Procedures Although FESS can be
Systemic antibiotics are used in the postopera- used effectively for most medically recalcitrant
tive period, and their use may be prolonged when sinus disease, there are still occasional circum-
severe, chronic inflammation is present. Agents cov- stances under which open sinus procedures may be
ering the typical sinus flora, such as amoxicillin/ indicated.
clavulanate, cephalosporins, or quinolones, are the
most common antibiotics chosen in uncomplicated MAXILLARY SINUS. CALDWELL-LUC OPERATION. In cases
cases. When there is known exposed osteitic bone, of symptomatic maxillary sinus mucoceles, antro-
broader coverage with clindamycin and TMP-SMX choanal polyps, mycetoma, or foreign bodies not
may be indicated. If postoperative endoscopy reveals accessible via an intranasal endoscopic approach, the
purulence, this material should be cultured and traditional open procedure has long been the Cald-
antibiotic therapy tailored appropriately. Patients well-Luc procedure. This procedure may be per-
may be instructed to irrigate the nose with saline formed under general anesthesia or locoregional
solution twice daily. For the majority of patients anesthesia via blocks of the infraorbital, sphenopala-
with chronic sinusitis, surgery alone does not result tine, and posterosuperior alveolar nerve. Topical 4%
in a permanent disease resolution. Long-term, cul- cocaine can be placed intranasally in the region of
ture-directed, systemic antibiotics and prolonged the anterior ethmoid nerve and the medial wall of
use of topical nasal corticosteroids are frequently the maxillary sinus.
required. Occasionally, antibiotics are added to the Technique. The procedure begins with a gin-
nasal irrigation solution for patients with recalci- givobuccal incision, made from the second molar to
trant chronic sinusitis. In some circumstances, such the ipsilateral canine tooth (Figure 34–14). The inci-
as in aspirin-sensitivity triad disease failing multiple sion should be made just above the apex of the buc-
previous sinus surgeries, long-term oral cortico- cogingival sulcus to preserve an inferior flap of soft
steroid therapy using a low-dose, alternating-day tissue that will facilitate closure. Dissection proceeds
regimen may be required to prevent recurrence. sharply through the submucosal tissue and the max-
It is critical to the ultimate success of endo- illary periostium down to bone. A periostial elevator
scopic sinus surgery that meticulous, sometimes is used to raise the periosteum and overlying soft tis-
aggressive, débridement be performed in the weeks sue superiorly to the level of the infraorbital fora-
following the procedure. At each postoperative men, being careful not to injure the neurovascular
visit, the nasal cavities are sprayed with tetracaine bundle. Medially, the periosteum is elevated to the
and a nasal decongestant, and cocaine may be pyriform aperture. Once adequate exposure is
applied with nasal applicators as needed. Since the achieved, the maxillary sinus in entered through its
mucosa is particularly sensitive in the early postop- anterior wall using an osteotome or cutting bur. The
erative period, the patient is instructed to take an antrum is entered superior to the roots of the canine
oral narcotic/analgesic before arriving. The goal of and premolar teeth. A sphenoid punch and a Kerri-
these postoperative débridements is to clear crusts, son rongeur are used to remove additional bone and
osteitic bone fragments, and forming scar tissue enhance exposure. Bone can be removed superiorly,
before these factors create persistent inflammation medial and lateral to the infraorbital nerve, preserv-
and disease recurrence. In some instances, diseased ing the infraorbital foramen itself.
sinus cells that were missed in the operation will be The approach gives good visualization of all
recognized and need to be opened. As in the oper- portions of the maxillary sinus and allows complete
ating room, mucosal preservation is paramount in removal of infectious material and masses that
780 Ballenger’s Otorhinolaryngology
Once the lacrimal bone, frontal process of the scar, medial canthal blunting, or medial canthal
maxilla, lamina papyracea, and orbital process of webbing. Webbing can be addressed with a Z-plasty
frontal bone have been widely exposed, the ethmoid at a later time or may be prevented by performing
is entered through the lacrimal fossa with a mallet one at the time of the initial surgery. Injury to the
and gouge or drill. The opening is circumferentially lacrimal system can also occur, with epiphora as a
enlarged with the Kerrison rongeur. When the fron- consequence. If dissection proceeds into the orbit,
toethmoid suture is reached, no further bone should serious complications such as cranial nerve injury or
be removed superiorly as this represents the level of visual loss are possible. Retrobulbar hematoma and
the anterior cranial fossa. The lamina papyracea is cerebrospinal fluid leak are other less common but
taken down to allow complete exenteration of the potentially catastrophic complications of the exter-
ethmoid cells. Working intranasally, an uncinectomy nal ethmoidectomy.
and anterior ethmoidectomy will link the ethmoid
cavity to the middle meatus. The middle turbinate FRONTAL SINUS. Open approaches to the frontal sinus
should not be removed. are indicated for chronic, complicated frontal sinusi-
In some cases, the frontal sinus may be dis- tis that has not responded to trephination or con-
rupted during the external ethmoidectomy proce- ventional endoscopic sinus surgery. Other indica-
dure. To promote drainage of the frontal sinus, tions include intracranial or orbital extension of dis-
Silastic stents have sometimes been placed extending ease, mucocele or mucopyocele, and osteomyelitis of
from the frontal sinus to the anterior aspect of the the frontal bone.
inferior turbinate and secured with a permanent
suture. A period of at least 6 weeks is needed to pro- TREPHINATION. This approach to the frontal sinus is
duce a mucosally lined tract between the frontal useful in the face of acute infection when mucosal
sinus and the middle meatus. Even with stenting, bleeding may hamper an intranasal endoscopic
stenosis tends to occur, and the orbital contents have approach. It is safe and rapidly performed and can
a tendency to medialize into the frontal recess and decompress a pus-filled frontal sinus prior to a more
interfere with sinus outflow. definitive procedure. The procedure is also useful in
At the end of the procedure, the nose is packed conjunction with FESS to help locate the natural
with 1 cm gauze or preformed surgical sponges drainage pathway of the frontal sinus and to visual-
impregnated with antibiotic ointment. The perios- ize the ostium from above and below.
teum and subcutaneous tissues are closed with 3-0
Technique. An incision is made beneath the
absorbable sutures, and skin closure is accomplished
medial portion of the eyebrow, taking care to bevel
with 6-0 nylon or mild chromic sutures.
the incision parallel to the hair follicles. The incision
Complications. A poorly designed incision can is carried through skin, subcutaneous tissue, and the
result in cosmetic problems such as a hypertrophic periosteum over the frontal sinus floor. Once the
782 Ballenger’s Otorhinolaryngology
incision is completed, the wound can be retracted sinus obliteration may be the only viable option. The
superiorly and medially over the anterior table of the technique has the advantage of unparalleled visuali-
frontal sinus. A drill is used to make a hole into the zation of the entire frontal sinus and elimination of
sinus in a controlled fashion (Figure 34–16). If the the need to reconstruct the nasofrontal drainage
hole is made with a diameter greater than 4 mm, an outflow. The negatives of the technique include the
endoscope can be inserted to visualize the interior of external scar, potential for forehead hypesthesia, and
the sinus. Purulence is removed for culture, and the the loss of a connection between the nose and
sinus is irrigated. The wound is closed with deep sinus through which endoscopic surveillance can be
absorbable sutures and nylon or prolene on the skin. performed.
A catheter may be left in the trephination and
Technique The osteoplastic flap frontal sinus
brought out through the wound to allow for irriga-
obliteration can be performed through either a gull-
tion in the postoperative period.
wing suprabrow incision or a bicoronal approach
FRONTAL SINUS OBLITERATION WITH OSTEOPLASTIC with the incision behind the hairline. Typically, the
FLAP. Frontal sinus obliteration is an old procedure type of incision is determined by the patient’s hair-
that has been revived and refined for use in recalci- line and the presence of suitable forehead creases in
trant cases of frontal sinusitis. After endoscopic sur- which to place the scar. A 6-foot Caldwell radi-
gery, the frontal sinus ostium is sometimes very ograph of the sinuses is obtained preoperatively, and
difficult to keep open from within the nose when a template of the frontal sinus is fashioned and ster-
osteoneogenesis is present. More extensive intranasal ilized. The patient’s face and hair are prepared for a
drill-out procedures may be successful in establish- bicoronal approach, and the abdomen is prepared
ing long-term patency of a frontal sinus drainage for harvest of abdominal fat.
pathway, but many times it is not possible to main- The bicoronal incision is made approximately
tain an opening into the sinus with any endoscopic 2 cm behind the hairline and curved laterally toward
or open surgical technique. In these patients, frontal the ears on both sides (Figure 34–17). Since the scalp
is very vascular, hemostasis must be maintained with
Raney clips and careful cautery (avoiding hair folli-
cles) to prevent excessive blood loss. The flap is ele-
vated above the level of the pericranium down to the
root of the nose and superior orbital rims. Near the placing the fat graft. The frontal ostium is occluded
orbits, the supraorbital neurovascular bundle should with pericranium or temporalis muscle to obliterate
be identified and protected. With the flap elevated, the connection to the nasal cavity. Abdominal fat is
the template is placed to show the borders of the usually harvested through a periumbilical incision
frontal sinus, which are marked with a pen. Other and cut to fit snugly within the confines of the sinus.
techniques used to define the sinus boundaries are When the graft is in place, the bone flap is replaced
transillumination of the sinus through a trephina- and fixed with small titanium plates to recreate the
tion or the use of surgical navigation. Once the bor- normal frontal contour. Drains are placed in the
ders are marked, the periosteum is incised along the incision, and the wound is closed in layers.
marked edges and elevated 1 to 2 mm (Figure
34–18). The periosteal flap remains attached inferi- Complications The most significant disad-
orly at the orbital rims to preserve a blood supply. vantage of a frontal sinus obliteration procedure is
An oscillating saw is used to make the bone the loss of the ability to image the sinus following
cuts through the anterior table of the frontal sinus. the procedure. This can make assessment of postop-
The cuts are beveled at about a 45-degree angle
directed toward the sinus, both to prevent inadver-
tent penetration outside the sinus and to assist in
repositioning the flap at the end of the procedure.
Even with this degree of beveling, care must be taken
to avoid cutting the posterior table of a very shallow
sinus. With the bony cuts completed, the intersinus
septum is cut and the flap is elevated with an
osteotome. The bone flap, with the periosteum
attached superficially, is reflected inferiorly to expose
the sinus (Figure 34–19). To perform an obliteration
successfully, it is absolutely critical to remove all of
the mucosa from within the sinus. The gross mucosa
is relatively easily stripped from the sinus and its
recesses. However, rests of mucosa exist within the
small foramina of Breschet in the bone of the ante-
rior and posterior tables. Therefore, all of the bony FIGURE 34–19. The osteoplastic flap approach to
surfaces of the frontal sinus must be meticulously frontal sinus obliteration. Here the osteoplastic flap has
burred down under microscopic visualization before been elevated, and the frontal sinus can be seen.
784 Ballenger’s Otorhinolaryngology
erative frontal sinus complaints difficult and delay cus, nasal septum, and floor of the nose are injected
detection of some late complications. Perioperative with 1% lidocaine with 1:100,000 epinephrine. A
complications of the osteoplastic frontal sinus oblit- scalpel is used to make an incision in the upper labial
eration procedure include hematoma, infection or sulcus, leaving a cuff of mucosa attached to the gin-
abscess of the bicoronal or abdominal wound, and giva to facilitate closure. The incision is carried
dural injury from bone cuts outside the sinus. The down to the maxillary bone, and the periosteum is
major long-term complications of obliteration are elevated to the inferior margin of the pyriform aper-
pain or altered sensation, visible bony defects, and ture until the anterior nasal spine is exposed. The
mucocele formation. Pain and sensory abnormali- right septal periosteum is incised at the caudal mar-
ties often result from trauma or sectioning of the gin, and mucoperichondrial flaps are elevated along
supraorbital nerve. Bone defects can occur from the right side of the septum and along both floors of
depression or protrusion of the osteoplastic flap or the nasal cavities. The septum is divided at the bony-
the development of hyperostosis. Mucoceles take cartilaginous junction, and mucoperiosteal flaps are
many years to develop but can ultimately lead to elevated bilaterally from the bony septum. The
extensive operations to secondarily remove the pockets along the nasal floors are then connected
entrapped mucosa. The frontal recess is the most with the septal pockets, and the cartilaginous sep-
likely place for mucosa to have been incompletely tum is dislocated from the maxillary crest toward the
removed, but there are always crevasses around the left. The perpendicular plate of the ethmoid is then
periphery of the frontal sinus that can harbor rests removed with forceps, taking care not to place any
of mucosa. Incomplete separation of the nasal cavity torque on the superior attachment of the bone to the
from the obliterated sinus can eventually result in an ethmoid roof. Once the rostrum of the sphenoid is
infected graft and fat necrosis. reached, fluoroscopy or surgical navigation may be
used to verify proper positioning. The anterior face
SPHENOID SINUS. Although the sphenoid sinus is read- of the sphenoid can then be entered directly in the
ily accessible endoscopically through the nose, exter- midline or by first locating the natural ostia and
nal approaches are frequently used to achieve wider using these as the superior and lateral landmarks.
exposure for resection of masses or for pituitary sur- For pituitary surgery, the speculum is then inserted,
gery. Some techniques, such as the external eth- and the procedure is generally turned over to neuro-
moidectomy and transantral approaches, are seldom surgery. After pituitary tumor resection, the sphe-
used today because of the oblique angle toward the noid mucosa is often stripped away, and the sinus is
sphenoid. Most commonly, the open procedures obliterated with fat or bone grafts. The septal flaps
involve operating through the nasal septum to the are carefully reapproximated, and the septum is
face of the sphenoid. This can be accomplished via a returned to the midline in the maxillary crest. The
transnasal septoplasty approach, an open rhino- sublabial incision is closed with absorbable suture,
plasty-type incision, or a sublabial incision. The and the nose is packed.
transnasal approach has become more popular with
the increased use of the endoscope; however, the EXTERNAL RHINOPLASTY TECHNIQUE. The sublabial
technique requires a relatively large nose unless an approach was first described by Cushing and was
alar incision is used. The external rhinoplasty inci- then reintroduced and popularized by Hardy in
1968.37 Although it has become the standard, draw-
sion gives unparalleled access and visualization but
backs to this approach include limited exposure sec-
has the potential to leave a noticeable columellar scar.
ondary to the overhanging upper lip, loss of nasal
The sublabial approach is the one most often
tip projection from resection of the anterior nasal
employed because it is easy, leaves no nasal scars, does
spine, postoperative dental hypesthesia, and diffi-
not depend on nasal size, and allows the speculum to
culty with denture fitting in older patients. The
be placed in the midline. The drawbacks involve oral
external rhinoplasty approach was designed to avoid
contamination of the wound and difficulties with
these limitations of the traditional sublabial tech-
oral incisions in denture wearers.
nique.38 In this procedure, the nasal columella,
SUBLABIAL, TRANSSEPTAL TECHNIQUE. After induction dome, septum, and nasal floors are injected with 1%
of general anesthesia, the upper gingivobuccal sul- lidocaine with 1:100,000 epinephrine. A columellar
Sinusitis and Polyposis 785
flap is created with an external rhinoplasty incision for mucosal preservation in endoscopic sinus sur-
and elevated onto the dome of the nose. The medial gery has reduced the incidence of postoperative scar-
crural ligaments are divided to expose the caudal ring and sinus dysfunction requiring revision
edge of the septal cartilage. A mucoperichondrial surgery. With the current armamentarium available
flap is then raised on the left side of the septum for early diagnosis and aggressive treatment, most
beyond the bony-cartilaginous junction and onto sinus disease can be controlled and serious compli-
the maxillary crest and floor of the nose. At this cations averted.
point, the cartilage is separated posteriorly and infe- However, considering the prevalence of rhi-
riorly so that posterior and inferior tunnels can be nosinusitis, its economic cost, and quality of life
elevated on the right side and connected. Once the impact on those who suffer with it, there is much
speculum is inserted, the perpendicular plate of the about the pathophysiology of the disease that has yet
ethmoid is resected and the vomer followed to the to be learned. In particular, chronic rhinosinusitis
anterior face of the sphenoid sinus. The sphenoid is that is recalcitrant to current methods of medical
entered, removing the mucosa, intersinus septum, and surgical management awaits a new therapeutic
and posterior wall to reach the pituitary. After the approach. As with many areas in medicine, the
hypophysectomy is performed by neurosurgery, the future of diagnosis and treatment in sinus disease
sphenoid is obliterated, and the septal flaps are will likely use the rapidly expanding tools of molec-
replaced. The medial crura is repaired with 4-0 ular biology and the unfolding knowledge of the
chromic suture. The columellar incision is closed human genome. Already there has been the discov-
with 5-0 mild chromic, and the nose is packed. ery that some patients with recurrent sinusitis have
alterations in the membrane ion channel gene that is
Complications The nasal complications are
responsible for cystic fibrosis.39 Perhaps there are
typically related to the septoplasty portion of the
other subtle, undiscovered differences at the
procedure. These include septal perforation, saddle
genomic level that predispose patients to chronic
deformity, and tip deformity. Epistaxis and wound
sinonasal inflammation. As the underlying mecha-
infection are also possible nasal problems postoper-
nisms of chronic sinus disease are uncovered, more
atively. Potentially serious neurologic and vascular
directed pharmacologic therapy may be devised that
complications may occur in sphenoid surgery since
spares the patient the side effects and complications
the carotid artery and optic nerves travel in the lat-
of systemic corticosteroids. Ultimately, specific
eral wall of the sinus. Even if the optic nerve is not
genetic markers associated with an increased risk of
injured directly during surgery, overpacking of the
sinusitis may be identified. With this information,
sinus with fat can cause optic chiasmal compression
early genetic screening will allow preventive treat-
and visual loss. Another possible complication is
ment or even gene therapy to be instituted prior
cerebrospinal fluid leak, which should be treated
to the onset of symptoms. This has already begun
when it is recognized intraoperatively. During the
with other types of diseases, and it is only a mat-
postoperative period, patients must be closely mon-
ter of time before the methodology is applied to
itored for evidence of change in mental status or
rhinosinusitis.
signs of active bleeding. The cause of these findings
will generally be discovered through radiologic eval-
uation, and the proper intervention can be planned
and undertaken by the operative team.
REFERENCES
1. National disease and therapeutic index. Plymouth
Meeting (PA): IMS Inc., 1994. p. 963–76.
FUTURE DIRECTIONS 2. Benson V, Marano MA. Current estimates from the
There have been many recent advances in the med- National Health Interview Survey, 1992. Vital Health
ical and surgical approaches to sinus disease. Com- Stat 1994;189:12.
puterized guidance systems continue to improve and 3. Ray NF, Baruniak JN, Thamer M, et al. Health care
have the potential to assist the surgeon greatly in expenditures for sinusitis in 1996: contributions of
operating safely at the skull base for difficult sinus asthma, rhinitis, and other airway disorders. J
disease. An improved understanding of the necessity Allergy Clin Immunol 1999;103:408–14.
786 Ballenger’s Otorhinolaryngology
4. Brook I, Gooch WM, Jenkins SG, et al. Medical man- 20. Shin SH, Park JY, Jeon CH, et al. Quantitative analy-
agement of acute bacterial sinusitis. Recommenda- sis of eotaxin and RANTES messenger RNA in nasal
tion of a clinical advisory committee on pediatric polyps: association of tissue and nasal eosinophils.
and adult sinusitis. Ann Otol Rhinol Laryngol Laryngoscope 2000;110:1353–7.
2000;109(5 Pt 3, Suppl):2–20. 21. Chandler JR, Langenbrunner DJ, Stevens ER. The
5. McCaig LF, Hughes JM. Trends in antimicrobial pathogenesis of orbital complications in acute
drug prescribing among office-based physicians in sinusitis. Laryngoscope 1970;80:1414–28.
the United States. JAMA 1995;273:214–9. 22. Hoyt DJ, Fisher SR. Otolaryngologic management of
6. Ober NS. Respiratory tract infections: consider patients with subdural empyema. Laryngoscope
the total cost of care. Drug Benefit Trends 1998; 1991;101:20–4.
10:23–9. 23. Kennedy DW. A 48-year-old man with recurrent
7. Khan R, Dolata J, Lindberg S. Effects of inflamma- sinusitis. JAMA 2000;283:2143–50.
tory mediators on ciliary function in vitro. Rhinol- 24. Havas TE, Motbey JA, Gullane PJ. Prevalence of inci-
ogy 1995;33:22–5. dental abnormalities on computed tomography
8. Borman KR, Brown PM, Mezera KK, Jhaveri H. Occult scans of the paranasal sinuses. Arch Otolaryngol
fever in surgical intensive care unit patients is seldom Head Neck Surg 1988;114:856–9.
caused by sinusitis. Am J Surg 1992; 164:412–5. 25. Lund VJ, Kennedy DW. Staging for rhinosinusitis.
9. Vandenbussche T, De Moor S, Bachert C, Van Otolaryngol Head Neck Surg 1997;117(3 Pt
Cauwenberge P. Value of antral puncture in the 2):S35–40.
intensive care patient with fever of unknown origin. 26. Kaliner MA, Osguthorpe JD, Fireman P, et al.
Laryngoscope 2000;110(10 Pt 1):1702–6. Sinusitis: bench to bedside. Current findings, future
10. Lanza DC, Kennedy DW. Adult rhinosinusitis directions. J Allergy Clin Immunol 1997;99 Suppl:
defined. Otolaryngol Head Neck Surg 1997;117(3 Pt S829–48.
2):S1–7. 27. Hueston WJ, Eberlein C, Johnson D, Mainous AG.
11. Bachert C, Wagenmann M, Rudack C, et al. The role Criteria used by clinicians to differentiate sinusitis
of cytokines in infectious sinusitis and nasal polypo- from viral upper respiratory infection. J Fam Pract
sis. Allergy 1998;53:2–13. 1998;46:487–92.
12. Wardlaw AJ. Molecular basis for selective eosinophil 28. Aronovitz GH. Antimicrobial therapy of acute otitis
trafficking in asthma: a multistep paradigm. J media: review of treatment recommendations. Clin
Allergy Clin Immunol 1999;104:917–26. Ther 2000;22:29–39.
13. Stringer SP, Ryan MW. Chronic invasive fungal rhi- 29. Wawrose SF, Tami TA, Amoils CP. The role of guaife-
nosinusitis. Otolaryngol Clin North Am 2000; nesin in the treatment of sinonasal disease in
33:375–87. patients infected with the human immunodeficiency
14. deShazo RD, O’Brien M, Chapin K, et al. A new clas- virus (HIV). Laryngoscope 1992;102:1225–8.
sification and diagnostic criteria for invasive fungal 30. Naumann H. Pathologische Anatomie der chronis-
sinusitis. Arch Otolaryngol Head Neck Surg 1997; chen Rhinitis and Sinusitis. In: Proceedings of the
123:1181–8. VIIIth International Congress of Otorhinolaryngol-
15. Bent JP, Kuhn FA. Diagnosis of allergic fungal sinusi- ogy. Amsterdam: Excerpta Medica; 1965. p. 80.
tis. Otolaryngol Head Neck Surg 1994;111:580–8. 31. Messerklinger W. Endoscopy of the nose. Baltimore:
16. Ferguson BJ. Definitions of fungal rhinosinusitis. Urban & Schwarzenberg; 1978.
Otolaryngol Clin North Am 2000;33:227–35. 32. Kennedy DW, Goodstein ML, Miller NR, Zinreich
17. Ponikau JU, Sherris DA, Kern EB, et al. The diagno- SJ. Endoscopic transnasal orbital decompression.
sis and incidence of allergic fungal sinusitis. Mayo Arch Otolaryngol Head Neck Surg 1990;116:
Clin Proc 1999;74:877–84. 275–82.
18. Kirsch JP, White JA. Nasal polyposis. La State Med J 33. Kennedy DW, Josephson JS, Zinreich SJ, et al. Endo-
1996;142:11–4. scopic sinus surgery for mucoceles: a viable alterna-
19. Drake-Lee AB, Lowe D, Swanston A, Grace A. Clini- tive. Laryngoscope 1989;99:885–95.
cal profile and recurrence of nasal polyps. J Laryngol 34. Stammberger H. Functional endoscopic sinus sur-
Otol 1984;98:783–93. gery. Philadelphia: BC Decker; 1991.
Sinusitis and Polyposis 787
35. Setliff RC. The hummer: a remedy for apprehension 38. Koltai PJ, Goufmam DB, Barnes SM, Steiniger JR.
in functional endoscopic sinus surgery. Otolaryngol Transsphenoidal hypophysectomy through the
Clin North Am 1996;29:95–104. external rhinoplasty approach. Otolaryngol Head
36. McDonald TJ, Pearson BW. Follow-up on maxillary Neck Surg 1994;111:197–200.
artery ligation for epistaxis. Arch Otolaryngol 1980; 39. Wang X, Moylan B, Leopold DA, et al. Mutation in
106:635–8. the gene responsible for cystic fibrosis and predispo-
37. Hardy J. Transsphenoidal hypophysectomy. J Neuro- sition to chronic rhinosinusitis in the general popu-
surg 1971;34:582–94. lation. JAMA 2000;284:1814–9.
CHAPTER 35
The craniofacial region is the most common loca- structures are asensate to pain, including the brain,
tion in which pain drives patients to seek medical most of the dura, the ventricles, and the cranium.
attention.1 The wide diversity of causes and the The afferents converge on nuclei in the brainstem
extreme overlap of historical features coupled with where multiple synaptic connections occur includ-
nonspecific physical findings serve to challenge the ing transmission to the ipsi- and contralateral thala-
physician’s ability to diagnose and ultimately relieve mus and the somatosensory cerebral cortex. The
or control patients’ craniofacial pain. However, an thalamic nuclei appear to play a role in the affective
understanding of the different types of craniofacial response to pain, whereas the cortical centers’ role is
pain provides a powerful tool to meet the challenge. in localization and intensity recognition of noxious
stimuli.2 The extensive convergence of afferent neu-
rons in brainstem nuclei, however, limits the brain’s
INNERVATION FOR PAIN ability to distinguish between sources. The result is
Nociceptors serve as the sense organs in which nox- referral of pain to tissues with a past experience rec-
ious stimuli create a response that excites afferent ognized as pain.3 Specific patterns of referral of pain
nerve fibers that provide the brain with information are common; for example, from the TMJ and mus-
about location, intensity, quality, and duration of the cles of mastication, radiation is to the ear, cheek, and
response.2 Neurochemicals responsible for this exci- temple4; from the tonsillar fossa and supraglottic lar-
tation include serotonin and substance P as well as ynx to the middle ear; and from the maxillary sinus
other neurotransmitters. These afferent fibers are to the maxillary teeth, whereas pain from the sphe-
carried to the central nervous system in cranial noid sinus is more often referred to the vertex or
nerves V, IX, X, and XI and the first three cervical occiput, and, of course, angina is sometimes referred
nerves. to the jaw.
Pain-sensitive innervation of facial structures
is extensive, whereas intracranial pain sensation is
limited to specific structures. The extracranial tissues
PATHOPHYSIOLOGY
innervated for pain sensation include the muscles of Multiple mechanisms resulting in excitation of
the head and neck, the scalp and facial skin, nociceptive neurons (ie, generating the perception
sinonasal mucosa and perichondrium, temporo- of pain) are partially understood. One common
mandibular joint (TMJ) synovium and capsule, mechanism is sustained muscle contraction result-
tooth pulp, the external and middle ear, orbital con- ing in tension headache. The exact source of excita-
tents, salivary glands, cervical spine, and craniofacial tion is unclear but may be the result of ischemic
periosteum. Intracranial structures with nociceptive changes or the production of nitric oxide.5 Another
neurons include major arteries, specifically the inter- common scenario is vasodilation of intracranial
nal carotids, vertebral basilars, middle meningeals, arteries stimulating trigeminal sensory pathways,
ophthalmics, and the circle of Willis, and the major which release vasoactive peptides that increase the
venous sinuses. Nonvascular structures with pain pain response.6 The vasodilation seems linked to
nerve fibers are represented by cranial nerves V, VI, subtypes of serotonin 5-hydroxytryptamine (5-HT)
VII, IX, and X and the upper three cervical nerves receptors in vessel walls. Other subtypes of 5-HT
themselves, as well as the pituitary fossa and the base receptors, such as 5-HT1B, yield vasoconstriction
of skull dura mater. The remaining intracranial and inhibit the pain response.7 It is this basis on
788
Headache and Facial Pain 789
which triptan antimigraine agents have their effect example, some migraineurs have been found to
by selectively binding to 5-HT1B receptors. An have defective release of endogenous opiates,10 and
inflammatory mechanism is thought to be respon- lowered cortical pain thresholds occur in chronic
sible when neuropeptides such as substance P are tension headaches.11
released with mucosal inflammation. These result in
neural excitation, resulting in the perception of
pain. 8 Neural inflammation following injury or
CLASSIFICATION
tumor invasion has an excitatory effect. Direct Understanding headache and facial pain is essential
nerve pressure may induce nociceptor activity, as to facilitate diagnosis and treatment. To this end,
seen in foraminal stenosis. Many agents that result definitions and features of clinical syndromes were
in vasodilation can trigger headache including organized by the International Headache Society
hypoxia, carbon monoxide, caffeine withdrawal, (IHS).12 This classification, with inclusion of diag-
acute alcohol withdrawal, oral contraceptives, hypo- nostic criteria for headaches, cranial neuralgias, and
glycemia, and antihypertensive and other vasodila- facial pain, was created in 1988 and has facilitated
tors such as nitroglycerin and monosodium the diagnostic approach and management of cran-
glutamate found in Chinese food.9 Finally, cerebral iofacial pain across many medical fields. Table 35–1
mechanisms are also thought to play a role. For lists the classification of most headaches, neuralgias,
TABLE 35–1. International Headache Society Classification of Headache and Facial Pain
Migraine type Malignant hypertension (accelerated)
Without aura (common migraine) Preeclampsia and eclampsia
With aura (classic migraine)
Nonvascular intracranial disorder
With prolonged aura (complicated migraine)
Benign intracranial hypertension (pseudotumor
Ophthalmoplegic
cerebri)
Retinal
Post–lumbar puncture headache
Tension type Cerebrospinal fluid fistula headache
Episodic (muscle contraction headache) Intracranial infection
Chronic (chronic daily headache) Meningitis
Oromandibular dysfunction (myofascial pain Encephalitis
dysfunction syndrome) (temporomandibular joint Brain abscess
pain dysfunction syndrome) Subdural empyema
Intracranial neoplasm
Cluster (Horton’s cephalalgia)
Headache from substance exposure or withdrawal
Post-traumatic headache
Acute exposure
Vascular intracranial disorder Nitrate- or nitrite-induced headache (hotdog
Transient ischemic attack–associated headache headache)
Intracranial hematoma Monosodium glutamate–induced headache
Subarachnoid hemorrhage (Chinese restaurant syndrome)
Unruptured aneurysm Carbon monoxide–induced headache
Giant cell arteritis (temporal arteritis) Alcohol-induced headache
Carotid or vertebral artery pain Chronic exposure
Dissection Ergotamine-induced headache
Carotidynia Analgesics abuse headache
Cerebral venous thrombosis Oral contraceptives use
Acute arterial hypertension Acute withdrawal
Pheochromocytoma Alcohol (hangover)
Continued
790 Ballenger’s Otorhinolaryngology
and facial pains. Greater detail can be found in the system or systemic complaints (see Table 35–3 for
IHS classification publication. specific serious conditions in which headache is a
presenting symptom16). Warning features of the
headache include sudden onset and highest severity,
PATIENT EVALUATION steady crescendo of intensity, awakening with
History is the essential tool to establish a diagnosis headache, and exacerbation by coughing or strain-
for headache or facial pain. It must be comprehen- ing. Dangerous associated systemic symptoms
sive to ensure accuracy of diagnosis. Once the fea- include fever, sudden vomiting, declining mental
tures of the cephalalgia are discovered, one can refer status, syncope, or seizures. Specific physical ail-
to the IHS classification to determine which specific ments such as stiff neck, tender or enlarged tempo-
diagnostic criteria are fulfilled (Table 35–2).13–15 ral artery, unilateral rhinorrhea, skull percussion
Serious or even life-threatening conditions tenderness, or focal neurologic defects such as visual
associated with headache usually will present with field loss, diplopia, hemiparesis, and facial nerve
distinct characteristics of the headache and nervous palsy should be alarming. Finally, a history of preex-
Headache and Facial Pain 791
Continued
792 Ballenger’s Otorhinolaryngology
isting malignancy or immunosuppression may her- ment recommendations (see Table 35–1 for specific
ald a serious condition.17 conditions in the classification system).
The physical examination is guided by history
and clinical suspicions. Routine measures should
include a check of blood pressure and temperature;
MIGRAINE-TYPE HEADACHES
assessment of mental status and cranial nerve func- Migraines comprise the second most common form
tion; and a visual examination inclusive of pupil size, of headache, with a prevalence of 18% in women
extraocular movement, visual fields, and fundus- and 6% in men and costing billions of dollars for
copy. Range of motion testing of the jaw and neck treatment and lost productivity.18 Its peak age of
should be performed along with palpation of the onset is in the second or third decade, but children
TMJ and muscles of mastication and paraspinal and even infants may also be affected.19 Migraine
musculature searching for trigger points for neuritic headaches usually occur as recurrent episodes of
or muscular pain. Abnormalities may be observed in severe, throbbing, unilateral head pain of sudden
the external or middle ear, the sinonasal passages, onset lasting 4 to 72 hours. However, 40% of
the mouth, and dentition, or herpetic lesions may be migraineurs have bilateral pain. The headache often
seen in dermatomes. Palpation of the temporal strikes after awakening in the morning. In children,
arteries should also be performed. Asymmetric skull migraine headaches usually end between 2 and 48
percussion tenderness may suggest a subdural hours. Routine activities of daily living exacerbate
process. Laboratory testing, including cerebrospinal the symptoms. Coexisting symptoms with the
fluid (CSF), should be limited and guided by clinical headache are common including nausea, vomiting,
impression. Radiologic imaging with computed photophobia, and phonophobia. Stress is the usual
tomography (CT), magnetic resonance imaging precipitating factor. A family history of migraine is
(MRI), or magnetic resonance angiography (MRA) often present.
may be indicated when organic pathology is sus- Migraine is divided into several types: those
pected or to reassure the patient. without aura (formerly common migraine) and those
with aura (formerly classic migraine) are the two
most common by far. Migraine without aura is the
SPECIFIC CLINICAL SYNDROMES most common type. It lacks any preheadache warn-
The characteristic features of many craniofacial pain ing symptoms. Migraine with aura is also common,
diagnoses are presented along with specific treat- comprising 20% of migraine sufferers. The typical
Headache and Facial Pain 793
TABLE 35–3. Life- or Organ-Threatening Causes of pain. Specific feelings include mood changes,
Headaches fatigue, anorexia, or autonomic symptoms such as
diarrhea or frequent urination. The postdrome
Subarachnoid hemorrhage essentially consists of general fatigue, irritability, and
Intracranial aneurysm food cravings or anorexia. The IHS classification
Meningitis requires that the following criteria be met to diag-
nose migraine: For migraine without aura, at least
Encephalitis
five attacks lasting 4 to 72 hours, with at least two of
Major artery dissection the following features present: unilaterally, pulsatile
Giant cell arteritis (temporal arteritis) quality, moderate to severe intensity, and exacerba-
Acute glaucoma tion by physical activity. The headache must be asso-
ciated with nausea, vomiting, photophobia, or
Hypertensive encephalopathy
phonophobia. For migraine with aura, at least two
Carbon monoxide poisoning attacks with at least three of the following must
Benign intracranial hypertension (pseudotumor occur: one or more reversible aural symptoms
cerebri) occurs, the symptom has a gradual onset over more
Cerebral venous thrombosis than 4 minutes, the aura resolves in less than 1 hour,
Preeclampsia and eclampsia
and the time between aura and headache is less than
1 hour.12 Some migraine sufferers will complain of
Cerebral vascular accident aural symptoms and not experience headache.
Mass lesion Treatment of migraine disorders includes initi-
Neoplasm ation of supportive and educational measures such
Abscess as a headache diary to decrease the frequency of
Intracranial hematoma attacks. Medical therapy falls into two major cate-
Cerebrospinal fluid fistula gories: symptomatic and preventive treatment. The
former attempts to abort attacks at their onset or
Adapted from Edlow JA, Caplan LR. Avoiding pitfalls in control pain during the headache. Specific measures
the diagnosis of subarachnoid hemorrhage. N Engl J Med prove useful including the application of ice, isola-
2000;342:29–36.
tion in a dark quiet room, using biofeedback or
Copyright © 2000 Massachusetts Medical Society.
acupuncture, and inducing sleep, as well as avoiding
known triggers (Table 35–4).13,21
aura lasts less than 1 hour and immediately precedes Symptomatic treatment must be individual-
the onset of cephalalgia. It may be precipitated by ized to provide adequate relief with minimal risk
menses, pregnancy, oral contraceptives, certain and side effects. Stratified care for which a variety of
foods, or bright lights. Migraine with prolonged aura treatment choices are available to the patient has
has symptoms of the aura that last through and proven successful.22 Relief should not be limited to
beyond the headache up to 7 days. Features of aura headache but also constitutional symptoms such as
include focal neurologic symptoms including visual nausea and vomiting or insomnia. Factors influenc-
changes such as scotomata or sensory and motor ing choice of drugs should include the frequency
disturbances such as paresthesia, hemiparesis, or that medications will be required, contraindications,
asphasia. Brainstem dysfunction may also occur, route of administration, prior medication successes
resulting in ataxia, lethargy, diplopia, tinnitus, ver- and failures, or the need for breakthrough headache
tigo, or dysarthria. Ophthalmologic and retinal therapy.13 The earlier therapy is initiated, the more
migraine are rare but result in paresis of ipsi- or con- likely a good or complete response will occur. Non-
tralateral oculomotor nerves or monocular blind- specific migraine therapy includes analgesics and
ness secondary to retinal ischemia, respectively.20 judicious use of opiates for only severe attacks. Spe-
Prodromes and postdromes are also common cific therapy uses compounds that are known ago-
features, occurring in approximately 60% of nists of the 5-HT1 receptor and include ergot
migraine patients.13 They experience premonition derivatives and synthetic triptan compounds. Often
phenomena hours to days before the onset of head antiemetics or metoclopramide should be given first
794 Ballenger’s Otorhinolaryngology
to avoid worsening or triggering nausea. To avoid NSAID = nonsteroidal anti-inflammatory drug. Adapted
chronic ergotamine-induced headache, it should not from Saper JR,13 Wilkinson M,21 Silberstein SD and Young
be taken more than 2 days a week.23 In addition WB,23 Young WB,24 Logemann CD and Rankin LM,25 Maizels
M,26 and Finkel AG et al.27
to nausea, angina may be induced by these
compounds; thus, their use in patients with risk of
coronary artery disease is contraindicated (see necessary. Finally, in difficult to treat cases, referral
Table 35–5 for agents available for abortive to a headache center or neurologist is appropriate.
therapy13,21,23–27). For children, Annequin and associates reviewed the
The recurrence rate for headache in a 24-hour use of various agents and found good effectiveness
period is reported for some drugs: intranasal dihy- for both acetaminophen and ibuprofen. Oral dihy-
droergotamine mesylate has a 14% relapse, whereas droergotamine mesylate and sumatriptan in any
triptans relapse between 22 and 45%,25 and form were also effective.19 Opiates should be
intranasal lidocaine relapses 40% of the time.26 It is avoided. Again, abortive therapy should be initiated
important to realize that severe attacks can be so dis- early in the attack.
abling that occasional referral to the emergency Prophylactic therapy is indicated when the fre-
department or admission for pain management is quency of episodes is greater than two per week.
Headache and Facial Pain 795
Dosages should be titrated within recommended occipital region or trapezius muscles. The onset is
levels, and therapeutic trials of any agent should last gradual, whereas the quality is dull, nonthrobbing,
at least 3 weeks. Specific prophylactic agents are and constant, sometimes lasting for weeks. These
listed in Table 35–6.7,19,27–29 Preventive medical ther- headaches typically do not have associated auto-
apy in children has had some success, although fewer nomic symptoms as migraine headaches do,
reports exist. Among specific agents used for chil- although it is possible when the headaches are
dren, propranolol is most frequently used. Other severe. The cephalalgia is triggered or exacerbated by
regimens make use of metoprolol, valproate, flunar- stress or anxiety in most patients. Some evidence has
izine, cyproheptadine, and pizotifen, a serotonin discounted the idea that persistent muscle contrac-
receptor antagonist.19 tion is the cause of the pain. Instead, new theories
suggest an abnormality in central pain control.30 The
subdivision of episodic tension-type headaches, previ-
TENSION-TYPE HEADACHE ously referred to as muscle contraction headaches,
Tension-type headaches include a variety of previ- requires certain diagnostic criteria, specifically at
ously described craniofacial pain conditions such as least 10 prior episodes of headaches less than 15 days
tension headache, stress headache, muscle contrac- a month, lasting 1 half hour to 1 week and having at
tion headache, fibromyalgia, chronic daily headache, least two of the following characteristics: a tighten-
myofascial pain syndrome, and TMJ dysfunction ing quality, mild-to-moderate intensity, bilaterality,
syndrome. This category of headaches is by far the and no exacerbation by routine exertion.30
most common, afflicting approximately 80% of the The other category of tension-type headache is
adult population, but these headaches usually do not chronic and was previously labeled chronic daily
result in a physician evaluation. The IHS delineated headache. Some debate still exists as to whether all
both episodic and chronic varieties of tension-type chronic daily headaches are tension type. The IHS cri-
headaches and noted whether there is an associated teria for chronic tension-type headaches are the same as
pericranial muscle disorder, more specifically, mus- the episodic variety, with the exception that headache
cular tenderness or increased electromyographic frequency is greater than or equal to 15 days per
activity. It is more likely to occur in women, and month for at least 6 months. The IHS also recognizes
usually a family history of headaches is present. The that migraine headaches can transform into a chronic
headaches are characteristically bilateral, with a daily headache with features more similar to tension-
tightening or band-like sensation in the frontotem- type headaches. This may represent an evolution of
poral region around the head and spreading to the the headache process or often is related to overuse of
treating drugs. According to Silberstein and Lipton,
TABLE 35–6. Prophylactic Medications for chronic daily headache must be divided into both
Migraine7,19,27–29 tension type and migrainous type, as well as other
entities.31 They note that the chronic tension type
Antidepressants: amitriptyline, nortriptyline, doxepin, constitutes about 25% of all daily headache patients.
or trazodone Treatment of tension-type headaches uses non-
Ergotamine in a sustained-release form (Bellergal) pharmacologic and medical therapy. First, chronic
medication overuse must be eliminated, a step that
Beta blockers: metoprolol, atenolol, or propranolol will improve many cephalalgia sufferers. Depression
Nonsteroidal anti-inflammatory drugs (NSAIDs): should be treated if present. Nonmedical remedies
naproxen, ibuprofen, or aspirin include reassurance, muscle relaxation, simple mus-
cle exercises, stress management, biofeedback, and
Calcium channel blockers: verapamil, nifedipine,
physical therapy with thermal modulation, ultra-
nimodipine, or flunarizine
sonography, or electrical stimulation. Pharmacother-
Anticonvulsants: divalproex, valproic acid, gabapentin, apy varies between episodic and chronic varieties.
or topiramate Most patients who suffer episodic tension-type
headache will respond to analgesics, such as aspirin
Others: methysergide, fluoxetine, cyproheptadine,
or nonsteroidal anti-inflammatory drugs (NSAIDs).
pizotifen, riboflavin, or lithium
Antidepressants, especially amitriptyline, have also
796 Ballenger’s Otorhinolaryngology
proven effective. Agents capable of fostering depend- noted.33 The etiology is unclear, but several mecha-
ence are best avoided. These include caffeine, opiates, nisms are suspected. Circadian hormonal fluctua-
and benzodiazepines. tion suggests a hypothalamic dysfunction, whereas
The use of medications in the management of excitation of a nerve plexus in the carotid sheath and
chronic tension-type headaches is more diverse. adventitia may increase trigeminal discharge rates,
Injection of local anesthetics into trigger points may resulting in facial pain.34 A subset of patients
provide sustained relief.32 Amitriptyline has been demonstrate an autosomal dominant transmission
used most often, with proven success.31 Sodium val- in their families.
proate, topiramate, L-5-hydroxytryptophan, and L- Variants of cluster headache also occur. Sluder’s
arginine have also been used with reported success. “lower half ” neuralgia refers to cluster headaches
Injection of botulinum toxin (Botox) into pericra- limited to the maxillary area with autonomic symp-
nial muscles has recently been shown to be safe and toms.34 It is more common in women in their thir-
effective, although the mechanism of relieving pain ties and forties. Chronic paroxysmal hemicrania
is poorly understood.31 (Sjaastad’s syndrome) is a variant with shorter, more
frequent attacks, occurs more often in women, and
is absolutely responsive to indomethacin.12 SUNCT
CLUSTER HEADACHES syndrome (an acronym for short-lasting unilateral
Cluster headaches, previously known as Horton’s neuralgiform headache attacks with conjunctival
cephalalgia, are less common than tension-type or injection, tearing, sweating, and rhinorrhea) is a
migraine-type headaches; however, the severity of the cluster-like headache, mostly in men, in which
headaches is much greater. They affect men more attacks last 10 to 60 seconds. It may be precipitated
often than women. They are unilateral, excruciating, by touch to the nose or periorbital area, chewing, or
and located around the eyes or in the maxilla and usu- ingestion of citrus fruits.35
ally occur in middle age. The episodes typically last Treatment of cluster headaches has abortive
minutes to 3 hours. They tend to occur several times measures and prophylactic therapy. Along with pro-
per day for several weeks, and then long headache- viding reassurance for the patient, episodes can be
free periods occur; hence, they occur in clusters. Ten ended with inhalation of 100% oxygen for 10 min-
percent of patients will have chronic episodes. No utes. Administration of ergotamine sublingually or
aura or nausea occurs, but the cephalalgia is associ- rectally works within 1 hour. Dihydroergotamine
ated with unilateral lacrimation, rhinorrhea, and intramuscularly or intravenously provides relief in 30
injected conjunctiva. Ptosis and miosis may also minutes or 10 minutes, respectively. Sumatriptan
occur. The headaches often wake a patient at the same works best when given subcutaneously, taking about
time each night. Typically, the patient “searches for 10 minutes to take effect. These four agents all work
relief” by pacing or rocking back and forth. Alcohol by inducing a central vasocontriction.33 Intranasal 4%
and histamine injections are capable of precipitating lidocaine may also be effective. At least three episodes
attacks, and attacks are more common in the spring of cephalalgia should be treated with any one agent
or fall.33 The IHS classification of cluster headaches before declaring it a failure and moving to another
requires meeting the following diagnostic criteria: at agent. Analgesics are too slow to be effective, and cor-
least five episodes of classic cluster headache (charac- ticosteroids have not been proven to be beneficial.
teristics as outlined above) occurring with a frequency Prophylactic medications are the mainstay of
of every other day up to eight times per day.12 treatment. In general, they should be used during
Intracranial lesions, associated with the cav- the months when the cluster headaches are occur-
ernous sinus or in other locations, as well as viral ring and gradually discontinued after at least a 2-
meningitis and skull base invasion by nasopharyn- week headache-free period.34 Effective prophylaxis
geal carcinoma, may produce cluster-like headaches has been achieved with a variety of agents and is
that are more apt to be chronic. Therefore, a patient most often achieved using calcium channel blockers
with atypical features of cluster headache should such as nifedipine or verapamil, low-dose ergota-
raise suspicions of an organic lesion, especially when mine in sustained-release form, lithium carbonate,
periodicity of headaches is lacking or an incomplete and methysergide for no greater than 4 months to
response to known efficacious medications is avoid the rare complication of retroperitoneal fibro-
Headache and Facial Pain 797
sis. Multidrug therapy may be necessary. Cortico- headache as a presenting symptom. It is moderate to
steroids over 3 to 4 weeks may be helpful. Newer severe and on the side of the hematoma. Ipsilateral
approaches have studied valproate, intranasal cap- skull tenderness to percussion is common. Hemo-
saicin, pizotifen, and phototherapy with bright light, tympanum or mastoid bruising may occur. Associ-
with all finding significant success. Histamine desen- ated symptoms include altered level of consciousness
sitization may offer relief to patients with chronic and sometimes nausea and vomiting, as well as focal
cluster headaches refractory to treatment.33 Invasive central nervous system changes. There is usually an
approaches for refractory cases include trigeminal antecedent history of head trauma, although the
nerve blockade and blockade of the sphenopalatine trauma may be temporally remote. Anticoagulated
ganglion. The most effective procedure for typical patients may relay only minor head bumps. Diagno-
cluster headache is radiofrequency ablation of the sis is confirmed by CT of the head. Treatment typi-
trigeminal ganglion.34 When sphenopalatine gan- cally involves a craniotomy for drainage, but
glion (Sluder’s) neuralgia is the diagnosis, removal spontaneous resolution may occur over time. Once
of a precipitating septal spur or coagulation of the the hematoma is resolved, the headache ceases to
ganglion may be beneficial. occur.
formed next if the CT was negative for blood or untreated patients. This is secondary to involvement
mass effect. Abnormal findings include elevated CSF of the ophthalmic artery. Prednisone is the drug of
pressure and red blood cells in the CSF. As traumatic choice and should be administered in high daily
taps may lead to the presence of red blood cells, their doses of 60 mg. Pain reduces dramatically within
presence should be correlated with the CSF pressure. days. Once headache has gone into remission and
Xanthochromia is a much more specific finding for the ESR corrects, prednisone can be tapered over a
subarachnoid hemorrhage. If any test indicates that period of weeks to a daily maintenance dose of 5 to
a subarachnoid hemorrhage has occurred, angiogra- 10 mg while continuing to check for a rise in the
phy and neurosurgical consultation are warranted ESR.38 Often treatment must be continued for sev-
urgently for treatment of the aneurysm or arteriove- eral years to avoid the complication of blindness.15
nous malformation. Radiographically detected Sometimes the segmental excision of the temporal
unruptured aneurysms and vascular malformations artery relieves the patient of localized tenderness.
should also receive neurosurgical evaluation to pre- However, this does not preclude the need for treat-
vent catastrophic hemorrhage.37 ment with corticosteroids.
Giant Cell Arteritis Giant cell arteritis, often called Carotid Artery Pain Carotid artery pain may
temporal arteritis, is associated with polymyalgia occur secondary to dissection or idiopathic carotidy-
rheumatica. Essentially, they are different manifesta- nia or after endarterectomy. Carotid artery dissec-
tions of the same condition. The cause is unknown, tion is characterized by head and neck pain on the
but speculation relates immune responses, infectious side of the condition following trivial trauma in a
triggers, and genetic susceptibility.38 The condition young or middle-aged patient. It may cause referred
mostly affects women over 50 years of age. It presents otalgia,39 Horner’s syndrome, lower cranial nerve
as a new-onset, daily, intermittent or continuous, palsies, and pulsatile tinnitus. Hours later, signs of
temporal localized headache that is moderate to cerebral or retinal ischemia develop.40 Dissection can
severe, burning sharp or throbbing, unilateral or be demonstrated by ultrasonography, MRI with
bilateral and lasts months to years.17 MRA, intra-arterial angiography, or surgical find-
Patients with giant cell arteritis complain of ings. For treatment, early anticoagulation is essential
aching of the jaw during chewing, weight loss, gen- to avoid the 15% risk of mortality. This is followed
eralized fatigue, and low-grade fever and often have by warfarin for 6 months. If ischemic signs persist
extremity pain attributable to coexistent polymyal- after acute heparinization, surgical intervention may
gia rheumatica. Visual symptoms include blurring, be warranted.40 Carotidynia is a self-limited inflam-
scotomata, and even sudden blindness. Physical mation of the carotid fascia or adventitia. It may be
findings consist of palpably thickened or tender induced by viral infection. Physical findings include
scalp arteries that may have a diminished or absent carotid tenderness, swelling, or intense pulsations.
pulse. Palpation of muscle does not reveal trigger Structural evaluation of the artery is normal. Treat-
points, and muscle strength is typically normal. An ment with NSAIDs may alleviate the pain until
erythrocyte sedimentation rate (ESR) is almost spontaneous resolution occurs.
always elevated over 50 mm per hour in patients
with giant cell arteritis. If the diagnosis is suspected, Arterial Hypertension Arterial hypertension can
a temporal artery biopsy is essential to confirm the be acute or chronic. Chronic hypertension is not
diagnosis. Inflammation in the artery is often seg- typically associated with headache. On the other
mental; therefore, a 5 cm long segment of artery hand, acute hypertension certainly may cause cepha-
should be excised; even then, false negatives may lalgia. The acute rise in blood pressure can be sec-
occur.38 Histologic examination of involved vessels ondary to administration of pressors, vasoactive
reveals necrosis in the vessel’s media with infiltration glomus tumors including pheochromocytoma,
of macrophages and giant cell formation. Color malignant hypertension (including hypertensive
duplex ultrasonography is being investigated as a encephalopathy), or preeclampsia and eclampsia.
diagnostic tool to potentially replace biopsy. Treat- Typically, headache begins with diastolic pressures
ment should begin immediately to avoid sudden greater than 115 mm Hg. It is throbbing, associated
blindness, a complication found in up to 30% of with nausea, and does not respond to analgesics.27
Headache and Facial Pain 799
Treatment involves controlling and correcting the puncture or CSF fistula. The headache appears or
source of the hypertension. Once this is achieved, the worsens when the head is upright and resolves after
headache resolves within 7 days.12 lying down. The pain is constant when the head is
upright and is located in the occipital region or ver-
HEADACHE ASSOCIATED WITH NONVASCULAR tex. Nausea is common, and vomiting relieves the
headache during the regurgitation. Oculomotor or
INTRACRANIAL DISORDERS abducens palsies have been reported. Resolution is
The IHS classifies six intracranial conditions as non- rapid (usually within several days) following lumbar
vascular causes of headache. The symptoms, signs, puncture unless a persistent fistula occurs at the tap
and diagnostic investigations of four of these are site. If this is suspected, a blood patch of the epidural
presented below. space at the site of puncture is curative. This condi-
High CSF pressure associated headache may be tion may occur without lumbar puncture and
caused by benign intracranial hypertension, formerly should raise suspicions of post-traumatic, iatro-
known as pseudotumor cerebri or otitic hydro- genic, or spontaneous CSF fistula. If this occurs, site
cephalus, and high-pressure hydrocephalus that identification by intrathecal metrizamide CT or
sometimes follows head trauma. Benign intracranial myelography should be performed and a surgical
hypertension is defined by the findings of papil- repair initiated.
ledema: an otherwise normal neurologic examina- Intracranial infection includes meningitis,
tion (with a rare exception being abducens palsy); no encephalitis, brain abscess, or subdural empyema,
intracranial mass, venous sinus thrombosis, or ven- which may present with a generalized, bilateral,
tricular enlargement on head CT or MRI; a normal severe, constant headache often with nuchal rigidity,
protein, white cell count, and culture in the CSF; and, positive Kernig’s and Brudzinski’s signs, and fever.
most importantly, an increased intracranial pressure The onset is rapid, usually over several hours.17
of greater than 200 mm of water on lumbar puncture Ambiguous presentations may occur in immuno-
or intraventricular pressure monitor.12 The associated suppressed patients, atypical infections such as
headache is intermittent, retro-orbital, with gradual tuberculosis, fungal meningitis, neurosyphilis, or
worsening, and is exacerbated by coughing or Val- epidural abscess. If a head CT has ruled out an
salva’s maneuver. Associated symptoms include uni- intracranial mass, culture and antigenic studies of
lateral or bilateral pulsatile tinnitus,41 visual dimming CSF from lumbar puncture are diagnostic.27 Treat-
occurring for a minute or two at a time, eventual ment requires appropriate intravenous antibiotic
constriction of visual fields, and possible blindness. It therapy and surgical drainage of abscesses.
may be triggered by otitis media or mastoiditis, irreg- Primary or metastatic intracranial neoplasms
ular menses, recent rapid weight gain, corticosteroid present with discrete or generalized, intermittent or
withdrawal, or ingestion of vitamin A, tetracycline, continuous, mild to moderate, unilateral, dull
or nalidixic acid. Treatment consists of weight reduc- headache that worsens over time in 30% of patients.
tion, a low-sodium diet, and diuretics, specifically Early morning headache is a warning symptom, as is
acetazolamide or furosemide. Lumbar puncture can exacerbation by Valsalva’s maneuver or cough. Sud-
be used and repeated to reduce CSF pressure acutely den vomiting, cranial nerve dysfunction, and
to relieve headache. Cerebrospinal fluid diversion by seizures may occur.17,27 Control of pain may be ini-
a ventriculoperitoneal shunt may be necessary for tially achieved with non-narcotic analgesics, but,
refractory cases or when visual fields fail to eventually, narcotics or neuralgia medications
improve.27 Transnasal, transethmoidal optic nerve become necessary. Removal of the neoplasm, when
decompression with release of the optic nerve sheath feasible, is usually curative of the headache.
and annulus of Zinn may also be necessary to correct
chronic visual field disturbances. High-pressure HEADACHE ASSOCIATED WITH SUBSTANCES OR
hydrocephalus differs from benign intracranial hyper-
THEIR WITHDRAWAL
tension by the identification of enlarged ventricles on
head CT or MRI. Headaches are often caused by ingestion or with-
Low CSF pressure also commonly precipitates a drawal of specific substances. The onset of a
headache. This may be in response to a lumbar headache during carbon monoxide poisoning and
800 Ballenger’s Otorhinolaryngology
the hangover after drinking alcohol serve as prime nia, and tremor. Persistent abstinence is the main-
examples. Several particular conditions warrant stay of treatment but may require hospitalization to
greater description. Headache induced by chronic prevent the patient from consuming more of the
intake or withdrawal after chronic use of some med- offending medication.
icines is a common phenomenon. Patients typically
have a history of a different type of headache, usu- HEADACHES ASSOCIATED WITH A METABOLIC
ally migraine, in the past that did not occur daily.
Escalating regular use of acute headache remedies to
DISORDER
greater than 2 days per week may “transform” Hypoxia, as seen in high-altitude headache, is a
migraine into a chronic daily headache.42 The cepha- known source of cephalalgia. Descent and oxygen
lalgia occurs daily (often early in the morning) and therapy are the treatment. A more common cause of
is generalized, bilateral, dull, and of moderate sever- chronic hypoxia is found in sleep apnea syndrome,
ity. It may be associated with nausea and be brought in which morning headache is common. It is diffuse,
on with mild exertion. Tolerance to the offending dull, and mild and may be associated with short-
analgesic seems to allow less and less relief to the term memory loss and inability to concentrate. The
patient, resulting in the use of increased dosages. diagnosis is suggested by more significant symptoms
Finally, headache-free intervals cease to exist. Both of the syndrome, specifically fatigue, daytime som-
ergotamine and dihydroergotamine have been nolence, and apneas witnessed by a bed partner. Res-
implicated, as have non-narcotic and narcotic anal- olution of the headache occurs quickly following
gesics. Common examples include aspirin, aceta- correction of the hypoxia by continuous positive
minophen, NSAIDs, barbiturates, codeine, hydro- airway pressure or surgical intervention.
codone, oxycodone, and propoxyphene. The IHS
noted that use of ergot derivatives for 3 months puts HEADACHE OR FACIAL PAIN ASSOCIATED WITH
the patient at risk, as does taking more than 50 g of
aspirin or more than 100 tablets of an analgesic per
CRANIOFACIAL OR CERVICAL DISORDERS
month. Resolution within a month after discontinu- When pathology afflicts any extracranial organ of
ing the substance is typical. the head or the skull itself, pain may ensue. Facial or
Treatment requires understanding on the part head pain is localized to the affected structure but
of the patient along with complete elimination of the may radiate or be referred. If the pathology is cor-
problem medication for at least 2 months. No substi- rected, headache resolves in less than 1 month.
tution to another analgesic should occur. Avoidance Examples affecting the cranial bones include
of tyramine and caffeine in the diet is recommended, osteomyelitis, multiple myeloma, and Paget’s disease.
whereas use of antidepressants is recommended and Cervicogenic headache is a relatively common
helpful. Nonpharmacologic modalities should be condition created by a disorder afflicting the cervical
employed, more specifically, biofeedback, transcuta- spine, often following neck trauma. Women are
neous electrical nerve stimulation (TENS), and phys- more frequently affected than men. It is character-
ical therapy. Inpatient withdrawal may be necessary. ized by fluctuating or constant headache that is uni-
Prophylactic therapy for the primary headache should lateral, unchanging, dull, and nonpulsatile. It tends
also be instituted to decrease the need for ongoing to start at the occiput and radiate to the frontal
abortive medications. region, where the pain is most intense. If it is bilat-
Headache from withdrawal of a chronically eral, one side is usually of worse intensity. Pain may
used substance may also occur. It typically follows a also radiate into the shoulder or arm. Attacks are
period of abstinence from the agent of less than 12 precipitated by awkward positions or neck move-
to 48 hours and is relieved by ingestion of the sub- ment or palpation of trigger points such as the
stance. Persistent elimination of the substance allows greater occipital nerve or over the C2 vertebral
resolution of the headache within 14 days. Frequent body.43 Associated symptoms of nausea and photo-
examples consist of caffeine, ergot derivatives, and phobia or phonophobia are present in 50% of
narcotics.12 The headache is diffuse, dull, and mild to patients. Neck examination reveals a reduced range
moderate in severity. It may be associated with nerv- of motion of the spine and possibly muscle tender-
ousness, restlessness, nausea and vomiting, insom- ness, spasm, hypertrophy, or atrophy. Criteria for its
Headache and Facial Pain 801
diagnosis have been proposed by Sjaastad and uncertain diagnosis of sinusitis or to evaluate
Fredriksen.44 These criteria essentially define all of response to treatment. As plain films have poor sen-
the features of the syndrome as represented above. sitivity, a screening coronal sinus CT has become the
Cervical radiographic data reveal either abnor- imaging study of choice. Treatment requires medical
malities on flexion and extension films, abnormal therapy to reverse the inflammatory cause of the
posture, or evidence of bone or joint pathology. Ipsi- headache and includes antibiotics, decongestants,
lateral injection of local anesthetics for blockade of and possibly corticosteroids, with analgesics used in
the greater occipital nerve or the C2 root will relieve the interim for symptomatic relief until the sinusitis
pain not only in the innervation zones but also in is reversed.
the frontotemporal region.44 Treatment centers Rhinologic headaches other than those caused
around physical therapy and stretching exercises, use by sinusitis also occur, albeit much more rarely.
of NSAIDs, and chronic nerve blockade for refrac- Nasal anatomic abnormalities occasionally associ-
tory cases. ated with facial pain include impacted septal devia-
Sinonasal disorders are a frequent source of tions or spurs, hypertrophic turbinates, and even an
headaches but are probably overcredited by the pop- occasional large maxillary retention cyst.3 However,
ulation as a whole. However, frontal headache and most sinonasal neoplasms do not cause pain. The
facial pain are two of the three major symptoms sug- cause of rhinogenic pain may be related to direct
gesting the presence of sinusitis, the other being sensory stimulation from two mucosal surfaces con-
purulent nasal drainage. Acute sinusitis is a leading tacting each other. The pain is usually dull and
cause of facial pain, second only to dental disorders. aching and unilateral. An anatomic abnormality can
The IHS classified headache from sinus origin as be seen on examination after decongesting the nose.
when it is associated with purulent drainage and Topical lidocaine can be used as a diagnostic test as
they begin together; when plain radiography, CT, the pain should diminish or disappear after appli-
MRI, or transillumination reveal opacification or cation if the cause is mucosal contact. Medication
air-fluid levels in one or more sinuses; and when the may effectively control turbinate hypertrophy, but
sinusitis is treated, the headache resolves.12 The surgical approaches are effective in managing the
cephalalgia is pressure-like or dull, of moderate anatomic defects.39
intensity, unilateral or bilateral, periorbital, wors- Elongated styloid process, better known as
ened by bending or with Valsalsa’s maneuver, worse Eagle’s syndrome, consists of recurrent throat and
in the morning, and associated with purulent nasal neck pain exacerbated by swallowing. Otalgia, dys-
drainage, nasal obstruction, altered sense of smell, phagia, and foreign-body sensation are often present
exacerbating asthma, cough, malaise, and dizziness. and are secondary to an elongated styloid process
Nausea and visual change are infrequent associated impinging on the carotid plexus or branches of cra-
symptoms.8,39,45 nial nerve IX. It may develop subsequent to tonsil-
Pain with the inflammatory process lasts days lectomy because of inflammatory changes. Palpation
or weeks with fluctuating severity. The location and of the styloid process in the tonsil fossa exacerbates
extent of the sinusitis do not correlate well with the the dull pain, whereas injection of a local anesthetic
severity or site of pain.45 However, a few tendencies in a diagnostic maneuver provides relief. A lateral
are common. The area overlying an infected sinus is plain film of the head reveals a styloid process
often tender. Pain for sinusitis referred to upper greater than 2.5 cm long.46 Reassurance and medical
maxillary teeth is typically originating in the maxil- therapy with NSAIDs or corticosteroid injection
lary sinus. Occipital or vertex pain from sinusitis is around the stylohyoid ligament may be successful.
most likely to represent sphenoid sinus disease. Any Otherwise, treatment involves surgical shortening of
infected sinus can refer pain to the frontal, retro- the calcified stylohyoid ligament (elongated styloid
orbital, and temporal regions. Physical examination process) through the tonsillar fossa.39
finds tenderness to percussion over involved sinuses. A burning sensation in the oral mucosa is an
Transillumination is infrequently useful to delineate uncommon but not rare complaint. The condition is
the presence of sinusitis. Other physical findings known as glossodynia, burning mouth syndrome, or
center around inflammatory changes in the nose. oral dysesthesia. It most often occurs in women and
Radiographic imaging is helpful to confirm an is chronic, with a prevalence of about 5%.47 Local,
802 Ballenger’s Otorhinolaryngology
systemic, and psychogenic factors play a role in cau- graphic series may reveal a joint abnormality. The
sation. Local factors include mucosal lesions, oral usual indications for imaging include suspected frac-
candidiasis, local chemical irritation, and xerosto- tures, degenerative joint disease, ankylosis, or tumors.
mia. Systemic factors consist of iron, zinc, or vita- Management of TMJ disease includes reassur-
min B12 deficiency and the use of female replacement ance, education, NSAIDs, restriction of jaw opening,
hormones, sedatives, antihypertensives, or antide- a soft diet, and physical therapy. Occasionally,
pressants. Anxiety and depression are associated biofeedback or corticosteroid injection may be help-
with glossodynia. Physical examination is usually ful. If pain is chronic, tricyclic antidepressants may
normal without a mucosal lesion. Treatment be beneficial. Because of the potential for depend-
includes reassurance; discontinuing smoking and ency in chronic conditions, narcotics are best
alcohol-containing mouthwashes; drinking cooler avoided. Acute disk or condylar displacements may
coffee; therapeutic trials of nystatin oral rinse or require manual reduction to relieve pain and restore
dexamethasone solution to rinse and expectorate; range of motion or relieve a joint locked open or
iron, zinc, or vitamin B12 replacement therapy; oral closed. Often sedation or general anesthesia is nec-
lubrication or use of salivary stimulants; and using essary to relax the muscles to facilitate the manual
antidepressants. reduction. The use of a bite appliance may alleviate
Temporomandibular joint disorders are frequent chronic headache or muscle pain secondary to brux-
causes of facial pain and headache. These disorders ism or joint pain secondary to anterior disk dis-
are divided into two major groups: those with placement.48 Arthrocentesis, sclerotic therapy, and
demonstrable organic disease (uncommon) and arthroscopic surgery are reserved for chronic dislo-
those of myofascial origin from masticatory muscles cations, disk derangements, or condylar anomalies.
(very common). The IHS established the following Oromandibular dysfunction involves pain in the
diagnostic criteria for TMJ disease, at least two of TMJ without organic disease. Other terms describing
which must be met: pain with jaw motion, noise this condition include myofascial pain dysfunction
with jaw movement, decreased range of motion, and syndrome and TMJ pain dysfunction syndrome. The
a tender joint. These are associated with abnormal etiology of pain seems to have its origin in myofascial
TMJ radiographs and pain that is mild to moderate tissues or central processes disinhibiting sensory pain
and centered over the TMJ.12 Women are far more pathways. The IHS system classified this as a tension-
likely to suffer from TMJ pain. The pain is located type headache that does not purely meet the criteria of
preauricularly and in the temporal region of the episodic or chronic tension-type headaches. A diagno-
head; is intermittent, lasting hours to days; is mild to sis requires at least three of the following: the creation
moderate in intensity; can be unilateral or bilateral; of noise with jaw movement, limited range of motion,
and is exacerbated by jaw movement. Associated fea- pain during jaw use, locking of the jaw, or a history of
tures include otalgia, bruxism, trismus, TMJ crepi- clenching or grinding of the teeth.12 The pain is typi-
tus, and jaw locking. Usually, no muscular trigger cally a continuous, dull, aching, poorly localized, usu-
point exists, and there are no nausea or visual ally unilateral discomfort of mild-to-moderate degree
changes. Etiology of the discomfort includes dis- involving the ear, angle of the jaw, and temple. The pain
eased joints that can occur on the basis of arthritis rarely wakes the patient, and the location of pain may
(the most common cause), traumatic causes such as shift. The patterns of referred pain often do not make
fractures or dislocations, internal derangements of neurologic sense. It may be associated with swelling,
the intra-articular disk, or developmental defects. numbness, stiffness, or erythema. The hallmarks of this
Physical findings include audible joint clicking myalgia are the presence of trigger points that, when
on one side or both and decreased range of motion. palpated, reproduce the referred pain.49 Examination
Normal vertical opening between central incisors will reproduce the pain when masticatory and neck
ranges from 42 to 55 mm.17 Palpation should cover muscles are palpated. Full range of jaw motion may be
the head and neck musculature and TMJs including lost with this disorder. A trigger point injection of an
intraoral pterygoid palpation, noting any asymme- anesthetic (like 1% procaine) can confirm that point’s
try, tenderness, spasm, hypertrophy, atrophy, trigger- significance by relieving the pain.49
ing of referred pain, or crepitus when opening or Therapy consists of reassurance, modification
closing. If pathology is suspected, a TMJ radio- to a soft diet, physical therapy, trigger point local
Headache and Facial Pain 803
anesthetic injection, and medications. Amitriptyline of involved nerves may be paretic. The pain subsides
for at least 2 months is an effective choice, whereas within 6 months of the onset, but the motor palsies
NSAIDs may or may not be. Occlusal splints reliev- have a poor prognosis for complete recovery. Treat-
ing bruxism may help, as might attention to abnor- ment of the acute phase consists of a 10-day course
mal occlusal factors that can precipitate the of prednisone and acyclovir. Nonsteroidal anti-
disorder.32 Because of the self-limited nature of the inflammatory drugs or opiates may be necessary to
condition, invasive approaches should be avoided. control pain. Acute herpes zoster is common in lym-
phoma patients, so a new outbreak should raise sus-
picions about that possible comorbidity.
CRANIAL NEURALGIAS Chronic postherpetic neuralgia exists when her-
Cranial neuralgias are conditions affecting nerves pes zoster pain persists for more than 6 months. It
with sensory functions in the head and neck, result- remains in the distribution of the originally afflicted
ing in severe stabbing or throbbing pain in the dis- nerve. It is more likely to occur in patients who are
tribution of the involved nerve. They can involve any over 60 years old when the acute infection starts, and
cranial nerve with sensory fibers or cervical roots in this group, it is less likely to spontaneously resolve.12
one, two, or three. The conditions are subdivided Nonsteroidal anti-inflammatory drugs and opiates fail
into persistent painful disorders and paroxysms of to relieve the neuralgia. Instead, anticonvulsants are
pain (tic-like) disorders. more effective and may be paired with tricyclic anti-
Traumatic injury to a nerve or inflammatory depressants or baclofen to enhance their efficacy.
changes can result in chronic neuralgia. Trauma or Other inflammatory neuralgia syndromes
surgery to the cranium or face may result in entrap- include the following: (1) Tolosa-Hunt syndrome:
ment neuritis or formation of a neuroma, typically 2 episodic unilateral orbital pain with palsies in one
to 6 months later. The occurrence is greatest in the or more of cranial nerves III, IV, and VI. Episodes
third branch of the trigeminal nerve because of the last about 8 weeks untreated but generally resolve
frequency of injury related to mandible fracture or within 3 days after starting corticosteroids. It has
tooth extraction. Symptoms include hypersensitiv- been related to granulation tissue at the cavernous
ity and pain to light touch, pain in an area of skin sinus or superior orbital fissure or in the orbit.12 (2)
that has lost its sensory innervation, and aggravation Gradenigo’s syndrome: progressive, intense, unilat-
by cold or emotional duress. The pain is sharp and eral, retro-orbital pain with abducens palsy and
lancinating. A central cause of a neuritic pain can otorrhea secondary to petrous apicitis of the tempo-
occur as anesthesia dolorosa following surgical abla- ral bone. (3) Raeder’s paratrigeminal neuralgia:
tion of the trigeminal ganglion. The condition is retro-orbital pain with intact trigeminal sensation
characterized by sharp pain and numbness in the and an incomplete Horner’s syndrome, resulting in
distribution of any or all branches of the trigeminal an ipsilateral dilated pupil. The paratrigeminal space
nerve after trigeminal rhizotomy or trauma. Treat- housing the gasserian ganglion of cranial nerve V,
ment uses anticonvulsant medications, in particular, cranial nerves III and IV, and the carotid artery may
carbamazepine, or sometimes baclofen or clon- be encroached on by abnormal vascular structures
azepam. Amitriptyline has also been employed with and produce the syndrome.9
success.36 Injection of local anesthetics into trigger Trigeminal neuralgia (TGN), previously called
points or surgical resection or repair of neuromas is tic douloureux, is the most common cranial neural-
necessary for refractory cases. gia and most often affects adults over 50 years old
Inflammatory conditions are also well known and women more than men. Typically, recurrent
to cause neuralgia. A prime example is acute herpes episodes of unilateral, excruciating, stabbing pain
zoster of a branch of the trigeminal nerve, the sev- occur most often in the distribution of the maxillary
enth cranial nerve, or cervical roots. The ophthalmic and mandibular branches of the trigeminal nerve.
branch of cranial nerve V is the most commonly During an episode, ipsilateral twitching may
involved nerve. An intense burning or stabbing pain occur—hence the name “painful tic.” They occur
is in the distribution of the involved nerve and is fol- without warning, while patients are awake, and recur
lowed within 1 week by a herpetic eruption in the several to many times a day, with each episode last-
skin distribution of the same nerve. Motor divisions ing seconds to minutes. Numbness does not occur.
804 Ballenger’s Otorhinolaryngology
Light touching of the face may precipitate an attack, superior laryngeal nerve affecting the cricothyroid
as can movement of the trigger zone by talking, muscle. Injection of local anesthetic as a nerve
chewing, or shaving. Physical findings include an blockade confirms the diagnosis when pain is
intact neurologic examination and the presence of a relieved.39 The condition is managed with anticon-
trigger zone most often located in the nasolabial fold, vulsants as in TGN or with surgical sectioning of the
lips, or gums. Diagnostic evaluation should include superior laryngeal nerve.
an MRI of the head and a lumbar puncture if the Occipital neuralgia is a paroxysmal stabbing
MRI is normal. The former is to rule out central aching pain over the occiput in the distribution of
causes including vascular anomalies or aneurysm, the greater or lesser occipital nerve combined with
tumor, cholesteatoma, or multiple sclerosis (MS). reduced sensation in the same area. Associated
Patients with MS are predisposed to TGN, and 2% of symptoms include visual disturbances, dizziness,
patients with TGN have multiple sclerosis.17 The lat- nausea, tinnitus, and scalp paresthesias. The physical
ter is to rule out MS, neurosyphilis, and cryptococcal findings include a positive Tinel’s sign or palpable
or tuberculous meningitis. Treatment of idiopathic tenderness of the involved occipital nerve.50 Confir-
TGN includes patient education and reassurance mation of the diagnosis is made by obtaining relief
with pharmacologic control. Carbamazepine will from pain after an injection of local anesthetic is
provide symptomatic relief acutely in the majority of performed to block the nerve. Management consists
patients.17 Other agents shown to be effective include of heat, physical therapy, rest, TENS units, NSAIDs,
gabapentin, phenytoin, baclofen, sodium valproate, baclofen, or carbamazepine. Cervical collars are of
and chlorphenesin. Any drug should be employed for questionable benefit. Invasive measures for refrac-
at least 2 weeks, and medications may be used in tory cases include local blockade with bupivacaine
combination. Tricyclic antidepressants and NSAIDs in combination with an injectable corticosteroid,
may also be beneficial. Surgical radiofrequency abla- alcohol blockade, or even nerve section.50
tion, specifically trigeminal rhizotomy, is recom-
mended for patients refractory to medical therapy, UNCLASSIFIABLE FACIAL PAIN (ATYPICAL
whereas temporary blockade may be indicated for
patients experiencing intense activation of the dis-
FACIAL PAIN)
ease. See Chapter 20 for vascular compression syn- Atypical facial pain fails to fit the profile of any specific
dromes and their management. craniofacial condition. The prosopalgia (facial pain) is
Glossopharyngeal neuralgia is a disorder similar unilateral or bilateral, is located in the face and upper
to TGN but affecting cranial nerve IX instead. Men neck, and is a constant ache or burning with excruci-
in their forties or fifties are more likely to have this ating exacerbations. It does not localize to anatomic
disorder. The pain characteristics include repetitive, regions or have relation to specific structures as TMJ
brief attacks of lancinating pain located in the soft arthralgia or myofascial pain does. It lasts for years, is
palate, base of the tongue, pharynx, and ear. The exacerbated by stress, and is associated with paresthe-
trigger point is located in the tonsil fossa and can be sias of the face or mouth.17 Comorbidities include
provoked by swallowing or yawning. Associated chronic fatigue, depression, personality disorders, irri-
symptoms may include hiccoughing, nausea, vertigo, table bowel syndrome, and other idiopathic pain dis-
tinnitus, aural fullness, hearing loss, dysgeusia, orders. The cause is unknown, but theories propose
bradycardia, and syncope. Evaluation and manage- central causes for which neuroregulation of pain input
ment are identical to those for TGN.39 is disinhibited, systemic causes for which tyramine
Superior laryngeal neuralgia is characterized by metabolism is deficient,51 and psychogenic causes for
unilateral lancinating attacks of pain at the side of which personality disorders are linked to the develop-
the larynx over the thyrohyoid membrane. Pain ment of chronic pain conditions.
radiates to the ear and submandibular region and is Treatment involves a multidisciplinary ap-
precipitated by swallowing, straining the voice, play- proach. Each patient should be reassured, receive only
ing a musical instrument, or turning the head. The essential dentistry, and sparingly use analgesics. Tri-
pain paroxysms last minutes to hours for days or cyclic antidepressants are the mainstay of therapy;
weeks at a time. Dysphonia may be present second- they should be taken at night and titrated up to a
ary to involvement of the external branch of the desired response. Other options include serotonin
Headache and Facial Pain 805
reuptake inhibitors, monoamine oxidase inhibitors, 15. Lance JW. Headache and face pain. Med J Aust
benzodiazepines, and phenothiazine. Once a good 2000;172:450–5.
response has occurred, therapy should be maintained 16. Edlow JA, Caplan LR. Avoiding pitfalls in the diag-
until the patient has been pain free for several months nosis of subarachnoid hemorrhage. N Engl J Med
before it is discontinued.51 Psychiatric evaluation may 2000;342:29–36.
be beneficial. Refractory cases might respond to one 17. Montgomery MT. Extraoral facial pain. Emerg Med
of the several neurosurgical procedures. Clin North Am 2000;18:577–600.
18. Stewart WF, Lipton RB, Celentano DD, Reed ML.
Prevalence of migraine headache in the United
REFERENCES States. JAMA 1992;267:64–9.
1. Dalessio D, Silberstein S. Wolff ’s headache. New 19. Annequin D, Tourniaire B, Massiou H. Migraine and
York: Oxford University Press; 1993. headache in childhood and adolescence. Pediatr Clin
2. Sessle BJ. Neural mechanisms and pathways in cran- North Am 2000;47:617–31.
iofacial pain. Can J Neurol Sci 1999;26 Suppl:S7–11. 20. Solomon S. Migraine diagnosis and clinical sympto-
3. Chow JM. Rhinologic headaches. Otolaryngol Head matology. Headache 1994;34 Suppl:S8–12.
Neck Surg 1994;111:211–8. 21. Wilkinson M. Migraine treatment: the British per-
4. Wright EF. Referred craniofacial pain patterns in spective. Headache 1994;34 Suppl:S13–6.
patients with temporomandibular disorder. J Am 22. Lipton RB, Stewart WF, Stone AM, et al. Stratified
Dent Assoc 2000;131:1307–15. care vs step care strategies for migraine. JAMA
5. Jensen R, Olesen J. Tension-type headache: an 2000;284:2599–605.
update on mechanisms and treatment. Curr Opin 23. Silberstein SD, Young WB. Safety and efficiency of
Neurol 2000;13:285–9. ergotamine tartrate and dihydroergotamine in the
6. Hargreaves RJ, Shepheard SL. Pathophysiology of treatment of migraine and status migrainosus. Neu-
migraine—new insights. Can J Neurol Sci 1999;26 rology 1995;45:577–84.
Suppl:S12–9. 24. Young WB. Appropriate use of ergotamine tartrate and
7. Hamel E. The biology of serotonin receptors: focus dihydroergotamine in the treatment of migraine: cur-
on migraine pathophysiology and treatment. Can J rent perspectives. Headache 1997;37 Suppl: S42–5.
Neurol Sci 1999;26 Suppl:S2–6. 25. Logemann CD, Rankin LM. Newer intranasal
8. Schor DI. Headache and facial pain—the role of the migraine medications. Am Fam Physician 2000;61:
paranasal sinuses: a literature review. Cranio 180–6.
1993;11:36–47. 26. Maizels M, Scott B, Cohen W, Chen W. Intranasal
9. Ballenger JJ. Headache and neuralgia of the face. In: lidocaine for treatment of migraine. JAMA 1996;
Ballenger JJ, Snow JB, editors. Otorhinolaryngology 276:319–21.
head and neck surgery. Baltimore: Williams & 27. Finkel AG, Mann JD, Lundeen TF. Headache and facial
Wilkins; 1996. p. 158–62. pain. In: Bailey BJ, Calhoun KH, Deskin RW, et al, edi-
10. Ansemi B, Baldi E, Cassaci F, Salman S. Endogenous tors. Head and neck surgery-otolaryngology. 2nd ed.
opinoids in cerebrospinal fluids and blood in idio- Philadelphia: Lippincott-Raven; 1998. p. 287–304.
pathic headache sufferers. Headache 1998;20:294. 28. Becker WJ. Evidence based migraine prophylactic drug
11. Jensen R. Pathophysiological mechanisms of ten- therapy. Can J Neurol Sci 1999;26 Suppl:S27–32.
sion-type headache: a review of epidemiological and 29. Truelove EL. The chemotherapeutic management of
experimental studies. Cephalalgia 1999;19:602–21. chronic and persistent orofacial pain. Dent Clin
12. Headache Classification Committee of the Interna- North Am 1994;38:559–88.
tional Headache Society. Classification and diagnos- 30. Silberstein SD. Tension-type headaches. Headache
tic criteria for headache disorders, cranial neuralgias 1994;34 Suppl:S2–7.
and facial pain. Cephalalgia 1988;8 Suppl 7:1–96. 31. Silberstein SD, Lipton RB. Chronic daily headache.
13. Saper JR. Diagnosis and symptomatic treatment of Curr Opin Neurol 2000;13:277–83.
migraine. Headache 1997;37 Suppl:S1–14. 32. Benoliel R, Sharav Y. Craniofacial pain of myofascial
14. Smetana GW. The diagnostic value of historical fea- origin: temporomandibular pain and tension-type
tures in primary headache syndromes: a compre- headache. Compend Contin Educ Dent 1998;19:
hensive review. Arch Intern Med 2000;160:2729–37. 701–21.
806 Ballenger’s Otorhinolaryngology
33. Mendizabal JE, Umana E, Zweifler RM. Cluster 43. Vincent MB. Cervicogenic headache: clinical aspects.
headache: Horton’s cephalalgia revisited. South Med Clin Exp Rheumatol 2000;18 Suppl:S7–S10.
J 1998;91:606–17. 44. Sjaastad O, Fredriksen TA. Cervicogenic headache:
34. Mathew NT. Cluster headache. Neurology 1992;42 criteria, classification and epidemiology. Clin Exp
Suppl 2:22–31. Rheumatol 2000;18 Suppl:S3–6.
35. Pareja JA, Sjaastad O. SUNCT syndrome: a clinical 45. Tarabichi M. Characteristics of sinus-related pain.
review. Headache 1997;37:195–202. Otolaryngol Head Neck Surg 2000;122:842–7.
36. Benoliel R, Eliav E, Elishoov H, Sharav Y. Diagnosis 46. Balbuena L, Hayes D, Ramirez SG, Johnson R. Eagle’s
and treatment of persistent pain after trauma to the syndrome (elongated styloid process). South Med J
head and neck. J Oral Maxillofac Surg 1994;52: 1997;90:331–4.
1138–47; discussion 1147–8. 47. Hakeberg M, Berggren U, Hagglin C, Ahlqwist M.
37. Raps EC, Rogers JD, Galetta SL, et al. The clinical Reported burning mouth symptoms among middle-
spectrum of unruptured intracranial aneurysms. aged and elderly women. Eur J Oral Sci 1997; 105:
Arch Neurol 1994;51:447–8. 539–43.
38. Meskimen S, Cook TD, Blake RL. Management of 48. Major PW, Nebbe B. Use and effectiveness of splint
giant cell arteritis and polymyalgia rheumatica. Am appliance therapy: review of literature. Cranio
Fam Physician 2000;61:2061–8, 2073. 1997:15:159–66.
39. Levine HL. Otorhinolaryngologic causes of headache. 49. Graff-Radford SB. Facial pain. Curr Opin Neurol
Med Clin North Am 1991;75:195–210. 2000;13:291–6.
40. Guillon B, Lévy C, Bousser MG. Internal carotid artery 50. Kuhn WF, Kuhn SC, Gilberstadt H. Occipital neural-
dissection: an update. J Neurol Sci 1998;153:146–58. gias: clinical recognition of a complicated headache.
41. Sismanis A. Pulsatile tinnitus. Am J Otol 1998; A case series and literature review. J Orofac Pain
19:472–7. 1997;11:158–65.
42. Mathew NT, Kurman R, Perez F. Drug induced 51. Feinmann C, Peatfield R. Orofacial neuralgia. Diag-
refractory headache—clinical features and manage- nosis and treatment guidelines. Drugs 1993;46:
ment. Headache 1990;30:634–8. 263–8.
CHAPTER 36
807
808 Ballenger’s Otorhinolaryngology
Fungiform papillomas present as exophytic sinuses, and 1% in the frontal and sphenoid sinuses.2
septal lesions. Histologically, they have a nonkera- As in other areas of the head and neck, the tumor
tinizing squamous epithelium covering a fibrovas- may present with varying degrees of differentiation.
cular stroma. In contrast to the other varieties of Glandular carcinomas are the next most com-
papilloma, they are not associated with malignant mon tumors, comprising 4 to 15% of all sinus neo-
degeneration.2 plasms.6 Of these, adenocarcinomas are the most
Inverted papillomas (IPs) are characterized by common, representing 5 to 19% of nasal and
a squamous or transitional cell epithelium sur- paranasal sinus tumors.7–9 There is a lack of consis-
rounding a fibrovascular stroma with endophytic tency in the literature regarding the classification of
growth. They are most often found on the lateral these tumors. In general, these tumors are classified
nasal wall and have been reported to be associated as low grade on the basis of uniform glandular archi-
with squamous cell carcinoma in 5 to 15% of tecture and uniform cytologic characteristics. High-
patients.3 grade adenocarcinomas have a predominantly solid
Cylindrical cell papillomas, also known as growth pattern and moderate to prominent nuclear
oncocytic schneiderian papillomas, share with IPs pleomorphism.5 The prognostic significance of the
both their localization to the lateral nasal wall and two types is debatable, but it is felt that the low-
their association with malignant disease. Pathologi- grade adenocarcinomas have a propensity toward
cally, the epithelial lining contains multiple layers of local recurrence and rarely metastasize, whereas
eosinophilic cells, goblet cells, and microcysts full of high-grade adenocarcinomas more frequently dis-
mucin.2 play regional and distant metastases.5
Additional benign tumors of epithelial origin Adenoid cystic carcinomas are somewhat less
include adenomas, cholesteatomas, and dermoids. common than adenocarcinomas but still comprise a
Adenomas of the sinonasal tract are histologically sizable portion of sinonasal tumors in most studies.
identical to those arising in other areas of the body. The tumor consists of groups of small cells
They occur most commonly in the fourth to sev- arranged in one of several patterns described as
enth decade and usually involve the nasal septum. tubular, cribriform, and solid.5,10 Low-grade ade-
Excision is curative in over 90% of all cases. Simi- noid cystic carcinomas are defined as those with less
larly, cholesteatomas and dermoids pathologically than 30% solid component.5 Conversely, high-grade
resemble those seen in other areas of the body and carcinomas consist of tumors with a greater than
are relatively rare in the sinonasal region. 30% solid component (Figure 36–1). High-grade
Cholesteatomas are composed of desquamated carcinomas are characterized by a shorter survival
epithelium, whereas dermoid tumors contain spe- period and more frequent incidence of distant
cialized dermal appendages.4 When they do occur metastases.5 Both subtypes have a predilection for
in the sinuses, they are typically in the frontal or perineural invasion.5,11
ethmoid sinuses.4 Mucoepidermoid carcinoma (Figure 36–2) is
Fibrous dysplasia has been described as occa- an extremely rare form of glandular carcinoma. It
sionally arising within the maxilla. It occurs in both is composed of a combination of squamous cells
polyostotic and monostotic forms, with monostotic and glandular, mucus-producing, basal cells.2 They
being more common. Growth is slow, and treatment are notable for their propensity toward distant
consists of local excision for lesions that are physi- metastases.10
cally obstructive or cosmetically deforming.4 The Although rare, two tumors of neuroectodermal
surgery typically is conservative and involves a origin are occasionally encountered. These are
sculpting excision of the lesion to restore the tumor sinonasal melanoma and olfactory neuroblastoma
site to its natural contour. (esthesioneurocytoma, esthesioneuroblastoma).
Malignant epithelial neoplasms constitute the Melanoma of the sinuses represents less than 7% of
majority of sinonasal tumors, representing 45 to all sinonasal malignancies. It does not differ signifi-
80% of all sinus neoplasia.5,6 Of these, squamous cell cantly from that in other parts of the body, although
carcinoma is the most common. Sixty percent of 30% have been noted to be amelanotic.5,12,13
these neoplasms arise in the maxillary sinus, 20 to Melanoma may have plasmacytoid, spindle cell, or
30% in the nasal cavity, 10 to 15% in the ethmoid epithelioid cytologic features.12 Additionally, archi-
Neoplasms of the Nose and Paranasal Sinuses 809
tectural patterns vary and may be sarcoma-like, or diffuse sheets of tumor cells with a lack of
epithelioid, or pleomorphic.12 Immunohistochemi- stroma.2 Immunohistochemical staining is helpful as
cal staining is helpful and should include anti-S100, esthesioneuroblastoma displays a sustentacular cell
HMB-45, and antivimentin.2,12 pattern of S-100 staining as well as positive staining
Olfactory neuroblastoma (Figure 36–3) is the for neurofilament protein, neuron-specific enolase,
second tumor of neuroectodermal origin that may and synaptophysin.2,12,14 Electron microscopy aids in
arise in the paranasal region. This neoplasm presents the diagnosis of this tumor by allowing one to iden-
with one of two cell patterns. It may have either a tify cells containing microtubules and neurofila-
nesting pattern of small cells surrounded by stroma ments that are specific to this neoplasm.2
Lymphoma makes up approximately 18% of the frequency has risen to 7 per 100,000.1 These
all nonsquamous malignancies of the paranasal tumors occur in all races, and there is no gender
sinuses.13 Most commonly, this consists of diffuse predilection.
large B-cell lymphoma; however, natural killer/T-cell The histologic differential diagnosis of paranasal
lymphoma is quite common.15 sinus tumors is enormous. However, squamous cell
A myriad of neoplasms, both benign and carcinoma is by far the most frequently encountered
malignant, may be found in the nose and paranasal malignancy, accounting for up to 80% of all neo-
sinuses. Even benign processes can have devastating plasms according to some studies.1 This is followed by
consequences owing to local invasion or destruction the salivary gland tumors (4 to 15%) and sarcomas (4
in the presence of the numerous vital structures to 6%).1 Other pathologic entities such as lym-
located in the area. Malignant tumors have a worse phomas, esthesioneuroblastomas, and melanomas are
prognosis, but whether one histologic subtype is usually represented in most case series but rarely
worse than another is subject to debate. make up a substantial percentage in any one study.
Of the different sites, the maxillary sinus is
commonly identified as the primary site, represent-
EPIDEMIOLOGY ing 55 to 80%.16 It is followed by the nasal cavity (27
The greatest obstacle in understanding nasal and to 33%), the ethmoid sinuses (9 to 10%), and the
paranasal sinus tumors is the rarity with which they frontal and sphenoid sinuses (1 to 2%).6,17,18
occur. This rarity frustrates clinical studies exploring Environmental factors play a large role in the
treatment options. Similarly, the low incidence, development of paranasal sinus malignancy. Up to
combined with their nonspecific symptoms, often 44% of these tumors are attributed to occupational
leads to a critical delay in diagnosis. Commonly exposures. The most well known is the association
cited data indicate that these neoplasms account for between wood dust and adenocarcinoma. Exposure
0.2 to 0.8% of all carcinomas and for 3% of those to wood dust increases the relative risk of adenocar-
occurring in the upper aerodigestive tract.1 Demo- cinoma by 540 times.10 However, it should be noted
graphically, these tumors occur predominantly in that squamous cell carcinoma also shares this rela-
the age range from 50 to 90 years. Their frequency in tionship to wood dust, with prolonged exposure
the young is low, being 0.1 to 0.3 per 100,000 in the resulting in a 21 times increase in relative risk.
first decade of life.1 However, by the eighth decade, Smoking has also been suggested to play a role in
Neoplasms of the Nose and Paranasal Sinuses 811
nasal and paranasal sinus cancers. Additionally, TABLE 36–3. Symptoms of Nasal and Paranasal
numerous other industrial substances have been Sinus Tumors
shown to be associated with the development of
paranasal sinus malignancy (Table 36–2). 6,19 Early Late
Interestingly, there is also evidence that envi- Nasal obstruction Epistaxis
ronmental pollution may be associated with an
Rhinorrhea Cranial nerve dysfunction
increasing incidence of paranasal sinus malig-
nancy.19 In a recent retrospective study, Calderon- Proptosis
Garciduenas et al found substantial increases in the Facial pain
rates of paranasal malignancy when comparing the Facial swelling
years 1976 to 1986 and 1987 to 1998.19 They postu-
Trismus
lated that this might be related to increasing expo-
sure to complex chemical pollutants in their patient
population during these time periods.
related to either nasal obstruction or nerve involve- On CT, malignant tumors of the paranasal
ment. A gross assessment of visual acuity and oculo- sinuses and nasal cavity appear as dense, homoge-
motor function should be undertaken. If an neous, destructive masses. The primary benefit of
abnormality is noted, a more thorough examination CT scans is the detailed demonstration of bony
by an ophthalmologist is warranted for reasons of structure.20 Finely cut coronal scans provide infor-
treatment planning. Finally, facial/palatal anesthesia mation regarding the integrity of both the orbital
should be noted to assess involvement of the trigem- walls and skull base (Figure 36–4). Posterior exten-
inal nerves. sion of the tumor toward the pterygopalatine fossa,
Fiber-optic assessment of the nasal cavity may pterygomaxillary fissure, and infratemporal fossa
be performed with either a flexible or a rigid endo- may also be appreciated.20 Although not diagnostic,
scope. This portion of the examination provides CT scans may also provide evidence of advanced
information on the origin of the tumor, where it perineural invasion through the demonstration of
extends, and its size. Occasionally, owing to the late enlarged neural foramina. The primary disadvantage
presentation and advanced stage of disease, this por- of CT is the inability to distinguish between soft tis-
tion of the examination is limited because of the dif- sue and retained secretions. Another disadvantage is
ficulty in passing the endoscope posterior to the that although CT can give one an idea of the
tumor. This is especially true of nasal cavity and eth- integrity of the orbital wall and skull base, this often
moid sinus tumors that tend to obstruct the nasal does not correlate with orbital or dural invasion.
cavity. Decongestants and topical anesthesia are Magnetic resonance imaging is more sensitive
helpful in this endeavor. in determining the true extent of tumor expansion.
On T1-weighted images, most tumors exhibit a low
signal intensity that enhances after the administra-
IMAGING tion of gadolinium. On T2-weighted images, these
Various imaging options are available to the practi- tumors show a higher signal intensity than muscle
tioner evaluating the patient with paranasal sinus but are not as bright as secretions20 (Figure 36–5).
cancer. However, the two most commonly employed The primary advantage of MRI is the ability to dis-
today are computed tomography (CT) and magnetic tinguish nasal secretions from tumor mass. Addi-
resonance imaging (MRI). Both provide informa- tionally, MRI allows accurate prediction of both
tion useful in treatment planning. In practice, the dural involvement and venous sinus invasion.
majority of patients undergo both types of imaging Specifically, the presence of pial enhancement, focal
prior to receiving treatment. dural nodules, or dural thickening of more than 5
mm is highly sensitive and accurate in predicting the patients, (3) a correlation between T stage and treat-
presence of dural invasion.18 Disadvantages of MRI ment, and (4) a correlation between T stage and sur-
are its inability to provide information regarding the vival. Unfortunately, such a system has not been
invasion of compact bone.20 Additionally, like CT, developed for paranasal sinus tumors. The lack of
MRI is not accurate in predicting perineural or uniformity in staging is a major impediment to
orbital involvement.18 comparing treatment modalities from various stud-
Angiography should be reserved specifically for ies. Since paranasal sinus tumors are so rare and no
patients in whom there is suspected internal carotid one clinic can hope to have a large number of
artery involvement. When carotid artery involve- patients to study, such comparisons are mandatory
ment is suspected, magnetic resonance angiography to form conclusions concerning the proper treat-
will often suffice to confirm or refute it.21,22 Indica- ment of patients with paranasal sinus malignancy.
tions for conventional angiography are (1) prepa- In the United States, the favored staging system
ration for embolization of a vascular lesion is that proposed by the American Joint Committee
preoperatively, (2) to define intracranial arterial on Cancer (Table 36–4). It is largely based on Ohn-
anatomy in a patient who is to undergo arterial gren’s line.23 This classification divides the facial
bypass, and (3) balloon occlusion testing in a patient
who will likely have the carotid artery sacrificed.
Most patients benefit from multiple imaging TABLE 36–4. American Joint Committee on Cancer
modalities during the workup of their paranasal Staging System for Malignant Neoplasms of the
neoplasm. Key issues, such as orbital involvement, Maxillary Sinus
skull base invasion, and vascular involvement, play T1 Limited to antral mucosa without bony erosion
significant roles in determining the proper treatment
T2 Bony erosion of the infrastructure (hard palate,
modality for the individual patient.
middle nasal meatus, or inferior nasal meatus)
T3 Invasion of cheek skin, posterior wall of sinus, or
STAGING anterior ethmoid cells
In an analysis of the various staging systems
T4 Invasion of orbital contents, cribriform plate,
employed for maxillary cancer, Willatt et al listed
posterior ethmoid cells, sphenoid sinus,
four goals that an adequate staging system should
nasopharynx, soft palate, pterygopalatine fossa,
meet.23 They include (1) a balanced distribution of
infratemporal fossa, or skull base
staging, (2) the ability to stage the majority of
814 Ballenger’s Otorhinolaryngology
skeleton into two parts by a theoretical plane drawn sinus malignancy, its variation from the AJCC
from the medial canthus of the eye to the angle of staging of maxillary cancer makes analysis of stud-
the mandible. Tumors of the maxillary sinus poste- ies using the different staging systems difficult.
rior to this plane have a poorer prognosis. However, However, for the present time, the UICC staging
this staging system fails to classify tumors that do system is the most complete system currently in
not originate in the maxillary sinus. Obviously, this use.
is a major limitation in discussing the wide variety of
tumors that may occur in the nasal cavity and eth-
moid sinuses.
PROGNOSIS
One method to overcome this difficulty is to Because of the previously discussed difficulty in
describe individually the site of involvement for comparing various clinical studies, it is difficult to
each patient. This is cumbersome and presents dif- state the extent that various clinical factors play in
ficulty in outcome analysis. As an alternative, many prognosis. Clearly, an advanced stage is associated
authors now use the staging system proposed by with a worse prognosis. In fact, it has been asserted
the International Union Against Cancer (UICC) that the most accurate predictor of poor prognosis
(Table 36–5). Although the UICC staging system is the T category.10,13,24 For example, although the
accounts for the most common sites of paranasal overall total 5-year survival for patients with
paranasal sinus malignancy may range from 40 to
50%, patients categorized as T1 and T2 may have a
5-year survival as high as 70%.7–10,13,16 Conversely,
TABLE 36–5. International Union Against Cancer patients with a tumor category of T3 or T4 com-
(UICC) Staging System for Malignant Neoplasms monly have 5-year survivals as low as 30%. 10
Maxillary sinus Specifically, tumors with anterior skull base
T1 Tumor is limited to the antral mucosa with no
involvement are known to have the worst progno-
erosion or destruction of bone
sis.10,18 Because of this, many authors have argued
that a shorter delay in diagnosis would result in
T2 Tumor causes bone erosion or destruction, lower T categories at the time of presentation and
except for the posterior antral wall, including improvement in overall survival.25
extension into the hard palate and/or the middle Lymph node involvement at the time of diag-
nasal meatus nosis is known to be associated with a uniformly dis-
T3 Tumor invades any of the following: bone of the mal prognosis.8,10,26 This manifestation of disease is
posterior wall of maxillary sinus, subcutaneous rare in patients with paranasal sinus tumors and
tissues, skin of cheek, floor or medial wall of approximates 10% in most series.7,8,16,25 It is because
orbit, infratemporal fossa, pterygoid plates, of the poor prognosis associated with lymph node
ethmoid sinuses disease that some clinicians now recommend for
T4 Tumor invades orbital contents beyond the floor patients with advanced stages of paranasal sinus
or medial wall including any of the following: malignancy elective treatment of the N0 neck.
the orbital apex, cribriform plate, base of skull, Interestingly, many studies have shown that
nasopharynx, sphenoid, frontal sinuses histologic subtype does not play a role in the overall
prognosis.7,9,10,13,27 However, this is contradicted by
Ethmoid sinus
other reports demonstrating improved survival in
T1 Tumor is confined to the ethmoid with or tumors such as adenoid cystic carcinoma and lym-
without bone erosion phoma and poor survival rates in undifferentiated
T2 Tumor extends into the nasal cavity carcinoma as well as melanoma.8,9 Additionally,
T3 Tumor extends to the anterior orbit and/or some investigators feel that tumor differentiation
maxillary sinus plays a role in prognosis, with well to moderately dif-
ferentiated tumors having significantly better prog-
T4 Tumor with intracranial extension, orbital
nosis than poorly differentiated tumors.8 The true
extension including apex, involving sphenoid
extent that histology and differentiation play in
and/or frontal sinus and/or skin of external nose
patient prognosis remains to be clarified.
Neoplasms of the Nose and Paranasal Sinuses 815
cell carcinoma.32 In fact, the most important factor tumor, many authors caution that patients should be
in deciding on an endoscopic approach is not the prepared preoperatively for the possibility of con-
type of tumor but rather the extent. Early tumors version to an open procedure.29,32
limited to the lateral nasal wall are good candidates Most surgeons would agree that in the hands of
for endoscopic resection (Figure 36–6). This may a skilled endoscopist, endoscopic resection of early
range from endoscopic medial maxillectomy to total nasal and paranasal sinus tumors is appropriate.
ethmoidectomy with mucosal stripping and the However, care must be taken to ensure that negative
drilling of potentially involved bone.31 A contraindi- surgical margins are obtained as this has been shown
cation to an endoscopic approach is invasion of to improve significantly patient prognosis.31 Addi-
inaccessible areas, including the lateral part of the tionally, because of the risk of recurrence, frequent
maxillary sinus, periorbita, lacrimal sac, supraorbital follow-up with serial endoscopic examination is
ethmoid cells, frontal sinus, and skull base.31 Cer- strongly encouraged. Regardless of treatment
tainly, the current standard dictates that the vast approach, the role of serial endoscopy is established
majority of patients with malignant lesions should for follow-up of the patient’s nasal or surgical cavity.
be treated with an open en bloc resection. Addition- Complications include cerebrospinal fluid (CSF)
ally, even when one is dealing with a low-grade leaks, visual/orbital injury, synechia, and changes in
the sense of smell.
best avoided through careful removal of all frontal to the sinonasal region, tumors that extend to the
sinus and frontal recess mucosa followed by obliter- pterygopalatine fossa, sphenoid sinus, or nasophar-
ation of the frontal recess with fascia and bone ynx are best approached through the lateral
chips34 in patients undergoing “cranialization” or face/skull base 6 (Figure 36–11). The most well-
obliteration. Reconstructed or preserved frontal described approach is the lateral facial split or the
sinuses will require radiographic follow-up. Addi- infratemporal fossa type C procedure of Fisch and
tional complications include the poor cosmetic out- Mattox.6 The approach consists of a preauricular or
comes that may result when the anterior table must modified Blair incision. The temporalis muscle is
be resected. This defect is best reconstructed with a elevated and swung over the zygoma. Additionally,
split calvarial bone graft.34 the zygoma may be removed, the pes anserinus of
the facial nerve divided, retracted, or skeletonized,
Anterior Lateral Skull Base Approach Although and the mandible disarticulated and advanced
standard transfacial approaches offer good access anteriorly. This provides exposure of the internal
Neoplasms of the Nose and Paranasal Sinuses 819
the resection. Endoscopic guidance has added a plate region. Small dural defects may be closed pri-
minimally invasive component to guide the marily, but larger defects that prohibit primary clo-
intranasal cuts for small tumors of the anterior part sure are grafted with cadaveric dura. At the end of
of the skull base. In the more uncommon scenario, the procedure, the pericranial flap is sutured to the
the approach has the additional advantage of hav- dura, bone flaps are replaced, and the skin is closed.
ing no facial incisions. The intracranial exposure is A lumbar drain, CSF-penetrating antibiotics, and
recommended as the first step to ensure that the high-dose corticosteroids are recommended in the
tumor is not unresectable owing to transdural or perioperative period.6
brain invasion. In addition to the inherent morbidity of a
The procedure involves a bicoronal incision craniotomy, a significant disadvantage of the
with bifrontal craniotomy. An anteriorly based per- approach is the limited access to the inferior and
icranial flap is created to provide an anatomic divi- medial parts of the orbit as well as the maxillary
sion between the dura and sinuses at the end of the sinus. For this reason, the procedure should be
procedure. An anterior osteotomy is placed above combined with a transfacial approach when there
the supraorbital rims. The frontal lobes are gently is involvement of the floor of the maxilla, the base
retracted to provide access to the anterior cranial of the nasal septum, or the soft tissues of the face
floor. The dura is then elevated except where it is or when one suspects that the excision will include
directly involved in tumor and in the cribriform orbital exenteration (Figure 36–13). The com-
Neoplasms of the Nose and Paranasal Sinuses 821
bined craniofacial resection has allowed better This technique may allow resection of one side of
access to the inferior and lateral nasal walls. This the cribriform plate with preservation of contralat-
reduces operative morbidity by decreasing the eral olfactory fibers. The craniofacial approach
amount of retraction needed on the frontal lobes allows definite confirmation of tumor resectability
and providing greater ease in obtaining adequate from the dura/brain. If tumor is grossly through
hemostasis.36 dura or into brain, these patients are at higher risk
Specific complications related to the cranial or for carcinomatous meningitis. For our team, this
craniofacial approach include CSF leak, meningitis, has been a contraindication for craniofacial resec-
and pneumocephalus. Our practice has been to use tion on patients with high-grade tumors. The
a tracheostomy to decrease the incidence of pneu- lesions in these patients are typically not resected,
mocephalus. However, should it occur, it may be eas- and the patients are referred for multimodality
ily treated with aspiration. The other complications therapy.
are rare when a pericranial flap has been used in
conjunction with adequate perioperative antibiotics
and a lumbar drain.36
RADIATION THERAPY
The subfrontal craniofacial approach has Radiation therapy plays a large role in the treatment
been used for anterior skull base resections and of patients with paranasal sinus tumors. Because of
offers the advantage of minimal brain retraction.37 the late stage in which most of the patients present,
822 Ballenger’s Otorhinolaryngology
multimodality therapy is nearly universal. 6,26,38 borders of the radiated tumor and the potential for
Additionally, in rare patients with early-stage can- increased surgical morbidity in the irradiated
cers, radiation therapy alone has been shown to be field. 6 The pathologic results from the surgical
as effective as surgical excision.20,38,39 Some neo- specimen may be used to guide the radiation treat-
plasms such as lymphomas, plasmacytomas, and ment. This is extremely important when dealing
esthesioneuroblastomas appear to be especially with areas such as the orbit, where intraoperative
radiosensitive.6,10,38 examination and subsequent pathology may be the
There is no clear evidence supporting preop- only way to determine definitively the presence of
erative radiation versus postoperative radiation.6,27 tumor and help define required doses yet minimize
Each has its distinct advantages and disadvantages. morbidity.38
Postoperative radiation currently appears to be the Notwithstanding, there are persuasive argu-
most popular choice for several reasons. The dose ments for the use of preoperative radiation therapy
of radiation that may be given is lower when using as well. In common situations in which there is
radiation to control microscopic residual disease, involvement of vital structures (orbit, dura, etc),
resulting in less morbidity.38 Postoperative doses preoperative irradiation can be used to “sterilize”
may range between 60 and 70 Gy. Patients who are these areas. This strategy is frequently used to pre-
not operative candidates may receive doses as high serve the eye when radiographic evaluation
as 74 to 79 Gy.40 Another reason for postoperative demonstrates that the structure is at risk. Debate
irradiation is the difficulty in determining the true continues as to whether this serves to preserve
Neoplasms of the Nose and Paranasal Sinuses 823
anatomic structures and improve survival. Some osteoradionecrosis, retinopathy, and medial canthus
argue that preradiation surgery devascularizes the fistula.16,40,41 The rates of these complications
tumor bed, making the residual tumor less increase as higher doses of radiation are used. For
radiosensitive secondary to hypoxia. When there instance, the retina and optic nerve exhibit a toler-
are grossly positive margins after surgery, higher ance of approximately 50 Gy. Parsons et al found
doses of radiation are required to eradicate the dis- the rate of unilateral blindness in these patients to
ease.38 It has been shown by Polin et al that presur- be as high as 33%.39 Bilateral blindness occurred in
gical response to radiation therapy is predictive of 10% of the patients. Structures surrounding the
patient prognosis.14 In their study of patients with orbit are also important to consider. The risk of
esthesioneuroblastomas, patients with a favorable injury to the lacrimal gland with resulting corneal
response to radiation demonstrated a significantly ulceration, opacification, or vascularization in-
higher rate of disease-free survival. creases substantially with doses greater than 30 Gy.39
As with surgery, there are numerous risks to Neurologic sequelae are less common (10%). The
radiation treatment. The majority relate to damage rates of these complications have diminished
to the orbits and brain. Reported complications markedly with the use of CT for treatment plan-
include blindness, central nervous system sequelae, ning.42 Computed tomographic scans allow for pre-
otitis media, nasolacrimal duct obstruction, sinusi- cise localization of both the tumor and surrounding
tis, nasal bone destruction, chronic orbital pain, critical structures. This localization provides for
824 Ballenger’s Otorhinolaryngology
treatment planning that minimizes radiation given apy, there is a trend toward using preoperative
to surrounding structures. radiotherapy and/or chemotherapy with the goal of
preserving structures such as the orbit. Proponents
of orbital preservation argue that the orbit is sur-
CHEMOTHERAPY rounded by a layer of periosteum that is resistant to
Several trials have evaluated the effects of tumor invasion.46,47 This argument has been fur-
chemotherapy in treating patients with paranasal thered by clinicoanatomic studies demonstrating
sinus tumors. Although results have been promis- the presence of a distinct fascial layer separating
ing, there is no definitive evidence that chemother- orbital fat from periorbita as well as an infrequent
apy improves survival. However, several studies incidence of tumor invasion of orbital con-
have shown evidence of tumor regression with the tents.45,48,49 Proponents argue that for this reason,
addition of chemotherapy.38,43 For instance, Brasnu there is rarely a reason to remove the orbit at the
and colleagues have used cisplatin as a neoadjuvant time of surgical resection.
chemotherapy prior to surgical resection in the Surgeons favoring radical excision of the orbit
treatment of adenocarcinoma reaching the skull point out that there is no reliable radiographic
base.41 In this setting, the investigators achieved a means to determine the extent of orbital involve-
22.7% complete clinical response and a 13.6% ment. Additionally, with the use of neoadjuvant
complete histologic response. As with radiation radiation treatment, it can be difficult to determine
therapy, a response to chemotherapy was found to the extent of orbital involvement at the time of sur-
be predictive of a better prognosis.14,41 The morbid- gical excision. The function of the eye must also be
ity of this treatment was minimal and was not considered when making the decision to pursue
increased by the addition of postoperative radiation preservation. Stern et al have shown that ocular
therapy. Platinum-based chemotherapy has also function tends to be poor when the orbital floor is
been shown to be effective against esthesioneurob- removed during excision.50 There is also the mor-
lastomas and other paranasal sinus tumors as bidity of radiation therapy to consider. Postradia-
well.14,38,43 Alternatively, Sakai et al noted 5-fluo- tion complications involving the orbit include
rouracil (5-FU) in combination with radiation and keratitis, cataracts, retinopathy, glaucoma, and
surgical curettage to be relatively effective with min- chronic pain. As has been previously discussed, the
imal morbidity, although Tsujii and Tsuji found no rates of these complications can be quite high.
difference in patients whether they were treated At the present time, the decision to preserve the
with 5-FU or not.42,44 Although chemotherapy has eye is made on an individual basis. Clinical studies
not shown an improvement in overall survival, it demonstrate that as long as the periorbita is not
must be remembered that it is difficult to prove an involved, it is oncologically sound to leave the orbit
improvement in survival with any therapy for this intact. However, attention must be paid to the
disease. Further research is required and should be chances of obtaining useful function from the pre-
encouraged. served organ. This analysis should be based on both
the amount of resected orbital floor as well as the
final amount of radiation the orbit will receive. As
CONTROVERSIAL TOPICS IN Stern et al pointed out, “Strong consideration should
PARANASAL SINUS TUMORS be given to orbital exenteration at the time of surgery
Obviously, there is still much to be learned concern- when the orbital floor is resected—especially if post-
ing the optimal management of paranasal sinus operative radiation fields will include the eye.”50
malignancy. However, two topics in particular war-
rant consideration. ELECTIVE TREATMENT OF THE NECK
Traditionally, elective treatment of the N0 neck has
ORBITAL PRESERVATION not been advocated secondary to the low rate of
In the past, radical excision with orbital exentera- occult lymph nodal disease.6,40 Additionally, many
tion was performed if the tumor approached the argue that the primary lymphatic watershed of the
orbit.45 With the emphasis on multimodality ther- sinonasal region is the retropharynx. Therefore, the
Neoplasms of the Nose and Paranasal Sinuses 825
areas most likely to contain regional cancer reside in sinuses and nasal cavity. Arch Otolaryngol 1983;
this region and not in the neck. This dogma has 109:662–8.
recently been challenged based on the following rea- 6. Osguthorpe JD. Sinus neoplasia. Arch Otolaryngol
soning: the rate of lymph nodal recurrence ranges Head Neck Surg 1994;120:19–25.
from 12 to 28%.27 Patients with neck relapse are 7. Haraguchi H, Ebihara S, Saikawa M, et al. Malignant
known to have inferior long-term survival and a tumors of the nasal cavity: review of a 60-case series.
higher risk of distant metastases compared with Jpn J Clin Oncol 1995;25:188–94.
those who did not have locoregional failure. This 8. Harbo G, Grau C, Bundgaard T, et al. Cancer of the
work has been corroborated by Paulino et al, who nasal cavity and paranasal sinuses. A clinico-patholog-
also found that patients with T3 and T4 tumors have ical study of 277 patients. Acta Oncol 1997;36:45–50.
a higher rate of nodal recurrence and those patients 9. Svane-Knudsen V, Jorgensen KE, Hansen O, et al.
with nodal recurrence had poorer survival rates.51 In Cancer of the nasal cavity and paranasal sinuses: a
addition to this, Le et al demonstrated that elective series of 115 patients. Rhinology 1998;36:12–4.
neck irradiation effectively prevented nodal recur- 10. Alvarez I, Suarez C, Rodrigo JP, et al. Prognostic fac-
rence in the 25 patients in whom it was used.52 For tors in paranasal sinus cancer. Am J Otolaryngol
this reason, it is now considered reasonable to irra- 1995;16:109–14.
diate the N0 neck in the presence of a primary 11. Naficy S, Disher MJ, Esclamado RM. Adenoid cystic
tumor of advanced stage (T3 and T4). carcinoma of the paranasal sinuses. Am J Rhinol
1999;13:311–4.
12. Brandwein MS, Rothstein A, Lawson W, et al.
CONCLUSION Sinonasal melanoma. A clinicopathologic study of
What we know concerning nasal and paranasal sinus 25 cases and literature meta-analysis. Arch Oto-
tumors stands in stark contrast to the questions that laryngol Head Neck Surg 1997;123:290–6.
need to be answered. Small cohorts and isolated case 13. Kraus DH, Sterman BM, Levine HL, et al. Factors
presentations contribute relatively little toward influencing survival in ethmoid sinus cancer. Arch
global understanding. As consensus is reached Otolaryngol Head Neck Surg 1992;118:367–72.
regarding staging, cross-study comparisons will be 14. Polin RS, Sheehan JP, Chenelle AG, et al. The role of
facilitated. This will undoubtedly lead to a greater preoperative adjuvant treatment in the management
understanding of these tumors in terms of patho- of esthesioneuroblastoma: the University of Virginia
genesis, prognosis, and optimal treatment options. experience. Neurosurgery 1998;42:1029–37.
15. Cuadra-Garcia I, Proulxx GM, Wu CL, et al.
Sinonasal lymphoma: a clinicopathologic analysis of
REFERENCES 58 cases from the Massachusetts General Hospital.
1. Osguthorpe JD. Preface. In: Osguthorpe JD, editor. Am J Surg Pathol 1999;23:1356–69.
The Otolaryngologic Clinics of North America— 16. Paulino AC, Marks JE, Bricker P, et al. Results of
paranasal sinus tumors. Philadelphia: WB Saunders; treatment of patients with maxillary sinus carci-
1995. p. xi–ii. noma. Cancer 1998;83:457–65.
2. Mortignoni G, Huvos AG. Assessment of patients 17. Sievers KW, Greess H, Baum U, et al. Paranasal
with suspected sinonasal neoplasm. In: Kraus DH, sinuses and nasopharynx CT and MRI. Eur J Radiol
Levine HL, editors. Nasal neoplasia. New York: 2000;33:185–202.
Thieme; 1997. p. 21–42. 18. Eisen MD, Yousem DM, Montone KT, et al. Use of
3. Sukenik MA, Casiano R. Endoscopic medial maxil- preoperative MR to predict dural, perineural, and
lectomy for inverted papillomas of the paranasal venous sinus invasion of skull base tumors. AJNR
sinuses: value of the intraoperative endoscopic Am J Neuroradiol 1996;17:1937–45.
examination. Laryngoscope 2000;110:39–42. 19. Calderon-Garciduenas L, Delgado R, Calderon-Gar-
4. Blaugrund S, Parisier SC. Benign tumors of the ciduenas A, et al. Malignant neoplasms of the nasal
nasal sinuses. Otolaryngol Clin North Am 1971;4: cavity and paranasal sinuses: a series of 256 patients
143–57. in Mexico City and Monterrey. Is air pollution the
5. Goepfert H, Luna M, Lindberg RD, White AK. missing link? Otolaryngol Head Neck Surg
Malignant salivary gland tumors of the paranasal 2000;122:499–508.
826 Ballenger’s Otorhinolaryngology
20. Giri SP, Reddy EK, Gemer LS, et al. Management of 35. Weisman R. Lateral rhinotomy and medial maxil-
advanced squamous cell carcinomas of the maxillary lectomy. Otolaryngol Clin North Am 1995;28:
sinus. Cancer 1992;69:657–61. 1145–56.
21. Lund VL, Howard DJ. Tumors of the paranasal 36. McCutcheon IE, Blacklock JB, Weber RS, et al. Ante-
sinuses. In: Gershwin ME, Incaudo GA, editors. Dis- rior transcranial (craniofacial) resection of tumors
eases of the sinuses. Totowa (NY): Humana Press; of the paranasal sinuses: surgical technique and
1996. p. 291–310. results. Neurosurgery 1996;38:471–9.
22. Mosesson RE, Som PM. The radiographic evaluation 37. Marenette L, Moore CE. Subcranial approach to
of sinonasal tumors: an overview. Otolaryngol Clin tumors of the anterior cranial base. Otolaryngol
North Am 1995;28:1097–115. Head Neck Surg 2000;122:466–7.
23. Willatt DJ, Morton RP, McCormick MS, Stell PM. 38. Raben A, Pfister D, Harrison LB. Radiation therapy
Staging of maxillary cancer. Which classification? and chemotherapy in the management of cancers of
Ann Otol Rhinol Laryngol 1987;96:137–41. the nasal cavity and paranasal sinuses. In: Kraus DH,
24. Curran AJ, Gullane PJ, Waldron J, et al. Surgical sal- Levine HL, editors. Nasal neoplasia. New York:
vage after failed radiation for paranasal sinus malig- Thieme; 1997.
nancy. Laryngoscope 1998;108:1618–22. 39. Parsons JT, Bova FJ, Fitzgerald CR, et al. Severe dry
25. Tufano RP, Mokadam NA, Montone KT, et al. Malig- eye syndrome following external beam irradiation.
nant tumors of the nose and paranasal sinuses: Hos- Int J Radiat Oncol Biol Phys 1994;30:775–80.
pital of the University of Pennsylvania experience 40. Parsons JT, Kimsey FC, Mendenhall WM, et al. Radi-
1990-1997. Am J Rhinol 1999;13:117–23. ation therapy for sinus malignancies. Otolaryngol
26. MacNab TI, Flores AD, Anderson DW. Treatment of Clin North Am 1995;28:1259–68.
paranasal sinus malignancy: the BCCA experience. J 41. Brasnu D, Laccourreye O, Bassot V, et al. Cisplatin-
Otolaryngol 1992;21:244–8. based neoadjuvant chemotherapy and combined
27. Flores AD, Anderson SW, Doyle PJ, et al. Paranasal resection for ethmoid sinus adenocarcinoma reach-
sinus malignancy—a retrospective analysis of treat- ing and/or invading the skull base. Arch Otolaryngol
ment methods. J Otolaryngol 1984;13:141–6. Head Neck Surg 1996;122:765–8.
28. Waitz G, Wigand ME. Results of endoscopic sinus 42. Tsujii H, Tsuji H. [Several factors for improving
surgery for the treatment of inverted papillomas. results of radiation therapy]. Gan No Rinsho
Laryngoscope 1992;102:917–22. 1990;36:2393–7.
29. Stankiewicz JA, Girgis SJ. Endoscopic surgical treat- 43. McElroy EA, Buckner JC, Lewis JE. Chemotherapy
ment of nasal and paranasal sinus inverted papil- for advanced esthesioneuroblastoma: the Mayo
loma. Otolaryngol Head Neck Surg 1993;109:988–95. Clinic experience. Neurosurgery 1998;42:1023–7.
30. Myers EN, Petruzzelli GJ. Endoscopic sinus survey 44. Sakai S, Hohki A, Fuchihata H, Tanaka Y. Multidisci-
for inverted papilloma. Laryngoscope 1993;103: plinary treatment of maxillary sinus carcinoma.
711. Cancer 1983;52:1360–4.
31. Rice DH. Endonasal surgery for nasal wall tumors. 45. Perry C, Levine PA, Williamson BR, Cantrell RW.
Otolaryngol Clin North Am 1995;28:1117–25. Preservation of the eye in paranasal sinus cancer sur-
32. Levine HL, Timen SM, Papsidero MJ. Endoscopic gery. Arch Otolaryngol Head Neck Surg 1988;114:
management of nasal and sinus neoplasms. In: 632–4.
Kraus DH, Levine HL, editors. Nasal neoplasia. New 46. McCary WS, Levine PA. Management of the eye in
York: Thieme; 1997. p. 21–42. the treatment of sinonasal cancers. Otolaryngol Clin
33. Maniglia AJ, Phillips DA. Midfacial degloving for North Am 1995;28:1231–8.
the management of nasal sinus and skull base neo- 47. Stern SJ, Callender DL. Management of the orbit. In:
plasms. Otolaryngol Clin North Am 1995;28: Kraus DH, Levine HL, editors. Nasal neoplasia. New
1127–43. York: Thieme; 1997.
34. Catalano PJ, Sen C. Management of anterior eth- 48. Larson DL, Christ JE, Jesse RH. Preservation of the
moid and frontal sinus tumors. Otolaryngol Clin orbital contents in cancer of the maxillary sinus.
North Am 1995;28:1157–74. Arch Otolaryngol 1982;108:370–2.
Neoplasms of the Nose and Paranasal Sinuses 827
49. Tiwari R, van der Wal J, van der Wal I, Snow G. Stud- 51. Paulino AC, Fisher SG, Marks J. Is prophylactic neck
ies of the anatomy and pathology of the orbit in car- irradiation indicated in patients with squamous cell
cinoma of the maxillary sinus and their impact on carcinoma of the maxillary sinus? Int J Radiat Oncol
preservation of the eye in maxillectomy. Head Neck Biol Phys 1997;39:283–9.
1998;20:193–6. 52. Le Q, Fu KK, Kaplan MJ, et al. Lymph node metas-
50. Stern SJ, Goepfert H, Clayman G, et al. Orbital tasis in maxillary sinus carcinoma. Int J Radiat
preservation in maxillectomy. Otolaryngol Head Oncol Biol Phys 2000;46:541–9.
Neck Surg 1993;109:111–5.
CHAPTER 37
The normal auricle has a well-recognized configura- primates have poorly developed external muscula-
tion of depressions and projections. Although there ture and mobility. As an immobile structure, the
are many variations, significant deviations from auricle appears to facilitate localization of high-fre-
“normal” are immediately evident. In particular, quency sounds.1 In other species, the auricle can be
prominent ears are readily apparent and are a rela- manipulated to determine the direction of sound
tively frequent cause of patient concern. and to protect the internal auditory structures. Vol-
Correction of the outstanding ear requires a untary apposition of the tragus and antitragus pro-
careful understanding of the discrete elements that tects the ear from water and insect entry.
comprise the normal ear. Careful anatomic analysis
to determine the precise cause allows appropriate
preoperative planning for the correction of a pro- ANATOMY
truding ear. In selecting appropriate techniques from
the many that are described in the literature, the sur-
SURFACE FEATURES
geon must place greatest emphasis on reliably The vertical axis of the ear along its longest dimen-
achieving a natural-looking improvement. In gen- sion is rotated approximately 20 degrees from the
eral, techniques that reposition rather than resect vertical axis of the skull. The width should be
cartilage may be safer and are therefore preferred. approximately 55% of the length. “Idealized” dimen-
sions are 63.5 mm by 35.3 mm for males and
59.0 mm by 32.5 mm for females.3 The auricle is
EMBRYOLOGY 85% of adult size by 3 years of age and is 90 to 95%
Development of the auricle or pinna is initially visi- of full size by 5 to 6 years of age, although it may
ble in the 39-day-old embryo.1 The auricle is formed elongate an additional 1 to 1.5 cm during life.5 The
from six mesenchymal proliferations (hillocks of helical rim along its lateral edge is approximately 1
His) at the dorsal ends of the first and second to 2 cm from the mastoid skin. The angle of protru-
branchial arches surrounding the first branchial sion of the auricle or the auriculomastoid angle is
groove. These elements begin in the lower neck and usually between 15 and 30 degrees.
ascend to the level of the eyes at the side of the head Among important surface features is the helix,
during gestation. Cartilage formation is visible in the the prominent rim of the auricle (Figure 37–1). Par-
seventh week, and hillock fusion occurs in the twelfth allel and anterior to the helix is another prominence
week of gestation. The recognizable shape of the known as the antihelix or antihelical fold. Superiorly,
auricle is visible by the twentieth week of gestation. the antihelix divides into a superior and an inferior
Although each of the six hillocks was previously cor- crus, which surround the fossa triangularis. The
related to a specific element of the auricle, current depression between the helix and antihelix is known
studies suggest that the first branchial arch elements as the scapha or scaphoid fossa. The antihelical fold
contribute to the tragus and the second branchial surrounds the concha, a deep cavity posterior to the
arch elements form the remaining structures.2–4 external auditory meatus. The crus helicis, which
Despite much speculation, the functional role represents the beginning of the helix, divides the con-
of the auricle in humans remains unclear. Unlike the cha into a superior portion, the cymba conchae, and
pinnae of other species, the auricles of humans and an inferior portion, the cavum conchae. The cavity
828
Reconstruction of the Outstanding Ear 829
formed by the concha on the anterior (lateral) sur- auricle with the side of the head and the intrinsic lig-
face of the ear corresponds to a bulge or convexity on aments connect various parts of the cartilage to itself
the posterior (medial) surface of the ear that is and to the external auditory meatus. The intrinsic
known as the eminence of the concha. group of muscles is rudimentary and serves no recog-
Anterior to the concha and partially covering nizable functional purpose. These include the major
the external auditory meatus is the tragus. The anti- helix, minor helix, tragus, antitragus, transverse, and
tragus is posteroinferior to the tragus and is sepa- oblique muscles. The extrinsic muscles include the
rated from it by the intertragic notch. Below the anterior auricularis, superior auricularis, and poste-
antitragus is the lobule that is composed of areolar rior auricularis. Certain individuals may have limited
tissue and fat. Anatomic variations such as preauric- control of these muscles to “wiggle” the auricle.
ular tags or Darwin’s tubercle, a small projection The arterial supply of the auricle is derived
along the helix, may be present on the ear and from the anterior auricular branch of the superficial
should be recognized and documented in the pre- temporal artery, the posterior auricular branch of the
operative assessment.6 external carotid artery, and a branch of the occipital
artery. Venous drainage is from the posterior auricu-
lar vein and the superficial temporal, external jugular,
STRUCTURAL FEATURES and retromandibular veins. Lymphatic drainage from
Except for the lobule, the auricle is supported by the ear moves anteriorly to the parotid lymph nodes
thin, flexible elastic fibrocartilage. This cartilaginous and posteriorly to the cervical lymphatics.
framework is 0.5 to 1.0 mm thick and covered by a Innervation to the extrinsic muscles is supplied
minimum of subcutaneous tissue.4 The skin is by the facial nerve (cranial nerve [CN] VII). The
loosely adherent to the posterior surface and helix posterior auricularis is innervated by the posterior
of the auricular cartilage. The close approximation auricular branch of the facial nerve proximal to the
of the skin to the anterior surface of the cartilage pes anserinus.1 The temporal branch of the facial
provides the auricle with its unique topographic fea- nerve innervates both the anterior and superior
tures (Figure 37–2). auricularis. Many nerve branches contribute to the
The auricle has two groups of ligaments and sensory innervation of the auricle. The greater auric-
musculature. The extrinsic ligaments connect the ular nerve (C3) and the mastoid branch of the lesser
830 Ballenger’s Otorhinolaryngology
occipital nerve (C2, C3) carry sensation from the PATHOGENESIS OF THE
posterior surface of the auricle. The auriculotempo- OUTSTANDING EAR
ral nerve (CN V3) provides sensory innervation to
the anterosuperior portion of the auricle. Branches Malformations of the auricle are not unusual and
from the facial nerve (CN VII) and Arnold’s nerve range from complete absence to macrotia. The inci-
(CN X) innervate the concha.4–6 dence of abnormally protruding ears is approxi-
Reconstruction of the Outstanding Ear 831
mately 5% in Caucasians.7 As the auricle assumes a The most common cause of outstanding ears is
recognizable form by the end of the twelfth gesta- the lack of development of the antihelical fold (Figure
tional week, the greatest number of malformations 37–3). This malformation of the antihelix is present in
occur. Although they may be a dominant or recessive approximately two-thirds of all cases of protruding
trait, most ear deformations are inherited as an ears. However, other pathologic features may also
autosomal dominant trait with incomplete pene- contribute to the outstanding ear. A wide, protruding
trance.8 Understanding the pathogenesis of these conchal wall is present in approximately one-third of
deformities aids the plastic surgeon in developing an all cases. Additionally, the prominent concha is often
operative plan. accompanied by a thickened antitragus.10
Davis and Kittowski pointed out that during The outstanding ear is a single entity within a
development, the ear protrudes from the head wide spectrum of auricular malformation. Depend-
because the crura of the antihelix are not formed.9 ing on the degree of severity, the protruding ear may
The margins of the auricle curl in the sixth fetal also have structural abnormalities seen in the classi-
month to form the helix, followed by the folding of cally described “lop ear” and/or “cup ear.” The term
the antihelix and the development of the superior “lop ear” is used to describe a deformity of the helix
and inferior crura. The formation of the antihelix characterized by a thin, flat ear that is acutely folded
and its crura brings the auricle closer to the head. downward at the superior pole. In the “cup ear”
deformity, weak cartilage with resulting limpness of children with protruding ears are commonly sub-
the auricle results in cupping or deepening of the jected to severe ridicule by their young peers.11–13
conchal bowl. The “cup ear” is often smaller than A comprehensive and quantitative approach
normal and folded on itself. Poor development of for complete evaluation of the patient’s ears is essen-
the superior portion of the ear results in a short, tial.12 The auricles are compared with each other,
thickened helix and a deformed antihelix (Figure both in overall symmetry and projection from the
37–4). The surgical techniques used to correct the head. The proportion of the auricles to facial fea-
outstanding ear may be applied to the “lop ear” and tures and the head must be appreciated. The appear-
to the “cup ear,” but the correction of these malfor- ance of the auricles is judged by the symmetry from
mations extends beyond the scope of this chapter.7–10 the front along the lateral helical rim. The superior
aspect of the auricles should be level with the eye-
brows. Additionally, development of the surface
PREOPERATIVE EVALUATION landmarks should be noted, along with additional
Patients with outstanding ears typically present early features such as preauricular tags. The individual
in childhood, although some present in adulthood. features within the auricle should be assessed in rela-
The optimal age for surgical correction is between 4 tion to other surface landmarks. For example, there
and 6 years of age. At this age, the auricle is near or at should be a balance between the size and promi-
full adult size, and the child is capable of participat- nence of the helix and antihelix or between the tra-
ing in the postoperative care of the ear. Also, the child gus and antitragus. Finally, the redundancy of the
is typically about to enter school, and, unfortunately, postauricular skin should be noted, and the thick-
ness and stiffness of the cartilage should be assessed
and compared between the ears.
Precise measurements can be made to docu-
ment the height, width, and axis of the auricle. Addi-
tionally, the angular relationships of the auricle and
concha to the mastoid can be documented. Symme-
try between the two ears can also be compared by a
standard set of measurements, which can provide
standards for assessment preoperatively and intra-
operatively.13
Although the classic description of the out-
standing ear attributes this deformity to the absence
of the antihelical fold, two other attributes must be
carefully assessed. Overprojection of the concha
and/or the lobule will also contribute to the appear-
ance of the protruding ear. Consideration and cor-
rection of these elements will contribute to the
ultimate goal of a normal-appearing auricle.
As with any cosmetic procedure, preoperative
and postoperative photographs are absolutely criti-
cal for careful planning of the surgical procedure
and to document changes to the auricle. Uniform
lighting and views of the auricle should be used
before and after the surgery. The photographs
should include a full-face anterior and full-head
posterior view, an oblique/lateral view of both sides
of the head, and close-up views of the ears. For
patients with long hair, a hair clip or headband can
be useful to prevent the hair from obstructing accu-
FIGURE 37–4. “Cup ear” deformity. rate photodocumentation.
Reconstruction of the Outstanding Ear 833
GOALS OF SURGERY FOR THE at times, unrealistic expectations for the surgery may
OUTSTANDING EAR exist. If this is the case, surgery should be deferred,
and referral for counseling may be appropriate.
The primary goal of otoplasty is to re-establish a Coexisting anomalies, bleeding disorders, and
“natural” appearance to the auricle and the relation- any history or tendency toward hypertrophic scar-
ship of the auricle with the head. Careful assessment ring or keloid formation should be noted and
of the outstanding ear, as described above, will reveal addressed preoperatively.
those individual elements of the auricle that con-
tribute to its abnormal appearance. McDowell pro-
vided guidelines that should be considered when
SURGICAL TECHNIQUES: A
undertaking correction of the protruding ear14: HISTORICAL PERSPECTIVE
1. Symmetry of shape and protrusion of the ears In 1845, Dieffenbach described correction of the out-
should vary no more than 3 mm. Correction will standing ear through removal of skin from the back of
often require bilateral alterations. the ear and suturing of the auricular cartilage to the
2. Maintain the normal appearance and curvature periosteum of the mastoid bone.15 In 1881, Ely and
of the auricular components. The helix should others described similar procedures with the addi-
arch backward naturally from its crus. It should tional excision of the posterior portion of the auricu-
be furled at its superior aspect and lead smoothly lar cartilage.16 More complicated procedures were later
to the lobule. The antihelix should similarly described that involved complex cartilage manipula-
curve forward into the superior crus. tions and even the use of fascia lata. However, these
3. The distance of the helical rim from the mastoid procedures are now primarily of historical interest
skin should be 10 to 12 mm at the superior pole, because they resulted in ears that were abnormally flat-
16 to 18 mm at the middle one-third, and 20 to tened against the head and that often had sharp visible
22 mm at the level of the cauda helix. The proper edges, excess skin wrinkling, and other problems.
auriculomastoid angle is 15 to 25 degrees. In 1910, Luckett identified the absence or
Achieving these distances may require reduction underdevelopment of the antihelical fold as the cause
of the classic protruding ear.17 His technique for the
of an overly large conchal bowl.
correction of this deformity involved the excision of
4. The helical rim should not be seen beyond the
a crescent-shaped segment of posterior skin and car-
antihelix from the frontal view, at least down to
tilage from the intended site of the antihelical fold
the mid-ear.
and re-creation of the antihelix by everting and
5. The postauricular sulcus should be preserved.
suturing together the cartilage edges. Unfortunately,
6. Protrusion of the upper one-third of the ear must
this approach resulted in less than optimal results
be corrected. Protrusion of the lower ear may be
and fell out of favor. Nevertheless, Luckett’s identifi-
tolerable, but only if the superior portion of the
cation of the primary cause of protruding ears led to
auricle has been corrected.
the development of currently employed techniques.
7. All visible surfaces should be smooth, without
Otoplasty techniques have evolved toward the
buckles, puckering, scars, and ridges that would
goal of a natural-appearing ear that is not too close
reveal operative manipulation.
to the head and does not have sharp ridges along the
Although the physical dimensions and struc- anterior surface of the auricle. Davis and Kittowski
tural features are essential in the evaluation of the described a technique in which the new antihelix
outstanding ear, the subjective assessment of the fold was placed in line with the inferior crus. In their
patient and his/her parents is also important. The approach, skin was removed from the posterior
surgeon should understand precisely what a patient auricular surfaces of the concha and mastoid.9 Car-
dislikes about his/her ears and what he/she hopes the tilage was then removed from the region of the new
operation will achieve. This will help the surgeon antihelix, and the remaining edges were everted and
determine if surgery can achieve the patient’s desires sutured together.
and whether the patient’s goals are realistic. Thus, the Young would later modify this approach by
surgeon can explain the specific goals and limitations creating the new antihelix along the superior crus.18
of otoplasty to the patient and his/her parents. Also, Becker advocated multiple incisions along natural
834 Ballenger’s Otorhinolaryngology
lines of the cartilage to shape a new antihelix and to less dissection of the ear and less surgical trauma
conceal surgical ridges along normal folds of the than other approaches. Surgeons also found this
auricle.19 However, this method still required exci- approach relatively easy to learn and to teach.
sion of cartilage. Although the results from this Whereas Mustarde’s technique addressed the
approach were gratifying, like other cartilage-split- most common deformity of the protruding ear, the
ting procedures, the excision of cartilage from the absent antihelix, Furnas described a suture fixation
antihelix occasionally left a sharpened ridge. This method to address the deep conchal bowl.23 Furnas
ridge was reported to be acceptable to most patients described the placement of a permanent suture to
at the time but was disconcerting to the surgeon adjust the apposition of the conchal bowl to the
seeking a natural-looking result.6 mastoid periosteum, decreasing the angle between
In the late 1950s, Gibson and Davis demon- the concha and the mastoid. Additionally, a suture
strated techniques to modify the shape of cartilage.20 from the fossa triangularis to the temporalis fascia
Disruption of perichondrium from one side of the may further correct conchal height or contour. Care
cartilage led to bowing of the cartilage toward the must be taken when placing the suture to avoid rota-
surface with the intact perichondrium. Nachlas and tion of the auricle anteriorly with resultant external
associates and Stenstrom and Heftner described pro- auditory canal narrowing.
cedures based on this cartilage-sculpting princi-
ple.11,21 Access to the anterior surface of the auricular
cartilage involves a posterior auricular incision and
COMBINATION TECHNIQUES
either dissection over the helical rim or an incision Subsequent to the description of mattress suture
through the auricular cartilage. Various instruments techniques, cartilage-cutting approaches have
such as a wire brush, rasp, or diamond bur are used remained useful in combination with suture tech-
to disrupt the anterior perichondrium to permit
bowing of the cartilage to form a new antihelix.
These techniques are technically complex, requiring
a great deal of surgical experience.
niques. Pitanguy and Flemming devised a method to technically difficult procedures that require substan-
create an island flap of cartilage that was secured tial surgical experience.
anteriorly to the rest of the conchal cartilage by place-
ment of permanent horizontal mattress sutures.24
Converse and Wood-Smith described a technique of
MATTRESS SUTURE OTOPLASTY: METHOD OF
thinning portions of the cartilage between incisions TARDY
that followed natural lines of the cartilage. This tech- Mattress suture techniques with modifications are
nique facilitated the creation of an island of cartilage widely used today. One approach will be reviewed in
that sets anteriorly to the rest of the conchal cartilage detail here (Figure 37–6).6 Suture fixation techniques
to refashion the antihelix.25 The technique of Farrior are relatively easy to perform and do not require
requires the removal of multiple longitudinal wedges incisions or excisions of the cartilage that perma-
from the level of the superior crus and the location of nently alter cartilage characteristics or leave perma-
the new antihelical fold.26 The auricular cartilage is nent postoperative stigmata.
then incised to permit shaping by the placement of Although the horizontal mattress suture is the
horizontal mattress sutures. primary mode of repair in this technique, it is
All of these techniques have been employed by important to emphasize the importance of address-
experienced surgeons to create a gently curved ing thick and inflexible cartilage. The mattress suture
appearance to the antihelix and a pleasing appear- procedure is frequently augmented by thinning,
ance to the postoperative ear. The cartilage-cutting weakening, and occasionally limited incision of the
techniques may be especially useful when large cartilage to achieve natural and symmetric results.
anatomic deformities must be corrected or when the Thinning the cartilage by shave excision or with a
auricular cartilage is especially inflexible or thick. bur and incisions through the cartilage to facilitate
However, the caveat must be repeated that these are folding will reduce the tension on the horizontal
mattress sutures. Thus, every surgeon performing The new antihelix is created by manipulating
otoplasty must be comfortable addressing the pro- the auricular cartilage and blending this fold into the
truding ear with more than one technique. Knowl- inferior crus. Temporary 4-0 silk marking sutures
edge of one technique only is inadequate. may be placed from anterior to posterior to mark
In the operating room, the ears are reassessed the location of the horizontal mattress sutures and
with regard to the causes of protrusion. Special thereby precisely guide their placement. This
attention is directed to the depth of the conchal method avoids the use of ink or sharp needles to
bowl, the position of the lobule, and the strength guide placement of the permanent sutures.
and flexibility of the auricular cartilage. The periau- Once the new antihelix has been marked, 4-0
ricular areas are prepared with a sterile cleansing braided nylon (Tevdek) horizontal mattress sutures
solution (hexachlorophene or povidone-iodine) and are placed sequentially, from caudal to cephalad along
draped with sterile towels. The postauricular skin the neoantihelical fold. These horizontal mattress
and subcutaneous tissue are infiltrated with local sutures are placed through the posterior perichon-
anesthetic (eg, 1% lidocaine with 1/100,000 epi- drium, auricular cartilage, and anterior perichon-
nephrine) for analgesia and hemostasis. The head is drium. Careful palpation with the free hand along the
draped in a manner that permits comparison of anterior surface of the auricle ensures that the needle
both ears intraoperatively. does not pass through the anterior skin. Incorpora-
A fusiform or “elliptical dumbbell”-shaped inci- tion of the anterior perichondrium in the horizontal
sion is made posteriorly, exposing the portion of mattress suture is necessary to prevent the suture
auricular cartilage in the area of the soon-to-be- from tearing through the cartilage when it is tied
formed antihelix. Care is taken to avoid removal of down. Additionally, the sutures are not placed near
skin in the postauricular sulcus, which would cause the incision site to prevent future suture extrusion.
flattening of the ear against the head. The skin is The horizontal mattress sutures are placed from
excised, leaving the posterior deep soft tissue and caudal to cephalad and test-tied. Sutures are removed
perichondrium that facilitates later scar formation, and replaced as necessary to achieve the desired fold
which is the strength of the repair. The remaining skin on the auricular cartilage and then held with a hemo-
is undermined to the postauricular sulcus and to the stat. The sutures are tied securely once the antihelix
helical rim. Meticulous hemostasis should be main- has been completely formed. Typically, four or more
tained at this juncture and throughout the procedure. mattress sutures are necessary to distribute the ten-
A deep conchal bowl, when it exists, may be sion evenly and to hold the repair until sufficient scar
addressed initially. Undermining along the posterior tissue forms, usually in 2 to 3 months. If the sutures
aspect of the cartilage reveals the posterior eminence are adequately placed, it is unnecessary to overcor-
of auricular cartilage underlying the conchal bowl. rect the repositioning of the auricle since the sutures
Excess cartilage in the posterior eminence frequently will maintain their position without slippage. The
causes this area to impinge on the mastoid process, postauricular skin is closed with a fast-absorbing 5-0
preventing the ear from resting closer to the head. chromic gut suture in a continuous fashion.
Using a scalpel, small disks of cartilage can be shaved Following creation of a neoantihelical fold, the
from this region to allow retropositioning of the position of the lobule is assessed. Ideally, the helix
auricle. This cartilage sculpturing is often sufficient and antihelix should be in the same plane as the lob-
to retroposition the ear and makes conchal setback ule. Commonly, simple skin excision and reattach-
sutures unnecessary. Excision of cartilage in this area ment are sufficient to position the lobule in the
will weaken the cartilage, reducing overall tension on appropriate plane, although more extensive inter-
the mattress sutures that will be placed in the antihe- vention may be required at times.
lix region. Great care is taken to achieve partial-thick- The procedure is completed on the opposite
ness excision of cartilage, and through-and-through ear. Frequent comparison between both ears ensures
excision is avoided. Nevertheless, on occasion, the as symmetric a repair as possible. Given the nature of
auricle with a very deep cavum conchae may require auricular deformities, complete symmetry between
conchal setback sutures or, rarely, the excision of a both ears is nearly impossible (Figure 37–7).
semilunar segment of cartilage within the cavum At the conclusion of the surgery, a conforming
conchae to reconstruct the neoantihelix properly. dressing is applied followed by a bulky head dress-
Reconstruction of the Outstanding Ear 837
A B
C D
838 Ballenger’s Otorhinolaryngology
E F
G H
FIGURE 37–7. Preoperative (A to E) and postoperative (F to H) photographs of a patient who underwent left oto-
plasty with the technique described here. This patient had a relatively minor deformity of the right ear and was not
disturbed by it, so only a left otoplasty was performed.
Reconstruction of the Outstanding Ear 839
ing, which is removed and replaced with a smaller The cartilaginous framework is avascular, and
dressing that the patient wears for an additional 36 incisions of the cartilage and manipulation of the
to 72 hours. thin skin–subcutaneous envelope may compromise
the structural integrity of the auricle. Meticulous
hemostasis during otoplasty and a postoperative
OUTCOMES AND COMPLICATIONS pressure dressing are valuable measures for prevent-
Surveys have demonstrated high rates of patient sat- ing postoperative complications. Immediate and late
isfaction (82 to 95%) following otoplasty.21,27,28 Unsat- complications, if unrecognized, may lead to unde-
isfactory cosmetic results were reported in 4.8 to sirable anatomic sequelae. Chondritis and necrosis
13.6% of cases; the rate was often higher for cartilage- of the auricle are among the most feared and poten-
cutting techniques.29 Rates of relapse of auricular pro- tially devastating complications. Early manifesta-
trusion range from 2 to 13%.27,30,31 Interestingly, more tions of these situations must be quickly identified
than almost half of the patients in this group reported and managed to protect the integrity and appear-
an injury in the postoperative period.30 ance of the auricle. Intraoperatively, great care must
Regardless of the surgical techniques employed, be taken during dissection, and hemostasis must be
complications (Table 37–1) are reported to occur at diligently maintained. In the event that a hematoma
rates ranging from 7.1 to 11.4%.13,27,28,30 In the early forms, the wound must be opened and the
postoperative period, patient concerns regarding hematoma evacuated rapidly. Otherwise, infection
postoperative pain or periauricular “tightness” leading to perichondritis, chondritis, and permanent
should be taken seriously as they may herald the cosmetic deformity may ensue.
presence of a hematoma. Physical examination might Infection may occur secondary to an unevacu-
reveal fluctuance under a tense, dusky area of skin. ated hematoma but may also result from lapses in
The incidence of hematoma formation is about 3% sterile technique or the presence of contaminated
and occurs slightly more often in cartilage-cutting suture. Evolution to perichondritis occurs in
techniques.28 approximately 1% of all cases.28 Treatment must be
aggressively implemented to prevent chondritis and
resulting cartilage necrosis and auricular deformity.
TABLE 37–1. Otoplasty Complications Antibiotic treatment must empirically cover
Pseudomonas aeruginosa. Persistent infection may
Early complications also necessitate the removal of permanent sutures
Hematoma and débridement locally. Preoperatively, a single
Infection dose of a broad-spectrum antibiotic can minimize
Perichondritis/chondritis and permanent auricular the risk of infection.
deformity In the late postoperative period, patients may
Late complications complain of paresthesias and hypersensitivity, espe-
Paresthesia/hypersensitivity cially to cold temperatures in the weeks to months
Suture extrusion following otoplasty. These symptoms may indicate
Suture granuloma formation that injury may have occurred that is related to
Skin necrosis aggressive traction on the sutures intraoperatively or
Hypertrophic scarring as a result of nerve transection. The complaints usu-
Keloid fomation ally resolve or become tolerable over the next 4 to 6
months without active intervention.
Anatomic/esthetic complications
Over the long term, permanent sutures may
Inadequate correction
induce granuloma formation or be extruded. Suture
Antihelix overcorrection and hidden helix
extrusion may occur in as many as 10% of patients,
Telephone ear
but, typically, the area heals without adverse seque-
Prominent concha
lae. In placing sutures, care must be taken in distrib-
Malposition of the lobule
uting cartilage tension over an adequate number of
Sharp cartilage edges
permanent cartilage-shaping sutures. Additionally,
Distortion of the external auditory canal (stenosis)
techniques to weaken the cartilage may decrease the
840 Ballenger’s Otorhinolaryngology
overall tension applied to the sutures and decrease 3. Farkas LG. Anthropometry of normal and anom-
the risk of suture extrusion. alous ears. Clin Plast Surg 1978;5:401–12.
As the wound heals, there is some risk of 4. Weerda H. Embryology and structural anatomy of
hypertrophic scarring and keloid formation, espe- the external ear. Facial Plast Surg 1985;2:85–91.
cially on the posterior surface. This is more common 5. Larrabee WF, Makielski KH. Surgical anatomy of the
in younger patients, patients with a history of scar- face. New York: Raven Press; 1983.
ring, and in African American and Asian American 6. Kotler HS, Tardy ME. Reconstruction of the outstand-
patients. Conservative treatment includes triamci- ing ear (otoplasty). In: Ballenger JJ, Snow JB, editors.
nolone acetonide injection weekly. Scar excision and Otorhinolaryngology head and neck surgery. 15th ed.
closure without tension are also a consideration. Baltimore: Williams and Wilkins; 1996. p. 989–1002.
Esthetic complications arise from either 7. Bardach J. Congenital ear deformities. Surgery for
incomplete or overly aggressive treatment of the congenital and acquired malformations of the auri-
original deformity. Although not considered a defor- cle. In: Cummings CW, Frederickson JM, Harker LA,
mity in the nonoperated ear, a helical rim that is Krause CJ, et al, editors. Otolaryngology—head and
retropositioned relative to the antihelix is undesir- neck surgery. St. Louis: Mosby; 1986. p. 2861–98.
able and is usually secondary to overcorrection of 8. Potter E. A hereditary ear malformation transmitted
the neoantihelix. This deformity can be seen if Mus- through five generations. J Hered 1937;28:255–8.
tarde sutures are drawn too tightly or if overaggres- 9. Davis JD, Kittowski EA. Abnormal prominence of
sive skin excision is undertaken. the ears: a method of readjustment. Surgery 1937;2:
In undertaking conchal repositioning, care 835–48.
must be taken in suture placement. Sutures placed 10. Tanzer RC. Congenital deformities. Deformities of the
too far posteriorly on the concha or too far anteri- auricle. In: Converse JM, editor. Reconstructive plas-
orly on the mastoid can result in stenosis of the tic surgery. 2nd ed. Philadelphia: WB Saunders; 1977.
external auditory canal. p. 1671–1719.
Overcorrection of the middle portion of the
11. Nachlas NE, Duncan D, Trail M. Otoplasty. Arch
ear leads to a “telephone ear” deformity owing to the
Otolaryngol 1970;91:44–9.
relative prominence of the superior and inferior
12. Aguilar EA. Congenital auricular malformation. In:
poles. One commonly described cause of the tele-
Bailey BJ, Calhoun KH, Deskin RW, Johnson JT, et al,
phone ear deformity is over-reduction of the hyper-
editors. Head and neck surgery—otolaryngology. 2nd
trophic concha. Alternatively, overcorrection of the
ed. Philadelphia: Lippincott-Raven; 1998. p. 2753–67.
upper and lower poles may result in the “reverse tele-
13. Nachlas NE, Smith HW, Keen MS. Otoplasty. In:
phone ear” deformity.
Papel ID, Nachlas NE, editors. Facial plastic and
As discussed in this chapter, otoplasty methods
reconstructive surgery. St. Louis: Mosby-Year Book;
that incise rather than reposition cartilage run the
1992. p. 256–69.
risk of visible sharp edges or prominent creases.
With significant attention focused on the anti- 14. McDowell AJ. Goals in otoplasty for protruding ears.
helical fold and addressing the cavum concha, the Plast Reconstr Surg 1968;41:17–27.
position of the lobule may be overlooked. The lob- 15. Dieffenbach JF. Die Operative Chirurgie. Leipzig
ule and helix should lie in approximately the same (Germany): FA Bruckhaus; 1845.
plane. Although amputation of the cauda helices or 16. Ely E. An operation for prominence of the auricles.
cauda repositioning is sometimes necessary, most Arch Otolaryngol 1881;10:97.
commonly, excision of a soft tissue triangular seg- 17. Luckett WH. A new operation for prominent ears
ment from the posterior lobular surface is effective. based on the anatomy of the deformity. Surg
Gynecol Obstet 1910;10:635–47.
18. Young F. The correction of abnormally prominent
REFERENCES ears. Surg Gynecol Obstet 1944;78:541–50.
1. Gulya AJ. Developmental anatomy of the ear. In: 19. Becker OJ. Surgical correction of the abnormally
Glascock ME, Shambaugh GE, editors. Surgery of the protruding ear. Arch Otolaryngol 1949;50:541–60.
ear. 4th ed. Philadelphia: WB Saunders; 1990. p. 5–33. 20. Gibson T, Davis WB. The distortion of autogenous
2. Wood-Jones F, I-Chuan W. Development of the cartilage grafts: its cause and prevention. Br J Plast
external ear. J Anat 1934;68:255. Surg 1958;10:257.
Reconstruction of the Outstanding Ear 841
21. Stenstrom SJ, Heftner J. The Stenstrom otoplasty. 26. Farrior RT. A method of otoplasty. Arch Otolaryngol
Clin Plast Surg 1978;5:465–70. 1959;69:400–8.
22. Mustarde JC. Correction of prominent ears using 27. Minderjhan A, Huttl WR, Hildmann H. Mustarde’s
simple mattress sutures. Br J Plast Surg 1963;16: otoplasty: evaluation of correlation between clinical
170–6. and statistical findings. J Maxillofac Surg 1980;8:
23. Furnas DW. Correction of prominent ears by con- 241–50.
chamastoid sutures. Plast Reconstr Surg 1968;42: 28. Goode RL, Profitt SD, Rafaty FM. Complications of
189–93. otoplasty. Arch Otolaryngol 1970;91:352–5.
24. Pitanguy I, Flemming I. Plastic operations of the 29. Davis JS. Prominent ears. Clin Plast Surg 1978;5:471–7.
auricle. In: Naumann HH, editor. Head and neck 30. Adamson PA, McGraw BL, Tropper GJ. Otoplasty:
surgery. Philadelphia: WB Saunders; 1982. p. 1–18. critical review of clinical results. Laryngoscope 1991;
25. Converse JM, Wood-Smith D. Technical details in 101:883–8.
the surgical correction of the lop ear deformity. Plast 31. Maniglia AJ, Maniglia JJ, Witten BR. Otoplasty: an
Reconstr Surg 1963;31:118–28. eclectic technique. Laryngoscope 1977;87:1359–68.
CHAPTER 38
INCISIONS AND EXCISIONS incision creates a visible but symmetric scar that, if
meticulously repaired, fades acceptably with time.
External nasal incisions should be sited in incon-
Open rhinoplasty incision approaches may be
spicuous areas, leading to minimal distortion of
preferable.
nasal features and symmetry.1 Junctions of facial
Mature nasal scars on exposed nasal epithe-
landmarks hide surgical scars well; therefore, inci-
lium (ie, not camouflaged in landmark junctions or
sions along the nasomaxillary groove, the alar-facial
natural folds) may be rendered less conspicuous
junction, and the columellar-labial (or nasolabial)
with superficial mechanical dermabrasion. Minimal
junction heal inconspicuously. Lesion excision in
these areas should be preplanned so that the ulti-
mate suture line(s) will symmetrically re-create these
natural landmark borders. Strict attention to main-
taining or re-creating symmetry leads to superior
esthetic results. Local pedicle flaps transposed into
these areas should be similarly designed.
Natural folds created by the synergistic inter-
action of muscle groups at the root of the nose pro-
vide ideal sites for incision and excision camouflage.
Horizontal, oblique, and vertical wrinkles apparent
in this area, blending into the glabellar region, pro-
vide wide latitude in scar camouflage in the aging
patient (Figure 38–1). Redundant nasal and glabel-
lar skin allows considerable excisional license with-
out sacrificing normal landmarks. It is usually
possible and always preferable to reconstitute these
natural folds during the course of repair.
Alternate, but less ideal, incision sites exist.
Midcolumellar incisions generally heal with mini-
mal scar evidence,2 although the lateral columellar
incision lends similar surgical access and creates less
potential scar. Staggered or W-shaped incisions in
the caudal midcolumellar area are acceptable for
tumor excision and as an approach to external
rhinoplasty procedures.
Congenital nasal tumors (dermoid cysts,
lymphangiomas) in children require incisional
approaches through the nasal dorsum, with wide
exposure required for total excision. A precise FIGURE 38–1. Favorable lines for incision and excision
midline dorsal incision or semilunar transverse in the nasal and paranasal region.
842
Nasal Reconstruction and Rhinoplasty 843
used when more abundant tissue is required for repair fold should be preserved or reconstituted to achieve
or adjacent skin is inadequate or unsatisfactory. They bilateral facial symmetry, with incisions falling in the
use unipedicled flaps of similar texture, thickness, and nasolabial crease. The inherent elasticity and redun-
color from adjacent regions (glabella, forehead, scalp, dancy of skin allow a variety of geometric designs in
cheek, neck). A second stage of repair is required to creating advancement flaps with ultimate suture
transect the bridge of the flap, reconstructing both the lines lying in favorable areas for camouflage.
defect and donor site to render them inconspicuous. Advancement flaps along the dorsum of the
Regional flaps are invariably designed and transposed nose may be created after transverse fusiform exci-
from areas of relative epithelial excess and redun- sion of lesions, diminishing the defect when possi-
dancy in the head and neck. ble by shortening the nose and accomplishing
hump removal.
ADVANCEMENT FLAPS
Advancement flaps are created when tissue is under-
ROTATION FLAPS
mined and advanced generally in a straight line, A local flap in which the axis is created in a plane dif-
along the same axis as the defect. ferent from that of the defect is termed a rotation
Mobile cheek skin may be undermined and flap. Rotation flaps are extremely useful in nasal
advanced to repair heminasal defects of varying pro- repair, particularly when designed so that the donor
portions (Figure 38–3, A and B). Design is such that site may be closed in an inconspicuous straight line,
ultimate closure falls in the nasolabial fold and infra- natural fold, or landmark junction. Typical ideal
ciliary area and at the junction of the nose to the face donor sites are the nasolabial fold (Figure 38–5, A
(Figure 38–4, A to C). Where possible, the nasolabial and B) and glabellar regions (Figure 38–6, A and B).
FIGURE 38–3. A and B, Cheek advancement flap for lateral nasal reconstruction.
Nasal Reconstruction and Rhinoplasty 845
FIGURE 38–5. A and B, Nasolabial rotation flap for reconstruction of a nasal alar defect. The alar-facial junction is
reconstituted.
reducing taping (Steri-strips) or tissue glues (His- possibilities for nasal defect repair. Transposition
toacryl blue, Dermabond) enhance wound approxi- flaps ordinarily allow primary closure of defects
mation and allow earlier removal of sutures. Light larger than those repaired with the simpler
compression bandages are used for 24 to 48 hours advancement and rotation flaps. When the flaps
and then removed and replaced by Neodecadron are properly designed, little tension is created on
ophthalmic ointment to keep the suture lines free of suture lines, and “dog ears” or “standing cones” are
debris and clot, maximizing early healing. minimized.
Properly designed and executed, rotation flaps In addition to the classic transposition flap
of adjacent nasal tissue may be expected to provide design, bilobed transposition flaps, rhomboid trans-
superior three-dimensional reconstruction of surgi- position flaps, and the standard ubiquitous Z-plasty
cal and traumatic nasal defects within several weeks are superior methods of epithelial nasal reconstruc-
of repair. Defatting and “touch-up” procedures are tion with adjacent tissue.
rarely necessary. Light dermabrasion of the resulting The classic transposition flap design is useful in
fine nasal scars, 3 to 4 months later, can favorably the glabellar area, transposing redundant, lax tissue
enhance the blending effect. to upper lateral nasal defects. Proper design allows
the ultimate incision lines to fall in or near natural
folds, creating effective camouflage (Figure 38–7).
TRANSPOSITION FLAPS Similar designs can take advantage of redundant
By far the most versatile of adjacent flaps is the nasolabial fold cheek tissue, sliding tissue medially to
transposition flap. Transposition flap designs provide ample cover for lateral nasal tissue deficits;
available for nasal repair are varied and reliable. an undesirable side effect of this maneuver is the
The variety of designs possible with transposed partial obliteration of the nasolabial groove, which is
flaps provides the surgeon with many near-equal a highly desirable landmark.
Nasal Reconstruction and Rhinoplasty 847
A tissue-abundant and versatile example of Abundant glabellar skin with vertical wrinkles,
transposition flaps is the bilobed flap (Figure 38–8, A common in the aging face, combines favorably with
to C), consisting of two lobes separated by more or the lax skin of the inner canthus area to supply tis-
less of an angle and based on a common pedicle. sue for the glabellar bilobed flap. The primary lobe
This variety of flap design has several general appli- of the flap is of ideal thickness and color match for
cations in facial repair and two specific applications dorsal nasal repair. The glabellar skin, which consti-
in nasal repair. Ideally, the dual flaps used should be tutes the secondary flap, is often thicker than inner
similar (although not necessarily exact) in size and canthal skin and must be carefully thinned after
designed to rotate no more than 90 degrees for undermining to match evenly at the suture line.
repair. In practice, this angle can vary from 45 to Heavy, thick eyebrows extending into the glabellar
almost 120 degrees, depending on the location of the midline may impair the cosmetic effectiveness of
defect. In the upper half of the nose, in which the this transposition flap.
primary donor site of the bilobed flap may be easily Similar principles are involved in deriving
reduced in size by undermining and advancement of donor skin for nasal resurfacing from redundant
its edges, the required size of the secondary donor nasolabial fold skin (Figure 38–9, A and B). The sec-
flap may be reduced accordingly. The major advan- ondary donor site is closed primarily in the fold, effec-
tage of the bilobed flap is derived from its use of the tively camouflaging its presence. For large nasal
laxity (elasticity) and redundancy of tissue along two defects especially, the cosmetic appearance of the
axes at approximately right angles to each other, healed flap is preferable in most situations to free skin
compounding these tissues into one flap. or composite grafts. Tissue defects of the nonmobile
848 Ballenger’s Otorhinolaryngology
skin of the nasal tip and infratip lobule are better the head and neck to allow nondelayed primary ele-
repaired with full-thickness skin grafts harvested from vation and transposition. As circulatory efficiency in
the nasolabial fold or preauricular skin, however. the flaps approaches its optimum level (14 to 21
The principles involved in bilobed flap design days), the bridge of the flap is transected, final repair
can be used in a variety of reconstructive situations of the recipient site is effected, and all or a portion of
around the head and neck. the unused pedicle either is replaced in its previous
anatomic bed or is discarded if donor site repair is
unnecessary. Regional flaps from the midline fore-
REGIONAL FLAPS head, scalp, and temple provide excellent tissue of
Pedicle skin flaps designed and transposed from appropriate bulk and near-ideal color match for
head and neck regions other than those immediately nasal reconstitution. Furthermore, the ultimate
adjacent to the nose are termed regional flaps. They donor sites in these areas are easily and effectively
are judiciously used when tissue in more abundance camouflaged, making them the site of choice for
than that provided by adjacent flaps is required or regional flap nasal repair. Tissue derived from cervi-
when flap transport of buried skin, bone, or cartilage cal and more distant unexposed regions (shoulder,
is required for framework reconstitution. In the lat- arm) lacks this ideal color match potential.
ter incidence, the flap becomes a composite or com-
pound flap and always requires delay and staging of
14 to 21 days before total elevation and transposition
MIDLINE FOREHEAD FLAP
of the pedicle to the recipient site. Regional flaps are Of all of the subtotal forehead flaps described for
mainly designed around vigorous named vessels in nasal reconstitution, the precise midline (or para-
Nasal Reconstruction and Rhinoplasty 849
FIGURE 38–9. A and B, Paranasal bilobed transposition flap for reconstruction of lateral nasal defect.
adds unnecessary vascular hazard to the repair and designed to reconstitute nasal form. Redundant
often unsightly fullness in the tunnel region. forehead skin created by tissue expansion is invari-
Fourteen to 18 days after primary flap eleva- ably stiff, less flexible and pliable; it is not consid-
tion and transfer, the vascular viability of the trans- ered ideal for nasal reconstruction.
posed tissue is challenged by circumferential
tourniquet compression; generally, division of the
flap bridge is safely accomplished at this time. Most
SCALPING FLAPS
of the flap is discarded, restoring only sufficient tis- Broad exposure of scalp and forehead tissue may be
sue to reconstitute the oblique wrinkle lines at the primarily elevated and transposed without fear of
root of the nose. Camouflage is excellent. vascular embarrassment for near-total nasal recon-
The esthetic advantage of the midline flap is stitution (Figure 38–11). In older men with balding
apparent to all surgeons who use it regularly. tendencies, the donor site portion of the flap is best
Oblique, transverse, and “off-center” forehead flaps designed to lie on the scalp, ideally at the vertex of
impose a higher penalty in ultimate scar legacy and the skull. In younger patients and in women, the lat-
therefore are less ideal esthetic choices. Midline erally placed skin superficial to the frontalis muscle
flaps, carefully designed, preserve forehead symme- is the donor tissue; a postauricular full-thickness
try and expression. skin graft covers the forehead defect over the intact
In near-total nasal reconstruction, midline frontalis muscle. Careful flap design with a reverse
forehead flaps can serve as the internal epithelial lin- planning pattern technique provides ample tissue
ing for the new nose, underlying a scalp flap for alar simulation by enfolding skin edges for both
Nasal Reconstruction and Rhinoplasty 851
SKIN GRAFTS
Although infrequently used, skin grafts of split and
full thickness are useful in nasal repair. The alterna-
tives of primary closure or adjacent flap repair are
generally preferable because of the inherent advan-
tages previously detailed.
Skin grafts possess several distinct assets when
employed for one-stage repair when no sacrifice of
surrounding tissue is required: no further incisions
852 Ballenger’s Otorhinolaryngology
are required adjacent to the defect, and planning is Deep shave excision repair of the nose afflicted
certainly less complex and sophisticated. Normal with rhinophyma may dictate the need for near-total
landmarks are generally undisturbed, and, should skin graft repair of the nose. Shave excision and der-
the graft fail for any reason, secondary grafting can mabrasion with preservation of epithelial islands,
proceed almost immediately after wound débride- however, uniformly lead to re-epithelialization of
ment, freshening, and infection control. remarkable esthetic appearance, thereby obviating
Superficial nasal epithelial defects of the lower grafting.
half of the nose (trauma, burns, surgical excisions) Grafts applied to the nose require delicate han-
are readily repaired with skin grafts derived from dling and special attention to detail in the operative
nasolabial, preauricular, or postauricular skin. The and postoperative periods. Human noses are by no
postauricular site has been shown by experience to means inanimate; consequently, immobilization of
be a less ideal color match than skin derived from skin grafts by means of stents or sutured-bolus dress-
the first two sites. An ideal but neglected donor site ings is necessary for the critical early period of 4 to 5
in older patients is redundant skin of the nasolabial days. Tie-over bolus dressings compressing the graft
fold. Full-thickness skin donated from this site is dressed with Adaptic or Telfa gauze provide light but
abundant and of excellent color match and allows reliable immobilization and protection of the graft.
camouflage of the donor defect in the nasolabial In contradistinction, adjacent flaps require no com-
crease. Full-thickness defects of the nasal lobule and pression dressing and thus provide convenience to
columella heal beautifully with nasolabial fold full- the patient and early return to normal activities.
thickness skin grafts. Similarly, the preauricular and Split-thickness skin grafts seldom satisfy the
glabellar areas may harbor redundant skin with sim- need for three-dimensional augmentation or efface-
ilar advantages. Seldom does the need arise to graft ment of nasal defects; they may become depressed
with skin derived from the more classic distant skin and thinner with time, seldom provide appropriate
graft sites (inner arm, abdomen, thigh, buttocks). covering for implants of bone and cartilage, and
Nasal Reconstruction and Rhinoplasty 853
carry none of their own blood supply. For these rea- relationship of bone and cartilage to surrounding
sons and those previously outlined, adjacent flaps structures, the degree of postoperative thickening
remain the tissue of choice for immediate nasal and/or relaxation of tissues, and the role of interre-
repair in all areas except the nasal tip and infratip lated structures in the production of the deformity
lobule. Specifically, grafts are generally inappropriate must be realized and evaluated.
in areas of dense scarring and/or irradiation with Variations in rhinoplasty are manifold, rang-
consequently poor recipient site blood supply. ing from minor corrections to complete reconstruc-
tion of the nose. Esthetic rhinoplasty aims at the
creation of a nose that can be considered ideally pro-
ESTHETIC SEPTORHINOPLASTY portioned, but proper physiologic function is essen-
Patients today seek functional and esthetic improve- tial. In post-traumatic deformities and many
ments in nasal appearance more than ever before. developmental and congenital deformities, the cor-
Rhinoplasty refinements currently allow subtle as rection of respiratory derangements is paramount,
well as major modifications with little discomfort, and esthetics, although significant, is secondary.
early healing, and predictable results. Perhaps no Some congenital deformities, such as the cleft lip or
other surgical procedure blends artistic and techni- bifid nose, encompass both functional and cosmetic
cal skills to the degree required in esthetic rhino- requirements of a special nature.
plasty. Although it is one of the more common
operations performed, only a few surgeons ever
master its subtleties and nuances. ESTHETIC RHINOPLASTY
An artistic ability to visualize in advance the The objective of esthetic nasal plastic surgery is the
ultimate result is a critical skill necessary to surgi- creation of a nose that is in harmony with the other
cal excellence. Successful rhinoplasty is initially features of the face. This simple statement represents
preceded by careful analytic assessment of the nasal a complex problem. The explanation of what is
configuration, the deformity, and its relationship to “beautiful” or “ideal” has been an age-old question,
the surrounding facial features. A realistic estimate and the answer involves a multiplicity of emotional
of surgical correction, based on the possibilities reactions and prejudices. In addition, values and
and limitations imposed by the characteristics of assessments of beauty vary within different age
the nasal tissues, is formulated—the preoperative groups and social structures. To evaluate what is
“game plan.” The goal of the surgery is to fashion a beautiful entails a study of physical and cultural
natural nose that is in harmony with its surround- anthropology, ethnology, psychology, and esthetics,
ing facial features and does not draw attention to the ramifications of which may be endless.
itself.
The master surgeon is separated from the Anthropometric Factors The anthropometrist
novice by the ability to predict the favorable and uses basic measurements to divide and subdivide the
compensate for the unfavorable healing factors that face (Figures 38–12 and 38–13).3 Designated points
influence ultimate nasal appearance evolving over in the midline of the face are labeled as follows: the
many years. Only with continued experience and trichion, located in the center of the forehead at the
study, coupled with a continued impartial analysis hairline; the nasion, at the frontonasal suture line;
of one’s own long-term results, can the latter capa- the subnasale, a point at the root of the nasal spine;
bility be developed and refined. and the gnathion, the most anterior point of the
The truly capable surgeon must have wide symphysis of the mandible. If horizontal lines are
knowledge of predictable procedures to be imple- drawn through these points, the face is normally
mented in the unlimited variety of nasal configura- divided into three equal parts. If, in profile view,
tions encountered. Strict adherence to basic another line is projected from the upper rim of the
principles does not necessarily always produce the external auditory canal (the auricular point) to the
ideal result. It is essential that an understanding of lower rim of the orbit or infraorbital point, a line
dynamic nasal structure transcend the components known as the Frankfort horizontal is formed. This
of static bone and cartilage; the relationship of shape line divides the face into two equal parts from the
and form to muscle tension and skin texture, the trichion to the gnathion (see Figure 38–12).
854 Ballenger’s Otorhinolaryngology
the third part of the face, and equal to the nose and
to the forehead,” and have set up our blocks accord-
ingly. After dividing these three groups into equal
spaces, we are immediately led to certain observa-
tions. Although this spacing is equal, it is not
monotonous for the forms lying next to each other
occupy different numbers of spaces. Nevertheless,
the proportions are equal, indicating a certain regu-
larity in size, shape, and position of forms.4 For
example, the forehead occupies one entire group or
one-third of the height of the face. The eye from the
brow to lower lid fills one-third of the height of the
nose, or, again, one can observe that the upper lip is
to the lower lip and the chin as the height of the nos-
tril is to the remainder of the nose. In this manner,
one can divide and subdivide and compare indefi-
nitely. It is interesting to notice that the eye tends to
group a large area with a small one and to compare
this grouping with other similar groupings of large
and small areas.
The midline is the most obvious division of the
front view. In the midline of the face, the measure-
ment used is the width of one eye for “the space
between the eyes is equal to the size of one eye” (da
Vinci). Furthermore, by the size of the eye, the face
FIGURE 38–12. Anthropometric measurements of the is divided into five equal vertical sections. These may
“normal” face. The ideal face is equally divided into fifths. again be equally divided, and mathematical compar-
isons may be made, as before, to prove pleasing
points of interest. An example is that the alae nasi
Many of the basic observations on the divi-
occupy the space between the two inner canthi or
sions of the face were originally described in the fif-
one eye’s breadth.
teenth century by Leonardo da Vinci in the section
of his notebooks entitled “Of the Parts of the Face.” Psychological Factors The importance of beauty
We use his accepted statement, “The space from the and the concept of our own body image, that is, the
chin to the beginning of the bottom of the nose is attitude regarding our physiognomy and body struc-
ture, are potent factors in the emotional and intel-
lectual development of the individual.4
The nose, being a conspicuous organ, has def-
inite secondary sexual characteristics and is fre-
quently referred to as masculine or feminine. The
patient with a poor body image, especially one who
has an unconscious sexual or libidinous misidentifi-
cation, may suffer a severe conflict because of a mas-
culine or feminine appearance or the erroneous
belief of such an appearance. Some of the most
remarkable psychological changes in patients are in
these individuals, often out of proportion to the sur-
gical result. Regardless of the physical change from a
masculine to a feminine nose, if the patient believes
FIGURE 38–13. Relatively ideal facial dimensions. that the change has wrought a new identification
Nasal Reconstruction and Rhinoplasty 855
with his or her sex, the psychic change is spectacular. This attitude is based on a multiplicity of factors
This psychic change is usually based on unconscious varying according to the body image and cultural
factors, the patient never being aware of the reasons values of individual conditioning, particularly dur-
for the dramatic change in attitude. ing the formative years, when it often becomes part
The psychological factors basic to an evalua- of the unconscious mind.
tion of one’s appearance are instinctive and condi- In any ethnic group, beauty is the approxima-
tioned; therefore, much of the individual’s reaction tion of the so-called norm; for Western civilization,
depends on his or her concept of the body image. To we have depicted this norm by mathematical pro-
a great extent, this is influenced or conditioned in portions. It is therefore a form of esthetic ethnocen-
early life, usually by the attitude of the parents. The trism influenced by extraneous factors of culture. A
individual with a distorted and unrealistic self-image great latitude in the variety and balance of features
is usually an emotionally disturbed person. A realis- exists, so there are no absolute rules by which beauty
tic appraisal of one’s own image, within reasonable may be determined.
limits, is usually indicative of a mature individual.5
Patients seeking rhinoplastic surgery for a Anatomic Description The nose on frontal view
gross deformity usually have a realistic view of them- is in the shape of a pyramid, of which approximately
selves and a valid reason for correction of the defor- the upper two-fifths comprise the bony vault and the
mity. The individual with a minor defect may harbor lower three-fifths the cartilaginous vault (Figure
a poor self-image and sometimes exaggerates the 38–14). The upper narrow end joins the forehead at
deformity. The surgeon’s ability to understand the the glabella and is called the radix nasi or root of the
motives and needs of patients seeking esthetic sur- nose, and its free angle at the lower point is termed
gery is summarized by certain exhibited clues and the tip or apex nasi. The two elliptical orifices, the
characteristics. Diagnostic clues tending to identify nares, are separated from each other by a skin carti-
the patient with a good prognosis include (1) obvi- lage septum known as the columella. The lateral sur-
ous disfigurement, (2) occupational reason for seek- faces of the nose form the dorsum by their union in
ing surgery to improve appearance, (3) a realistic the midline. The lateral surface ends below in a
wish to appear younger, and (4) a statement that the rounded eminence, the ala nasi.
patient has “wanted to do this for a long time.” A less The bony vault is composed of the two nasal
ideal (or guarded) prognosis might be expected, bones, which are set on the nasal process of the
according to Schulman, in patients who (1) state an frontal bone above, the frontal process of the maxilla
unrealistic motive (“so I can look more masculine”), laterally, and the perpendicular plate of the ethmoid
(2) request surgery on a sudden whim, (3) expect and the septal cartilage below.
surgery to be the solution to all of their problems (eg, The upper portion of the cartilaginous vault
“to save my marriage”), (4) exhibit a history of hos- consists of the two upper lateral cartilages, which are
pitalization or treatment of recurrent psychiatric ill-
ness, (5) relentlessly go “surgeon shopping,” (6) have
undergone repeated surgery with consistent dissatis-
faction, (7) are unable or unwilling to follow impor-
tant instructions provided by surgeon or staff, (8)
exhibit obsessive-compulsive tendencies, and (9)
interact poorly with office personnel.
In summary, we can state that the motivations
for and the psychological effects of rhinoplastic sur-
gery are a complex subject. A few factors are
reviewed, and an evaluation and a definition of
beauty from perceptual and conceptual views are
attempted.
Beauty of the human face is neither abstract
nor absolute; it varies among different ethnic groups FIGURE 38–14. Normal anatomy of the lateral wall of
and is subject to the projection of the individual. the nose.
856 Ballenger’s Otorhinolaryngology
triangular and fuse with the septum in the midline. The skin covering the external nose is thin and
The upper margins underride the nasal bones and contains an areolar type of subcutaneous tissue. It is
the frontal process of the maxillae and are attached loosely attached in its upper half, but in its lower
to them by connective tissue. The lower cartilagi- portions it is intimately bound to the lower lateral
nous vault is composed of two lower lateral cartilages cartilages and may sometimes be thick and fatty and
(alar cartilages), which are of variable shape and contain many sebaceous glands (Figure 38–16). The
more or less frame the nares and help in forming the skin continues into the nares to supply lining to the
alae. The two medial crura are attached to each other nasal vestibule.
by fibrous tissue and to the lower end of the septum The muscles of the nose lie directly subjacent
by skin, making up the columella and the membra- to the skin, and, occasionally, muscle bundles are
nous septum. Fairly near the midline, the lateral attached to the cutis itself. The muscles comprise the
crura may slightly overlap the upper lateral cartilage procerus, nasalis, depressor septi, dilator naris pos-
and are attached to the lower rim of the upper lateral terior, dilator naris anterior, and angular head of the
cartilage and the septum by connective tissue. They quadratus labii superioris (Figure 38–17).
are also intimately attached to the overlying skin. The blood supply of the external nose is prin-
The medial crura are loosely attached to the nasal cipally through the angular and lateral nasal
septum and to each other by connective tissue. A few branches of the external maxillary artery and the
small loose cartilages (minor alar cartilages) are infraorbital branch of the internal maxillary artery.
occasionally found laterally or just above the lateral The internal nose is supplied by the sphenopalatine
crura. branches of the internal maxillary artery and the
The septum consists of both cartilage and ethmoids from the ophthalmic artery. The veins ter-
bone. The septal cartilage is a single quadrilateral minate in the anterior facial and ophthalmic veins.
plate of cartilage that forms the anteroinferior por- The motor nerve supply to the nose is by the
tion of the septum. It unites with the bony portion facial nerve. The sensory supply includes the
of the septum behind with the perpendicular plate infratrochlear and nasal branches from the oph-
of the ethmoid, resting below on the groove of the thalmic division of the trigeminal nerve and the
vomer, the maxillary crest, and the maxillary spine infraorbital nerves from the maxillary division of the
(Figure 38–15). A tail-like posterior projection of the trigeminal nerve. The nasal septum is innervated by
cartilage between the perpendicular plate and vomer the ethmoid and nasopalatine nerves from the first
is known as the sphenoid process. A small strip of and second divisions of the trigeminal nerve, respec-
cartilage, which is often absent, lies over the nasal
spine and maxillary crests and is known as the
vomeronasal cartilage of Jacobson.
position by firm fibrous attachments. A long, short, directly on the face, and the use of computer imag-
elevated, or depressed septum, long or short upper ing. All may be of value. It is, however, difficult to
lateral cartilages, the shape of the nasal bones and measure so subjective an abstraction as beauty in
maxillary processes, the spine of the maxilla, and the angles or degrees because of the many variables in
direction and tension of the surrounding muscles physiognomy. Rather, one should strive to attain a
and fibrous connective tissue are determining fac- harmonious relationship of all of the features. A
tors in the position and shape of the nasal tip. simple but valuable method of studying the rela-
We are frequently surprised to note what tionship of facial features is by the use of sketches
remarkable changes in shape and position are accom- made on the reverse side of the photograph. The
plished by simply dissecting the tip free from the sur- photograph is held up to a light or placed on a
rounding tissues. A further change is also noted when roentgen film shadow box, and by pencil sketching
the last remaining suspensory attachment of the tip and shading, the ultimate desired result may be
is freed by dissection of the alar cartilage from the depicted.
enveloping skin. The skin at the nasal tip is immobile Whether or not sketches are made on them,
because of its firm adherence to the cartilage by dense pre- and postoperative photographs are an integral
fibrous connective tissue. This firm union aids in sus- part of the surgical routine (Figure 38–19). In all
pending and positioning the tip; thus, to mobilize it plastic surgical undertakings, photographs are
properly, the alar cartilage is detached from the over- absolutely essential and should form a part of the
lying and surrounding skin. Occasionally, this may be patient’s record. A series of standardized and uniform
all that is required to change the shape and direction photographs is more informative than the most care-
of the tip. This is usually accomplished at the onset of fully detailed notes, both as a planning and self-
the rhinoplastic operation. With mobilizing of the instructional device and as a necessary medicolegal
alar cartilages, the muscle fibers are also detached. record.8 Series of 5 × 7 inch black and white prints
The muscles involved are the nasalis (transverse and combined with color 2 × 2 inch color slides make
alar), dilator nares, depressor septi, and, occasionally, ideal records in rhinoplasty photography and serve
a few slips of the caput angularis of the quadratus as an ideal immediate reference when projected full
labii superioris. size in the operating room during surgery.8 Preoper-
The muscles that surround and envelop the ative photographs are followed by postoperative
nose are part of the mimetic muscles of the face, views taken at 1 week and then at 1, 3, 6, 12, 18, and
which have no real fascial covering such as covers the 24 months. This carefully standardized photographic
skeletal muscles of the body. Instead, they are found composite provides a clear uniform panorama of the
below and in the panniculus adiposus or superficial dynamics of healing affecting the ultimate result and
fascia, and the fibers are inserted directly into the is a superior teaching record as well. The Frankfort
dermis and cutis of the skin. This arrangement of horizontal line is used in proper positioning of the
muscle fibers is a direct outgrowth of the highly patient, providing uniformity and standardization
complex development of speech, whereby small from sitting to sitting. The following views are pre-
muscle fibers were needed superficially to allow mul- ferred (Figure 38–19): (1) frontal, (2) basal, (3) right
tiple variations of facial movements. lateral, (4) left lateral, and (5) right lateral, smiling.
Using single-lens reflex cameras, photograph-
Planning the Correction In planning the correc- ing with properly positioned dual electronic flash
tion of the nasal deformity, the component features units and a pastel background complementary to
of the face and the general body build of the patient skin tone (blue or green) is rapid and relatively sim-
must be considered. Frequently, failure to consider ple. A fast, sharp lens of approximately 105 mm focal
the relationship of the nose with the chin, maxilla, length avoids parallax distortion and provides pre-
and forehead mars an otherwise perfect rhinoplasty cise uniformity. Commercial photographers are fre-
and results in a nose that appears unnatural for the quently used, but it is to the surgeon’s advantage
particular individual.7 personally to master the details of precise photogra-
Procedures that have been advocated for analy- phy. The advent of digital photography will provide
sis of deformity include marking angles on photo- significant recording and storage capabilities for
graphs, mechanical measuring instruments used nasal images.
Nasal Reconstruction and Rhinoplasty 859
A B
C D
FIGURE 38–19. Typical preferred pre- and postoperative rhinoplasty photographic views (smiling view optional).
860 Ballenger’s Otorhinolaryngology
Classic Steps of Rhinoplasty Rhinoplasty tions. The optimum time for operation in respect to
remains the most challenging of all esthetic opera- the physiologic and psychological condition of the
tions because no two procedures are ever identical. patient (and the surgeon) should be chosen. Patients
Each patient’s nasal configuration and structure are counseled that the procedure will be a meaning-
require individual and unique operative planning ful and exciting event in their lives with long-range
and surgical reconstruction. Therefore, no single implications rather than a necessarily unpleasant
technique, even though mastered, will prepare the experience.
surgeon for the varied anatomic patterns encoun- A complete physical examination is indicated,
tered. It is essential to regard rhinoplasty as one including routine laboratory tests such as blood
operation planned to reconstitute and shape the count, urinalysis, and chemical and coagulation pro-
anatomic features of the nose into a new, more files. Untoward bleeding histories should be com-
pleasing relationship with one another and the sur- prehensively resolved before proceeding. Recent
rounding facial features. Rhinoplasty should be upper respiratory infections, skin pustules, or aller-
approached as an anatomic dissection of the nasal gic exacerbations may be sufficient reasons to post-
structures requiring alteration, conservatively shap- pone surgery. Conditions such as anemia, metabolic
ing and repositioning these anatomic elements. disorders, or nutritional deficiency states con-
Many more problems and complications arise from traindicate any elective procedure. A patient who is
overcorrection of nasal abnormalities than from con- a poor anatomic surgical risk usually heals poorly
servative correction. Inappropriate technique and unpredictably. An exacting history is essential to
applied persistently without regard for existing determine if any medication currently taken by the
anatomy creates frequent complications. One tru- patient could create bleeding or untoward drug
ism, that it is not what is removed in rhinoplasty that interaction.
is important but what is left behind, remains valid. General planning of the operative sequence
Furthermore, one must comprehend clearly the should be carried out before surgery, with a well-
dynamic aspects of operative rhinoplasty because all devised “game plan.” Intraoperative improvisation
surgical steps are interrelated and interdependent: may be necessary but only if complementary to a
most maneuvers lead to a temporary deformity to be careful preoperative game plan. Photographic evalu-
corrected by the steps that follow. ation with the patient, clearly defining exact patient
Most corrections of the long nose associated expectations and demonstrating realistic expecta-
with a hump or dorsal prominence follow the basic tions as well as anatomic limitations, is mandatory
principles formulated by Jacques Joseph in the first before embarking on surgical repair. The patient
half of the twentieth century. His monumental trea- must clearly comprehend the details, ramifications,
tise, Nasenplastic und Sonstige Gesichtplastik, pub- limitations, and potential complications of the pro-
lished in 1931, has proved its fundamental cedure. This informed consent discussion is purely a
soundness for over half a century. physician-patient encounter; no individual or list of
The procedure varies in each patient by the written “helpful hints” supplants this critical part of
amount of tissue excised and/or the relative reposi- the preoperative conditioning.
tioning, reorientation, and/or grafting of anatomic
structures. Classically, then, rhinoplasty consists of Preoperative Medication The cardinal rules in
the following interrelated steps (Figure 38–20): preoperative medication of patients are to use as few
different categories of drugs as possible and prefer-
1. Septoplasty
ably to employ drugs whose actions may be reversed
2. Tip remodeling, projection, and cephalic rotation
or antagonized. Too often, patients scheduled for
3. Hump removal (establishing the profile line)
rhinoplasty are given a wide array of different drugs,
4. Narrowing of the nose with osteotomies
which confuse the pharmacologic picture consider-
5. Final correction of subtle deformities
ably—certainly, a therapeutic error. Reliance on pre-
Preoperative Preparations Thorough, compul- dictable narcotic and phenothiazine and neuroleptic
sive preparation by the surgeon before surgery drugs only has been found safe and effective, partic-
ensures a streamlined operative procedure, designed ularly with a combination of local infiltration and
to achieve esthetic satisfaction and avoid complica- intravenous analgesia and anesthesia, carefully
Nasal Reconstruction and Rhinoplasty 861
A B
C D
E F
G H
862 Ballenger’s Otorhinolaryngology
I J
K L
FIGURE 38–20. The classic steps of reduction rhinoplasty. A, Surgical anatomy of the nose. B, Variability of upper and
lower lateral cartilages. C, Intercartilaginous incision. D, Alternative approach: transcartilaginous incision. E, Volume
reduction of ala cartilage. F, Cartilaginous hump removal. G, Bony hump removal initiated. H, Bony hump removal
completed. I, Medial oblique osteotomies. J, Low curved lateral osteotomy initiated. K, Completion of low curved lat-
eral osteotomy. L, Infracture with nasal narrowing completed.
titrated, controlled, and monitored by a medical fuse a thin plane of anesthesia and vasoconstrictive
anesthesiologist. Individual drug titration in each influence in the favorable tissue plane just above the
patient, with the drug slowly infused in minimal cartilage structure of the nose, where most dissection
intravenous increments, provides a safe and com- will be performed. Small amounts of infiltration
fortable combination of euphoria, analgesia, and anesthesia are added at the alar margins, piriform
obtundency. General anesthesia may be used with aperture, columella, and nasal septum. No attempt is
equal facility. made to create a specific block anesthesia of specific
One or two small gauze pads (neurosurgical sensory nerves. This method effectively anesthetizes
cottonoids) moistened with 5% cocaine solution are the operative field, creates excellent vasoconstriction,
placed in each nasal passage. Superb surface anes- and avoids distortion of the nasal structures (a com-
thesia with intense nasoconstriction and turbinate mon error). Seldom is more than 4 to 5 mL of anes-
shrinkage results. thetic solution required. Overaggressive injection
Minimal intranasal subcutaneous infiltration leads to tissue ballooning, feature distortion, and
of standard 1% lidocaine (Xylocaine) with 1:100,000 consequent impaired surgical judgment.
epinephrine (freshly mixed) is conservatively It is essential that 10 to 15 minutes be allowed
accomplished. Infiltration occurs only as the No. 27 to elapse between the completion of injection and
gauge needle is being withdrawn to avoid the possi- the initiation of surgical steps, thereby ensuring
bility of direct vessel injection. The intent is to dif- intense vasoconstriction, minimal bleeding, unre-
Nasal Reconstruction and Rhinoplasty 863
stricted vision, and, consequently, improved surgical pled with the final result intended. A philosophy of a
technique. The surgeon must use a strong head light systematic incremental anatomic approach to tip sur-
to maximize visualization. gery is highly useful to achieve consistently natural
The patient cleanses his face and nose gently results. Conservative reduction of the volume of the
with hexachlorophene the morning of surgery, rins- cephalic margin of the lateral crus, preserving a sub-
ing thoroughly. No disinfectant is applied to the nose stantially complete, undisturbed strip of residual alar
or face at surgery. Vibrissae are trimmed only if cartilage, is a preferred operation in individuals in
excessively long. whom nasal tip changes are intended to be modest.
As the tip deformity or asymmetry encountered
Surgery of the Nasal Tip Philosophy of Tip Sculp- becomes more profound, more aggressive techniques
ture Sculpture of the nasal tip is regarded, and are required, from weakened and complete strip
properly so, as the most exacting aspect of nasal techniques to significant interruption of the residual
plastic surgery. The surgeon is challenged by the complete strip with profound alteration in the alar
essentially bilateral, animate, and mobile nasal cartilage size, attitude, and anatomy. Cartilage struc-
anatomic components. Because no single surgical tural grafts to influence the size, shape, projection,
technique may be used successfully in correction of and support of the tip are often invaluable.
the endless anatomic tip variations encountered, the Tip sculpture cannot be successfully under-
surgeon must analyze each anatomic situation and taken, let alone mastered, until the major and minor
make a reasoned judgment about which approaches tip support mechanisms are appreciated, respected,
and tip modification techniques will result in a pre- and preserved or, when indicated, reconstructed
dictably natural appearance. Factored into this judg- (Table 38–1). Loss of tip support and projection in
ment decision must be consideration of, among the postoperative healing period is one of the most
other things, the strength, thickness, and attitude of common surgical errors in rhinoplasty. This tip
the alar cartilages, the degree of tip projection, the
tip skin and subcutaneous thickness, the columellar
length, the length of the nose, the width of the tip, TABLE 38–1. Tip Support Mechanisms
and the tip-lip angulation and relationship. Major
One fundamental principle of tip surgery is
Size, shape, and resilience of the medial and lateral
that normal or ideal anatomic features of the tip
crura
should be preserved and, if possible, remain undis-
turbed by surgical dissection, and abnormal features Medial crural footplate attachment to the caudal
must be analyzed, exposed, reanalyzed, and corrected border of the quadrangular cartilage
by reduction, augmentation, or shape modification.3 Attachment of the upper lateral cartilages (caudal
Surgeons have gradually come to understand border) to the alar cartilages (cephalic border)
that radical excision and extensive sacrifice of alar
Minor*
cartilage and other tip support mechanisms all too
frequently result in eventual unnatural or “surgical” Ligamentous sling spanning the paired domes of the
tips. What appears pleasant and natural in the early alar cartilages
postoperative period may heal poorly because of Cartilaginous septal dorsum
overaggressive attempts to modify the anatomy more
Sesamoid complex extending the support of the
extensively than the tissues allow. Cross-cutting or
lateral crura to the piriform aperture
morselization of the lateral crura may provide an
excellent early appearance but commonly results in Attachment of the alar cartilages to the overlying skin
distortion or loss of tip support as the soft tissues and musculature
“shrink-wrap” the weakened cartilages over time. Nasal spine
Rhinoplasty is, after all, a compromise operation in
Membranous septum
which tissue sacrifices are made to achieve a more
favorable appearance. It therefore becomes judicious *On occasion, because of extreme anatomic variability, a
to develop a reasoned, planned approach to the nasal “minor” tip support may assume the importance of one of
tip based entirely on the anatomy encountered cou- the more major supports.
864 Ballenger’s Otorhinolaryngology
“ptosis” is usually the inevitable result of the sacrifice Tip projection in every rhinoplasty operation is
of nasal tip support mechanisms. inevitably enhanced, reduced, or preserved in its orig-
In the majority of patients, the major tip sup- inal state. Anatomic situations in which each of these
port mechanisms (Figure 38–21) consist of (1) the outcomes is desirable and intended are regularly
size, shape, and resiliency of the medial and lateral encountered in a diverse rhinoplasty practice. The
crura; (2) the wrap-around attachment of the desirable surgical goal in every operation is preserva-
medial crural footplates to the caudal end of the tion of the projection already existent if, as is true in
quadrilateral cartilage; and (3) the soft tissue attach- the majority of rhinoplasty patients, preoperative pro-
ment of the caudal margin of the upper lateral car- jection of the tip is satisfactory. Other patients require
tilage to the cephalic margin of the alar cartilage. an increase in the projection of the tip relative to the
Compensatory re-establishment of major tip sup- intended new profile line. A predictable variety of reli-
port should be considered if, during the operation, able operative methods exists for creating or aug-
any or all of these major tip support mechanisms are menting tip projection; they are discussed later in this
compromised in any fashion. chapter. Finally, in a limited but clearly definable
The minor tip support mechanisms that, in group of patients with overprojecting tips, a calcu-
certain anatomic configurations, may assume major lated intentional reduction of excessive tip projection
support importance include (1) the dorsal cartilagi- is desirable to effect intentional retroprojection.
nous septum, (2) the interdomal ligament, (3) the Successfully achieving these diverse surgical
membranous septum, (4) the nasal spine, (5) the results requires an understanding of and a healthy
surrounding skin and soft tissues, and (6) the alar respect for the major and minor tip support mecha-
sidewalls. nisms, seasoned by the recognition of the intraopera-
Nasal Reconstruction and Rhinoplasty 865
tive surgical tip dynamic principles that interact in the varying anatomy encountered. Whenever possi-
every tip operation. It clearly follows that the appro- ble, a complete strip operation is used, reserving
priate tip incisions and approaches should be planned to more risky interrupted strip techniques for anatomic
preserve as many tip supports as possible. Alar cartilage situations in which more profound refinement
sculpturing should similarly respect this principle by changes and significant rotation are desirable.
conserving the volume and integrity of the lateral crus
S URGICAL A PPROACHES TO THE T IP. N ONDELIVERY
and avoiding, in all but the most extreme anatomic
APPROACHES. In anatomic situations in which the
situation, radical excision and sacrifice of tip cartilage.
nasal tip anatomy is favorable, only conservative
The surgeon should differentiate clearly
refinements are necessary, and nondelivery
among incisions, approaches, and techniques. Inci-
approaches possess great value. Less dissection and
sions are simply methods of gaining access to the
less disturbance of the tip anatomy are necessary,
underlying supportive structures of the nose and by
and this reduces the chance for asymmetry, error,
themselves have little importance. Approaches to
and unfavorable healing. Properly executed (when
the nasal tip provide important exposure to the
indicated), nondelivery approaches therefore allow
skeletal structures and consist of procedures to
the surgeon to control the healing process more
deliver the tip cartilages or to avoid complete deliv-
accurately than when more radical approaches and
ery, or to operate on the alar cartilages without
techniques are chosen.
removing them from their anatomic beds. Sculp-
The transcartilaginous approach is preferred
turing techniques are defined as surgical modifica-
because of its simplicity and ease of use (Figure
tions: excision, reconstruction, or orientation of the
38–22). The same tip refinements, however, may be
alar cartilages calculated to cause significant
accomplished through the retrograde approach.
changes in the definition, size, orientation, and pro-
These approaches are chosen in patients whose tip
jection of the nasal tip. Because of the amazing
anatomy is fundamentally satisfactory, requiring only
complexity of anatomic configurations encountered
volume reduction to accomplish a thinning sculpture
in nasal tip surgery, further modifications are fre-
of the cephalic or medial margin of the lateral crus.
quently used to ensure stable refinements.
When tip projection is to be enhanced by the use of
It is important to assess several factors before
cartilage tip grafts, nondelivery approaches are pre-
selecting the appropriate tip procedure. In planning tip
ferred because precise recipient pockets may be more
remodeling, the surgeon must determine whether the
accurately created in the infratip lobule undisturbed
tip requires (1) a reduction in the volume of the alar
by the minimal dissection inherent in nondelivery
cartilages, (2) a change in the attitude and orientation
approaches. If sutured-in-place tip grafts are
of the alar cartilages, (3) a change in the projection of
planned, a delivery or open approach is preferred.
the tip, (4) a cephalic rotation with a subsequent
increase in the columellar inclination (nasolabial DELIVERY APPROACHES. Delivering the alar carti-
angle), (5) a bilateral narrowing of the angle of the lages as individual bipedicle chondrocutaneous
domes, and (6) reduction of the interdomal distance. flaps through intercartilaginous and marginal inci-
Ideally, conservative reduction of the volume sions is the preferred approach when the nasal tip
of the cephalic margin of the lateral crus, preserving anatomy is more abnormal (broad, asymmetric,
the majority of the crus while maintaining a etc) or when more dramatic tip refinements are
complete (uninterrupted) strip of alar cartilage, is necessary. Significant modifications in the alar car-
preferred. This procedure is satisfactory and appro- tilage shape, attitude, and orientation are more pre-
priately safe when minimal conservational tip dictably attained when the cartilages are delivered
refinement and rotation are required. As the tip (Figure 38–23). The basal photograph is usually
deformity increases in size and complexity, more helpful in determining which patients may best be
aggressive techniques are required. A philosophy of approached in this manner. If the triangularity of
a graduated incremental anatomic approach to nasal the tip from below is satisfactory and only modest
tip surgery has proved useful. This implies that no volume reduction of the lateral crus appears neces-
routine tip procedure is ever used; instead, the sary, the nondelivery approach serves well. If, how-
appropriate incisions, approaches, and tip sculpturing ever, on basal and frontal views, the alar cartilages
techniques are selected based entirely on an analysis of flare unpleasantly (Figure 38–24), tip triangularity
866 Ballenger’s Otorhinolaryngology
A B
FIGURE 38–24. A, Basal view of a patient demonstrating a square- or trapezoid-shaped amorphous nasal tip, in which
the delivery approach is preferred to refine cartilages and suture them together with a transdomal suture to achieve
favorable triangularity. B, Improved basal view appearance 1 year after surgery.
is unsatisfactory or the tip appears too amorphous anatomically confusing in its form (as in certain sec-
and bulbous, the domal angles are too wide, and the ondary revision cases), the open approach is consid-
interdomal distance is excessive, a delivery approach ered. The transcolumellar scar is of negligible
is chosen to correct these esthetic deficiencies more importance in this decision because it routinely
thoroughly. Transdomal suture narrowing of broad
domes (Figure 38–25), an effective and preferred
technique, is effected by means of the delivery
approach. In similar fashion, interrupted strip tech-
niques (rarely employed) for more radical tip
refinement and cephalic rotation are more effi-
ciently accomplished when the cartilages are deliv-
ered. The increased surgical exposure provides the
surgeon with an improved binocular view of the tip
anatomy and affords the added ease of bimanual
surgical modifications.
OPEN (EXTERNAL) APPROACH. The external or open
approach to the nasal tip is in reality a more aggres-
sive form of the delivery approach and is chosen
with discretion in specific nasal tip deformities (Fig- FIGURE 38–25. The triangular effect achieved by trans-
ure 38–26). When the nasal tip is highly asymmetric, domal suturing of the alar cartilage domes, narrowing
markedly overprojected, severely underprojected, or both the interdomal space and the bilateral domal angle.
Nasal Reconstruction and Rhinoplasty 869
heals inconspicuously when meticulously repaired. Three broad categories of nasal tip sculpturing
The anatomic view is unparalleled through this procedures may be identified. Although additional
approach, affording the surgeon diagnostic informa- subtle technical variations exist, the three primary
tion unavailable through traditional closed categories are (1) volume reduction with residual
approaches. These technical virtues must be bal- complete strip, (2) volume reduction with suture
anced with the potential disadvantages of an reorientation of the residual complete strip, and (3)
enlarged scar bed, slightly delayed healing with some volume reduction with interrupted strip.
prolongation of tip edema, and an increased operat- Preserving intact the major portion of the resid-
ing time. Clearly, when subtle and conservative tip ual complete strip of the alar cartilage is always pre-
surgery is indicated by the patient’s existent ferred when the anatomy of the alar cartilages and
anatomy, the open approach is unnecessary. their surrounding soft tissue investments allows. This
preservative approach retains the supportive advan-
ALAR CARTILAGE SCULPTURING TECHNIQUES. The tage of the intact cartilage strip (thus “mimicking”
choice of the technique used to modify the alar car- nature), discourages cephalic rotation when it is
tilages and the relationship of the nasal tip with the undesirable, eliminates many of the potential hazards
remaining nasal structures should be based entirely of more radical techniques, and tends to produce a
on the anatomy encountered and the predicted result more natural final result (Figures 38–27 and 38–28).
desired, as defined from the known dynamics of Techniques involving a weakened (or suture-
long-term healing. The astounding diversity of tip reoriented) residual complete strip have all the fore-
anatomic situations encountered demands a broad going positive virtues and allow the surgeon to effect
diversification of surgical planning and execution by reorientation of the breadth of the domal angle, pro-
the experienced surgeon. jection modification, and narrowing refinement, so
870 Ballenger’s Otorhinolaryngology
desirable in the ideal postoperative appearance (Fig- tical fashion somewhere along its extent to refine
ures 38–29 and 38–30). The control of favorable severe anatomic deficits9 (Figures 38–31 and 38–32).
healing is enhanced with these techniques, with the When significant cephalic rotation is indicated,
risk of complication diminished considerably. interrupted strip techniques are considered. The
Despite a laudable desire to preserve the risks of asymmetric healing are higher when the alar
integrity of the residual complete strip whenever cartilages are divided, however, and initial loss of tip
possible, anatomic situations are occasionally support occurs immediately. The latter problem
encountered in which the shape, breadth, and orien- must be recognized and countermeasures taken dur-
tation of the alar cartilages must be changed more ing surgery to ensure that sufficient tip support is
radically by interrupting the complete strip in a ver- reconstituted. Shoring struts in the columella,
FIGURE 38–28. Patient before (A) and 1 year after (B) rhinoplasty using the transcartilaginous approach, preserving
a generous complete strip of alar cartilage.
Nasal Reconstruction and Rhinoplasty 871
FIGURE 38–30. Patient before (A) and 1 year after (B) surgery. The nasal tip has been refined using a weakened com-
plete strip technique with a transdomal suture repair created through a delivery approach.
872 Ballenger’s Otorhinolaryngology
FIGURE 38–32. Patient before (A) and 1 year after (B) rhinoplasty using a delivery approach and interrupted-strip
technique for refinement of the nasal tip. Heavy bulbous cartilages accompanied by thick skin and subcutaneous tis-
sues dictated the need for this more radical technique.
Nasal Reconstruction and Rhinoplasty 873
and slight additional projection (Figure 38–36). aiding in the creation of a distinct “double break,”
Plumping grafts of cartilage fragments, introduced but should never extend to the apex of the tip skin
into the base of the columella through a low lateral lest a tent-pole appearance develops. If the medial
columellar incision, provide an additional platform crural footplates diverge in a widely splayed fashion,
for the tip projection resulting from the strut. Carti- further tip projection may be gained by resecting
lage struts should be shaped with a gentle curve to excessive intercrural soft tissue and suturing the
match the anatomy of the curved columella, at times medial crura together.
TIP ROTATION. In many patients undergoing rhino- but increments of rotation may also be realized from
plasty, cephalic rotation of the nasal tip complex (alar additional adjunctive procedures on nasal structures
cartilages, columella, and nasal base) assumes major adjacent to the alar cartilages, which exert a favor-
importance in the surgical event, whereas in other able influence on calibrated tip rotation methods.
individuals, the prevention of upward rotation is vital. Shortening of the caudal edge of the septum, excision
Certain well-defined and reliable principles may be of the caudal margins of overlong upper lateral carti-
invoked by the nasal surgeon essentially to calibrate lages, and septal shortening with a high transfixion
the degree of tip rotation (or prevention thereof). incision are regularly used to enhance the effects of a
The dynamics of healing play a critical role in tip planned degree of tip rotation.11
rotation principles; the control of these postopera- Because tip rotation is only one of the many
tive healing changes distinguishes rhinoplasty from objectives of rhinoplasty, decisions regarding rota-
less elegant procedures. In the past, over-rotation of tion must be interrelated with planning for tip vol-
the nasal tip created an unhealthy stigma for the ume reduction, alar cartilage thinning reduction,
rhinoplasty procedure. Most individuals recognize and modifications in the attitude and angulation of
and prefer the esthetic advantages of the stronger the alar cartilages.
nose possessed of sufficient length to impart charac- The techniques and healing dynamics described
ter and suitable proportions to the face. are not absolute but are reasonably predictable. Most
The planned degree of tip rotation depends on tip rotation techniques may be incorporated in an
a variety of factors, which often include (1) the organizational scheme that incorporates three proce-
length of the nose, (2) the length of the face, (3) the dures preserving a complete, intact strip of alar car-
length of the upper lip, (4) facial balance and pro- tilage (Figure 38–37) and three additional procedures
portions, (5) the patient’s esthetic desires, and (6) involving interrupted strip techniques (Figure
the surgeon’s esthetic judgment. 38–38). Unique anatomic situations are regularly
An important distinction must be drawn encountered that require modifications of this
between tip rotation and tip projection. Although cer- scheme to achieve a more refined result, but the fun-
tain tip rotation techniques may result in desirable damental principles elaborated remain constant. In
increases in tip projection, the converse is not true. addition, the thickness and strength of the alar carti-
Tip rotation and projection, in fact, complement lages, along with the character of their enveloping
each other, and their proper achievement in individ- soft tissue and skin, dictate, to a degree, which tech-
ual patients is constantly interrelated. A classic niques may safely and predictably be used in each
example of this interdependent relationship is illus- anatomic situation.
trated by the almost inevitable loss of tip projection
when interrupted strip techniques are chosen to
enhance cephalic rotation; steps must be planned to
restore adequate long-term tip projection by one of
the several methods recommended.
Finally, a distinction must be drawn between
true tip rotation and the illusion of tip rotation
achieved by contouring cartilage grafts placed in the
infratip lobule, columella, and nasolabial angle.
Favorable modifications in the tip-lip complex profile
areas with autogenous implants may obviate the need
for any actual tip rotation, thus preserving a long, and
at times more desirable, nasal appearance. Reduction
of the nasal profile, particularly the supratip cartilagi-
nous pyramid, may also impart the illusion of rota- FIGURE 38–37. A to C, Preserving an intact strip of
tion and a shortened nose, although occasionally at lower lateral cartilage tends to resist upward rotation.
the expense of a strong and narrow dorsum. The greater the tissue void created, the greater is the ten-
Nasal tip rotation results fundamentally from dency of scar tissue contracture to result in slight upward
planned surgical modifications of the alar cartilages, rotation as the tissue void is closed.
876 Ballenger’s Otorhinolaryngology
Complete strip techniques are always preferable addition of adjunctive procedures to achieve cephalic
tip procedures when the nasal anatomy permits, and elevation of the tip such as septal shortening with a
the goals of the surgical procedure may be met with- high septal transfixion or on designing illusions of
out resorting to the less predictable interrupted strip tip rotation with a high septal transfixion or the use
procedures. Preserving a complete, uninterrupted of cartilage battens, struts, or plumping implants.
segment of alar cartilage remnant contributes to a
more stable and better supported nasal tip that tends TIP ROTATION WITH INTERRUPTED STRIP TECHNIQUES.
to resist cephalic rotation during healing. When the integrity and spring of the alar cartilage
Interrupted strip techniques, combined with are broken, cephalic rotation is fostered by virtue of
volume reduction of excessive alar cartilage, tend to upward scar contracture forces acting inexorably on
result in a more substantial degree of cephalic rota- alar cartilage segments, which are now more flail and
tion of the tip complex. Once the complete strip of less supported. These techniques are particularly
residual alar cartilage is divided (interrupted), the useful when the attitude of the alar cartilages is one
result is a relative instability of the nasal tip, on of a profound downward inclination, imparting a
which the forces of upward scar contraction create depressed or snarl-like appearance to the nose. Cau-
a variable degree of cephalic rotation, underscoring tion must be exercised constantly in the use of inter-
the principle that during scar contracture, tissues rupted strips in patients with thin skin and/or more
are generally moved from areas of instability (in this delicate cartilages because the absence of good tip-
case, the unstable nasal tip cartilages) toward areas supporting structures sets the stage for loss of pro-
of stability (the bony-cartilaginous nasal pyramid). jection, alar collapse, notching, pinching, and
asymmetry.
TIP ROTATION WITH COMPLETE STRIP TECHNIQUES. Vol-
ume reduction of the alar cartilage causes a tissue LATERAL INTERRUPTION TECHNIQUES. In anatomic situ-
deficit of minimal, moderate, or maximal propor- ations in which cephalic rotation is desirable and the
tions, depending on the degree of cartilage removal anatomy of the bridge between the medial and lateral
indicated or desirable. Essentially, no cephalic tip crus (the “dome”) is esthetically pleasing, lateral inter-
rotation results from minimal volume reduction ruption of the residual complete strip has merit9 (see
alone, whereas the greater tissue void resulting from Figure 38–38). Avoiding interruption of the strip
moderate to maximal volume reduction tends to medially fosters symmetric healing and reduces the
create progressively greater degrees of minimal tip likelihood that uneven tip-defining points will
rotation. Indeed, preservation of the complete strip become evident months after the operation. The lat-
is regularly indicated and preferred to resist the eral interruption allows the reduced alar cartilage to
forces of upward rotation when the preoperative be pulled moderately upward by scar tissue during
nasal length is to be maintained. healing, but because the dividing cut is sited more lat-
Substantial planned tip rotation when complete erally and therefore more deeply in the soft tissues of
strip techniques are used depends therefore on the the tip, notching, pinching, and other asymmetries
Nasal Reconstruction and Rhinoplasty 877
A high anterior septal angle caused by an A less common cause of excess nasal tip pro-
overdeveloped quadrilateral cartilage component jection is an overlarge nasal bony spine, which seem-
may spuriously elevate the tip to an abnormally for- ingly imparts an upward thrust of the tip
ward projecting position (Figure 38–43), even when components (which may otherwise be of normal
associated with otherwise perfectly normal tip dimensions). Compounding this abnormal appear-
anatomy.12 This condition tends to “tent” the tip ance is often a coexistent blunting of the nasolabial
away from the face and “tether” the upper lip, pro- angle, which may appear full, webbed, and excessively
ducing an indefinite nasolabial angle and, on occa- obtuse, with no obvious demarcation between the tip
sion, creating abnormal exposure of the maxillary and columella. The upper lip may appear short, teth-
gingiva, particularly on smiling. Correction ered, and tense, often exposing excessive gingiva in
demands a departure from the normal operative facial repose as well as in animation. Rongeur or
sequence of correcting the tip first. The initial surgi- osteotome reduction of the overlarge spine and asso-
cal steps are planned to lower the cartilaginous pro- ciated caudal quadrilateral cartilage and soft tissue is
file first, releasing the tip from an abnormal a surgical prerequisite to tip retrodisplacement.
overprojected influence. Further tip refinement Tip overprojection may occur as a result of an
measures can then be carried out as desired and overly long columella associated with excessively long
indicated by the alar cartilage anatomy. medial crura. In this deformity, the infratip lobule is
commonly insufficient, creating the effect of
extremely large and disproportionate nostrils.13 This
deformity suggests the use of an external approach
to the nasal tip to shorten the columellar length as
well as that of the medial crura.
Various combinations of the foregoing hyper-
trophic anatomic problems may contribute to the
overprojecting tip problem. In preoperative analysis,
each nasal component must be compulsively identi-
fied and analyzed; only then can a definitive plan for
natural correction be conceived. Generally, a combi-
nation of weakening of the major tip support mech-
anisms associated with reduction of the components
responsible for the tip overprojection is carried out
incrementally and as conservatively as possible to
achieve the desired normal final result in a progres-
sive fashion. The various components capable of cre-
ating or contributing to overprojection of the nose
are shown in Table 38–2.
Iatrogenic overprojection may occur when sur-
geons intent on profoundly increasing tip projection
produce an unnaturally sharp and projected tip con-
figuration (often associated with over-rotation of the undergo modification to create a pleasing and natu-
tip).4 These misadventures commonly result from ral profile alignment. If the nose is overlarge with a
overaggressive tip surgery in which portions of the convex profile, reduction of the three segments is
lateral crus are borrowed and rotated medially to required. Less commonly (except in revision rhino-
increase medial crus projection. plasty), profile augmentation with autograft materi-
als must be accomplished.
ALAR BASE REDUCTION. Appropriate retroprojection The surgeon visualizes the ultimate intended
of the projecting nose typically requires diminishing profile, extending from the nasofrontal angle to the
the various major and minor tip support mecha- tip-defining point, and then on around the infratip
nisms to retroposition the tip closer to the face. A lobule and columella to the nasolabial angle. The
concomitant reduction of the alar component length extent of reduction of bone, cartilage, and soft tissue
and lateral flare (occasioned by tip retropositioning) always depends on and should be guided by stable tip
is usually required to improve nasal balance and har- projection; therefore, positioning the projection of the
mony. Alar wedge excisions of various geometric tip at the outset of the operative procedure is beneficial.13
designs and dimensions are necessary to balance alar Because the thickness of the investing soft tissues and
length and position (Figure 38–44). The exact geom- skin varies at different areas of the profile and from
etry of these excisions is determined by the present patient to patient, dissimilar portions of cartilage and
and intended shape of the nostril aperture, the degree bone must be removed to create a straight or slightly
and attitude of the lateral alar flare, the width and concave profile ultimately.14 Strong, high profiles
shape of the nostril sill, and the thickness of the alae. generally suit the patient best in the long term, con-
It is axiomatic that the surgeon creating alar reduc- tributing to a more elegant nose on profile and
tion by excision of alar or nostril floor tissue should oblique views and also a more narrow nasal appear-
always err on the side of conservatism and strive for ance on frontal view (Figure 38–45). Over-reduced
symmetric repair because overaggressive and asym- profiles result in a washed-out, indefinite, and
metric tissue resection leads to an almost irreversible widened appearance from the front, separating the
situation of disharmony and even nostril stenosis. eyes inadequately and reflecting light poorly.
In planning profile alignment, the two stable
Profile Alignment Three anatomic nasal compo- reference points are the existing (or planned)
nents are responsible for the preoperative profile nasofrontal angle and the tip-defining point. Esthetics
appearance: the nasal bones, the cartilaginous septum, are generally best served when profile reduction
and the alar cartilages. Generally, all three must results in a high, straight-line profile in men and the
leading edge of the tip just slightly higher in women.
A gentle slope of no more than 2 to 3 mm should exist
between the caudal part of the cartilaginous dorsum
and the most anteriorly projecting aspect of the nasal
tip. Reversal of the usual preoperative tip-supratip
relationship is required to achieve this esthetic ideal.
The degree and angulation of the “hump
removal” depend on various factors, the most
important of which are the size of the various
involved anatomic components and the surgeon’s
confidence in the stability of postoperative tip pro-
jection.14 These must be balanced with the personal
preference for profile appearance combined with the
surgeon’s value judgment of facial esthetics.
FIGURE 38–44. Alar wedge excisions of various geo- Surgical access to the nasal dorsum is gained
metric designs and dimensions are necessary to improve through the transcartilaginous, intercartilaginous, or
the alar flaring found in certain patients. The exact transcolumellar incision, depending on which
design of each tissue removal depends on the dimensions approach was used during tip refinement. In
of the alar sidewalls and the nostril itself. endonasal approaches, a complete transfixion inci-
Nasal Reconstruction and Rhinoplasty 881
FIGURE 38–45. Patient before (A) and 1 year after (B) rhinoplasty. A strong, high profile has been maintained.
sion for exposure is unnecessary and may compro- The soft tissues over the cartilaginous dorsum
mise tip support by sacrificing the attachment of the are elevated by means of scalpel dissection with a No.
medial crural footplates to the caudal septum. 15c blade (Figure 38–47), and the periosteum over the
The plane of tissue elevation over the nasal dor- bony pyramid is lifted from its stable bony attach-
sum is important for several reasons. A relatively avas-
cular potential plane exists intimate (superficial) to
the perichondrium of the cartilaginous vault and just
below the periosteum of the bony vault.3,6 Elevating
the soft tissue flap in this important plane (Figure
38–46) preserves the thickest possible ultimate epithe-
lial soft tissue covering to cushion the newly formed
bony and cartilaginous profile. Generally, only suffi-
cient skin is elevated to gain access to the bony and
cartilaginous profile; therefore, wide undermining is
unnecessary in the typical rhinoplasty. In older
patients with redundant and less elastic skin, or when
access is needed for major autograft augmentation,
wider undermining is carried out.15 Even in the latter
instance, the periosteal soft tissue layer over the FIGURE 38–46. Favorable tissue dissection plane of the
intended site of the low lateral osteotomies is pre- nose, located intimate to the cartilaginous structure of
served intact to help stabilize the mobile bony pyra- the nose, beneath the overlying superficial muscu-
mid after infracture osteotomy maneuvers. loaponeurotic system fascial network.
882 Ballenger’s Otorhinolaryngology
ment with the knife and sharp Joseph elevator (Figure method, the cartilaginous dorsum is reduced by
38–48). Because the periosteum inserts into the inter- incrementally shaving away the cartilaginous dor-
nasal suture line in the midline, the periosteum is sum until an ideal tip-supratip relationship is estab-
lifted on either side of this suture and the space is lished (Figure 38–49), followed by sharp osteotome
brought into continuity with the sharp scissors. Little removal of the residual bony hump.
or no bleeding should ensue during uncovering of the If only minimal hump removal is contem-
nasal skeleton in these important planes, allowing plated, the knife is positioned at the osseocartilagi-
direct visual assessment of the anatomy encountered. nous junction, plunged through this area, and then
Either of two methods of profile alignment is advanced caudally to and around the anterior sep-
preferred: incremental or en bloc.14 In the first tal angle of the caudal portion of the septum. In
FIGURE 38–48. Elevation of the periosteum overlying FIGURE 38–49. Incremental reduction of the cartilagi-
the bony pyramid. nous pyramid.
Nasal Reconstruction and Rhinoplasty 883
large cartilaginous reductions, a portion of the assessed by stretching the partial transfixion incision
upper lateral cartilage attachment to the quadrilat- posteriorly, lies exposed for geometric shortening or
eral cartilage must be removed with the dorsal repositioning.
septum, but leaving these two cartilaginous com- In patients in whom the nasofrontal angle is
ponents attached by the intact underlying poorly defined or in need of retropositioning, weak-
mucoperichondrial bridge. ening of the bone in the desired area is accomplished
A Rubin osteotome, honed to razor sharpness before bony hump removal. At the exact site in the
for each procedure and seated in the opening made midline where the nasofrontal angle is desired, a 2
by the knife at the osseocartilaginous junction, is mm osteotome is plunged transcutaneously into the
advanced cephalically to remove the desired degree midline of the nasal bones3 (Figure 38–51). By angu-
of bony hump in continuity with the cartilaginous lating this small osteotome laterally on either side,
hump (Figure 38–50). the exact cephalic extent of bony hump removal may
Any remaining irregularities are corrected be controlled by scoring the bone in a horizontal line
under direct vision with a knife and sharp tungsten at the nasofrontal angle. During the bony hump
carbide rasp. Palpating the skin of the dorsum with removal phase of profile alignment, the nasal bones
the examining finger moistened with hydrogen per- fracture cephalically where this weakening maneuver
oxide often provides clues to unseen irregularities, has established a bony dehiscence, allowing the sur-
as does intranasal palpation of the profile with the geon some additional control over the ultimate site
noncutting edge of the No. 15 blade. of the nasofrontal angle. Creating a more caudally
Except in large or severely twisted noses, it is placed angle provides the illusion of a shorter nose
unnecessary and potentially harmful to separate the without actually shortening it, whereas establishing
upper lateral cartilages from the septum by cutting a more cephalically placed angle creates the appear-
through the mucoperichondrial bridge of tissue ance of a longer nose.
connecting them at the nasal valve.16 In patients in whom the nasofrontal angle is
Redundant soft tissue around the anterior sep- overly deep, augmentation with residual septal car-
tal angle may be trimmed away to improve tip- tilage or remnants of the excised alar cartilages pro-
supratip definition. The caudal edge of the septum, vides a beneficial esthetic refinement (Figure 38–52).
Further profile enhancements may be favor- nasolabial angle and thereby contribute to improved
ably developed with contouring cartilage grafts posi- profile appearance.17 The illusion of tip rotation and
tioned along the dorsum, supratip area, infratip nasal shortening results from this maneuver (Figure
lobule, columella, and nasolabial angle. In the last 38–53), reducing the degree of actual shortening
site, so-called “plumping” grafts are commonly used required and preserving a longer and often more ele-
to open an otherwise acute or unsatisfactory gant nose.
A B
FIGURE 38–52. Patient before (A) and 1 year after (B) rhinoplasty whose profile has been improved by cartilaginous
grafts positioned at the nasolabial angle and supratip dorsum.
Nasal Reconstruction and Rhinoplasty 885
FIGURE 38–53. Patient before (A) and 1 year after (B) rhinoplasty, illustrating the benefits of augmentation of the
retracted nasolabial angle and supratip dorsum.
Bony Pyramid Narrowing and Alignment Sig- preferable). The upper lateral cartilages are also
nificant advances have been made over the past two moved medially because of their stable attachment
decades in the reduction of osteotomy trauma in cephalically to the undersurface of the nasal bones.
rhinoplasty surgery. Osteotomies, the most trau- To facilitate atraumatic low lateral osteotomy
matic of all nasal surgical maneuvers, are best execution, medial oblique osteotomies angled later-
delayed until the final step in the planned surgical ally 15 to 20 degrees from the vertical midline are
sequence, when vasoconstriction exerts its maximal preferred (Figure 38–54). By creating an osteotomy
influence and the nasal splint may be promptly dehiscence at the intended cephalic apex of the lat-
positioned.3,18,19 eral osteotomy, the surgeon exerts added control of
Profile alignment in the typical reduction the exact site of backfracture in the lateral bony side-
rhinoplasty inevitably results in an excessive plateau- wall. A 2 or 3 mm sharp micro-osteotome is posi-
like width of the nasal dorsum, requiring narrowing tioned intranasally at the cephalic extent of the
of the bony and cartilaginous pyramid to restore a removal of the bony hump (if no hump removal has
natural and more narrow frontal appearance to the been necessary, the site of positioning is at the cau-
nose. The lateral bony sidewalls (consisting of the dal extent of the nasal bones in the midline). The
nasal bones and maxillary ascending processes) osteotome is advanced cephalo-obliquely to its
must be completely mobilized by nongreenstick intended apex at an angle of 10 to 15 degrees,
fractures and moved medially (exceptions may exist depending on the shape of the nasal bony side-
in older patients with more fragile bones in whom wall. Little trauma results from medial oblique
greenstick fractures may be acceptable or even osteotomies, which prevent the ever-present possi-
886 Ballenger’s Otorhinolaryngology
the osteotome pathway. Large guarded osteotomies Nasal dressings are now applied. No intranasal
destroy this vital periosteal sling, potentially render- dressing or packing is necessary in routine rhino-
ing the bony fragments unstable and susceptible to plasty. If septoplasty has been an integral part of the
eccentric or asymmetric healing. In addition, trauma operation, a folded strip of Telfa is placed into each
from large osteotomes may produce increased bleed- nostril along the floor of the nose to absorb
ing, edema, and unnecessary ecchymosis. drainage. The previously placed transseptal quilting
In deviated noses characterized by essentially mattress suture (Figure 38–56) acts as a sole inter-
convex or concave bony asymmetries, excessively nal nasal splint for the septum,3 completely obliter-
wide or extremely thick bones (including revision ating the submucoperichondrial dead spaces and
rhinoplasty), double lateral osteotomies or percuta- fixing the septal elements in place during healing.
neous osteotomies may be considered for improved The external splint consists of a layer of compressed
mobilization and regularization.18 This decision is Gelfoam placed along the dorsum and stabilized in
best determined preoperatively to allow the higher place with flesh-colored Micropore tape, extending
osteotomy to be accomplished before the low lateral over and laterally beyond the lateral osteotomy sites.
osteotomy. Reversing this order necessitates attempt- A small aluminum and Velcro splint applied firmly
ing the higher osteotomy on an already mobilized over the nasal dorsum completes the operation
lateral bony sidewall, a more difficult task. (Figure 38–57).
On completion of satisfactory osteotomies and
suitable esthetic nasal narrowing, the profile line is Postsurgical Considerations The care of the
finally inspected and palpated for irregularities or postrhinoplasty patient is directed toward patient
inadequate alignment. Because the upper lateral car- comfort, reduction of swelling and edema, patency
tilages move medially with the bony sidewalls fol- of the nasal airway, and compression/stabilization of
lowing osteotomies, their dorsal margins should be the nose.
trimmed to sit flush with or slightly lower than the Whether the patient is discharged on the after-
cartilaginous profile line. Excess soft tissue, if pres- noon of or the morning after surgery, all intranasal
ent, is excised and the new nasal dorsum is inspected dressings are removed from the nose before the
for and cleaned of any debris. Any profile grafts to be patient leaves. A detailed list of instructions is sup-
placed to improve the ultimate intended profile line plied for the patient or accompanying family mem-
are now scalpel-sculptured to size and placed ber (Table 38–3); the important aspects of these
accordingly. If limited undermining of the overlying “do’s” and “don’ts” are emphasized. Prevention of
dorsal epithelium has occurred, grafts may be placed trauma to the nose is clearly the most important
with no requirement for suture fixation. If a large consideration. Oral decongestant therapy is helpful,
subcutaneous pocket exists, however, transcuta-
neous pull-out 5-0 mild chromic catgut sutures are
used to fix the grafts into the intended site. The
sutures, cut flush with the skin at 5 to 7 days, retract
into the subcutaneous space and are absorbed.
Final subtle nasal refinements are now com-
pleted and may include caudal septal reduction,
resection of excessive vestibular skin and mucous
membrane, trimming of the caudal margins of the
upper lateral cartilages (only if overlong or pro-
jecting into the vestibule), columellar narrowing,
and bilateral alar base reduction. These final
maneuvers are carried out with the assistant main-
taining constant finger pressure over the lateral FIGURE 38–56. Quilting mattress transseptal suture
osteotomy sites to prevent even minimal oozing woven back and forth through the dissected septum to
and intraoperative swelling. All incisions are closed close dead space, coapt the mucoperichondrial flap(s),
completely with 5-0 chromic catgut suture. No per- and internally support the reconstructed septal compo-
manent sutures are used. nents. Inset: Sagittal view.
888 Ballenger’s Otorhinolaryngology
A B
FIGURE 38–57. Nasal splint applied to a reconstructed nose and maintained for 5 to 7 days to support, splint, and
protect the nose. A strip of Gelfoam is initially laid over the dorsum to protect and compress the skin.
but the value of corticosteroids and antibiotics in Septal resection without rhinoplasty found many
routine rhinoplasty is conjectural. advocates for radical removal of the septum at the
The external splint is removed 5 to 7 days after turn of the century. In 1937, Peer expressed the
surgery. An important consideration should be gentle opinion that radical removal might be necessary for
removal of the tape and splint by bluntly dissecting certain types of deflection but emphasized the need
the nasal skin from the overlying splint with a dull for a section of cartilage in the anterior position to
instrument without disturbing or tenting up the heal- replace the septum for nasal support.20 Fomon and
ing skin. Failure to follow this policy may lead to dis- associates in 1946, 1948, and 1951 described a sim-
turbance of the newly forming subcutaneous ilar method but incorporated the rhinoplastic
fibroblastic layer over the nasal dorsum, with addi- approach of Joseph.21 The adherents to this method
tional unwanted scarring and even abrupt hematoma. did not clearly define the limitations of this proce-
dure with regard to rhinoplasty, although this was
foreshadowed. These techniques apply primarily to
SEPTUM IN RHINOPLASTY the correction of the deviated /dislocated septum
The role of the septum in rhinoplasty has always alone and are rarely indicated when combined with
been subject to debate. The difficulty arises because rhinoplasty, except in the badly traumatized nose.
of a lack of definition, namely, between the septal A more complex problem arises with com-
operation performed as an entity and its being per- bined correction of both an external and a septal
formed as a combined operation with rhinoplasty. deformity. Radical removal of the septum performed
Nasal Reconstruction and Rhinoplasty 889
with extensive rhinoplasty can result in a depressed the septum without sacrifice of large sections of car-
nose because of a lack of septal support. The excep- tilage. Radical removal of the septum may then be
tion is the severely traumatized nose. In these cases, required, but a dorsal implant of a bone or cartilage
the dorsum is depressed, and it is impossible to shift graft is necessary to correct the depression.
890 Ballenger’s Otorhinolaryngology
FIGURE 38–58. Deviation of the external nose caused by nasal septal deflection, before (A) and after (B) correction.
Nasal Reconstruction and Rhinoplasty 891
FIGURE 38–59. Patient before (A) and 1 year after (B) septorhinoplasty using preservative reconstruction of the nasal
septum.
imprisoned cartilage. Their development is com- The vomer and premaxilla are enveloped by a
pleted at age 15 years. Indication of the bilateral ori- periosteal covering that separates the bony portion
gin of the vomer is evidenced in the infant by a deep of the septum from the cartilaginous septum,
groove between the two plates. The groove is some- which, in turn, is enveloped in perichondrium.
what flattened in adults. Microscopic studies of sections removed from the
The premaxilla parallels the development of junction of bone and cartilage in the vomeroseptal
the vomer, but after the child is 6 years old, it devel- maxillary crest region revealed the perichondrial
ops rapidly. The ethmoid bone begins to ossify dur- envelopment of the septal cartilage and its fusion
ing the first year of postfetal life, and ossification is with the periosteum of the bone below. The two
not completed until the end of the seventeenth year. opposing membranes form a smooth surface
At birth, neither the palate bones nor the supe- between bone and cartilage, especially at the junc-
rior maxillae rise into a crest for the support of the tion of the vomer, maxillary crest, and maxillary
lower edge of the septum, but in the adult, these spine, where the groove of the vomer is usually shal-
bones have marked crests. The upward growth of the low or flat. This region is therefore a weak point and
crests, along with the development of the premaxilla a frequent site of traumatic dislocations. Further-
and vomer, combined with the downward growth of more, the bones themselves form a smooth surface.
the septum from the ethmoid ossification centers and The lower end of the vomer is smooth and rests on
the downward expansion of the cranial cavity, may the smooth concave surface of the maxillary crest,
account for many deviations and dislocations of the which, in turn, rests on the smooth concave surface
septum. This disproportion of growth with pressure of the nasal spine.
on the cartilaginous septum has been emphasized as From observations made at the operating
a causative factor in septal deformities. table, in the majority of patients, a dislocation is
892 Ballenger’s Otorhinolaryngology
usually accompanied by a deviation of the vomer bone and cartilage has fortunately given way to
and maxillary crest and spine along with the septal more conservative procedures involving structural
cartilage. These findings are either developmental in preservation and reconstruction. Aside from his-
origin or traumatic at age 6 or 7. Trauma in early torical significance, there remains little purpose in
childhood is an important factor because the max- retaining the term submucous resection, with its
illary crests and vomer are not completely ossified, more radical implications. The term reconstruction
and a slight shifting of these tissues may cause the of the nasal septum or septoplasty conveys the
crest and vomer, as they develop, to grow to the side. meaning of contemporary septal operations more
This situation results in a flattening of the vomerian clearly.
groove and the loss of its lip on the side of devia- Preservative septal surgery is further justified
tion. Some of these deviations may have their origin by normal anatomy. Few “normal” septa are per-
in birth trauma. Cases in which the septal cartilage fectly straight, existing without imperfection. Minor
is displaced from the vomer and maxillary crest are septal irregularities after appropriate reconstruction
usually traumatic in origin, the injury occurring, in are inconsequential provided that they create no
most instances, some time after the child reaches obstruction and contribute to no external nasal
the age of 6 or 7. Complicated septal dislocation, deformity. Radical septal resections in pursuit of a
accompanied by buckling, twisting, and reduplica- “straight” septum are therefore generally without
tion of cartilage and marked internal deformity of virtue.
depression and deviation, invariably results from Septal reconstruction is usually carried out
trauma.24 with (and usually as an integral part of ) rhino-
Some developmental factors in the etiology of plasty. Reduction rhinoplasties invariably diminish
the dislocated septum may be gathered from the breathing space. Reconstructive septoplasty can
embryonal description of the nasopalatal relation- rescue an airway otherwise potentially compro-
ship and the influence of palatal development on the mised by a purely esthetic procedure. Invariably,
floor of the septum. Formation of the premaxilla, the deformed septum contributes to the anatomic
eruption of the permanent incisor teeth, asymmetric deficit inherent in the twisted nose and is best cor-
development of the maxillary sinuses, thumb suck- rected at the outset of septorhinoplasty. lt is fre-
ing and tongue pressure habits with resultant shift- quently remarkable at the operating table how
ing of the alveolar ridge, mouth breathing, and initial septoplasty transforms the crooked nose into
congenital deformities such as cleft lip and palate are near-perfect cartilaginous alignment. As in all sur-
some causative factors that may account for devel- gery for which perfection is the goal, a secondary
opmental disturbances. The eruption of the perma- procedure of lesser magnitude may be occasionally
nent incisor teeth and its effect on the septum were required (less than 5% of all procedures), and all
well described by Mosher, who believed that defor- patients deserve to know that fact before undergo-
mities of the septum are infrequent and rarely ing a reconstructive procedure (“the crooked nose
marked in children before the second dentition. The has a memory”).
disproportion in growth among the premaxilla, Finally, preservative conservation septal sur-
vomer, and ethmoid, with downward encroachment gery should totally negate the most severe sequelae
of the cranial cavity, is probably the dominant factor, of more radical septal resections: columellar retrac-
however. tion, saddle nose, airway collapse, loss of tip support,
and septal perforation. The latter conditions present
Nasal Septal Reconstruction Introduction and
complex difficult reconstructive exercises and are
Philosophy The functions of the nasal septum have
better avoided than risked.
been described as follows: (1) support of the exter-
nal nose, (2) regulation of air flow, and (3) support PRINCIPLES OF SEPTAL RECONSTRUCTION. If the preced-
of nasal mucosa. ing philosophy is accepted, certain precepts emerge
Since the turn of the last century, procedures as cardinal to all septal surgery. These precepts have
designed to improve the nasal airway while pre- as their basis an increasingly detailed, atraumatic
serving these functions have been developed (and dissection and mobilization of the septal compo-
occasionally discarded). The classic submucous nents, an assessment of the obstructive problem,
resection with sacrifice of considerable portions of and, finally, a reconstruction and realignment after
Nasal Reconstruction and Rhinoplasty 893
minimal tissue sacrifice. These major steps involve 6. In septorhinoplasty of the twisted nose, gener-
the following surgical phases, not always carried out ally, the septal realignment is best created before
in this sequence: tip and profile reconstruction. Septoplasty in
combined procedures frequently requires more
1. Whenever possible, elevate the mucoperichondr-
technical ingenuity than rhinoplasty.
ial flap only on one side.
7. Assiduously avoid removal of septal cartilage
2. Atraumatically disarticulate the attachment of
contributing important strength to the structure
the quadrilateral cartilage to the perpendicular
of the external nose.
plate of the ethmoid and to the vomer. If a
8. Dissect from the “known to the unknown” to
vertical angulation exists just caudal to this
best avoid development of tears and flap perfo-
articulation, a common site of deviation, the
ration. If perforations are created, repair with
disarticulation can be positioned at this
fine suture technique.
angulation.
9. Unless it contributes to deformity, preserve the
3. Mobilize the quadrilateral cartilage along the
upper lateral cartilage attachment to the septum.
floor of the nose at the maxillary crest. A narrow
10. Control and stabilize final septal alignment with
horizontal strip of cartilage may be removed to
judiciously placed transseptal sutures, thereby
facilitate this mobilization without compromis-
preventing cartilage segment overrides, hema-
ing septal support.
toma, and unfavorable fibrosis. The need for
4. Isolate the bony septum between its bilaterally
long-term septal splints is thereby lessened or
elevated mucoperiosteal flaps and medially
negated.
reposition or resect the portion creating
11. Avoid long-term intranasal packing and tam-
obstruction (bone grafts are commonly taken at
ponade, a more traditional than useful exercise.
this juncture).
12. Constantly reassess and diagnose the obstruc-
5. Realign the cartilaginous septum with the
tive problem during the course of septal sur-
conservative manipulations to be described
gery with inspection combined with intranasal
subsequently.
palpation. As in rhinoplasty, the anatomic
6. Stabilize all realigned septal segments with quilt-
metamorphosis in septoplasty is dynamic and
ing mattress transseptal absorbable sutures dur-
interdependent, each surgical step often dra-
ing the healing phase.
matically influencing the next. Remain flexible
Certain vital fundamental technical concepts in ideas and approach, ready to incorporate
are required to accomplish these goals of septal surgical options as required.
reconstruction: 13. Understand that airway improvement, particu-
larly in the twisted nose (or as the sequela of
1. Perform all septal surgery under direct vision.
old comminuted fractures), may require nasal
Intense fiber-optic head lighting, long nasal spec-
osteotomies to achieve optimum breathing space.
ula, complete septal mobilization, and effective
vasoconstriction make this an easily realized sur-
PROGRESSIVE INTEGRATED TECHNIQUE OF SEPTAL
gical prerequisite.
RECONSTRUCTION. The surgical steps described sub-
2. Preserve the contralateral mucoperichondrial
sequently have been evaluated over a period of 30
flap for support, septal cartilage nutrition, and
years and found to be effective in 90% of all septal
stability. Exceptions to this principle exist but are
deformities.3,25 They are based on the principles of
infrequent.
structural preservation and septal realignment
3. Preserve the caudal septal relationship with the
rather than resection, with final suture stabilization
membranous columella and feet of the medial
of the realigned septal components. Deviation from
crura. Severe caudal subluxation may negate this
these principles is not usually required, except in the
principle.
rarer anatomic circumstances to be described.
4. Dissect and mobilize the septal components fully
before final deformity diagnosis. Only now should ANESTHESIA AND ANALGESIA. With few exceptions, sep-
the extent of a conservative resection be planned. toplasty and septorhinoplasty are performed under a
5. Resist the temptation to resect more radically in combination of monitored intravenous analgesia,
pursuit of a “perfectly straight” septum. local infiltration, and topical anesthesia. The
894 Ballenger’s Otorhinolaryngology
patient’s comfort is ensured, little bleeding develops, MOBILIZATION OF QUADRILATERAL CARTILAGE. Ele-
and the patient’s condition is constantly monitored vation of the mucoperichondrial septal flap is usu-
by the anesthesiologist. Intravenous sedation is ally initiated through a vertical incision placed 2 to
administered in titrated fashion until patient com- 3 mm cephalic to the caudal end of the septal carti-
fort and tranquilization are achieved. lage on the concave side of the septum (Figure
Neurosurgical cottonoids containing 5% 38–60). Actually, it makes little difference on which
cocaine solution (color coded for easy identifica- side this incision is placed. Preserving the normal
tion) are positioned under direct vision in each attachment of the mucoperichondrial flap on the
nasal cavity. One or two on either side ensure ade- convex side of the septal deformity, however, seems
quate topical anesthesia, vasoconstriction, and nasal technically easier. If severe caudal septal dislocation
tamponade. The mucoperichondrial flap on the exists, a hemitransfixion or complete transfixion
intended side of dissection (ordinarily the concave incision is generally used.
side) is generously infiltrated with a standard solu- The submucoperichondrial plane is located
tion of 1% lidocaine with epinephrine. Accurately and developed with a semisharp Dunning elevator
piercing the submucoperichondrial plane with a under direct vision (Figure 38–61). If fracture adhe-
No. 27 gauge needle provides a “hydraulic dissec- sions, cartilage overlaps, or severe scarring interferes,
tion,” facilitating a rapid and bloodless flap eleva- the dissection is carried out by bypassing these vex-
tion. Additional infiltration anesthesia is used ing areas and dissecting above or below as required
according to the planned extent of septal dissection. initially to circumvent areas of difficult dissection.
Twelve to 15 minutes of delay should now Proper hydraulic lidocaine infiltration, as described,
ensue while vasoconstriction becomes intense. Dur- facilitates this elevation technique.
ing this period, final inspection and palpation of the This dissection plane is continued onto the
cocainized internal nose often reveal irregularities ethmoid perpendicular plate and vomer, elevating
high in the nasal vaults not previously seen. Radi- the continuous ipsilateral mucoperichondrial
ograph evaluation at this juncture may aid in surgi- mucoperiosteal space. Moderate pressure with the
cal planning. The value of palpation of the deformed tip of the elevator at the junction (articulation) of
septum and of the structural strength of the nasal the cartilaginous and bony septal components disar-
tip supportive elements cannot be overemphasized. ticulates these elements and initiates the dissection
of the contralateral mucoperiosteal flap (Figure lage may be held by a subluxation along the maxillary
38–62). Because this area is a common site of septal crest, which is overcome by resecting a horizontal
fractures and angulation, the disarticulation can also strip of cartilage (and frequently bone) from along
be accomplished in a previous fracture line. the floor of the nose. Any fibrous tissue bands further
A reassessment of the septal anatomy (and contributing to a displaced position of the cartilage
deformity) is now in order. This initial dissection fre- are divided with sharp knife dissection. These steps
quently has allowed the quadrilateral cartilage to will now have completely freed and mobilized the
return to the midline without further surgery, being quadrilateral cartilage and usually allow its return to
freed from a deviated ethmoid or vomer. The carti- the midline without further surgical manipulation.
CORRECTION OF BONY OBSTRUCTION. Deformities of is carried out, as described later. If the airway
the bony septum, particularly those high in the nasal remains unsatisfactory, what creates the problem
vault, are now exposed between the blades of a long and how is it most easily and conservatively cor-
nasal speculum; selective resection of obstructing rected? Once these questions are answered, a variety
bone is gently carried out with small biting (Taka- of the following corrections are variously carried
hashi) forceps until the airway is clear (Fig- out, depending on the existent deformity, its loca-
ure 38–63). Larger pieces of bone required for graft tion, and its extent.
or implants may be resected with fine osteotomes,
heavy scissors, or bone-biting forceps. Great care ANCILLARY CORRECTIVE PROCEDURES. Significant
should be taken in older patients (particularly osteo- obstructing deformities along the floor of the nose
porotic women) to remove only small portions of (cartilaginous or bony spurs and ridges, which often
the perpendicular plate of the ethmoid. The vomer contribute to drying, ulceration, and bleeding) may
provides an excellent source of bone-grafting mate- require an approach created by elevating a second
rial; flaps should be completely and bilaterally ele- compartment of periosteum along the floor of the
vated to avoid creating flap tears or avulsions during nose (Figure 38–64). The periosteum overlying the
vomerine resection. premaxilla and maxillary crest is incised, and a sub-
These steps in surgical dissection of the sep- mucoperiosteal pocket is created with the elevator.
tum are relatively routinely carried out in most The two compartments (subperiosteal and subperi-
patients and frequently are all that is required to chondrial) are then connected, exposing the maxil-
establish a greatly improved airway. At this point in lary crest deformity for osteotome and/or rongeur
the septal reconstruction, a reassessment is in order removal.
before further surgery. Visually and palpably, the A vertical angulation of the septum, if con-
septal alignment is evaluated. If alignment is satis- tributing to deformity and obstruction (often the
factory and the airway adequate, flap suture closure site of an old fracture), may be removed with a con-
servative vertical cartilage strip resection or wedge
resections, with realignment carried out by
absorbable suture technique (Figure 38–65).
Similarly, horizontal septal angulations or
spurs are resected by means of conservative hori-
zontal strips or wedges, again leaving all remaining
cartilage segments securely attached to the con-
tralateral undissected mucoperichondrium. Thin-
ning the quadrilateral cartilage with shave excision
FIGURE 38–65. Vertical (A) or horizontal (B) angulations of the nasal septum may be removed with wedge resections.
techniques in a horizontal or vertical plane may con- niques to resist the temptation to resect significant
tribute to airway improvement without significantly caudal segments, thereby risking columellar retrac-
altering the supportive strength of the cartilage (Fig- tion and loss of tip support.
ure 38–66). A vertical incision (or narrow cartilage exci-
Significant dislocation of the caudal septum sion) cephalic to the point of angulation, combined
from the midline, whether developmental or trau- with freeing the caudal segment from the nasal floor,
matic, requires ingenuity in reconstructive tech- generally creates a caudal “swinging door” segment
that is sutured to the midline columella and occa-
sionally to the midline mucoperiosteum. Further
weakening of a deformed caudal segment without
total structural sacrifice may be created by generous
“cross-hatching,” shave excision and even conserva-
tive morselization. Limited contralateral mucoperi-
chondrial flap elevation at the caudal segment
facilitates its realignment.
An overlong caudal septum, malaligned or not,
may require thinning or shortening to facilitate
repositioning, particularly during septorhinoplasty
procedures.
Occasionally, a previously fractured nasal spine,
positioned off the midline, will require refracturing
and fixation to the midline to reposition the caudal
septum adequately. Unless it deforms the nasolabial
angle, the spine is seldom sacrificed, to avoid poten-
tial loss of tip support and columellar retraction.
Deformed upper lateral cartilages, the product
of maldevelopment or trauma, are occasionally
responsible for misalignment of the cartilaginous
septum. Inspection and palpation confirm this sus-
picion. Submucosal dissection and freeing of the
upper lateral cartilages from the septum allow fur-
FIGURE 38–66. Shave excision techniques in overly ther septal mobilization and realignment. This situ-
thick quadrilateral cartilages may substantially improve ation, however, is rarely encountered. Preserving the
the nasal airway. upper lateral septal attachment is preferred.
898 Ballenger’s Otorhinolaryngology
Final correction of some varieties of badly slight depression and can be particularly helpful in
twisted noses may require realignment of the bony camouflaging a slightly deviated dorsum without
nasal pyramid to mobilize and straighten the septum risking breaking the dorsal support with surgical
(and therefore the nose) completely. Such instances manipulations.
are ordinarily the consequence of old trauma. Finally, the complete nasal surgeon should be
Persistent airway blockade after careful septal aware of the septal reconstructive advantages
reconstruction is occasionally caused by enlargement offered by the technique of external rhinoplasty.2
of the inferior turbinate to fill partially the concavity Advantages include a superb direct vision approach,
created by septal deviation. Return of the septum to direct anterior appraisal of the deformed elements,
midline further diminishes the airway. Partial sacri- and superior suture realignment of reconstructed
fice of the inferior turbinate (resection, cautery, freez- septal elements.
ing, crushing, etc) has never seemed appropriate or
physiologic. The author prefers a submucosal eleva- PRESERVATION OF REALIGNMENT. With progressive use
tion of the turbinate tissue with resection of the bulky of the foregoing integrated techniques, most devi-
bone of the inferior concha (Figure 38–67). The ated septa may be appropriately reconstructed rather
turbinate is reattached with absorbable sutures and than resected, and septal functions may be preserved
now occupies considerably less space than originally. without embarrassing septal support. Controlling
Infrequently, in the most severe quadrilateral the healing process totally is not possible, but it can
cartilage deformities, extensive cross-hatching, be favorably influenced by the suture techniques to
crushing, or morselization of the cartilage is used to be described.
“break the spring” totally.26 These procedures are All incisions, including any small flap perfora-
generally reserved for the more caudal portions of tions that occasionally occur, are closed with 5-0
the quadrilateral cartilage and are used only in the absorbable suture.
severest deformities. Bilateral mucoperichondrial A series of similar transseptal transperichondr-
flap elevation is usually required, and precise healing ial through-and-through sutures are now positioned
is often less predictable than when more conserva- to coapt the septal flap(s), thereby closing all dead
tive measures are employed. space (see Figure 38–56). Hemostasis is promoted,
Implantation of autogenous cartilaginous sup- and hematoma is avoided. Further fixation sutures to
ports in the columella is frequently used, lending preserve the realignment of cartilage segments are
support to the tip, correcting retracted columellar positioned after the manner of Wright to prevent
deformities, and enhancing the nasolabial angle slippage and overriding. The presence of one intact
anatomy.27 Thin cartilage wafers positioned along undissected mucoperichondrial flap provides a great
the cartilaginous profile line are useful in effacing a advantage in stabilizing the septal reconstruction.
Septal splints are required only rarely when
these methods are used. Telfa gauze rolls are placed
in each nasal vault to absorb drainage and splint
lightly the dissected flaps and are removed in 12 to
24 hours.
If osteotomies have been performed, or after
the occasional external septorhinoplasty, an external
cast is applied for 7 days.
REFERENCES
1. Burget GC, Menich FJ. Aesthetic reconstruction of
the nose. St. Louis: CV Mosby; 1994.
2. Johnson CM, Toriumi DM. Open structure rhino-
FIGURE 38–67. Reduction of an enlarged turbinate plasty. Philadelphia: WB Saunders; 1990.
mass is effected by submucosal resection of the enlarged 3. Tardy ME. Rhinoplasty: the art and the science.
bony concha, preserving the majority of turbinate tissue. Philadelphia: WB Saunders; 1997.
Nasal Reconstruction and Rhinoplasty 899
4. Sheen JH, Sheen A. Aesthetic rhinoplasty. 2nd ed. St. 17. Walter C. Composite grafts in nasal surgery. Arch
Louis: CV Mosby; 1987. Otolaryngol 1969;90:622–36.
5. Goin JM, Goin MK. Changing the body. Baltimore: 18. Wright WK. Lateral osteotomy in rhinoplasty. Arch
Williams and Wilkins; 1981. Otolaryngol 1963;78:680–9.
6. Tardy ME. Surgical anatomy of the nose. New York: 19. Farrior RT. Corrective surgery of the nasal frame-
Raven Press; 1991. work. J Fla Med Assoc 1968;45:276.
7. Tardy ME, Thomas JR, Brown RJ. Facial aesthetic 20. Peer LA. An operation to repair lateral displacement
surgery. St. Louis: CV Mosby; 1995. of the lower border of the septal cartilage. Arch Oto-
8. Tardy ME, Brown RJ, Childs C. Principles of pho- laryngol 1937;25:475–90.
tography in facial plastic surgery. New York: Thieme; 21. Fomon S, Gilbert JG, Silver AG, Syracuse VR. Plastic
1992. repair of the obstructing nasal septum. Arch Oto-
9. Goldman IB. Nasal tip correction with special refer- laryngol 1948;47:7–23.
ence to the medial crura. Trans Am Acad Ophthal- 22. Frye H. Nasal skeletal trauma and the interlocked
mol Otolaryngol 1964;68:854–66. stress of the septal cartilage. Br J Plast Surg 1967;20:
10. Tardy ME. Rhinoplasty tip ptosis: etiology and pre- 146.
vention. Laryngoscope 1973;83:923–9. 23. Becker OJ. Problems of the septum in rhinoplastic
11. Parkes ML, Brennan HG. High septal transfixion to surgery. Arch Otolaryngol 1951;53:622–41.
shorten the nose. Plast Reconstr Surg 1970;45:487–92. 24. Farrior RT. Septorhinoplasty in children. Otolaryn-
12. Aiach G, Levignac J. Aesthetic rhinoplasty. London: gol Clin North Am 1970;3:345–64.
Churchill Livingstone; 1991. 25. Tardy ME. Reconstructive surgery of the deviated
13. Nolst-Trenite G. Rhinoplasty. The Hague: 1993. septum and nose. Memphis (TN): Richards Manu-
14. Wright WK. Study on hump removal in rhinoplasty. facturing Company; 1982.
Laryngoscope 1967;77:508–17. 26. Frye H. Cartilage and cartilage grafts: basic proper-
15. Smith TW. The selection of patients for rhinoplasty. ties of tissue and its components responsible for
Arch Otolaryngol 1971;94:56–8. them. Plast Reconstr Surg 1967;40:426–37.
16. Frye H. Interlocked stresses of cartilage. Br J Plast 27. Denecke HJ, Meyer R. Corrective and reconstructive
Surg 1966;19:276–81. rhinoplasty. New York: Springer; 1967.
CHAPTER 39
Facial Fractures
Paul J. Donald, MD, Jonathan Sykes, MD
With high-speed auto travel, the increasing partici- portion of an internal carotid artery, or a fracture
pation in sports by people of all ages and both gen- through the basisphenoid bone may tear the cav-
ders, and especially the high incidence of violent ernous portion of the internal carotid artery.
crime, facial fractures continue to be important After the patient’s condition has been stabi-
injuries in our society. Management of facial frac- lized, careful physical and radiographic examination
tures, contrary to the pattern of care in other coun- of the cervical spine must be performed to rule out
tries of the world, is, in the United States, spread cervical spinal injury. At this point, a careful evalua-
across the disciplines of oral surgery, plastic surgery, tion of the other important systems is performed.
and otolaryngology. Because of the comprehensive Treatment of the patient with facial trauma
training in head and neck anatomy and physiology, should include a thorough history and physical
the otolaryngologist is uniquely prepared to best examination to determine the location and extent of
deal with these injuries. However, it is vitally impor- all injuries.1 The goal of treatment of patients with
tant for the specialist to have a working knowledge craniomaxillofacial injuries should be reconstitution
of dental occlusion and facial esthetics and an of all injured regions.2 Both soft tissue and bony
understanding of the healing of membrane bone. injuries should be assessed, and a treatment plan
The first encounter with the patient with a should be established. The goals of treatment should
facial fracture is usually in the emergency depart- be the restoration of function and appearance. The
ment. The patient is often the victim of an accident premorbid form and function of dental, skeletal, and
that involves many body systems, and, almost soft tissues should be re-established as much as pos-
always, attention to these injuries takes precedence. sible. Recent photographs and dental records, if
The exception to this is the initial attention to the available, are most helpful to establish the pretrau-
airway. Extensive soft tissue contusion, bilateral matic appearance.
mandibular body fractures, and Le Fort fractures of If the initial injury involves skin or mucosal
the maxilla can all result in airway obstruction. In lacerations, attempts should be made to use these
mandibular fractures, a nasotracheal intubation is lacerations when possible for the approach to frac-
appropriate; however, in maxillary fractures, there is ture repair. If no epithelial injury is present,
always a risk of fracture to the cribriform plate or approaches to fractures should attempt to maximize
the fovea ethmoidalis. Intubation by the nasal route exposure while minimizing scarring and risk to adja-
presents the danger of intracranial passage of the cent neurovascular structures.
tube so that oral intubation, cricothyroidotomy, or As thorough a history as possible is taken.
tracheostomy should be used to secure the airway. Often, however, these patients have suffered multi-
Rarely will fractures of the facial skeleton present ple injuries and may be either unconscious or intu-
with life-threatening hemorrhage. The only time in bated. Information may be gleaned from any
the author’s experience in which a problem of seri- friends or relatives at the scene or the police or
ous hemorrhage occurred was in an instance of a Le ambulance attendants. Physical examination
Fort III fracture in which both of the internal max- includes a careful inspection of dental occlusion,
illary arteries were severed. Rarely, associated frac- examination of the facial contour, and palpation of
tures of the temporal bone may rupture the petrous the facial bones. A computed tomographic (CT)
900
Facial Fractures 901
scan of the facial skeleton is crucial in securing the TABLE 39–2. Principles of Fracture Repair
correct diagnosis.
After fracture diagnosis is completed, a system- Repair of both skeletal and soft tissue injuries
atic treatment plan is established. Surgical treatment Use of lacerations when possible
of facial fractures involves adequate exposure, metic- Use of mucosal incisions when possible
ulous reduction, and stable fracture fixation. Surgical
Exposure of all fractures adequately for fracture
approaches should use transmucosal incisions or inci-
reduction
sions that are camouflaged in relaxed skin tension
lines or at the junctions of facial esthetic units.3 Of Reduction of all fractures
course, the incision and approach chosen must not Stabilization of fractures
compromise the basic principle of providing adequate Fixation of all fractures adequately to allow bone
exposure for diagnosis and treatment of any fracture. healing
After exposing the facial fracture, meticulous reduc-
tion must be performed and maintained until ade-
quate fixation of the fracture can be done. Precise the management of facial fractures. Dental occlusion,
reduction is imperative when rigid fixation is used. simply stated, is the relationship of the maxillary to
Fixation techniques should allow for complete bone the mandibular teeth. The most important func-
healing with reconstitution in three dimensions: tional relationship is that of their cutting and grind-
height (superior-inferior), width (lateral-medial), and ing surfaces. This relationship largely depends on the
depth or projection (anterior-posterior). relative position of the teeth and their angulation to
Repair of soft tissue injuries is often as impor- one another. In 1899, Angle described three basic
tant as fracture treatment in the complete restoration types of occlusion.4 Certain subtypes of this system,
of the patient with craniomaxillofacial injuries. This as well as other classifications of occlusion, have been
is especially true in the periorbital region, where devised, sometimes adding to the confusion rather
injuries such as telecanthus, enophthalmos, and than clarifying the problem. In the Angle system, the
dysopia often accompany the skeletal injury. Com- reference point is the relationship of the first maxil-
plete treatment of facial injuries requires attention to lary molar tooth with the mandibular molar tooth
these soft tissue injuries and accurate reattachment of below it. Each molar commonly has four grinding
soft tissue fascial layers after fracture repair. surfaces called cusps. The cusps adjacent to the
The basic principles of diagnosis and initial tongue are called lingual and those adjacent to the
treatment of patients with facial fractures are listed cheek buccal. Those cusps situated toward the
in Table 39–1. The principles of fracture repair are oropharynx in the posterior aspect of the oral cavity
listed in Table 39–2. Adherence to these principles are described as distal, and those located more ante-
will maximize function and appearance. riorly are mesial (Figure 39–1).
Class I occlusion is the ideal form (Figure
39–2). In this type, the mesial buccal cusp of the first
DENTAL OCCLUSION maxillary molar fits in the groove on the lateral or
The key to proper fracture reduction is the restora- buccal surface of the first mandibular molar tooth.
tion of the patient’s premorbid occlusion. The under- The buccal cusps of the maxillary teeth overlap the
standing of dental occlusion is an essential element in buccal surfaces of the mandibular molars.
In Class II occlusion, the mesial buccal cusp of
the first maxillary molar is mesial, or in front of the
TABLE 39–1. Principles of Diagnosis and Initial buccal groove of the first mandibular molar (Figure
Treatment of Facial Fractures 39–3). It may be over the first mandibular molar’s
mesial cusp or even between it and the second pre-
Establishment and securing airway
molar (bicuspid). In Class III occlusion, the reverse
Control of bleeding of class II is seen. The mesial buccal cusp of the first
Detailed history maxillary molar now sits over the corresponding
mandibular molar’s distal cusp or between it and the
Careful physical examination
second molar (Figure 39–4).
902 Ballenger’s Otorhinolaryngology
transection or avulsion of the nerve, full sensation A fracture is considered simple when both the exter-
often returns within 9 months to a year. nal skin and oral mucosa are intact or compound
The muscles of mastication inserting on the (open) when a laceration in the skin or intraoral
mandible include the temporalis, internal pterygoid, mucosa is present. If the patient is dentulous and the
external pterygoid, and masseter. All of these mus- fracture line passes into the tooth root, the fracture
cles contribute to the movement of the temporo- is theoretically compounded because the periodon-
mandibular joint, a synovial joint with both hinge tal pocket of that tooth often extends to the fracture
and gliding action. This joint contains a capsule with site. If the fracture is incomplete and involves only
a fibrocartilaginous disk. The capsule is densely one cortex, it is termed “greenstick.” The commin-
innervated with proprioceptive and sensory fibers, uted mandible fracture is one with several fragments
which are extremely sensitive to subtle changes in of bone. Mandibular fractures are most commonly
movement of one or both joints. A slight alteration characterized by anatomic location (Figure 39–8).
in occlusion from muscle spasm or a displaced frac- The most frequent location of fractures of the
ture may alter the central perception of joint posi- mandible is the condylar-subcondylar region. Other
tion. Feedback loops in the central nervous system common sites include the body and mandibular
force the contralateral muscles of mastication to angle. The coronoid process is rarely fractured. An
compensate. This series of events may lead to alveolar ridge fracture involves the occlusal surface
chronic temporomandibular joint syndrome in an of a part of the mandible but does not extend into
unrepaired or poorly repaired mandibular fracture. the inferior cortical surface (Figure 39–9).
Understanding the various attachments of the Mandibular fractures can also be classified as
aforementioned muscles of mastication, as well as dentulous, edentulous, or pediatric. The latter cate-
the mylohyoid, geniohyoid, genioglossus, and digas- gory is important because of the vulnerability of
tric muscles, is important in understanding the unerupted dentition and the conical shape of the
forces of displacement in a mandibular fracture. The unerupted teeth, which do not hold a wire ligature
floor of the mouth and extrinsic tongue muscles well. The accuracy in approximation of the edentu-
tend to displace fractures posteriorly and inferiorly. lous mandible is not as critical as is the exacting task
The medial pterygoid and masseter muscles act as a of establishing the preinjury occlusion of the dentu-
sling in the posterior body and angle area and tend lous mandible. A denture can compensate for minor
to elevate a displaced fragment of the angle or pos- irregularities in the edentulous jaw.
terior body. Condylar fractures are displaced by the The final classification may be made according
pull of the lateral pterygoid muscle, which rotates to the stability of the fracture. Vertical instability
and dislocates the fracture medially.6 results from the pull of the temporalis, masseter, and
pterygoid muscles. The angle of pull of these muscles
will tend to impact a jaw fracture that is obliquely
CLASSIFICATION inclined from distal to mesial (posterior to anterior),
Fractures of the mandible may be classified accord- rendering it stable. On the other hand, if the inclina-
ing to specific characteristics and anatomic location. tion is the opposite direction, then the forces of these
muscles will distract the distal segment in a superior (Figure 39–10). A fracture becomes horizontally
and medial direction. An interesting scenario pres- unstable by virtue of its obliquity in the occlusal
ents itself regarding an unfavorably inclined fracture plane. A fracture with an angulation running from
in the distal part of the body, near the angle, just the buccal to the lingual surface in a posterior to
anterior to the third molar tooth. While the tooth is anterior direction is favorably aligned, whereas that
present, the fracture will not dislocate, but if the in the opposing obliquity is unstable by virtue of the
tooth is extracted, the fracture becomes unstable pull of the mylohoid muscle (Figure 39–11).
involved. When there is one fracture in the will delineate the degree of fragment overlap or
mandibular arch, one must always be aware that displacement into the infratemporal fossa (Figure
there may be an occult fracture in the contralateral 39–15). If a parasymphyseal or symphyseal fracture
ramus or condyle. The panoramic radiograph, the is suggested clinically, but not visualized on plain
so-called Panorex film, is excellent for viewing frac- radiographs, the CT scan will demonstrate it. Den-
tures of the ramus, angle, and body 7 (Figure tal fractures are best diagnosed with dental occlusal
39–13). This type of radiograph is limited, how- films. If the patient sustains massive trauma, as in
ever, in visualizing the symphyseal area as well as a motor vehicle accident or other collision, CT
telescoping fractures of the condylar area. A modi- scans of other pertinent anatomic areas should be
fied Towne’s view usually visualizes significant frac- taken, including full facial and cervical spine films.8
tures of the condyles (Figure 39–14). If a strong The scan is usually extended superiorly to rule out
suspicion of subcondylar fracture exists, a CT scan any intracranial injury.
TREATMENT
After an adequate history and physical examination
have been obtained and a radiographic assessment
has confirmed the physical findings and ruled out
any “occult” fracture, treatment is contingent on the
following factors: (1) presence or absence of other
serious trauma, either intracranial, intrathoracic, or
intra-abdominal; clearance of the cervical spine by a
qualified neurosurgeon or orthopedist; (2) adequate
surgical consent from the patient; (3) a thorough
dental evaluation, including preoperative documen-
tation of occlusion; and (4) availability of bridge-
work or dentures that accompany the patient to the
operating room.
Although many authorities recommended sur-
gical intervention as early as possible to prevent
infection, there is no conclusive evidence for
this.5,8–10 To decrease the incidence of infection, it is
best to administer preoperative antibiotics. Surgery
should be done as soon as possible with the previ-
ously mentioned factors taken into consideration. It
must be emphasized that repairing a mandibular
fracture is not, in the true sense of the word, an
emergency but rather should be done as soon as pos-
sible when safe. Some fractures of the mandible do
not require surgical intervention. Most commonly,
nondisplaced ramus fractures, as well as some sub- FIGURE 39–15. Linear tomogram demonstrating dislo-
condylar fractures, when there is no complaint of cation of the mandibular condyle into the infratemporal
malocclusion, should be treated with a soft diet. The fossa.
910 Ballenger’s Otorhinolaryngology
remainder of mandible fractures,5 especially when wire, bending it in half, and twisting in a small
there is malocclusion, should be treated either by loop.
closed or open reduction or, in some cases, both. The idea of the eyelet wire is to capture two
The cornerstone of facial fracture repair is still independent teeth on each side of a mandibular
intermaxillary fixation. This method of repair entails fracture and then fix these to two adjacent pairs of
the ligation of the teeth of each arch to those that maxillary teeth (Figure 39–16). The ends of the wire
oppose it. According to Dingman and Natvig, ligation are directed from the buccal side through the inter-
of teeth to each other dates back to the time of Hip- dental space below the contact point and close to the
pocrates.1 The ancients advised fixing the teeth to one gum between the pair of mandibular teeth distal to
another with gold wire or linen thread. The Greek the fracture. In Figure 39–16, A, each wire is brought
physician Soranos of Ephesus first described the con- around the neck of each tooth, and the end of one is
cept of support of the fractured jaw by a barrel-type passed through the loop and twisted to its mate at a
bandage in the second century AD.11 These first meth- comfortable distance from the loop. The wire liga-
ods appeared to rely on healing resulting from the ture now captures the two teeth (Figure 39–16, B).
wiring of adjacent teeth in the same arch. William of Care is taken to be sure that the wire is pushed below
Saliceto, who practiced in Bologna and Verona, first the embrasure of each tooth and cinched around the
suggested interarch fixation for mandibular fractures tooth neck. The pair of teeth mesial to the fracture
in the thirteenth century. He used waxed, twisted silk line is now ligated in the same way. Similar wires are
threads and bound “the injured to the uninjured jaw.” placed in the same fashion around the maxillary
It remained for Gilmer, in 1887, to be the first to pro- teeth that occlude with the opposing wired
pose actual rigid interdental and intermaxillary fixa- mandibular teeth. Pairs of mandibular and maxil-
tion, which he accomplished with iron wire.12 lary teeth are captured with eyelet wires on the
Intermaxillary fixation began by separately opposite side of the arch for additional stabilization
wiring each tooth of the maxillary and mandibular (Figure 39–16, C). The patient is placed in premor-
arches and then connecting these wires one by one bid occlusion, and each loop on the mandibular side
as the teeth were brought into occlusion. From this is individually wired to the loop above. The fracture
method, certain modifications were made and is now fixed, and the wires are checked on a weekly
evolved into the method we know today. The most basis. Occasionally, the interloop wires may loosen
significant contribution was the development of the or break and may need tightening or replacement.
arch bar. Grunell Hammond, in 1871, may have The wire eyelet itself may also come loose and
described the first arch bar, a firm wire that went require tightening. Wires are removed at 3 weeks for
around the lingual and buccal surfaces of the teeth. subcondylar fractures and 6 weeks for others.
Sauer, in 1882, used a circumferential gold wire with
a spring attachment. These evolved into the Erich Arch Bars Erich arch bars generally come in a roll.
and Jelenko arch bars we recognize today. The Erich The correct length of bar for each arch is measured
bar, the one most commonly used, is a malleable by placing one end of the bar on the most distal
metal bar that easily adapts to the buccal surfaces of tooth in the arch on which it is to be fixed. The bar
the teeth and has hooks to which intermaxillary is bent around to the space between the central inci-
wires or rubber bands can be attached. The Jelanko sors. This length is now doubled, and the bar is cut
bar is rigid and difficult to accommodate to the den- from the roll. Adjustments are made for missing
tal arches. Only the application of eyelet wires and molar teeth. If significant gaps of two or more teeth
the Erich arch bar will be described. are present, the gap can be filled in with a pad of cold
cure acrylic pressed into the bar.
Eyelet Wires The eyelet wire is best used for sub- Once trimmed to length, the bar is carefully
condylar fractures, greenstick fractures, and favor- contoured to the teeth by hand. Great care is taken to
ably aligned noncomminuted mandibular fractures shape the distal ends to fit around the last teeth in
in patients who are cooperative and compliant. The the arch so that the bar will not dig into the cheek.
eyelet wire may also be used as temporary fixation Each bar is placed over the buccal surfaces of the
until definitive fixation is done. The wire is con- teeth and wired into position with the hooks facing
structed by taking a half-length of No. 26 gauge away from the occlusal surface.
Facial Fractures 911
The best teeth for securing the bar are the is taken to prevent injury to the interdental papilla;
molars and premolars. The canine has the longest however, in patients with periodontal disease, this
root but has a shape that is not conducive to reten- may be unavoidable. The wire is placed around the
tion of a wire. The incisor teeth, because of their peg- tooth adjacent to the interdental space. The two ends
like configuration, hold the wire even more poorly. If are twisted together with forceps while a periosteal
enough teeth are present in the arch, the four incisor elevator holds the wire at the level of the neck of the
teeth of each arch are left unligated. For the purposes tooth (Figure 39–18). The wire is twisted until tight.
of orientation, the application of the arch bar to the The resulting knot is turned into a tight loop and
maxillary teeth will be described first. A 6-inch piece placed away from the lug on the arch bar. Its end is
of prestretched 26-gauge wire is passed through the twisted away from the cheek. The molar and premo-
interdental space below the bar (Figure 39–17). Care lar teeth are all ligated to the arch bar using the ante-
rior wire above the bar and the posterior below for- device are essential features in the follow-up regi-
mulation. All of the wires are twisted in a clockwise men. Dental caries can lead to the formation of den-
direction (see Figure 39–18). This convention helps tal abscess during the healing phase, which, in turn,
in tightening loose wires during follow-up. results in osteomyelitis of the jaw.
Special attention is spent in securing the Nutritional advice is important. The average
canine tooth. Its long root embedded in thick bone weight loss in our patient population following inter-
makes it the key anchor for the bar. Because of its maxillary fixation is 15 lb. A booklet on dental
unfavorable shape, adaptation of the wire ligature hygiene and nutrition is supplied to each patient, with
enhances its holding ability. The wire is placed above instruction on brushing technique and diets that can
the bar, both anteriorly and posteriorly to the tooth, be employed while in fixation. Of course, only food
and then looped around the anterior aspect of the with a consistency that can be sucked in the free space
bar (Figure 39–19). around the back of the teeth can be used. Balanced
Once bars have been placed on both upper and high-calorie supplements such as Ensure-Plus® and
lower teeth, they are secured to one another either Sustacal® can be used to augment caloric intake.
with wire or elastics (Figure 39–20). Dental wax may These products come in both liquid and pudding
be placed on a protrusive edge that irritates the soft forms and are quite palatable. When the patient is
tissues. The patient is also given a stick of wax and fixed into occlusion by either Erich arch bars or eye-
instructed how to apply it to irritating wire or lugs. let wires, it is important to supply the patient with
All patients are followed on a weekly basis to check wire cutters so that if he or she vomits, the interoc-
for bar stability and tightness of the interarch wires. clusal connection can be cut to prevent aspiration.
Loose wires are tightened and broken wires replaced.
Additionally, careful attention is paid to dental Gunning Splints In the edentulous patient, the
hygiene and nutrition. Already carious dentition, a patient’s reduced mandible can be maintained by the
condition not uncommon in patients with facial use of Gunning splints. In 1861, T. P. Gunning of
fractures, is usually the reflection of past neglect. New York was, according to Dingman and Natvig,5
Careful and insistent instructions in proper brush- the first to describe the use of intermaxillary splints,
ing technique and use of a “water pick” type of which he fabricated from vulcanite. To make the
splint, a dental impression of the jaws is taken with can fit into the mandibular splint in a lock and key
an impression compound such as alginate and type of articulation. Care is taken so that the normal
poured up in stone. The stone model of the preocclusal relationship is established between the
mandible is cut at the fracture line and realigned in mandible and the maxilla. An arch bar is imbedded
the normal anatomic position and fixed with sticky into the splint prior to hardening so that the splints
wax. An impression of the realigned model is taken, can be ligated together.
and a hot-cured acrylic stent is made. A stent is also At the time of surgery, the mandibular fracture
made of the maxilla. A flange and corresponding is reduced and the splint fixed to the jaw by at least
groove are constructed so that the maxillary splint four circum-mandibular wires. A pair of drop wires
suspends the upper splint from the bone of the piri- The presence of posteriorly displaced bilateral
form apertures and from the zygomata by wires that parasymphyseal fractures constitutes an airway
encircle the arches. Once the flanges on each side of emergency. An adequate airway should be estab-
one splint are fitted into the slots of the correspon- lished promptly by placing the fractured anterior
ding splint, then the lugs of the maxillary and mandibular segment in one’s forefinger and thumb
mandibular arch bars are wired together. Alterna- and projecting it anteriorly. Often an emergency tra-
tively, the splint may be fixed with screws that pass cheostomy or cricothyrotomy is indicated.
through the splint and the unfractured alveolar ridge. Treatment of a parasymphyseal fracture with
A cruder type of splint can be made in the only intermaxillary fixation in these cases is not usu-
operating room at the time of fracture reduction in ally adequate. It is often necessary to stabilize these
the edentulous patient using cold cure acrylic. A lock fractures with interosseous wires, plate, or a lingual
and key arrangement is constructed, and arch bars splint to prevent a permanent crossbite.5,13–15 The
are pressed into the lateral surfaces of the acrylic approach to open reduction of these fractures can
before it cures. This is a less precise splint and less be either intraoral or external but is usually internal.
comfortable for the patient. Any denture, even one Care must be taken to avoid avulsing the mental
that is broken, will serve well as a Gunning splint. nerve by way of either approach.
Even a loose fitting denture will provide adequate
stabilization of the fracture. Fractures of the Body and Angle of the Mandible
Fractures of the mandibular body in patients with
Fractures of the Parasymphyseal Area These good dentition have the advantage of strong articu-
fractures tend to occur in an oblique line, sometimes lating mandibular and maxillary teeth. Intermaxil-
even approaching the midline from the mental fora- lary fixation stabilizes many of these fractures
men (Figure 39–21). The mental foramen is the sufficiently, alleviating the need for open reduction.
most commonly involved site of a parasymphyseal The forces generated by the pterygomasseteric sling
fracture. A “pure” symphyseal fracture, that is, a frac- may distract these fractures, requiring open reduc-
ture through the middle incisors, is rare. Either an tion. Once closed reduction is accomplished by
ipsilateral or contralateral fracture of the angle, means of Erich arch bars, a decision can be made
ramus, or condyle often accompanies unilateral whether the repair is stable. If not, an open reduc-
parasymphyseal fractures. Parasymphyseal fractures tion can be approached by means of a gingivobuc-
may present with a crossbite on the involved side cal incision intraorally. 16 Rarely, an extraoral
from the posterior pull of the mylohyoid. This is approach will be necessary, and a modified Risdon
especially true when there is a concomitant ipsilat- incision is made with care taken to preserve the
eral fracture of the ascending portion of the marginal mandibular branch of the facial nerve.
mandible. Loose anterior dentition, ecchymotic Angle fractures may be treated the same way as
mucosa, and grossly mobile fractured segments are body fractures. If the oblique line of fracture is in a
the hallmarks of these fractures. favorable direction, closed reduction is adequate.
When there is an “unfavorable” fracture, open approach require an experienced surgeon. Extraoral
reduction is often necessary. approaches have the advantage of increased expo-
sure and increased visualization in the region of the
Fractures of the Condylar Process and Ramus posterior part of the body, angle, and ramus. Exter-
Subcondylar fractures are usually handled by closed nal exposure requires a cervical incision; however,
reduction. Fractures of the mandibular ramus can this involves potential risk to the marginal mandibu-
be treated in a similar fashion to condylar fractures; lar branch of the facial nerve.
that is, if there is displacement of the fractures and The incision and approach chosen for a given
malocclusion results, closed reduction may be all fracture of the mandible depend on several factors.
that is needed. If there is a massive comminution, These include the location and type of the fracture,
severe telescoping, or just displacement that is not the available instrumentation and technology, and,
adequately reduced by closed reduction, open reduc- most important, the surgeon’s comfort with the
tion should be undertaken to avoid occlusal discrep- given approach. The choice for fractures of the sym-
ancies. Severe condylar fractures are defined as (1) physeal and parasymphyseal region is intraoral.
telescoping greater than 1.5 cm, (2) a condylar head Linear posterior fractures may be approached intra-
displaced out of the condylar fossa, or (3) bilateral orally, whereas more comminuted fractures or frac-
subcondylar fractures associated with a Le Fort or tures with significant bone loss usually require an
maxillary fracture. extraoral approach. The approach chosen should
The open approach is facilitated by an inci- allow adequate exposure to diagnose, reduce, and
sion in the preauricular area extending into the immobilize the given fracture.
temporal hairline, going deep to the temporalis fas- The symphyseal and parasymphyseal regions
cia.5,17 A flap of superficial temporalis fascia should of the mandible are easily approached through
be raised and the root of the zygoma followed either an intraoral or an extraoral route. The intra-
down to the fracture site. The trunk of the facial oral incision is made from canine tooth to canine
nerve is avoided by staying on the zygomatic tooth, leaving an adequate mucosal cuff for closure
process of the temporal bone, tracking down to the of the incision (Figure 39–22). Subperiosteal dissec-
glenoid fossa. With a gentle retraction of the supe- tion is made, identifying and preserving the mental
rior parotid tissues, the fossa can be exposed and nerves. The symphyseal and parasymphyseal regions
the fracture reduced by means of either a wire or a
are also easily approached through an external sub-
miniplate. Alternatives to repair of a condylar frac-
mental incision oriented in relaxed skin tension
ture include a Kirschner wire placed by way of the
lines. Reapproximation of the mentalis muscle must
angle of the mandible projected superiorly toward
be carefully performed to prevent postoperative pto-
the glenoid fossa.18,19 External pin fixation with a
sis of the soft tissues of the chin.
Morris biphase and plating techniques have also
The approach to the mandibular fracture pos-
been described.20,21
terior to the mental foramina depends on the sur-
Open Reduction Before performing open reduc- geon’s experience and the degree of the fracture.12
tion of a mandible fracture, it is always advisable, if Intraoral approaches to the body and angle are best
possible, to place the patient in closed reduction to performed by making a gingivobuccal incision
establish the occlusal relationship of the teeth. It is immediately adjacent to the fracture. Repair of pos-
folly to attempt an open reduction of any sort when terior mandibular fractures requires surgical experi-
the maxillomandibular dental relationships have not ence and advanced technology to achieve fracture
yet been established. reduction fixation. Fracture fixation is achieved by a
transbuccal system placed through transcutaneous
Surgical Approaches Intraoral approaches have facial stab incisions (Figure 39–23). The extraoral
the advantages of scar camouflage and a more direct approach to fractures of the mandibular body, angle,
approach to fracture reduction and fixation. These or ramus is made through a transcervical incision
approaches require more elaborate instrumentation two fingerbreadths below the angle of the mandible.
to allow precise fracture fixation. Intraoral incisions Care is taken to elevate the marginal mandibular
allow less direct visualization of fractures; adequate branch of the facial nerve to prevent injury. This
exposure and accurate reduction through this approach is preferred when the patient has signifi-
916 Ballenger’s Otorhinolaryngology
cant comminution of the fracture or bone loss. In intermaxillary fixation should also be used for
each of these cases, a larger reconstruction plate may approximately 6 weeks for stable bone repair.
be required for repair. The external approach allows The rationale for the use of rigid internal fixa-
greater exposure for placement of large reconstruc- tion for repair of mandibular fractures is well docu-
tion plates. mented.13,24 With interosseous wire fixation, there is
As instrumentation and technology have pro- a clinically proven decrease in mouth opening seen
gressed, treatment of mandibular fractures has 6 months after release of intermaxillary fixation.15–18
evolved, but the goals have not changed. These goals Additionally, experimental and clinical evidence
include anatomic and functional stability of the against wire fixation includes muscle atrophy18 and
mandible. Reduction and stabilization of any histologic changes in the temporomandibular joint19
mandibular fracture should result in a pain-free after prolonged periods of intermaxillary fixation.
function of the mandible without any eventual Although an increased rate of infection has not been
changes in the temporomandibular joint. conclusively shown with intermaxillary fixation and
The strength of any bony fixation must be ade- interosseous wiring, the increased bone movement
quate to overcome any forces that will act on the with nonrigid fixation makes this a theoretical con-
repaired bone during function.22 As previously men- sideration. As knowledge and technology have pro-
tioned, former techniques used wire fixation with gressed, rigid internal fixation has become the
interosseous wiring.13,23 This method allows the standard in most centers for treatment of mandibu-
bone to heal indirectly. Wire fixation is rarely used lar fractures. This allows the direct form of bone
today. The only theoretical advantage of wire fixa- healing. Use of this type of bone repair requires sur-
tion for repair of mandibular fractures is the possi- gical experience, advanced technology, and patient
bility of increased flexibility in cases with significant compliance. Direct bone healing can be achieved
bone loss or comminution. In these situations, if only with rigid fixation. If properly applied, stable
rigid fixation is applied without proper restoration rigid fixation of the mandible obviates the need for
of premorbid occlusion, the result can be either poor intermaxillary fixation.
occlusion or eventual change in the temporo- Rigid fixation of the mandible can be per-
mandibular joint. If interosseous wiring is used, formed by a variety of methods. The fracture is usu-
Facial Fractures 917
A B
FIGURE 39–24. Transbuccal system for intraoral plating. A, Plate holder passed through a stab wound in the cheek.
The buccal retractor is being secured to the plate holder. B, The drill hole has been made through the plate holder, and
now the screw will be placed to fix the plate to the mandible.
918 Ballenger’s Otorhinolaryngology
the so-called lines of osteosynthesis (Figure 39–26). duce microfractures and destabilize the fixation
At the angle, only one plate is needed, but two plates (Figure 39–28).22,27
are required at the parasymphyseal area because of Another means to achieve stable rigid fixation
the two lines of osteosynthesis. The plates are 0.9 is the placement of lag screws.20 This method
mm thick and have either 4 to 6 holes or 8 to 16 employs a basic principle of woodworking and
holes. The diameter of the screw holes is 2.1 mm, applies compression across the fracture line with
and the holes are beveled at 30 degrees. Their rigid- minimal direct bone healing. This technique
ity and tensile strength are well within the forces of requires adequate exposure and subperiosteal
mastication and other forces normally encountered undermining to allow placement of long screws that
in mandibular activity. In angle fractures, the plate is engage sufficient bone for fixation.
placed at the external oblique line and in the sym- Lag-screw fixation requires that there will be
physeal area, one at the inferior line and one in the sufficient obliquity to the fracture line to allow at
superior line of osteosynthesis (Figure 39–27). The least two, preferably three, lag screws to be placed at
plates are placed in such a fashion to avoid contact a significant distance from one another that will
with the tooth roots, although such contact is of no catch both mandibular cortices, thus stabilizing the
consequence in most instances. Care must be taken reduction. The exception to this is the mandibular
to avoid overtightening of the screws as this will pro- angle, where one screw is sufficient to achieve ade-
quate fixation. This technique is not applicable to anteriorly located fractures in the parasymphyseal
all mandibular fractures and takes a degree of and mesial body, an intraoral approach can be
understanding of the dynamics of mandibular done. For those fractures near the angle, the trans-
function and skill in inserting the screws appropri- buccal approach is employed. A trochar is intro-
ately. Through an intraoral approach, the fracture duced through a stab incision in the cheek, and the
line is exposed, and the fracture is reduced and penetrating point is removed prior to introducing
then maintained by arch bars or eyelet wires. For the drill bit (Figure 39–29). A drill guide is placed
A B
If rigid fixation is stable, the patient may be consideration is the importance of the tooth in the
taken out of intermaxillary fixation and allowed to stability of the fracture. This is especially cogent in
function. Of course, this decision is based on the sta- the circumstance of the erupted third molar tooth
bility of the rigid fixation and on the individual that lies in an unfavorably aligned fracture of the
patient’s compliance. If either the fixation stability mandibular angle. In such a fracture, the line
or patient compliance is in question, the patient may extends obliquely from anterior to posterior as it
be left in intermaxillary fixation for up to 6 weeks. proceeds from the occlusal surface to the inferior
border of the mandible. If the molar is in the distal
Dental Injury Injury to the dentition is a com- fragment, its occlusion with the maxillary third
mon accompaniment to fractures of the mandible molar above it will preclude its displacement. If this
and maxilla. A chipping of a tooth that does not molar is extracted, the pull of the medial pterygoid
extend to the dentin can be managed by the dentist and masseter muscles will displace the distal frag-
by grinding the occlusal surface smooth. Such ment upward. The wisdom tooth, being the most
injuries are usually unaccompanied by pain. Larger poorly calcified in the mouth, is the most suscepti-
fractures of the tooth substance expose the dentin ble of all to caries. One should probably remove a
or pulp and are painful. It is important to dress the carious or impacted third molar in such a circum-
tooth immediately with a dental compound that stance and achieve fixation by an open technique.
not only protects the tooth but also alleviates dis- Any dental trauma can cause pulp necrosis,
comfort. A mixture of zinc oxide and eugenol done even without a root fracture. It is important to fol-
with a metal spatula or a glass plate forms a sticky low up patients after facial fractures with vitality
compound with the consistency of putty that hard- testing of the teeth. Once viability is lost, then a root
ens when wet by the saliva. Eugenol helps to soothe canal procedure should be done to prevent abscess
the pain. Other proprietary compounds such as and tooth loss.
Dycal may be used. Later, the dentist can restore the The final consideration is that of avulsed teeth.
tooth with a crown. In the case of fracturing of a Such teeth should be immediately replaced in the
slab of tooth face in a vertical direction, especially avulsion socket and fixed by wires to the adjacent
from the incisors, the tooth can be repaired by teeth for splinting. Many such teeth later become
bonding. nonvital and require root canal procedures. Most are
Avulsion of the crown at the gum line is man- retained, however, and their preservation helps
aged either by the extraction of the root or by appli- greatly in the maintenance of dental arch integrity.
cation of a dressing until the tooth can later be
restored with a crown. If the dentition is neglected Postoperative Care Drains are usually placed in
and carious, then extraction is the best solution. open reduction wounds of the body, angle, and
Dental fractures that occur through the root ramus. These drains are usually removed on the first
present a special problem. Root fractures seriously postoperative day. Local wound care to the suture line
jeopardize the viability of the tooth. If the soft tissue is best done with peroxide cleaning and antibiotic
of the pulp is sufficiently traumatized, the tooth will ointment to avoid infection. Intraoral care should
die. Once the pulp undergoes necrosis, the stage is begin as soon as possible and consist of a water pick
set for the development of a root abscess. This may to the dentition but not the suture line and/or gargle
occur a short time after the injury or may be delayed of a solution of mouthwash and peroxide. The lingual
for years. If such an abscess were to occur during aspect of the dentition is inaccessible in the patient
intermaxillary fixation, an osteomyelitis and even a with closed reduction in intermaxillary fixation. The
nonunion could occur. effervescence of the peroxide will help to débride the
The management of a tooth in the line of frac- areas of the gum, gingiva, and teeth of the lingual sur-
ture is controversial. Some guidelines do exist that face.14 These patients often complain of pain, espe-
may be of help. If the tooth is carious and the root is cially in the first 2 postoperative weeks because of the
fractured, then the tooth should be removed. If a spasm of the pterygoid and masseter muscles while
carious tooth has a fracture through the periodontal the patient is in intermaxillary fixation. Codeine and
ligament, but the root is intact, extraction should be acetaminophen with codeine syrup are useful anal-
seriously entertained. If the tooth is healthy, the vital gesics during this immediate postoperative phase.
922 Ballenger’s Otorhinolaryngology
Persistence pain beyond 2 weeks requires nonsurgical management problems for the surgeon. With the
examination of the operative site as well as a radi- absence of teeth, the alveolar cortical bone undergoes
ographic study to determine whether there has been total resorption. The superior portion of the
a shift in the fracture site. mandible is greatly attenuated. The overall height of
The increased metabolic demands of healing the mandible, therefore, is much less than that of a
and the difficulty of eating while in intermaxillary tooth-bearing mandible. Maintaining correct
fixation make adequate nutrition a common prob- mandibular height, however, especially in the case of
lem. Liquid diets must be supplemented with a pro- angle, ramus, and condyle fractures, is essential to
tein powder as well as whole milk. It is not avoid possible temporomandibular joint problems.
uncommon for patients to sustain severe weight loss Ideally, in a completely edentulous patient with
during the ensuing 6 weeks of intermaxillary fixa- mandible fractures, the dentures can simply be wired
tion. Dietary counseling is often helpful. If the into place. In the maxilla, screws used in plating
patient remains in intermaxillary fixation, weekly techniques or Kirschner wires are excellent means of
checkups to tighten the intermaxillary wires are fixing the upper denture to the palate. The lower
absolutely necessary. If the wire ligatures are used for denture is affixed using circum-mandibular wires.
intermaxillary fixation, the wire stretches, loosening The patient should be kept in some form of inter-
the fixation. If there is not close contact with the maxillary fixation for at least 6 weeks.
maxillary and mandibular teeth, a lingual version Another form of fixation, although less accept-
may develop. This results in a severe malunion if not able, is a cap splint. This can be especially helpful in
corrected before fibro-osseous union occurs. Tight- a fracture involving the body or symphyseal area. The
ening of the wires every week prevents this from cap splint is formed by placing acrylic over the ridge
happening. Dental checkups, when possible, are also of the mandible with the fracture and affixing it to
necessary in the case of impending dental abscess. the mandible, using circum-mandibular wires. When
Intermaxillary fixation may be removed 5 to 6 dentures are not available or the fracture is in an area
weeks postoperatively, providing that there is no evi- that cannot be splinted but intermaxillary fixation is
dence of a nonunion. Nonunion can best be assessed necessary, dental impressions can be made as a tem-
by palpation at the fracture site. If there is pain in the plate for Gunning splints. Gunning splints can be
mandible and not the teeth at the operative site, a affixed to the edentulous upper and lower jaw by
nonunion or fibrous union should be strongly sus- means of the same techniques used to affix dentures.
pected, especially when accompanied by mobility. Open reduction is necessary in edentulous
Another technique is the “torque test,” which mandibles with unfavorable “fracture lines” and in
involves placing a standard wooden tongue blade on severely comminuted fractures. Interosseous wiring
the side of the fracture and having the patient bite can be accomplished in the same fashion as with
down and break the tongue blade.15 If there is no tooth-bearing mandibles. Intermaxillary fixation,
bone pain with this procedure, a good union has however, must be used in this situation. Compression
been achieved, and the arch bars may be removed. plating is also convenient in these cases by way of
The patient is still cautioned to remain on a soft diet either the external or intraoral approach. The advan-
for 2 to 3 additional weeks. tage of using a compression plate is that rigid fixation
When arch bars are removed, a dental consul- is achieved that does not require intermaxillary fixa-
tation is needed to inspect the teeth for occlusal dis- tion. In elderly patients, however, especially those with
crepancy. Orthodontia may provide the necessary osteoporosis of the mandible, placement of a secure
correction. Major malunions may require osteotomy plate may be difficult and may loosen with time.
of the involved segment and repositioning with fur-
ther intermaxillary fixation. With an accurate initial Pediatric Mandibular Fractures A mandibular
assessment, careful surgical technique, and good fracture in a patient younger than 15 years requires a
postoperative care, the need for further adjustments knowledge of the state of both permanent and decid-
of occlusion should be infrequent. uous dentition. The tooth buds of the permanent
teeth are located below the roots of the deciduous
Special Considerations: The Edentulous Mandible teeth. Surgical trauma to the tooth buds may retard or
The fractured edentulous mandible presents specific completely negate the buds’ ability to erupt later. Pri-
Facial Fractures 923
mary teeth are fully erupted usually by the second or require interventional therapy. Therefore, one can
third year of life. The central incisors are the first teeth expect nearly one of five children with a mandible
to appear, followed by the lateral incisors, first molars, fracture to have some sort of difficulty that may
cuspids, and second molars. The shedding of these require later intervention. It is recommended that
teeth occurs in the same order and is usually complete these patients be followed closely postoperatively
by 12 years of age. Therefore, in the first 12 years of by a dentist and/or orthodontist, and the use of
life, there are tooth buds of permanent teeth or par- braces and elastics may be necessary to promote
tially erupted permanent teeth that may be endan- growth and development of the fracture area.29 The
gered by surgery. The presence of these tooth buds remodeling of untreated subcondylar fractures is
also makes the tooth-bearing areas of the mandible in well documented.30,31
a child more prone to fracture than in an adult. They,
in effect, create a more porous bony surface with less Severe Mandibular Fractures If the trauma is
structural support. from an explosion or a gunshot wound, or if the
In the tooth-bearing areas of a mandibular blunt trauma is excessively severe, there can be mul-
fracture in a pediatric patient, an overlapping cap tiple missing pieces of mandible.32,33 In these cases,
splint provides adequate, stable reduction to pro- open reduction and exploration are mandatory if
mote anatomic bone healing. Because of the ability the patient’s condition permits. The bony fragments
of children to heal rapidly, the splint is required only that do not have periosteal attachments should be
for approximately 4 weeks. In the angle area, if the removed and the area débrided and cleaned aggres-
fracture is in an unfavorable line, open reduction sively. Often in these fractures, there are portions of
may be attempted. Radiographic documentation of mandible that are pedicled on small pieces of perios-
the proximity of the erupting of the third molar bud teum. If less than 25% of the bone surface area is
and second molar tooth bud should always be con- attached to periosteum, most surgeons would agree
firmed. If the fracture line is close to a tooth bud, that débridement is necessary to prevent this from
closed reduction may be necessary. Arch bars can be becoming a sequestrum.
used in a pediatric patient with wire ligatures; how- Gunshot wounds require soft tissue débride-
ever, they may cause premature shedding of the ment, especially high-velocity wounds in which there
deciduous teeth. Generally, intermaxillary fixation is may be a large temporary cavity. A discussion of bal-
not necessary in a child for safe healing of a fracture listics is beyond the scope of this chapter. Let it suf-
of the symphysis or body. Condylar fractures in the fice to say that high-velocity weapons cause extensive
pediatric population have been seen to remodel soft tissue damage from both the impact of the
completely without surgical intervention; therefore, weapon and the secondary missile effect of the mobi-
no treatment is recommended. lized bone through soft tissues. The use of external
pin fixation and the application of the biphase appli-
Complications in Pediatric Fractures The tooth ance of the mandibular segments alleviate the possi-
buds of an infant or young child are especially sus- bility of infection that would otherwise be incurred
ceptible to damage that may cause deformities of by placement of a foreign body such as a plate in a
the erupted mature tooth later.28 A long-term fol- potentially grossly infected wound.
low-up study of 28 children with mandibular frac- If the wound can be cleaned adequately and
tures was done by McGuirt and Salisbury.29 The soft tissue coverage achieved, a long mandibular
mean length of follow-up was 101⁄2 years. The chil- plate can be used to approximate the (usually) mul-
dren were divided into condylar only, noncondylar, tiple segments. Once healing has taken place and the
and condylar fractures with other facial fractures. infection is cleared, in 6 months to 1 year this area
Forty-six percent of the patients had temporo- can be reconstructed using autogenous bone from a
mandibular joint compromise. Five patients were variety of sources or a free flap (Figure 39–31).32
concerned about their external facial asymmetry. A
medical/dental team reviewed abnormalities in
47% of the patients radiographically. Sixteen per-
ZYGOMATIC FRACTURES
cent of the overall group were thought to be both The zygoma is the third most frequently fractured
clinically and radiographically abnormal enough to facial bone, with 85% of fractures occurring in men.
924 Ballenger’s Otorhinolaryngology
A B
fracture of the arch pushing into the temporal fossa generally are clinically insignificant. When discussing
often results in restriction in movement of the jaw a fracture of the zygoma, one must realize the impor-
because of impingement of the arch on the coronoid tance of the intimate association to the lateral canthal
process. The fractures of the zygoma tend to occur at tendon and the suspensory ligaments of the globe.
the articulations with the aforementioned bones. There is some downward displacement in many frac-
The body of the zygoma, which makes up the infer- tures of the zygoma because of the previously men-
olateral orbital wall and is often the point of impact tioned traction of the masseter; therefore, the globe
from trauma, is rarely fractured because it is the position can change. The entire globe can be pulled
thickest part of the bone. Comminuted fractures of down because of downward displacement of the sus-
the zygomatic body are a difficult problem in surgi- pensory ligament of Lockwood, which attaches to
cal management. Whitnall’s tubercle, located on the lateral aspect of
the orbital process of the zygoma. Also associated
with the floor of the orbit are the inferior oblique and
SURGICAL ANATOMY inferior rectus muscles, which are most often
The zygoma has four suture lines connecting it with entrapped when the floor of the orbit is badly frac-
the temporal, frontal, maxillary, and sphenoid bones. tured (blowout fracture). Impalement of the muscles
In addition to the temporalis and masseter muscles, on a fracture fragment puts the muscle into spasm,
the lesser and greater zygomatic muscles also insert which limits upward gaze. True entrapment of these
on its surface. The orbital process of the zygoma muscles, which is rare, must be corrected surgically.
makes up the anterolateral portion of the infraorbital
foramen in the floor of the orbit. It is not uncom-
mon, with a severe zygoma fracture, for there to be a
DIAGNOSIS
herniation of orbital contents through the fracture of History and physical examination are of primary
the maxillary zygomatic suture line. The infraorbital importance in evaluating a zygomatic fracture. The
nerve exits from the infraorbital foramen at the artic- patient gives a history of having received a blow
ulation of the zygoma and maxilla. Damage to this from a fist, a ball, or other blunt object or has been
nerve causes hypesthesia of the cheek on the affected involved in an automobile or motorcycle accident.
side as well as the lateral aspect of the nose. From the He or she complains of localized pain and often has
body of the zygoma exit two sensory nerves, the numbness over the ipsilateral cheek. If there is sig-
zygomatic frontal and zygomatic temporal, which nificant herniation of fat into the maxillary sinus,
926 Ballenger’s Otorhinolaryngology
diplopia ensues from herniation of orbital fat or intraocular injury is common, an ophthalmologic
entrapment of the inferior rectus and/or inferior consultation should be obtained in all cases.
oblique muscles. With no herniation of fat or evi- There is palpable facial skeletal asymmetry over
dence of an orbital floor dehiscence, inferior dis- the malar eminence and zygomatic arch if the
placement of the zygomatic compound distracts swelling is not too severe. One may place a gloved fin-
Whitnall’s tubercle and therefore the ligament of ger into the oral cavity to feel the zygomatic buttress
Lockwood, causing the same problem of diplopia.6 and appreciate crepitus and swelling. This movement
Trismus can result from impingement of the is exquisitely tender to a patient with a fracture.
zygomatic arch on the coronoid process of the There is trismus in some of these patients, defined as
mandible. Often there is substantial masseter and the inability to open the mouth more than 3 cm. In
temporalis spasm from contusion to that area, which the absence of severe swelling, a fracture of the arch
may produce trismus even if the arch is intact. and the infraorbital rim can be palpated. The patient
The patient with a zygomatic fracture may also may be unable to raise the affected eye from the
have epistaxis from bleeding into the maxillary equator and experiences diplopia (Figure 39–33). A
sinus, the blood exiting by way of the ostium of the forced duction test should be done on all patients
maxillary sinus and nose. On inspection, the patient with diplopia. A positive test indicates entrapment of
has severe periorbital ecchymosis and swelling as the inferior rectus or inferior oblique muscle. Table
well as a lateral subconjunctival hemorrhage sec- 39–3 provides a listing of signs and symptoms of
ondary to tearing of vessels of the canthi. Blood in zygomatic fractures.
the anterior chamber (hyphema) indicates severe Zygomatic fractures can be classified according
damage to the globe, and an emergency ophthalmo- to their severity. An isolated fracture of the zygo-
logic consultation is mandatory.34 Hemorrhage matic arch may occur with no orbital involvement.
restricted to the subconjunctiva does not imply seri- However, most fractures involve the four suture lines
ous damage to the globe per se. Enophthalmos is previously alluded to. Fracture of the zygomatico-
common secondary to fat and muscle herniation maxillary suture line and orbital floor without
into the maxillary sinus. Because concomitant involvement of the frontal zygomatic or frontal tem-
TABLE 39–3. Symptoms and Signs of Zygomatic surgical intervention. The only strict indications for
Fractures surgery are relief of trismus and correction of
diplopia from an inferior displacement and entrap-
Symptoms Signs ment of the inferior rectus and inferior oblique mus-
Pain Infraorbital tenderness cles. Most often, the patient desires repair for
cosmetic reasons. If there is ipsilateral numbness
Double vision Lack of conjugate gaze
after a fracture, this improves, in the large majority
Numbness Hypoesthesia: cheek, upper teeth of cases, with no surgical intervention. Therefore,
Epistaxis Malar flattening numbness of the cheek should not be the only indi-
Hypo-ophthalmus/enophthalmos cation for surgery. When obtaining the patient’s con-
Trismus Subconjunctival hemorrhage sent for surgery, one must be careful to give counsel
Cosmetic deformity
about the proximity of the globe to the surgical site
and alert the patient to the real risk of retrobulbar
hematoma and retinal tear from retraction of the
poral suture line constitutes an impure blowout globe.34 These complications are extremely rare with
fracture. A pure blowout fracture refers to a dehis- careful surgical technique. More important in pre-
cence of the orbital floor with an intact orbital rim.35 operative counseling, if an infraorbital rim approach
A severely comminuted body fracture requires is needed, is to inform the patient of the possibilities
extensive exposure and is managed differently than a of prolonged lower lid edema and the possibility of
tripod fracture. The treatment of these various frac- ectropion. The onset of visual field changes,
tures differs, and diagnosis should be confirmed
with radiographs.
Standard facial films including Waters’, Cald-
well’s, Towne’s, and submental vertex views are usu-
ally obtained on these patients. This battery of films
helps rule out associated facial fractures. The Waters’
and submental vertex views are of great help in diag-
nosis. The Waters’ view can reveal an orbital floor
dehiscence by the classic teardrop sign indicating her-
niation of orbital contents into the maxillary sinus.
There is often blood in the maxillary sinus, however,
which may obscure this sign. Also, the orbital rim,
frontozygomatic suture line, and body of the zygoma
are well visualized with the Waters’ view. The sub-
mental vertex view is excellent for evaluating the
zygomatic arch. Although most zygomatic fractures
are readily diagnosed on plain radiographs, the CT
scan affords a more accurate rendition of the fracture
details. It is especially good at depicting the degree
and severity of orbital floor fractures (Figure 39–34)
and in detecting fractures of the orbital apex. Subtle
unilateral associated fractures of the palate will be
detected as well. Three-dimensional CT scanning
provides a dramatic view of the fracture but adds lit-
tle to the therapeutic decision-making process.
diplopia, or a change in the patient’s visual acuity stabilize the fracture, both laterally and inferiorly.
requires an ophthalmologic consultation. The “classic” technique of placing a plate or wire in
One of the possible occult injuries of a zygo- the frontal zygomatic fracture line and the zygomati-
matico-orbital fracture is a retinal tear. Traction of comaxillary suture line at the infraorbital rim pro-
the globe during surgery to repair a zygoma may vides adequate stabilization for a large majority of
extend a small, insignificant retinal tear, creating a fractures. Some fractures treated in this manner are
large visual field defect. This can be avoided by lim- not adequately stabilized and require antral packing
iting retraction of the globe to short periods of time or an intraoral approach to reduce the inferior aspect
and using extreme caution. of the fracture. One-point fixation techniques have
Serious intraocular injury mandates delay of been described using either a Kirschner wire36 or,
repair until the globe has stabilized. Otherwise, the more recently, a rigid miniplate.37–39
timing of the repair of a zygomatic fracture depends Fractures of the zygomatic arch (Figure 39–35)
on the degree of soft tissue swelling. If swelling is with a significant cosmetic defect or trismus can be
severe, waiting for 5 to 10 days is acceptable, and elevated by means of a Gillies incision in the tempo-
moving the zygoma will not be a significant problem ral hairline (Figure 39–36, A) and reduced directly.
during that time. After 10 to 14 days, the zygoma may The temporal branch of the facial nerve is avoided
form a fibrous union, making mobilization of the by placing the elevator deep to the superficial fascia
fracture difficult. A good rule of thumb is to reduce of the temporalis muscle. The Boies elevator is
the fracture as soon as the swelling has subsided placed under the arch, and the fragments are levered
enough to compare both zygomas intraoperatively. into position (Figure 39–36, B). A plate is rarely ever
required for fixation because of the splinting action
Surgical Technique Multiple techniques have been of the underlying temporalis muscle.
used to repair a zygoma fracture. The four fracture For the open technique, a supraorbital brow
lines imply that there should be points of fixation to incision is made within the brow line or as an
amount of pressure is initially required to get the underside of the zygomatic buttress. In most tri-
screw started. This is not usually a problem in the malar fractures, this step is entirely unnecessary.
lateral orbital wall but may be impossible in the Compound comminuted fractures of the body
infraorbital rim. A microplate is adapted to the (Figure 39–41, A) require a direct approach by way
infraorbital rim, and two drill holes are placed on of either a coronal scalp incision or extending the
either side of the fracture line (Figure 39–40). The infraorbital incision superiorly and the upper brow
screws are placed in the infraorbital and lateral incision laterally. Either a rigid miniplate or multiple
orbital rims, providing the necessary two-point fix- interosseous wires can be used to fix multiple com-
ation. Some individuals add an additional plate at minuted body fractures. When interosseous wiring is
the inferior aspect of the zygomatic buttress. This used for the compound body fracture, it is some-
will require an additional incision in the gingival times necessary to maintain elevation of the zygoma
buccal sulcus such as an extended Caldwell-Luc inci- as it tends to prolapse. This can be done with an
sion. A subperiosteal elevation will expose the external pin fixation device such as a Morris biphase,
stabilizing it superiorly to the frontal bone. Properly face while sleeping. This protective device is best
placed rigid miniplate fixation eliminates the need retained for at least 2 weeks but can be removed
for an external device and is the method of choice when the patient is not sleeping. The zygoma
(Figure 39–41, B). guard is necessary in patients who have had
interosseus wiring of a trimalar fracture, a reduced
Postoperative Care After surgery, if the fracture but not rigidly fixed arch fracture, or an unstable
is unstable, a head dressing should be applied to fracture with multiple comminution. Most frac-
hold a zygoma guard in place (Figure 39–42). This tures fixed with a rigid plating system will not need
will not necessarily protect the zygomatic arch the guard.
from collapsing with some pressure but will Routine wound care is administered in the
remind the patient not to roll on that side of the postoperative period, and the sutures should be
A B
FIGURE 39–41. A, Complex body fracture of zygoma. B, At least three-point stabilization is required for adequate fix-
ation. Reproduced with permission from Donald PJ. Zygomatic fractures. In: English GM, editor. Otolaryngology.
Philadelphia: JB Lippincott; in press.
the face of the anterior maxilla, and across the fractures of the midface are comminuted and that
orbital floor, including the infraorbital foramen. within the confines of the midfacial skeleton, these
The fracture line goes through the lateral wall of the multiple fractures may take on many configura-
maxilla extending to the pterygoid plates, usually tions.45–47 The concept of the structural pillars of the
higher than the Le Fort I. Le Fort III fractures are midface (Figure 39–44) helps to elucidate the key
lateral fractures extending across the orbital floor areas of fracture and therefore the subsequent stabi-
into the lateral orbit through the zygoma. They can lization of the midface as it relates to both potential
include the frontal zygomatic suture line. If the cosmetic deformities and functional problems. An
zygoma moves during palpation of the palate, a Le understanding of these structural pillars not only
Fort III fracture is present. aids in assessment of the severity of the fracture but
Le Fort fractures are commonly found in com- also provides an excellent strategic framework for
binations. A Le Fort I fracture may have an associ- surgical intervention.
ated Le Fort II or III on the side of impact. A Le Fort There are three main buttresses of the midfa-
II fracture may be a Le Fort III fracture on the side cial cranial complex.47 Going from anterior to pos-
of the impact. The exact classification of the frac- terior, the anteriormost buttress is the nasal
tures on each side is important because of the dif- maxillary buttress extending from the maxillary
ferences of treatment associated with the different alveolus along the piriform aperture up to the
types. One should refer to the fractures based on the medial side of the orbit through the anterior
type of fracture on each side, for instance, left Le lacrimal crest, the frontal process of the maxilla to
Fort III or right Le Fort I. the superior orbital rim, and ending at the frontal
bone of the cranium.
The zygomatic buttress extends from the max-
FURTHER CONSIDERATIONS illary alveolus above the anterior molar teeth to the
Structural Pillars of the Midface Le Fort’s classi- zygomatic process of the frontal bone with a vertical
fication was surprisingly complete in its description component consisting of the zygomatic arch articu-
of the midfacial fractures, although there are certain lating with the zygomatic process of the temporal
limitations to his original descriptions. The classifi- bone at the base of the skull.
cation of Le Fort fractures is based on the most The buttress of the pterygomaxillary alveolus
superior fracture line involved in the fractures and articulates with the base of the skull through the
does not take into account the fact that many of the orbital process of the palatine bone, articulating pos-
Facial Fractures 935
A B
FIGURE 39–44. A and B, Biomechanical stress curves of the middle third of the face.
teriorly with the sphenoid bone. The pterygoid por- always the possibility of midfacial telescoping, which
tion of this vertical buttress consists of the pterygoid results in a shortened midface.46–48
plates extending inferiorly and anteriorly toward the
maxilla. The horizontal system of buttresses divides
the oral, nasal, and orbital regions of the face.
DIAGNOSIS
If one considered these pillars in midfacial frac- Eliciting an accurate history on a patient with severe
tures, therapy should be directed toward the stabiliza- midfacial injury is often difficult or impossible
tion of as many of these buttresses as possible. because of associated intracranial, abdominal, or
Probably the two most important areas of stabilization intrathoracic injuries. The motor vehicle accident
are the nasal maxillary buttress and the zygomatic but- victim may also be inebriated. If the patient is con-
tress. The more posterior vertical pterygomaxillary scious, however, and does not have any life-threat-
buttress is more inaccessible surgically, although the ening injuries requiring emergency surgical
most inferior portion of it can be stabilized if neces- intervention, a thorough history is helpful in ascer-
sary. In severely comminuted Le Fort fractures, the taining the extent and severity of facial injury.
surgeon must appreciate the advantage of open Because the maxilla forms the anterior floor
reduction and internal fixation of multiple fragments of the orbit, there may be herniation of the orbital
in their anatomic positions, especially those relating soft tissues into the maxillary sinus, similar to that
to this buttress complex. Without proper reduction of seen in a blowout fracture. Diplopia may be a com-
the midface fractures or proper stabilization of con- plaint in Le Fort II or III fractures. Complaints of
comitant subcondylar mandibular fractures, there is blurred vision or a change in visual acuity mandate
936 Ballenger’s Otorhinolaryngology
an ophthalmologic evaluation. Epiphora may also the palate in these cases may require considerable
be a component of compound fractures involving force.
the lacrimal duct and/or the inferior medial orbital
area. Difficulty in breathing is a common problem
from congestion associated with edema from the
IMAGING
fractures as well as physical derangement of the Radiologic diagnosis of Le Fort fractures is a very
nasal bones and septal structures. Bleeding from the important adjunct to their treatment. Many midfa-
maxillary or ethmoid ostia or from lacerations cial fractures can be assessed with sinus radiographs,
within the nasal cavity may cause severe nasal but the precision of the CT scan is a huge advantage
obstruction. Patient complaints of a salty taste in in delineating the extent and severity of midfacial
the mouth should alert the physician of the possi- fractures. Central injuries can be ruled out by extend-
bility of a cerebrospinal fluid leak. Most commonly, ing the scan through the head; any nasal-frontal or
these are found in the cribriform plate or the roof of frontal sinus components can be delineated, and
the ethmoid sinuses.5,6 Displacement of the maxilla fractures of the sphenoid and orbital apex are excel-
causes the patient to complain of malocclusion. lently portrayed. Scans in both the axial and coronal
Although there may be either buccal or lingual ver- planes are necessary for the most complete analysis.
sion, the most common occlusal abnormality is an Magnetic resonance imaging is of little added assis-
open-bite deformity. The open-bite deformity is tance except in the case of cerebral trauma or com-
caused by the powerful forces of the pterygoid mus- promise of the optic nerves. Three-dimensional
cles distracting the posterior part of the maxilla reconstruction, although spectacular, offers little
inferiorly.6 A blow directed anteriorly causes dis- additional information that will guide therapy.
placement of the maxilla posteriorly, resulting in a
so-called “dish face” deformity and a Class III mal-
occlusion. A more detailed discussion of dental
TREATMENT
occlusion is given earlier in this chapter. As in all patients involved in trauma, the fundamen-
Airway compromise is often the presenting tal precepts of trauma care apply. The airway is of
symptom. The posteroinferior displacement of the great importance in these patients. A displaced Le
fractured maxilla by the pterygoid muscles tends to Fort fracture can compromise the airway, especially
decrease the airway. This, coupled with attendant if it is associated with concomitant massive swelling
swelling and hemorrhage, may produce airway of the tongue and oropharynx.5,6 A cricothyroido-
obstruction. tomy may be required urgently. Endotracheal intu-
On physical examination, the patient may have bation should be avoided because of the problems of
periorbital ecchymosis, massive tissue swelling, or poor visualization, the possibility of aggravating a
subconjunctival hemorrhage if the infraorbital rim is cervical spine injury, and the possibility of causing
involved. Dental examination confirms the previously injury to the central nervous system from the endo-
mentioned findings relating to open bite, lingual/buc- tracheal tube. Nasotracheal intubation is even worse
cal version, and Class III malocclusion. Bony crepitus because of the danger of intracranial intubation
of the midface, especially in severely comminuted through a fracture line in the skull base. Tra-
injuries, is common. Also, extensive fractures in the cheostomy preferably should not be done in the
presence of a large communication with the antrum emergency room but performed electively in the
and the nose cause subcutaneous emphysema. operating room. All other injuries should be ruled
Nasal or pharyngeal hemorrhage may be mas- out, including intra-abdominal, intrathoracic, and
sive. This is important because most patients are intracranial injuries. The cervical spine should
evaluated in the supine position. Nasal and pharyn- undergo radiographic evaluation.
geal bleeding drains toward the posterior part of the If the patient is to undergo immediate general
pharynx and may go unnoticed. Palpation reveals a anesthesia for a related injury and is hemodynami-
mobile palate. If the palate does not move even cally stable, immediate repair can be undertaken if
though there appear to be gross occlusal differences good radiographic documentation of the injury has
and/or obvious fractures, it is because the midface been obtained. Often, if a patient is rushed to the
has impacted into an immobile position.49 To move operating room because of a life-threatening injury,
Facial Fractures 937
proper radiographs may not have been obtained, coronal incision has the advantage of providing
and if a Le Fort fracture is suspected, the patient exposure to the zygomatic arch and the nasoeth-
should be placed temporarily into intermaxillary fix- moid region. This obviates the need for a Lynch inci-
ation and undergo tracheostomy. In this emergency sion for nasoethmoid exposure.
situation, the patient can be more fully evaluated The incisions used depend on the location and
radiographically at a later time to ascertain the extent of the fractures. Most Le Fort fractures do not
extent of the midfacial fractures. Definitive repair of manifest as the original description but are combi-
all fractures may be delayed for up to 10 days before nations of complex fractures of the midface and
bony union may make reduction difficult. Thorough require knowledge of multiple surgical approaches.
preoperative planning to repair these fractures In patients with dentition, arch bars and inter-
includes ophthalmologic examination, dental evalu- maxillary fixation are initially applied to re-establish
ation, and clearance by neurosurgeons if there are pretrauma occlusion. In edentulous patients, splint
concomitant intracranial injuries. Repair should also or denture containing an arch bar is fixed to the
be delayed until the status of the cervical spine is mandible or maxilla to re-establish appropriate
determined. skeletal relationships. This is performed with cir-
cum-mandibular wires or drop wires from the piri-
Surgical Approaches Incisions used to approach form rim or zygoma. The maxillary (palatal) splint
midfacial fractures vary according to the specific may also be fixed to the palate with two transpalatal
location of the fracture. Isolated Le Fort I fractures screws. In any case, splints or dentures are placed to
are usually approached by an extended sublabial re-establish the occlusal and skeletal relationship.
incision (Figures 39–45 and 39–46). This incision In patients in whom midfacial fractures are
allows exposure of the zygomaticomaxillary but- displaced, disimpaction of fractures may be required
tresses and piriform apertures bilaterally. If the frac- before placement of intermaxillary fixation. Disim-
ture involves the infraorbital rim (Le Fort II), a paction is best achieved by use of the Rowe-Killey
transconjunctival-lateral canthotomy or subciliary disimpaction forceps (Figure 39–47). The straighter
incision is usually used to expose these fracture sites. blade is placed in the nasal cavity along the nasal
If a Le Fort II fracture is more extensive and greater floor and the more curved blade over the alveolar
exposure to the nasoethmoid complex is required, ridge and along the palate. With the handles firmly
an external Lynch incision or extended coronal inci- grasped, a downward and anterior pull will disim-
sion may be used. The frontozygomatic suture line pact the maxilla and restore it into its normal rela-
may be approached by a coronal, brow, or extended tionship with the mandible and skull base. After the
upper blepharoplasty (supratarsal) incision. The occlusal relationship is re-established, all fracture
sites are fully exposed. The facial skeleton should tresses is established on each side. Titanium low-
then be reconstituted in three dimensions: height, profile miniplates in an “L,” “X,” or square configu-
width, and depth.46,47 Careful attention should be ration are placed on the anterior buttresses and
paid to re-establishing all important facial but- usually an “L”-shaped plate on the undercurve of
tresses. In particular, the vertical zygomaticomaxil- each zygoma onto the maxilla bilaterally (Figure
lary and nasomaxillary buttresses should be carefully 39–48). More recently, low-profile absorbable plates
reduced and fixated to re-establish vertical facial of polymers composed of polyglycolic or polylactic
height. All rigid fixation should be applied with suf- acid or a combination have been employed in place
ficient stability to counteract any forces that could of titanium plates. These plates are reputed to retain
disrupt bone repair during healing. sufficient strength to maintain fixation over the crit-
For a Le Fort I fracture, a two-point stabiliza- ical period of healing and are then absorbed. This is
tion at the nasomaxillary and zygomaticofacial but- especially an advantage in children in whom the
FIGURE 39–47. Maxillary disimpaction using Rowe-Killey forceps. A, Pair forceps. B, Forceps applied on one side. C,
Forceps applied on both sides.
Facial Fractures 939
metal plates may impede bony facial growth at correct position to establish the occlusal template for
suture lines. In adults, the principal advantages are the maxillary dentition to approximate accurately.
in preventing pain that is occasionally seen with the Rigid fixation of all mandibular fractures is vital to
metal plates and with time eliminating the palpable ensure this relationship. Displaced subcondylar frac-
plate at the lateral and infraorbital rims. The dura- tures must be fixed to provide the stable platform
bility and utility of absorbable plating systems have even when only unilateral. Undisplaced subcondylar
yet to stand the test of time. fractures are usually sufficiently stable to avoid rigid
Le Fort II fractures require fixation at the infra- fixation. The goals of reduction and fixation of the Le
orbital rim and the zygomaticomaxillary buttresses. Fort III fracture must be clearly borne in mind as fix-
If the nasal bones are comminuted, microplates are ation proceeds. First, the supporting buttresses of the
used on the nasal bones. The infraorbital rims will face must be re-established. Second, the functional
be fixed with microplates as well. As in most elements must be restored, such as the correct orbital
instances, the miniplates have too high a profile and volume, including an adequately restored orbital
will be obvious through the skin. floor with orbital contents free of entrapment, a
The Le Fort III fracture is often a devastating patent nasal airway bilaterally, and maxillary sinuses
injury usually accompanied by cerebral trauma. It is that will adequately drain. Third, all-important
not uncommon to have a staged type of treatment in esthetic landmarks must be restored, such as the
which the neurosurgeon controls the intracranial orbital rims, nasal dorsum, and malar eminences. It
injury and the management of the facial component is not necessary and, in some instances, is indeed
is limited to the performance of a tracheostomy and impossible to approximate every small maxillary
the application of arch bars and interdental elastic fragment. The lateral orbital rims and the buttresses
bands. The treatment of the maxillary fracture is are fixed with miniplates and the nasal dorsum and
delayed until the patient’s neurologic status has sta- infraorbital rims with microplates (Figure 39–49).
bilized. The shattered maxilla must be fixed between Occasionally, small fragments in key positions may
two stable platforms. The cranium provides the supe- require fixation with fine wire or even suture mate-
rior stabilization point and the mandible the inferior. rial. The use of titanium wire will prevent interfer-
All displaced fractures of the cranial vault must be ence in subsequent scans.
restored to their normal anatomic position. Similarly, If rigid fixation is considered stable and if the
all fractures of the mandible must be rigidly fixed in patient is compliant, intermaxillary fixation may be
940 Ballenger’s Otorhinolaryngology
removed at the conclusion of the operation or The telecanthus may be unilateral or bilateral.
within the first 1 to 2 weeks after the operation. If The natural contraction of the orbicularis oculi,
the stability is in question (ie, with bone comminu- whose tendonous extension comprises the bulk of
tion or bone loss), intermaxillary fixation should be the medial canthal tendon, pulls the medial canthus
left in place for up to 6 to 8 weeks. This will help away from the midline. This produces a blunting of
maintain the occlusion while bone healing occurs.
NASOFRONTAL-ETHMOIDAL
FRACTURES AND TRAUMATIC
TELECANTHUS
A central blow to the face created by a small-diame-
ter object, such as the head of a hammer, may not
produce a Le Fort type maxillary fracture but, if of
sufficient force, may cause a severely comminuted
nasal fracture that shatters the medial orbital walls
and telescopes into the ethmoid block, lodging the
fractured bones under the nasal process of the
frontal bone (Figure 39–50). Not uncommonly, this
nasofrontal-ethmoidal fracture will be accompanied
by telecanthus that results from either the shearing
away of the medial canthal tendons or a displace-
ment of the lacrimal and maxillary bones into which
the tendon or tendons insert. The nasal dorsum is
essentially displaced into the fractured anterior eth-
moid cells (Figure 39–51). This injury produces a
typical clinical picture of a patient with a “pig snout”
deformity consisting of a flattened nasal dorsum FIGURE 39–50. Nasofrontal complex fracture. Note
with an exaggerated excessively superiorly rotated nasal bones driven under the frontal bones. Reproduced
tip (Figure 39–52). with permission from Donald PJ et al.51
Facial Fractures 941
A B
The repair of the nasoethmoidal fracture con- the fractured lamina papyracea on both sides, insert
sists of disimpacting the nose from the collapsed two bone hooks into the ethmoid block, and turn
ethmoid sinuses and, if there is telecanthus, repair- the hooks nasally and then apply a down and for-
ing one or both canthal tendons. It is often a diffi- ward traction (Figure 39–55). This will usually pull
cult task and should be undertaken as soon as the fractured nasal bones into their normal
possible after the accident. One method, using bilat- anatomic position, where they can then be fixed to
eral Lynch incisions, of disimpacting the fragments the frontal bone with a microplate. A badly com-
in the ethmoid is to dissect the periorbita away from minuted nasal fracture may have insufficient bone
to hold even the small 0.8 mm screws required for exists, then some kind of stabilization must be cre-
microplate fixation. A solution to this is the use of ated to prevent the wire from pulling through. The
suspension wires and lead plates.51 The wires are Kazanjian button may be created by twisting the two
driven from one side of the nose to the other with wires passed through the tendon into the configura-
the nasal skeleton in the reduced position. The wires tion of a rosette.35 Another method is the use of a
penetrate skin, nasal bone, and ethmoid sinuses on Dacron bolster (Figure 39–57), which is usually used
one side and then pass through the septum and the to stabilize hemostatic sutures placed in the aorta.51
same structures of the other side (Figure 39–56). It In a unilateral canthal repair, the wire can be secured
must be remembered that the plates act simply as to the bone of the medial wall of the opposite orbit.
anchoring sites for the wires and not as a means of If enough bone of adequate strength is present on
narrowing the nose. Overtightening of the wires can the ipsilateral side, then that would be preferable. A
lead to underlying skin necrosis. The wires are bone graft on the opposite side of the nose can be
removed after 3 weeks. used or even two holes in a microplate that has been
Obtaining an excellent cosmetic result in the used to stabilize the nasal bones. It is vital to place
reduction of dislocated medial canthal tendons is the tendon high and posterior with some small over-
one of the most demanding tasks in the surgery of correction as some degree of relapse is almost
facial trauma. The repair is best done as soon as pos- inevitable.
sible after the accident. Late repairs are notoriously The worse injury is the bilateral canthal ten-
noted for their less than optimal results. Often the don avulsion. The Converse-Hogan open sky tech-
tendon comes away with a fragment of attached nique is probably the most effective (Figure
lacrimal bone. In those instances, two small holes are 39–58).52 This method wires one canthal tendon to
placed in the bone that will serve as anchor points that of the opposite side and supports the skin of the
for the wire used in fixation. If no anchoring bone nasal area with lead plates.
abscess. The treatment of choice is the osteoplastic duct is somewhat controversial. The author prefers
flap and fat obliteration procedure. to do the osteoplastic flap and fat obliteration oper-
The area of the frontal sinus that is the most ation to eliminate the duct. Others prefer the Lynch
difficult to visualize radiographically is the region of procedure combined with a nasal septal or medially
the frontonasal duct. The most important radi- based lateral nasal wall flap, the so-called Sewall-
ographic sign is the presence of fluid in the sinus as Boyden flap.58 Removal of the intersinus septum will
demonstrated by sinus opacification. If this persists allow egress of mucus from the fractured to the non-
over a 3-week period, the index of suspicion regard- fractured side. More lately, the interest in functional
ing the possibility of a duct fracture is high. If the endoscopic sinus surgery has prompted some to do a
patient sustained an anterior wall fracture and early conservative removal of the duct through the nose.
intervention for its repair is undergone, then, at the These procedures have yet to stand the test of time.
same time, a sinus endoscope can be placed through The most serious of all of the frontal sinus
the site of the fracture and the duct visualized injuries is the “through-and-through fracture.”59 In
directly. If, however, there is a suspicion of an isolated this dramatic injury, the frontal skin is lacerated,
duct fracture, then a trephine hole in the orbital roof both anterior and posterior walls of the sinus are
will provide access to wash the sinus out with saline, fractured, often with extensive comminution, the
install some cocaine, and then place a radiopaque dye dura is torn, and the brain is contused (Figure
within the sinus cavity. A subsequent radiograph will 39–60). The frontal sinus is often merely an inferior
show presence of the dye within the nose if the duct extension of a larger compound cranial fracture.
is patent and absence of the contrast material if the Approximately 50% of individuals afflicted by a
duct is fractured. Surgical treatment of the fractured through-and-through injury die at the scene of the
accident. Often the first encounter with the patient by 2. Sykes JM, Donald PJ. In: Meyerhoff WL, Rice DH,
the otolaryngologist is during the craniotomy being editors. Reconstruction of the head and neck.
done by the neurosurgeon to remedy the patient’s Philadelphia: WB Saunders; 1992. p. 923.
intracranial injuries. Usually, a large anterior cran- 3. Sykes JM, Murakami C. Principles of local flaps in
iotomy has been done. Once the neurosurgeon has head and neck reconstruction. Oper Tech Otolaryn-
controlled the central hemorrhage, removed the devi- gol Head Neck Surg 1993;4:2.
talized brain, and repaired the dura, the otolaryngol- 4. Angle EH. Classification of malocclusion. Dent Cos-
ogist needs to manage the severely damaged frontal mos 1899;41:248.
sinus. This is best done by the cranialization proce- 5. Dingman RO, Natvig P. Surgery of facial fractures.
dure59 (Figure 39–61). The anterior wall fragments are Philadelphia: WB Saunders; 1969.
removed, divested of mucosa, and thoroughly irri- 6. Mathog R. Maxillofacial trauma. Baltimore:
gated and débrided to ensure the removal of all of the Williams & Wilkins; 1984.
contaminants acquired at the trauma scene. The bone 7. Chayra GA, Meador LR, Laskin DM. Comparison of
fragments are stored in povidone-iodine until the end panoramic and standard radiographs for the diag-
of the procedure. The posterior wall of the frontal nosis of mandibular fractures. J Oral Maxillofac Surg
sinus is completely removed with a rongeur and a cut- 1986;44:677–9.
ting bur. The anterior cranial fossa is now entirely in 8. Hemmings KW. Fracture of the cervical spine com-
continuity with the cavity of the frontal sinus. The plicating bilateral fractures of the mandible. A case
cutting bur is used to thoroughly remove all vestiges report. Br J Oral Maxillofac Surg 1985;23:279–83.
of sinus mucosa including the small projections into 9. Kruger E, Schilli W. Oral and maxillofacial trauma-
the vascular pits in the frontal sinus anterior wall and tology. Chicago: Quintessence; 1982.
floor. This is the most important step in the proce- 10. Foster CA, Sherman JE. Surgery of facial bone frac-
dure. Any remaining mucosa provides the potential tures. New York: Churchill Livingstone; 1987.
for its regrowth and subsequent infection. The 11. Hoffman-Axthelm W. The treatment of mandibular
mucosa of the nasofrontal duct is inverted on itself fractures and dislocations: a historical perspective. In:
toward the anterior ethmoid sinuses. The duct is Kruger E, Schilli W, editors. Oral and maxillofacial
plugged with a block of temporalis muscle or bone traumatology. Chicago: Quintessence; 1982. p. 17.
dust. The anterior wall fragments are restored, and the 12. Gilmer TL. A case of fracture of the lower jaw with
dural graft will expand with time and fill the new remarks on treatment. Arch Dent 1887;4:388.
space created in the anterior cranial fossa. 13. Kellman R. Repair of mandibular fractures via com-
pression plating and more traditional techniques: a
comparison of results. Laryngoscope 1984;94:1560–7.
CONCLUSIONS 14. Szabo G, Kovacs A, Pulay G. Champy plates in
In summary, treatment of facial fractures requires a mandibular surgery. Int J Oral Surg 1984;13:290–3.
multisystem approach. All bony and soft tissue 15. Gaynor E, Stephanak W. Prosthetic splinting as an
injuries should be diagnosed, and reconstitution of alternative in the treatment of mandibular fractures.
all tissue layers should be performed, if possible. The Ear Nose Throat J 1983;62:32–43.
advancement of technology has enabled rigid fixa- 16. Chuong R, Donoff R. Intraoral open reduction of
tion to become the standard of care for the fixation mandible fractures. Int J Oral Surg 1985;14:22–8.
of most facial fractures. More precise stability and 17. Donald PJ, Bernstein L. Open reduction for sub-
fixation of fractures have become possible, and inter- condylar fractures of the mandible. In: Bernstein L,
maxillary fixation is used less frequently. Well- editor. Plastic and reconstructive surgery of the head
planned incisions minimize scarring. Adequate and neck: the 3rd International Symposium. Vol 2.
exposure, precise reduction, and stable fixation New York: Grune and Stratton; 1981. p. 357–63.
remain the hallmarks of treatment of facial fractures. 18. Brown E, Obeid G. Simplified method for the inter-
nal fixation of fractures of the mandibular condyle.
J Oral Maxillofac Surg 1984;22:145–50.
REFERENCES 19. Wennogle C, Delo R. A pin in groove technique for
1. Dingman RO, Natvig P. Surgery of facial fractures. reduction of displaced subcondylar fractures of the
Philadelphia: WB Saunders; 1964. mandible. J Oral Maxillofac Surg 1985;43:659–65.
Facial Fractures 949
20. Fernandez J, Mathog R. Open treatment on condylar 38. Champy M, Lodde JP, Kahn JL, Kielwasser P.
fractures with biphase technique. Arch Otolaryngol Attempt at systemization in the treatment of isolated
Head Neck Surg 1987;113:262–3. fractures of the zygomatic bone: technique and
21. Ikemura K. Treatment of condylar fractures with results. J Otolaryngol 1986;15:39–43.
other mandible fractures. J Oral Maxillofac Surg 39. Eisele D, Duckert L. Single point stabilization of
1985;43:810–3. zygomatic fractures with minicompression plates.
22. Kellman RM, Marentette LJ. Atlas of craniomaxillo- Arch Otolaryngol Head Neck Surg 1987;113:267–70.
facial fixation. New York: Raven Press; 1995. 40. Burres S, Cohn A, Mathog R. Repair of orbital
23. Freihofer HM, Sailer HF. Experiences with intraoral blowout fractures with Marlex mesh and Gelfilm.
wiring of mandibular fractures. J Maxillofac Surg Laryngoscope 1981;91:1881–6.
1973;1:248. 41. Weintraub B, Cacin R, Jacobs M. Extrusion of an
24. Larsen OD, Nielsen A. Mandibular fractures: II. A infected orbital floor prosthesis after 15 years. Plast
follow-up study of 229 patients. Scand J Plast Recon- Reconstr Surg 1981;68:506.
str Surg 1976;10:219–26. 42. Kohn R, Romano PE, Puklin JE. Lacrimal obstruc-
25. Michelet FX, Deymes J, Dessus B. Osteosynthesis tion after migration of orbital floor implant. Am J
with miniaturized screwed plates in maxillo-facial Ophthalmol 1976;82:934–6.
surgery. J Maxillofac Surg 1973;1:79–84. 43. Fujii N, Yamshiro M. Classification of malar com-
26. Champy M, Lodde JP, Schmitt R, et al. Mandibular plex fractures using computed tomography. J Oral
osteosynthesis by minature screwed plates via a buc- Maxillofac Surg 1983;41:562–7.
cal approach. J Maxillofac Surg 1978;6:14–21. 44. Godoy J, Mathog R. Malar fractures associated with
27. Glineburg RW, Laskin DM, Blaustein DI. The effects exophthalmos. Arch Otolaryngol 1985;111:174–7.
of immobilization of the primate temporomandibu- 45. Le Fort R. Etude experimentale sur les fractures de la
lar joint. A histological study and histochemical machoire supèrieure. Rev Chir (Paris) 1901;23:
study. J Oral Maxillofac Surg 1982;40:3–8. 208–360.
28. Mekubjian S. Mandibular fracture in a five week old 46. Stanley RB. Reconstruction of the midfacial vertical
infant. J Oral Maxillofac Surg 1985;43:814–5. dimension following Le Fort fractures. Arch Oto-
29. McGuirt WF, Salisbury PL. Mandibular fractures: laryngol 1984;110:571–5.
their effect on growth and dentition. Arch Otolaryn- 47. Manson P, Hoopes J, Su C. Structural pillars of the
gol Head Neck Surg 1987;113:257–61. facial skeleton: an approach to the management of
30. Leake D. Long term follow up of fractures of the Le Fort fractures. Plast Reconstr Surg 1980;66:54–62.
mandible condyle in children. Plast Reconstr Surg 48. Manson P, Crawley W, Yaremchuk M. Midface frac-
1971;47:127. tures: advantages of immediate extended open
31. Boyne PJ. Osseous repair and mandibular growth reduction and bone grafting. Plast Reconstr Surg
after subcondylar fractures. J Oral Surg 1969;25:300. 1985;76:1–12.
32. Close L, Lomba J. Facial reconstruction following 49. Close LG. Fractures of the maxilla. Ear Nose Throat
blast injury. Head Neck Surg 1983;6:639–52. J 1983;62:365–70.
33. Shuker S. Management of comminuted mandibular 50. Gunter H. Konstitutionelle Anomalien des Augenab-
war injuries with multiple circumferential wires. J strandes und der Interorbitalbrilite. Virchows Arch A
Oral Maxillofac Surg 1986;44:152–5. Pathol Anat Histopathol 1933;290–373.
34. Binder P. Evaluation of the eye following periorbital 51. Donald PJ, Gluckman JL, Rice DH. The sinuses. Vol
trauma. Head Neck Surg 1978;1:134–47. I. New York: Raven Press; 1995.
35. Converse JM. Surgical treatment of facial injuries. 52. Converse JM, Hogan VM. Open-sky approach for
3rd ed. Baltimore: Williams and Wilkins; 1974. reduction of naso-orbital fractures. Case report.
36. Fryer MP, Brown JB, Davis G. Internal wire pin fix- Plast Reconstr Surg 1970;46:396–8.
ation for fracture dislocation of the zygoma: 53. Friedman CD, Constatino PD, Tagaki S, Chow LC.
twenty-year review. Plast Reconstr Surg 1969;44: BoneSource hydroxyapatite cement: a novel bioma-
576–81. terial for craniofacial reconstruction. J Biomed
37. Luhr H. Vitallium Luhr systems for reconstructive Mater Res 1998;43:428–32.
surgery of the facial skeleton. Otolaryngol Clin 54. Nahum AM. The biomechanics of maxillofacial
North Am 1987;20:573–606. trauma. Clin Plast Surg 1975;2:59–64.
950 Ballenger’s Otorhinolaryngology
55. Lang J. Clinical anatomy of the nose, nasal cavity 58. Barron SH, Dedo HH, Henry CR. The mucope-
and paranasal sinuses. New York: Georg Thieme riosteal flap in frontal sinus surgery (the Sewall-Boy-
Verlag; 1989. den-McNaught operation). Laryngoscope 1973;83:
56. Donald PJ. Tenacity of frontal sinus mucosa. Oto- 1266–80.
laryngol Head Neck Surg 1979;87:557–66. 59. Donald PJ. Frontal sinus and nasofrontoethmoidal
57. Donald PJ, Ettin M. The safety of frontal sinus fat complex fractures. Self-instructional package. No.
obliteration when sinus walls are missing. Laryngo- 804000. Alexandria (VA): American Academy of
scope 1986;96:190–3. Otolaryngology-Head and Neck Surgery; 1980.
CHAPTER 40
The goals of head and neck reconstructive surgeons, struction of the maxilla accelerated. A MEDLINE
namely, the restoration of function and esthetics in search for articles on “maxilla and reconstruction”
an expeditious manner with minimal surgical mor- produced 11 works from 1960 to 1980, 51 from 1980
bidity,1 are tested as rigorously by defects of the jaws to 1990, and 96 from 1998 to 2000. There are cur-
as by any other problem we face. We are in the midst rently multiple soft and hard tissue options in clini-
of a revolution in reconstructive surgery. Advances in cal use. Rapid refinement and ongoing research in
vascularized tissue transfer and custom fabrication of methods and materials for maxillary reconstruction
reconstructive flaps are occurring rapidly. Although now recapitulate the evolution of mandibular recon-
research propels us toward a future in which we will struction through the 1990s. It is an exciting time for
no longer need to remove tumors and provide head and neck and facial plastic surgeons interested
replacement tissues, we must maintain currency with in reconstruction of the jaws.
such methods while we wait for what O’Leary et al The jaws are the nucleus of many of the most
aptly termed in 1994 “the molecular reconstructive sophisticated structural systems in the body.
‘cocktails’ from the shelf of the next millennium.”2 Although other bones in the body support more
No more than 20 years ago, a chapter on recon- weight or more directly protect individual vital
struction of the jaws would have focused on the structures, only the jaws serve so many functions in
mandible, for which there were many surgical so many ways. Masticatory forces approach 10,000
options (no matter how unsatisfactory they might pounds per square inch between upper and lower
have been). Maxillary defects were almost exclusively molars, and load rates exceed 2,000 N/second.3 Yet a
a problem for the maxillofacial prosthodontist, and grain of sand measuring only 0.06 mm between the
few surgical options existed. With the perfection and same teeth causes the muscles of mastication to
acceptance of vascularized free tissue transfer, release their load within hundredths of a second.
mandibular repair and replacement have become The jaws anchor and support the upper portals of
routine. After a decade of clinical experience, the the aerodigestive tract. They surround or otherwise
fibula has emerged as most facial plastic and recon- protect important neurovascular conduits, including
structive surgeons’ donor site of choice for manage- some of the major extracranial vasculature of the
ment of mandibular defects. head and neck. They house and nurture developing
Conversely, surgical repair of most maxillary tooth buds in the neonate and child. They facilitate
defects was limited to rudimentary adaptation of respiration, speech, chewing, swallowing, communi-
regional flaps until the 1990s. Whether because of cation, facial expression, and thus social interaction.
pessimism over the potential to achieve successful When part or all of the maxilla or mandible is
surgical reconstruction or because of optimism that lost to disease or injury, it would be ideal to provide
ongoing research in free tissue transfer would soon exact restoration or reconstruction. Were it possible
produce new methods far superior to the compro- to provide a perfect replacement, function and
mises then available, the literature of maxillary appearance would not suffer, and the patient would
defect management focused largely on prosthetics have no post-treatment deficit. Although advances
until the end of the twentieth century. As free tissue in modern reconstructive methodology have
transfer became routine, interest in surgical recon- brought us closer to this goal, it remains elusive.
951
952 Ballenger’s Otorhinolaryngology
A damaged structure can be restored (returned ture but also with consideration of functional deficits.
to its normal state using original or identical materials As so many advances in head and neck reconstruction
and methods), reconstructed (brought to its normal are being made every month, we will discuss some of
state using new or additional materials), or replaced. the most promising methods on the cutting edge
All three alternatives exist for management of defects despite their current status as investigational. History
or loss of the jaws, although some of the most sophis- suggests that many will have become routine between
ticated restorative techniques are not yet available for preparation and publication of this work.
routine clinical use. This chapter will address the man- Table 40–1 summarizes the spectrum of struc-
agement of each defect not only in terms of lost struc- tural and functional deficits attendant on loss of part
TABLE 40–1. Defects, Deficits, and Options for Management of the Maxilla and Mandible
Defect * Structural Deficit Functional Deficit Reconstructive Options
Maxilla
Oroantral fistula 1–3 Lost integrity of antrum Loss of air and water seal Local flaps, buccal fat pad
Alveolar ridge loss 2–3 Tooth-bearing tissue Dentition lost, possible Prosthesis, bone graft,
oroantral fistula distraction
Palatal shelf 1–3 Teeth plus antrum/ Chewing, swallowing, Prosthesis, free flap
nasal cavity nasal regurgitation, (myocutaneous,
speech osteomyocutaneous)
Hemimaxilla 2–4 All of above plus lip All of above All of above
and check support
Hemimaxilla 3–4 All of above plus orbital All of above plus diplopia All of above
plus orbital floor integrity and support
Hemimaxilla 4–5 All of above plus All of above plus All of above; megaflap
plus orbit contents of orbit sequelae of exenteration
More than 5 All of above plus All of above plus nasal/ All of above
hemimaxilla midfacial structure lip/midfacial support
Mandible
Body posterior to 2 Lower facial support, Chewing, swallowing, Plate, soft tissue, bone graft
mental foramen part of dental arch appearance or flap (fibula, scapula, iliac;
radius if small defect)
Ramus 3 Jaw stability and Chewing, swallowing, Plate, free flap (fibula)
function appearance
Condyle 3 As above As above Plate with prosthesis,
free fibula
Anterior arch 4–5 Tongue, lip, and facial Eating, speech, airway Free flap (fibula, scapula, iliac)
support, teeth integrity, appearance
Hemimandible 3–4 All of above All of above Plate, free flap (fibula, scapula,
iliac crest)
More than 5 All of above All of above Free flap—fibula is over-
hemimandible whelmingly tissue of choice
or all of the jaws, along with relative severity and Constantino et al demonstrated the ability to fill
current recommendations for management. 2.5 cm defects in dog mandibles using DO in 1993.10
Regeneration was achieved at a rate of 1 mm per day,
and function was normal at 1 year in all test animals.
RESTORATION More recent studies verify this work and support its
Restoration is the building up of something to its promise.11,12 As mechanical limitations in appliance
original and complete form using original materials design are overcome, DO will become a routine clin-
and methods.4 Distraction osteogenesis (DO) is prob- ical tool. Recent reports of clinical use in humans sup-
ably the only management method with any clinical port the impression that DO will soon be a mainstay
utility at present that approaches true restoration of in reconstruction of bony defects of the jaws.13,14
lost bone. It spans or augments bony defects by trac- The use of osteoinductive morphogens,
tion-induced neo-osteogenesis of the remaining orig- although not yet a routine clinical tool, offers a sec-
inal structure. Anecdotally accepted to have been ond alternative for restoration of bony architecture.
introduced by Cordovilla in 1905 and first published Bone morphogenetic proteins (BMPs) belong to the
by Putti in 1921,5 this technique was brought to prac- family of transforming growth factor-beta sub-
tical clinical utility with work by Ilizarov and others in stances and play an important role in the growth and
the 1990s.6 The methodology includes interruption of development of numerous tissues.15 Work to date is
the cortical envelope (if intact) with maintenance of promising, but clinical application of BMPs to stim-
periosteal integrity to the mobilized end plate. Pins or ulate replacement bone has not reached the stage of
other secure devices are anchored in the mobile seg- practical utility. Work is being done on application
ment of bone, and controlled force is applied to the of BMPs in absorbable collagen sponge16 and differ-
anchors. Healing occurs within the periosteal enve- ent forms of hydroxyapatite,17 but such techniques
lope by neo-osteogenesis between the advancing end have not yet reached practical application. It appears
plate and the remaining bone. Segmental ends can be clear that BMPs will play a significant role in the true
advanced toward each other to close gaps, and restoration of bony architecture in the head and
anchors in depressed or malaligned segments can be neck as soon as the proper combination of mor-
used to direct neo-osteogenesis for augmentation or phogen, carrier, and methodology is found.
realignment of the defect. There are now commercial
appliances and systems available for DO, and the lit-
erature is replete with references to its clinical utility
RECONSTRUCTION
in management of defects of the jaws (Figure 40–1).7–9 To reconstruct is to rebuild.3 There are many options
for reconstruction of the jaws. Modern osseous
autografting dates to 1867 and the pioneering work
of Ollier.18 Tibial bone was used prior to World War
I, with the iliac crest rising in popularity as a donor
soon after World War II.19 Calvarial bone has been
used for about 15 years but was boosted in popular-
ity by the publication of a technique for temporal
harvesting by Spear and Wiegering in 1987.20 Rib has
long been used for grafting in the head and neck.
The safety and utility of autogenous bone grafting
were documented by series such as Kline and Wolfe’s
1,000 personal cases and 12,672 surveyed cases.21
Thus, free autogenous bone grafting was a work-
horse in the management of maxillary and
mandibular defects until the era of practical free tis-
sue transfer, despite the relatively high failure rate in
recipient beds contaminated by oral secretions.22
FIGURE 40–1. External distraction osteogenesis device. Osseous autografts remain useful in the manage-
Courtesy of W. Lorenz Surgical. ment of small (< 4 cm) defects of the mandible and
954 Ballenger’s Otorhinolaryngology
in closure of many defects resulting from maxillec- of mandibular loss and deviation but not restoring
tomy for which vascularized osteocutaneous free tis- the native structure or its actual function. However,
sue transfer is neither required nor justified.23 So, the reported success rate of this technique falls off
despite the wide acceptance of vascularized free tis- rapidly beyond the first postoperative year, even in
sue transfer and its use by the author since 1993, free lateral mandibular defects posterior to the mental
nonvascularized bone grafts continue to have a lim- foramen (the most forgiving location in terms of
ited but important role in head and neck recon- reconstructive requirement and success). Reports of
struction. There is even recent literature on 40 to 50% failure after 1 year are common for tech-
improving the outcome of osseous autografts.24 niques of mandibular reconstruction using a combi-
Osseous allografts have been used in jaw nation of soft tissue and plating, even when
reconstruction for many years. Freeze-dried irradi- vascularized free tissue transfer is used for the soft
ated fibula and other processed cadaver tissues were tissue component.29 Plate breakage is common, as is
popular for a brief period in the 1980s, and auto- exposure, leading some authors to recommend
grafting of explanted tumorous mandibles after plates and soft tissue only for temporary use in
chemical manipulation and irradiation to 120 cGy mandibular reconstruction.30 Most authors have
was advocated briefly.25 However, more modern found this to be true regardless of the kind of plate
methods of management have largely relegated the chosen. One study suggests that modern plate tech-
above to historical significance. nology and materials science have not lessened the
The use of bone-like alloplastic substances as incidence of plate exposure and have not eliminated
scaffolding for neo-osteogenesis is well documented the problem of plate breakage,31 although another
and supported by histologic26 and clinical27 reports. found the latest lower-profile mandibular recon-
One exception to this is the use of hydroxyapatite in struction plates to have breakage and extrusion rates
mandibular defects secured with a reconstruction of about 4% each in a series of 27 cases,32 which is
plate,28 a technique not supported by any current lit- certainly an acceptable rate of failure, given the
erature or experience. problem and alternatives for management.
The wide variation in reported plate breakage
FUNCTIONAL AND COSMETIC rates demonstrates, at least in part, the sensitivity of
this complex methodology to technical factors such
RECONSTRUCTION as the mechanics of hardware placement. The use
Functional reconstruction is defined as creation of of a given plate-and-screw system must be taught
sufficient structure to return an organ or region to rigorously and in detail if the method is to achieve
function, even though neither function nor struc- clinical success. The use of non–self-tapping screws
ture exactly replicates the pretreatment or preinjury requires meticulous attention to the process of
state. This describes the vast majority of flap and drilling and tapping holes in bone. If the drill and
graft procedures as well as the use of hardware tap are not inserted and maintained perfectly
and/or soft tissue to replace bone. Appearance straight along the desired axis or the threads are not
and/or function are often enhanced by substituting cut perfectly perpendicular to the axis of the hole,
tissue of another kind for the resected specimen. the screw will be loose in the hole and stabilization
Thus, for example, resected tongue tissue is routinely will not be achieved. Even the use of self-tapping
replaced with regional or free flaps despite the cur- screws requires great care in the drilling of the holes
rent impossibility of restoring volitional mobility to and driving of the screws, for the same reasons.
the reconstruction. Perioral soft tissues can be On a temporary basis, the mandibular bone
replaced with a variety of soft tissue flaps and grafts, segments to either side of a defect can be stabilized
but this will not restore the function of the oral and the defect spanned with a number of plating sys-
sphincter. Similarly, ablation of a maxillectomy tems. Although far from a complete functionally
defect with soft tissue and/or bone may enhance oral restorative technique, proper selection and place-
function and/or appearance, but the region cannot ment of a plate can provide a patient with satisfactory
be returned to its prepathologic state. appearance, stabilization, and comfort for relatively
Soft tissue can also be used to augment a lateral normal social function, with the notable exception of
mandibular defect, effacing the cosmetic deformity chewing and swallowing. Liquids can be taken fairly
Reconstruction of the Maxilla and Mandible 955
well by patients having such procedures, and the suc- maxilla is the floor of the orbit above it. The medial
cess rate is commonly reported as adequate for wall delineates the lateral limit of the nasal cavity
patients with poor prognoses or insufficient physio- and contains the nasolacrimal duct. The maxillary
logic reserve to remain under anesthesia on the oper- floor consists of the hard palate and the alveolar
ating table for an additional few hours for a more ridge. The walls of the maxilla delineate the maxil-
formal reconstruction. However, Komisar reported lary sinus, being contained within the central por-
no significant improvement in functional or social tion of the maxilla. In addition, many of the muscles
rehabilitation of mandibulectomy patients from sim- of facial expression and mastication are anchored on
ple restoration of mandibular continuity with a plate the maxilla. The orbicularis oris and oculi, zygo-
in an analysis of patients for whom vascularized tis- maticus, buccinator, and various levators and
sue transfers were not provided.33 depressors, together with the overlying skin and/or
intraoral mucosa, constitute the units of the lower
eyelid, cheek, upper lip, and oral commissure. The
VASCULARIZED FREE TISSUE
medial and lateral pterygoid muscles originate at the
TRANSFER pterygoid plates along the posterior wall of the max-
Vascularized free tissue transfer has reached routine illa. Finally, the two horizontal and three vertical
status in the United States in every academic and buttresses of the maxilla are responsible for midfa-
most major community medical centers for cial projection and vertical facial height.
patients of all ages.34 A decade ago, one could intel- Muzaffar et al called the maxilla the “keystone
ligently question the value of free flap transfers of the midface.”39 They elegantly described it as unit-
because long-term outcome studies had not been ing “… the key mid-facial elements—the orbits, the
done, few surgeons and medical centers had the zygomaticomaxillary complex, the nasal unit, and the
technical ability and physical plant required for stomatognathic complex” into a functional and est-
optimum microsurgical management, and tech- hetic unit. Most maxillary defects are thus complex in
niques had not been refined sufficiently to offer nature, involving more than one surface or cavity and
consistently high success rates. However, each of affecting more than one function of the midface.
those questions has been answered well. Numerous Quoting Muzaffar et al again, “In reconstructing
studies support the statement that vascularized free maxillary defects secondary to trauma, ablative
flap reconstruction is both highly successful and tumor surgery, or congenital deformities, the surgeon
cost effective for appropriately chosen head and must obliterate the defect, provide adequate struc-
neck surgery patients.35,36 See Chapter 41 for the
spectrum of available free flaps.
MANAGEMENT OF MAXILLARY
DEFECTS
GOALS OF MANAGEMENT
The goals set forth by Hoopes and Edgerton in 1966
for surgical reconstruction of maxillectomy defects
remain as valid today as when they were published,
namely, obtain a healed wound, restore palatal com-
petence and function, support the orbit or fill the
orbital cavity in exenteration, obliterate the maxil-
lectomy defect, and restore facial contour.37
tural support to each of the midfacial units, and prosthesis remains a viable option for many patients
address the essential functions of the midface.”39 suffering loss of part or all of the maxilla, despite the
The maxilla is often described as being a compromises inherent in such management. Dental
trilevel structure, with unique functions attributed reconstruction and rehabilitation can be integral
to each level. The floor of the maxilla houses the with palatal defect management by including pros-
upper dental arch and separates the oral cavity from thetic dentition in the prosthetic unit. Of course,
the antrum. The middle level contains the antrum retention of a prosthesis requires sufficient hard
and the path for its aeration. It serves as a vertical and/or soft tissue to anchor, support, and stabilize
buttress for dissipation of masticatory forces and the device.
lends support and definition to the lips and the soft Removable palatal prostheses are more
tissue vault of the nose. The upper level defines and acceptable to patients comfortable with the concept
supports the orbit and cheek and carries vasculature of removable dental prostheses than to those with
and sensory innervation to the midface. a full complement of natural teeth, and the eden-
The maxillae separate several cavities from one tulous proportion of most of the world’s popula-
another. The alveolar ridges and hard palate separate tion is dropping. A recent British study found so
the oral cavity from the antra, and the central por- predictable an improvement in the oral health of
tion of the hard palate separates the oral cavity from the general population that a lack of natural teeth
the nasal cavity. The medial maxillary walls separate will affect 25% of the British population between
the antra from the nasal cavities, and the orbital 65 and 74 years of age in 2008, down from 52% 20
processes separate the orbital contents from the years before. 42 In the United States, the rate is
antra. The posterior walls of the maxillae separate expected to decline from an observed 37% of all
the antra from the pterygopalatine fossae. Americans in 1997 to 15% in 2020.43 This suggests
a decline in the number of future patients likely to
accept and be satisfied with removable maxillary
SPECTRUM OF MAXILLARY LOSS prosthetics. But it is important to note that educa-
The tissue deficit from maxillary surgery or injury tion, economic status, and social function (the
may be as small as a single dental alveolus or as large same socioeconomic factors that correlate strongly
as the entire party wall between the nasal and oral with facial trauma and with cancer of the head and
cavities. Even a tiny defect such as an oroantral fis- neck) are independent predictors of low functional
tula through the alveolus of an extracted tooth can dental status.44 As the population of the United
cause major dysfunction and require repair. Further, States is growing at a rate close to that of reduction
surgical repair of even a tiny defect such as this has in tooth loss,43 the absolute number of edentulous
a significant failure rate, and much effort has been patients in a given age group is expected to remain
directed toward such reconstruction.40 Management constant. These are the patients who are both at
of an aggressive maxillary sinus tumor can create a greatest risk for head and neck cancer and least
defect that spans the distance from the oral cavity to likely to expend the resources for state-of-the-art
the anterior part of the skull base. Repair may reconstruction. As a result, the role of removable
require re-creation of the roof of the mouth, the maxillofacial prosthodontics in maxillary recon-
floor of the orbit, and support for the cheeks and struction will not likely dwindle below its current
lips. Aggressive ablation of such a tumor may also level of activity.
require resection of the orbital confines and con- On the other hand, a progressive increase in
tents, further complicating reconstruction. oral health awareness and improvement in the oral
health of civilized societies suggests an increasing
demand for dental rehabilitation as an integral
MAXILLOFACIAL PROSTHODONTICS component of maxillofacial reconstruction.
Prostheses have been the mainstays of management Advances in implantology have made osseointe-
of maxillary defects for hundreds of years. Most grated implantation of posts, anchors, and other
maxillary defects resulting from oncologic surgery means of securing dental arch restorations and
were managed with removable prosthetic obturation external maxillofacial prostheses readily available to
until the last decade of the twentieth century.41 As those with the economic resources to obtain them.
long as there is a defect amenable to obturation, a The spectrum of available management methods
Reconstruction of the Maxilla and Mandible 957
now ranges from a removable obturator with rudi- SURGICAL CONSIDERATIONS FOR OPTIMAL
mentary dentition and facial support to vascular- MANAGEMENT WITH AN OBTURATOR
ized free osteocutaneous flap reconstruction with
osseointegrated dental implants and fixed full-arch Because removable prosthodontic management of
dental restorations. As a result, it is now more maxillectomy defects remains a valuable tool for the
important than ever to identify the needs and head and neck surgeon, it is appropriate to discuss
desires of individual patients regarding maxillofa- the special surgical considerations necessary to opti-
cial reconstruction and rehabilitation. mize results. Davison et al included concise guide-
One of the biggest problems facing the patient lines for maxillectomy to facilitate the best possible
in need of a maxillary prosthesis is the availability fit, retention, and function of an obturator in a
of a maxillofacial prosthodontist. As Gotay and recent work on reconstruction of maxillectomy
Yates pointed out, “… the majority work in private defects.47 These include the following:
practice or a dental school, are primarily involved • Leaving the largest amount of hard palate possible
in clinical work or teaching, and see few cancer without compromising margins
patients. Inadequate reimbursement and lack of • Preserving periodontal support for sound teeth
collaboration with surgeons were cited as barriers adjacent to the defect (eg, making adjacent bony
to involvement in cancer patient care.”45 Cost-ben- cuts through the center of the next alveolus, not
efit analyses have been done comparing microsur- between)
gical reconstruction with traditional regional flap • Lining the soft tissue cavity with split-thickness
methods, but no such analysis appears in the liter- skin
ature comparing maxillofacial prosthodontic man- • Positioning the graft so that the resulting scar
agement with surgical reconstruction. As attention band at its junction with residual buccal mucosa
is directed toward the cost effectiveness of clinical aids retention of the obturator flange
methodology, removable prosthetic management • Removing turbinate if it might compromise seat-
of maxillary defects may emerge as a societal ing of an adequate obturator
choice. However, it is far from ideal and necessi- • Preserving nondiseased medial palatal mucosa for
tates many functional and esthetic compromises use as coverage of the medial bony margin
much better addressed by modern methods of tis- • Resecting all of the soft palate when more than
sue transfer. half must be taken anteroposteriorly for tumor
Although head and neck surgeons traditionally management
express concern about the quality of prosthetic
devices available to their patients, studies have SURGICAL MANAGEMENT OF MAXILLARY
shown that “Correlations between anatomic condi-
tions and denture quality and patient satisfaction are DEFECTS
weak.”46 Further, authors repeatedly suggest that psy- Oroantral Fistulae and Other Defects of the Pos-
chological factors predominate in the acceptance of terior Part of the Maxilla Although maxillary
and adaptation to removable dentures. As a result, reconstruction is most often associated with man-
the lack of insurance coverage for maxillofacial agement of head and neck cancer, the most common
prosthodontics is the biggest single factor control- causes of oroantral communications are dental.40
ling the availability of these important clinical serv- Communication between the oral cavity and the
ices to head and neck cancer patients. maxillary antrum causes chronic sinusitis when it
There are many patients for whom a remov- persists over time, compounding the problem of
able prosthetic management plan is preferable to achieving closure of defects resulting from dental
surgical reconstruction of maxillary defects. This disease and its treatment.
group includes patients who have had multiple Unfortunately, the historical mainstay of man-
recurrences, patients with medical compromise agement for most maxillary defects, the palatal obtu-
affecting the likely success of surgical reconstruction, rator, is of little help in managing oroantral fistulae
and patients whose personal philosophies favor in the edentulous patient. The most important fac-
seeking the quickest, simplest treatment that will tor in retention of an upper dental prosthesis is the
allow them reasonable function despite some major integrity of the seal of the base of the appliance
compromises from ideality. against the oral tissues. An oroantral communica-
958 Ballenger’s Otorhinolaryngology
tion allows air to get beneath the flange of the pros- major advances in maxillary reconstruction, with
thesis, preventing the development of an adequate reports of success using groin,58 latissimus,59 lateral
seal to retain the device. arm,60 scapula,61 and radial forearm62 flaps.
This problem deserves specific mention both
because of its commonality and the generally CURRENT MANAGEMENT OF MAXILLARY
acknowledged difficulty in achieving closure.48
Oroantral fistulae have perplexed the surgeon for cen-
DEFECTS
turies. Closure techniques reported in the latter half Functional wound closure, to prevent central nerv-
of the twentieth century include gold foil (a method ous system infection and eliminate dead space, has a
in intermittent use for over a hundred years),49 higher priority in reconstruction of midfacial defects
methylmethacrylate,50 skin flaps, mucosal flaps,40 and than does cosmesis.63 Further, despite major
transposition of the buccal fat pad.51 Although most advances in midfacial reconstruction, a prosthesis
otolaryngologist-head and neck surgeons have tried remains an important part of rehabilitation for
to facilitate antral drainage and aeration in the belief many maxillectomy defects in conjunction with vas-
that this enhances the success of closure of palatal cularized free tissue transfer.64 Thus, optimal current
defects that communicate with the antrum, there is management of defects resulting from maxillectomy
literature suggesting that this is not necessary.52 requires an armamentarium encompassing sophisti-
As summarized by Davison et al,47 flaps of buc- cated surgical skills, prosthodontics, and a rehabili-
cal, alveolar, and/or palatal mucosa or mucoperiso- tative team for residual deficits in communicating
teum remain the most commonly used management and taking nutrition.
methods for relatively small openings through the Optimal management of maxillary defects
posterior part of the palate into the maxillary sinus. requires an understanding of the composite nature
There is growing evidence, however, that the buccal of the tissue loss. Reconstruction of communicating
fat pad produces reliable closure with fewer draw- maxillary defects most often requires replacement of
backs than other methods in current use.51 three separate tissue layers, those being the soft tissue
linings of the two cavities whose party wall has been
Historical Approaches to Maxillary Reconstruc- violated and the bone of the wall itself. If one con-
tion Early attempts at surgical reconstruction of siders the functions of these layers rather than their
maxillary defects used local or regional soft tissue histology, one recognizes that the bone is primarily a
flaps with limited success.53,54 Perhaps the first staged barrier to penetration of the soft tissue on either side,
maxillary reconstruction to use both bone and soft with dissipation of forces a secondary but by no
tissue was reported by Campbell in 1948.55 He used means insignificant contribution. Thus, if soft tissue
temporalis muscle and palatal mucosa in the first of sufficient strength and puncture resistance could
stage, followed by placement of an iliac crest graft. be provided, it might not be necessary to replace the
This reconstruction was reportedly able to retain bony component of every communicating maxillary
and support a traditional maxillary denture. Subse- defect. Alternatively, because the consequence of pen-
quent work by numerous surgeons saw method- etration of the party wall between the oral cavity and
ologic progress through pedicled regional flaps56 to the antrum is transfer of air and contaminated sub-
pedicled regional flaps with free nonvascularized stances into the antrum, simple obliteration of the
autogenous bone grafts39 to free vascularized tissue antral cavity might suffice in lieu of restoration of
transfers of all kinds. Prior to the advent of routine bony integrity. Then there would be no open cavity
free tissue transfers, the mainstays of maxillary into which penetration could allow spread of alien
reconstruction were pedicled myocutaneous flaps substances. Both approaches are in current use.
with free nonvascularized cranial, iliac, or rib bone
autografts. LOCAL AND REGIONAL FLAPS FOR MAXILLARY
Various combinations and permutations of
RECONSTRUCTION
vascularized and nonvascularized soft and hard tis-
sue were then tried, including such innovative juxta- Contemporary Use of Local Flaps Even compos-
positions as free iliac bone with vascularized jejunal ite defects involving skin and muscle and oroantral
transfer.57 Advances in microsurgery facilitated communication may be amenable to reconstruction
Reconstruction of the Maxilla and Mandible 959
with local flaps alone. Creative use of cheek, buccal The deltopectoral flap has also been used for
fat, and palatal mucosal flaps may produce excellent obliteration/reconstruction of maxillectomy defects,
results in carefully selected patients.65 Even the later- as typified by Konno et al’s series of 46 patients
ally based forehead flap, which was once quite pop- reported 20 years ago.79 However, this is primarily of
ular for midfacial and intraoral reconstruction,66,67 use when free tissue transfer is not an option.
still has occasional use.
Microvascular Free Flaps for Maxillary Recon-
TEMPORALIS MUSCLE FLAPS. Flaps based on the tem- struction Taylor et al’s original report of success-
poralis muscle are successful and popular for man- ful transfer of vascularized fibula presaged the
agement of intermediate-sized defects of the modern era of jaw reconstruction.80 Subsequent
posterior part of the maxilla, especially when the investigators refined the principles and practice of
orbital floor is included in the resection. Temporalis vascularized fibular transfer, with Hidalgo et al’s
flaps can be muscular,68 fascial,69 myofascial,70 seminal work over the last decade of the twentieth
myocutaneous,71 or osteomyocutaneous.72 Flaps century presenting and later confirming the reliabil-
based on the temporalis muscle are often mobile ity and versatility of free osteocutaneous tissue
enough to use on contralateral defects,73 especially if transfer for head and neck reconstruction.81
extended to include attached galea. The scapula, fibula, and radius are the most
The placement of free nonvascularized bone frequently described osteocutaneous flaps for recon-
within a temporalis flap has been described for max- struction of the maxillary region. Each donor site
illectomy defect reconstruction.74 However, recent has its own advantages and disadvantages. To quote
work has suggested that the vascular source for Schusterman et al,
neoepithelialization of the flap’s surface originates in … no one flap can be used for all defects; certain flaps
the tissue surrounding the defect rather than the are better suited for specific situations. The radial fore-
flap, possibly explaining less than universal success arm flap is the best choice for small defects around the
from use of a free nonvascularized bone graft within orbit because it provides a small segment of bone and
a vascularized flap in this application.75 a thin, pliable paddle of soft tissue. The fibula, iliac
crest, and scapula flaps are useful for larger defects
involving the maxilla, where bulk and a strong bone
BUCCINATOR MUSCULOMUCOSAL FLAP. Pribaz et al
buttress are required for prosthetic support and stabi-
reported 18 reconstructions of midfacial defects of
lization.64
all kinds using a posteriorly based musculomucosal
flap of buccinator that they believed was nourished The scapula can be used after an osteotomy to
by the facial vessels.76 Although not widely known reconstruct the orbital floor and the maxillary but-
or used, this flap seems to offer a valuable alterna- tress simultaneously. Separate skin islands can be
tive to regional flaps, especially when other local tis- used for reconstruction of the palate and the cheek,
sue is not available. Licameli and Dolan determined although parascapular skin and subcutaneous tissue
with cadaver dissections that the blood supply is are often quite bulky and not an ideal donor for
from the buccal (buccinator) artery (a branch of the reconstruction of the cheek and intraoral lining.
internal maxillary) and published a more recent
series of reconstructions of the soft palate and SCAPULAR AND PARASCAPULAR FLAPS. The fasciocuta-
retromolar trigone with this flap to support further neous parascapular free flap has been in clinical use
its use.77 for about two decades (Figure 40–3). It was defined
within the distribution of the circumflex scapular
Chest Flaps The pectoralis major myocutaneous artery by Saijo in 1978.82 Teot et al described the use
flap has been used for reconstruction of large max- of lateral scapular bone 3 years later with the first
illectomy defects.78 Although it will fill the defect three reported cases,83 and the addition of a skin
resulting from a total maxillectomy, with the bulk of paddle was presented by Nasif ’s group a year after
muscle obliterating the antral cavity and the orbit if that.84 Subsequently, Coleman and Sultan demon-
necessary, it does not readily reach high enough strated that the angular artery, a branch of the tho-
without resection of the medial third of the clavicle, racodorsal artery, supplies the most inferior aspect
and dental rehabilitation is difficult or impossible. of the lateral scapula.85 The addition of this vascular
960 Ballenger’s Otorhinolaryngology
eral authors for defects involving the orbital floor TREATMENT PLANNING
and inferior rim. Vascularized scapular blade is the
alternative osteocutaneous flap of choice by some It is necessary to consider the bone defect first when
authors.96 planning reconstruction of composite defects of the
mandible and lip. Without adequate restoration of
skeletal support in the region of the anterior
MANDIBULAR RECONSTRUCTION mandibular arch, soft tissue reconstruction cannot
achieve firm apposition of the upper and lower lips.
MANDIBULAR ANATOMY Restoration of bony continuity is recommended for
The mandible is unique among the bones of the all patients with segmental mandibular defects since
body. As part of the stomatognathic system, the the rate of hardware failure and/or exposure is
mandible is suspended in space by muscles. It is reported to be at least 25% by multiple authors.97
free to move within an envelope of motion defined The mandible may be invaded by tumors of
by its ligamentous attachments to other bones and the oral cavity. In these cases, reconstruction must
by interdental contacts in patients with teeth. The include the restoration of both the soft tissue and
ligaments of the temporomandibular joint com- bony anatomy. Depending on the extent of tumor
bine with the stylomandibular ligament to place resection, the residual mandible may not have suffi-
firm limits on mandibular excursion. Muscular cient stock to withstand the forces of mastication. In
attachments also limit mandibular movement, but considering reconstruction, important anatomic
these limitations are less well defined because of the variables include the location and length of the
distensibility and length tension phenomenon of defect and any associated soft tissue, skin, or neu-
muscle. rovascular involvement.98
The muscles of mastication control mandibu- Although it is not clear that all mandibular
lar movement, inserting on a significant portion of defects require reconstruction, there is obvious ben-
the overall surface of the mandible and exerting efit in many instances. For instance, resection of the
strong force on it during chewing. Suprahyoid anterior mandibular arch produces the “Andy
muscles connect the mandible to the hyoid. The Gump” deformity (Figure 40–5), which is a complete
genioglossus and mylohyoid form the floor of the loss of anterior oromuscular support and oral com-
mouth, further defining mandibular orientation and petence. Because this is such a debilitating functional
movement. and esthetic problem, it is important to reconstruct
The anatomic regions of the mandible include this defect at the time of resection.99 The use of an
the condyle and condylar neck, sigmoid notch, immediate microvascular bone-containing free flap
coronoid process, ramus, angle, body, alveolar is the optimal method to restore form and function
process, parasymphysis, and symphysis. Within the to the lower third of the face and also allows the
alveolar process are the teeth and supporting struc- patient to wear a functional dental prosthesis. Other
tures, including the periodontal ligament and the absolute indications for this type of reconstruction
neurovascular bundles. The inferior alveolar artery, include through-and-through mandibular defects
vein, and nerve course through the inferior alveolar (which require reconstruction not only of bone but
canal within the body of the mandible to supply the also of mucosa and external skin), severe mandibu-
teeth. The periodontium derives blood supply both lar osteoradionecrosis, and failure of previous
from periapical vessels and from perforating vessels attempts at mandibular reconstruction.
in the alveolar bone. The gingival blood supply is A variety of osseocutaneous free flaps have been
extraperiosteal and originates in the vessels of the described to reconstruct the mandible. The fibula is
face and neck. the most advantageous donor site, although the iliac
When natural teeth are lost, the alveolar crest may also be used.100 The free fibula flap provides
process resorbs, leaving the reduced height of basal the greatest length of bone and a minimal donor-site
bone of the maxilla and mandible. The relative bulk defect. Multiple osteotomies can be made in the bone
and anatomic contours of the jaws must be appreci- to properly contour it (Figure 40–6), and dental reha-
ated if appropriate reconstructive methods and bilitation can be achieved with primary or secondary
materials are to be chosen. dental implants. The iliac crest free flap provides
Reconstruction of the Maxilla and Mandible 963
SPECIFIC CONSIDERATIONS
There is little question that vascularized fibula is the
donor site of choice for reconstruction of most FIGURE 40–7. Fibular free flap reconstruction of an
mandibular defects.103 The results of fibular free flap anterior mandibular arch.
964 Ballenger’s Otorhinolaryngology
9. Judge B, Hamlar D, Rimell FL. Mandibular distrac- 24. Lalikos JF, Mooney MP, Janosky J, et al. Bacterial
tion osteogenesis in a neonate. Arch Otolaryngol exposure required to induce rabbit calvarial bone
Head Neck Surg 1999;125:1029–32. graft infection by superficial contamination. J Cran-
10. Costantino PD, Friedman CD, Shindo ML, et al. iofac Surg 1994;5:247–52.
Experimental mandibular regrowth by distraction 25. Jisander S, Aspenberg P, Salemark L, Wennerberg J.
osteogenesis. Arch Otolaryngol Head Neck Surg Mandibular reconstruction by secondary reimplan-
1993;119:511–6. tation of resected segments: a preliminary report. Int
11. Cho BC, Lee JH, Baik BS, et al. Distraction osteogen- J Oral Maxillofac Surg 1995;24:288–92.
esis of free interpositional membranous bone: exper- 26. Holmes RE, Wardrop RW, Wolford LM. Hydroxy-
imental design. J Craniofac Surg 1999;10:123–7. lapatite as a bone graft substitute in orthognathic
12. Oda T, Sawaki Y, Fukuta K, Ueda M. Segmental surgery: histologic and histometric findings. J Oral
mandibular reconstruction by distraction osteogen- Maxillofac Surg 1988;46:661–71.
esis under skin flaps. Int J Oral Maxillofac Surg 27. Cottrell DA, Wolford LM. Long-term evaluation of
1998;27:9–13. the use of coralline hydroxyapatite in orthognathic
13. Rachmiel A, Aizenbud D, Eleftheriou S, et al. Extra- surgery. J Oral Maxillofac Surg 1998;56:935–41.
oral vs. intraoral distraction osteogenesis in the 28. Klotch DW, Prein J. Mandibular reconstruction
treatment of hemifacial microsomia. Ann Plast Surg using AO plates. Am J Surg 1987;154:384–8.
2000;45:386–94. 29. Blackwell KE, Buchbinder D, Urken ML. Lateral
14. Wangerin K. [Untitled abstract]. Mund Kiefer mandibular reconstruction using soft-tissue free
Gesichtschir 2000;4 Suppl 1:S226–36. flaps and plates. Arch Otolaryngol Head Neck Surg
15. Helm GA, Alden TD, Sheehan JP, Kallmes D. Bone 1996;122:672–8.
morphogenetic proteins and bone morphogenetic 30. Ueyama Y, Naitoh R, Yamagata A, Matsumura T.
protein gene therapy in neurological surgery: a Analysis of reconstruction of mandibular defects
review. Neurosurgery 2000;46:1213–22. using single stainless steel A-O reconstruction plates.
16. Barboza EP, Duarte ME, Geolas L, et al. Ridge aug- J Oral Maxillofac Surg 1996;54:858–62.
mentation following implantation of recombinant 31. Klotch DW, Gal TJ, Gal R. Assessment of plate use
human bone morphogenetic protein-2 in the dog. J for mandibular reconstruction: has changing tech-
Periodontol 2000;71:488–96. nology made a difference? Otolaryngol Head Neck
17. Yoshida K, Bessho K, Fujimura K, et al. Enhance- Surg 1999;121:388–92.
ment by recombinant human bone morphogenetic 32. Blackwell KE, Lacombe V. The bridging lateral
protein-2 of bone formation by means of porous mandibular reconstruction plate revisited. Arch
hydroxyapatite in mandibular bone defects. J Dent Otolaryngol Head Neck Surg 1999;125:988–93.
Res 1999;78:1505–10. 33. Komisar A. The functional result of mandibular
18. Ollier L. Traité experimental et clinique de la regen- reconstruction. Laryngoscope 100:364–74.
eration des os et de la production artificelle du tissu 34. Serletti JM, Higgins JP, Moran S, Orlando GS. Fac-
osseux. Paris: P. Masson et fils; 1867. tors affecting outcome in free-tissue transfer in the
19. Robertson IM, Barron JN. A method of treatment of elderly. Plast Reconstr Surg 2000;106:66–70.
chronic osteitis. J Bone Joint Surg 1946;28:19–24. 35. Talesnik A, Markowitz B, Calcaterra T, et al. Cost and
20. Spear SL,Wiegering CE. Temporal fossa bone grafts: outcome of osteocutaneous free-tissue transfer versus
a new technique in craniofacial surgery. Plast Recon- pedicled soft-tissue reconstruction for composite
str Surg 1987;79:531–4. mandibular defects. Plast Reconstr Surg 1996;97:
21. Kline RM, Wolfe SA. Complications associated with 1167–78.
the harvesting of cranial bone grafts. Plast Reconstr 36. Gallivan KH, Reiter D. Acute postoperative alcohol
Surg 1995;95:5–13. withdrawal and free flap manidibular reconstruc-
22. Lawson W, Biller HF. Mandibular reconstruction: tion. Arch Facial Plast Surg 2001;3:264–6.
bone graft techniques. Otolaryngol Head Neck Surg 37. Hoopes JE, Edgerton MT. Surgical rehabilitation
1982;90:589–94. after radical maxillectomy and orbital exenteration.
23. Foster RD, Anthony JP, Singer MI, et al. Reconstruc- Md State Med J 1966;15:91–7.
tion of complex midfacial defects. Plast Reconstr 38. Cordeiro PG, Santamaria E. A classification system
Surg 1997;99:1555–65. and algorithm for reconstruction of maxillectomy
Reconstruction of the Maxilla and Mandible 969
and midfacial defects. Plast Reconstr Surg 2000; 54. Elliott RA. Use of nasolabial skin flap to cover intra-
105:2331–46. oral defects. Plast Reconstr Surg 1976;58:201–4.
39. Muzaffar A, Adams WP, Hartog JM, et al. Maxillary 55. Campbell HH. Reconstruction of the left maxilla.
reconstruction: functional and aesthetic considera- Plast Reconstr Surg 1948;3:66–70.
tions. Plast Reconstr Surg 1999;104:2172–84. 56. Konno A, Togawa K, Iizuka K. Primary reconstruc-
40. Guven O. A clinical study on oroantral fistulae. J tion after total or extended total maxillectomy for
Craniomaxillofac Surg 1998;26:267–71. maxillary cancer. Plast Reconstr Surg 1981;67:440–8.
41. Curtis TA, Beumer J. Restoration of acquired hard 57. Inoue T, Harashina T, Asanami S, Fujino T. Recon-
palate defects: etiology, disability, and rehabilitation. struction of the hard palate using free iliac bone cov-
In: Beumer J, Curtis TA, Marunick MT, editors. Max- ered with jejunal flap. Br J Plast Surg 1988;41:143–7.
illofacial rehabilitation: prosthodontic and surgical 58. Panje WR, Krause CJ, Bardach J, Baker SR. Recon-
considerations. St. Louis: Ishiyaku EuroAmerica; struction of intraoral defects with the free groin flap.
1996. Arch Otolaryngol 1977;103:78–85.
42. Hemmings K, Griffiths B, Hobkirk J, Scully C. Clini- 59. Baker SR. Closure of large orbito-maxillary defects
cal review: ABC of oral health. BMJ 2000;321:438–41. with free latissimus dorsi myocutaneous flaps. Head
43. Carlsson GE. The geography of prosthodontics. Int J Neck Surg 1984;6:828–35.
Prosthodont 1997;10:407–10. 60. Matlou HS, Larson DL, Kuhn JC, et al. Lateral arm
44. Appollonio I, Carabellese C, Frattola A, Trabucchi M. free flap in oral cavity reconstruction: a functional
Dental status, quality of life, and mortality in an older evaluation. Head Neck Surg 1989;11:205–10.
community population: a multivariate approach. J 61. Swartz WM, Bains JL, Newton ED, et al. The osteo-
Am Geriatr Soc 1997;45:1315–23. cutaneous scapular flap for mandibular and maxil-
45. Gotay CC, Yates JW. The long-term impact of a lary reconstruction. Plast Reconstr Surg 1986;77:
training program in maxillofacial prosthodontics. J 530–8.
Cancer Educ 1988;3:181–6. 62. Vaughan ED. The radial forearm free flap in orofacial
46. Carlsson GE. Clinical morbidity and sequelae of reconstruction: personal experience in 120 consecu-
treatment with complete dentures. J Prosthet Dent tive cases. J Craniomaxillofac Surg 1990;18:2–13.
1998;79:17–23. 63. Gurtner GC, Evans GR. Advances in head and neck
47. Davison SP, Sherris DA, Meland NB. An algorithm reconstruction. Plast Reconstr Surg 2000;106:672–82.
for maxillectomy defect reconstruction. Laryngo- 64. Schusterman MA, Reece GP, Miller MJ. Osseous free
scope 1998;108:215–9. flaps for orbit and midface reconstruction. Am J
48. Salins PC, Kishore SK. Anteriorly based palatal flap Surg 1993;166:341–5.
for closure of large oroantral fistula. Oral Surg Oral 65. Pandolfi PJ, Yavuzer R, Jackson IT. Three-layer clo-
Med Oral Pathol Oral Radiol Endod 1996;82:253–6. sure of an oroantral-cutaneous defect. Int J Oral
49. Goldman EH, Stratigos GT, Arthur AL. Treatment of Maxillofac Surg 2000;29:24–6.
oroantral fistula by gold foil closure: report of a case. 66. Chambers RG, Cohn ES. Palatal reconstruction uti-
J Oral Surg 1969;27:875–7. lizing retrieved forehead flap. J Surg Oncol 1975;7:
50. Awang MN, Greene MW, King RC, et al. Closure of 191–7.
oroantral fistula. Int J Oral Maxillofac Surg 1988; 67. Kavarana NM. Use of a folded forehead flap for
17:110–5. reconstruction after a large excision of the full
51. el-Hakim IE, el-Fakharany AM. The use of the pedi- thickness of the cheek. Plast Reconstr Surg 1975;56:
cled buccal fat pad (BFP) and palatal rotating flaps 629–32.
in closure of oroantral communication and palatal 68. Dexter WS, Jacob RF. Prosthetic rehabilitation after
defects. J Laryngol Otol 1999;113:834–8. maxillectomy and temporalis flap reconstruction: a
52. Car M, Juretic M. Treatment of oroantral communi- clinical report. J Prosthet Dent 2000;83:283–6.
cations after tooth extraction. Is drainage into the 69. Rose EH, Norris MS. The versatile temporoparietal
nose necessary or not? Acta Otolaryngol (Stockh) fascial flap. Adaptability to a variety of composite
1998;118:844–6. defects. Plast Reconstr Surg 1990;85:224–2.
53. Edgerton MT, Zovickian A. Reconstruction of major 70. Goel A, Gahankari D. Extended subgaleal fascia-per-
defects of the palate. Plast Reconstr Surg 1956;17: icranial temporalis flap for skull base reconstruction.
105–12. Acta Neurochir (Wein) 1995;135:203–5.
970 Ballenger’s Otorhinolaryngology
71. Koch A, Hollmann K, Undt G, et al. Reconstruction 86. Coleman SC, Burkey BB, Day TA, et al. Increasing
of the orbital roof after tumor resection with a pedi- use of the scapula osteocutaneous free flap. Laryn-
cled muscle calvarial flap—the calvaria temporalis goscope 2000;110:1419–24.
flap. Fortschr Kiefer Gesichtschir 1994;39:50–2. 87. Frodel JL, Funk GF, Capper DT. Osseointegrated
72. Andres CJ, Newton AD, Schriener JE, Shore JW. implants: a comparative study of bone thickness in
Orbital prosthesis following temporal muscle or four vascularized bone flaps. Plast Reconstr Surg
forehead flap reconstruction: use of optics and illu- 1993;92:449–55.
sions. J Prosthet Dent 1992;67:390–3. 88. Holle J, Vinzenz K, Würinger E, et al. The prefabri-
73. Fukuta K, Jackson IT, Collares MV, et al. The volume cated combined scapula flap for bony and soft-tissue
limitation of the galeal temporalis flap in facial aug- reconstruction in maxillofacial defects—a new
mentation. Br J Plast Surg 1991;44:281–4. method. Plast Reconstr Surg 1996;98:542–52.
74. Cordeiro PG, Santamaria E, Kraus DH, et al. Recon- 89. Canales FL, Furnas H, Glafkides M, et al. Microsurgical
struction of total maxillectomy defects with preser- transfer of the rectus abdominis muscle using the supe-
vation of the orbital contents. Plast Reconstr Surg rior epigastric vessels. Ann Plast Surg 1990;24:534–7.
1998;102:1874–84. 90. Uglesic V, Virag M, Varga S, et al. Reconstruction fol-
75. Cheung LK. Microvascular network of the heal- lowing radical maxillectomy with flaps supplied by
ing surface over the temporalis flap in maxillary the subscapular artery. J Craniomaxillofac Surg
reconstruction. Int J Oral Maxillofac Surg 1999;28: 2000;28:153–60.
469–74. 91. Yamamoto Y, Nohira K, Minakawa H, et al. The
76. Pribaz J, Stephens W, Crespo L, Gifford G. A new combined flap based on a single vascular source: a
intraoral flap: facial artery musculomucosal clinical experience with 32 cases. Plast Reconstr Surg
(FAMM) flap. Plast Reconstr Surg 1992;90:421–9. 1996;97:1385–9.
77. Licameli GR, Dolan R. Buccinator musculomucosal 92. Soutar DS, Scheker LR, Tanner NS, McGregor IA.
flap: applications in intraoral reconstruction. Arch The radial forearm flap: a versatile method for intra-
Otolaryngol Head Neck Surg 1998;124:69–72. oral reconstruction. Br J Plast Surg 1983;36:1–8.
78. Thomas WO. Facial arteriovenous malformation 93. Santamaria E, Granados M, Barrera-Franco JL.
managed with ablative surgery and dual rotational Radial forearm free tissue transfer for head and neck
flap reconstruction. South Med J 1994;87:1178–82. reconstruction: versatility and reliability of a single
79. Konno A, Togawa K, Iizuka K. Primary reconstruc- donor site. Microsurgery 2000;20:195–201.
tion after total or extended total maxillectomy for 94. Richardson D, Fisher SE, Vaughan ED, Brown JS.
maxillary cancer. Plast Reconstr Surg 1981;67:440–8. Radial forearm flap donor-site complications and
80. Taylor GI, Miller GD, Ham FJ. The free vascularized morbidity: a prospective study. Plast Reconstr Surg
bone graft. A clinical extension of microvascular 1997;99:109–15.
techniques. Plast Reconstr Surg 1975;55:533–44. 95. McLoughlin PM, Gilhooly M, Phillips JG. Recon-
81. Hidalgo DA, Disa JJ, Cordeiro PG, Hu QY. A review struction of the infraorbital margin with a compos-
of 716 consecutive free flaps for oncologic surgical ite microvascular free flap. Br J Oral Maxillofac Surg
defects: refinement in donor-site selection and tech- 1993;31:227–9.
nique. Plast Reconstr Surg 1998;102:722–32; discus- 96. Swartz WM, Banis JC, Newton ED, et al. The osteo-
sion 733–4. cutaneous scapular flap for mandibular and maxillary
82. Saijo M. The vascular territories of the dorsal trunk: reconstruction. Plast Reconstr Surg 1986;77:530–45.
a reappraisal for potential flap donor sites. Br J Plast 97. Nicholson RE, Schuller DE, Forrest LA, et al. Factors
Surg 1978;31:200–4. involved in long- and short-term mandibular plate
83. Teot L, Bosse JP, Moufarrege R, et al. The scapular crest exposure. Arch Otolaryngol Head Neck Surg
pedicled bone graft. Int J Microsurg 1981;38:257–62. 1997;123:217–22.
84. Nasif TM, Vidal L, Bovet JL, et al. The parascapular 98. Futran ND. Mandibular defect. In: Gates GA, editor.
flap: a new cutaneous microsurgical free flap. Plast Current therapy in otolaryngology-head and neck
Reconstr Surg 1982;69:591–600. surgery. 6th ed. St Louis: Mosby; 1994. p. 327–30.
85. Coleman J, Sultan M. The bipedicled osteocutaneous 99. Urken ML, Cheney ML, Sullivan MJ, Biller HF. Atlas
scapular flap: a new subscapular system free flap. of regional and free flaps for head and neck recon-
Plast Reconstr Surg 1991;87:682–92. struction. New York: Raven Press; 1995.
Reconstruction of the Maxilla and Mandible 971
100. Hidalgo DA. Fibula free flap: a new method of 109. Shindo ML, Sinha UK, Rice DH. Sensory recovery
mandibular reconstruction. Plast Reconstr Surg in noninnervated free flaps for head and neck
1989;84:71–9. reconstruction. Laryngoscope 1995;105:1290–3.
101. Urken ML, Weinberg H, Vickery C, et al. The inter- 110. Bastian RW, Riggs LC. Role of sensation in swal-
nal oblique-iliac crest free flap in composite defects lowing function. Laryngoscope 1999;109:1974–7.
of the oral cavity involving bone, skin, and mucosa. 111. Yi Z, Jian-Guo Z, Guang-Yan Y, et al. Reconstruc-
Laryngoscope 1991;101:257–70. tion plates to bridge mandibular defects: a clinical
102. Moscoso JF, Keller J, Genden E, et al. Vascularized and experimental investigation in biomechanical
bone flaps in oromandibular reconstruction. A com- aspects. Int J Oral Maxillofac Surg 1999;28:
parative anatomic study of bone stock from various 445–50.
donor sites to assess suitability for enosseous dental 112. Inigo F, Rojo P, Ysunza A, Jimenez Y. Three differ-
implants. Arch Otolaryngol Head Neck Surg ent techniques for mandibular reconstruction after
1994;120:36–43. hemimandibulectomy. J Craniofac Surg 1997;8:
103. Futran ND, Alsarraf R. Microvascular free-flap 58–64.
reconstruction in the head and neck. JAMA 113. Gur E, Chiodo A, Pang CY, et al. The vascularized
2000;284:1761–3. pig fibula bone flap model: effects of multiple seg-
104. Schusterman MA, Reece GP, Miller MJ, Harris S. mental osteotomies on growth and viability. Plast
The osteocutaneous free fibula flap: is the skin pad- Reconstr Surg 1999;103:1436–42.
dle reliable? Plast Reconstr Surg 1992;90:787–93. 114. Wax MK, Winslow CP, Hansen J, et al. A retrospec-
105. Cheng AC, Wee AG, Morrison D, Maxymiw WG. tive analysis of temporomandibular joint recon-
Hinged mandibular removable complete denture struction with free fibula microvascular flap.
for post-mandibulectomy patients. J Prosthet Dent Laryngoscope 2000;110:977–81.
1999;82:103–6. 115. Wessberg GA, Wolford LM, Epker BN. Simultane-
106. Anthony JP, Foster RD, Kaplan MJ, et al. Fibular ous inferior alveolar nerve graft and osseous recon-
free flap reconstruction of the “true” lateral struction of the mandible. J Oral Maxillofac Surg
mandibular defect. Ann Plast Surg 1997;38:137–46. 1982; 40:384–90.
107. Rhee JS, Weisz DJ, Hirigoyen MB, et al. Intraoper- 116. Kaban LB, Upton J. Cross mental nerve graft for
ative mapping of sensate flaps. Electrophysiologic restoration of lip sensation after inferior alveolar
techniques and neurosomal boundaries. Arch Oto- nerve damage: report of a case. J Oral Maxillofac
laryngol Head Neck Surg 1997;123:823–9. Surg 1986;44:649–51.
108. Hayden RE. Free flap transfer for restoration of 117. Sanger JR, Matloub HS, Yousif NJ. Sequential con-
sensation and lubrication to the reconstructed oral nection of flaps: a logical approach to customized
cavity and pharynx. Otolaryngol Clin North Am mandibular reconstruction. Am J Surg 1990;160:
1994;27:1185–99. 402–4.
CHAPTER 41
The primary role of oncologic surgery is the curative require a well-vascularized host bed. Revasculariza-
resection of tumor. Equally important, however, is the tion of skin and mucosal grafts follows three phases:
subsequent reconstruction and rehabilitation, which serum imbibition (plasmotic circulation), revascular-
should lead to an optimal functional and cosmetic ization, and organization.1
result. The type of flap or graft employed in recon- Serum imbibition begins when the graft is
struction is dictated by the location and size of the placed on the recipient site and lasts about 48 hours.
defect, and every attempt should be made to replace A thin layer of fibrin clot forms between the host bed
like tissue with like tissue. Simple mucosal defects may and the skin graft, temporarily anchoring it in place.
be allowed to heal secondarily or may require minor Nutrients from the plasma transudate, which come
grafting procedures. Larger resections incorporating from the dilated capillaries of the host bed, diffuse
skin, mucosa, muscle, or bone demand more complex into the graft.2
reconstruction, employing free flaps or compound Revascularization of the graft begins with the
myocutaneous flaps. The ideal reconstructive modal- ingrowth of the vascular buds from the host bed.
ity should be performed as a single-stage procedure The process of revascularization, although some-
while providing effective rehabilitation with mini- what controversial, is believed to occur by two
mum donor-site morbidity. A wide variety of recon- processes, neovascularization (ingrowth of vessels
structive choices are available today. It is important to from the host into the graft) and inosculation (direct
be familiar with these options while understanding anastomoses of graft and host vessels).1
their advantages and limitations. The organization phase begins with the infil-
tration of leukocytes soon after the graft is placed on
GRAFTS the host. As the graft revascularizes, the leukocytes
disappear. Fibroblasts begin to infiltrate the fibrin
Smaller oral cavity and oropharyngeal defects may network by day 4, and as the fibroblasts proliferate,
be allowed to heal by secondary intention. This is the fibrin resorbs. By day 9, the process is complete.
appropriate when subsequent wound contracture
produces a minimal functional deficit. Defects of the
hard palate, where underlying palatal bone has been TYPES OF GRAFTS
preserved, are best allowed to heal by secondary The location and size of the defect typically dictate
intention. Similarly, defects of the tonsillar area, soft the type of graft to be selected for reconstruction.
palate, buccal mucosa, and tongue heal effectively by
secondary intention with minimal contracture. Con- Split-Thickness Skin Graft Split-thickness skin
versely, only the smallest defects of the anterior floor grafts (STSGs) consist of the epidermis and a por-
of the mouth may be allowed to heal by secondary tion of the dermis. The thickness of the graft varies.
intention as scar contracture typically produces Thin grafts are harvested at a thickness of 0.005 to
some degree of ankyloglossia. 0.012 in, moderate grafts at 0.012 to 0.018 in, and
thick grafts at 0.018 to 0.028 in. Thinner grafts are
more readily nourished and have a high survival rate
GRAFT PHYSIOLOGY but are more liable to contract. Because adnexal
Epithelial grafts are free tissue grafts that depend structures (hair follicles, sebaceous and sweat
entirely on the recipient bed for their viability and so glands) are located in the deeper portion of the der-
972
Flaps and Grafts in the Head and Neck 973
mis, thicker grafts may grow hair and reflect donor- lialize on its own and thus must be closed primarily
site morphology (Figure 41–1).2 or be covered with a STSG.
Split-thickness grafts are excellent choices for
coverage of areas that require surveillance for tumor Dermal Grafts Dermal grafts are mentioned pri-
recurrence. Split-thickness skin grafts work well in marily for historical interest. These grafts are har-
the oral cavity and oropharynx when bulk is not vested after the epidermal layer has been raised.
required and when coverage is needed to prevent They have been used in the past for oral and pha-
excessive wound contraction. ryngeal reconstruction and have been placed in the
They are often meshed, allowing for expansion subcutaneous layer to improve facial contouring.
to cover more surface area. This is particularly These grafts have been used to protect the carotid
appropriate for large superficial defects of the scalp. artery when salivary leaks and skin breakdown
Powered dermatomes enable these grafts to be har- might lead to carotid exposure and blowout. This
vested with ease and precision. The anterior thigh, technique has been largely abandoned because of
with its large surface area, is the favored donor site. complications of epithelialization of the graft on
Critical to the successful take of the skin graft is exposure to air or saliva and the growth of retained
immobilization. This can be accomplished in some epithelium beneath the skin, resulting in chol-
cases by simply suturing the central portion of the esteatoma formation.
graft, but, in other cases, specifically contoured bol-
Mucosal Grafts Buccal mucosa is the usual donor
sters may be needed to ensure fixation.
site for mucosal grafts. The graft obtained should
Full-Thickness Skin Grafts Full-thickness skin not exceed 2 × 3 cm to prevent excessive scarring
grafts (FTSGs) contain the epidermis and the entire with subsequent trismus. Buccal grafts are often
dermal layer. These grafts are most commonly used used for airway reconstruction for which desqua-
to cover defects of the nasal tip, lateral ear, or eyelids mating skin is not desirable.
after the excision of cutaneous skin malignancies.
The color and texture of the donor and recipient site FLAPS
should match as closely as possible. Preauricular,
postauricular, and supraclavicular skin is ideal for CLASSIFICATION
most facial defects, whereas upper eyelid skin should
A flap is a unit of tissue that may be advanced or
be used to replace upper and lower lid defects.
rotated into a surgical defect while maintaining its
Because of their thickness, FTSGs do not contract.
original blood supply. Understanding its vascular sup-
This quality, however, also leads to slower revascu-
ply is crucial to flap design and success. Flaps are de-
larization and a lower take rate. Unlike the STSG
fined as “random,”“axial,” or “free” depending on their
donor site, the FTSG donor site cannot re-epithe-
pattern of blood supply. Random flaps derive nutri-
tion from local, small, unnamed vessels of the dermal-
subdermal plexus and are therefore severely restricted
with respect to size. Axial pattern flaps are based on
recognizable, usually named arteriovenous pedicles.
An axial flap may include a “random” extension at the
distal portion of the flap, increasing the amount of
skin available. Free flaps are pedicled, axial pattern
grafts detached from a distant site (Figure 41–2).
Flaps are classified as local, regional, and dis-
tant depending on their location. Tissues that are
immediately adjacent to the defect are called local
flaps. Local flaps usually have a random vascular pat-
FIGURE 41–1. Diagrammatic representation of skin and tern. Regional flaps possess an axial vascular pattern
subcutaneous tissue. The thickness of various types of and are typically advanced and transferred from a
skin grafts is illustrated. Reproduced with permission more distal site while maintaining its vascular pedi-
from Petruzzelli GJ and Johnson JT.2 cal attachment. Free or distant flaps are pedicled
974 Ballenger’s Otorhinolaryngology
composite grafts that require separation of the vas- the 1980s, with the pectoralis myocutaneous flap
cular pedicle from the donor site with subsequent taking the lead while becoming the “workhorse” for
reanastomosis within the recipient bed. head and neck reconstruction.
Many of these pedicled flaps can be modified
PEDICLED REGIONAL FLAPS to include a bone or cartilage graft. This modifica-
tion has been largely replaced with free osseocuta-
Prior to the development of pedicled regional flaps, neous flaps, which offer superior reconstructive
head and neck reconstruction options consisted of options with a higher success rate.
primary closure, local flaps, or delayed procedures A wide variety of pedicled regional flaps are
requiring prolonged hospitalization. These options available (Table 41–1) and are described in more
were less than effective for large defects. Primary clo- detail.
sure of the oral cavity often reduced the functional
volume or tethered the tongue, causing ankyloglos- Pectoralis Major Myocutaneous Flap Since the
sia, dysarthria, or dysphagia. Such techniques also introduction of the pectoralis major myocutaneous
led to stenosis of the oropharynx and hypopharynx, flap in 1979, it has become the most commonly used
with similar morbidity. The limitations of blood pedicled regional flap for head and neck reconstruc-
supply with random pattern flaps frequently created tion while providing coverage for most defects of the
a relatively short flap, and attempts to reconstruct head and neck from the scalp and skull base to the
more distant sites were often associated with necro- cervical region and hypopharynx.
sis of the distal part of the flap. In addition, local flap The pectoralis major muscle is a large fan-
rotation often resulted in stricture and tethering. shaped structure located over the anterior upper
Delayed flaps required multiple surgical procedures chest. This muscle is attached laterally to the medial
over a prolonged period of time. surface of the humeral head, medially to the ster-
Bakamjian introduced the two-stage deltopec- num, and inferiorly to the lower ribs. It adducts and
toral flap for pharyngoesophageal reconstruction in medially rotates the humerus. The pectoral branch
1965.3 Other regional flaps were subsequently intro- of the thoracoacromial artery is its primary blood
duced, but it was only when Ariyan developed the supply, with a minor contribution by a small branch
pectoralis major myocutaneous flap in 1979 that the of the lateral thoracic artery. Its vascular pedicle is
use of regional pedicled flaps became widespread.4 located in the clavipectoral fascia as it runs on the
Regional flaps dominated the reconstructive scene in undersurface of the pectoralis major muscle along
Flaps and Grafts in the Head and Neck 975
a = artery; n = nerve.
an axis from the shoulder to the xiphoid (Figure inates several disadvantages of the myocutaneous
41–3).5 The pectoralis major muscle receives a minor flap, including excessive bulk, chest wall deformity,
contribution from the lateral thoracic artery; how- and transposition of hair to the aerodigestive tract.
ever, this vessel is typically divided, allowing for a The incidence of partial flap loss ranges from 4 to
more effective arc of rotation. 14% and total flap necrosis from 1 to 7%.7
This flap has many advantages for head and The pectoralis major myocutaneous flap con-
neck reconstruction. It is reliable, easy to raise, and tinues to play an important role in head and neck
in close proximity to the head and neck recipient reconstruction, reflecting its versatility, reliability,
site. It can be raised quickly with the patient in the and ease of harvest.
supine position, and the donor-site defect can usu-
ally be closed, primarily when a relatively large skin Trapezius Myocutaneous Flap The trapezius is a
paddle is harvested. large, broad, flat, triangular muscle of the back and
This flap may be fashioned as a myocutaneous shoulder. It originates on the external occipital pro-
or myofascial flap for the reconstruction of oral cav- tuberance near the nuchal line and spinous
ity or pharyngeal defects.6 The myofascial flap elim- processes of C7 to T12 and inserts onto the lateral
976 Ballenger’s Otorhinolaryngology
third of the clavicle, the acromion, and the spine of tion.9 In these cases, a delayed procedure may be
the scapula. The trapezius acts to steady the scapula. required to maintain the viability of the distal por-
Four arteries, the transverse cervical, dorsal scapular, tion of the flap. The donor site usually requires a
occipital, and perforating branches of the STSG.
paraspinous vasculature, supply this broad muscle. The lateral island trapezius flap, first presented
Although the transverse cervical is its primary blood by Panje10 and Demergasso11 in 1978, is based on the
supply, collateral circulation allows for the design of transverse cervical vessels (Figure 41–5). This is the
three musculocutaneous flaps through different least reliable of the three flaps as mobilization is
pedicles, the superior flap, island (lateral) flap, and dependent on the course and length of the trans-
lower (posterior) flap. verse cervical artery and vein. Both vessels must be
The superior flap, first described by Conley in patent for this flap to survive, so this flap is not rec-
1972, receives its primary vascular supply from the ommended after radical neck dissection in which
perforating branches of the posterior intercostal sacrifice of these vessels often takes place. This flap
arteries with minor contribution by the occipital works well for soft tissue defects of the ipsilateral lat-
branches.8 This flap requires a simple dissection eral and anterior neck, oral cavity, and pharynx. The
without the need for identification of the feeding flap itself is technically easy to develop, and the
vessels and is useful for closure of ipsilateral regional donor-site defect may be closed primarily.
skin or pharyngeal defects. It is a superiorly based The use of the lower trapezius myocutaneous
flap and, as such, is not prone to wound separation island flap (LTMIF) was first introduced by Baek et
secondary to gravitational pull (Figure 41–4). al in 1980.12 This flap provides the greatest length
The trapezius muscle is located outside the and arc of rotation and therefore is the most versa-
radiated field and its blood supply is not typically tile. It is primarily supplied by the transverse cervi-
threatened during radical neck dissections. cal vessels, but the dorsal scapular artery feeds the
A major disadvantage is its limited length, pre- distal portion of the flap. Both arteries usually arise
venting the flap from extending across the midline. from the thyrocervical trunk, with a great deal of
The most distal portion of the flap, lateral to the variability in their origin and course. The LTMIF is
acromion, may not survive if the transverse cervical often based solely on the transverse cervical vessels
artery has been ligated during a radical neck dissec- as the preservation of the dorsal scapular vascular
Flaps and Grafts in the Head and Neck 977
A B C
FIGURE 41–7. A, Squamous cell carcinoma of the parotid with skin exposure. B, Deltopectoral flap raised and rotated
into the defect. C, The deltopectoral flap is inset into the cervical defect. Xeroform bolster placed over the split-thick-
ness skin graft.
solved by detaching the zygomatic arch prior to rota- posterior branch, which extends into the parietal
tion of the flap and then reattaching the arch with region, acts as the distal vascular pedicle (Figure
reconstruction plates.23 41–8). Dissection of the vascular pedicle is best
A major complication of the temporalis muscle monitored with intraoperative Doppler ultrasonog-
flap is injury to the frontal branch of the facial nerve. raphy. The auriculotemporal nerve runs with the
Clauser et al noted an incidence of 19.2% transient vascular pedicle and is usually sacrificed, leading to
paresis and 2.7% permanent paralysis.22 Fibrosis of temporal numbness.
the retromolar trigone region has been experienced The donor site is well hidden within the hair-
in oropharyngeal reconstruction and is best managed line, creating minimal morbidity. Alopecia is occa-
with postoperative jaw opening exercises.22 sionally produced.
This flap is reliable but has a limited role This well-vascularized fascial flap is useful for
beyond facial reanimation. Its primary use is to cover resurfacing the orbit, midface, and lateral oral
small to moderate-sized defects of the orbit, lateral defects and is available for auricular reconstruction.
aspect of the face, and lateral part of the skull base. The flap may include the overlying hair-bearing skin
to reconstruct a brow and mustache.24 The inclusion
Temporoparietal Fascial Flap The temporopari- of a split calvarial bone graft with overlying galea
etal fascia can be used as a pedicled or free flap. This aponeurosis creates a composite flap for the recon-
thin, pliable flap may resurface a significant area struction of the orbit or zygoma.
without bulk.
This fascia is the superficial covering that over- Platysma Myocutaneous Flap The platysma
lies the temporalis muscle and continues on as the myocutaneous flap has several advantages for use in
superficial aponeurotic system inferiorly and the oral cavity reconstruction.25 It is located within the
galea aponeurosis superiorly. Its vascular supply surgical field, easy to elevate, and pliable and has
arises from the superficial temporal artery and vein minimal donor-site morbidity.
and may be isolated 3 cm superior to the root of the This flap is created from the broad sheet of
helix prior to its division into an anterior and a pos- muscle that arises from the fascia covering the upper
terior branch. The anterior branch, which extends parts of the deltoid and pectoralis major muscles. It
into the frontal region, is often ligated 3 to 4 cm ascends across the clavicle and up the neck, reaching
from its takeoff. Further peripheral dissection risks the lower border of the mandible and lateral half of
injury to the frontal branch of the facial nerve. The the lower lip. The platysmal myocutaneous flap
980 Ballenger’s Otorhinolaryngology
motor innervation. This neurovascular bundle Postoperatively, this puts the vascular pedicle
enters the muscle at a single neurovascular hilum on at risk of compression in the region of the anterior
its internal (costal) surface 6 to 12 cm from the sub- axilla by the upper arm. The reconstructive surgeon
scapular artery and 1 to 4 cm medial to the lateral needs to be familiar with the anatomy of the axilla,
border of the muscle.29 The artery gives off one to the axillary vessels, and their variations. Finally,
three large branches to the serratus anterior muscle owing to the shoulder dysfunction that may arise,
before dividing at the hilum to supply the latissimus. this flap should be avoided if the trapezius muscle,
The long thoracic nerve provides cutaneous sensory pectoralis major muscle, or spinal accessory nerve
innervation. The vascular supply of the latissimus has previously been compromised.23,31
dorsi muscle is not affected by prior radiation. In summary, this is a reliable and versatile flap
Reconstruction can be performed employing either that works well as a pedicled or free flap. It may pro-
a pedicled or free flap technique with equally high vide coverage to distant areas, such as the scalp, lat-
success rates30 (Figure 41–9). eral part of the skull base, and orbitomaxillary
The flap does have some disadvantages. A lat- region, where a flap with a large surface area is
eral decubitus position is needed to harvest this flap, required. It is also an excellent option for dynamic
creating a need for intraoperative repositioning. In reconstruction after total glossectomy.
addition, when pedicled, the flap is passed through
the axilla between the pectoralis major and minor Gastric Pull-up The gastric pull-up plays an
muscles. important role in reconstruction of total pharyngo-
esophageal defects when the tumor extends into the
cervical esophagus. The gastric pull-up allows for sin-
gle-stage reconstruction with good oral rehabilita-
tion. The gastric tube is a well-vascularized flap that
may be used in a previously irradiated or operated
field. The technique requires a general surgical team
to mobilize the stomach and to create the gastric
tube. Posterior mediastinal dissection is performed
through both the diaphragm and a cervical approach
(Figures 41–10 and 41–11). With adequate mobiliza-
tion, the distal portion of the flap may reach the soft
palate. The flap is contraindicated in patients with
severe pulmonary and hepatobiliary disease. Mortal-
ity rates as high as 18% and an incidence of severe
complications reaching 50% have been reported.32,33
The morbidity and mortality can be decreased to
acceptable levels in carefully selected patients.
FREE FLAPS
Although microvascular free tissue transfer was
introduced in the 1970s, it was not until the late
1980s that free flaps became popular. Pedicled
regional flaps dominated the 1980s, reflective of
their ease of use with shortened operative time
while eliminating the skills required in microvascu-
FIGURE 41–9. The latissimus dorsi myocutaneous flap: lar surgery.
A, flap design; B, flap dissection; C, rotation of flap. The use of microvascular free tissue transfer
Reproduced with permission from Shindo ML, Sullivan blossomed in the late 1980s and has become one of
MJ. Muscular and myocutaneous pedicled flaps. Oto- the primary reconstructive modalities in head and
laryngol Clin North Am 1994;27:166. neck surgery. Flap survival rates ranging from 91 to
982 Ballenger’s Otorhinolaryngology
99% are routinely achieved, reflecting a more pre- was now possible in defects that had previously
dictable axial blood supply.34,35 Free tissue transfer required a delayed procedure. Prior radiation did
also allows for more donor-site options relating to not affect flap survival.36,37
size, thickness, and the need to include bone or The success of free tissue transfer goes far
innervation potential. Single-stage reconstruction beyond designing of flap dimensions. It requires
A B
FIGURE 41–11. A, Proximal esophagus resected en bloc with hypopharynx. Note the mobilized gastric tube. B, Gas-
tric tube in place. Note the pharyngogastric anastomosis.
Flaps and Grafts in the Head and Neck 983
careful planning and begins with an understanding floor-of-mouth defects. With the addition of sensory
of both the donor-site vascular pedicles and recipi- reinnervation, it has become quite useful for tongue
ent-site vessel options. Careful harvest of the nutri- and hemilaryngopharyngeal reconstruction.
ent vascular pedicle is required, taking into account This flap is harvested from the volar surface
the length of pedicle needed to prevent tension on of the forearm. The vascular supply is the radial
the vascular anastomosis while avoiding excessive artery and the cephalic vein or the venae comi-
length, which might result in twisting and kinking. tantes (Figure 41–12).
The highly vascular nature of the head and neck Although a composite bone graft can be
region normally provides a plethora of recipient ves- obtained by adding a portion of the radius, no more
sels to choose from. Previous or associated surgical
resection required in a neck dissection may severely
limit recipient vessel options. Prior radiation to the
neck may lead to atherosclerosis of the recipient
artery.38 Determination of the length of the vascular
pedicle and choice of recipient vessels are ultimately
made at the time of resection and reconstruction.
The most critical aspect of microvascular
reanastomosis is the accurate apposition of the cut
edges of the vessels and maintenance of intimal con-
tinuity. The venous anastomosis is typically more
demanding technically, given the thin and delicate
walls of veins, and may lead to venous thrombosis,
the most common cause of flap failure. The critical
period for venous thrombosis is the first 3 to 5 days.
A variety of choices are generally available in the
neck for recipient vessel selection, although it does
partially depend on the region to be reconstructed.
The most common choices for recipient arteries are
the ipsilateral lower branches of the external carotid
artery or branches of the thyrocervical trunk.38 When
ipsilateral recipient vessels are not available, con- A
tralateral neck vessels may be used as an alternative
option. Interposition vein grafts may be necessary if
the pedicle length is inadequate.38 The primary recip-
ient veins are the external and internal jugular veins
and the transverse cervical vein. When these options
are not available on the ipsilateral neck, the contralat-
eral neck veins would be the next alternative.38
Some have raised the question of cost effec-
tiveness in the use of microvascular free tissue trans-
fer. Several studies have shown that the cost of free
flaps is ultimately comparable to pedicled regional
flaps. This slightly higher cost is more than offset by
the superior functional results and lower complica- B
tion rates.39,40
FIGURE 41–12. A, Pictorial representation of radial fas-
Radial Forearm Free Flap The radial forearm free ciocutaneous flap. Reproduced with permission from Sil-
flap is the most frequently chosen free flap for head ver CE, Rubin JS, editors. Atlas of head and neck surgery.
and neck reconstruction. This pliable, robust flap Philadelphia: Churchill Livingstone; 1999. B, Intraopera-
has the ideal thinness for pharyngeal, palatal, and tive harvest of radial forearm free flap.
984 Ballenger’s Otorhinolaryngology
than 40% of the radius can be used without signifi- is harvested with the flap to provide sensation to the
cantly increasing the risk of a radius fracture. Such flap (Figure 41–13).
fractures may adversely affect wrist mobility and The primary limitation for this flap is the small
hand strength. Because of the small size of this bone caliber of the vascular pedicle with its associated
graft and the significant morbidity related to the decreased survival rate.23
fracture, other composite grafts, such as the fibular
and the scapular flaps, are usually better choices Lateral Thigh Fasciocutaneous Flap The lateral
when bone is required. thigh flap is a lower extremity version of the lateral
The ability to provide sensation to the flap has arm flap while providing a much larger surface area.
also made this flap particularly advantageous in oral Hayden and Dreschler have described harvesting a
cavity and pharyngeal reconstruction. The lateral graft measuring 27 × 14 cm; however, the exact lim-
antibrachial cutaneous nerve, which runs with the its of the graft size have not been established.42 This
cephalic vein, is the nerve most commonly used for flap has been used successfully in reconstructing total
reinnervation. The medial antibrachial cutaneous laryngopharyngectomy and total glossectomy defects
nerve is also available. and may effectively resurface large soft tissue defects
The biggest concern with harvesting this flap is in the cervical region. The donor site is usually closed
adequate perfusion of the hand by the ulnar artery primarily leaving an esthetically acceptable linear scar
via the palmar arch. It is crucial that the Allen test is with minimal donor-site morbidity.
properly performed preoperatively to assess the per- The skin paddle is centered over the intermus-
fusion of the hand by the ulnar artery when the cular septum, which separates the vastus lateralis
radial artery is occluded. Doppler ultrasonographic and the iliotibial tract anteriorly from the biceps
evaluation is also helpful in evaluating patency of
the ulnar artery. Despite careful preoperative testing,
if inadequate perfusion of the hand is discovered, a
reverse vein graft can be placed to reconstitute flow
through the radial artery.
Complications primarily arise at the donor
site. In addition to the risk of radius fracture, failure
to raise the flap in a suprafascial plane may lead to
poor skin graft take and tendon exposure with sub-
sequent wrist and hand dysfunction.41
femoris posteriorly (Figure 41–14). It can be roughly free flap allows coverage of large scalp and cranial
located by drawing a line from the greater trochanter defects anywhere on the calvarium.
to the lateral epicondyle. The third perforator of the The anatomy of this flap was discussed earlier
profunda femoris artery, which is usually the domi- in the pedicled regional flaps section.
nant vascular supply to the flap, can be found A vascular pedicle as long as 12 cm can be
emerging from the septum at the midpoint of this obtained by dissecting up to its takeoff from the axil-
line. Although the third perforator is usually the lary vessels.
dominant blood supply, any one of the second to As with the pedicled version, a lateral decubi-
fourth perforators may prove to be the dominant tus position is required in its harvesting. In addition,
vessel. A sensate flap can be obtained by harvesting donor-site morbidity with shoulder dysfunction
the lateral femoral cutaneous nerve. may develop.
Preoperative evaluation is extremely impor-
tant. If peripheral vascular disease exists, another Rectus Abdominis Free Flap The popularity of
donor site should be chosen. Because the thickness the rectus abdominis free flap relates to its ease to
of the flap depends on the body habitus of the harvest, long vascular pedicle, and excellent reliabil-
patient, the donor site must be carefully evaluated to ity, with a success rate as high as 97.5%.43 It provides
match the needs of the recipient defect. This flap is a large surface area and bulk, making it particularly
rarely used in obese patients. useful in extensive skull base defects. It is also effec-
The complication rate compares favorably to tive in covering the orbitomaxillary regions and
other more commonly used free and pedicled flaps.42 reconstructing total glossectomy defects. The bulk of
Donor-site morbidity includes seroma formation the flap depends on body habitus. The flap can be
and compartment syndrome. The risk of compart- harvested using the entire rectus as a small single
ment syndrome has been significantly minimized by island flap or as multiple skin islands. Attempts at a
wide undermining to avoid excessive tension and use sensate flap have generally not been successful.
of an active drain. The flap is thicker inferiorly and then thins out
superiorly above the costal margin.
Latissimus Dorsi Free Flap The latissimus dorsi The rectus abdominis muscle arises from the
flap can be harvested as a pedicled or free flap. pubic crest and symphysis pubis and inserts into the
Although the pedicled flap can reach up to the fifth to seventh costal cartilages. The muscle is
orbitomaxillary and lateral skull base lesions, the enveloped anteriorly and posteriorly by the rectus
sheath. It has two dominant vascular pedicles, the 15 cm. The deep inferior epigastric artery and vein
deep inferior epigastric and the superior epigastric can be found entering the lateral border of the rec-
vessels. The two vascular systems anastomose in the tus muscle halfway between the pubis and umbili-
region above the umbilicus through a system of cus, about 3 to 4 cm below the arcuate line.
small caliber vessels called “choke vessels.”44 The Topographically, the arcuate line is located approxi-
deep inferior epigastric artery, with its large vessel mately at the level of the anterior superior iliac
diameter, is the preferred vascular pedicle for har- spine. The arcuate line is an important anatomic
vest. It gives rise to the major musculocutaneous marker, not only to identify the vascular pedicle but
perforators and thus supplies a larger area of skin also to identify the transition zone where the poste-
(Figure 41–15, A). The largest concentration of cuta- rior sheath is composed of all three aponeuroses of
neous perforators is located in the paraumbilical the oblique muscles superiorly and only the trans-
region, with the cutaneous vessels radiating superi- versalis fascia inferiorly. This creates a potential weak
orly and laterally toward the costophrenic angle. The area below the arcuate line that puts it at risk for a
flap is designed to capture these perforators (Figure ventral hernia if the anterior sheath is not carefully
41–15, B). The pedicle length can be extended up to reapproximated in this region.
Donor-site morbidity is a major limitation,
and this includes acute pain, ventral hernia, gait dis-
turbance, and paresthesias with radiculopathy.
Contraindications for this flap are previous
abdominal surgery, intrapelvic surgery, inguinal
herniorrhaphy, and vascular surgery on the iliac
system.23
length. Despite the fact that the bone is thinner and infrequent and consists of shoulder weakness and
not as strong as the iliac crest or fibular bone graft, it diminished range of motion.50
is still a viable option for mandibular reconstruction Harvesting this flap requires special positioning
and may permit the placement of osseointegrated and makes synchronous two-team surgery difficult.
dental implants. Harvesting this bone does require This flap is well suited for composite defects
the detachment and reattachment of the teres major that require a large amount of soft tissue. Its thinness
muscle to the remaining scapula to prevent donor- and pliability also make it quite useful in palatal and
site morbidity. This flap provides a larger surface area orbital floor reconstruction. With de-epithelializing,
of skin for reconstruction than the fibular or iliac this flap becomes useful for reconstruction of mid-
crest composite flap. The two skin flaps can also be face defects.49
placed in different three-dimensional orientations
since they have separate pedicles and may be used to
resurface two contiguous sites (Figure 41–19).49
VISCERAL FLAPS
The donor-site defect, which is closed prima- Visceral flaps provide certain advantages over cuta-
rily, is located posteriorly, making it cosmetically neous flaps. They provide a thin, pliable mucosal
advantageous. Donor-site morbidity is relatively surface that is particularly beneficial in oral cavity
grafts or to revascularize areas of osteoradionecrosis greater curvature of the stomach and the transverse
and osteomyelitis. The omentum is also well suited colon. The greater curvature of the stomach and the
for the augmentation of the midface, reflecting its omentum are both supplied by the right and left gas-
ability to be subdivided into compartments. troepiploic arteries. The right gastroepiploic is usu-
The greater omentum is a large, double-layered ally chosen as the pedicle because of its larger vessel
peritoneum that hangs from its attachments to the diameter and longer pedicle length. This flap is rela-
tively easy to harvest but has the drawback of requir- grafts provide excellent coverage with minimal con-
ing a laparotomy (Figure 41–23). tracture. Local flaps are useful for the reconstruction
This flap is contraindicated in patients with a of moderate-sized floor-of-mouth defects. Mucous
history of gastric outlet obstruction and peptic ulcer membrane, platysma, and nasolabial flaps are read-
disease. ily available and provide dependable and adequate
coverage in most patients. They are associated with
RECONSTRUCTION OF REGIONAL few functional and cosmetic consequences and min-
imal donor-site morbidity.59
DEFECTS The tunneled, inferiorly based nasolabial flap is
ORAL CAVITY AND PHARYNX well suited for anterior intraoral defects. By using
both cheeks as the donor site, up to 25 cm2 of tissue
Reconstruction of the oral cavity and pharynx can may be provided for intraoral lining. The blood sup-
be a challenging endeavor, and one must take into ply from the labial artery is excellent, making delay
consideration the needs for normal deglutition and unnecessary. The flaps maintain a supple floor of the
speech. Small intraoral defects may be allowed to mouth, allowing for mobility of the remaining
heal by secondary intention. Mucous membrane tongue. They provide excellent coverage for the
exposed mandible after removal of the alveolus or
lingual cortex with minimal bulk. Donor-site mor-
bidity is minor, and cosmesis is excellent (Figure
41–24).59
Xerostomia is a significant problem with oral
cavity cancers that require surgery and radiation
therapy. The visceral flaps, including the jejunal
patch and gastro-omental flap, have the advantage
of providing tissue that continues to secrete mucus,
making them appropriate for postradiation failures.
These flaps work particularly well in areas for which
a thin flap is preferred, such as the floor of the
mouth, alveolar ridge, pharyngeal wall, and buccal
mucosa. The jejunal flap can be folded in on itself to
reconstruct a soft palate defect. Gastro-omental flaps
are more appropriate when the oral cavity defect is
associated with a large soft tissue neck defect. These
visceral flaps may be the only flaps that are thin and
pliable in an obese patient.
Large defects of the floor of mouth and
oropharynx can be readily reconstructed with a
pedicled regional flap. The pectoralis major myocu-
taneous flap is the flap of choice when a quick reli-
able flap is desired. A fasciocutaneous modification
is appropriate when a large flap with less bulk is
FIGURE 41–23. Schematic view of the free gastro-omen- required.
tal flap being harvested. The left gastroepiploic vessels Tongue mobility, adequate bulk, and sensation
have been sectioned. A stapling device has been employed are key factors in planning oral cavity reconstruc-
to section a piece of the greater curvature from the rest of tion. The radial forearm free flap meets these needs
the stomach. The stomach flap with the omentum is pedi- and represents the preferred choice for reconstruc-
cled on the right gastroepiploic vessels. Reproduced with tion after partial glossectomy. In addition, this flap
permission from Hayden RE. Microvascular free flaps for can be bivalved to reconstruct both the tongue and
soft-tissue defects. Otolaryngol Clin North Am 1991; the floor of the mouth. The lateral arm flap is an
24:1343. alternative if the radial forearm is not available.60,61
Flaps and Grafts in the Head and Neck 993
13. Rosen HM. The extended trapezius musculocuta- 27. Cannon CR, Johns ME, Atkins JP, et al. Reconstruc-
neous flap for cranio-orbital facial reconstruction. tion of the oral cavity using the platysma myocuta-
Plast Reconstr Surg 1985;75:318–24. neous flap. Arch Otolaryngol 1982;108:491–4.
14. Cummings CW, Eisele DW, Coltrera MD. Lower 28. Persky MS, Kaufman D, Cohen NL. Platysma
trapezius myocutaneous island flap. Arch Otolaryn- myocutaneous flap for intraoral defects. Arch Oto-
gol Head Neck Surg 1989;115:1181–5. laryngol 1983;109:463–4.
15. Jianu J. Paralizie faciale dupa exterparea unei tumori 29. Quillen CG, Shearin JC, Geogiade NG. Use of the
a parotidei, tratata prin operatia Dlui Gomoiu. Bull latissimus dorsi myocutaneous island flap for recon-
Mem Soc Chir Bucharest 1908;22. struction in the head and neck area. Plast Reconstr
16. Kierner AC, Aigner M, Zelenka I, et al. The blood Surg 1978;62:113–7.
supply of the sternocleidomastoid muscle and its 30. Haughey BH, Fredrickson JM. The latissimus dorsi
clinical implications. Arch Surg 1999;134:144–7. donor site. Otolaryngol Head Neck Surg 1991;117:
17. Tiwari R. Experiences with the sternocleidomastoid 1129–34.
muscle and myocutaneous flaps. J Laryngol Otol 31. Har-el G, Bhaya M, Sundaram K. Latissimus dorsi
1990;104:315–21. myocutaneous flap for secondary head and neck
18. Sebastian P, Cherian T, Ahamed MI, et al. The ster- reconstruction. Am J Otolaryngol 1999;20:287–93.
nomastoid island myocutaneous flap for oral cancer 32. Surkin MI, Lawson W, Biller HF. Analysis of the
reconstruction. Arch Otolaryngol Head Neck Surg methods of pharyngoesophageal reconstruction.
1994;120:629–32. Head Neck 1984;6:953–70.
19. Kingdom TT, Singer MI. Enhanced reliability and 33. Lam KH, Wong J, Lim ST, Ong GB. Pharyngogastric
renewed applications of the deltopectoral flap in anastomosis following pharyngolaryngoesophagec-
head and neck reconstruction. Laryngoscope tomy. Analysis of 157 cases. World J Surg 1981;5:
1996;106:1230–3. 509–16.
20. Hamaker RC. Oral cavity and oropharyngeal recon- 34. Blackwell KE. Unsurpassed reliability of free flaps for
struction. In: Cummings CW, et al, editors. Oto- head and neck reconstruction. Arch Otolaryngol
laryngology-head and neck surgery. St. Louis: Head Neck Surg 1999;125:295–9.
Mosby-Year Book; 1986. 35. Urken ML, Weinberg H, Buchbinder D, et al.
21. Verneuil AAS. De la creation d’une fausse articula- Microvascular free flaps in head and neck recon-
tion par section ou resection patielle de l’os maxil- struction. Arch Otolaryngol Head Neck Surg 1994;
laire inferieur. Arch Gen Med 1872;15:284. 120:633–40.
22. Clauser L, Curioni C, Spanio S. The use of the tempo- 36. Schusterman MA, Miller MJ, Reece GP, et al. A sin-
ralis muscle flap in facial and craniofacial reconstruc- gle center’s experience with 308 free flaps for repair
tive surgery. A review of 182 cases. J Craniomaxillofac of head and neck cancer defects. Plast Reconstr Surg
Surg 1995;23:203–14. 1994;93:472–8.
23. Shindo ML, Sullivan MJ. Muscular and myocuta- 37. Shestak KC, Jones NF. Microsurgical free-tissue
neous pedicled flaps. Otolaryngol Clin North Am transfer in the elderly patient. Plast Reconstr Surg
1994;27:161–72. 1991;88:259–63.
24. Allegretti JP, Panje WR. The temporoparietal fas- 38. Urken ML. Recipient vessel selection in free tissue
cial flap in head and neck reconstruction: the transfer to the head and neck. In: Urken ML, Cheney
workhorse from above. In: Friedman M, editor. ML, Sullivan MJ, Biller HF, editors. Atlas of regional
Flaps for head and neck reconstruction. Part 1. and free flaps for head and neck reconstruction. New
Oper Tech Otolaryngol Head Neck Surg 2000;11: York: Raven Press; 1995. p. 331–7.
143–6. 39. Tsue TT, Desyatnikova SS, Deleyiannis FW, et al.
25. Verschuur HP, Dassonville O, Santini J, et al. Com- Comparison of cost and function in reconstruction
plications of the myocutaneous platysma flap in of the posterior oral cavity and oropharynx. Arch
intraoral reconstruction. Head Neck 1998;20: Otolaryngol Head Neck Surg 1997;123:731–7.
623–9. 40. Kroll SS, Evans GR, Goldberg D, et al. A comparison
26. McGuirt WF, Matthews BL, Brody JA, et al. Platysma of resource costs for head and neck reconstruction
myocutaneous flap: caveats reexamined. Laryngo- with free and pectoralis flaps. Plast Reconstr Surg
scope 1991;101:1238–44. 1996;99:1282–6.
996 Ballenger’s Otorhinolaryngology
41. Lutz BS, Wei F, Chang SC, et al. Donor site morbid- reconstruction. Plast Reconstr Surg 1998;102:
ity after suprafascial elevation of the radial forearm 473–7.
flap: a prospective study in 95 consecutive cases. 54. Kamei Y, Torii S, Hasegawa T, Nishizeki O. Endoscopic
Plast Reconstr Surg 1999;103:132–7. omental harvest. Plast Reconstr Surg 1998;102:2450–3.
42. Hayden RE, Deschler DG. Lateral thigh free flap for 55. Sullivan MJ, Urken ML. Free jejunal autograft. In:
head and neck reconstruction. Laryngoscope 1999; Urken ML, Cheney ML, Sullivan MJ, Biller HF, edi-
109:1490–4. tors. Atlas of regional and free flaps for head and
43. Cordeiro PG, Santamaria E. The extended, pedicled neck reconstruction. New York: Raven Press; 1995.
rectus abdominis free tissue transfer for head and p. 307–19.
neck reconstruction. Ann Plast Surg 1997;39:53–9. 56. Haughey BH. The jejunal free flap in oral cavity and
44. Taylor GI, Palmer JH. The vascular territories pharyngeal reconstruction. J Laryngol Otol 1994;27:
(angiosomes) of the body: experimental and clinical 680–2.
applications. Br J Plast Surg 1987;40:113–31. 57. Yonekawa Y, Yasargil M. Brain vascularization by
45. O’Leary MJ, Martin PJ, Hayden RE. The neurocuta- transplanted omentum: a possible treatment of cere-
neous free fibula flap in mandibular reconstruction. bral ischemia. Neurosurgery 1977;1:256–9.
Otolaryngol Clin North Am 1994;27:1081–96. 58. Vineberg A. Revascularization of the right and left
46. Urken ML, Sullivan MJ. Fibular osteocutaneous free coronary arterial systems: internal mammary artery
flap. In: Urken ML, Cheney ML, Sullivan MJ, Biller implantation, epicardiectomy, and free omental graft
HF, editors. Atlas of regional and free flaps for head operation. Am J Cardiol 1967;19:344–53.
and neck reconstruction. New York: Raven Press; 59. Atkins JP, Keane WM. Repair of the floor of the
1995. p. 291–306. mouth with local flaps. In: Snow JB, editor. Contro-
47. Carroll WR, Esclamado R. Preoperative vascular versy in otolaryngology. Philadelphia: WB Saunders;
imaging for the fibular osteocutaneous flap. Arch 1980. p. 520–34.
Otolaryngol Head Neck Surg 1996;122:708–12. 60. Ross DA, Thomson JG, Restifo R, et al. The extended
48. Turk JB, Vuillemin T, Raveh J. Revascularized bone lateral arm free flap for head and neck reconstruc-
grafts for craniofacial reconstruction. Otolaryngol tion: the Yale experience. Laryngoscope 1996;
Clin North Am 1994;27:955–82. 106:14–8.
49. Hayden RE, Fredrickson JM. Microvascular surgery 61. Sullivan MJ, Carroll WR, Kuriloff DB. Lateral arm
for head and neck reconstruction. In: Paparella MM, free flap in head and neck reconstruction. Arch Oto-
Shumrick DA, Gluckman JL, Meyerhoff WL, editors. laryngol Head Neck Surg 1992;118:1095–101.
Otolaryngology. 3rd ed. Vol IV. Philadelphia: WB 62. Takamatsu A, Harashina T, Inoue T. Selection of
Saunders; 1991. p. 2667–80. appropriate recipient vessels in difficult, microsurgi-
50. Coleman SC, Burkey BB, Day TA, et al. Increasing cal head and neck reconstruction. J Reconstr Micro-
use of the scapula osteocutaneous free flap. Laryn- surg 1996;12:499–507.
goscope 2000;110:1419–24. 63. Shektman A, Silver C, Strauch B. A re-evaluation of
51. Rosenberg MH, Sultan MR, Bessler M, Treat MR. hypopharyngeal reconstruction: pedicled flaps ver-
Laparoscopic harvesting of jejunal free flaps. Ann sus microvascular free flaps. Plast Reconstr Surg
Plast Surg 1995;34:250–3. 1997;100:1691–6.
52. Saltz R. Endoscopic harvest of the omental and jeju- 64. Schusterman MA, Shestak K, deVries EJ, et al.
nal free flaps. Clin Plast Surg 1995;22:747–54. Reconstruction of the cervical esophagus: free jeju-
53. Gherardini G, Gurlek A, Staley CA, et al. Laparo- nal transfer versus gastric pull-up. Plast Reconstr
scopic harvesting of jejunal free flaps for esophageal Surg 1990;85:16–21.
CHAPTER 42
The child born with a malformed ear faces a lifelong acid receptors are uniquely expressed in the devel-
hearing and communication impairment along with oping organ of Corti; medications that affect
the social stigma of a facial deformity. Associated retinoic acid metabolism, such as isotretinoin (Accu-
disturbances of the vestibular system may add the tane, Roche, Nutley, New Jersey), can lead to embry-
developmental hurdle of a motor delay. Frequently, opathies, including inner ear malformation.1
there are additional anomalies, such as mandibular The cochleovestibular ganglia develop from
hypoplasia, as well as other facial and skeletal defor- the otic placode epithelium. The nerve fibers them-
mities. There may be dysfunction of associated neu- selves not only influence sensory cell development
ral pathways, including cranial nerves and but are also directed to the developing inner ear by
intracranial structures. Additionally, there are psy- the sensory cells.2
chological factors to be considered, including As the membranous structures of the inner ear
parental guilt, peer ridicule, and the shame of “being form, they become enveloped in a cartilaginous cap-
different.” Educationally and economically, these sule, which eventually gives rise to the petrous por-
hearing-impaired children face the prospect of lim- tion of the temporal bone. Concurrently, the
ited opportunities. The appropriate management structures that originate from the first pharyngeal
involves recognizing the problems and limitations of pouch develop separately, but adjacent to, the otic
therapy, which need to be thoroughly understood by capsule derivatives. The pouch begins to form in the
the parents and, when appropriate, the patient. 3 to 4 mm embryo and expands into a tubotympanic
recess, which will eventually give rise to the
EMBRYOLOGY OF ATRESIA AND eustachian tube, middle ear space, and mastoid air
cell system. The third branchial arch migrates supe-
MICROTIA riorly to the level of the recess, and its artery (the
In the 3 to 4 mm embryo (3 to 4 weeks), the first internal carotid) comes to lie dorsal to the
indications of aural ontogenesis are the first and sec- eustachian tube. Variations in this relationship may
ond branchiomeric structures and the otic placode, result in a lateralized displacement of the internal
an ectodermal thickening on the lateral surface of carotid artery into the middle ear space. In adults, an
the head opposite the fourth ventricle. The placode ectopic carotid artery can be mistaken for a middle
invaginates to first form a pit and then a vesicle ear mass, such as a glomus tumor.
detached from its surface origin. This otocyst forms As the pharyngeal pouches form in the 3 to
the inner ear membranous structures, with the 4 mm embryo, corresponding grooves develop on
endolymphatic duct developing first at the 6 mm the external surface of the nascent cervical region.
stage, followed by the appearance of the semicircu- The first of these branchial clefts deepens until it
lar ducts and the cochlear diverticulum at the 15 approaches the tubotympanic recess, being sepa-
mm stage (6 weeks). By the end of the third month, rated only by the thin layer of mesoderm destined to
the cochlea is fully coiled. become the middle fibrous layer of the tympanic
The cranial nerves entering the otocyst exert an membrane. Subsequently, in the 30 mm embryo (8
inductive influence to produce neuroepithelium, for weeks), the primordial external canal becomes
which retinoic acid is a potent morphogen. Retinoic occluded by an ectodermal plug. By the twenty-first
997
998 Ballenger’s Otorhinolaryngology
bella, syphilis), ischemic injury (hemifacial microso- ing on the degree of the abnormality, the microtic
mia), or toxin exposure (thalidomide, isotretinoin). ear may be classified into three grades. In grade I,
Although inner ear abnormalities, such as the auricle is developed and, though misshapen, has
Usher’s syndrome, Waardenburg’s syndrome, and a readily recognizable, characteristic anatomy (Fig-
the neurofibromatoses, are becoming understood on ure 42–2). In grade II, the helix is rudimentary and
a molecular biologic basis, the genetic basis of exter- the lobule developed (Figure 42–3). In grade III, an
nal and middle ear anomalies generally remains amorphous skin tag is present9 (Figure 42–4). In all
poorly characterized.5 Aural atresia occurs in stages, wide variations of morphology exist. The
approximately 1 in 20,000 live births. Although the pinna may be fully formed with a transverse and
inner and middle ears develop separately, inner ear low-set orientation. There may be accessory
abnormalities coexist in 12 to 50% of cases. Atresia appendages of the pinna (pretragal tags with or
is bilateral in 30% of cases, occurring more com- without cartilage) and preauricular sinus tracts. The
monly in males and in the right ear.6 external canal may be stenotic or atretic to varying
It is not surprising that an embryonic insult degrees10 (Figure 42–5). In cases of stenosis,
severe enough to cause aural atresia would also affect entrapped squamous epithelium may lead to a
other organ systems. The following organs or sys- retention cholesteatoma with bone destruction.
tems may be anomalous in patients with atresia:
neurocranium defects (Crouzon’s disease or cranio-
facial dysostosis), central nervous system (mental
retardation), oral cavity (first and second branchial
arch syndromes), the eye (Goldenhar’s syndrome),
the neck (branchial fistulae), the CHARGE associa-
tion (coloboma, heart defect, choanal atresia,
retarded growth, genitourinary defects, and ear
anomalies), Treacher Collins syndrome (mandibulo-
facial dysostosis), Duane’s syndrome (abducens
palsy with retracted globe), VATER complex (prob-
able disorganization of the primitive streak with
impairment of early mesodermal migration causing
vertebral defects, anal atresia, tracheoesophageal fis-
tula, renal defects, and genital anomalies), and Pierre
Robin syndrome. Chromosomal anomalies affect-
ing the external and middle ears include Turner’s
syndrome and trisomy 13 to 15, 18, 21, and 22
syndromes.7
Anomalies of the ear in the absence of syn-
dromes are usually not familial. From the above
information, it is obvious that other congenital
anomalies should be assiduously sought; some, such
as renal dysgenesis, may not be readily apparent. A
chromosomal analysis may be indicated. As progress
is made in the identification of genes and their prod-
ucts in the recently mapped human genome, the
genetic basis for many of these disorders may pro-
vide a means of treatment or prevention.8
TABLE 42–2. Congenital Atresia Classification the canal is small, a postauricular approach will
improve operative exposure. Frequently, even the
Class I. A. Aerated normal middle ear space young child’s ear canal has a sufficient diameter to
B. Developed oval window with mobile stapes admit an adequately sized ear speculum, even though
C. Oval window not obstructed by facial nerve the length of the canal is shorter.
Class II. A. Narrowed, but aerated, middle ear space Once the middle ear is entered, the surgeon
B. Fixed stapes, oval window aplasia needs to decide if the chain is fixed. If so, what is the
C. Oval window not obstructed by facial nerve cause of the fixation (see Table 42–1). First, the
motility of the incus and malleus is ascertained. Is
Class III. A. Nonaerated, hypoplastic middle ear space
the fixation in the epitympanum and, if not, where
B. Oval window obstructed by facial nerve
(Figure 42–7)? Drilling away the bone over the
C. Tegmen low hanging, obstructs access to
malleus head and body of the incus provides the
middle ear space
required exposure to explore this area. Is the stape-
dial tendon ossified? If the stapes is fixed, mobiliza-
tion may produce a sustained improvement.
patent canal, intact tympanic membrane, aerated Alternatively, a stapedectomy using a replacement
middle ear cleft, normal facial nerve, and mobile prosthesis with an oval window tissue graft to pre-
stapes has the potential for excellent hearing (Table vent a perilymphatic leak may be performed. In
42–2, class I). Conversely, an ear with canal atresia, a some cases, the surgeon may elect to defer stapes
narrowed and poorly aerated middle ear space, and surgery until the child is grown.
an anomalously positioned facial nerve occluding A gap interrupting the ossicular chain’s conti-
the oval window is destined to have poor postoper- nuity occurs most commonly at the incudostapedial
ative hearing (see Table 42–2, class III). Between joint, either owing to absence of the lenticular
these two extremes is an array of anomalies with process and/or long process of the incus or the stapes
variable surgical outcomes. Even with sophisticated arch. The presence of a mobile stapes facilitates the
imaging techniques, the preoperative prediction of surgery and greatly improves the operative result. A
what awaits the otologist is not always accurate.19 variety of techniques have proven useful in the
Surgeons wishing to correct congenital con- restoration of ossicular chain continuity by means of
ductive hearing losses are embarking on a procedure bridging an existing gap. If there is a small distance
with significant potential complications. Generally, between the stapes capitulum and the long process
the initial attempt is the procedure most likely to of the incus, a tragal cartilage graft can successfully
improve the hearing. Unplanned revisions are often negotiate the gap. Deficiencies of the long process of
more complex and less successful. Additionally, if a the incus can be corrected by either interposing the
significant sensorineural hearing loss occurs after reshaped incus between the mobile stapes and the
surgery in a patient with bilateral malformations, the malleus handle or using an alloplastic prosthesis
opposite ear is effectively excluded from surgical cor- designed for this purpose (type III tympanoplasty).
rection since it becomes the better hearing ear. When the stapes arch is absent, similar procedures
Before assuming this responsibility, especially in can be performed to bridge the gap from either the
children, the otologic surgeon must have sufficient malleus handle or the undersurface of the drumhead
experience to maximize the likelihood of a success- to the mobile footplate (type IV tympanoplasty). A
ful outcome. coexisting fixation of the stapes or obstruction of the
The presence of a conductive hearing loss in an oval window by the facial nerve increases the techni-
ear with a normal canal and mobile drumhead gener- cal difficulty, yields poorer hearing results, and
ally indicates that the ossicular chain is not transmit- increases the chance of complications, such as sen-
ting sound energy to the cochlea. Isolated ossicular sorineural hearing loss or facial nerve injury.20
malformations involving the stapes arch and long
process of the incus may not be appreciated on CT Surgery for Microtia and Canal Stenosis or Atre-
studies. In these cases, the middle ear can be explored sia Congenital malformations of the auricle, exter-
by elevating a tympanomeatal flap and assessing the nal canal, and middle ear may occur as isolated
normalcy of the ossicular transduction mechanism. If abnormalities or in various combinations. Recon-
1004 Ballenger’s Otorhinolaryngology
struction of the external ear is usually performed by stage is performed after several months. The auricle
a plastic surgeon, whereas external auditory canal is freed from the scalp, and a split-thickness skin
and middle ear defects are corrected by the otolo- graft is applied to create a postauricular sulcus. At a
gist; both work as a team to achieve the optimal third stage, several months later, the tragus is cre-
result. ated. An alternative technique for the treatment of
Microtia surgery is technically difficult, and severe grade III microtia is to use a lifelike pros-
not infrequently, the results are somewhat disap- thetic ear, which is attached to surgically implanted
pointing. The surgery should be performed by indi- titanium posts that securely hold the auricle in a
viduals with special expertise.21 Auricular normal anatomic position.
reconstruction is an elective procedure. The defor- The timing of the microtia and atresia repairs
mity can usually be masked by a longer hair style. requires close communication between the sur-
Generally, the slight deformity of a grade I microtia geons. Because scarring interferes with the auricular
may be cosmetically acceptable. Reconstruction of a repair, reconstruction of the atresia is deferred until
moderately deformed grade II microtia must be the auricular cartilaginous scaffolding is completed.
individualized. Correction of a severe grade III However, it is important to position the recon-
microtia requires several staged procedures. During structed auricle correctly so that it aligns with the
the first stage, a segment of cartilage is obtained meatal opening and the middle ear. The meatal,
from the lower costochondral skeleton. It is then canal, and middle ear reconstruction is frequently
carved to the appropriate shape to form a scaffold performed as part of the second or third stage of the
for the new auricle. This process requires an artistic auricular reconstruction.13,22
appreciation of the external ear folds. The graft is A postauricular approach is used, with great
implanted into a subcutaneous pocket at the appro- care being taken to avoid exposing the scaffold (Fig-
priate position. A portion of the microtic skin tag is ure 42–8). Temporalis fascia is harvested for recon-
maintained to construct the lobule. The second struction of the tympanic membrane. The
Microtia, Canal Atresia, and Middle Ear Anomalies 1005
periosteum of the lateral surface of the temporal the facial nerve will prevent inadvertent injury. A
bone is elevated. A bony circular canal is created by facial nerve monitor may facilitate identification of
drilling between the glenoid fossa anteriorly and the the nerve in atretic ears.
tegmen plate superiorly while trying to avoid enter- Visualization of the facial nerve as a landmark
ing mastoid air cells posteriorly (Figure 42–9). Con- permits the opening of the atresia plate to approxi-
tinuous suction irrigation cools the bone and clears mate the size of a normal middle ear opening. While
away blood and bone dust while the water enhances drilling on this plate, it must be remembered that
the translucency of the wet bone. This permits visu- the malleus handle may be fused to it. Precautions
alization of structures such as dura, facial nerve, and must be taken to avoid drilling on the mobilized
glenoid fossa through the intact thinned bone. The atresia remnant since this may transmit traumatic
surgeon should anticipate that the facial nerve will vibratory energy through the ossicular chain to the
be located more anteriorly and more laterally than in inner ear and result in a permanent sensorineural
the normal temporal bone. The nerve frequently fol- hearing loss.
lows a C-shaped path in its course between the The status of the ossicular chain is assessed
geniculate ganglion and its point of emergence from (Figure 42–10). If the stapes is mobile, an appropri-
the temporal bone. The purposeful identification of ate ossicular reconstruction is performed (Figure
42–11). If it is fixed or the oval window is obscured compress the skin grafts against the underlying
by the facial nerve, the ossicular reconstruction bone and soft tissue. The postauricular incision is
should be deferred. Temporalis fascia is used to fab- reapproximated using absorbable sutures.
ricate a new tympanic membrane (Figure 42–12). A
meatal opening is made in the area of the imperfo- Risks and Benefits of Atresia Surgery Atresia
rate concha, incising the skin, to create a rectangu- surgery is technically demanding. The results
larly shaped, anteriorly based conchal skin flap. The achieved are directly related to the experience and
underlying cartilage and soft tissue are removed to skill of the operating surgeon. Generally, hearing
debulk the flap and create an opening that commu- improvement to a serviceable level can be achieved
nicates with the drilled out external canal (Figure in approximately 65 to 75% of selected patients.23,24
42–13). The conchal flap is rotated to resurface the Complications of surgery include the small risk of
anterior third of the external canal and is stabilized facial paralysis, a severe to profound sensorineural
by suturing to the adjacent soft tissues (Figure hearing loss, stenosis requiring additional surgery,
42–14). A thin split-thickness skin graft is harvested persistent otorrhea, and tympanic membrane graft
from the lower abdomen and is used to resurface failure with perforation.
the remaining ear canal. The canal is packed snugly In children with a unilateral atresia and a nor-
with Gelfoam (Upjohn, Kalamazoo, Michigan) to mal contralateral ear, surgery may not be routinely
indicated.19 The potential benefit of this sophisti- 11. Schuknecht HF. Congenital aural atresia. Laryngo-
cated surgery, that is, achieving binaural hearing, scope 1989;99:908–17.
may not justify the risk of complications. In binau- 12. Curtin HD. Congential malformations of the ear.
ral cases, the successful creation of an external canal, Otolaryngol Clin North Am 1988;21:317–36.
even when hearing cannot be improved, will allow 13. Jahrsdoerfer RA, Garcia ET, Yeakley JW, et al. Sur-
the use of an ear-level air-conduction hearing aid to face contour three-dimensional imaging in congen-
restore hearing without using a cumbersome bone- ital aural atresia. Arch Otolaryngol Head Neck Surg
conduction aid. Thus, in bilateral cases in which the 1993;119:95–9.
facial nerve obstructs the oval window or when a 14. Andrews JC, Anzai Y, Mankovich NJ, et al. Three-
hearing improvement cannot be achieved, providing dimensional CT scan reconstruction for the assess-
the patient with a stable, skin-lined canal is a worthy ment of congenital aural atresia. Am J Otol 1992;
goal in and of itself. 13:236–40.
15. Jahrsdoerfer RA, Yeakley JW, Hall JW, et al. High-res-
REFERENCES olution CT scanning and auditory brain stem
response in congenital aural atresia: patient selection
1. Lefebvre PP, Malgrange B, Staecker H, et al. Retinoic and surgical correlation. Otolaryngol Head Neck
acid stimulates regeneration of mammalian auditory Surg 1985;93:292–8.
hair cells. Science 1993;260:692–5. 16. Granstrom G, Bergstrom K, Tjellstrom A. The bone-
2. Anson BJ, Davies J, Duckert LG. Embryology of the anchored hearing aid and bone-anchored epithesis
ear. In: Paparella MM, Shumrick DA, Gluckman JL, for congenital ear malformations. Otolaryngol Head
et al, editors. Otolaryngology. 4th ed. Philadelphia: Neck Surg 1993;109:46–53.
JB Lippincott; 1991. p. 3–21. 17. van der Pouw KT, Snik AF, Cremers CW. Audiomet-
3. Williams GH. Developmental anatomy of the ear. In: ric results of bilateral bone-anchored hearing aid
English GM, editor. Otolaryngology. Philadelphia: JB application in patients with bilateral congenital aural
Lippincott; 1990. atresia. Laryngoscope 1998;108:548–53.
4. Nager GT, Proctor B. Anatomic variations and 18. Tjellstrom A, Hakansson B. The bone anchored
anomalies involving the facial canal. Otolaryngol hearing aid (BAHA) design principles, indications
Clin North Am 1991;24:531–53. and long-term clinical results. Otolaryngol Clin
5. Snow JB. Preface. Otolaryngol Clin North Am North Am 1995;115:1–20.
1992;25:xv–i. 19. Trigg DJ, Applebaum EL. Indications for the surgical
6. Jafek BW, Nager GT, Strife J. Congenital aural atre- repair of unilateral aural atresia in children. Am J
sia: analysis of 311 cases. Trans Am Acad Ophthal- Otol 1998;19:679–84.
mol Otolaryngol 1975;80:580–95. 20. Jahrsdoerfer RA, Lambert PR. Facial nerve injury in
7. Sando IS, Shibahara Y, Wood RP. Congenital anom- congenital aural atresia surgery. Am J Otol 1998;19:
alies of the external and middle ear. In: Bluestone 283–7.
CD, Stool SE, editors. Pediatric otolaryngology. 21. Chandrasekhar SS, De la Cruz A, Garrido E.
Philadelphia: WB Saunders; 1990. p. 271–302. Surgery of congenital aural atresia. Am J Otol 1995;
8. Bergstrom LB. Anomalies of the ear. In: English GM, 16:713–7.
editor. Otolaryngology. Philadelphia: JB Lippincott; 22. Bellucci RJ. Congenital aural malformations: diag-
1990. nosis and treatment. Otolaryngol Clin North Am
9. Teunissen EB, Cremers CWRJ. Classification of con- 1981;14:95–124.
genital middle ear anomalies. Report on 144 ears. 23. Shih L, Crabtree JA. Long-term surgical results
Ann Otol Rhinol Laryngol 1993;102:606–12. for congenital aural atresia. Laryngoscope 1993;103:
10. Jahrsdoerfer RA, Yeakley JW, Aguilar EA, et al. Grad- 1097–102.
ing system for the selection of patients with congen- 24. Lambert PR. Congenital aural atresia: stability of
ital aural atresia. Am J Otol 1992;13:6–12. surgical results. Laryngoscope 1998;108:1801–5.
CHAPTER 43
The mouth or oral cavity is divided into two com- styloid, and hyoid bones. They are the genioglossus,
partments: the vestibule or external compartment styloglossus, and hyoglossus and are able to move the
(vestibulum oris) and the internal compartment tongue in various directions. The intrinsic muscles are
(cavum oris). The vestibule is the space external to the superior and inferior longitudinal, transverse, and
the maxillary and mandibular alveolar ridges and vertical and, because of their orientation, impart great
teeth and within the lips and buccal mucosa. Inter- diversity to the movements of the tongue. The tongue
nal to the alveolar ridges and teeth, the oral cavity is attached to the floor of the mouth ventrally and
proper is the space bounded by the hard and soft anteriorly and centrally by the frenulum.
parts of the palate superiorly (ie, the roof of the The posterior third of the tongue is divided
mouth) and the lingual mucosa inferiorly (ie, the from the anterior two-thirds by the sulcus terminalis,
floor of the mouth and covering over the genioglos- which is a V-shaped groove, with its apex being pos-
sus, geniohyoid, and mylohyoid, which lie under the terior (Figure 43–1). The foramen cecum is at the
tongue). The anterior two-thirds of the tongue, apex of the sulcus and marks the origin of the thy-
bound posteriorly by the line of circumvallate papil- roglossal duct. The lingual tonsil constitutes most of
lae, are also part of the oral cavity proper. the posterior one-third of the tongue and varies in
The anterior pillars of the palatine tonsils sep- size. Anteriorly, the tongue is covered by a thin
arate the oral cavity from the oropharynx. mucous membrane closely attached to the underly-
The pharynx is a fibromuscular tube that serves
as a conduit for both the respiratory and digestive
tracts. It is divided regionally into three segments:
Superiorly, the nasopharynx is a posterior extension
of the nasal cavities and ends at the level of the soft
palate. The oropharynx is the region between the soft
palate and the base of the tongue, down to the supe-
rior tip of the epiglottis, bounded laterally by the
palatoglossal and palatopharyngeal arches. The
laryngopharynx is posterior to the larynx and
extends from the superior border of the epiglottis to
the inferior aspect of the cricoid cartilage.
TONGUE
The mobile anterior two-thirds of the tongue are
divided into four parts: tip, lateral borders, dorsum,
and ventral surface. The dorsal surface faces the hard
palate and the ventral surface faces the floor of the FIGURE 43–1. The dorsal surface of the tongue. Fili-
mouth. The lingual muscles are extrinsic and intrinsic. form papillae cover the dorsum. The lingual tonsil and
The extrinsic muscles are attached to the mandibular, palatine tonsils are part of Waldeyer’s ring.
1009
1010 Ballenger’s Otorhinolaryngology
ing muscles. Posteriorly, the mucosa is thick and mandibular gland and the hypoglossal nerve. The
more freely moveable. glossopharyngeal nerve passes around the posterior
border and lateral surface of the stylopharyngeal
muscle to reach the posterior part of the tongue
INNERVATION OF THE TONGUE deep to the hypoglossus muscle.
The motor nerve to the tongue is the hypoglossal The trigeminal nerve (CN V) provides the gen-
(cranial nerve [CN] XII), except for the palatoglos- eral sensation to the anterior two-thirds of the
sus muscle, which receives its innervation from the tongue through the lingual nerve, whereas taste is
glossopharyngeal (CN IX) nerve. The hypoglossal subserved by CN VII (Figure 43–2). The glossopha-
nerve runs forward just above the greater cornu of ryngeal nerve provides both taste and general sensa-
the hyoid bone and has a course along the outer sur- tion to the posterior third of the tongue and the
face of the hyoglossus muscle, where it is accompa- circumvallate papillae.
nied by the lingual vein. The two major sensory
nerves of the tongue are the lingual (CN V3) for the
anterior two-thirds and the glossopharyngeal for the
TASTE BUDS
posterior one-third. The lingual nerve, a branch of Taste buds in the human tongue, soft palate, phar-
mandibular division of the fifth cranial nerve the ynx, larynx, epiglottis, and esophagus are not dis-
also receives the chorda tympani from the facial tributed evenly. Most taste buds are found in the
nerve (CN VII) (Table 43–1). The lingual nerve runs tongue, and in humans, there appear to be fewer
along the lateral border of the tongue above the sub- extralingual taste buds than in laboratory animals.
TABLE 43–1. Relationship of the Branchial Arches and Their Nerves to the Sensation of the Tongue
Neural Branch Cranial Nerve Branchial Arch Sensory Modality Served
Lingual nerve V First arch Sensation to anterior two-thirds of tongue
Chorda tympani VII Second arch Taste to anterior two-thirds of tongue
Glossopharyngeal IX Third arch Taste and sensation to posterior one-third of tongue
In the tongue, taste buds are associated with three Ebner’s glands produce proteins that are involved in
types of gustatory papillae, whereas extralingually, pheromone reception. For these functions to occur,
they are found on smooth epithelial surfaces. The it has been hypothesized that the glands must have
number of taste buds varies among individuals, access to detailed information about the chemical
ranging between 500 and 20,000, with most in the composition of the oral cavity. Supposedly, taste
2,000 to 5,000 range.1 buds in the circumvallate papillae provide this infor-
There are four types of lingual papillae: fili- mation and help to control the activity of Ebner’s
form, fungiform, foliate, and circumvallate. Filiform glands.3
papillae are distributed throughout the dorsum of As stated above, extralingual taste buds are not
the tongue but do not have taste buds and function found on papillae and are instead located within the
in the tactile aspects of feeding. Fungiform papillae epithelium. Extralingual taste buds tend not to be as
are located on the anterior two-thirds of the tongue, well described as those on the tongue but still have
number about 200, and usually contain one taste some pattern of distribution that may be important
bud each.2 They are shaped like mushrooms—hence functionally. Palatal taste buds are often located near
their name, with the taste bud(s) found on their dor- the opening of ducts of mucus-secreting glands.4
sal surface epithelium. The foliate papillae are found Taste buds are made up of 50 to 150 neuroep-
on the posterolateral sides of the tongue. There is ithelial cells arranged in a compact gourd-shaped
only one foliate papilla on each side of the tongue, structure (Figure 43–3). Each receptor cell extends
but each is a large structure arranged in a series of from the basement membrane of the epithelium to
clefts that have grown beneath the tongue surface. the epithelial surface, and the cells are arranged like
The more rostral clefts, or the lateral rugae, contain sections of an orange. At the epithelial surface of
no secretory ducts or taste buds. The more caudal each taste bud, there is a small opening called the
clefts are called the foliate papillae folds and have taste pore, a channel that allows the microvilli of
ducts from lingual salivary glands (Ebner’s glands) taste receptor cells access to gustatory stimuli. Tight
between the folds as well as a thinner epithelial lin- junctions between taste receptor cells restrict the
ing that contains taste buds. Unlike taste buds on access of gustatory stimuli to the microvilli at the
fungiform papillae, these taste buds are not found apices. There are generally four types of cells within
on the dorsal surface epithelium but instead face a each taste bud, and there is no firm agreement about
cleft. In humans, there is an average of 600 taste buds the function or the origin of each type. The four
in each foliate papilla, and each papilla is composed types of cells are basal cells, type I (dark cells), type
of between two and nine folds. The circumvallate II (light cells), and type III (intermediate cells).1
papillae are found on the tongue just anterior to the Basal cells are small, undifferentiated, round
sulcus terminalis. Humans have between 8 and 12 of cells near the basement membrane, from which
them arranged in a V-shaped formation. Circumval- most of the other taste bud cell types are thought to
late papillae are large mushroom-shaped structures be derived. The other three types of cells are more
surrounded by a circular sulcus (vallum) and con- elongated and bipolar, with microvilli at the apices
tain an average of 250 taste buds each. The taste buds and synapses with afferent fibers at the bases. These
are located along the walls of the sulcus, both on the are thought to be the actual taste receptor cells. Over
papillae and on the adjacent epithelium. Secretions 50% of the taste receptor cells are type I, or dark
from Ebner’s glands are released from ducts located cells. They have long microvilli and dense, mem-
at the base of the sulcus.1 brane-bound granules near the cell apex. Type II, or
The function of Ebner’s glands has been under light, cells have shorter microvilli, a lighter cyto-
some debate recently. Traditionally, they were plasm, and membranous vesicles near the apex. Type
thought of as ancillary to taste buds and were mainly III, or intermediate, cells have characteristics of both
involved in simply washing the vallum, but some type I and II cells.1
studies have suggested that they serve some addi- It is unclear whether the existence of four dif-
tional purposes. One of these is the production of ferent cell types means that they have different func-
digestive enzymes, in particular lipase, which is tions or that they come from different cell lines.
important in the neonatal period when the pancreas Some studies suggest that the different cell types are
is still immature. Also, it has been shown that simply cells in different stages of development, with
1012 Ballenger’s Otorhinolaryngology
the basal cells turning into dark cells, which turn of subjective experience. Therefore, it is often neces-
into intermediate cells, which turn into light cells. sary to use the study of animal models, from which,
Other studies suggest that the light cells come from for several reasons, the results are not always gener-
a separate cell line. Nevertheless, all three receptor alizable to humans. Further, it is necessary to qualify
cell types are known to synapse with afferent neu- the concept of primary taste modalities. According
rons, which make the arrangement complex when to Brand, the criteria for the designation of a pri-
cells are turning over. The life span of an individual mary taste quality include
taste cell is only 10 to 14 days, and the cells are con- 1) psychophysical and descriptive data that tend to iso-
stantly being replaced, with the new cells constantly late one primary taste from another on the basis of sta-
re-establishing connections with afferent nerve tistical criteria, 2) electrophysiologic evidence that
fibers to maintain taste sensation.1 reports unique neural transduction features of the
putative taste modality, and 3) biochemical and
molecular biological evidence that identifies and local-
TASTE izes unique receptors and cellular responses to the can-
didate primary modality.5
The world of taste perception and the explanation of
its mechanism of transduction is one convoluted at Generally, these criteria have been fulfilled for
several different levels. Most importantly, taste sweet, salty, sour, and bitter tastes, with evidence
should not be confused with flavor as the latter is gradually proving for umami as well. Umami is the
actually a combined perception of gustation and most recently discovered taste sensation that with
olfaction. Additionally, one must understand that continued research is slowly proving to be the fifth
the study of taste relies on psychophysical percep- primary taste. Since the major prototypical stimulus
tion and is thus prone to the error and complication for this taste has been shown to be the sodium salt of
Anatomy and Physiology of the Oral Cavity and Pharynx 1013
L-glutamic acid (monosodium glutamate), it is not noid process. The condylar process is separated from
surprising that umami means delicious in Japanese. the coronoid process by the mandibular notch,
It is a naturally occurring ingredient in many Asian which forms the concave superior border of the
foods. Given that the central nervous system harbors mandible. On the internal aspect of the ramus is the
a multitude of receptors for glutamate, umami large mandibular foramen, which is the entrance to
research has focused on the similarities and differ- the mandibular canal. The mandibular canal trans-
ences between receptors in the central nervous sys- mits the alveolar vessels and nerves. Branches of
tem and taste cells. For more information on the these vessels and the mental nerve emerge from the
senses of smell and taste, see Chapter 27. mental foramen, inferior to the second premolar
tooth on the lateral side of each mandible. Inferiorly
and slightly anteriorly from the mandibular foramen
FLOOR OF THE MOUTH on the internal surface of the mandible runs the
The floor of the mouth contains the submandibular mylohyoid groove. This groove indicates the course
and sublingual salivary glands and the extrinsic mus- taken by the mylohyoid nerve and vessels. Extending
culature. It is supported by the paired mylohyoid superiorly and posteriorly from the symphysis of the
muscles. The two muscles arise from the mandible mandibular bodies is the mylohyoid line. Just supe-
and insert into a median raphe that extends posteri- rior to the anterior end of the mylohyoid line are
orly to the anterior surface of the hyoid bone. The two small sharp mental spines, which serve as
muscles are so firm that swelling owing to infection attachments for the genioglossus muscle.
above them can encroach on the airway. The palatine processes of the maxillae and the
horizontal plates of the palatine bones form the ante-
rior bony part of the palate (Figure 43–4). In hard
BONES OF THE ORAL CAVITY palates of young people, a suture line, the palatine
The mandibles form the skeleton of the lower jaw raphe, is visible between the premaxillary part of the
and the inferior part of the face They are the largest maxilla and palatine processes of the maxillae. This
and strongest facial bones. Each mandible consists represents the site of fusion of the median and lat-
of two parts: the horizontal body and the vertical eral palatine processes during the twelfth week of
oblong ramus. The ramus ascends vertically from prenatal development. In older people, this suture
the posterior aspect of the body at the angle of the line is often absent. Contained within the hard palate
mandible. The superior part of the ramus has two are several canals. The incisive canal transmits the
processes: the posterior condylar process with a nasopalatine nerve and the terminal branch of the
head, or condyle, and a neck and the anterior coro- sphenopalatine artery. The incisive foramen is
1014 Ballenger’s Otorhinolaryngology
located posterior to the maxillary central incisor lingual artery continues anteriorly and divides,
teeth. Medial to the third molar tooth, the greater sending the deep lingual artery superoanteriorly to
palatine foramen opens on the lateral border of the supply the tip of the tongue and sending the sub-
bony palate. It is the inferior orifice of the greater lingual branch to the sublingual gland and the floor
palatine canal. The greater palatine vessels and nerve of the mouth.
emerge from this foramen and run anteriorly in two
grooves on the palate. The lesser palatine foramina
transmit the lesser palatine nerves and vessels to the
BLOOD SUPPLY OF THE PHARNYX
soft palate and adjacent structures. AND TONSIL
Fixed in the alveoli of the mandibular and The chief blood supply to the pharynx is derived
maxillary bones are teeth. Although not bones, they from the ascending pharyngeal and tonsillar
will be described here for completeness. Deciduous branches of the external maxillary artery and from
teeth begin to develop before birth. The first tooth the descending palatine branch of the internal max-
usually erupts at 6 to 8 months and the last by 24 illary artery (Figure 43–5). The tonsillar arteries,
months of age. The deciduous teeth are shed branches of the external maxillary artery, are the
between 6 and 12 years of age and are replaced by chief vessels to the tonsil, although the ascending
permanent teeth. Eruption of permanent teeth is palatine sometimes takes their place. The tonsillar
usually complete by 18 years of age, except for the arteries (or ascending pharyngeal artery) pass
third molars. If they are malposed or impacted, they upward through the superior constrictor muscle,
may not erupt. There are 10 deciduous teeth in each giving branches to the soft palate and tonsil. The
jaw (2 medial incisors, 2 lateral incisors, 2 canines, dorsal lingual artery ascends to the base of the
2 first molars, and 2 second molars). There are 16 tongue and sends branches to the tonsil and tonsil-
permanent teeth in each jaw (2 medial incisors, 2 lar pillars. The descending palatine artery supplies
lateral incisors, 2 canines, 2 first premolars, 2 second the tonsil and soft palate from above, forming an
premolars, 2 first molars, 2 second molars, and 2 anastomosis with the ascending palatine.
third molars). The permanent teeth are numbered 1
to 32, starting with the right maxillary third molar
as #1 and continuing to the mandible, with the left WALDEYER’S RING
third molar as #17 and the right third mandibular Waldeyer’s ring is a “ring” of lymphoid tissue, which
molar as #32. provides the first contact of ingested or inhaled
pathogens with the lymphoid system intimately
BLOOD SUPPLY TO THE ORAL CAVITY related to epithelium. It is composed of the (1) ade-
noid, (2) palatine tonsils, (3) lingual tonsil, (4) lat- geal constrictor muscle. Condensations of the fascia
eral pharyngeal bands, (5) scattered lymphoid folli- form a capsule. From the tonsillar capsule, trabeculae
cles, and (6) nodules near the eustachian tube. This extend into the parenchyma of the tonsil and support
lymphoid tissue has only efferent lymphatics, much blood vessels, nerves, and efferent lymphatic vessels.
as Peyer’s patches in the bowel, and is strategically Contractions of the superior constrictor, palatoglos-
located to sample everything that enters the aerodi- sus, and palatopharyngeus (as in swallowing) cause
gestive tract. Waldeyer’s ring is involved in the devel- compression of the tonsil. The free surface of the ton-
opment of non–thymus-related lymphocytes or B sil is covered by a closely adherent stratified squamous
cells, particularly in the first few years of life. Pro- epithelium that extends into blind pouches or crypts.
duction of major classes of immunoglobulins and T The epithelium lining the crypts is thin and, in fact,
lymphocytes with intact effector function of cell- may be a semipermeable membrane that “lends” itself
mediated or “delayed” immunity can be attributed to sampling ingested material. The crypts, 8 to 10 in
to elements of the ring. number, are usually compound, extend deep into the
substance of the tonsil, and come into intimate con-
tact with the lymphatic germinating follicles, suggest-
ADENOID ing permeability. With swelling of the tonsil, the
The adenoid (also known as the pharyngeal or bottom of the crypts remains relatively fixed; thus, the
Luschka’s tonsil) is a lobulated mass of lymphoid tis- crypts become longer. The germinating follicles are
sue found on the superior and posterior walls of the centers in which mother cells of the leukocytic group
nasopharynx. The adenoid has no crypts but vertical form young lymphoid cells. The interfollicular tissue
folds lined by respiratory epithelium. It is composed is made up of lymphoid cells in various stages of
of lymphoid tissue in a delicate reticulum of fibers development. Above the tonsil and between the pillars
and acts as a peripherally placed lymph node from is the supratonsillar fossa.
which efferent lymph ducts pass to the cervical chain.
The exposed surface of the adenoid is covered by
stratified and pseudostratified epithelium. Groups of
LINGUAL TONSIL
lymphoid cells are differentiated in the form of more The lingual tonsil constitutes part of the base of the
or less rounded or oval areas with pale centers and tongue and extends from the foramen cecum to the
darker margins. These lymphoid follicles or germ epiglottis. This sessile midline lymphoid accumula-
centers have the pseudonym germ centers of Good- tion is covered by stratified squamous epithelium. It
sir. Unlike the palatine tonsil, the adenoid has no cap- is poorly separated from the tongue musculature by
sule. The incoming air from nasal breathing contacts a layer of fibrous tissue. It consists of numerous
the adenoid, and foreign substances initiate immune rounded or crater-like elevations of lymphoid tissue
responses. The adenoids are capable of considerable in the center of which a duct of a mucous gland
hyperplasia and can obstruct the airway under opens.
adverse conditions (see Chapter 44).
In the midline of the nasopharynx, surrounded
by the adenoid, is a depressed structure, the pharyn-
LYMPHATICS OF THE ORAL CAVITY
geal bursa, which represents the remnants of the The lymphatic drainage of the oral cavity is com-
notochord. Thornwaldt’s disease is an infection of posed of both superficial and deep vessels that ulti-
this bursa. mately drain into the submental, submandibular,
upper jugular, and, occasionally, spinal accessory
lymph nodes. Cancers arising in the buccal mucosa
PALATINE TONSILS primarily drain into the preglandular lymph nodes
The palatine tonsils, also known as the faucial tonsils, of the submandibular triangle and secondarily drain
are grape-like masses of lymphoid tissue lying into the upper jugular lymph nodes of the deep jugu-
between the palatoglossus muscle (anterior pillar) lar chain. Contralateral metastases are infrequent.
and the palatopharyngeus muscle (posterior pillar). The lymphatic network overlying the gingiva
The lateral surface of each tonsil is covered by pha- of maxillary and mandibular bones joins the lingual
ryngeal fascia and attached to the superior pharyn- and buccal surfaces. The preglandular submandibu-
1016 Ballenger’s Otorhinolaryngology
lar lymph nodes represent the primary drainage altered by obstruction caused by infection, neoplastic
route for both systems. involvement, previous surgery, and irradiation.
The superficial lymphatic vessels of the floor of
the mouth connect with the gingival system before
draining to the preglandular submandibular lymph
MINOR SALIVARY GLANDS
nodes (Figure 43–6). The superficial system located There are 600 to 1,000 minor salivary glands
in the anterior part of the floor of the mouth crosses throughout the oral cavity and oropharynx, with the
the midline and drains into either the ipsilateral or greatest concentration found in the palate. The hard
contralateral preglandular lymph nodes. The deep palate has 250 minor salivary glands and the soft
collecting system drains into the same preglandular palate has 150, with their parasympathetic innerva-
lymph nodes before draining into the subdigastric tion coming from the sphenopalatine ganglion. The
lymph nodes of the internal jugular chain. remaining minor salivary glands of the oral cavity
A second pathway bypasses the submandibular and oropharynx receive their parasympathetic
lymph nodes and drains into the jugular omohyoid innervation from the lingual and glossopharyngeal
lymph nodes. Additionally, an efferent upper jugular nerves. Each gland has its own excretory duct emp-
pathway crosses the midline and bypasses the sub- tying directly into the oral cavity or oropharynx. The
mandibular lymph nodes (Figure 43–7). vascular supply, venous outflow, and lymphatic
The tongue possesses both a superficial and a drainage correspond to the region of the oral cavity
deep lymphatic system. No midline separation exists, and oropharynx where the glands are located.
so crossover into contralateral lymphatics is not
uncommon. Lymphatic capillaries in the anterior
portion of the tongue tend to drain into the submen-
PHYSIOLOGY
tal and midjugular lymph nodes, the lymphatics from Saliva is the secretory product of the three paired
the middle third to submandibular or digastric lymph major salivary glands and the 600 to 1,000 minor
nodes, and those from the base of the tongue to the salivary glands. It has a myriad of functions, includ-
upper jugular lymph nodes (Figure 43–8). The nor- ing aiding in digestion, gustation, protection against
mal anatomic configuration of the lymph flow can be infection, dental caries and cancer, mastication, de-
REGULATION OF SALIVA
One to 11⁄2 L of saliva are produced daily. The rate of
FIGURE 43–7. Drawing demonstrating the upper jugular flow varies during the day but averages 1 mL/min.
efferent lymphatic communicating pathway when the During sleep, practically no saliva is produced by the
submandibular group of lymph nodes has been bypassed. major salivary glands. Resting flow is estimated to be
around 0.33 to 0.65 mL/min, which can increase to
1.7 mL/min when stimulated. In the unstimulated is chewed while the tongue constantly repositions it
state, saliva from the major salivary glands is pro- to keep it between the teeth. The soft palate is in con-
duced predominantly by the submandibular glands tact with the tongue, and the tongue holds the food
(69%), followed by the parotid glands (26%) and the in a ball ready to begin the oral stage of swallowing.
sublingual glands (5%). During stimulation, the In the oral stage of the swallow, the tongue and, to
parotid glands significantly increase saliva produc- some extent, the buccal musculature move the food
tion and supplant the submandibular glands with bolus from the front of the oral cavity to the anterior
67% of saliva production. The minor salivary glands faucial arch, where the swallowing reflex is initiated.
remain constant in their production of saliva at 7 The pharyngeal stage has four defined compo-
to 8%. nents: velopharyngeal closure; peristalsis of the
superior, middle, and inferior pharyngeal constric-
tor muscles; airway protection; and cricopharyngeal
SPEECH relaxation. These are reflexive and are mediated in
The production of speech requires a source of air the brainstem in the reticular formation immedi-
flow (lungs), a sound generator (vocal folds), and a ately adjacent to the respiratory center. There is
resonator (pharynx and oral cavity; the nose is coordination between the two centers. The larynx is
included in the resonating chamber when the palate elevated and closed (see Chapter 47), protecting the
is lowered). Articulators change the form of the airway,11 while the piriform sinuses contract and the
vocal tract. The structures that affect articulation cricopharyngeus muscle relaxes.12 These reflex
are the lips, tongue, mandible, teeth, palate, phar- movements are in sequence and overlap one
ynx, and larynx; specifically, the gestures of these another.13 This happens very rapidly as shown on
structures in articulation include opening, pursing, videofluoroscopic analysis, where in a single frame
and tensing of the lips; position, configuration, and (1⁄24 of a second), the barium from the piriform sin-
dynamics of the tip, margins, dorsum, and base of suses empties into the esophagus.
the tongue; opening and closure of the velopharyn- In the final esophageal stage, the bolus moves
geal valve by the palate and pharynx; movement of down the esophagus assisted by gravity, positive
the side walls of the pharynx; and raising and low- external pressure, peristalsis of the esophageal mus-
ering of the larynx. Articulators play the dominant culature, and negative intraesophageal pressure.
role in producing speech sounds represented by
consonants.
The dimensions of the vocal tract affect reso- ACKNOWLEDGMENT
nance. With resonance, formants or dominant fre-
Dr. Lowry expresses appreciation to the following
quencies emerge that can be altered or tuned by
medical students who assisted in the development of
changing the shape of the vocal tract.6–9 Formants
this chapter: Esmael N. Amjad, Jennifer G. Andrus,
are used to produce a voice quality unique to the
Patrick C. Barth, Lisa Grunebaum, Brian Kung,
individual. They determine vowel quality and pro-
Spencer Payne, and Joseph L. Smith.
vide a unique personal voice timbre. The two lowest
formants determine most of the vowel color, and the
third, fourth, and fifth determine the personal voice
timbre (see Chapters 47 and 49).
REFERENCES
1. Linden RWA. Taste. Br Dent J 1993;175:243–52.
2. Slavkin HC. Reflections of taste for oral health pro-
SWALLOWING fessionals. J Am Dent Assoc 1997;128:1697–701.
Swallowing is a complex and complicated function 3. Sbarbati A, Crescimanno C, Osculati F. The anatomy
and is divided into four overlapping phases: oral and functional role of the circumvallate papilla/von
preparatory stage, oral stage, pharyngeal stage, and Ebner gland complex. Med Hypotheses 1999;53:
esophageal stage.10 The first two are voluntary, and 40–4.
the third and fourth are involuntary. In the oral 4. Miller IJ, Bartoshuk LM. Taste perception, taste bud
preparatory stage, the lips are sealed, and the cheeks distribution, and spatial relationships. In: Getchell
tense to hold the muscles close to the teeth. The food TV, Doty RL, Bartoshuk LM, Snow JB, editors. Smell
Anatomy and Physiology of the Oral Cavity and Pharynx 1019
and taste in health and disease. New York: Raven 9. Baer T, Gore JC, Gracco LC, Nye PW. Analysis of vocal
Press; 1991. p. 205–33. tract shape and dimensions using magnetic resonance
5. Brand JG. Receptor and transduction processes for imaging: vowels. J Acoust Soc Am 1991;90:799–828.
umami taste. J Nutr 2000;130 Suppl 4:942–5. 10. Logeman JE. Mechanisms of normal and abnormal
6. Sundberg J. Vocal tract resonance in professional swallowing. In: Schuller DE, editor. Otolaryngology-
voice. In: Sataloff RD, editor. The science and art of head and neck surgery. 2nd ed. St. Louis: CV Mosby;
clinical care. 2nd ed. San Diego (CA): Singular Pub- 1986. p. 1741–9.
lishing Group; 1997. p. 47–64. 11. Donner MW, Bosma JF, Robertson DL. Anatomy
7. Sundberg J, Lindblom B, Liljencrants J. Formant fre- and physiology of the pharynx. Gastrointest Radiol
quency estimates for abruptly changing area func- 1985;10:196–212.
tions: a comparison between calculations and 12. Cook IJ. Cricopharyngeal function and dysfunction.
measurements. J Acoust Soc Am 1992;91:3478–82. Dysphagia 1993;8:244–51.
8. Dang J, Honda K. Acoustic characteristics of the pir- 13. Palmer JB, Tanaka E, Siebens AA. Motions of the
iform fossa in models and humans. J Acoust Soc Am posterior pharyngeal walls in swallowing. Laryngo-
1997;101:456–65. scope 1988;98:414–7.
CHAPTER 44
The oral cavity and oropharynx are contiguous characterized by cough, coryza, conjunctivitis, a gen-
anatomic regions, and diseases of these two areas eralized maculopapular rash, and Koplik’s spots.
should be considered together. A careful and sys- Koplik’s spots are red lesions with a pale blue center
tematic examination of the oral cavity will include and are found on the buccal mucosa, most com-
the oropharynx. These regions are frequently monly opposite the lower molars. They appear 24 to
exposed to the same external factors. Infectious, 48 hours before the rash. With varicella (chicken-
inflammatory, and traumatic conditions frequently pox), a generalized pruritic vesicular eruption usu-
affect both regions. ally begins on the trunk, spreading to the head and
Although the nasopharynx is distinct from the extremities, and is accompanied by mild systemic
oral cavity and oropharynx, the most common pedi- symptoms. Vesicles can affect any mucous mem-
atric conditions affecting this area involve the adenoid brane, including the oral cavity and pharynx. The
tissue either through infection, hyperplasia, or both. vesicles rupture, progressing to shallow ulcers that
In most cases, the tonsils are also involved, and it is resemble aphthous ulcers.
only logical that the adenoids and tonsils be discussed
together. Congenital anomalies and neoplasms of the
nasopharynx are discussed in other chapters.
INFLAMMATORY DISORDERS
Systemic inflammatory diseases frequently affect the
ORAL MANIFESTATIONS OF SYSTEMIC oral cavity and oropharynx. Significant sequelae may
develop if there is a delay in diagnosis and treatment.
DISEASES Behçet’s syndrome is rare in children. It is an
Lesions of the oral cavity and oropharynx may be inflammatory disorder of unknown etiology charac-
presenting signs of an undetected systemic condi- terized by recurrent oral and genital ulcers and ocu-
tion. These regions are readily accessible to the oto- lar inflammation such as uveitis and iridocyclitis.
laryngologist, and with the proper equipment and a The initial complaint is usually that of a painful oral
little patience, a thorough examination can usually ulcer indistinguishable from an aphthous ulcer. The
be performed. Awareness and familiarity of the oral diagnosis should be suspected when the triad of
and oropharyngeal manifestations of systemic dis- findings is present but may be difficult because mul-
eases are important for their early diagnosis. Some tifocal involvement may not occur simultaneously.
diseases can be diagnosed because of a characteristic The most common significant complication is scar-
presentation. Many other signs, however, are non- ring about the eye, leading to visual loss and even
specific, but their presence, especially when accom- blindness. Corticosteroids, chlorambucil, and acy-
panied by symptoms and signs of disease in other clovir have been used to treat this condition.
regions of the body, should alert the otolaryngologist Reiter’s syndrome is another condition of
to the possibility of a systemic condition. unknown cause that is uncommon in children. It
occurs primarily in young men and classically pres-
ents with urethritis, uveitis, conjunctivitis, and arthri-
INFECTIONS tis. Oral lesions often occur and are characterized by
Several common viral childhood infections have superficial, erythematous ulcers, which are sur-
oropharyngeal manifestations. Rubeola (measles) is rounded by white annular lines.1 When the ulcers
1020
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1021
occur on the tongue, the condition may be mistaken rounded by an erythematous rim. These lesions may
for geographic tongue. Although the ulcers usually merge and typically spread symmetrically over the
present after the onset of the disease, their appearance extremities. Oral lesions occur in 50% of cases, usu-
helps to establish the diagnosis. Most children recover ally simultaneously with the skin lesion, but in 25%
without complications. Treatment is supportive. of patients, skin involvement is absent, making diag-
Wegener’s granulomatosis may affect the oral nosis difficult. The lips, tongue, and floor of the
cavity. Gingival hyperplasia is the most common mouth are most often affected. The lesions begin as
early oral lesion.2 Lingual, palatal, and buccal ulcers vesicles and bullae that rupture, producing superfi-
are also common. Characteristically, they are painful cial ulcers and hemorrhagic crusts, especially about
and surrounded by an erythematous rim. the lips (Figure 44–1). The diagnosis is made clini-
Erythema multiforme is an acute inflammatory cally. Treatment of the minor form consists of local
disorder of unknown etiology involving the skin and care and antihistamines. Treatment of Stevens-John-
mucous membranes. Its onset has been associated son’s syndrome requires systemic corticosteroids
with infections, autoimmune disease, emotional and, if possible, eliminating the causative agent.
stress, and medications, including penicillins, Pemphigus vulgaris, pemphigoid, and cicatri-
cephalosporins, and sulfonamides. It affects males cial pemphigoid (benign mucous membrane pem-
more than females and usually occurs in patients 10 phigoid) are autoimmune vesiculobullous disorders
to 30 years old.3 There are two forms of the disease. of the skin and mucous membranes. They occur
Erythema multiforme minor causes minimal skin primarily in patients between 40 and 60 years but
and mucosal damage and is self-limited, lasting 2 to may affect children. Differentiation among these
3 weeks. Erythema multiforme major (Stevens-John- conditions is based on clinical, histologic, and
son syndrome) is associated with systemic manifes- immunologic criteria. All conditions are character-
tations, purulent conjunctivitis, and hemorrhagic, ized by a loss of cohesion among epidermal cells
necrotic skin and mucosal lesions. It is common with (acantholysis), with a resulting cleft and accumula-
drug ingestion and may result in death, primarily tion of intradermal fluid and blisters. In pemphigus
from pulmonary involvement. vulgaris, the cleft is in the suprabasal layer and in
The skin lesions usually begin on the palms pemphigoid at the basement membrane zone. Loss
and feet and are often accompanied by fever, of epidermis by rubbing skin and mucous mem-
malaise, and fatigue. The characteristic appearance is branes (Nikolsky’s sign) occurs in pemphigus vul-
the “target” or “iris” lesion, a central bulla sur- garis but not in pemphigoid.
Pemphigus vulgaris is the most common form incidence in children 1 to 2 years.5 It is characterized
of pemphigus, representing over 90% of cases. It by 4 to 5 days of high fever, bilateral conjunctivitis,
presents initially in the oral cavity in 60% of cases, polymorphous erythematous rash, erythema and
and in over 90%, there will be oral cavity involve- edema of the extremities (Figure 44–2), cervical
ment. In children, almost all cases begin in the oral lymphadenopathy, and oropharyngeal changes,
cavity.4 Vesicles and bullae form and rupture, leaving including strawberry tongue; dry, fissured lips; pha-
painful, superficial ulcers. These lesions are nonspe- ryngeal injection; and necrotic pharyngitis. Early
cific and are often indistinguishable from erythema diagnosis and treatment are paramount. Kawasaki
multiforme. Cases limited to the oral cavity are dif- disease is the most common cause of acquired car-
ficult to diagnose. The presence of lesions on the diac disease in children under 5 years of age. Fifteen
skin and other mucosal surfaces should raise the sus- to 20% of untreated children will develop cardiac
picion for this disease. Patients are treated with cor- complications, with coronary artery aneurysm being
ticosteroids and immunosuppressants. Although the the most serious. Patients are treated with intra-
prognosis is generally good, serious cases can be life venous gammaglobulin and aspirin.
threatening. Sjögren’s syndrome is a collagen vascular dis-
Cicatricial pemphigoid begins in the oral cav- ease characterized by the triad of keratoconjunctivi-
ity in 95% of cases and eventually involves the oral tis, xerostomia, and arthritis. The xerostomia results
mucosa in all cases. Desquamative gingivitis is the from the lymphocytic infiltration of the salivary
most common lesion. The mucosal lesions are char- glands and causes dental caries and fissures and
acterized by recurrent vesicles or small bullae that ulcers of the tongue, lips, and buccal mucosa. A
rupture, causing erosions. The skin and other labial biopsy will establish the diagnosis by demon-
mucosal surfaces are less frequently involved. Bul- strating lymphocytic infiltration of the minor sali-
lous pemphigoid is primarily a cutaneous disease vary glands.
characterized by bullous lesions that rupture, leaving Systemic lupus erythematosus is a generalized
denuded areas. The oral mucosal lesions develop in vasculitis affecting many organ systems. It primarily
40% of cases. Cicatricial and bullous pemphigoid are affects adolescents and young women. Twenty-five
treated with systemic corticosteroids. percent of patients with systemic lupus erythemato-
Kawasaki’s disease (mucocutaneous lymph sus have oral lesions. Xerostomia and its associated
node syndrome) is an acute multisystem vasculitis conditions are common. Other findings include
of unknown etiology. It is a disease occurring pri- petechiae, hemorrhagic bullae, and white keratotic
marily in children under 5 years of age, with a peak plaques on the tongue and oral mucosa.6
be involved. In addition, vesiculopapular lesions are mucosa and near the vermilion borders, forming
found on the palms and soles.7 Associated pain and typical “cold sores,” and rupture over a course of 10
fever may occur. This disease is self-limited, and the to 14 days. Herpes labialis develops when the lips are
treatment is supportive. involved. In most cases, treatment is symptomatic,
but acyclovir may be beneficial.
Herpes Simplex Herpes simplex virus (HSV)
infection may present in two ways in the orophar- Herpes Zoster Herpes zoster results from reacti-
ynx: a primary infection, primary herpetic gingivos- vation of the dormant varicella virus in the sensory
tomatitis, and recurrent or secondary herpes. ganglia. Oral and skin lesions develop along the dis-
Primary herpetic gingivostomatitis is a common ill- tribution of the second and third branches of the
ness in the preschool child. Initially, it begins with a trigeminal nerve. A classic trigeminal skin pattern
prodrome of nonspecific symptoms, including fever establishes the diagnosis. Herpes zoster is uncom-
and malaise. Within a day or two, the oral mucosa mon in infants and children and usually occurs in
becomes painful and erythematous. Vesicles form elderly patients. Treatment is with topical antiviral
and rupture within 24 hours, and the ulcers heal in agents such as acyclovir.
about 2 weeks. The ulcers form a gray pseudomem-
brane, may coalesce, and cover most of the oral cav- Cytomegalovirus Infection Cytomegalovirus
(CMV) is a member of the herpes family, and CMV
ity (Figure 44–3). Diffuse bilateral lymphadenopathy
infections are becoming more prevalent, especially
is common. In addition to the oral mucosa, lips, and
with the increasing number of immunosuppressed
tongue, the gingiva is almost always affected but
and immunodeficient patients. In the oral cavity,
often without the formation of vesicles. Diagnosis is
these infections are characterized by large ulcers of the
made by viral studies and biopsy, which will reveal
mucosa and exudative pharyngotonsillitis, which is
intranuclear inclusion bodies.
similar to that of infectious mononucleosis but less
The HSV will remain dormant in the neuro-
severe. Frequently, there is an associated cervical lym-
ganglion cells for life. Activation of the virus will phadenopathy. Treatment is primarily symptomatic.
result in recurrent herpes. Precipitating factors
include sunlight, fever, bacterial infections, stress, Infectious Mononucleosis Oropharyngeal signs
immunodeficiency, and other systemic illness. Clin- are prominent in infectious mononucleosis. Chil-
ically, there may be an initial period of burning in dren, adolescents, and young adults frequently pres-
the mouth. Multiple vesicles appear on the oral ent with a sore throat, grossly enlarged tonsils with a
gray membraneous exudate, and edema and the oral cavity and oropharynx. The virus causes the
petechiae of the soft palate (Figure 44–4). Other formation of exophytic, cauliflower-like lesions.
manifestations include cervical lymphadenopathy, Papillomas are found most commonly on the soft
which can be marked, hepatosplenomegaly, fever, palate and tongue. Treatment involves surgical exci-
malaise, and fatigue. Treatment is usually support- sion with a laser, electrocautery blade, or knife. His-
ive, but when the tonsillar hypertrophy and pharyn- tologic analysis establishes the diagnosis and should
geal edema cause respiratory distress, corticosteroids always be performed because of the possibility of
are used. malignant transformation. Recurrences of papil-
loma in the oral cavity and oropharynx are relatively
Human Immunodeficiency Virus Infection uncommon after complete excision.
There are at least 40 oral manifestations of human
immunodeficiency virus (HIV) infection, and the
most common sites of involvement are the palate,
BACTERIAL INFECTIONS
tongue, lips, and buccal mucosa.8,9 Signs that suggest Streptococcal Infections Group A beta-hemolytic
the possibility of HIV infection include oral candidi- streptococcus may cause severe pharyngitis. Patients
asis; recurrent herpetic and aphthous ulcers; angular complain of fever, malaise, sore throat, odynophagia,
cheilitis; hairy leukoplakia, a white corrugated lesion dysphagia, otalgia, and halitosis. The oropharynx and,
found at the lateral borders of the tongue; periodon- to a lesser extent, the oral cavity are swollen and red,
titis; gingivitis, especially bleeding ulcerative gingivi- and the tonsils are covered with exudates. Strawberry
tis; papillomas; and diffuse parotitis. Kaposi’s tongue, small red spots on the tongue, is a common
sarcoma is highly suggestive of HIV infection. In the finding. Examination of the neck may reveal swollen,
oral cavity, it may present early as a pigmented mac- tender lymph nodes. Since other bacterial pathogens
ule, papule, or patch or as a hemorrhagic lesion. may account for a similar presentation, cultures are
These lesions may progress to necrosis and ulcera- required to make a definitive diagnosis. Scarlet fever
tion. Later, Kaposi’s sarcoma may appear as a lobu- produces a diffuse erythematous rash that is caused
lated tumor with or without ulceration. In children, by an erythrogenic toxin produced by the group A
the most common signs of HIV infection are oral beta-hemolytic streptococcus. Rheumatic fever and
candidiasis, diffuse parotitis, and oral ulcers.10 glomerulonephritis are potential complications of
streptococcal pharyngitis. When streptococcus is sus-
Recurrent Respiratory Papillomatosis The pected, antibiotics should be started before culture
human papillomavirus causes recurrent respiratory results have been reported. Penicillin and amoxicillin
papillomatosis of the airway and may also involve are initial choices.
Diphtheria Diphtheria, which is caused by Patients complain of burning, dryness, and pain in
Corynebacterium diphtheriae, is rare in the United the mouth. Thrush is characterized by the presence
States but not uncommon in other parts of the world. of fine white lacey plaques covering the mucosa of
The primary site of involvement is the oropharynx, the oral cavity, usually the tongue, hard palate, and
where it presents as a necrotizing pharyngitis associ- buccal mucosa. When the plaque is disrupted, a raw
ated with severe erythema and a thick pseudomem- surface remains. In children with diabetes or
brane. The disease may progress to involve the larynx immunodeficiency, severe invasive oropharyngeal
and trachea, leading to airway obstruction. The bac- and esophageal candidiasis may develop. The diag-
teria produce exotoxins, which may cause systemtic nosis is usually made on clinical grounds. Smears
symptoms, including cardiac and neurologic seque- may demonstrate hyphae, but cultures are required
lae. Corynebacterium diphtheriae may be identified on for a definitive diagnosis.
stains from the pseudomembrane, but cultures are Acute atrophic candidiasis occurs primarily as
required for definitive diagnosis. Treatment for diph- a result of long-term antibiotics, long-term corticos-
theria consists of airway support, antitoxin, and teroids, or immunosuppressive agents and is much
antibiotics (see Chapter 52). less frequent than thrush. Patients complain of sore
throat, burning of the mouth, and foul taste. Exam-
Syphilis and Gonorrhea Both syphilis and gon- ination reveals red, ulcerated mucosa rather than a
orrhea may involve the oral cavity and oropharynx. pseudomembrane.
A classic feature of congenital syphilis is Hutchin-
Angular cheilitis is manifest by pain and ery-
son’s teeth, hypoplastic teeth with notching of cen-
thema and microfissures at the oral commissure. As
tral incisors. Rhagades, atrophic glossitis, and a high
the condition continues, erosions of the skin and
arched palate are other common oral signs. In
desquamation of epithelium surrounded by hyper-
acquired syphilis, the primary lesion is a chancre,
keratosis develop.
an enlarging ulcer surrounded by induration. If
Before treating a candidal infection, a search for
untreated, this resolves spontaneously, but second-
an underlying condition should be made. Most chil-
ary mucosal lesions, most commonly superficial
dren can be treated with a topical, antifungal agent,
ulcers covered by a grayish-white membrane, will
and if this fails, a systemic agent such as ketoconazole,
develop. The oral lesions of tertiary syphilis include
fluconazole, and even amphotericin can be used.
gummas of the palate, granulomatous lesions that
may destroy and perforate the palate, and atrophic Other fungal agents may occasionally involve
glossitis. Although it is uncommon, gonorrhea may the oral cavity. Histoplasmosis may cause ulcers in
affect this region, primarily the oropharynx. A gono- the oral cavity. In immunosuppressed and chroni-
coccal infection must be considered in any patient cally ill patients, mucormycosis may manifest as an
presenting with a membranous pharyngitis (see ulcer or granuloma, usually on the hard palate.
Chapter 30).
MISCELLANEOUS CONDITIONS OF THE ORAL
FUNGAL INFECTIONS CAVITY
Candidiasis is the most common fungal infection of Leukoplakia Leukoplakia is characterized by the
the oral cavity. Candida albicans is an opportunistic presence of a white plaque on the oral mucosa. It is
microorganism and part of the normal oral flora. primarily a condition of adults and has a prevalence
When there is a reduction in the normal oral flora or of 0.1 to 5%. It is considered a precancerous lesion,
a decrease in the host resistance, it becomes increas- with malignant transformation occurring in 2 to 6%
ingly prevalent and causes an overt infection. Pre- of patients. If the plaque adheres to the mucosa and
disposing conditions include long-term antibiotic keratosis is present, the chance of malignancy
use, diabetes, corticosteroid therapy, and any condi- increases. Although it is uncommon in children, it
tion causing immunosuppression. Three presenta- has been noted in children with candidiasis and
tions are common in children. some viral infections.
Pseudomembranous candidiasis (thrush) is the Hairy leukoplakia is characterized by slightly
most common candidal infection in the oral cavity. elevated, corrugated white plaque usually found on
It occurs in all age groups but most often in infants. the lateral borders of the tongue. It suggests the
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1027
development of acquired immune deficiency syn- painful, multiple, pinpoint ulcers. These ulcers may
drome (AIDS) in patients with HIV infection. coalesce, leaving large, irregular ulcers. Herpetiform
lesions are found in all locations in the oral cavity,
Aphthous Stomatitis Recurrent aphthous stom- persist for 1 to 2 weeks, and recur at 1- to 3-year
atitis is the most common condition affecting the intervals. Treatment for all forms of aphthous stom-
oral mucosa. The exact etiology is unknown, but atitis is symptomatic. Topical corticosteroids, topi-
recent studies suggest that an altered cellular cal lidocaine, and mouthwashes may reduce the
immune response is a predisposing factor. It occurs pain. In severe cases, intralesional or systemic corti-
in all age groups but usually appears initially in older costeroids and acyclovir may help.
children and adolescents. The condition is more
common in females. Twenty-four to 48 hours before Lichen Planus Lichen planus is a common
the appearance of the ulcers, there is a prodrome of inflammatory disorder of the skin and mucous
a tingling, burning feeling and erythema in the oral membranes. It primarily affects middle-aged adults
cavity. There are three forms of ulcers based on their but may occur in older children and adolescents. Its
size, number, and duration. Minor aphthous ulcers cause is unknown, but the disease is a cell-mediated
occur in 80% of the cases. They are painful, shallow, immune response that has been associated with sev-
ovoid ulcers less than 0.6 cm in size. The ulcers are eral autoimmune diseases. Oral lichen planus is
covered by a gray membrane and surrounded by a usually found on the tongue, buccal mucosa, and
red halo. They may be found alone or in groups, gingiva. It may follow a course of exacerbations and
most often on nonkeratinized oral mucosa, such as remissions. There are two variants. The reticular
the buccal mucosa, lips, and tongue. They resolve form, the most common type, is characterized by
within 2 weeks without scarring and usually recur in small white papules, which may be isolated or may
1- to 5-month intervals. Major aphthous ulcers are a coalesce to form interlacing white lines (Wickham’s
more severe form of the condition. They are charac- striae). They frequently occur with bilateral sym-
terized by one to five ulcers that are larger than 0.6 metry. The reticular form causes no symptoms. The
cm and more painful than minor ulcers (Figure erosive form is manifested by painful ulcers with
44–5). In addition to the sites of minor ulcers, major papules or lines at the periphery. Malignant trans-
ulcers also occur on the soft palate, floor of the formation may potentially occur with the erosive
mouth, and peritonsillar area. They persist for 3 to 6 form. Diagnosis is established by a biopsy of the
weeks, may leave a scar, and recur in 1- to 3-month edges of the lesions. Asymptomatic lesions require
intervals. Herpetiform ulcers, the least common no treatment, whereas painful ones may be treated
form of the condition, are characterized by crops of with topical, injectable, or systemic corticosteroids.
Burning Mouth Syndrome Burning mouth syn- Fissured Tongue This condition is characterized
drome is a disorder of peri- and postmenopausal by multiple fissures or grooves on the dorsum of the
women. Patients complain of burning on the tip and tongue. The fissured tongue is usually asymptomatic
lateral border of the tongue, which appears normal. but may become irritated if food particles, bacteria,
It is caused by a local neuropathy. Treatment or fungi become trapped in the fissures. It is believed
includes amitriptyline and clonazepam. to be an inherited disorder and has been associated
with the genetic disorders Melkersson-Rosenthal
Median Rhomboid Glossitis Median rhomboid syndrome and Down syndrome. Melkersson-Rosen-
glossitis is a congenital disorder caused by the per- thal syndrome is characterized by recurrent facial
sistence of the tuberculum impar. As a result, a rhom- nerve palsy and edema of the face and mouth. Fis-
boid area free of papillae appears on the dorsal suring of the tongue is not pathognomic of Melk-
surface of the tongue. It may present as a smooth, red ersson-Rosenthal syndrome but occurs frequently in
plaque or a firm, raised, smooth, red mass (Figure it. No treatment is required.
44–6). Some cases have been associated with Candida
infections. In most cases, no treatment is necessary. Hairy Tongue This is a common disorder that is
characterized by the hypertrophy and growth of the
Geographic Tongue Geographic tongue (benign filiform papillae on the dorsal surface of the tongue,
migratory glossitis) occurs in all age groups, with a giving the tongue a hairy appearance. The papillae
prevalence of 1 to 2%. Although the exact etiology may become colonized with pigmented bacteria, pro-
is unknown, it may be an inherited condition. The ducing multiple colors. Black hairy tongue is a com-
condition results from a loss of filiform papillae. It mon presentation. The cause remains unknown,
is characterized by a white margin of desquamating although certain predisposing factors have been iden-
epithelium of various sizes and shapes on the dor- tified, including tobacco abuse, oral antibiotics, poor
sum of the tongue surrounding a central, red, oral hygiene, and radiation therapy. The disorder is
atrophic area (Figure 44–7). These lesions disappear benign and usually asymptomatic. Long papillae may
and migrate to other areas of the tongue. Similar cause discomfort and may be treated with brushing.
lesions may occur on the oral mucosa. The condi-
tion is chronic and may persist for years. Treatment Macroglossia The tongue may appear enlarged in
is not necessary. many conditions. Relative macroglossia occurs when
the tongue is normal in size, but anomalies of the the floor of the mouth and presents as a soft, pain-
surrounding structures make it appear large. Pierre less, ballotable, submandibular mass. It may present
Robin syndrome and Down syndrome are two such with or without intraoral involvement, with the
examples. Primary macroglossia is hypertrophy of diagnosis being more difficult if there is no visible
the tongue musculature, whereas secondary intraoral lesion. Simple ranulas may be treated with
macroglossia is caused by infiltration of tongue tis- marsupialization or excision of the sublingual gland.
sue.11 Causes of primary macroglossia include Excision of the sublingual gland with evacuation of
hypothyroidism, acromegaly, and Beckwith-Wiede- the ranula is the recommended treatment for plung-
mann syndrome. Beckwith-Wiedemann syndrome ing ranulas.
is an autosomal genetic disorder characterized by
organomegaly, omphalocele, hypoglycemia, and
DENTAL INFECTIONS AND CYSTS
macroglossia. Many children with this syndrome are
at risk for developing airway obstruction. The causes Dental infections arise from dental caries, trauma to
of secondary macroglossia are varied and include the teeth, and periodontal disease. The pulp of the
lymphangioma, hemangioma, rhabdomyosarcoma, tooth becomes inflamed and then necroses, leading
angioneurotic edema, amyloidosis, glycogen storage to low-grade chronic inflammation or abscess for-
diseases, neurofibromatosis, actinomycosis, syphilis, mation. The infected tooth will be painful, tender,
and tuberculosis. sensitive to changes in pressure and temperature, and
slightly mobile and will feel raised. The surrounding
Ranulas There are two types of ranulas, and they gingiva will be raised and inflamed, and a draining
occur in all age groups. The simple ranula is a cystic fistulous tract may develop, indicating pulpal necro-
lesion of the floor of the mouth representing either sis and abscess in the root canal. A tract may even
a mucocele from obstruction of the sublingual gland develop to the face. Electrical vitality testing may
or a mucus extravasation pseudocyst from the sub- demonstrate diminished or absent responses. Dental
lingual gland.12 It appears as a blue, superficial, non- infections may remain localized to the dentoalveolar
tender, fluctuant mass and is usually found on one process; spread along fascial planes to other regions
side of the floor of the mouth (Figure 44–8). Small of the face, head, and neck; or become disseminated.
ranulas are asymptomatic, whereas larger ones may As the infection progresses, radiographic findings
cause speech and swallowing problems. The plung- appear and include widening of the periodontal
ing ranula is less common. It arises from a mucus membrane space, radiolucency of the periapical
extravasation pseudocyst that has extended through bone, and osteitis and destruction of the alveolar
1030 Ballenger’s Otorhinolaryngology
bone. The extent and severity of the infection do not frequent recurrences, despite surgery. Other odon-
correlate with the radiographic findings.13 Treatment togenic cysts include the developmental lateral peri-
of dental infections consists of antibiotics and root odontal cyst and botryoid odontogenic cyst.
canal therapy or tooth extraction.
Inflammation of the tooth pulp, gingiva, and BENIGN LESIONS OF THE GINGIVA,
periodontal structures may cause epithelial prolifer-
ation, leading to the development of certain odon-
MANDIBLE, AND MAXILLA
togenic cysts. The periapical cyst accounts for at Many benign soft tissue lesions arise from the gingiva.
least 65% of odontogenic cysts. Necrosis of the The pyogenic granuloma is a smooth, red, soft,
tooth pulp causes chronic inflammation, leading to pedunculated lesion that bleeds easily. It develops as a
granuloma formation. Further inflammation within response to trauma and is treated by local excision.
the granuloma stimulates cyst formation. The most The peripheral giant cell reparative granuloma also
common symptom is discomfort with biting. Large develops from trauma. It presents as a sessile reddish
cysts may present as compressible masses in the mass of vascular tissue that bleeds easily and is most
palate or vestibule. Radiographically, the periapical often found on the gingiva anterior to the premolars.
cyst appears as a well-defined periapical lucency. Treatment is with excision or curettage. Epstein’s
Dental cysts, which develop from the gingiva, and pearls are small keratin cysts found on the alveoli or
inflammatory follicular cysts, which develop from palate of the newborn. They are transient, exfoliating
dental follicles of unerupted permanent teeth, occur within a few weeks. The congenital epulis is usually
infrequently. found on the anterior maxillary gingiva, presenting as
The dentigerous cyst, the second most com- a pink, round, lobulated, pedunculated, mucosa-cov-
mon odontogenic cyst, develops from expansion of ered mass. Excision is curative. The melanotic ecto-
an impacted tooth follicle. It occurs most often in dermal tumor of infancy occurs in the first 6 months
the mandibular third molar. Most of these cysts are of life and usually on the anterior maxilla near the
asymptomatic and are found on dental radiographs. junction of the globular and maxillary processes. It
Large cysts may expand, causing displacement of presents as a firm, well-circumscribed mass that may
adjacent structures, infections, and pathologic jaw be pigmented and may cause facial swelling and nasal
fractures. Radiographically, it appears as a unilocu- obstruction. Treatment is complete excision.
lar, pericoronal radiolucency. The odontogenic ker- A variety of benign tumors develop from the
atocyst is associated with bone destruction and mandible and maxilla. Odontogenic tumors arise
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1031
from the precursors of tooth formation. The odon- TONSILS AND ADENOID
toma, the most common odontogenic tumor, is a
Diseases of the tonsils and adenoid are some of the
hamartoma arising from a mixture of dentin,
most common problems seen in children. Adenoton-
enamel, and cementum. It is often associated with
sillar disease can be broadly classified as infectious,
dentigerous cysts. It grows by expansion but rarely
obstructive, and miscellaneous. The “miscellaneous”
becomes large enough to be symptomatic. Treat-
group includes unilateral tonsillar hypertrophy and
ment is with enucleation. The ameloblastoma arises
tonsilloliths.
from tissue involved in enamel formation. Initially, it
presents as a painless, hard mass, but cystic degener-
ation and softening develop. Ameloblastomas may INFECTIONS
be locally aggressive, infiltrating into adjacent tissue
Tonsillitis Acute tonsillitis is defined as an acute
and causing significant deformity. Radiographs
infection of the tonsils with symptoms of sore throat,
demonstrate a multicystic, osteolytic, and expansile
fever, odynophagia, and general malaise. Physical
lesion.14 Treatment is complete excision. Myxomas
findings include tonsillar hypertrophy and erythema
occur most often in children over 10 years of age and
and exudates on the tonsillar surfaces. There may be
young adults. They also present as painless masses,
associated cervical lymphadenopathy, skin rashes,
often associated with loose teeth. Myxomas are
and fever. The disease is usually self-limited, lasting
locally aggressive, infiltrating into neighboring bone.
from 7 to 14 days, but during this period there may
They require wide resection, but recurrence is not
be significant loss of time from school or work.
uncommon. Adenoameloblastoma, cementoma, and
An episode of acute tonsillitis may progress to
cementoblastoma are rare odontogenic tumors.
recurrent acute tonsillitis, repeated episodes of acute
Nonodontogenic tumors of the jaws arise from
tonsillitis followed by periods in which the patient is
tissues other than dental precursors. The most com- asymptomatic. During each acute episode, the
mon lesion is the torus, an exophytic, mucosa-covered, patient may develop symptoms of acute tonsillitis.
bony overgrowth. It is usually noted after puberty. It In addition to the signs of acute tonsillitis, patients
occurs in the midline of the palate in 20% of the pop- experiencing recurrent acute tonsillitis may develop
ulation. In 8% of the population, a torus occurs near enlarged tonsillar crypts that accumulate debris, per-
the midline of the lingual surface of the mandible, and sistent erythema of the tonsils, and dilated blood
80% of these mandibular tori are bilateral. Most are vessels on the surface of the tonsils.
asymptomatic and require no treatment. Many pathogens may be cultured from the sur-
Fibrous dysplasia of the jaws is found more face and the core of the tonsils and may cause acute
often in the maxilla and is usually monostotic. It fre- tonsillitis. Of greatest concern is group A beta-
quently presents as painless swelling in the canine hemolytic streptococcus because it may lead to the
fossa or zygoma. These lesions grow rapidly from development of rheumatic cardiac disease and
early childhood to early adolescence, causing facial glomerulonephritis. Group A beta-hemolytic strep-
swelling and even proptosis. With puberty, fibrous tococcus may be isolated on the tonsil surface but in
dysplasia tends to stabilize. Conservative subtotal up to 60% of cases may be found deep within the
resection is recommended for lesions causing cos- tonsillar crypts.15 Therefore, cultures of the tonsil
metic or functional problems. surface may not detect group A beta-hemolytic
The giant cell reparative granuloma occurs pri- streptococcus as the cause of acute tonsillitis.
marily in patients 10 to 20 years of age and more Treatment of acute tonsillitis should be based
often involves the mandible. It presents as a non- on clinical judgment, taking into consideration the
tender intraoral mass with an accompanying entire clinical picture rather than just cultures of the
mandibular deformity. This lesion is treated with tonsil surface. Antimicrobial therapy may be started
curettage or excision. Other causes of nonodonto- even in the absence of a positive culture for group A
genic tumors of the jaws include osteoma, eso- beta-hemolytic streptococcus. In most cases, peni-
sinophilic granuloma, aneurysmal bone cysts, cillin and amoxicillin are the initial drugs of choice.
hemorrhagic bone cysts, and cherubism. Malignant If there is a history of treated recurrent acute tonsil-
neoplasmas of the oral cavity and oropharynx are litis, the responsible pathogens are likely to be β-lac-
discussed in Chapter 61. tamase-producing bacteria, and a β-lactamase-stable
1032 Ballenger’s Otorhinolaryngology
antibiotic, such as amoxicillin-clavulanate, should of the soft palate. The oral airway may be compro-
be used.16 mised. The diagnosis of a peritonsillar space infec-
Some patients may be carriers of group A beta- tion is usually made clinically, but it may be difficult
hemolytic streptococcus. If the patient is asympto- to distinguish between cellulitis and an early abscess.
matic, no treatment is necessary. Patients who Patients with a suspected peritonsillar infec-
experience frequent episodes of acute tonsillitis, tion should be hydrated and given intravenous
infect other patients, or develop complications antibiotics and analgesics. If there is no improve-
should be treated. An initial course of antibiotics ment after 48 hours, airway compromise, or definite
may eradicate the bacteria and carrier state. Adeno- abscess formation, drainage should be considered.
tonsillectomy is indicated for treatment failures. There is no consensus regarding the best technique.
Children who continue to experience recurrent Options include needle aspiration, incision and
acute tonsillitis, despite adequate antibiotic therapy, drainage, and immediate tonsillectomy. Needle aspi-
should be considered for tonsillectomy and ade- ration and incision and drainage have success rates
noidectomy. In over 70% of cases, core tonsil and greater than 90%, but there is a 10 to 15% risk of
core adenoid tissue harbor the same pathogens, and abscess recurrence.19 Immediate tonsillectomy is
both tonsillectomy and adenoidectomy lead to their curative and prevents recurrence, but in many
eradication.17 Patients with three or more episodes patients, tonsillectomy may not be necessary. Tonsil-
of acute tonsillitis within a year are candidates for lectomy should be performed in patients with a his-
tonsillectomy and adenoidectomy.18 It is important tory of recurrent infections or previous abscess.
to document the dates of the last two infections,
degree of fever, severity of disease, results of any Adenoiditis The adenoid tissue may become
throat cultures, and response to antibiotics. infected during an upper respiratory tract infection,
Chronic tonsillitis is defined as persistent ton- causing fever, nasal obstruction, purulent rhinor-
sillar infection and usually occurs in older children rhea, postnasal discharge, and cough. These signs
and young adults. Patients complain of constant and symptoms are nonspecific and can occur with
throat pain, halitosis, and fatigue. Examination of respiratory tract infections and sinusitis. Examina-
the tonsils reveals hypertrophy, erythema, and tion with a mirror or telescope may demonstrate
enlarged crypts filled with debris. Chronic tonsillitis inflamed, swollen adenoid covered with exudates.
is treated with tonsillectomy if the symptoms are Treatment is with antibiotics, and if the condition
severe or the persistent infection interferes with nor- becomes recurrent, antibiotics with activity against
mal activities. β-lactamase-producing microorganisms are recom-
mended. If the condition persists, adenoidectomy is
Peritonsillar Infections Peritonsillar infections performed.
occur in all age groups but more often in adolescents The relationship between adenoid infections
and young adults. It is the most frequent head and and sinusitis has not been clearly established. Since
neck space infection in children and the most com- the presentation of these two conditions is similar,
mon complication of acute tonsillitis. Infections of adenoiditis may be misdiagnosed as sinusitis, and
the tonsillar crypts extend beyond the tonsillar cap- adenoiditis may be a causal factor in pediatric
sule to involve the peritonsillar space. Most infec- sinusitis. In a child with chronic sinusitis, it has been
tions occur in the superior pole of the tonsil, but suggested that an adenoidectomy be performed a
some involve the midtonsillar area and inferior pole. minimum of 3 months prior to pediatric endoscopic
The infection begins as a cellulitis and progresses to sinus surgery.20 If there is significant improvement of
an abscess. symptoms, sinus surgery may be avoided.
Patients complain of fever, unilateral sore
throat, odynophagia, and trismus. The examination
may be difficult because of the inability to open the
OBSTRUCTION
mouth. The classic signs include a muffled voice; Upper airway obstruction is the second most com-
drooling, unilateral swelling, and erythema of the mon indication for tonsillectomy and adenoidectomy
superior tonsillar pole; deviation of the uvula to the in children and may present in an acute or chronic
opposite side; and bulging of the posterolateral part fashion. Infections, such as mononucleosis or peri-
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1033
tonsillar abscess, may cause acute upper airway flow at both the mouth and nose during sleep. There
obstruction. With a history of sore throat and dys- is a repetitive hypopnea (reduction in breathing) or
phagia, examination may reveal an acute infection apnea (cessation of breathing). Obstructive sleep
with signs of airway obstruction. Some children may apnea is caused by an obstruction in the upper air-
be managed as outpatients with antibiotics and corti- way, and there is a vigorous effort to overcome this
costeroids. Others may require hospitalization, espe- obstruction. Obstructive sleep apnea must be distin-
cially to monitor and secure the airway. If symptoms guished from the less common central sleep apnea in
persist, an emergency tonsillectomy and adenoidec- which the cause is in the brainstem. With central
tomy may be required. These patients may need to sleep apnea (CSA), the neural drive to the respira-
recover in a carefully monitored environment such as tory muscles is temporarily abolished, and there is
a pediatric intensive care unit. Sudden relief of upper little effort to breathe.
airway obstruction may cause postobstructive pul- If the diagnosis is equivocal, a lateral neck
monary edema. Fluid may extravasate into the alveoli radiograph can be performed to assess the size of
with a rapid change in intrathoracic pressure. Imme- the tonsils, adenoid, and nasopharyngeal airway.
diate recognition of this problem is essential. Treat- Either polysomnography or sleep sonography will
ment consists of intubation with the administration provide objective data regarding the presence and
of positive end-expiratory pressure and diuretics. degree of obstruction. During polysomnography,
Chronic upper airway obstruction most often the frequency of apneas per hour (apnea index),
occurs when both tonsils and adenoid are enlarged apneas and hypopneas per hour (hypopnea-apnea
but may occur when either is enlarged. A thorough index), and arousals per hour (arousal index) is
history is important to establish the diagnosis. Ques- recorded. The severity of oxygen desaturation,
tions regarding mouth breathing, snoring, snorting, degree of hypercapnia, and frequency and grade of
gasping, and apnea should be elicited. Parents should any cardiac arrhythmia should also be recorded.
be asked about a child’s sleep habits. Restless sleep, Although polysomnography provides the best
extension of the neck during sleep, enuresis, frequent objective measurement for obstruction, it is expen-
waking, growth disturbances, and failure to thrive sive and inconvenient for most children and their
suggest airway obstruction. Dysphagia and choking families. For normal, nonsyndromic children, there
on solid foods indicate obstructing tonsils, whereas is a close correlation between the results obtained
hyponasal speech suggests enlarged adenoid tissue. from polysomnography and sleep sonography.21
The obstruction is related to the relative size of
the tonsils and adenoid. An oral examination will
usually reveal enlarged, obstructing tonsils. MISCELLANEOUS CONDITIONS
Nasopharyngeal examination, which is usually per- Tonsilloliths Tonsilloliths are concretions of
formed with a nasopharyngoscope, may be per- epithelial debris that develop within the depth of the
formed in cooperative children and reveals the size tonsillar crypts. Prior tonsil infections have sealed
of the adenoid and presence of obstruction. Collapse the opening of the crypts, allowing the collection of
of the pharyngeal musculature and lymphoid struc- the the debris. Tonsilloliths appear as gritty, caseous
tures into the airway during sleep increases the white or yellow calculi up to 1 cm in size and have a
obstruction. Children with poor neuromuscular foul odor. They may be removed with a blunt instru-
tone may be more susceptible to airway collapse ment or water irrigation but frequently recur. If the
during sleep, whereas children with craniofacial patient is concerned about the condition, tonsillec-
anomalies may be at greater risk for obstruction tomy will eliminate the condition.
from lymphoid hypertrophy. In these children, the
tonsils and adenoid may not appear enlarged but Unilateral Tonsillar Enlargement The finding of
may contribute to the obstruction. Depending on a unilaterally enlarged tonsil often raises the concern
the obstructing tissue, tonsillectomy and/or ade- of a neoplasm within the tonsil or tonsillar fossa. In
noidectomy can be performed. most cases, the larger-appearing tonsil is situated
Children with obstructing tonsils and adenoid more medially within the tonsillar fossa, giving the
may have obstructive sleep apnea (OSA). Sleep impression of enlargement. In some cases, the
apnea is defined as the intermittent cessation of air enlargement is caused by a unilateral infection. Only
1034 Ballenger’s Otorhinolaryngology
rarely is the enlargement caused by a malignancy. In oropharynx. The palate is palpated to detect the
these cases, the tonsil is not only enlarged, but the presence of a submucous or frank palatal cleft. A
surface appears abnormal, with areas of necrosis and complete adenoidectomy should be considered with
ulceration. If a malignancy is suspected, the tonsil is great caution if a cleft is detected because there is an
removed and sent for appropriate studies. increased likelihood of developing velopharyngeal
insufficiency. If a cleft exists, superior adenoid tissue
Otitis Media with Effusion The adenoid affects may be removed, leaving the base to participate in
eustachian tube function in some patients. Regardless velopharyngeal closure.
of the size, removal of adenoid tissue may reduce the Two urinary catheters are used to retract the soft
extrinsic mechanical obstruction of the eustachian palate, and the nasopharynx is visualized with a mir-
tube, improving the ventilatory function of the ror. A curette is placed at the base of the vomer and
eustachian tube and allowing for equalization of pres- advanced, removing the bulk of the adenoid. Any
sure.22 In addition, adenoidectomy has been shown to additional pieces of tissue can be removed in a simi-
decrease the recurrence rates of otitis media.23 Ade- lar fashion. When the adenoid has been removed,
noidectomy should be considered in any child with sponges are placed into the nasopharynx to help with
evidence of nasal obstruction or adenoiditis and who hemostasis. The sponges are removed individually,
is undergoing tympanostomy tube placement. It and hemostasis is obtained with suction electro-
should also be considered in any child in whom tym- cautery. Cauterization should not be performed near
panostomy tubes are being replaced (see Chapter 9). the eustachian tube orifice to prevent development of
scarring and subsequent eustachian tube dysfunction.
TECHNIQUE OF TONSILLECTOMY AND Tonsillectomy is performed next. The superior
ADENOIDECTOMY pole of the tonsil is grasped with an Allis clamp. The
mucosa of the anterior tonsillar pillar is incised with
There are a variety of techniques for removal of the an electrocautery blade (Figure 44–9). The plane of
tonsils and adenoids. For a tonsillectomy, dissection the tonsil capsule is identified. As the tonsil is
in the subcapsular plane can be performed with a retracted medially, dissection continues inferiorly in
knife, protected electrocautery blade, harmonic this plane (Figure 44–10). The inferior attachment
scalpel, or laser. Hemostasis can be obtained with of the tonsil is severed with cautery. Hemostasis is
electrocautery, suture ligation, and topical thrombin. achieved using a suction cautery. A Hurd retractor
The adenoid can be removed with a curette, adeno- may be used to expose areas of the tonsillar fossa to
tome, or powered instrument. obtain better hemostasis. After hemostasis is
Today, most procedures are performed under achieved, the catheters and mouth gag are removed.
general anesthesia. The patient is intubated and
placed supine in the Rose position with a roll under Complications Bleeding is the most serious com-
the shoulders. A mouth gag is placed to expose the plication of tonsillectomy and occurs in up to 3% of
important spaces are the prevertebral, retropharyn- The lateral pharyngeal (parapharyngeal) space
geal, lateral pharyngeal, and submandibular (Figure is cone shaped, with its base at the petrous portion
44–12). The masticator, parotid, and peritonsillar of the temporal bone and its apex at the hyoid bone.
spaces also have significance. Its contents include lymph nodes receiving afferents
The prevertebral space lies between preverte- from the nasal cavity, paranasal sinuses, nasophar-
bral fascia and the vertebral bodies and extends from ynx, oropharynx, and mastoid tip; the carotid artery;
the base of the skull to the coccyx.26 Infections of this internal jugular vein; cranial nerves IX, X, XI, and
space may spread from the base of the skull to the XII; and the cervical sympathetic chain. The carotid
psoas muscles. sheath pierces this space at its apex. The lateral pha-
The retropharyngeal space lies between the ryngeal space communicates with the submandibu-
prevertebral fascia and the fascia covering the poste- lar, retropharyngeal, and parotid spaces and is in
rior pharyngeal wall and esophagus. It extends from close proximity to the masticator and peritonsillar
the skull base to the tracheal bifurcation. It contains spaces. The lateral pharyngeal space is the most fre-
lymph nodes that receive afferent lymphatic vessels quently involved with serious infections and most
from the nose, nasopharynx, paranasal sinuses, frequent route of spread of infection from one
oropharynx, and middle ear. These lymph nodes are region to another.
prominent in children under 5 years of age and The submandibular space is divided by the
begin to atrophy after this age. This space is a major mylohyoid muscle into two compartments, the sub-
route for spread of infection into the mediastinum. lingual space superiorly and submandibular space
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1037
proper inferiorly. The two compartments are con- is frequently isolated from abscesses. The gram-pos-
nected through an opening between the mylohyoid itive aerobes, beta-hemolytic streptococcus and
and geniohyoid muscles and communicate with Staphyloccocus aureus, are the predominant
their counterparts on the opposite side. The sub- pathogens. Gram-negative aerobes and anaerobes
mandibular space is bound by the floor of the are also common. Anaerobes are especially promi-
mouth, tongue, mandible, anterior layer of deep cer- nent when an odontogenic infection is the primary
vical fascia, and hyoid bone. It contains the sublin- source. Beta-lactamase-producing microorganisms
gual and submandibular glands, lingual and have been found with increasing frequency in head
hypoglossal nerves, facial artery, and lymph nodes. and neck space infections.27
The parotid space is formed when the anterior With the significant presence of gram-negative
layer of deep cervical fascia splits and invests the and β-lactamase-producing bacteria, penicillin is no
parotid gland. The medial portion of the fascia is longer the initial antibiotic of choice in the treat-
incomplete and communicates with the lateral pha- ment of these infections. Before culture and sensi-
ryngeal space. Infections of the parotid may extend tivity results have been obtained, the empirically
medially into the lateral pharyngeal space. chosen antibiotic should have activity against gram-
The masticator space surrounds the masseter, positive and negative aerobes, anaerobes, and β-lac-
temporalis, and internal pterygoid muscles and tamase-producing microorganisms. Antibiotic
ramus of the mandible and is adjacent to the lateral combinations, such as clindamycin and cefuroxime
pharyngeal space. Since its fascia surrounds muscles, and ampicillin and sulbactam, are excellent initial
it offers some resistance to the spread of infections. choices.
The peritonsillar space is bound by the capsule The diagnosis of a head and neck space infec-
of the palatine tonsil, the anterior and posterior ton- tion can often be made after a history and physical
sillar pillars, and superior constrictor muscle. Peri- examination. Most patients should have a complete
tonsillar abscesses may progress to involve the lateral blood count with differential, electrolytes, and coag-
pharyngeal space and carotid sheath. ulation studies. If a primary source is suspected,
Many microorganisms are responsible for Gram stains and cultures of the infection should be
head and neck space infections, reflecting the taken, and if there is evidence of sepsis, blood cul-
numerous possible sources. A mixed bacterial flora tures should be taken.
1038 Ballenger’s Otorhinolaryngology
Radiologic studies help in determining the Although the cause and clinical presentation of
extent and severity of the infection, the primary these infections are dependent on the space
source, and the presence of complications. The spe- involved, there are several important principles that
cific studies are determined in the individual case. apply to most of these infections. In children, infec-
Both the suspected source and affected space should tions of the upper aerodigestive tract are the most
be evaluated. Anteroposterior and lateral neck films common cause of head and neck space infections,
may demonstrate airway compromise, tracheal devi- whereas odontogenic infections are the most com-
ation, and widening of the retropharyngeal space, mon cause in adults. It is not uncommon to fail to
indicating cellulitis or an abscess (Figure 44–13). An identify a primary source of the infection. Oropha-
air-fluid level in the retropharyngeal space confirms ryngeal pain, fever, and limitation of jaw and/or
an abscess. Chest radiographs are required to evalu- neck movement are present in most of these infec-
ate the airway and the mediastinum. tions. Initial treatment consists of intravenous
Contrast-enhanced computed tomography antibiotics, hydration, and analgesics.
(CT) is the most valuable radiologic study. It is Peritonsillar abscess is the most frequent head
excellent for evaluation of all of the fascial spaces and neck space infection in children and the most
and may demonstrate findings of infection such as common complication of acute tonsillitis. Most
soft tissue edema, obliteration of fat planes, devia- infections occur in the superior pole, but some
tion of structures, and airway compromise. It is involve the midtonsillar area and inferior pole. The
excellent for differentiating between an abscess and infection begins as a cellulitis and progresses to an
cellulitis. The finding of a rim-enhancing lesion or abscess.
fluid within the lesion is diagnostic for an abscess. The submandibular space is the second most
Contrast-enhanced CT will also demonstrate the frequent location for head and neck space infections
size and location of an abscess and its position rela- in children. Most infections are odontogenic in ori-
tive to the carotid artery and internal jugular vein gin, usually from the second and third lower molars,
(Figure 44–14). Contrast-enhanced magnetic reso- which penetrate the mylohyoid muscle into the sub-
nance imaging (MRI) may be used, but it does not mandibular space.28 Infections of the submandibular
appear to offer any advantages over CT. Ultrasonog- gland and nodes are other sources of infections. In
raphy may help localize an abscess. children, it is not uncommon to find no primary
source.29 Ludwig’s angina is a rapidly spreading cel- and supportive therapy may be sufficient to treat
lulitis in the superior part of this space. early cases. With Ludwig’s angina, airway obstruc-
The initial presentation is dependent on the site tion is a main concern. The airway must be secured
of the infection. If the infection begins in the sublin- with an endotracheal tube, often using fiber-optic
gual space superior to the mylohyoid muscle, pain, intubation or a tracheostomy. After the airway is
dysphagia, drooling, and muffled voice are promi- secured, the submandibular space is drained. In
nent symptoms. Examination may reveal swelling Ludwig’s angina, colored, weeping exudate, not
and tenderness of the floor of the mouth, and the frank purulence, is usually found. Drains are placed
tongue may be displaced posteriorly, causing airway deep to the mylohyoid muscle and into the sublin-
compromise. Infections beginning in the sub- gual space.
mandibular space inferior to the mylohyoid muscle Retropharyngeal space infections usually
present with cervical pain associated with tense, occur primarily as a sequela of upper respiratory
brawny suprahyoid and submental edema. An infec- tract infections that drain into the retropharyngeal
tion beginning in either space may spread both to its lymph nodes. The disease occurs primarily in
adjacent space and to the other side, producing a true young children. Retropharyngeal infections do
Ludwig’s angina. When the entire submandibular occur in adults, and the incidence in adults may be
space is involved, the presentation is a combination greater than has been previously recognized.30 For-
of the sublingual space and submandibular space eign bodies and trauma are other causes of these
proper infections. Dysphagia and airway compro- infections.
mise are more severe because of the increased degree There is often a history of a recent upper res-
of tissue tension. Trismus is prominent because of piratory tract infection. Symptoms include fever,
involvement of the suprahyoid muscles. sore throat, odynophagia, dysphagia, drooling, muf-
The diagnosis of submandibular space infec- fled voice, and difficulty breathing. Examination
tions can usually be made clinically. Plain lateral and may reveal torticollis; limitation of neck movement;
anteroposterior neck radiographs may reveal airway cervical tenderness; boggy, inflamed orpharyngeal
compromise, whereas CT with contrast may demon- mucosa; and bulging of the posterior pharyngeal
strate an abscess. Panoramic tomography may help wall to one side. The classic presentation occurs in
to determine the primary source of infection. less than 10% of children.31
Treatment must be aggressive. Intravenous With a retropharyngeal space infection, lateral
antibiotics, management of the primary source, neck radiograph findings include air in the soft tis-
1040 Ballenger’s Otorhinolaryngology
terior cervical masses to evaluate for the presence of additional studies may be needed. If it is not estab-
nasopharyngeal carcinoma (see Chapter 60). lished, diagnostic studies can be performed. These
All neck masses should be examined for size, may include blood and urine studies, skin tests, plain
multiplicity, laterality, tenderness, color, mobility, radiographs, ultrasonography, CT, MRI, biopsy, and
consistency, surrounding tissue changes, and the endoscopy.
presence of bruits and thrills. Soft, compressible In a child with a suspected malignancy, chest
masses are characteristic of congenital cysts, heman- radiography should always be performed because
giomas, and lymphangioma. Lymphomas often many children with lymphoma of the neck have
present as firm, rubbery, nontender masses. Palpable abnormal chest radiographs.36 Both CT and MRI
cervical lymph nodes are unusual in adults but can identify the consistency of a neck mass and
common in children. Localized unilateral cervical delineate its size and extent. Magnetic resonance
lymphadenopathy is usually associated with gram- imaging has several advantages and is preferred over
positive bacterial infections, whereas viral infections CT for the evaluation of cervical masses.37 Magnetic
usually cause bilateral or generalized lympha- resonance imaging is more sensitive to changes in
denopathy. In a child, any lymph node larger than 2 contrast between the mass and normal tissue, pro-
cm, especially if it is enlarging, should be evaluated. viding superior resolution. It demonstrates better
The location of the mass is especially important. anatomic detail, has multiplanar capability, and
Specific lesions have a predilection for specific sites, involves no radiation exposure. Computed tomog-
and the location may point to a benign or malignant raphy and MRI can be combined with contrast to
condition. Congenital lesions are usually found in demonstrate vascular lesions.
the midline or anterior cervical triangle. Metastatic If no diagnosis can be established or a malig-
malignancies are distributed along the pathways of nancy is suspected in a child, an excisional biopsy is
the cervical lymphatic channels. In children, a supra- preferred. With localized lesions, an excisional biopsy
clavicular mass is suggestive of a lymphoma.36 may be curative and provides for a sufficient amount
After completing the history and physical of tissue for additional studies, such as permanent
examination, the diagnosis may be apparent, and no and frozen section, electron microscopy, and tumor
1042 Ballenger’s Otorhinolaryngology
ryngeus muscles contract to elevate the soft palate. Rathke’s pouch develops when remnants of the
The levator veli palatini lifts the muscular portion of buccal-mucosal invagination that forms the anterior
the soft palate upward and backward. Contraction lobe of the pituitary gland persist. A craniopharyn-
of the superior constrictor muscle narrows the goma is a tumor that arises from these remnants.
nasopharynx laterally and forms Passavant’s pad, a Symptoms take the form of pituitary-hypothalamic
prominence of the posterior pharyngeal wall. The derangements.
tensor veli palatini contributes to the closure of the The pharyngeal bursa of Thornwaldt is a mid-
isthmus during swallowing. Failure to separate the line nasopharyngeal structure located just inferior to
nasopharynx from the oropharynx results in Rathke’s pouch and represents the proximal end of
velopharyngeal insufficiency. There may be reflux of the notochord. It may form a cyst known as Thorn-
fluid into the nasal airway or difficulty producing waldt’s cyst. The cyst may become infected.
speech sounds such as “k.” Teratomas, dermoid cysts, and gliomas are rare
Along with the nose, the nasopharynx is a res- but may cause nasal obstruction and respiratory dis-
onating chamber that contributes to the quality of tress in newborns. Teratomas are often associated
the voice. Loss of the resonating capacity produces a with other congenital abnormalities. Mucous reten-
hyponasal voice or rhinolalia clausa. For certain tion cysts and hamartomas occur occasionally.
vowels, proper velopharyngeal opening is necessary
to avoid non-nasal speech. The nasopharynx acts as
a resonating chamber for these phonemes.
CHOANAL ATRESIA
The eustachian tube, which opens into the Choanal atresia results from the failure of the buc-
nasopharynx, is responsible for protection, ventila- copharyngeal membrane to regress so that the pos-
tion, and clearance of fluid from the middle ear cleft. terior part of the nasal cavity does not open into the
Proper function of the levator veli palatini and ten- nasopharynx. This developmental anomaly is dis-
sor veli palatini is essential for normal eustachian cussed in Chapter 46.
tube function. Children with anatomic abnormali-
ties of the palate such as cleft palate and dysfunction
of these muscles are likely to have problems with the
JUVENILE ANGIOFIBROMA
middle ear cleft. Enlarged, nasopharyngeal lymphoid Juvenile angiofibroma of the nasopharynx is rare but
tissue may also affect eustachian tube function. is the most common benign neoplasm of the
nasopharynx. It is discussed in Chapter 60.
EXAMINATION
Evaluation of the nasopharynx can be done by indi-
NASOPHARYNGEAL STENOSIS
rect and direct examination. Indirect mirror exami- Nasopharyngeal stenosis occurs when scar tissue
nation is limited by patient cooperation and mirror obstructs the nasopharynx.39 The posterior tonsillar
distortion of the image. Nasopharyngoscopy, either pillars and soft palate adhere to the posterior pha-
with a flexible or rigid telescope, provides excellent ryngeal wall. The degree of scarring varies from a
visualization of most of the important structures, thin band to a complete cicatrix, and the obstruc-
including the adenoid, eustachian tubes, and tion may be partial or complete. Most cases result
choanae. Direct examination in an operating room from tonsillectomy and adenoidectomy, but some
affords the best method of examination. The patient cases are secondary to infection.
is in the same position as for an adenoidectomy. The Nasopharyngeal stenosis may develop when
nasopharynx may be visualized with mirrors and tel- inferolateral adenoid tissue is removed and there is
escopes. Any suspicious areas may be palpated and simultaneous denuding or excision of the posterior
even biopsied. tonsillar pillar.24 Patients who undergo secondary ade-
noidectomy and have large lateral bands of lymphoid
tissue are more likely to develop this stenosis. Treat-
BENIGN LESIONS OF THE NASOPHARYNX ment is dependent on the location and severity of the
These lesions are discussed in Chapter 46 and will be stenosis and includes corticosteroid injection, lysis of
mentioned briefly. adhesions, and rotation and advancement flaps.
1044 Ballenger’s Otorhinolaryngology
A B
patient may not be obese, moderate weight reduc- 44–17) are the most widely performed procedures.
tion may improve the severity of the apnea. Alcohol, Uvulopalatoplasty reduces the soft palatal and uvu-
tobacco, and caffeine should be eliminated. lar tissue. It is an outpatient procedure that is often
Nonsurgical treatment of OSA includes posi- performed with a laser, and recently, radiofrequency
tioning, artificial airways, appliances, and positive energy ablation of these tissues has been used. Uvu-
airway pressure. The supine position often exacer- lopalatopharynoplasty, a more complex procedure,
bates OSA, and there are maneuvers and devices that eliminates the palatal, tonsil pillar and pharyngeal
can help one avoid this position. Nasopharyngeal redundancy by removing excess mucosal and sub-
and oral airways, tongue-retaining devices, and mucosal tissue. Submucosal resection of the
mandible advancement appliances may help im- palatoglossus and palatopharyngeus muscles and
prove snoring and OSA but are usually not well tol- removal of the posterior portion of the hard palate
erated. Continuous positive airway pressure (CPAP) with advancement of the soft palate are other proce-
and biphasic positive airway pressure (BiPAP) pro- dures that have been proposed.43
vide pneumatic stenting of the pharyngeal airway.
Their face mask delivery systems are cumbersome
and discomforting.
CENTRAL SLEEP APNEA
The goal of surgery for OSA is relief of airway Central sleep apnea is much less common than OSA
obstruction by increasing pharyngeal size, decreas- and must be distinguished from it. Central sleep
ing pharyngeal compliance, or both to maintain apnea occurs when the neural drive to the respiratory
adequate airflow. The specific procedure depends on muscles is temporarily abolished, resulting in an
the site of obstruction, and consideration includes absence of respiratory effort. There is little effort to
nasal surgery, tonsillectomy, adenoidectomy, palatal breathe. During sleep, respiration is controlled by an
surgery, tongue base reduction, genioglossal automatic feedback system. Sensory signals from
advancement with hyoid myotomy, and maxillo- multiple receptors are relayed to the brainstem, where
mandibular osteotomy and advancement. In severe, they are integrated, and the brainstem sends signals,
acute cases, tracheostomy may be considered. which stimulate the muscles of respiration and lungs.
The most common surgery performed for Any condition affecting this feedback system
OSA is palatal surgery. Redundant tissue of the soft may cause CSA. Congenital central alveolar
palate, uvula, tonsil pillars, and lateral pharyngeal hypoventilation, which results from a very low sen-
walls causes obstruction, and reduction in the size sitivity to increased PCO2, is a cause of CSA. Chronic
of these structures enlarges the airway. Uvulopalato- neuropathies may also impair the sensory compo-
plasty and uvulopalatopharyngoplasty (Figure nent. Bilateral brainstem lesions from vascular con-
1046 Ballenger’s Otorhinolaryngology
ditions, infections, and degenerative and metabolic 11. Rizer FM, Schechter GL, Richardson MA. Macroglos-
diseases affect integrative function and cause CSA. sia: etiologic considerations and management tech-
Neuromuscular diseases, such as polio, amyotrophic niques. Int J Pediatr Otorhinolaryngol 1985;8:
lateral sclerosis, and muscular dystrophies, impair 225–36.
motor function and may cause CSA. In addition, 12. Bartley JR, Morton RP. Simple sublingual ranulas:
chronic obstructive pulmonary disease and conges- pathogenesis and management. J Otolaryngol 1995;
tive heart failure are causes of CSA. 24:253–4.
With polysomnography, CSA can be diag- 13. Lawson W, Reino AJ. Odontogenic infections. In:
nosed, and its degree of severity and any associated Bailey BJ, editor. Head and neck surgery-otolaryn-
physiologic changes can be determined. Central gology. 2nd ed. Philadelphia: Lippincott-Raven
sleep apnea can also be confirmed by measuring Press; 1998. p. 671–81.
esophageal pressure, an index of respiratory effort, 14. Gonzalez C. Tumors of the mouth and pharynx. In:
during sleep.44 Bluestone CD, Stool SE, Kenna MA, editors. Pedi-
The primary treatment for CSA is nasal mask atric otolaryngology. Philadelphia: WB Saunders;
ventilation using CPAP, BIPAP, or intermittent pos- 1996. p. 1108–20.
itive pressure ventilation. Medications to stimulate 15. Mitchelmore IJ, Reily PG, Hay AJ, et al. Surface and
respiration and to increase the tone of the genioglos- core cultures in recurrent tonsillitis: prevalence and
sus and geniohyoid muscles have had limited suc- anaerobes and beta-lactamase producing organisms.
cess. In the most severe cases, tracheostomy with Eur J Clin Microbiol Infect Dis 1994;13:542–8.
ventilation may be required. 16. Brook I. Treatment of patients with acute recurrent
tonsillitis due to group A beta-haemolytic strepto-
cocci: a prospective randomized study comparing
REFERENCES penicillin and amoxicillin/clavulante potassium. J
1. Sharp JT. Reiter’s syndrome. Curr Prob Dermatol Antimicrobial Chemother 1989;24:227–33.
1973;5:157–79. 17. Dedio RM, Tom LWC, McGowan KL, et al. Microbi-
2. Handlers JP, Waterman J, Abrams AM, et al. Oral fea- ology of the tonsils and adenoids in a pediatric pop-
tures of Wegner’s granulomatosis. Arch Otolaryngol ulation. Arch Otolaryngol Head Neck Surg 1988;114:
Head Neck Surg 1985;111:267–70. 763–5.
3. Hurwitz S. Erythema multiforme: a review of its 18. Clinical indicators 2000. Am Acad Otolaryngol Head
characteristics, diagnostic criteria, and management. Neck Surg Bull 2000;19:19.
Pediatr Rev 1990;11:217–22. 19. Herzon FS. Pertitonsillar abscess: incidence, current
4. Lasarkis G, Stoufi E. Oral pemphigus vulgaris in a 6- management practices, and a proposal for treatment
year-old girl. Oral Surg Oral Med Oral Pathol Oral guidelines. Laryngoscope 1995;105 Suppl 74:1–17.
Radiol Endod 1990;69:609–13. 20. Clinical indicators 2000. Am Acad Otolaryngol Head
5. Yoskovitch A, Twefik TL, Duffy CM, et al. Head and Neck Surg Bull 2000;19:34.
neck manifestations of Kawasaki disease. Int J Pedi- 21. Marsh RR, Potsic WP, Pasquariello PS. Reliability of
atr Otorhinolaryngol 2000;52:123–9. sleep sonography in detecting upper airway obstruc-
6. Campbell SM, Montanaro A, Bardana EJ. Head and tion in children. Int J Pediatr Otorhinolaryngol 1989;
neck manifestations of autoimmune diseases. Am J 18:1–8.
Otolaryngol 1983;4:187–216. 22. Gates GA, Aver CS, Prihoda TJ, et al. Effectiveness of
7. Richardson HA, Leibovitz A. Hand, foot, and mouth adenoidectomy and tympanostomy tubes in the
disease in children. J Pediatr 1965;67:6–12. treatment of chronic otitis media with mucoid effu-
8. Terezhalmy GT. A checklist of common oral mani- sion. N Engl J Med 1987;317:1444–51.
festations of HIV infection. Cleve Clin J Med 1992; 23. Paradise JL, Bluestone CD, Rogers KD, et al. Efficacy
59:562–5. of adenoidectomy for recurrent otitis media in chil-
9. Lasarkis G. Color atlas of oral diseases. New York: dren previously treated with tympanostomy tube
Thieme Medical Publishers; 1988. placement. JAMA 1990;262:2066–73.
10. Hadfield PJ, Birchall MA, Novelli V, et al. The ENT 24. McLaughlin KE, Jacobs IN, Todd NW, et al. Manage-
manifestations of HIV infection in children. Clin ment of nasopharyngeal and oropharyngeal stenosis
Otolaryngol 1996;21:30–6. in children. Laryngoscope 1997;107:1322–31.
Diseases of the Oral Cavity, Oropharynx, and Nasopharynx 1047
25. Collier FA, Yglesias L. The relation of the spread of 35. Jaffe BF. Pediatric head and neck tumors: a study of
infection to fascial planes in the neck and thorax. 178 cases. Laryngoscope 1973;83:1644–51.
Surgery 1937;1:323–37. 36. Torsiglieri AJ, Tom LWC, Ross AJ, et al. Pediatric
26. Hollinshead W, editor. Anatomy for surgeons. Vol 1, neck masses: guidelines for evaluation. Int J Pediatr
3rd ed. Philadelphia: Harper & Row; 1982. p. 269–89. Otorhinolaryngol 1988;16:199–211.
27. Ungkanont K, Yellon RF, Weissman JL, et al. Head 37. Mafee MF, Campos M, Raju S, et al. Head and neck:
and neck space infections in infants and children. high field magnetic resonance imaging versus com-
Otolaryngol Head Neck Surg 1995;112:375–82. puted tomography. Otolaryngol Clin North Am
28. Tschiassny K. Ludwig’s angina. Arch Otolaryngol 1988;21:513–46.
1943;38:485–96. 38. McGuirt WF, McCabe BF. Significance of node
29. Blinder D. Idiopathic submandibular abscesses in biopsy before definitive treatment of cervical
children. Int J Oral Maxillofac Surg 1986;15:292–5. metastatic carcinoma. Laryngoscope 1978;88:594–7.
30. Barratt GE, Koopman C, Couthard S. Retropharyn- 39. Stevenson EW. Cicatrical stenosis of the nasophar-
geal abscess—a ten-year experience. Laryngoscope ynx. Laryngoscope 1968;79:2035–67.
1984;94:455–63. 40. Wake up America: a national sleep alert. Vol 1.
31. Thompson JW, Cohen SR, Reddix P. Retropharyn- Report of the National Commission on Sleep Disor-
geal abscess in children: a retrospective and histori- ders Research. January 1993.
cal analysis. Laryngoscope 1988;98:589–92. 41. Young T, Palta M, Demsey J, et al. The occurrence of
32. Nagy M, Pizzuto M, Blackstrom J, et al. Deep neck sleep-disordered breathing among middle-aged
infections in children: a new approach to diagnosis adults. N Engl J Med 1993;328:1230–5.
and treatment. Laryngoscope 1997;107:1627–34. 42. Schwab RJ, Goldberg AN. Upper airway assessment:
33. Lee JG, Helmus C. Cervical lymph node biopsy. radiographic and other imaging techniques. Oto-
Mich Med 1970;69:581–3. laryngol Clin North Am 1998;31:931–68.
34. Wetmore RF, Tom LWC. An approach to the 43. Woodson BT. Transpalatal advancement pharyngo-
pediatric neck mass. In: Johnson JT, Derkey C, plasty for obstructive sleep apnea. Oper Tech Oto-
Mendall-Brown MK, Newman RK, editors. Instruc- laryngol Head Neck Surg 2000;11:36–40.
tional courses. St. Louis: Mosby Year Book; 1991. 44. Guilleminault C, Robinson A. Central sleep apnea.
p. 160–8. Otolaryngol Clin North Am 1998;31:1049–65.
CHAPTER 45
Congenital lesions of the larynx are relatively rare; the faster the flow and the greater the created
however, in their laryngeal laboratory, Chen and negative pressure, with the net effect of further
Holinger found congenital laryngeal lesions in 33 of decreasing the airway lumen. The negative pres-
115 specimens.1 Of all of the anomalies noted, the sure generated during inspiration may also cause
most common deformity is of the cricoid cartilage. supraclavicular and sternal retractions and be
The lesions develop during respiratory differentia- associated with nasal flare.
tion, which occurs during the fourth to tenth weeks 2. Dysphonia, which may be caused by laryngeal
of gestation. The clinical manifestations of laryngeal lesions that interfere with vocalization, with voice
lesions fall into three broad categories: quality ranging from complete aphonia to
hoarseness.
1. Respiratory distress, which may range from com-
3. Failure of the larynx to close the airway during
plete obstruction with no air movement to minor
swallowing, which may cause feeding difficul-
types of stridor. The characteristics of the stridor
ties, with aspiration, cyanosis, or respiratory
are variable and depend on the site and degree of
compromise.
the obstruction. Most laryngeal lesions produce
stridor during the inspiratory phase. The reason Although this chapter deals only with laryn-
for this is found in Bernoulli’s principle, which geal lesions and airway distress, any airway lesion
states that when a fluid or a gas is in motion, the may result in stridor, tachycardia, tachypnea,
pressure exerted on the wall of the airway cyanosis, or restlessness. When evaluating patients
decreases as the velocity of the gas increases. A with these signs, a history and examination of the
well-known example is the wing of an airplane, entire airway should be performed. The history and
shown in Figure 45–1. When the site of the physical examination are the most important diag-
obstruction is in an area not firmly fixed or sup- nostic tools. Radiographic imaging (plain films,
ported, such as the supraglottis or larynx, as the computed tomography [CT], and magnetic reso-
air rushes into the airway, it produces a relatively nance imaging [MRI]) and laryngoscopy (direct
negative pressure, which tends to close the airway and indirect) are important adjuncts and are dis-
(Figure 45–2). The harder the child breathes in, cussed in each section.
1048
Congenital Anomalies of the Larynx 1049
A B
alter the supraglottis surgically in laryngomalacia.26 cuneiform cartilage and the aryepiglottic folds (Fig-
Schwartz, in 1944, removed a V-shaped wedge from ure 45–5). Care must be taken not to excise or trau-
an epiglottis with good results.5 Fearon and Ellis, in matize the strip of mucosa between the arytenoids in
1971, successfully treated a patient by suturing the posterior part of the glottis. Holinger and Konior
the epiglottis to the base of the tongue.27 In that believe that prophylactic antibiotics should be used
same year, hyomandibulopexy was advocated in and that most patients may be extubated in the
France.28,29 Templer and colleagues, in 1981, per- immediate postoperative period but should be
formed a supraglottectomy in an adult for long- observed overnight in the intensive care unit.15
standing stridor and obstructive sleep apnea
secondary to laryngomalacia.30 Lane and associates,
in 1984, excised the tips of the arytenoids, edema- ABSENT OR RUDIMENTARY
tous mucosa, a portion of the corniculate cartilages, EPIGLOTTIS
and a portion of the aryepiglottic fold with
microcupped forceps and Bellucci scissors.31 Seid
INCIDENCE
and colleagues successfully treated three patients The rare bifid epiglottis can be associated with stri-
with the laser in 1985.32 Since then, numerous case dor and aspiration. In the only thorough review of
reports have appeared in the literature.33 Zalzal and the world literature, Montreuil found only five
associates trimmed the lateral edges of the epiglottis, clearly documented cases.35 Since then, six additional
aryepiglottic folds, and the corniculate cartilages cases have been reported.36–38
with microlaryngeal scissors.19 Solomons and
Prescott recommended trimming the supraglottis
and performing an anterior epiglottopexy.16 The
SIGNS AND SYMPTOMS
trimming of the aryepiglottic folds may involve both Patients have presented with respiratory distress sec-
sides or only one side. Kelly and Gray recommended ondary to rotation of the two halves of the epiglot-
unilateral removal of redundant supraglottic tissue tis into the airway. The incidence of multiple
(supraglottoplasty) and to revise the other side if the congenital anomalies is high. A 44% incidence of
patient is not asymptomatic.34 We have recom- polydactyly has been reported.39 Graham and col-
mended doing both sides at one setting. Either leagues reported three cases of hypopituitarism.37
appears to give satisfactory results.
Holinger and Konior prefer the term supraglot-
toplasty to describe the surgical procedures for
DIAGNOSIS
removing the flaccid supraglottic tissues.15 These The only means of diagnosing a bifid epiglottis is
investigators used the laser to remove a portion of the with flexible or direct laryngoscopy (Figure 45–6).
1052 Ballenger’s Otorhinolaryngology
FIGURE 45–5. Example of supraglottoplasty with the FIGURE 45–6. Bifid epiglottis. Courtesy of Dr. L. D.
laser. Note the sparing of the posterior commissure. Holinger, Children’s Memorial Hospital, Chicago, Illinois.
Because of the high incidence of associated airway mature arrest of normal vigorous epithelial
lesions, direct laryngoscopy is suggested for all ingrowth into the larynx during the fourteenth to
patients. seventeenth stages of embryonic development.43 In
the embryonic larynx, a pharyngoglottic duct
divides the larynx into an anterior (membranous)
TREATMENT portion and a posterior (cartilaginous) portion.44
If the airway distress is significant, a tracheostomy is
warranted. Montreuil amputated the epiglottis with
good results.35 Healy and associates performed a tra-
SIGNS AND SYMPTOMS
cheostomy in two patients, and in time the epiglot- At delivery, the child makes strong respiratory efforts
tis matured, and both patients were decannulated but does not move air, cry, or manifest any stridor.
without surgical intervention on the epiglottis.39 The child becomes markedly cyanotic when the
umbilical cord is clamped. Most of these children die
at birth unless an emergency tracheostomy is per-
ATRESIA OF THE LARYNX formed. Some children survive if they have a large
Atresia occurs when the laryngeal opening fails to tracheoesophageal fistula and if the esophagus is
develop and an obstruction is created at or near the intubated. Not infrequently, a pharyngotracheal duct
glottis. Tracheal agenesis may also occur but is is present in the larynx. This should not be confused
thought to be a rarer lesion.40 with a tracheoesophageal fistula, which is located
much lower.
INCIDENCE AND ETIOLOGY
Congenital laryngeal atresia is a rare lesion, with
DIAGNOSIS
only 51 cases reported in the world literature in The diagnosis is most frequently made at autopsy.45
1987.41 It is thought to be the rarest laryngeal lesion, With the increased use of ultrasonography, the diag-
accounting for only 1 of 846 congenital lesions eval- nosis of laryngeal atresia can be made before birth
uated by Holinger and colleagues23,42 and none of by noting enlarged edematous lungs, compressed
433 congenital lesions evaluated by Fearon and fetal heart, severe ascites, and fetal hydrops.46–50
Ellis.27 The lesion is thought to arise from the pre- Smith and Bain outlined three types of laryngeal
Congenital Anomalies of the Larynx 1053
atresia deformities51; these investigators indicated tion (Figure 45–8).51,54,55 Most of the survivors have
that these types are not absolute but are gradations the membranous type 3 lesion or a type 2 lesion and
of a continuous spectrum. Type 1 involves the supra- a tracheoesophageal fistula, which allowed ventila-
glottic and infraglottic larynx with fused arytenoids, tion until a tracheostomy could be performed.
an absent vestibule, and a deformed cricoid. Type 2
involves only the cricoid (subglottic area) with nor-
mal arytenoids, vestibule, and vocal cords. Type 3
WEBS
involves a fused glottis with a normal vestibule and Laryngeal webs occur in the glottis. Rarely, webs
cricoid (Figure 45–7). The extent of the obstruction extend from the epiglottis to the lateral or posterior
can be diagnosed with ultrasonography.52 The sub- aspects of the hypopharynx and can result in signif-
glottic lesions have been found to be cartilaginous or icant airway compromise.56 Holinger and associates
membranous.44 When the lesion is diagnosed prena- described a patient with simultaneous supraglottic
tally, it is called congenital high airway obstruction and laryngeal webs.57 Most webs are located anteri-
syndrome (CHAOS).53 CHAOS results in a pre- orly and extend a varying length toward the ary-
dictable constellation of findings: large echogenic tenoids. The webs vary in thickness from a thin
lungs, flattened or inverted diaphragms, dilated air- structure to one that is thicker and more difficult to
ways distal to the obstruction, and fetal ascites eradicate. Benjamin and Mair described a rare type
and/or hydrops. Ultrasonography should be used to known as a congenital interarytenoid web, which
investigate the airway.53 limits the abduction of the arytenoids.58
TREATMENT INCIDENCE
The patient will not survive unless an emergency Congenital laryngeal webs are uncommon, consti-
tracheostomy is performed or the patient is venti- tuting 5% of all congenital laryngeal lesions.42,59
lated through a tracheoesophageal fistula. Tracheoe- Acquired lesions are more common than congenital
sophageal fistulae are frequently associated with this lesions, in a 60 to 40 ratio.60 Associated anomalies
condition and usually arise at the tracheal bifurca- are frequently seen, especially higher in the air-
way.59,61,62 Posterior glottic webs occur in only 1 to
4% of patients.60
the web. Many children are asymptomatic until they thesia.63 The flexible scope may also have a role in
are stressed, have an infection, or are intubated for a the initial diagnosis, but experience in using it in
surgical procedure. patients with laryngeal webs is limited. Lateral radi-
Vocal dysfunction is the most frequent symp- ographs of the neck may allow assessment of the
tom and was noted in 47 of 51 patients evaluated by width of the web.
Cohen.61 The severity of the dysphonia is not neces- Cohen divided laryngeal webs into four types,
sarily indicative of the severity of the web. Cohen based on their appearance and an estimation of the
reported on 11 patients who complained of apho- degree of airway obstruction.61 Type 1 is uniform in
nia, 16 with weak or whispery voices, 7 with husky thickness, with no subglottic extension, with the
voices, and 4 with some hoarseness. true vocal cords clearly visible in the web, and com-
The second most common symptom is airway promises less than 35% of the airway (Figure 45–9).
obstruction, and the severity is directly proportional Hoarseness is usually only slight. Type 2 is slightly
to the degree of obstruction. The compromise may thicker, with a significantly thicker anterior compo-
be so severe that stridor cannot be produced because nent that may extend into the subglottis. The web
of limited air movement through the larynx. If stri- restricts the airway by 35 to 50% and usually causes
dor is present, it will occur in both inspiratory and little airway distress, unless the patient has an acute
expiratory phases, and if the stridor is severe, the air- infection or is traumatized during intubation (Fig-
way must be secured with intubation or a tra- ure 45–10). The voice is usually husky. Type 3 is a
cheostomy. Forty percent of Cohen’s patients thick web that is solid anteriorly, with the true vocal
required a tracheostomy.61 cords not well delineated. The web restricts the air-
Croup rarely occurs in children younger than 6 way by 50 to 75%, and one notes marked vocal dys-
months. Cohen reported 15 of 51 children with a function, with a weak and whispery voice. Type 4 is
significant history of recurrent croup,61 of whom 7 a uniformly thick, solid web occluding 75 to 90% of
required tracheostomy, 9 presented with pneumo- the airway (Figure 45–11). Respiratory obstruction
nia, and 6 had tracheobronchitis. is severe, and the patient is almost always aphonic.
DIAGNOSIS TREATMENT
The only way to diagnose the extent of the web cor- Approximately 60% of patients require surgical
rectly is by direct laryngoscopy under general anes- intervention.62 Some webs are not repaired because
the patients succumb to other systemic complica- Most surgeons would resect the web and place the
tions. Of all patients with laryngeal webs, 30 to 40% keel through a laryngofissure. The airway results are
require a tracheostomy.61,62 The type of lesion dic- good, but the voice is poor.61
tates the surgical approach. In general, the thinner
webs are easier to treat; the more severe webs are
resistant to surgical management. It is difficult to SACCULAR CYSTS AND
obtain a crisp anterior commissure, and even if one LARYNGOCELES
is obtained, this does not ensure a good voice.
Type I lesions are not life threatening. Many do Laryngoceles and laryngeal saccular cysts are
not require surgery, but if surgery is performed, dila- thought to arise from the laryngeal or saccular
tions or excisions with a knife, scissors, or laser are appendage66–70 or from retention cysts resulting from
effective. Type 2 lesions require treatment, but not in obstruction of mucous gland ducts.71 Morgagni
childhood. Multiple procedures are necessary for incompletely described the saccule, and Galen also
excising small portions of the web in multiple steps. had mentioned it previously.72 The appendage arises
Corticosteroids and antibiotics decrease the amount from the anterior part of the ventricle, extends supe-
of scarring, and speech therapy may be necessary to riorly, and curves slightly posteriorly deep to the
maximize phonation. Type 3 lesions frequently false vocal cords and aryepiglottic folds. The orifice
require tracheostomy to establish the airway. The opens into the ventricle and measures only 0.5 to
child may develop progressive airway distress 1 mm. The ventriculosaccular fold probably serves
because of increased airway demands, trauma from to store mucus and direct it posteromedially to
intubation, or infection. These lesions may require lubricate the vocal cords.73 In the adult, the
multiple excisions and frequently necessitate the appendage extends as high as the superior border of
placement of a keel.64,65 McGuirt and associates the thyroid cartilage. Broyles found that 75% of the
described a method using the laser to develop flaps saccules measured 6 to 8 mm in length, 25% meas-
of the web and reported near-normal results in all ured more than 10 mm, and 7% measured more
patients.60 Type 4 lesions all require a tracheostomy than 15 mm.74 In the fetus, 25% extend as high as the
and excision of the web with placement of a keel. thyrohyoid membrane.72 The type of lesion that
Because they are tracheostomy dependent, these develops is based on the size of the saccule, whether
patients should be monitored with apnea monitors. there is free communication with the laryngeal
1056 Ballenger’s Otorhinolaryngology
SACCULAR CYSTS
Incidence Laryngeal saccular cysts are most likely
to become manifest in infancy.72 Congenital laryn-
geal cysts are rare, but the awareness of their possi-
bility is important because almost 50% of these cysts
are diagnosed at autopsy after the infant has asphyx-
iated.73 In 1967, Suehs and Powell found 27 reported
cases of congenital laryngeal cysts.76
FIGURE 45–13. Anterior saccular cyst. Courtesy of Dr. Diagnosis The definitive diagnosis is made with
L. D. Holinger, Children’s Memorial Hospital, Chicago, direct laryngoscopy, but because the symptoms are
Illinois. intermittent, more than one examination may be
necessary. Laryngoceles originate from the ventricle
and bulge out between the true and false vocal cords
Treatment Treatment of laryngeal cysts may or dissect posteriorly into the arytenoid and
require emergency tracheostomy.73,81,82 Mitchell and aryepiglottic fold. In general, three types have been
associates noted that 20% of their patients required described: internal, external, and mixed84; however,
emergency intervention.77 In the infant, the cysts this classification is artificial. The internal type is
should be treated primarily with endoscopic deroof- limited to the larynx, whereas the external type
ing or aspiration. Suehs and Powell recommended extends into the neck through the isthmus of the
endoscopic incision and drainage as needed.76 thyrohyoid membrane. The mixed type involves
Holinger and colleagues thought that smaller ante- both internal and external portions and is the most
rior saccular cysts could be effectively treated with common. Laryngoceles should be diagnosed with
cup forceps removal (excision biopsy) at the time of direct laryngoscopy when they are symptomatic, in
direct laryngoscopy.73 These investigators would not addition to radiographic findings. Trapnell has
attempt endoscopic dissection of the entire sac. emphasized that the radiographic appearance of a
Aspiration has also been recommended, but the inci- large saccule does not warrant the diagnosis of a
dence of recurrence is high.67,83 Mitchell and associ- laryngocele.87
ates reported successful treatment of 7 of 17 patients
with deroofing or marsupialization.77 A second
deroofing was required in six of the seven recur- Treatment Only symptomatic lesions require
rences. The remaining failure was treated with total treatment. DeSanto preferred the external ap-
excision through a laryngofissure. proach72; however, most of his experience was in
adults. The procedure described by Yarington and
Frazer provides adequate exposure for resection.88
LARYNGOCELES Holinger and associates emphasized that true laryn-
Incidence As of 1977, 300 laryngoceles had been goceles are rare in children and should be treated
recorded in the world literature. They may occur in endoscopically by deroofing with cup forceps.73 On
infants and children,84 and they cause airway occasion, the laryngocele can be aspirated, and a
obstruction.85 The presence of laryngoceles in this more orderly resection can be performed at a later
age group appears to be rare, however. Laryngoceles date.89 The laser is also an alternative.
1058 Ballenger’s Otorhinolaryngology
TREATMENT
The prognosis for a patient with this lesion is not
FIGURE 45–14. Classification of laryngeal and tra- favorable. In the review presented by Roth and col-
cheoesophageal clefts as proposed by Evans.98 leagues,96 24 patients died before surgical interven-
Congenital Anomalies of the Larynx 1059
ble gastrostomy to minimize the chance of aspira- Traumatic lesions are most frequent secondary to
tion of gastric contents. Robie and associates stretching of the recurrent laryngeal nerve during
reported that of 170 clefts repaired, 19 required revi- vaginal delivery or surgical trauma in management
sion surgery.113 of bronchogenic cysts, tracheoesophageal fistulae, or
patent ductus arteriosus.124 Infectious diseases such
as whooping cough, encephalitis, poliomyelitis,
VOCAL CORD PARALYSIS diphtheria, rabies, tetanus, syphilis, and botulism are
Vocal cord paralysis can be categorized into congen- now rarely seen but can cause vocal cord paralysis.123
ital and acquired lesions. One or both of the true Tumors of the brain and spinal column are also rare
vocal cords may be involved, and bilateral vocal cord but can cause unilateral or bilateral vocal cord
paralysis is more frequent.118–120 Apnea is frequently paralysis.
seen in bilateral vocal cord paralysis.121–123 Congeni- The pathophysiology of bilateral vocal cord
tal lesions are frequently associated with central paralysis is unclear, but the condition may result
nervous system lesions, including hydrocephalus, from (1) compression of the vagus nerves in their
meningomyelocele, Arnold-Chiari malformation, course through the foramen magnum, (2) traction
meningocele, encephalocele, cerebral agenesis, of the cervical rootlets of the vagus nerves by the
nucleus ambiguus dysgenesis, neuromuscular disor- caudal displacement of the brainstem, or (3)
ders, and myasthenia gravis.124,125 Arnold-Chiari is brainstem dysgenesis.129,130 Most authors favor the
the most frequent malformation and is likely a con- compression theory because, with timely decom-
tributing factor in most cases.126 pression of hydrocephalus or the Arnold-Chiari
malformation, the vocal cords regain function.
Familial bilateral vocal cord paralysis131–133 and per-
INCIDENCE AND ETIOLOGY sistent apnea after tracheostomy121 appear to be
Estimates of the frequency of vocal cord paralysis most appropriately explained by the dysgenesis
range from 1.5 to 23%120,127,128; according to some theory. Probably, more than one lesion can cause
authors, it ranks second in frequency among all con- vocal cord paralysis.
genital laryngeal lesions.124 Holinger and associates Laryngeal lesions such as subglottis stenosis,
found that congenital lesions were more frequent laryngomalacia, and posterior laryngeal clefts have
than acquired.125 The acquired group can be further also been associated with, but do not cause, vocal
categorized into traumatic, infectious, or neoplastic. cord paralysis.134
Congenital Anomalies of the Larynx 1061
SIGNS AND SYMPTOMS vocal cord function may not return for 11⁄2 years, if at
all. If intervention has been timely, the larynx should
Any of the three laryngeal functions of respiration,
be examined periodically to assess vocal cord func-
voice production, and deglutition can be affected by
tion. If the patient shows no evidence of function
vocal cord paralysis. With unilateral vocal cord paral-
within 1 to 2 weeks, a tracheostomy should be per-
ysis, the voice is breathy and weak, but the patient has
formed to relieve the airway distress,123 but central
an adequate airway unless stressed. Stridor, weak cry,
sleep apnea may continue even with appropriate
and some degree of respiratory distress can be seen in
early decompression.121 Once the tracheostomy is in
all patients with bilateral vocal cord paralysis.130 Dedo
place, periodic examinations will be necessary to
noted that if both the recurrent and superior laryn-
assess vocal cord function.
geal nerves are paralyzed, the vocal cords will be in
Approximately 50% of children with bilateral
the intermediate position, and the airway then will
vocal cord paralysis require tracheostomy.118,125,130
frequently be sufficient to allow adequate ventila-
Bluestone and colleagues reported a 50% mortal-
tion.124,135 If the recurrent nerves only are paralyzed,
ity rate secondary to shunt failure or infection in
the vocal cords will be in the paramedian position,
patients with Arnold-Chiari malformation. 130
resulting in an inadequate airway.
Of those who survive, 25 to 48% can be
Stridor is the most frequent presenting symp-
decannulated.119,129
tom of bilateral vocal cord paralysis,125 and its onset
may be sudden.130 Older children suppress laughing
and coughing because of the increased respiratory SUBGLOTTIC LESIONS
demand. The airway becomes narrower, and there The principal subglottic lesions are stenoses and
will be an increase in stridor and the development of hemangiomas.
nasal flaring, restlessness, and the use of accessory
respiratory muscles, with an indrawing of the ster-
num and epigastrium. The stridor may progress to STENOSIS
cyanosis, apnea, and respiratory and cardiac arrest if Stenoses of the subglottic area can be divided into
not recognized and treated. cartilaginous stenoses, which are usually congenital,
Aspiration and dysphagia are frequently noted and acquired membranous or soft tissue stenoses.
in patients with bilateral vocal cord paralysis.129,136
Pneumonia may first be apparent when signs of Incidence and Etiology A stenosis is considered
increasing cranial pressure appear. to be congenital when the patient has no history of
endotracheal intubation or trauma. The normal
DIAGNOSIS subglottic lumen is 4.5 to 5.5 mm in a full-term
neonate and 3.5 mm in a premature neonate. We do
The diagnosis is made by flexible laryngoscopy or
not know in how many infants’ extubations fail
direct laryngoscopy. Vocal cord mobility may be dif-
because of congenitally small cricoid cartilages.
ficult to examine in an infant, and the intermediate
Congenital subglottic stenosis is the third most
versus paramedian position may be impossible to
common congenital abnormality. Cricoid cartilage
assess.
deformities are usually congenital and consist of
abnormal shapes and sizes. The cricoid cartilage may
TREATMENT
have a normal shape but may be small or hypoplas-
Once the diagnosis of vocal cord paralysis is made, tic. It may also be elliptical, flattened, or otherwise
the airway should be secured if the patient has sig- distorted. The first tracheal ring can also be trapped
nificant airway distress. The airway is best estab- under the cricoid cartilage, resulting in a narrowed
lished with intubation, followed by a full workup to subglottis. The primary causes of acquired or mem-
ascertain the cause of the vocal cord paralysis. One branous subglottic stenosis (Figure 45–18) in chil-
must look specifically for associated findings of dren are (1) external injury from blunt trauma or a
meningomyelocele, Arnold-Chiari malformation, high tracheostomy and (2) internal injury from pro-
and hydrocephalus.125 If the compression of the longed intubation and chemical or thermal burns.
nerve is relieved within 24 hours, the vocal cords will External injuries are rare in infants. Internal trauma,
regain function within 2 weeks2125,130; otherwise, secondary to prolonged intubation, is thought to
1062 Ballenger’s Otorhinolaryngology
FIGURE 45–18. Membranous subglottic stenosis. FIGURE 45–19. Ulcerated right vocal process.
account for approximately 90% of acquired subglot- tion, and frequently one sees generalized inflamma-
tic stenosis.137,138 The incidence of stenoses after tion and edema of the ventricle that results in ven-
intubation ranges from 0.9 to 8.3%.139–142 The tricular protrusions. The long-term complications of
stenoses most frequently occur in the subglottis these lesions are characterized as posterior glottic
because (1) the cricoid cartilage is a complete circu- synechiae, “healed furrows,” posterior subglottic and
lar ring, without any “give” for edema; (2) the edema glottic stenoses (Figure 45–21), “healed fibrous nod-
can accumulate rapidly in the loose areolar tissue of ules,” submucosal mucous gland hyperplasia with
the subglottis; (3) the pseudostratified, ciliated ductal cysts, and submucosal fibrosis and stenosis.
columnar respiratory epithelium is delicate and eas- The scar tissue forms in the subglottis and limits the
ily traumatized; and (4) the narrowest portion of the airway.144–148 Healing is inhibited in part by poor
upper airway is in the subglottis and is therefore the blood supply in the subglottis and constant motion
most likely to be traumatized.138 of the larynx.
The pathophysiology of acquired subglottic Neonates tolerate prolonged intubation better
stenoses is well described. The endotracheal tube than adults. The reasons for this are unclear, but
causes pressure necrosis of the respiratory epithe- more pliable cartilage144 and the higher position
lium. Edema and superficial ulceration begin, and of the larynx in the neck146 have been suggested as
the normal ciliary flow is interrupted. As the ulcer considerations.
deepens, secondary infection of the areolar tissue Certain factors can increase the chances of
and perichondrium begin. Chondritis may eventu- developing subglottic stenosis. An oversized endo-
ally occur, with necrosis and collapse of the cricoid tracheal tube or a tube of appropriate size in a
cartilage. Benjamin characterized the traumatic patient with a small cricoid cartilage can increase the
lesions formed in the larynx with prolonged intuba- mucosal pressure and result in a deep ulceration.
tion.143 He noted that, in the acute phase, one sees Primary intubation can traumatize the subglottis. In
formation of posterolateral ulcerations at the vocal children, an endotracheal tube that allows a leak at
processes (“ulcerated troughs”) (Figure 45–19), and pressure less than 20 cm H2O should be chosen.
usually one sees an “intact median strip” of mucosa Reintubation,144,149 shearing motion of the tube on
and an “annular ulceration” of mucosa in the sub- movement of the head,150 and superimposed local or
glottis. “Tongues of granulation tissue” (Figure systemic bacterial infections145 increase the risk. Gas-
45–20) form anterior and posterior in the ulcera- troesophageal reflux can increase the inflammation
Congenital Anomalies of the Larynx 1063
FIGURE 45–20. Tongues of granulation tissue. FIGURE 45–21. Posterior glottic web.
and tissue trauma. Nasogastric tubes and endotra- hoarseness, abnormal cry, and aphonia will indicate
cheal tubes have been noted to cause pressure necro- that an anterior web is present. Dysphagia and aspi-
sis of the cricoid145 and increase the risk of reflux. ration pneumonia can occur.
Systemic factors such as immunodeficiency,
anemia, neutropenia, toxicity, hypoxia, dehydration, Diagnosis Soft tissue radiographs of the lateral
and poor perfusion increase the risk of developing neck may demonstrate subglottic narrowing. Xero-
mucosal ulceration and subsequent scar formation. radiography demonstrates the tissue–air interface
better and is believed by many to be the best method
Signs and Symptoms In the intubated neonate, for evaluating chronic airway problems.151–153 Com-
evidence of subglottic stenosis may not manifest puted tomographic scans do not give adequate addi-
until the patient is ready for extubation. If a sub- tional information.
glottic ulcer is present, the airway may be compro- Direct laryngoscopy is the most important
mised immediately or edema may accumulate over a diagnostic step in assessing the thickness and length
few hours. In some patients, symptoms do not of the stenosis and involvement of the larynx. Flexi-
develop until 2 to 4 weeks after intubation. If the ble fiber-optic laryngoscopy is most useful in assess-
patient has mild to moderate congenital subglottic ing vocal cord function.151 Because the flexible scope
stenosis, symptoms may not appear until an infec- provides only a limited view of the posterior part of
tion of the upper respiratory tract causes additional the glottis and subglottis, rigid endoscopy is neces-
narrowing and respiratory distress. sary to assess the size and patency of the lumen. The
If the stenosis is congenital, the only manifes- airway may be sized with the bronchoscope or endo-
tation may be prolonged or recurrent croup. A com- tracheal tubes. Storz Hopkins rod lens telescopes are
mon dictum is that “there is no such thing as croup especially important in visualizing the extent of the
under 1 year of age.” As respiratory demands in- stenosis in the subglottis. Because of the wide-angle
crease, the infant may become symptomatic.80 view, estimating the actual dimensions of the lumen
The main symptoms and signs relate to airway, is difficult. Often the narrowing is so great that only
voice, and feeding. Stridor is the primary sign and is the telescope can be used.
biphasic, with the inspiratory phase always louder.
With progressive narrowing of the airway, respira- Treatment Congenital subglottic stenosis that is
tory distress ensues. If the vocal cords are affected, mild and causing mild symptoms and signs can be
1064 Ballenger’s Otorhinolaryngology
treated expectantly. Some patients outgrow their microcauterization,162 cryosurgery,163,164 serial elec-
lesions and are unlikely to need surgical correc- trosurgical resection,165 and carbon dioxide laser.166
tion.154 Treatment must be individualized. The carbon dioxide laser appears to be the current
Tracheostomy is required in fewer than half of modality of choice.146,166–171 The laser can only be
patients with congenital subglottic stenosis.144 Nor- used to resect membranous stenosis, and the proce-
mal growth and development may allow decannula- dure has to be performed in stages. The more aggres-
tion within 2 to 5 years. sively the laser is used, the less the likelihood of a
The anterior cricoid split operation was initially successful outcome and the greater the risk of induc-
devised to treat acquired subglottic stenosis,155 and it ing additional scarring. Cotton and Manoukian
was later applied to patients with the congenital identified several factors associated with poor
form.156,157 This procedure breaks the cartilaginous results: (1) circumferential scarring, (2) scar tissue
cricoid ring anteriorly to allow expansion of the sub- greater than 1 cm in length, (3) scar in the posterior
glottis. It is used in patients who have confirmed commissure, (4) severe bacterial infection of the tra-
stenosis and failed extubation but do not require air- chea after a tracheostomy, (5) exposure of the peri-
way support and have mature lungs with oxygen chondrium or cartilage with the laser, (6) combined
requirements less than 35%. The procedure involves laryngotracheal stenosis, (7) failure of previous
making a vertical incision through the lower third of endoscopic procedures, and (8) previous loss of car-
the thyroid cartilage, the cricoid cartilage, and the tilaginous framework.172 Prophylactic systemic
first two tracheal rings. Many of the cricoid rings antibiotic therapy is recommended for endoscopic
spring open, and the endotracheal tubes are readily procedures. Adequate exposure of the subglottis is
seen through the incision. Others do not open to any necessary. The subglottiscope designed by Healy is
significant degree. Some surgeons have recom- useful if the patient does not have a tracheostomy in
mended placement of auricular or rib grafts at the place. Supraglottic jet ventilation provides the best
time of the decompression.158–160 The patient is left exposure. Thin webs are most appropriately treated
intubated with an endotracheal tube one size bigger with the laser.
for 5 to 7 days and is re-examined at the time of The open procedures have been traditionally
extubation. Corticosteroids are usually administered used for the more severe lesions. Surgeons are
3 to 5 days before planned extubation. increasingly using single-stage reconstruction.159,173
In weighing the advantages of endoscopic and This allows for more rapid correction of the prob-
open procedures, the surgeon must take into lem and is perhaps more cost effective. The hyoid
account the extent of the scarring and the expertise interposition was first reported by Looper.174 Bennett
required. The goal of any surgical procedure is to also reported the use of a hyoid bone graft for the
extubate or decannulate the patient by repairing the treatment of subglottic stenosis.175 Bone resorption
stenosis with minimal effect on the voice. was a problem, which led to the development of
Dilatation is useful if the ulceration is still pres- pedicle hyoid-sternohyoid myo-osseous flaps.176–178
ent and granulation tissue is forming. It is most The anterior cricoid split with endotracheal
appropriately used with immature scar or submu- tube stenting has been recommended for treatment
cosal fibrosis. Gentle dilation is performed with a of milder forms of stenosis. The standard recon-
round, smooth instrument, usually in conjunction struction has been with autogenous costal carti-
with corticosteroid injection.161 Aggressive dilatation lage.179–181 Because of its abundance, costal cartilage
with corticosteroid injection can induce additional is a better material to use than thyroid cartilage,
trauma and cause significant necrosis of the cartilage. hyoid bone, or muscle pedicle.
The use of corticosteroids is controversial. They The costal cartilage reconstruction has been the
tend to decrease scar formation through their anti- standard method for subglottic reconstruction for
inflammatory action and by delay of collagen syn- the past several years. The fifth or sixth cartilaginous
thesis. They may be used systemically or injected rib or costal margin cartilage is harvested. One inci-
locally. Corticosteroids have not been successfully sion can be used to harvest two ribs, but this is sel-
used to treat mature scar in the subglottis. dom necessary. The perichondrium is left on the
A variety of methods for endoscopic correction lateral surface of the rib, with incisions through it
of subglottic stenosis have been suggested, including along the superior and inferior borders and stripped
Congenital Anomalies of the Larynx 1065
from the medial surface. Some surgeons use the rib 1 mm per year of age up to 10 mm between the two
stripper on small double-prong hooks and a freer halves.172 An appropriate wedge of rib with the peri-
elevator. The incision in the neck is usually a U- chondrium facing the lumen is sutured into the pos-
shaped flap through the tracheostoma or a horizon- terior cricoid cleft. If a posterior graft has been
tal incision over the cricoid if a tracheostomy is not performed, a stent will be required to maintain the
in place. The larynx and trachea are exposed, and a lumen postoperatively. The current stent of choice is
midline incision is made through the length of the the Aboulker-styled Teflon stent, which is round.
stenosis. If the stenosis is severe, the lumen can first Unfortunately, it can cause significant blunting,
be identified with a 25-gauge needle under endo- trauma, and granulation tissue formation at the
scopic visualization. When only an anterior graft is anterior commissure.
used, the incision usually extends from the tracheal Once the posterior cricoid graft is positioned,
rings through the cricoid and the lower third of the the stent is placed and the anterior tracheal wall is
larynx. If a posterior graft and stent are required, a closed. Usually, posterior and anterior grafts are used
full laryngofissure will be necessary. The intralumi- concomitantly. When a stent is used, it must first be
nal scar and mucosa are incised strictly in the mid- positioned in the airway with the tracheostomy in
line. This is best performed by first marking the place. The best method of securing the tracheostomy
lumen transtracheally with a 25-gauge needle. Once to the stent is with wire, as described by Cotton and
the airway is open, the scar is not removed. The Manoukian.172 Placement must be checked endo-
length of the trachea and larynx to be reconstructed scopically. The stent should come to the level of the
is measured, and the rib graft is designed to fit the false vocal cords. If necessary, the stent length should
defect. The graft is elliptical, with the perichondrium be revised to hold the proper position. The rib is
toward the lumen. The rib is not thinned, and care sutured into place with 4-0 Vicryl or polydioxanone
is taken to shape the cartilage to be as wide as possi- suture, taking care to go through the cartilage and
ble, with a lip or shelf to prevent the graft from not allowing the suture to be exposed intraluminally.
falling into the airway (Figure 45–22). If suture is located in the lumen, granulation tissue
In patients with greater subglottic stenosis, a and chronic infection will result. The neck wound is
posterior graft is needed, and the posterior cricoid closed in layers. The stent is left in place for a vari-
lamina is divided in the midline to, but not through, able length of time based on the surgeon’s judgment
the hypopharyngeal mucosa. In complete stenosis, a and the severity of the stenosis.
four-quadrant split has been recommended. The Recently, auricular cartilage has been used as a
cricoid is separated to a distance of approximately graft material.158,159 It is useful because it is malleable;
its curved shape allows for greater anteroposterior Altered cry, hoarseness, barking cough, and failure
dimensions than available with the rib graft (Figure to thrive are the other frequently noted manifesta-
45–23). The auricular cartilage graft has not been tions. Recurrent croup is the most frequent erro-
used extensively with staged reconstructions. neous diagnosis.
The results of successful decannulation depend
in part on the severity of the stenosis. Viral infec- Diagnosis Lateral radiographic studies suggest a
tions with respiratory syncytial virus and bacterial subglottic abnormality consistent with heman-
infections with Pseudomonas have been associated gioma. This is not diagnostic, however, and the diag-
with an increased failure rate.182 The ultimate out- nosis can only be made endoscopically (Figure
come of grade 1 is 92% successful, that of grade 2 is 45–24). The appearance of these lesions is charac-
85% successful, that of grade 3 is 70% successful, teristic and can be made by the experienced endo-
and that of grade 4 is 36% successful.183 scopist without a biopsy. The lesion is sessile, fairly
firm, but compressible; pink, red, or bluish; and
poorly defined. The vessels are rarely, if ever, cav-
SUBGLOTTIC HEMANGIOMA ernous. If a biopsy is performed, the bleeding is usu-
Incidence and Etiology Congenital subglottic ally not profuse, but the airway must be maintained,
hemangiomas are relatively rare lesions and develop most frequently with a tracheostomy. The lesion is
primarily in the submucosa. Fifty percent are associ- usually unilateral or asymmetric. Multiple heman-
ated with cutaneous hemangiomas. No correlation giomas of the airway have been reported.185 A thor-
exists between the size of the cutaneous lesion and ough workup of the possible extent of the
the size of the laryngeal lesion.184 A 2 to 1 female pre- hemangioma in the mediastinum is recommended.
ponderance is recognized.
Treatment If the airway distress is significant at
Signs and Symptoms The subglottic hemangioma the time of diagnosis, immediate airway control will
develops in a typical growth pattern with increasing be necessary. Endoscopy may compromise the air-
size, usually causing symptoms in the first 8 weeks of way. If necessary, the airway may be secured with
life. Almost all of these lesions will become manifest intubation or a tracheostomy. If the patient is intu-
before 6 months of age. Some lesions extend into the bated, tracheostomy is more likely to be required.
perichondrium and tracheal rings and beyond the A wide range of treatments have been advo-
trachea. Variable and fluctuant respiratory distress cated. They include the following: tracheostomy
usually progresses to persistent distress. The stridor with observation and awaiting spontaneous resolu-
is more prominent on inspiration but is present dur- tion; prolonged endotracheal intubation, with and
ing expiration. The voice is altered to a varying without corticosteroid injection; injection of scle-
degree, depending on the involvement of the larynx. rosing agents; the use of systemic corticosteroids;
A B
FIGURE 45–23. Preoperative (A) and postoperative (B) photographs after a laryngotracheoplasty with auricular
cartilage.
Congenital Anomalies of the Larynx 1067
24. Reardon TJ. Congenital laryngeal stridor. Am J Med 41. Gatti WM, MacDonald E, Orfei E. Congenital laryn-
Sci 1907;134:242–52. geal atresia. Laryngoscope 1987;97:966–9.
25. Blackader AD, Muckleston HS. Inspiratory stridor 42. Holinger PH, Brown WT. Congenital webs, cysts,
and dyspnea in infants. Arch Pediatr 1909;26: laryngoceles and other anomalies of the larynx. Ann
401–16. Otol Rhinol Laryngol 1967;76:744–52.
26. Iglauer S. Epiglottidectomy for the relief of congen- 43. Woo P, Karmody CS. Congenital laryngeal atresia.
ital laryngeal stridor, with report of a case. Laryngo- Histopathologic study of two cases. Ann Otol Rhinol
scope 1922;32:56–9. Laryngol 1983;92:391–5.
27. Fearon B, Ellis D. The management of long term air- 44. McIlwain JC. The posterior glottis. J Otolaryngol
way problems in infants and children. Ann Otol Rhi- 1991;20 Suppl 2:1–24.
nol Laryngol 1971;80:669–77. 45. Asano S, Yamagiwa K, Konnai I. Congenital laryn-
28. Narcy P, Bobin S, Contencin P. Anomalies laryngies geal atresia: two autopsy cases, one describing the
du nouveau-ne apropos de 687 observations. Ann use of computed tomography. APMIS 2000;108:
Otolaryngol Chir Cervicofac 1984;101:363–73. 313–7.
29. Cagnol C, Garcin M, Unal D. Un cas de stridor 46. Dolkart LA, Reimers FT, Wertheimer IS, Wilson BO.
larynge congenital grave laoite pan hyomandibu- Prenatal diagnosis of laryngeal atresia. J Ultrasound
lopexie. J Fr Otorhinolaryngol 1971;20:625–6. Med 1992;11:496–8.
30. Templer J, Hast M, Thomas JR, Davis WE. Con- 47. Watson WJ, Thorp JM, Miller RC, et al. Prenatal
genital laryngeal stridor secondary to flaccid diagnosis of laryngeal atresia. Am J Obstet Gynecol
epiglottis, anomalous accessory cartilages and re- 1990;163:1456–7.
dundant aryepiglottic folds. Laryngoscope 1981;91: 48. Garel C, Legrand I, Elmaleh M, et al. Laryngeal ultra-
394–7. sonography in infants and children: anatomical cor-
31. Lane RW, Weider DJ, Steinem C, Marin-Padilla M. relation with fetal preparations. Pediatr Radiol 1990;
Laryngomalacia. A review and case report of surgi- 20:241–4.
cal treatment with resolution of pectus excavatum. 49. Balci S, Altinok G, Ozaltin F, et al. Laryngeal atresia
Arch Otolaryngol 1984;110:546–51. presenting as fetal ascites, olygohydramnios and lung
32. Seid AB, Park SM, Kearns MJ, Gugenheim S. Laser appearance mimicking cystic adenomatoid malfor-
division of the aryepiglottic folds for severe laryngo- mation in a 25-week-old fetus with Fraser syn-
malacia. Int J Pediatr Otorhinolaryngol 1985;10: drome. Prenat Diagn 1999;19:856–8.
153–8. 50. Morrison PJ, Macphail S, Williams D, et al. Laryngeal
33. Katin LI, Tucker JA. Laser supraarytenoidectomy for atresia or stenosis presenting as second-trimester
laryngomalacia with apnea. Trans Pa Acad Ophthal- fetal ascites—diagnosis and pathology in three inde-
mol Otolaryngol 1990;42:985–8. pendent cases. Prenat Diagn 1998;18:963–7.
34. Kelly SM, Gray SD. Unilateral endoscopic supraglot- 51. Smith II, Bain AD. Congenital atresia of the larynx.
toplasty for severe laryngomalacia. Arch Otolaryn- Ann Otol Rhinol Laryngol 1965;74:338–49.
gol Head Neck Surg 1995;121:1351–4. 52. Kalache KD, Chaoui R, Tennstedt C, Bollmann R.
35. Montreuil F. Bifid epiglottis, report of a case. Laryn- Prenatal diagnosis of laryngeal atresia in two cases of
goscope 1949;59:194–9. congenital high airway obstruction syndrome
36. DelMonico ML, Haar JG. Bifid epiglottis. Report of (CHAOS). Prenat Diagn 1997;17:577–81.
a case. Arch Otolaryngol 1972;96:178–81. 53. Hedrick MH, Ferro MM, Filly RA, et al. Congenital
37. Graham JM, Brown FE, Saunders RL, et al. Bifid high airway obstruction syndrome (CHAOS): a
epiglottis, hand anomalies, and congenital hypopi- potential for perinatal intervention. J Pediatr Surg
tuitarism [letter]. Lancet 1985;2:443. 1994;29:271–4.
38. Tobeck A. Halbseitige Aplasie der Epiglottis. Z 54. Peison B, Levitzky E, Sprowls JJ. Tracheoesophageal
Laryng Rhinol Otol 1949;28:502–3. fistula associated with tracheal atresia and malfor-
39. Healy GB, Holt GP, Tucker JA. Bifid epiglottis: a rare mation of the larynx. J Pediatr Surg 1970;5:464–7.
laryngeal anomaly. Laryngoscope 1976;86:1459–68. 55. Cohen MS, Rothschild MA, Moscoso J, Shlasko E.
40. Mar S, Essex C. Type 2 tracheal agenesis without tra- Perinatal management of unanticipated congenital
cheoesophageal fistula. Int J Pediatr Otorhinolaryn- laryngeal atresia. Arch Otolaryngol Head Neck Surg
gol 1997;39:159–61. 1998;124:1368–71.
Congenital Anomalies of the Larynx 1069
56. Gerson CR, Tansek K, Tucker GF Jr. Pharyngolaryn- 75. DeSanto LW, Devine KD, Weiland LH. Cysts of lar-
geal web. Report of a new anomaly. Ann Otol Rhinol ynx: classification. Laryngoscope 1970;80:145–76.
Laryngol 1983;92:331–2. 76. Suehs OW, Powell DB. Congenital cyst of the larynx
57. Holinger LD, Wong HW, Hemenway WG. Simulta- in infants. Laryngoscope 1967;77:654–62.
neous glottic and supraglottic laryngeal webs: report 77. Mitchell DB, Irwin BC, Bailey CM, Evans JN.
of a case. Arch Otolaryngol 1975;101:496–7. Cysts of the infant larynx. J Laryngol Otol 1987;
58. Benjamin B, Mair EA. Congenital interarytenoid 101:833–7.
web. Arch Otolaryngol Head Neck Surg 1991;117: 78. Holinger PH, Brown WT. Congenital webs, cysts,
1118–22. laryngoceles and other anomalies of the larynx. Ann
59. McHugh HE, Loch WE. Congenital webs of the lar- Otol Rhinol Laryngol 1967;76:744–52.
ynx. Laryngoscope 1942;52:43–65. 79. Shackelford GD, McAlister WH. Congenital laryn-
60. McGuirt WF, Salmon J, Blalock D. Normal speech geal cyst. AJR Am J Roentgenol 1972;114:289–92.
for patients with laryngeal webs: an achievable goal. 80. Cotton RT, Richardson MA. Congenital laryngeal
Laryngoscope 1984;94:1176–9. anomalies. Otolaryngol Clin North Am 1981;
61. Cohen SR. Congenital glottic webs in children. A ret- 14:203–18.
rospective review of 51 patients. Ann Otol Rhinol 81. English GM, DeBlanc GB. Laryngocele: a case pre-
Laryngol Suppl 1985;121:2–16. senting with acute airway obstruction. Laryngoscope
62. Benjamin B. Chevalier Jackson Lecture. Congenital 1968;78:386–95.
laryngeal webs. Ann Otol Rhinol Laryngol 1983; 82. Ferguson GB. Laryngocele. Laryngoscope 1967;
92:317–26. 77:1368–75.
63. Milczuk HA, Smith JD, Everts EC. Congenital laryn- 83. Donegan JO, Strife JL, Seid AB, et al. Internal laryn-
geal webs: surgical management and clinical embry- gocele and saccular cysts in children. Ann Otol Rhi-
ology. Int J Pediatr Otorhinolaryngol 2000;52:1–9. nol Laryngol 1980;89:409–13.
64. Parker DA, Das Gupta AR. An endoscopic Silastic 84. Canalis RF, Maxwell DS, Hemenway WG. Laryngo-
keel for anterior glottic webs. J Laryngol Otol 1987; cele—an updated review. J Otolaryngol 1977;6:
101:1055–61. 191–9.
65. Mouney DF, Lyons GD. Fixation of laryngeal stents. 85. Chu L, Gussack GS, Orr JB, Hood D. Neonatal laryn-
Laryngoscope 1985;95:905–7. goceles. A cause for airway obstruction. Arch Oto-
66. Laff HI. Cysts in the ventricular area of the larynx. laryngol Head Neck Surg 1994;120:454–8.
Laryngoscope 1953;63:227–40. 86. Baker HL, Baker SR, McClatchey KD. Manifestations
67. Davidson JI. Congenital cyst of the larynx. Lancet and management of laryngoceles. Head Neck Surg
1943;2:508–9. 1982;4:450–6.
68. Ahlen G, Ranstrom S. Congenital laryngeal cysts in 87. Trapnell DH. The radiological diagnosis of laryngo-
early infancy. Acta Otolaryngol (Stockh) 1944;32: celes. Clin Radiol 1962;13:68–72.
483–95. 88. Yarington CT, Frazer JP. An approach to the internal
69. Beautyman W, Haidak GL, Taylor M. Laryngopy- laryngocele and other submucosal lesions of the lar-
ocele: report of a fatal case. N Engl J Med 1959; ynx. Ann Otol Rhinol Laryngol 1966;75:956–60.
260:1025–7. 89. Thomas DM, Madden GJ. Bilateral laryngoceles. Ear
70. Horowitz S. Laryngoceles. J Laryngol Otol 1951; Nose Throat J 1993;72:819–21.
65:724–34. 90. Parsons DS, Herr T. Delayed diagnosis of a laryngo-
71. Hockmuth LN, Martin SJ. An obstructing laryngeal tracheoesophageal cleft. Int J Pediatr Otorhino-
cyst in a newborn. Conn Med 1962;26:691. laryngol 1997;39:169–73.
72. DeSanto LW. Laryngocele, laryngeal mucocele, large 91. Parsons DS, Stivers FE, Giovanetto DR, Phillips SE.
saccules, and laryngeal saccular cysts: a developmen- Type I posterior laryngeal clefts. Laryngoscope
tal spectrum. Laryngoscope 1974;84:1291–6. 1998;108:403–10.
73. Holinger LD, Barnes DR, Smid LJ, Holinger PH. 92. Samuel M, Burge DM, Griffiths DM. Prenatal diag-
Laryngocele and saccular cysts. Ann Otol Rhinol nosis of laryngotracheoesophageal clefts. Fetal Diagn
Laryngol 1978;87:675–85. Ther 1997;12:260–5.
74. Broyles EN. Anatomical observations concerning the 93. Cohen SR, Thompson JW. Ventral cleft of the larynx:
laryngeal appendix. Ann Otol Rhinol Laryngol a rare congenital laryngeal defect. Ann Otol Rhinol
1959;68:461–70. Laryngol 1990;99:281–5.
1070 Ballenger’s Otorhinolaryngology
94. Decreton SJ, Clement PA. Comparative study of 112. Froehlich P, Truy E, Stamm D, et al. Cleft larynx:
standard x-ray of the maxillary sinus and sinus- management and one-stage surgical repair by ante-
copy in children. Rhinology 1981;19:155–9. rior translaryngotracheal approach in two chil-
95. Pattisapu JV, Parent AD. Subdural empyemas in dren. Int J Pediatr Otorhinolaryngol 1993;27:73–8.
children. Pediatr Neurosci 1987;13:251–4. 113. Robie DK, Pearl RH, Gonsales C, et al. Operative
96. Roth B, Rose KG, Benz-Bohm G, Gunther H. strategy for recurrent laryngeal cleft: a case report
Laryngo-tracheo-oesophageal cleft. Clinical fea- and review of the literature. J Pediatr Surg 1991;
tures, diagnosis and therapy. Eur J Pediatr 1983; 26:971–3; discussion 973.
140:41–6. 114. Prescott CA. Cleft larynx: repair with a posterior
97. Finlay HV. Familial congenital stridor. Arch Dis cartilage graft. Int J Pediatr Otorhinolaryngol
Child 1949;24:219–23. 1995;31:91–4.
98. Evans JN. Management of the cleft larynx and tra- 115. Ahmad R, Horwitz PE, Sami KA, Rabeeah A. A
cheoesophageal clefts. Ann Otol Rhinol Laryngol bifurcated endobronchial tube in the management
1985;94:627–30. of laryngotracheo-oesophageal cleft repair [pub-
99. Jahrsdoerfer RA, Kirchner JA, Thaler SU. Cleft lar- lished erratum appears in Br J Anaesth 1994;
ynx. Arch Otolaryngol 1967;86:108–13. 72:371]. Br J Anaesth 1993;70:696–8.
100. Cohen SR. Cleft larynx. A report of seven cases. 116. Geiduschek JM, Inglis AF, O’Rourke PP, et al. Repair
Ann Otol Rhinol Laryngol 1975;84:747–56. of a laryngotracheoesophageal cleft in an infant by
101. Garel C, Hassan M, Hertz-Pannier L, et al. Contri- means of extracorporeal membrane oxygenation.
bution of MR in the diagnosis of ‘occult’ posterior Ann Otol Rhinol Laryngol 1993;102:827–33.
laryngeal cleft. Int J Pediatr Otorhinolaryngol 117. Cotton RT, Schreiber JT. Management of laryngo-
1992;24:177–81. tracheoesophageal cleft. Ann Otol Rhinol Laryngol
102. Delahunty JE, Cherry J. Congenital laryngeal cleft. 1981;90:401–5.
Ann Otol Rhinol Laryngol 1969;78:96–106. 118. Cohen SR, Geller KA, Birns JW, Thompson JW.
103. Corbally MT. Laryngo-tracheo-oesophageal cleft. Laryngeal paralysis in children: a long-term retro-
Arch Dis Child 1993;68:532–3. spective study. Ann Otol Rhinol Laryngol 1982;
104. Holinger LD, Tansek KM, Tucker GF Jr. Cleft lar- 91:417–24.
ynx with airway obstruction. Ann Otol Rhinol 119. Swift AC, Rogers J. Vocal cord paralysis in children.
Laryngol 1985;94:622–6. J Laryngol Otol 1987;101:169–71.
105. Tucker GF Jr, Maddalozzo J. “Occult” posterior 120. Phelan PD. “Oscopy” in children: laryngoscopy and
laryngeal cleft. Laryngoscope 1987;97:701–4. bronchoscopy. Aust Fam Physician 1979;8:853–7.
106. Tyler DC. Laryngeal cleft: report of eight patients 121. Hoffman HJ, Hendrick EB, Humphreys RP. Mani-
and a review of the literature. Am J Med Genet festations and management of Arnold-Chiari mal-
1985;21:61–75. formation in patients with myelomeningocele.
107. Walner DL, Stern Y, Collins M, et al. Does the pres- Childs Brain 1975;1:255–9.
ence of a tracheoesophageal fistula predict the out- 122. Krieger AJ, Detwiler JS, Trooskin SZ. Respiratory
come of laryngeal cleft repair? Arch Otolaryngol function in infants with Arnold-Chiari malforma-
Head Neck Surg 1999;125:782–4. tion. Laryngoscope 1976;86:718–23.
108. Petterson G. Inhibited separation of larynx and the 123. Cavanagh F. Vocal palsies in children. J Laryngol
upper part of trachea from oesophagus in a new- Otol 1955;69:399.
born. Acta Chir Scand 1955;110:250–4. 124. Dedo DD. Pediatric vocal cord paralysis. Laryngo-
109. Koltai PJ, Morgan D, Evans JN. Endoscopic repair scope 1979;89:1378–84.
of supraglottic laryngeal clefts. Arch Otolaryngol 125. Holinger LD, Holinger PC, Holinger PH. Etiology
Head Neck Surg 1991;117:273–8. of bilateral abductor vocal cord paralysis: a review
110. Nuutinen J, Karja J, Karjalainen P. Measurements of 389 cases. Ann Otol Rhinol Laryngol 1976;
of impaired mucociliary activity in children. Eur J 85:428–36.
Respir Dis 1983; Suppl 128:454–6. 126. Gardner E, O’Rahilly R, Prolo D. The Dandy-
111. Pettit PN, Butcher RB, Bethea MC, Danks DM. Walker and Arnold-Chiari malformations. Clinical,
Surgical correction of complete tracheoesophageal developmental, and teratological considerations.
cleft. Laryngoscope 1979;89:804–11. Arch Neurol 1975;32:395–407.
Congenital Anomalies of the Larynx 1071
127. Mackenzie IJ, Kerr AI, Cowan DL. A review of 141. Parkin JL, Stevens MH, Jung DL. Acquired and
endoscopies of the respiratory tract and oesopha- congenital subglottic stenosis in the infant. Ann
gus in a children’s hospital. Health Bull (Edinb) Otol Rhinol Laryngol 1976;85:573–81.
1984;42:78–80. 142. Whited RE. A prospective study of laryngotracheal
128. Richardson MA, Cotton RT. Anatomic abnormali- sequelae in long-term intubation. Laryngoscope
ties of the pediatric airway. Ear Nose Throat J 1984;94:367–77.
1985;64:47–60. 143. Benjamin B. Prolonged intubation injuries of the
129. Holinger PC, Holinger LD, Reichert TJ, Holinger larynx: endoscopic diagnosis, classification, and
PH. Respiratory obstruction and apnea in infants treatment. Ann Otol Rhinol Laryngol Suppl 1993;
with bilateral abductor vocal cord paralysis, 160:1–15.
meningomyelocele, hydrocephalus, and Arnold- 144. Holinger PH, Kutnick SL, Schild JA, Holinger LD.
Chiari malformation. J Pediatr 1978;92:368–73. Subglottic stenosis in infants and children. Ann
130. Bluestone CD, Delerme AN, Samuelson GH. Otol Rhinol Laryngol 1976;85:591–9.
Airway obstrucion due to vocal cord paralysis 145. Sasaki CT, Horiuchi M, Koss N. Tracheostomy-
in infants with hydrocephalus and meningo- related subglottic stenosis: bacteriologic pathogen-
myelocele. Ann Otol Rhinol Laryngol 1972;81: esis. Laryngoscope 1979;89:857–65.
778–84. 146. Healy GB. An experimental model for the
131. Gacek RR. Hereditary abductor vocal cord paraly- endoscopic correction of subglottic stenosis with
sis. Ann Otol Rhinol Laryngol 1976;85:90–3. clinical applications. Laryngoscope 1982;92:
132. Watters GV, Fitch N. Familial laryngeal abductor 1103–15.
paralysis and psychomotor retardation. Clin Genet 147. Cotton RT, Silver P, Nuwayhid NS. Chronic laryn-
1973;4:429–33. geal and tracheal stenosis. In: Paparella MM,
133. Plott D. Congenital laryngeal-abductor paralysis Shumrick DA, editors. Otolaryngology. 2nd ed.
due to nucleus ambiguus dysgenesis in three broth- Philadelphia: WB Saunders; 1980. p. 2931–50.
ers. N Engl J Med 1964;27:593–7. 148. Fee WE, Wilson GG. Tracheoesophageal space
134. Cohen SR, Geller KA, Birns JW, Thompson JW. abscess. Laryngoscope 1979;89:377–84.
Laryngeal paralysis in children: a long-term retro- 149. Lindholm CE. Prolonged endotracheal intubation,
spective study. Ann Otol Rhinol Laryngol 1982; a valuable alternative to tracheostomy. Bronches
91:417–24. 1968;18:398–408.
135. Holinger PC, Vuckovich DM, Holinger LD, 150. Pashley NR. Risk factors and prediction of out-
Holinger PH. Bilateral abductor vocal cord paraly- come in acquired subglottic stenosis in children.
sis in Charcot-Marie-Tooth disease. Ann Otol Rhi- Int J Pediatr Otorhinolaryngol 1982;4:1–6.
nol Laryngol 1979;88:205–9. 151. McMillan WG, Duvall AJ. Congenital subglottic
136. Bressler KL, Kaiser PC, Dunham ME, Holinger LD. stenosis. Arch Otolaryngol 1968;87:272–8.
Primary closure of persistent tracheocutaneous fis- 152. Marshak G, Grundfast KM. Subglottic stenosis.
tula in children. Ann Otol Rhinol Laryngol 1994; Pediatr Clin North Am 1981;28:941–8.
103:835–7. 153. Noyek AM. Xeroradiography in the assessment of
137. Cotton RT, Evans JN. Laryngotracheal reconstruc- the pediatric larynx and trachea. J Otolaryngol
tion in children. Five-year follow-up. Ann Otol 1976;5:468–74.
Rhinol Laryngol 1981;90:516–20. 154. Cotton RT. Management of subglottic stenosis in
138. Holinger LD. Treatment of severe subglottic steno- infancy and childhood: review of a consecutive
sis without tracheotomy: a preliminary report. Ann series of cases managed by surgical reconstruction.
Otol Rhinol Laryngol 1982;91:407–12. Ann Otol Rhinol Laryngol 1978;87:649.
139. Hawkins DB. Hyaline membrane disease of the 155. Cotton RT, Seid AB. Management of the extuba-
neonate prolonged intubation in management: tion problem in the premature child. Anterior
effects on the larynx. Laryngoscope 1978;88: cricoid split as an alternative to tracheotomy. Ann
201–24. Otol Rhinol Laryngol 1980;89:508–11.
140. Papsidero MJ, Pashley NR. Acquired stenosis of the 156. Cotton RT. Prevention and management of laryn-
upper airway in neonates. An increasing problem. geal stenosis in infants and children. J Pediatr Surg
Ann Otol Rhinol Laryngol 1980;89:512–4. 1985;20:845–51.
1072 Ballenger’s Otorhinolaryngology
157. Holinger LD, Stankiewicz JA, Livingston GL. Ante- 172. Cotton RT, Manoukian JJ. Glottic and subglottic
rior cricoid split: the Chicago experience with an stenosis. In: Cummings CW, Fredrickson JM,
alternative to tracheotomy. Laryngoscope 1987; Harker LA, et al, editors. Otolaryngology-head
97:19–24. and neck surgery. St. Louis: CV Mosby; 1986.
158. Lusk RP, Kang DR, Muntz HR. Auricular cartilage p. 2159–80.
grafts in laryngotracheal reconstruction. Ann Otol 173. Seid AB, Pransky SM, Kearns DB. One-stage laryn-
Rhinol Laryngol 1993;102:247–54. gotracheoplasty. Arch Otolaryngol Head Neck Surg
159. Lusk RP, Gray S, Muntz HR. Single-stage laryngo- 1991;117:408–10.
tracheal reconstruction. Arch Otolaryngol Head 174. Looper EA. The use of hyoid bone as graft in laryn-
Neck Surg 1991;117:171–3. geal stenosis. Arch Otolaryngol 1938;28:106.
160. Richardson MA, Inglis AF. A comparison of ante- 175. Bennett T. Laryngeal strictures. South Med J
rior cricoid split with and without costal cartilage 1960;53:1101.
graft for acquired subglottic stenosis. Int J Pediatr 176. Finnegan DA, Wong ML, Kashima HK. Hyoid
Otorhinolaryngol 1991;22:187–93. autograft repair of chronic subglottic stenosis. Ann
161. Otherson HB. Steroid therapy for tracheal stenosis Otol Rhinol Laryngol 1975;84:643–9.
in children. Ann Thorac Surg 1974;17:254. 177. Thawley SE, Ogura JH. Panel discussion: the man-
162. Kirchner FR, Toledo PS. Microcauterization in oto- agement of advanced laryngotracheal stenosis. Use
laryngology. Arch Otolaryngol 1974;99:198–202. of the hyoid graft for treatment of laryngotracheal
163. Rodgers BM, Talbert JL. Clinical applications of stenosis. Laryngoscope 1981;91:226–32.
endotracheal cryotherapy. J Pediatr Surg 178. Ward PH, Canalis R, Fee W, Smith G. Composite
1978;13:662–8. hyoid sternohyoid muscle grafts in humans: its use
164. Strome M, Donahoe PK. Advances in management in reconstruction of subglottic stenosis and the
of laryngeal and subglottic stenosis. J Pediatr Surg anterior tracheal wall. Arch Otolaryngol Head
1982;17:591–6. Neck Surg 1977;103:531–4.
165. Downing TP, Johnson DG. Excision of subglottic 179. Cotton RT. Pediatric laryngotracheal stenosis. J
stenosis with the urethral resectoscope. J Pediatr Pediatr Surg 1984;19:699–704.
Surg 1979;14:252–7. 180. Fearon B, Cinnamond M. Surgical correction of
166. Simpson GT, Strong MS, Healy GB, et al. Predictive subglottic stenosis of the larynx: clinical results of
factors of success or failure in the endoscopic man- the Fearon-Cotton operation. J Otolaryngol
agement of laryngeal and tracheal stenosis. Ann 1976;5:475–8.
Otol Rhinol Laryngol 1982;91:384–8. 181. Fearon B, Cotton RT. Surgical correction of sub-
167. Friedman EM, Healy GB, McGill TJ. Carbon diox- glottic stenosis of the larynx in infants and chil-
ide laser management of subglottic and tracheal dren. Progress report. Ann Otol Rhinol Laryngol
stenosis. Otolaryngol Clin North Am 1983;16: 1974;83:428–31.
871–7. 182. Ludemann JP, Hughes CA, Noah Z, Holinger LD.
168. Healy GB, McGill T, Simpson GT, Strong MS. The Complications of pediatric laryngotracheal recon-
use of the carbon dioxide laser in the pediatric air- struction: prevention strategies. Ann Otol Rhinol
way. J Pediatr Surg 1979;14:735–40. Laryngol 1999;108:1019–26.
169. Koufman JA, Thompson JN, Kohut RI. Endoscopic 183. Cotton RT, Gray SD, Miller RP. Update of the
management of subglottic stenosis with the CO2 Cincinnati experience in pediatric laryngotracheal
surgical laser. Otolaryngol Head Neck Surg 1981; reconstruction. Laryngoscope 1989;99:1111–6.
89:215–20. 184. Benjamin B. Congenital disorders. In: Cummings
170. Lyons GD, Owens R, Lousteau RJ, Trail ML. Car- CW, Fredrickson JM, Harker LA, et al, editors. Oto-
bon dioxide laser treatment of laryngeal stenosis. laryngology-head and neck surgery. St. Louis: CV
Arch Otolaryngol 1980;106:255–6. Mosby; 1986. p. 2329–38.
171. Strong MS, Healy GB, Vaughan CW, et al. Endo- 185. Wooley AL, Lusk RP. Multiple vascular lesions of
scopic management of laryngeal stenosis. Oto- an infant’s airway. Otolaryngol Head Neck Surg
laryngol Clin North Am 1979;12:797–805. 1994;111:305–8.
CHAPTER 46
Congenital head and neck anomalies represent a terior and inferior to the foregoing arches. In each
diverse group of clinical disorders. Frequently, these arch, a central artery develops, connecting the two
present as upper aerodigestive tract neoplasms and ventral and two dorsal aortas. The two ventral aor-
neck masses, with thyroglossal duct abnormalities tas fuse completely, whereas the two dorsal aortas
most common, followed by branchial arch defects, only fuse caudally. With continued development, the
lymphangiomas (cystic hygromas), and subcuta- ventral aortas become the external and common
neous vascular anomalies (hemangiomas, arteriove- carotid arteries, whereas the arteries of the first and
nous malformations). Less common are teratomas, second arch degenerate. Segments of the dorsal aor-
heterotopic neural tissue, and nasopharyngeal neo- tas persist as the internal carotid arteries along with
plasms. Additional disorders encountered include the artery of the third arch. The left fourth arch
congenital disorders of the oral cavity including cleft artery becomes the arch of the aorta, and the right
lip and palate, Pierre Robin sequence (PRS), and fourth arch artery becomes the proximal portion of
other aberrations such as primary ciliary dyskinesia, the subclavian artery. The primitive clefts pass
Kartagener’s syndrome, and craniofacial anomalies. between the corresponding arteries.1 The most
widely accepted theory of the genesis of branchial
cleft anomalies is that fistulae, sinuses, and cysts
CONGENITAL DISORDERS result from incomplete closure of the connection
OF THE NECK between the cleft and the pouch, with rupture of the
branchial plate. Recently, an induced first and sec-
BRANCHIAL CLEFT ANOMALIES ond branchial arch syndrome in an animal model
Lateral cervical lesions, termed branchial cleft cysts, was shown to be secondary to disturbed migration
are congenital developmental defects that arise from of neural crest tissue during early embryogenesis.2
the primitive branchial apparatus (branchial arch, Additionally, targeted mutations of two related basic
cleft, and pouches). First branchial cleft anomalies helix-loop-helix transcription factors in the devel-
are discussed elsewhere in this chapter. oping ventricles of the heart in mice have been asso-
ciated with branchial arch hypoplasia, suggesting a
Embryogenesis The branchial arches consist of molecular basis for branchial cleft anomalies.3 These
five parallel mesodermal bars, each with its nerve anomalies are generally lined with stratified squa-
supply and blood vessel (primitive aortic arches that mous epithelium containing subepithelial lymphoid
develop during the third and fourth embryonic follicles, keratin, hair follicles, sweat glands, cartilage,
weeks). The branchial arches are separated externally and sebaceous glands.
by branchial clefts consisting of ectoderm and inter-
nally by endodermally lined branchial (pharyngeal) Clinical Presentation Typically, branchial clefts
pouches. A branchial plate is located between each present as smooth, round, fluctuant, nontender
arch, separating pouch from cleft. The nerves are masses along the anterior border of the sternoclei-
anterior to their respective arteries, except in the fifth domastoid muscle, anywhere from the external audi-
arch, where the nerve is posterior to the artery. Cau- tory canal to the clavicle. During upper respiratory
dal to all of the arches is the twelfth nerve, which tract infections, a painful increase in size is common
arises from the epicardial ridge. The sternocleido- and occasionally may be associated with external
mastoid muscle is derived from cervical somites pos- drainage through an unrecognized fistula. Small
1073
1074 Ballenger’s Otorhinolaryngology
cysts may not be recognized until the second decade operative assessment with computed tomographic
in life. Male and female incidences are equal, and (CT) scanning or magnetic resonance imaging
nearly all of these lesions are recognized by the time (MRI) is essential and may be combined with a fis-
the patient reaches 30 years of age. tulogram or pharyngoesophagram when indicated.
A “stepladder” surgical approach is used to avoid
Second Branchial Cleft Anomalies Second long, cosmetically deforming incisions, paralleling
branchial cleft lesions are the most common anom- the sternocleidomastoid muscle. To avoid recur-
alies and are encountered most frequently in the rence, combined endoscopic examination for a pha-
anterior triangle of the neck along the anterior bor- ryngeal pouch and sinus tract with meticulous
der of the sternocleidomastoid muscle inferior to the dissection of a sinus tract, if present, will facilitate
angle of the mandible. The fistula tract, if present, complete resection.
ascends along the carotid sheath, crosses over the
hypoglossal and glossopharyngeal nerves, and Branchiogenic Carcinoma The hypothesis that
courses between the internal and external carotid squamous cell carcinoma arises in a branchial cleft
arteries. It ends in the tonsillar fossa, a second cyst (branchiogenic carcinoma) is controversial.
branchial pouch derivative. Cystic squamous cell carcinoma presenting in the
Second pouch remnants may form blind neck without an apparent primary is almost univer-
sinuses in the pharyngeal tonsil and frequently cause sally secondary to metastasis from a neoplasm aris-
recurrent unilateral tonsillitis. Treatment requires ing in the faucial or lingual tonsillar crypt
tonsillectomy and excision of the sinus tract. epithelium or nasopharyngeal tissue.6 Malignant
transformation in a branchial cleft cyst is therefore a
Third Branchial Cleft Anomalies Third branchial rarity. Management is wide excision of the tumor
cleft anomalies are unusual and constitute less than and ipsilateral radical neck dissection followed by
1% of all branchial cleft anomalies.4 The external radiation therapy.7
ostium occurs at the same position as the second
branchial cleft anomaly, and the cyst may be located
anywhere along the fistula. The fistula tract ascends LYMPHANGIOMAS, HEMANGIOMAS, AND
along the carotid sheath behind the internal carotid VASCULAR MALFORMATIONS
artery and over the hypoglossal nerve, and it enters
the piriform sinus, piercing the middle constrictor Congenital lymphangiomatous malformations of
muscle below the glossopharyngeal nerve. Clinically, the head and neck represent a wide clinical spec-
the anomaly may mimic suppurative thyroiditis or trum. Lymphangiomas result from abnormal devel-
symptoms of an external laryngocele and can cause opment of the lymphatic system at sites of
recurrent infection, discharge, and, rarely, stridor. lymphatic-venous connection, with obstruction of
lymph drainage from the affected area causing mul-
Fourth Branchial Cleft Anomalies Fourth ticystic endothelium-lined spaces. The neck is the
branchial cleft anomalies are extremely rare. Only 40 most common site (25% of all cases). Over half of
cases have been reported. The fistula tract descends these lesions are present at birth, with 90% becom-
along the carotid sheath, enters the chest, passing ing apparent by 2 years of age. Those lymphan-
under either the aortic arch on the left or the sub- giomas arising above the mylohyoid tend to extend
clavian artery on the right, and ascends in the neck from skin to mucosa and are more infiltrative,
to open at the apex of the piriform sinus. The sinus whereas those below are more discreet and cystic.
tract or cyst may become clinically manifested by
recurrent episodes of neck abscess or acute suppu- Cystic Hygroma Cystic hygromas are large lym-
rative thyroiditis (particularly in infants). A left pre- phangiomas most commonly found in the posterior
dominance has been reported in one series.5 triangle of the neck and axilla in children.8 Cervical
cystic hygromas commonly appear before 30 weeks
Treatment Complete surgical excision is the treat- gestation and are usually associated with karyotypic
ment of choice for branchial cleft anomalies and is abnormalities, various malformation syndromes,
indicated for recurrent infection, cosmetic defor- and several teratogenic agents.9 The prognosis is
mity, and potential for malignant degeneration. Pre- poor for these types of hygromas. By contrast, cys-
Congenital Anomalies of the Head and Neck 1075
tic hygroma developing late in pregnancy has a Most frequently, it occurs as a thyroglossal duct cyst
more favorable outcome and is more likely to be associated with a normal thyroid gland. Less com-
encountered by the head and neck surgeon. Cystic mon is total ectopia, appearing as a lingual thyroid.
hygromas are soft, painless, and compressible True lateral neck thyroid ectopia lateral to the
masses that may increase when the patient cries. carotid artery and jugular vein cannot be confirmed
Two-thirds are asymptomatic. After an upper respi- based on embryogenesis.10 Therefore, laterally situ-
ratory tract infection, however, sudden enlargement ated thyroid tissue should direct attention to the
with inflammation, infection, dysphagia, and stri- ipsilateral thyroid lobe. If papillary carcinoma is
dor may develop. This is more commonly seen if the found in an aberrant position, then either ipsilateral
anterior triangle of the neck is involved or in thyroid lobectomy with isthmusectomy or total thy-
patients with pharyngolaryngeal extension or intra- roidectomy is performed.
oral involvement.
Embryology In the 4-week-old embryo, the prim-
Vascular Lesions Other congenital vascular itive thyroid gland begins as a ventral diverticulum
lesions of the head and neck include hemangiomas of endodermal origin, arising in the floor of the
and arteriovenous malformations or lymphovenous pharynx between the tuberculum impar and the
lesions. Diagnostic imaging of these anomalies is copula. Ultimately, the site of origin of the divertic-
based on the need for surgical treatment. Only those ulum becomes the foramen cecum, and the copula
lesions that cause functional impairment or devel- becomes the posterior third of the tongue. The thy-
opmental disturbance are surgically addressed. roid descends caudally through or adjacent to the
Angiography, combined with MRI, allows separation primitive hyoid bone. The developing thyroglossal
into low-flow lesions (hemangiomas, venous, and duct reaches its final position in the midline of the
lymphatic malformations) and high-flow lesions
(arteriovenous malformations and invasive, com-
bined lymphovascular malformations).
neck and develops into the median lobe of the thy- anterior tongue protrusion and swallowing. Usually,
roid. The duct normally persists as a hollow stalk for the cysts are 1 to 3 cm in diameter and are smooth,
6 weeks and then atrophies. Thyroglossal duct round, and fluctuant.
anomalies result from a failure of complete obliter- A precise pathogenesis of thyroglossal duct
ation of the thyroglossal duct and are located any- cysts has not been determined. However, a heredi-
where along the descent of the gland. tary etiology is suspected. Overall, for non-Ameri-
cans, a predominantly autosomal dominant pattern
Lingual Thyroid Lingual thyroid presents in the of inheritance has been reported in older patients
midline as a sessile, nontender reddish mass in the (mean age 13.9 years) versus an autosomal recessive
base of the tongue, anterior to the valleculae. It is the pattern in younger patients (mean age 6.2 years).12 In
most frequent benign mass encountered in the the United States, on the other hand, a female pre-
oropharynx and, unlike other aberrant thyroid ponderance is observed with autosomal dominance
anomalies, has a 7 to 1 female preponderance. and a younger mean age, which may be accounted
Symptoms may include dysphagia, cough, dyspho- for by genetic imprinting that is felt to be secondary
nia, dyspnea, and hemorrhage. Lingual thyroid may to variations in DNA methylation.
become apparent during pregnancy because of
increased thyroid function, and approximately 70% HISTOPATHOLOGIC FEATURES. Thyroglossal duct cysts
of these women have hypothyroidism. and fistulae are lined with squamous, ciliated colum-
Lingual thyroid is covered with stratified squa- nar, or transitional cell epithelium. They may be
mous epithelium and often exhibits an abundant surrounded by fibrous tissue with infiltrating
aberrant vascular supply. The mass consists of nor- inflammatory cells lacking organized lymphoid tis-
mal or immature thyroid tissue, which may be either sue. Islands of ectopic thyroid tissue and mucous
functional or dysfunctional. Indications for surgical glands are not uncommonly identified. The cyst or
removal include uncontrollable hyperthyroidism, sinus tract is filled with mucoid or mucopurulent
hemorrhage, symptomatic enlargement, or a ques- material.
tion of malignancy. Carcinoma arising in a lingual
thyroid is rare, with only 26 cases reported.11 Preop- DIFFERENTIAL DIAGNOSIS. The differential diagnosis
eratively, a thyroid uptake study and scan should be includes dermoid cyst, pyramidal lobe hyper-
obtained to determine whether functioning thyroid plasia or cyst, teratoma, hamartoma, lipoma, seba-
tissue exists in its normal cervical location. Magnetic ceous cyst, cavernous hemangioma, hypertrophic
resonance imaging may also be of value because it lymph node, and malignant primary or metastatic
allows multiplanar imaging and provides the best neoplasm.
soft tissue definition. Excision is performed through
the transhyoid route. TREATMENT. As with lingual thyroid, a preoperative
thyroid scan and uptake study are mandatory, even
Thyroglossal Duct Anomalies Signs and Symp- though concomitant agenesis of the thyroid gland is
tons A thyroglossal duct cyst is the most common extremely rare. Malignant degeneration, recurrent
congenital neck mass and the second most common infections, undesirable cosmetic appearance, and,
of all childhood cervical neck masses. Cysts, sinuses, rarely, intermittent upper airway obstruction are
and fistulae of the thyroglossal duct manifest as indications for surgical excision of thyroglossal duct
anterior midline neck masses from the foramen cysts and fistulae. Incision and drainage may be nec-
cecum to the thyroid gland, typically before 20 years essary in the interim if an abscess has developed.
of age (most before 10 years). Thyroglossal ducts Because of the high recurrence rate after excision,
and fistulae are often asymptomatic. They may also the Sistrunk procedure is recommended to prevent
become recurrently infected during upper respira- recurrence.13 This involves a transverse incision over
tory tract infections, which can cause cyst enlarge- the cyst or a fusiform incision around an external
ment, abscess development, and rupture with fistula. All abnormal tissue, including the cyst, fis-
external sinus formation. Thyroglossal duct cysts are tula, body of the hyoid bone (preferably more than
most commonly found below the hyoid bone and 15 mm), and the fibrous cord extending to the fora-
above the thyroid gland, displaying movement with men cecum, should be resected. Recurrence devel-
Congenital Anomalies of the Head and Neck 1077
ops in up to 20% of cases as a result of failure to connective tissue sheath of the nerve are termed
remove all abnormal tissue, including accessory schwannomas and may appear as multiple neurofi-
ducts. Malignant degeneration of a thyroglossal duct bromas arising from cutaneous, visceral, and cranial
cyst is rare (0.7%).14 nerves in neurofibromatosis (NF) 1 or 2. The inci-
Approximately 150 cases of thyroglossal duct dence of head and neck manifestations in patients
carcinoma, predominantly of the papillary type, with NF (a genetic disease) varies between 14 and
have been reported. Additional cases of Hürthle cell 37%. In NF1 (classic von Recklinghausen’s disease),
adenoma have also been described.15 Most patients functional deficits include speech and voice abnor-
with papillary carcinoma are in their forties, malities, airway obstruction, dysphagia, facial pare-
although 20% are less than 20 years of age. Typically, sis, lip incompetence, and impaired mastication.
the neoplasm is small and clinically unsuspected, Patients with NF2 (bilateral acoustic schwannomas)
and, in rare cases, it may be associated with regional present with hearing loss.18
or distant metastasis. Rarely, squamous cell carci- Typically, neuromas appear as solitary, encap-
noma arising directly from the lining epithelium of sulated lesions with elongated, spindle-shaped cells
a thyroglossal duct remnant has been reported and, with an oval or flattened nucleus. Ganglioneuromas,
as a rule, has a poor prognosis. Treatment consists of rarely seen in the head or neck, are characterized by
excision of the thyroglossal duct cyst, total or near- ganglion and glial cells. Meningiomas are usually
total thyroidectomy, ablative radioactive iodine ther- benign and arise from embryonic arachnoid rests.
apy for residual metastatic thyroid neoplasm tissue, They may appear extracranially at the nasal root or
and careful interval follow-up with whole-body thy- in the sinuses. Whorl-like fibroblastic nuclei with
roid scanning. hyaline formations producing a sand-like appear-
ance may be present (psammoma body). Pharyngeal
neuromas are rare and appear as a smooth, firm,
THYMIC CYSTS rounded, and yellow mass. Symptoms depend on the
Cervical thymic cysts are extremely rare. Only 84 size and location of the tumor. If multiple brown
cases have been reported in the English language, discolorations of the skin or café au lait spots are
with most occurring asymptomatically in children present, neurofibroma may be suggested. Treatment
and adults. Only seven cases have involved patients is surgical excision, and resection must be complete
younger than 1 year of age.16 Cysts can arise from because recurrence is common.
nests of thymic tissue anywhere along the descent of
the thymic primordia from the angle of the
mandible to the mediastinum and are primarily CONGENITAL DISORDERS OF THE
located anterior and deep to the middle one-third of NOSE AND PARANASAL SINUSES
the sternocleidomastoid muscle. In up to 50% of
cervical thymic cysts, there is a mediastinal connec-
HETEROTOPIC NEURAL TISSUE
tion possibly requiring a sternotomy. Surgery is the Heterotopic neural tissue or gliomas may manifest
definitive treatment (Figure 46–2).16 Three addi- as isolated ectopic brain tissue with only a fibrous
tional cases of solid, ectopic, cervical thymus have band connecting it to the endocranium. A glioma
been reported requiring complete excision.17 may be of the external or endonasal type. The exter-
nal nasal glioma is typically found in the nasion as a
red, relatively firm, mobile mass located subcuta-
NEUROGENIC NEOPLASMS neously that does not increase in size when the
Congenital neurogenic lesions involving the head patient cries. The endonasal glioma is less common
and neck include all neoplasms or anomalies origi- and arises from the middle turbinate or the lateral
nating in the neural tissue or its covering. Two nasal vault, where it may be mistaken for a polyp. By
groups have been recognized: (1) heterotopic brain contrast, a meningocele is a hernial protrusion of the
lesions with developmental defects and (2) neo- meninges, and if it contains brain tissue, it is called
plasms of neurogenic origin including neurinomas, an encephalocele.
neurofibromas, neuromas, ganglioneuromas, and An encephalocele is caused by a defect of the
meningiomas. Neurinomas originating from the fetal skull and contains an ependyma-lined cavity
1078 Ballenger’s Otorhinolaryngology
filled with cerebrospinal fluid. Two basic types of her- orbital, in which the encephalocele extends through
nial protrusions are identified: the sincipital type and the spheno-orbital fissure into the posterior aspect of
the basal type. The sincipital type is uncommon and the orbit, resulting in pulsatile exophthalmos; and (3)
is associated with termination of the meninges near sphenomaxillary, in which the encephalocele herni-
the base of the nose. This type has three different ates through the spheno-orbital fissure into the orbit,
forms: (1) nasofrontal, in which the encephalocele with extension inferiorly through the inferior orbital
extends between the nasal and frontal bones, result- fissure into the pterygomaxillary fissure.19 This
ing in a midline swelling at the base of the nose; (2) results in a mass bulging into the cheek or into the
nasoethmoidal, in which a defect among the nasal, oropharynx, medial to the ramus of the mandible. In
frontal, and ethmoid bones allows the encephalocele all cases, unlike with gliomas, pulsations and an
to appear as a mass beneath the skin of the bony-car- increase in the size of the mass can be observed when
tilaginous junction; and (3) naso-orbital protrusion the patient coughs or strains. Computed tomography
of the encephalocele through the suture lines among and MRI are necessary to determine the appropriate
the lacrimal, frontal, and ethmoidal bones appearing combined transfacial and intracranial approach for
as a conjunctival mass. The basal type, in which the surgical resection.20
hernia extends into the naso-orbital and pharyngeal
region, is rarer than the sincipital. Three varieties
have been identified: (1) sphenoid-pharyngeal, in
DERMOID CYSTS
which the encephalocele extends through the eth- Dermoid cysts occasionally occur in the neck, usu-
moid or sphenoid bones or their sutures lines into ally in the midline. Overall, fewer than 10% of all
the nasal or nasopharyngeal cavity; (2) sphenoid- dermoid cysts occur in the head and neck. One-
Congenital Anomalies of the Head and Neck 1079
fourth are found in the floor of the mouth, with the abnormalities in the migration of the cephalic neu-
remainder in the periorbital region. These lesions ral crest following neural tube closure. Several cran-
are seen primarily in children and adolescents dur- iofacial abnormalities, including skull base defects
ing the second decade of life, but they also may and systemic malformations, have been described in
occur in infants. Cyst walls consist of squamous cell association with choanal atresia, including the
epithelium containing epidermal appendages. Peri- CHARGE association (Table 46–1). The CHARGE
orbital dermoids are thought to originate from dis- association is a nonrandom pattern of congenital
placement of epidermal elements during the anomalies that has an estimated prevalence of 1 in
intramembranous growth phase of the nasal bones 10,000 births. It occurs with choanal atresia (C =
in the embryo. Because of the variability in clinical coloboma; H = congenital heart disease; A = atresia
presentation and contiguous structure involvement, choanae; R = retarded growth and development; G =
segregation of periorbital lesions into three distinct genital anomalies in males; E = ear abnormalities
subgroups is helpful: (1) brow region dermoid cysts, and deafness). Almost all patients have malformed
(2) orbital region dermoid cysts, and (3) nasoglabel- pinnae and exhibit hypoplastic incudes, cochlear
lar dermoid cysts. Midline nasoglabellar cysts may anomalies, and absent semicircular canals on CT
have associated sinus tracts or fistulae (10 to 45%), scan (Figure 46–3). The majority demonstrate severe
which, in rare cases, may have intracranial exten- conductive or mixed hearing loss and vestibular dys-
sions. In those patients with intracranial extension, function.24 In addition, almost half exhibit facial
the sinus tract traverses either the cribriform plate or nerve palsies. Laryngotracheal anomalies occur in
foramen cecum and is attached to the dura, falx one-third of cases. The combination of malforma-
cerebri, or other intracranial structures.21 tions in the CHARGE association suggests that this
The treatment of choice is surgical excision syndrome is a polytopic developmental field defect
after CT and MRI to evaluate intracranial exten- involving the neural tube and neural crest cells.25
sion.22 All abnormal tissue must be removed to pre-
vent recurrences. In patients with intracranial Symptoms Respiratory distress at birth is the sine
extension, a bicoronal flap is employed to facilitate qua non of bilateral choanal atresia. In spite of vig-
removal and to prevent postoperative meningitis orous attempts at respiration, effective air exchange
and abscess formation. does not occur until the neonate begins to cry,
Other congenital midface cysts are those asso- bypassing the nasal obstruction. Once the crying
ciated with the facial clefts, including the nasoeth- ceases, however, the neonate’s mouth closes, and a
moidal cleft cyst, nasolabial cyst, subalar cleft cyst, pattern of cyclic obstruction gradually develops,
globulomaxillary cyst, cysts connected with cleft lip resulting in increasing respiratory failure. Because
or palate, premaxillary cyst, nasopalatine cyst, neonates are obligatory nasal breathers, placement
foraminal incisor cyst, and Jacobson’s organ cysts. of an oral airway or McGovern nipple is lifesaving.
By contrast, children with unilateral choanal atresia
CHOANAL ATRESIA
TABLE 46–1. Congenital Anomalies Associated with
Bilateral atresia of the choanae is the most frequently
Choanal Atresia
encountered congenital nasal anomaly (1 in 7,000 to
8,000 live births) and is a common cause of neona- Branchial anomalies
tal respiratory distress. Fifty to 60% of cases are CHARGE association
unilateral. A recent analysis of 47 CT scans or his-
topathologic sections demonstrated 29% pure bony, Humeroradial synostosis
71% mixed bony and membranous, and no pure Mandibular facial synostosis
membranous atresia.23 A female predisposition is
Microcephaly
seen in choanal atresia, and recent evidence points to
an autosomal recessive mode of inheritance. Micrognathia
Failure of breakdown of the buccopharyngeal Nasopharyngeal anomalies
membrane on gestational day 45 is considered to be
Palatal defects
the cause of choanal atresia. Other theories include
1080 Ballenger’s Otorhinolaryngology
present later in life with unilateral rhinorrhea with- perforation of the atresia plate followed by stenting
out respiratory distress. for 6 weeks with preservation of mucosal flaps.
Diagnosis The diagnosis of bilateral choanal atre- TRANSNASAL APPROACH. The most direct and sim-
sia is confirmed by the inability to pass a No. 5 or 6 plest route for choanal atresia repair is transnasal,
French feeding catheter at least 3 cm through the using a No. 2 Lempert or similar curette inserted 3
nose into the nasopharynx. In addition, direct obser- to 3.5 cm beyond the nares along the nasal floor
vation with nasofiber-optic endoscopy and CT scan and exerting firm pressure against the bony atresia
are essential to determine the type of obstruction. plate until it is perforated. The anterior nasal
Specifically, the CT scan demonstrates the thickness mucous membrane is sacrificed after satisfactory
of the atretic plate as well as its encroachment of the enlargement of the choana to permit placement of
posterior aspect of the medial part of the maxilla.26 a 3.5 mm Silastic endotracheal tube as a stent. Pos-
terior membranous flaps are developed in a stellate
Treatment Multiple methods are available to fashion to cover the denuded bone (Figures 46–4
repair choanal atresia. The appropriate method is and 46–5). Care must be taken to prevent injury to
determined by the age of the patient and whether the the roof of the choana and the skull base because
atresia is bilateral or unilateral. In all methods, the reported complications of this approach have
challenge is to provide adequate mucosal lining to the included meningitis, cerebrospinal fluid leaks,
new choana and to prevent granulation tissue for- brain injuries, Gradenigo’s syndrome, and cervical
mation and subsequent stenosis. Treatment requires vertebral subluxation. Studies indicate that
Congenital Anomalies of the Head and Neck 1081
transnasal curettage has a higher incidence of unilateral atresia. Although impaired palatal growth
restenosis than newer techniques and requires is a potential problem in the neonate, the procedure
additional revisions or dilatations. Other methods can be safely used in patients older than 5 years who
include the use of the carbon dioxide laser, endo- are treatment failures if one takes great care to avoid
scopic endonasal approach, and neodymium: injury to the posterior palatine canals.
yttrium-aluminum-garnet (Nd:YAG) laser tech- The procedure is carried out with the patient
nique. Currently, an endoscopic approach with a in the supine position and the neck extended. After
2.5 or 4 mm telescope and powered instrumenta- infiltration of local anesthesia, a horseshoe-type
tion using attachable burs and blades with contin- incision is developed several millimeters posterior to
uous suction is preferred, especially for neonates the alveolar ridge, and a mucoperiosteal flap is then
(Figure 46–6).27 After effective removal and stent- raised based on the greater palatine vessels. Once the
ing and the use of topical corticosteroids to dimin- posterior edge of the hard palate is reached, the
ish granulation tissue formation, stenosis may still mucosa is divided, providing access to the atretic
occur, and dilatation may be necessary. If this fails, plate. An attempt is made to maintain mucosal flaps
a transpalatal approach will be required. A on both sides of the atretic plate. The atretic plate,
transseptal approach, which is reserved for older posterior part of the vomer, and medial aspect of the
children with unilateral atresia, offers better expo- posterior part of the maxilla are removed with a dia-
sure of the posterior part of the vomer without risk mond bur, otologic curette, or rongeur (Figure
of palatal injury and impairment of growth. This 46–7). After removal of bone, mucosal flaps are
approach can be modified either via sublabial transposed to cover the superior and inner surfaces
extension or by an external rhinoplasty approach of the choana, with stents placed as previously
to improve visualization. described. The palatal flap is reapproximated anteri-
orly with absorbable sutures. If stenosis occurs after
TRANSPALATAL APPROACH. The transpalatal approach surgical repair, patients generally slowly develop
provides superior visualization of membranous or progressive respiratory difficulties. Revision surgery
bony atresia and may be useful for both bilateral and and/or dilatation may be necessary.
1082 Ballenger’s Otorhinolaryngology
through a transsphenoidal approach with a lower ryngeal canal. Most cervical teratomas occurring in
incidence of recurrence.33 Primary linear accelerated the neonate are benign. The tumor can surround or
stereotactic radiation therapy has also proven valu- encroach on the airway, thereby causing progressive
able in the initial management of this tumor. A long- dysphagia and airway obstruction.
term (greater than 5 years) follow-up is essential to Surgical removal must be carefully planned to
assess tumor control.34,35 ensure a controlled airway throughout the intraop-
erative and postoperative periods. Tracheostomy is
generally not necessary if orotracheal intubation is
TERATOMAS combined with a transoral removal of pedunculated
Teratomas are true neoplasms that contain tissues nasopharyngeal teratomas or with early excision of
foreign to the site in which they arise. The haphaz- cervical teratomas. Operative and postoperative
ard arrangement of tissue with asynchronous matu- bleeding in patients with nasopharyngeal teratomas
ration is believed to be attributable to escape from is usually only slight because these tumors are poorly
the controlling influence of the primitive streak vascularized, and if removal is complete, recurrences
notochord or adjacent structures. Teratomas grow are rare. More sessile tumors arising in the
aggressively, and in the head and neck, they most nasopharynx require a transpalatal approach. Malig-
commonly occur in the cervical area, followed by the nant metastasizing cervical teratoma is extremely
nasopharynx. Nasopharyngeal teratomas occur with rare.
a female-to-male ratio of 6 to 1. Overall, teratomas
of the head and neck comprise approximately 2 to CONGENITAL DISORDERS OF THE
9% of all teratomas.
Teratomas of the nasopharynx typically arise
ORAL CAVITY AND LIP
on the lateral or superior wall. Four basic types are Numerous congenital defects of the oral cavity and
recognized: (1) dermoid cyst, the most common related structures may occur. Common major
form, composed of ectoderm and mesoderm arising anomalies, such as cleft lip and palate, are described
as an epithelium-lined cavity with variable numbers in detail, whereas less common deformities are men-
of skin appendages; (2) teratoid cyst, derived from tioned for completeness.
all three germ layers but poorly differentiated; (3) Congenital lesions of the tongue include aglos-
true teratoma, composed of ectoderm, mesoderm, sia, microglossia, and macroglossia (secondary to
and endoderm, with specific tissue and organ differ- lymphangioma or hemangiomas or as commonly
entiation; and (4) epignathus, in which well-devel- found in Down syndrome). Ankyloglossia owing to
oped fetal parts are recognizable; this type of varying degrees of underdevelopment of the lingual
teratoma arises from the soft or hard palate and is frenulum is not uncommon. Indications for frenu-
frequently incompatible with life. loplasty with Z-plasty are notching of the protrud-
Clinically, dermoids are more common than ing tongue tip, inability to contact the maxillary
true teratomas, and in the nasopharynx, the der- alveolar ridge, and/or restriction of protrusion
moid cyst is the most common developmental beyond the mandibular alveolar ridge. Other glossal
anomaly found. Known as “hairy polyps,” these anomalies include dermoid cysts, hamartomas, lin-
lesions appear at birth as a pedunculated mass filling gual thyroid, fissured (scrotal) tongue, median
the nasopharynx, often with oropharyngeal exten- rhomboid “glossitis,” and enteric duplication cysts.
sion. Patients with teratomas have nasal obstruction, Nonodontogenic cysts derived from epithelial
dysphagia, and copious secretions. Infants with remnants trapped in embryonic fusion lines during
nasopharyngeal teratomas have a higher incidence the developmental stage include midline maxillary
of preterm birth, neonatal airway distress, and asso- cysts (median alveolar, nasal palatal, median palatal)
ciated congenital anomalies along with polyhydram- and lateral maxillary cysts (globomaxillary,
nios than do infants with dermoids.36 Computed nasolabial). Treatment varies from simple incision
tomography and MRI are critical to define the extent and drainage to removal of the cysts from the palatal
of the neoplasm and to exclude either a nasoen- side, with or without adjacent teeth. Noncleft lip
cephalomeningocele or intracranial extension of a congenital anomalies encountered include micros-
sphenoid-based teratoma through the craniopha- tomia, congenital pits, and “double lip.”
Congenital Anomalies of the Head and Neck 1085
Finally, congenital epulis or gingival granular million below the Cupid’s bow or tubercle, are used
cell tumor arises exclusively from the alveolar ridge for orientation in cleft lip repair.
and is a rare lesion of unknown origin found in The palate is composed of a hard anterior por-
newborn female infants. tion and a soft muscular posterior portion. The
anterior primary palate is formed by the alveolar
CLEFT LIP AND PALATE ridge and four incisor teeth plus the triangular pre-
maxilla. The remaining hard palate is formed by the
Cleft lip and palate are the most common congeni- palatine processes of the maxillary and palatine
tal malformations of the head and neck, occurring bones, which, with the soft palate, comprise the sec-
approximately once in every 700 births. The risk of ondary palate. The soft palate is a muscular curtain
additional siblings having a defect increases when an formed by the tensor veli palatini muscle innervated
older sibling is affected. Both cleft lip with or with- by the fifth cranial nerve and the levator veli palatini
out cleft palate and isolated cleft palate may be fur- muscle, musculae uvulae, and glossopalatine and
ther classified into those classes associated with palatopharyngeus muscles innervated by the pha-
(syndromic) or without (nonsyndromic) another ryngeal plexus.
recognized malformation. The cause of syndromic
clefting may be single-gene transmission, chromo- Embryogenesis Clefts of the lip, alveolar ridge, or
somal aberrations, teratogenicity, or environmental palate are midfacial soft tissue and skeletal fusion
factors. Recent evidence points to multigenic inher- abnormalities. In the normally developing fetus, the
itance with allelic variation at different loci. How- median nasal process fuses with the maxillary
ever, some pedigrees are monogenic, with either processes to form the upper lip, premaxilla, and cor-
autosomal dominance or recessive inheritance. responding segments of the alveolar process.
Exposure to teratogens such as ethanol, retinoids, or Together, the premaxilla and the alveolar ridge form
folate antagonists during the first trimester is associ- the primary palate. The palatal processes fuse with
ated with an increased risk of syndromic cleft lip or each other to form the secondary palate, along with
cleft palate.37 In addition, a dose-response relation- the nasal septum and premaxilla in the vicinity of
ship between maternal smoking and an increased the incisive foramen between gestational weeks 8
risk of having a child with cleft lip or cleft palate has and 10. Palatal growth proceeds posteriorly toward
been demonstrated.38 Associated head and neck the uvula. Failure of ingrowth of mesodermal tissue
anomalies such as maxillary or malar hypoplasia, at this point results in a lack of cohesion of the
abnormal pinnae or atresia, facial nerve paresis or palatal segments, causing a cleft palate, which may
paralysis, and mandibular dysmorphism or abnor- be seen in conjunction with clefts of the lip and/or
mal excursion may be identified. Nonsyndromic alveolar process or alone. Interruption in the migra-
clefting is associated with no obvious first or second tion of mesodermal tissue during the first 2 months
arch anomalies or systemic organ malformation. of embryonic life results in cleft lip deformities. Ulti-
Multifactorial inheritance is the cause of these clefts, mately, a lack of fusion of the median nasal processes
and calculated risk rates are essential to provide with the maxillary processes causes a cleft of the
genetic counseling to families. upper lip, premaxilla, and alveolar process. The inci-
dence of cleft palate increases in the presence of a
Anatomy The lips are a movable muscular sphinc- cleft lip, which occurs in an earlier stage than cleft
ter composed primarily of orbicularis oris muscle palate. Moreover, the tongue is positioned higher in
with motor supply from the seventh cranial nerve. the oral cavity in cleft lip, further interfering with
The lips are covered by skin on the outer surface and palatal fusion and leading to greater palatal clefting.
mucosa on the inner. The vermillion or lip edge
forms a junction with the skin (white line) that cre- Management The head and neck surgeon is part
ates a gentle arching in the upper lip or “Cupid’s of a cleft palate or craniofacial team that includes
bow.” The cephalic extension from the handle of the pediatrics, ophthalmology, general plastic surgery,
Cupid’s bow encloses a small depressed area at the neurosurgery, audiology, speech and language
base of the columella called the philtrum. These pathology, orthodontics, prosthodontics, oral sur-
anatomic landmarks, plus the protrusion of the ver- gery, genetics, dentistry, cytology, psychiatry, social
1086 Ballenger’s Otorhinolaryngology
work, and nursing. The goals of this team are to defects. Bilateral lip adhesion, if indicated, is per-
restore normal anatomy and physiology, with an formed when the patient is 2 to 4 weeks old, with
emphasis on muscular reconstruction of the lip definitive lip repair followed at 4 to 6 months of age.
and/or palate to allow normal facial development If no lip adhesion is necessary to align the underly-
and to minimize growth disturbance. ing maxillary segments before definitive lip repair,
The initial priority for infants with clefts is to bilateral lip repair is performed at 3 months.
establish adequate feeding and nutrition. Infants
with a unilateral or bilateral cleft lip and alveolar CLEFT PALATE. The basic defect, absence of the nasal
ridge feed generally well by either breast or bottle. floor, may be complete or incomplete, with or with-
Infants with bilateral cleft lip, alveolar ridge, and out associated cleft lip. The goals of cleft palate
palate have significant feeding problems and require repair are to close the defect without inhibiting max-
modified nipples, with feeding in the upright posi- illary arch growth, to achieve adequate velopharyn-
tion to minimize nasal regurgitation. geal function, and to normalize oronasal resonance
Although the timing of surgical repair is con- and speech patterns.40
troversial, most experts perform cleft lip repair at 3 Although the exact timing of the repair is con-
months of life and cleft palate repair at 12 months to troversial, the procedure is performed when the
establish a competent velopharyngeal sphincter. Two patient is 10 to 18 months old and may require pre-
schools of thought have evolved: one advocating operative orthopedic devices to move the premaxilla
early closure of the lip and palate, a procedure posteriorly and to expand the lateral maxillary seg-
imparting a high priority to early speech develop- ments, facilitating surgical closure of the lip. Of the
ment, and the other recommending delayed closure many techniques described for bilateral cleft palate
of the hard palate, thus according a high priority to repair, the two-flap palatoplasty by Bardach is com-
maxillary growth.39 Surgical treatment is dictated by monly employed: (1) complete two-layer closure
the anatomic defect, and a classification scheme is (oral and nasal sides) and (2) dissection, redirection,
helpful in planning surgical repair: (1) cleft lip, uni- and suturing of the soft palatal musculature.
lateral or bilateral; (2) cleft palate, either with uni- Secondary problems of cleft lip and palate that
lateral or bilateral cleft lip; and (3) isolated cleft require subsequent treatment include correction of
palate. nasal airway impairment, cosmetic nasal defects,
velopharyngeal insufficiency with associated hyper-
UNILATERAL CLEFT LIP. In the basic complete defect, nasality, and recurrent acute and chronic otitis media
the floor of the nose communicates with the oral with effusion.
cavity, and the alveolar defect passes through the
developing dentition. One sees significant nasal PIERRE ROBIN SEQUENCE. “Pierre Robin” is one of the
deformity, including columellar displacement, nasal most recognized diagnostic eponyms. It is a poorly
dome deformity, and alar flattening and retrodis- understood, nonspecific grouping of malformations,
placement. The goals of surgical repair are restora- however, which as yet have no prognostic significance.
tion of orbicularis muscle function, alar base, and The classic PRS of glossoptosis, micrognathia, and
columellar height and creation of symmetry of cleft palate (all three findings in 50% of cases) may
philtral columns, tip height, Cupid’s bow, and ver- occur as an isolated, nonsyndromic congenital disor-
million. This can be accomplished with a Millard der or as part of a larger anomaly that may include
rotation advancement procedure in concert with facial dysmorphism, cardiac defects, mental retarda-
either preoperative orthodontic appliances or lip tion, and/or musculoskeletal anomalies.41 Möbius’
adhesion. syndrome or nonprogressive congenital facial diplegia
is such an example of PRS, with concomitant brachial
BILATERAL CLEFT LIP. The floor of the nose is absent and thoracic muscle aplasia along with cranial neu-
bilaterally, and the nasal and oral cavities communi- ropathies (six and seven). Pierre Robin sequence has
cate freely. The central alveolar arch is displaced for- no sex predilection, and it may be secondary to an
ward and superiorly, whereas the nasal tip is intrauterine insult during the fourth month of gesta-
widened and the columella is short. The goals of tion or owing to hereditary causes. Syndromic PRS is
bilateral cleft lip repair are the same as for unilateral often associated with ocular anomalies (detached
Congenital Anomalies of the Head and Neck 1087
cilia syndrome, its most recognizable form is in pathologic correlation. Radiographics 1999;19:
Kartagener’s syndrome (bronchiectasis, chronic 121–46.
sinusitis, situs inversus, and sterility). It has also been 9. Gallagher PG, Mahoney MJ, Gosche JR. Cystic
recognized in Usher’s syndrome type I, congenital hygroma in the fetus and newborn. Semin Perinatol
heart disease, congenital esophageal dysfunction, 1999;23:341–56.
and cutaneous abnormalities including folliculitis, 10. Batsakis JG, El-Naggar AK, Luna MA. Thyroid gland
nummular eczema, and pyoderma gangrenosum. ectopias. Ann Otol Rhinol Laryngol 1996;105:
This disorder is characterized by defects in 996–1000.
axonemal dynein complexes probably secondary to 11. Winslow CP, Weisberger EC. Lingual thyroid and
mutations in the genes encoding cytoplasmic heavy neoplastic change: a review of the literature and
chains of the outer arms of the axonemes. Dyneins description of a case. Otolaryngol Head Neck Surg
are large multisubunit adenosine triphosphatases 1997;117:S100–2.
that interact with microtubules in cilia to generate 12. Greinwald JH Jr, Leichtman LG, Simko EJ. Heredi-
force. The resulting ultrastructural defect causes tary thyroglossal duct cysts. Arch Otolaryngol Head
impaired mucociliary clearance throughout the Neck Surg 1996;122:1094–6.
pulmonary and sinonasal passages. Early recogni- 13. Josephson GD, Spencer WR, Josephson JS. Thy-
tion and treatment of individuals with these disor- roglossal duct cyst: the New York Eye and Ear Infir-
ders could lead to reduction in irreversible sinus mary experience and a literature review. Ear Nose
and pulmonary complications with improved Throat J 1998;77:646–51.
survival.46,47 14. Organ GM, Organ CH. Thyroid gland and surgery
of the thyroglossal duct: exercise in applied embry-
ology. World J Surg 2000;24:886–90.
REFERENCES 15. Bardales RH, Shurland MJ, Korourian S, et al. Cyto-
logic findings in thyroglossal duct carcinoma. Am J
1. Mukherji SK, Fatterpekar G, Castillo M, et al. Imag- Clin Pathol 1996;106:615–9.
ing of congenital anomalies of the branchial appara- 16. Nguyen Q, de Tar M, Wells W, Crockett D. Cervical
tus. Neuroimaging Clin North Am 2000;10:75–93. thymic cyst: case reports and review of the literature.
2. Jacobsson C, Granstrom G. Clinical appearance of Laryngoscope 1996;106:247–52.
spontaneous and induced first and second branchial 17. Kacker A, April M, Markentel CB, Breuer F. Ectopic
arch syndromes. Scand J Plast Reconstr Surg Hand thymus presenting as a solid submandibular neck
Surg 1997;31:125–36. mass in an infant: case report and review of litera-
3. Srivastava D. HAND proteins: molecular mediators ture. Int J Pediatr Otorhinolaryngol 1999;49:241–5.
of cardiac development and congenital heart disease. 18. Sobol SE, Tewfik TL, Ortenberg J. Otolaryngologic
Trends Cardiovasc Medq 1999;9:11–8. manifestations of neurofibromatosis in children. J
4. Edmonds JL, Girord DA, Woodroof JM, Bruegger Otolaryngol 1997;26:13–9.
DE. Third branchial anomalies: avoiding recur- 19. Koral K, Geffner ME, Curran JG. Transsphenoidal
rences. Arch Otolaryngol Head Neck Surg 1997; and sphenoethmoidal encephalocoeles: report of
123:438–41. two cases and review of the literature. Australas
5. Nicollas R, Ducroz V, Garabedian EN, Trigilia JM. Radiol 2000;44:220–4.
Fourth branchial pouch anomalies: a study of six 20. Peter JC, Fieggen G. Congenital malformations of the
cases and review of the literature. Int J Pediatr brain—a neurosurgical prospective at the close of the
Otorhinolaryngol 1998;44:5–10. 20th century. Childs Nerv Syst 1999;15:635–45.
6. Thompson LD, Heffner DK. The clinical importance 21. Hong SW. Deep frontotemporal dermoid cyst pre-
of cystic squamous cell carcinomas in the neck: a senting as a discharging sinus: a case report and
study of 136 cases. Cancer 1998;82:944–56. review of literature. Br J Plast Surg 1998;51:255–7.
7. Hong KH, Moon WS, Chung GH. Radiological 22. Lowe LH, Booth TN, Joglar JM, Rollins NK. Midface
appearance of primary branchial cleft cyst carci- anomalies in children. Radiographics 2000;20:907–22.
noma. J Laryngol Otol 1999;113:1031–3. 23. Brown OE, Pownell P, Manning SC. Choanal atresia:
8. Koeller KK, Alamo L, Adair CF, Smirniotopoulos JG. a new anatomic classification and clinical manage-
Congenital cystic masses of the neck: radiologic- ment application. Laryngoscope 1996;106:97–101.
Congenital Anomalies of the Head and Neck 1089
24. Wiener-Vacher SR, Amanou L, Denise P, et al. experience of linac-based radiosurgery in the UK.
Vestibular function in children with the CHARGE Clin Oncol (R Coll Radiol) 1999;11:303–20.
association. Arch Otolaryngol Head Neck Surg 36. Coppit GL, Perkins JA, Manning SC. Nasopharyn-
1999;125:342–7. geal teratomas and dermoids: a review of the litera-
25. Tellier AL, Cormier-Daire V, Abadie V, et al. ture and case series. Int J Pediatr Otorhinolaryngol
CHARGE syndrome: report of 47 cases and review. 2000;30:219–27.
Am J Med Genet 1998;76:402–9. 37. Houdayer C, Bahuau M. Orofacial cleft defects:
26. Jones JE, Young E, Heier L. Congenital bony nasal inference from nature and nurture. Ann Genet
cavity deformities. Am J Rhinol 1998;12:81–6. 1998;4:89–117.
27. Park AH, Brockenbrough J, Stankiewicz J. 38. Chung KC, Kowalski CP, Kim HM, Buchman SR.
Endoscopic versus traditional approaches to Maternal cigarette smoking during pregnancy and
choanal atresia. Otolaryngol Clin North Am the risk of having a child with cleft lip/palate. Plast
2000;33:77–90. Reconstr Surg 2000;105:45–91.
28. Ikushima I, Korogi Y, Makita O, et al. MR imaging of 39. Molsted K. Treatment outcome in cleft lip and palate
Thornwaldt’s cysts. AJR Am J Roentgenol 1999; issues and perspectives. Crit Rev Oral Biol Med
172:1663–5. 1999;10:225–39.
29. Roncaroli F, Bacci A, Frank G, Calbucci F. Granulo- 40. LaRossa D. The state of the art in cleft palate sur-
matous hypophysitis caused by a ruptured intrasel- gery. Cleft Palate Craniofac J 2000;37:225–8.
lar Rathke’s cleft cyst: report of a case and review of 41. Prows CA, Bender PL. Beyond Pierre Robin
the literature. Neurosurgery 1998;43:146–9. sequence. Neonatal Netw 1999;18:13–9.
30. Borba LA, Al-Mefty O, Mrak RE, Suen J. Cranial 42. Marques IL, Babieri MA, Bettiol H. Etiopathogene-
chordomas in children and adolescents. J Neurosurg sis of isolated Robin sequence. Cleft Palate Craniofac
1996;84:584–91. J 1998;35:517–25.
31. Munzenrider JE, Liebsch NJ. Proton therapy for 43. Cruz MJ, Kerschner JE, Beste DJ, Conley SF. Pierre
tumors of the skull base. Strahlenther Onkol Robin sequence: secondary respiratory difficulties
1999;Suppl 2:57–63. and intrinsic feeding abnormalities. Laryngoscope
32. Scimeca PG, James-Herry AG, Black KS, et al. 1996;109:1632–6.
Chemotherapeutic treatment of malignant chor- 44. Lassaletta-Atienza L, Lopez-Rios F, Martin G, et al.
doma in children. J Pediatr Hematol Oncol 1996; Salivary gland heterotopia in the lower neck: a report
18:237–40. of five cases. Int J Pediatr Otorhinolaryngol 1998;
33. Norris JS, Pavaresh M, Afshar F. Primary transsphe- 43:153–61.
noidal microsurgery in treatment of craniopharyn- 45. Triglia JM, Nicollas R, Ducroz V, et al. First branchial
giomas. Br J Neurosurg 1998;12:305–12. cleft anomalies: a study of 39 cases and a review of
34. Habrand JL, Ganry O, Couanet D, et al. The role of the literature. Arch Otolaryngol Head Neck Surg
radiation therapy in the management of cranio- 1998;124:291–5.
pharyngioma: a 25-year experience and review of 46. Milisav I. Dynein and dynein-related genes. Cell
the literature. Int J Radiat Oncol Biol Phys 1999; Motil Cytoskeleton 1998;39:261–72.
44:255–63. 47. Teknos TN, Metson R, Chasse T, et al. New develop-
35. Sims E, Doughty D, Macauley E, et al. Stereotacti- ments in the diagnosis of Kartagener’s syndrome.
cally delivered cranial radiation therapy: a ten-year Otolaryngol Head Neck Surg 1997;116:68–74.
CHAPTER 47
The human larynx is a complex organ that functions The two lateral thyrohyoid ligaments, along with the
as a sphincter at the junction of the digestive tract median thyrohyoid ligament, are condensations of the
and respiratory tract and participates in the diverse thyrohyoid membrane; these structures attach the
physiologic aspects of airway protection, respiration, hyoid bone to the thyroid cartilage. At the attachment
and phonation. In his classic phylogenic observa- of the superior cornu to the alae of the thyroid, a pro-
tions, Negus allowed prioritization of the three func- tuberance called the superior tubercle is found. About
tions of the larynx.1 In order of their priority, these 1 cm anterior and superior to this tubercle, the supe-
are (1) protection of the lower airway, (2) respiration, rior laryngeal artery and the internal branch of the
and (3) phonation. To perform these roles, the inter- superior laryngeal nerve and associated lymphatics
nal and external structures of the larynx interact pierce the membrane to supply the supraglottic lar-
under precise neural control, producing in humans ynx. At this point, transcutaneous anesthesia of the
the most complex of laryngeal functions. Thus, the internal branch can be performed. Running obliquely
anatomy of the larynx reflects the specialization from the superior tubercle to the inferior tubercle
required by these multiple roles and is best under- (along the inferior margin of the thyroid cartilage) is a
stood in relation to its diverse physiologic behaviors. ridge called the oblique line, which serves as the
attachment point for the thyrohyoid, sternothyroid,
and inferior constrictor muscles.
ANATOMY The relationship of the surface anatomy to
internal laryngeal anatomy merits consideration.
LARYNGEAL CARTILAGES Most important is the level of the true cords in rela-
Thyroid Cartilage The thyroid cartilage is a shield- tion to the thyroid cartilage. An understanding of this
shaped structure that serves to protect the internal relationship is crucial to performing supraglottic
anatomy of the larynx.2–7 It is the largest cartilage of laryngectomy and phonosurgery (thyroplasty type I).
the larynx and is composed of two wings, the alae or In this regard, the midline vertical distance from the
laminae. The alae are fused in the midline and open thyroid notch to the inferior border of the thyroid
posteriorly (Figure 47–1). In the male, the alae fuse at cartilage ranges from 20 to 47 mm in men and 15.5
about 90 degrees, making a laryngeal prominence or to 38 mm in women.2,3 The anterior commissure is
Adam’s apple. In the female, this prominence is absent found at the midpoint between these landmarks. The
owing to the more oblique fusion angle of 120 degrees. posterior extent of the cords is anterior to the oblique
Superiorly, the fusion of the alae is deficient, account- line and is found in the middle third of this line.3
ing for the thyroid notch. Posteriorly, each ala has a The thyroid cartilage is lined by a thick layer of
superior and inferior horn or cornu. The inferior perichondrium on all surfaces except the inner sur-
cornu articulates with a facet on the cricoid cartilage to face at the anterior commissure. At this point are
form the cricothyroid joint. This is a synovial joint that attached five ligaments, which form the scaffolding
allows rotation of the cricoid cartilage. This rotation for the corresponding laryngeal folds. From superior
varies the tension placed on the vocal folds. The supe- to inferior, they are the median thyroepiglottic liga-
rior cornu attaches to the greater cornu of the hyoid ment (median thyrohyoid fold), bilateral vestibular
bone by way of the lateral thyrohyoid ligament. This ligaments (vestibular folds or false cords), and bilat-
ligament sometimes contains small triticeal cartilages. eral vocal ligaments (vocal folds) (Figure 47–2, A).
1090
Anatomy and Physiology of the Larynx 1091
A B
FIGURE 47–1. A, Anterior view of the cartilages and ligaments of the larynx and hyoid bone. B, Posterior view of the
cartilages, ligaments, and articulations of the larynx and hyoid. *Passage for superior laryngeal nerve and vessels. Repro-
duced with permission from Staubesand J, Taylor AN. Sabotta: atlas of human anatomy. Vol 1. 11th ed. Baltimore: Urban
and Schwarzenberg; 1990.
The attachment of these ligaments penetrates the Housed on the superior surface of the posterior
inner perichondrium, forming Broyle’s ligament. cricoid lamina are the paired arytenoid cartilages.
This ligament contains blood vessels and lymphatics Posterior to anterior, the cricoid lamina
and constitutes an important barrier to the spread of slopes steeply downward to form the anterior
laryngeal neoplasms. cricoid arch. In the midline, between the superior
portion of the arch and the inferior border of the
Cricoid Cartilage The cricoid cartilage is a com- thyroid cartilage, is the cricothyroid membrane. It
plete ring.2–7 It is the only supporting structure that is this structure that must be incised in performing
completely encircles the airway and serves as the an emergent cricothyrotomy.
major support for the functioning larynx. Its shape
is classically described as that of a signet ring, with Arytenoid Cartilages The arytenoids are paired
the anterior arch measuring 3 to 7 mm in height and cartilages that articulate with the posterosuperior
the posterior lamina about 20 to 30 mm in height.4–6 portion of the cricoid cartilage.2–7 Movement of these
Its inferior border is nearly horizontal and is cartilages and their attached vocal folds allows the
attached to the first tracheal cartilage by the crico- larynx its often diverse and complex functions. Each
tracheal ligament. arytenoid is roughly pyramidal in shape, giving it a
On the posterior surface of the cricoid, the pos- base, an apex, and three sides. The base of the ary-
terior cricoarytenoid muscles are attached in depres- tenoid provides the articular facet as well as the mus-
sions, which are separated by a midline vertical ridge. cular and vocal processes. The cricoarytenoid joint is
These muscles are the only abductors of the vocal a synovial joint with complex movements that are
folds. Attached to this midline vertical ridge are two somewhat debated. It appears, however, that the most
fasciculi of longitudinal fibers of the esophagus. important movement of the joint is a rocking motion
1092 Ballenger’s Otorhinolaryngology
A B
FIGURE 47–2. A, Sagittal view of the ligaments and articulations of the larynx. B, Posterolateral view of the intrinsic
musculature of the larynx. Reproduced with permission from Staubesand J, Taylor AN. Sabotta: atlas of human anatomy.
Vol 1. 11th ed. Baltimore: Urban and Schwarzenberg; 1990.
of the cartilage around the long axis of its facet. Lat- raised anterosuperiorly. This action pushes the
erally, the base forms a broad muscular process, and epiglottis against the base of the tongue, posteriorly
anteriorly, it forms the thinner vocal process. The displacing it over the laryngeal aditus. The epiglottis
anterolateral surface receives the vestibular ligament has two anterior attachments. Superiorly, it is
as well as the thyroarytenoid and vocalis muscles. attached to the hyoid bone by the hyoepiglottic liga-
The posterior surface receives muscular attachments, ment. Inferiorly at the stem or petiole, it is attached
and to the medial surface is attached the prominent to the inner surface of the thyroid cartilage just
posterior cricoarytenoid ligament. Sitting at the apex above the anterior commissure by the thyroepiglot-
of the arytenoid is the corniculate cartilage. tic ligament. The surface of the epiglottic cartilage
has multiple pits and is filled with mucous glands;
Corniculate and Cuneiform Cartilages These are these pits potentially allow the spread of cancer from
small, paired fibroelastic cartilages found in the lar- one surface of the epiglottis to the other.
ynx.4 The corniculate, or cartilage of Santorini, is The epiglottis may arbitrarily be divided into
housed on the apex of the arytenoid cartilage. The a suprahyoid and an infrahyoid portion. The
cuneiform, or cartilage of Wrisberg, when present, is suprahyoid portion is free on both of its laryngeal
lateral to the corniculate cartilages and is embedded and lingual surfaces, with the laryngeal mucosal
in the aryepiglottic fold. Although some feel that surface being more adherent than the lingual. As the
these cartilages are vestigial, they do appear to add mucosa of the laryngeal surface is reflected back
rigidity to the aryepiglottic fold.7 This rigidity aug- onto the base of the tongue, three folds result: two
ments the important rampart function of these folds, lateral glossoepiglottic folds and a median glos-
thus diverting swallowed matter laterally away from soepiglottic fold. The two depressions formed by
the larynx into the piriform sinuses. these folds are known as the valleculae (little
depression in Latin). The infrahyoid portion is free
Epiglottis The epiglottis is a leaf-shaped elastic only on its laryngeal or posterior surface. This sur-
fibrocartilage that functions mainly as a backstop face contains a small protuberance known as the
against the entrance of swallowed matter into the tubercle. Between the anterior surface and the thy-
laryngeal aditus.2–7 During swallowing, the larynx is rohyoid membrane and the thyroid cartilage exists
Anatomy and Physiology of the Larynx 1093
a fat pad within the preepiglottic space. Attached forms part of the medial wall of each piriform sinus.
laterally is the quadrangular membrane extending The inferior edge of the quadrangular membrane
to the arytenoid and corniculate cartilages, consti- constitutes the vestibular ligaments.
tuting the aryepiglottic folds. The conus elasticus is a thicker elastic structure
than the quadrangular membrane. It attaches inferi-
Ossification of Laryngeal Cartilages It has long orly at the superior border of the cricoid cartilage. It
been recognized that incomplete ossification of the then projects upward and medial to its superior
laryngeal cartilages can be mistaken for a foreign attachments, the anterior commissure of the thyroid
body on plain roentgenograms of the neck.8 This cartilage and the vocal process of the arytenoid.
particularly applies to ossification of the superior Between these superior attachments, the conus thick-
and inferior cornua of the thyroid cartilage and lin- ens to form the vocal ligament. Anteriorly, the conus
ear ossification of the posterior portion of the forms the cricothyroid membrane, and in the mid-
cricoid. Thus, the need for understanding the nor- line, this membrane condenses to form the cricothy-
mal ossification pattern of the larynx is self-evident. roid ligament (Figures 47–1 to 47–3). The superior
It is important to realize that only those structures extension of the conus (thyroglottic membrane)
composed of hyaline cartilage will undergo ossifica- parallels the superior surface of the true cord.
tion (ie, thyroid, cricoid, and arytenoid cartilages).8,9 Because it may normally be incomplete, it forms an
It should be noted that the hyoid bone is completely imperfect barrier to the inferior extension of the
ossified at 2 years of age and is generally not a point transglottic cancers (Figure 47–4).7
of radiographic confusion.
The thyroid cartilage undergoes ossification in MUSCLES
the male about age 20 and in the female a few years
later. Ossification begins posteroinferiorly on the Extrinsic Muscles The extrinsic muscles of the
lamina. It then extends anteriorly on the inferior larynx are those muscles of the laryngohyoid com-
border and superiorly at the posterior border. At this plex that serve to raise, lower, or stabilize the lar-
time, nuclei of ossification can be seen in the inferior ynx.2–7 Those muscles that elevate the larynx are the
and superior cornua. The cricoid and arytenoid car- thyrohyoid, stylohyoid, digastric, geniohyoid,
tilages undergo ossification somewhat later than the mylohyoid, and stylopharyngeus. These muscles
thyroid cartilage. Ossification of the cricoid cartilage are important in the elevation and anterior dis-
generally begins at the inferior border, although the placement of the larynx during swallowing. They
superior margin of the quadrate lamina may be an also help to suspend the larynx, via the hyoid bone,
early site of ossification. from the skull base and mandible. The principal
Neoplastic invasion of the laryngeal carti- depressors of the larynx are the omohyoid, ster-
lages generally takes place in the ossified portion of nothyroid, and sternohyoid. These muscles displace
the cartilage.10 The incomplete ossification pattern the larynx downward during inspiration. The mid-
may make it difficult to appreciate small areas of dle constrictor, inferior constrictor, and cricopha-
invasion. ryngeus muscles are also important extrinsic
laryngeal muscles. The proper functioning of these
muscles is crucial to the precisely timed swallowing
ELASTIC TISSUES reflex.
The elastic tissue of the larynx consists of two main
parts: (1) the quadrangular membrane of the supra- Intrinsic Muscles The intrinsic muscles of the
glottic larynx and (2) the thicker conus elasticus larynx are those muscles that are anatomically
and vocal ligaments of the glottic and infraglottic restricted to the larynx proper. They modify the size
larynx. of the glottic opening along with the length and ten-
The quadrangular membrane attaches anteri- sion on the vocal folds. They consist of multiple
orly to the lateral margin of the epiglottis and curves adductors but only a single abductor. With the
posteriorly to attach to the arytenoid and cornicu- exception of the interarytenoid, the intrinsic mus-
late cartilages. This structure and the overlying cles are paired, and these paired muscles appear to
mucosa constitute the aryepiglottic folds. Each fold act synchronously (Figure 47–5).
1094 Ballenger’s Otorhinolaryngology
CRICOTHYROID MUSCLE. The cricothyroid muscle is POSTERIOR CRICOARYTENOID MUSCLE. This muscle is
located on the external surface of the laryngeal car- the sole abductor of the vocal folds. It is seated in a
tilages. It is classically described as consisting of two depression on the posterior surface of the cricoid
bellies. The straight portion or pars recta attaches lamina, and its fibers run obliquely superior and
the lateral portion of the anterior arch of the cricoid lateral to attach onto the muscular process of the
cartilage to the inferior border of the thyroid carti- arytenoid cartilage. It is composed of two compart-
lage in a fairly vertical direction. The second belly, ments: horizontal and vertical bellies. Contraction
the pars obliqua, also from the anterolateral border of these fibers brings the muscular process medial,
of the cricoid arch, travels obliquely upward to posterior, and inferior while laterally rotating and
insert on the anterior portion of the inferior cornu. elevating the vocal process. This action abducts,
When the right and left cricothyroid muscles con- elongates, and thins the vocal folds while causing
tract, they rotate the cricoid at the cricothyroid the vocal fold edge to be rounded. The stretching of
joint. This action brings the anterior arch of the the vocal fold leads to passive stiffening of its layers.
cricoid superiorly toward the inferior border of the The complex function of this muscle has been stud-
thyroid laminae while displacing the posterior ied in the canine in which three distinct neuromus-
cricoid lamina (and the arytenoid cartilages) inferi- cular compartments are found. It is proposed that
orly. This inferior displacement increases the dis- the vertical and oblique bellies normally cause vocal
tance between the vocal processes and the anterior fold abduction during respiration, whereas the hor-
commissure; the result of this action is to lower, izontal belly is primarily used to adjust the position
stretch, and thin the vocal folds while bringing them of the vocal process during phonation.11,12
into a paramedian position. The stretching of the
vocal fold also sharpens the edge of the vocal fold LATERAL CRICOARYTENOID MUSCLE. This is the main
and passively stiffens the component layers of the antagonist of the posterior cricoarytenoid. It
vocal fold (Figure 47–6). Biomechanically, this attaches along the superior border of the cricoid car-
translates into a higher fundamental frequency pro- tilage and then sends its fibers posteriorly to insert
duced by the vocal folds. on the anterior portion of the muscular process.
Anatomy and Physiology of the Larynx 1095
A B
FIGURE 47–4. A, The thyroglottic membrane may be naturally dehiscent (arrow). B, Dehiscence in the thyroglottic
membrane can allow transglottic cancer to extend inferiorly along the paraglottic space (arrow). Courtesy of Dr. John
A. Kirchner.
Contraction of this muscle brings the muscular these transverse fibers are oblique fibers. These
process anterolaterally while adducting and lower- oblique fibers pass from the posterior portion of the
ing the vocal process. This results in adduction, elon- arytenoid on one side to the apex of the arytenoid
gation, and thinning of the vocal folds. The edge of on the other side, thus crossing in the midline.
the vocal fold becomes sharper, and its component Some fibers insert at the apex, whereas others travel
layers are passively stiffened. along the quadrangular membrane. These fibers
contract to narrow the laryngeal aditus. Those fibers
INTERARYTENOID/ARYEPIGLOTTIC MUSCLE. The inter- traveling along the quadrangular membrane (thus
arytenoid is the only unpaired intrinsic muscle, the aryepiglottic fold) constitute the aryepiglottic
consisting of two types of muscle fibers. The bulk of muscle.
the muscle consists of transverse fibers passing from
the posterior surface of one arytenoid cartilage to THYROARYTENOID MUSCLE. This muscle is classically
the posterior surface of the other. This muscle con- divided into the thyroarytenoid internus and exter-
tracts to bring together the arytenoid cartilages, nus. These have the same attachments, but the
thus assisting in closing the posterior portion of the internus lies deep or internal to the externus. In
glottis. This does not significantly affect the addition, the internus is more well developed than
mechanical properties of the vocal folds. Along with the externus.
1096 Ballenger’s Otorhinolaryngology
A B
FIGURE 47–5. A, The intrinsic muscles of the larynx and their actions. Heavy arrows indicate the direction of muscle
action, fine arrows indicate the motion of vocal ligaments, open arrows indicate the motion of cricoid and thyroid carti-
lages. Reproduced with permission from Ballenger JJ, editor. Diseases of the nose, throat, ear, head and neck. 13th ed.
Philadelphia: Lea & Febiger; 1985. B, Schematic presentation of the function of the laryngeal muscles. The left column
shows the location of the cartilages and the edge of the vocal folds when the laryngeal muscles are activated individually.
The arrow indicates the direction of the force exerted. CT = cricothyroid muscle; VOC = vocalis muscle; LCA = lateral
cricoarytenoid muscle; IA = interarytenoid muscle; PCA = posterior cricoarytenoid muscle; 1 = thyroid cartilage; 2 =
cricoid cartilage; 3 = arytenoid cartilage; 4 = vocal ligament; 5 = posterior cricoarytenoid ligament. The middle column
shows views from above. The right column presents contours of frontal sections at the middle of the membranous por-
tion of the vocal fold. The dotted line shows a control, where no muscle is activated. Reproduced with permission from
Hirano M, editor. Clinical examination of voice. New York: Springer-Verlag; 1981. Copyright Urban & Fischer Verlag.
The thyroarytenoid externus arises from the The thyroarytenoid internus or vocalis muscle
anterior commissure and inserts onto the lateral sur- attaches at the anterior commissure and inserts onto
face of the arytenoid cartilage. It contracts to bring the vocal process, sending a few slips of fibers below
the vocal process and anterior commissure closer to the vocal ligament onto the conus elasticus. It con-
each other, thus adducting the vocal folds. It also tracts to adduct, shorten, thicken, and lower the
contracts to adduct the false cords. The externus vocal fold while rounding its edge. The body (mus-
sends a few slips of muscle fibers onto the quadran- cle) of the vocal fold is actively stiffened, whereas the
gular membrane to establish the thyroepiglottic cover is passively slackened.
muscle. This muscle, like the aryepiglottic muscle, Recently, immunohistochemical staining for
acts to narrow the laryngeal inlet. myofibrillar adenosine triphosphatase reveals that
Anatomy and Physiology of the Larynx 1097
A B
Stratified squamous
epithelium
MUCOSA
EPITHELIUM
Superficial layer
Intermediate layer
Transition
Deep layer
Ciliated columnar
epithelium
INTERNAL ANATOMY
The internal anatomy of the larynx consists of three
compartments separated by two folds (see Figure
47–3).2–7 The three compartments are the vestibule,
ventricle, and infraglottic cavity. The false and true
vocal folds separate the above compartments. These
mucosa-lined compartments demarcate two spaces
of importance: the preepiglottic space and the para-
glottic space.
and corniculate cartilages with the interarytenoid
Vestibule A laryngoscopic view of the larynx muscle posteriorly. In the laryngoscopic view, the
reveals the vestibule as that portion of the larynx from anterior commissure is frequently hidden by the pro-
the tip of the epiglottis to the false or vestibular folds. tuberance of the epiglottis known as the tubercle.
Thus, the vestibule is bound by the epiglottis anteri- As previously discussed, the vestibular folds are
orly, the aryepiglottic folds laterally, and the arytenoid formed by mucosa overlying the vestibular ligament
1098 Ballenger’s Otorhinolaryngology
(inferior border of the quadrangular membrane). cricoid cartilage. Its lateral boundary is formed by
The submucosa of the ventricle contains numerous the conus elasticus and walls of the cricoid cartilage.
seromucinous glands. The secretions produced by
these exocrine glands provide both mechanical and Piriform Sinus Although the piriform sinus is
immune (lysozyme) protection for the vocal folds.15 anatomically part of the hypopharynx, under-
standing its anatomy and its relationship to the lar-
Ventricle The ventricle or sinus of Morgagni is the ynx is essential. The piriform sinus is a gutter
small space between the false and true vocal folds. formed by the aryepiglottic fold, arytenoid, and
The ventricle is often hidden during laryngoscopic superior cricoid medially and the thyrohyoid mem-
examination of the larynx unless exposed by lateral- brane and internal surface of the thyroid lamina
ization of the false vocal fold. At the anterior end of laterally. Superiorly, it begins at the lateral glos-
the ventricle is a diverticulum known as the laryn- soepiglottic fold. Inferiorly, the apex of the sinus
geal saccule. The saccule (of Hilton) is lined with blends with the esophageal inlet at about the supe-
mucous glands, which are thought to lubricate the rior border of the cricoid (Figure 47–7). Thus, can-
vocal folds. Fibers of the thyroarytenoid muscle line cer invasion of the apex implies the necessity of
the walls of the saccule and are thought to express
removing a portion of the cricoid if conservation
mucus from the saccule when they contract. The size
laryngectomy is planned.7
of the saccule is quite variable; however, it seldom
There are two important markings within the
extends above the superior border of the thyroid
piriform sinus. Anteriorly in the floor of the sinus,
cartilage. Abnormal dilatation of the saccule results
a small fold can be seen, which marks the course of
in an air-filled laryngocele that should be distin-
the superior laryngeal nerve. This submucosal
guished from a mucocele of the saccule (saccular
cyst), which lacks free communication with the ven- course of the nerve makes it possible to anesthetize
tricle and thus is not air filled.16 The vocal folds that the nerve topically in the piriform sinus. The sec-
form the inferior boundary of the ventricle are ond, more variable landmark is the protrusion
described in more detail in a separate section. made into the sinus from the superior cornu of the
thyroid cartilage. This smooth protrusion, which
Infraglottic Cavity The infraglottic cavity extends usually presents in the elderly, should not be con-
from the glottis down to the inferior border of the fused with neoplasm.
Mucosa The mucosa of the larynx is of two types: and the slit between them (rima glottidis) constitute
pseudostratified ciliated columnar cell (respiratory) the glottis. The glottis can be divided by a horizontal
epithelium and squamous cell epithelium. Much of line between the tips of the vocal processes. This
the larynx is surfaced by respiratory epithelium; imaginary line divides the glottis into an intermem-
however, the superior portion of the epiglottis, upper branous portion and an intercartilaginous portion.
portions of the aryepiglottic folds, and free edges of The anterior to posterior (length) ratio of the inter-
the vocal folds are surfaced by squamous cell epithe- membranous portion to the intercartilaginous is 3 to
lium. Beneath this covering epithelium is a variable 2; however, the ratio of cross-sectional areas defined
basement membrane, and separating these two is a by them is 2 to 3. Thus, owing to its more rectangu-
layer of loose fibrous stroma. It should be noted that lar shape, the intercartilaginous portion is larger.
this loose fibrous layer is absent on the true vocal Some have called this the respiratory portion of the
folds as well as the laryngeal (posterior) surface of the rima.4,17 The membranous or vibratory portion of
epiglottis. The absence of this layer on the posterior the vocal folds consists of three well-defined struc-
surface of the epiglottis accounts for the more intense tural layers. From superficial to deep, they are the
swelling of the lingual (anterior) surface of the epithelium, lamina propria (three layers), and vocalis
epiglottis in inflammatory conditions of the larynx. muscle. Hirano divided these layers according to a
body-cover concept (see Figure 47–6, A).17 The cover
Preepiglottic Space The preepiglottic space, as its consists of the overlying epithelium and the gelati-
name implies, lies anterior to the epiglottis, which nous superficial layer of the lamina propria. The
serves as its posterior boundary. It is bound superi- body consists of the vocalis muscle, which he likened
orly by the hyoepiglottic ligament and mucosa of the to thick rubber bands. Between these exists a transi-
valleculae and inferiorly by the thyroepiglottic liga- tion zone composed of the intermediate (elastic) and
ment. The anterior boundaries are the thyrohyoid deep (collagenous) layers of the lamina propria.
membrane and the inner surfaces of the thyroid According to this concept, the vocal folds consist of a
laminae. Laterally, the preepiglottic space opens in multilayered vibrator with increasing stiffness from
the paraglottic spaces. Cancer on the infrahyoid por- the cover to the body. Thus, the cover is responsible
tion of the epiglottis can penetrate this structure and for most of the vibratory action of the vocal folds. At
gain access to the preepiglottic space.
the anterior and posterior ends of the vocal folds
Paraglottic Space A paraglottic space, as its name exists an anterior and a posterior macula flava,
implies, lies on each side of the glottis. This space lies respectively. These are essentially a thickening of the
above and below the true and false vocal folds and is intermediate (elastic) layer of the lamina propria and
important in the transglottic and extralaryngeal are thought to function as “cushions” protecting the
spread of neoplasms. Medially, the space is bound by ends of the vocal folds from vibratory damage. It
the quadrangular membrane, ventricle, and conus should be noted that the same body-cover concept
elasticus. Laterally, it is bound by the perichondrium does not apply to the larynx of children because of
of the thyroid lamina and the cricothyroid mem- the more homogeneous nature of the lamina propria.
brane. Anterosuperiorly, the space opens in the pos- It is not until nearly the end of adolescence that the
terior portion of the preepiglottic space. The mucosa lamina matures into its adult form. In the senile lar-
of the piriform sinus forms the posterior boundary. ynx, the elastic layer and the vocalis muscle tend to
The relationships of this paraglottic space make it atrophy, whereas the collagenous layer thickens. The
important in considering the spread of laryngeal can- cover becomes thickened and edematous secondary
cer. Supraglottic cancer invading into this space may to changes in the superficial layer of the lamina,
quickly extend extralaryngeally. whereas the epithelium itself changes little.
The shape of the true and false vocal folds car-
ries biomechanical significance. When seen in coro-
VOCAL FOLDS nal section, both appear as valve-like structures, with
The anatomy of the vocal folds is complex and is thus the leaflets of the false folds pointing inferiorly and
considered separately. The vocal fold is considered those of the true folds pointing superiorly (see Figure
the structure between the vocal process of the ary- 47–3). Thus, the false folds passively impede egress of
tenoid and the anterior commissure. The vocal folds air, whereas the true folds impede its ingress. Work-
1100 Ballenger’s Otorhinolaryngology
ing with cadaver larynges, Brunton and Cash demon- The drainage of the supraglottic structures
strated that the false folds offered a resistance equal- (aryepiglottic folds and false cords) follows the supe-
ing 30 mm Hg to the egress of air from below, rior laryngeal and superior thyroid vessels. Thus, the
whereas the true folds offered a resistance equaling lymphatics flow from the piriform sinus through the
140 mm Hg to the ingress of air from above.18 Both thyrohyoid membrane to end primarily in the deep
structures offered little resistance to the opposite flow jugular chain around the carotid bifurcation. It
of air (ie, they act as one-way valves). should be noted that the epiglottis is a midline struc-
ture; thus, its lymphatic drainage is bilateral.
The lymphatic drainage of the ventricle is dif-
VESSELS ferent from the other supraglottic structures. Dye
Arteries and Veins The arterial supply to the lar- injected into the ventricle enters the paraglottic
ynx consists of the superior and inferior laryngeal space and is quickly spread by the lymphatic system
arteries.2–7 After the superior thyroid artery branches through the cricothyroid membrane and also into
off the external carotid, it courses lateral to the laryn- the ipsilateral lobe of the thyroid (justifying its resec-
gohyoid complex and gives off the superior laryngeal tion in laryngectomy).
artery at approximately the level of the hyoid bone. The true vocal folds are devoid of lymphatics,
This artery then runs anteromedially with the internal accounting for the high curability of cancer localized
branch of the superior laryngeal nerve to enter the to this structure.
thyrohyoid membrane inferior to the nerve. It then The subglottic larynx has two lymphatic
enters the submucosa of the piriform sinus and is dis- drainage systems. One system follows the inferior
tributed to intralaryngeal structures. The superior thyroid vessels to end in the lower portion of the
thyroid also gives off a cricothyroid branch that deep jugular chain as well as the subclavian, para-
courses horizontally below the thyroid cartilage. The tracheal, and tracheoesophageal chains. The other
inferior laryngeal artery is a branch of the inferior system pierces the cricothyroid membrane. This
thyroid artery that comes off the thyrocervical trunk system appears to receive lymphatics from both
branching from the subclavian artery. After coursing sides of the larynx and disseminate bilaterally to the
posterior to the cricothyroid joint with the recurrent middle deep cervical nodes as well as the prelaryn-
laryngeal nerve, the artery enters the larynx by pass- geal (Delphian) nodes.
ing through a gap in the inferior constrictor muscle
known as the Killian-Jamieson area. The artery is then PHYSIOLOGY
distributed to the remainder of the internal larynx,
making multiple anastomoses with the superior As previously stated, the three functions of the lar-
laryngeal artery. The venous supply parallels the arte- ynx in order of priority are (1) protection of the
rial supply. lower airway, (2) respiration, and (3) phonation.1 A
flawless performance of these functions requires an
Lymphatics An appreciation of the lymphatics of intact neuromuscular system to respond to both
the larynx is prerequisite to understanding the volitional and reflex signals presented to the larynx.
spread of cancer of the larynx, as well as the opera-
tive procedures designed to eradicate the disease.2–7,19
The lymphatics of the larynx are divided into super-
INNERVATION
ficial (intramucosal) and deep (submucosal) groups. The pattern of innervation to and from the larynx
The deep network is further divided into right and and the type and distribution of its receptors deter-
left halves, with little communication between them. mine the functional capabilities of the larynx. The
These two halves can be further divided into supra- larynx is innervated by the superior and inferior
glottic, glottic, and subglottic, with special consider- laryngeal nerves. The superior laryngeal nerve leaves
ation given to the ventricle in the supraglottic the nodose ganglion to pass between the carotid
region. Although the superficial network is richly artery and the laryngohyoid complex. It divides into
anastomotic throughout the larynx, it is the deep a larger internal and smaller external branch. The
network that is important in the spread of cancer internal branch pierces the thyrohyoid membrane
and will be given further consideration. with the superior laryngeal artery and becomes the
Anatomy and Physiology of the Larynx 1101
sensory supply to the ipsilateral supraglottic larynx, the folds.22,23 This sensory distribution facilitates the
whereas the external branch innervates the cricothy- supraglottic larynx in its role of preventing foreign
roid and inferior constrictor muscles. The inferior material from penetrating into the larynx.24 These
laryngeal nerve originates from the recurrent laryn- respond to a number of chemical stimuli and to
geal nerve and runs in the tracheoesophageal groove. water. The taste buds of the larynx tend to be most
It enters the larynx posterior to the cricothyroid sensitive to the pH and tonicity of the stimulus. In
joint and classically divides into an anterior adduc- this regard, the water receptors of the epiglottis
tor and a posterior abductor branch. This branch- appear to play a role in the production of prolonged
ing, however, is quite variable, as is the muscular apnea. When stimulated, they lead to a slowing of
innervation from the branches.4 respiration with an increase in tidal volume.
The receptors of the larynx can be divided into Chemoreceptors of the larynx are adapted to detect
mucosal, articular, and myotatic. These receptors chemicals that are not saline-like in composition and
mediate much of the reflex activity of the larynx. can play an important role in modifying reflexes
The mucosal receptors respond to stimuli such as involved in the maintenance of upper airway
touch, mucosal deformation (mechanoreceptors), patency.23 It is important to note that this same
and liquids. The articular receptors are located in the response does not occur with saline. It is felt that the
joint capsule and respond to deformation of the cap- receptors may be responding to the washout of chlo-
sule. The myotatic receptors respond to muscular ride ions.20 Theoretically, this may be the mechanism
stretch and appear to be most abundant in the by which cold-steam mist assists the child with croup
vocalis muscle.20 (slowing and deepening breathing, thus decreasing
turbulent flow).25 Interestingly, this response is more
Afferent System The sensory innervation to the potent early in life. This apneic response has also
mucosa of the supraglottic larynx is carried by the been implicated in sudden infant death syndrome.20
internal branch of the ipsilateral superior laryngeal The vocal folds also have touch receptors that are
nerve, which is divided into three divisions. The more abundant posteriorly than anteriorly. The affer-
superior division mainly supplies the mucosa of the ent impulses generated are delivered to the tractus
laryngeal surface of the epiglottis, the middle divi- solitarius through the ganglion nodosum.
sion supplies the mucosa of the true and false vocal
folds and the aryepiglottic fold, and the inferior divi- Efferent System The motor innervation is prima-
sion supplies the mucosa of the arytenoid, part of rily through the inferior laryngeal nerve. This nerve
the subglottis, the anterior wall of the hypopharynx, innervates all of the intrinsic muscles of the larynx
and the upper esophageal sphincter.21 The cricoary- except the cricothyroid, which is innervated by the
tenoid joint and thyroepiglottic ligament are both external branch of the superior laryngeal nerve. Each
innervated by the internal branch of the superior nerve is responsible for the muscles on the ipsilateral
laryngeal nerve. The inferior laryngeal nerve sup- side of the larynx, with the exception of the inter-
plies the major portions of mucosa below the glottis arytenoid muscle. Thus, the only unpaired muscle of
as well as muscle spindles of intrinsic muscles. The the larynx receives its innervation from both infe-
external branch of the superior laryngeal nerve con- rior laryngeal nerves. Injury to the recurrent laryn-
tains afferent fibers from the cricothyroid joint and geal nerve leaves the injured cord in the paramedian
from deep muscle receptors. position, resulting from the adductor effect of the
Histologic examination has revealed the pres- intact cricothyroid. Unilateral injury to the superior
ence of free nerve endings, Merkel cells, Meissner’s laryngeal nerve causes the posterior glottic opening
corpuscles, and taste buds scattered in the larynx. to rotate to the paralyzed side, bowing the paralyzed
Mechanoreceptors are located either in the superfi- cord.4,24 These changes in the larynx can be seen on
cial mucosa or in the muscles and laryngeal joints. laryngeal endoscopy.
Some of them are spontaneously active, whereas oth-
ers are silent until stimulated. The supraglottic larynx NEUROPHYSIOLOGY OF PROTECTIVE
also has chemical and thermal sensors. A large num-
FUNCTION
ber of taste buds populate the laryngeal surface of the
epiglottis and extend caudally along the aryepiglottic The glottic closure reflex is a polysynaptic reflex that
folds, reaching peak density at the caudal extreme of allows the larynx to protect the lower airway from
1102 Ballenger’s Otorhinolaryngology
penetration and aspiration. However, when exagger- with, but slightly precede, the descent of the
ated, this reflex accounts for the production of laryn- diaphragm. Through the work of many individuals,
gospasm. Protective closure of the larynx occurs in this observation is well supported.24,28,29 The respi-
three tiers. ratory center of the medulla, with the help of higher
In the first tier, the laryngeal inlet is contracted central nervous system and peripheral input, main-
by collapsing the aryepiglottic folds medially. The tains eupneic respiration. It drives the synchronous
anterior and posterior gaps are filled by the epiglot- opening of the glottis and descent of the diaphragm
tic tubercle and the arytenoid cartilages, respectively. during inspiration. The opening of the glottis is pri-
In the second tier, the false vocal folds are brought marily through the action of the posterior cricoary-
together. The final and most important tier occurs at tenoid. However, in hyperpneic conditions, the
the level of the true vocal folds. Because the valvular cricothyroid contracts rhythmically with the poste-
action of the true vocal folds resists ingress of mate- rior cricoarytenoid.28,29 The contraction of both of
rial, they offer the most important level of protec- these muscles increases the glottic aperture in both
tion. It should be noted that it is the thyroarytenoid anteroposterior and horizontal dimensions. During
or slips from this muscle that contract at each level phonation, the cricothyroid lengthens and passively
of closure. This muscle is one of the fastest contract- adducts the vocal folds. However, during respira-
ing of all striated muscles in the body. Classically, the tion, when contracted in concert with the posterior
afferent limb of this reflex occurs through stimula- cricoarytenoid, the effect is to lengthen the open
tion of touch, chemical, or thermal receptors in the glottis, thus increasing the cross-sectional area for
supraglottic larynx.26 airflow.
Laryngospasm occurs when stimulation of Understanding the role that the cricothyroid
the superior laryngeal nerve leads to a prolonged plays as an accessory muscle of inspiration underlies
adductor response. This response is maintained the rationale for superior laryngeal nerve section in
well after the initiating stimulus is removed, and the face of bilateral recurrent laryngeal nerve paral-
section of the superior laryngeal nerves abolishes ysis. Bilateral paralysis produces dyspnea, which will
the response. Clinically, this is typically seen in the lead to cricothyroid contraction, further adducting
setting of endotracheal intubation/extubation or the paralyzed folds. Unilateral superior laryngeal
after manipulation of the airway, especially if blood nerve section reduces glottic resistance by preventing
has contaminated the laryngeal inlet. The response its full adduction.
is dampened in the face of barbiturates, hypercap- The rhythmicity of the phrenic nerve and the
nia, positive intrathoracic pressure, and severe posterior cricoarytenoid can be increased by hyper-
hypoxia.27 capnia and ventilatory obstruction. It is lessened by
Although not classically considered part of the hypocapnia. The effect of ventilatory resistance on
protective reflex, reflex swallowing from stimulation posterior cricoarytenoid activity has been exten-
of the superior laryngeal nerve may have protective sively studied in the canine model. In this model,
functions. It has been shown that reflex swallowing when ventilatory resistance is eliminated, so is the
occurs with application of hypotonic fluids to the reflex abductor activity of the posterior cricoary-
supraglottic larynx, particularly the laryngeal surface tenoid. It is felt that the afferent limb of this reflex
of the epiglottis, glottis, and internal larynx. resides within the ascending vagus nerve and that
Although this is not the normal mechanism to initi- the end-organ receptors are located within the tho-
ate swallowing, it may serve to protect the larynx rax, although their precise location is unknown. The
against fluid that enters the laryngeal inlet.20 longer abductor activity is lost, the more difficult it
is to re-establish.30 This is the rationale for downsiz-
NEUROPHYSIOLOGY OF RESPIRATORY ing tracheotomy tubes (thus gradually increasing
ventilatory load) prior to decannulation.
FUNCTION The role of the larynx in controlling expiration
It is intuitive that if the larynx is the sphincter to the must also be considered. It is well known that the
lower airway, for respiration to occur, the sphincter control of respiratory rate occurs primarily through
needs to be actively opened during inspiration. variation of the expiratory phase. The time of expi-
Also, the opening of the folds must be synchronous ration is dependent on the ventilatory resistance pro-
Anatomy and Physiology of the Larynx 1103
duced by the glottis. As discussed above, the cricothy- control are not well defined. In some cases, the central
roid contracting with the posterior cricoarytenoid terminations of specific sensory receptors and the ori-
will give the maximal glottic opening and hence the gin of the motoneuron fibers are known, as in soma-
lowest ventilatory resistance. In this regard, cricothy- totopic organization for the face and limbs. To date,
roid contraction during expiration occurs when the studies of the role of the cerebral cortex in phonation
critical subglottic pressure change of 30 cm H2O/s is in primates reveal no such individual muscle repre-
exceeded and continues as long as positive subglottic sentation or somatotopic mapping of the laryngeal
pressure is maintained. As expected, this threshold system.20
for activation is reduced in hypercapnia (allowing for The role of peripheral mechanisms in phona-
quicker expiration and a faster respiratory rate) and tory control has been studied more successfully
increased in hypocapnia.31 using electromyography, airflow, and pressure stud-
ies in the vocal tract as well as imaging techniques,
which allow observation of the vocal tract during
NEUROPHYSIOLOGY OF PHONATION phonatory postures. It is important to consider that
The complex mechanisms of phonatory control phonation takes place in concert with upper articu-
coordinate central and peripheral components. Elec- lators, the lip, tongue, jaw, and velum.
tromyographic investigation of the control of Mechanical tissue deformation and, in partic-
peripheral neuromuscular systems involved in ular, the pull of the upper articulators on the larynx
phonation has demonstrated specific intrinsic and via the laryngeal-hyoid complex necessarily influ-
extrinsic muscle function in humans. Central mech- ence the phonatory environment. For example, Fig-
anisms are less well understood and often rely on ure 47–9 illustrates vocal tract shaping for four
animal models, which may only infer function in the distinct vowels. Note the apparent pull of the tongue
unique phonatory systems of the human. high and forward for production of /i/ (labeled “iy”),
As a general model, the larynx, as a system, in contrast to posterior and low posture for /a/
must respond to central commands from linguistic (labeled “aa”). The consequent constriction or, con-
and motor centers. Signals are then relayed to the versely, the opening of the posterior pharynx plays a
motor cortex in the precentral gyrus and on to motor key role in the acoustics of sound produced for each
nuclei in the brainstem and spinal cord. These sig- of these postures and influences laryngeal posturing
nals are transmitted to the respiratory, laryngeal, and for phonation.33
articulatory muscles responsible for speech and voice Electromyographic studies of specific muscle
production. These messages are influenced by the function indicate firing rates uniquely suited for
extrapyramidal system, including the cerebral cortex, fine control of laryngeal function. Contraction
cerebellum, and basal ganglia, exerting fine control times for the intrinsic muscles in several species are
of respiration, phonation, and articulation.32 presented in Table 47–1. Further, the high innerva-
Specific connectivity and the central control of tion ratio for human laryngeal muscles, estimated
brainstem motor neurons responsible for voluntary at 100 to 200 cells per motor unit,34 makes laryn-
control of phonation remain illusive. Laryngeal geal muscles capable of a great degree of precise
reflexes, which are key to the coordination of respira- control as required for adjustment of speaking fre-
tion, phonation, and deglutition, are understood pri- quency and intensity.
marily from the research focused on respiration and Intrinsic and extrinsic musculature, described
deglutition.20 Further, central projections to laryngeal previously in this chapter, influence specific action of
mechanisms are not consistent across species and laryngeal muscles during phonatory shaping of the
may differ from nonhuman primates to humans as glottis in sound production as described by Hirano
well. The nucleus tractus solitarius (NTS), periaque- (see Figure 47–5).32 Table 47–2 summarizes the
ductal gray, parabrachial nucleus, locus caeruleus, and influence of each of these muscles on the shape and
ventromedial nucleus of the thalamus are all areas tension of the glottis during phonation.
anatomically associated with the laryngeal system.20 It has been shown that the laryngeal muscles
Figure 47–8 illustrates branching of the superior start to contract about 100 to 200 ms prior to the
laryngeal nerve with central connectivity and projec- onset of phonation.35 Further, the most important
tions of the NTS. However, specific mechanisms of muscle in varying the phonation style (from
1104 Ballenger’s Otorhinolaryngology
A B
hypotense to hypertense) is the thyroarytenoid mus- chest register, the cricothyroid and vocalis, with the
cle.36 The frequency of vibration depends on the fol- possible contribution of the posterior cricoary-
lowing: (1) vibratory mass of both vocal folds, (2) tenoid, most consistently control changes in funda-
the anterior to posterior tension, (3) functional mental frequency.37
damping at high pitch, and (4) subglottic pressure. Lovquist and others later described elec-
In this regard, Gay and associates showed that in the tromyographic recordings obtained from four
Anatomy and Physiology of the Larynx 1105
intrinsic laryngeal muscles with simultaneous trans- in voiceless clustered sounds, with the lateral
illumination and acoustic signals.38 The vocalis and cricoarytenoid and the interarytenoid playing no
lateral cricoarytenoid muscles were observed to par- particular roles. Studies such as these underscore the
ticipate in the control of both articulation and complex interactive nature of laryngeal musculature
phonation. The interarytenoid muscle appeared to in phonatory/articulatory interaction.
be involved only in articulatory adjustments. Activ- In considering the phonatory process, a variety
ity in the cricothyroid was primarily related to of factors necessarily contribute to the acoustic
changes in fundamental frequency. This muscle also product as defined in Table 47–3. The psychoa-
showed an increase in activity for voiceless sounds. coustic parameters of pitch, loudness, quality, and
In addition, the vocalis muscle appeared to partici- fluctuation are correlated with acoustic qualities of
pate in glottal adduction without complete closure fundamental frequency, amplitude, waveform, and
TABLE 47–2. Characteristic Functions of the Laryngeal Muscles in Vocal Fold Adjustments
CT VOC LCA IA PCA
Position Paramed Adduct Adduct Adduct Abduct
Level Lower Lower Lower 0 Elevate
Length Elongate Shorten Elongate (Shorten) Elongate
Thickness Thin Thicken Thin (Thicken) Thin
Edge Sharpen Round Sharpen 0 Round
Muscle (body) Stiffen Stiffen Stiffen (Slacken) Stiffen
Mucosa (cover and transition) Stiffen Slacken Stiffen (Slacken) Stiffen
0 = no effect; ( ) = slightly; italics = markedly; CT = cricothyroid muscle; VOC = vocalis muscle; LCA = lateral cricoarytenoid
muscle; IA = interarytenoid muscle; PCA = posterior cricoarytenoid muscle.
Adapted from Hirano M. Clinical examination of voice. New York: Springer-Verlag; 1981.
acoustic spectrum. High-speed photography and namic theory of sound production. Vibration of the
observation of vocal fold vibration via videostrobo- vocal folds changes DC airflow into AC airflow, con-
scopic endoscopy reveal much about the behavior of verting aerodynamic energy to acoustic energy. The
the glottis during phonation.32,39 mucosal wave produced by these vibrations has been
The vibrations of the vocal folds are a passive captured on ultrahigh-speed photography by
phenomenon and represent the basis of the aerody- Hirano.32 The vibratory cycle is described as having
TABLE 47–3. Parameters in the Peripheral Process of the Production and Perception of Voice
Parameters That Regulate Parameters Parameters That
Vibratory Pattern of That Specify Specify Sound
Vocal Fold Vibratory Pattern Generated
Level Physiologic Physical Physical Acoustic Psychoacoustic
Parameters Neuromuscular (Primary) Fundamental Fundamental Pitch
control period frequency
Respiratory Expiratory Symmetry Amplitude Loudness
muscles force Periodicity (intensity)
Laryngeal Vocal fold Uniformity Waveform
muscles Position Glottal closure Acoustic Quality
Shape and size Amplitude spectrum
Elasticity Mucosal wave Fluctuations Fluctuations
Viscosity Speed of
Articulatory State of vocal excursion
muscles tract Glottal area
(Secondary) waveform
Pressure drop
across glottis
Volume velocity
Glottal
impedance
Adapted from Hirano M. Clinical examination of voice. New York: Springer-Verlag; 1981.
Anatomy and Physiology of the Larynx 1107
three phases: opening, closing, and closed. By con- ings using modern computers and software (Figure
vention, the cycle is described as beginning with the 47–10), Woo demonstrated male and female differ-
vocal folds closed. Frames 1 to 5 (see Figure 47–6, B) ences as well as influences of pitch and loudness.39
represent the opening phase. During this phase, sub- Women commonly demonstrate small posterior
glottic pressure increases, forcing the vocal folds glottal gaps that seem to have no pathologic acoustic
apart from an inferior to superior direction until the significance, whereas their glottal cycles have shorter
glottis opens, letting air escape and thus releasing closed phases than those of men. Mean peak glottal
subglottic pressure. As the elastic recoil of the vocal area is smaller in women, not only because of their
folds forces them back together, the portion of the smaller anatomic size but also owing to the fact that
vocal fold that was the last to open (superior portion) their higher frequency of vibration limits the lateral
is the last to close. Thus, the vocal folds close from excursion of the vocal folds, thereby reducing the
inferior to superior (frames 6 to 8). The folds then amplitude of vibration. As intensity increases, the
remain closed until the subglottic pressure builds up closing phase becomes shorter and the closed period
enough to force them open again. Anatomically, the becomes longer, suggesting that the closing patterns
movement of the mucosal wave depends on the soft of vocal folds are an especially important feature in
and compliant lamina propria and a healthy layered normal and pathologic phonation.
structure. In extracting complex details of glottal area The coordination of higher cortical centers
waveforms from videostrobolaryngoscopic record- interacts with specific musculature in the vocal tract
to produce acoustic products recognized as speech. vocal folds: a possible specialization for speech. Anat
The laryngeal contribution to this product continues Rec 1999;256:146–57.
to be revealed in basic studies of phonation as an 14. Sanders I. The microanatomy of the vocal folds. In:
interactive process. Rubin JS, Sataloff RT, Korovin GS, Gould WJ, edi-
tors. Diagnosis and treatment of voice disorders.
New York: Igaku-Shoin; 1995.
15. Gracco C, Kahane JC. Age-related changes in the
REFERENCES vestibular folds of the human larynx: a histomor-
1. Negus VE. The comparative anatomy and physiol- phometric study. J Voice 1989;3:204–12.
ogy of the larynx. London: Heinemann; 1949. 16. Holinger LD. Pharyngoceles, laryngoceles, and sac-
2. Maue WM, Dickinson DR. Cartilages and ligaments cular cysts. In: English GM, editor. Otolaryngology.
of the adult larynx. Arch Otolaryngol 1971;94:432–9. Vol 3. Philadelphia: JB Lippincott; 1993.
3. Meiteles LZ, Lin PT, Wenk EJ. An anatomic study of 17. Hirano M. Phonosurgical anatomy of the larynx. In:
the external laryngeal framework with surgical Ford CN, Bless DM, editors. Phonosurgery: assess-
implications. Otolaryngol Head Neck Surg 1992; ment and surgical management of voice disorders.
106:235–40. New York: Raven Press; 1991.
4. Hollinshead WH. Anatomy for Surgeons. Vol 1: the 18. Brunton TL, Cash T. The valvular action of the lar-
head and neck. 3rd ed. Philadelphia: JB Lippincott; ynx. J Anat Physiol 1883;17:363.
1982. 19. Johner CH. The lymphatics of the larynx. Otolaryn-
5. Spector GJ. Anatomy of the larynx. In: Ballenger JJ, gol Clin North Am 1970;3:439–51.
editor. Diseases of the nose, throat, ear, head and 20. Garrett DJ, Larson CR. Neurology of the laryngeal
neck. 13th ed. Philadelphia: Lea & Febiger; 1985. system. In: Ford CN, Bless DM, editors. Phono-
6. Hast MH. Anatomy of the larynx. In: English GM, surgery: assessment and surgical management of
editor. Otolaryngology. Vol 3. Philadelphia: JB Lip- voice disorders. New York: Raven Press; 1991.
pincott; 1993. 21. Sanders I, Mu L. Anatomy of human internal supe-
7. Sasaki CT, Driscoll BP, Gracco C. Anatomy and rior laryngeal nerve. Anat Rec 1998;252:646–56.
physiology of the larynx. In: Ballenger JJ, Snow JB, 22. Anderson JW, Sant’Ambrogio FB, Mathew OP, San-
editors. Otorhinolaryngology head and neck sur- t’Ambrogio G. Water-responsive laryngeal receptors
gery. 15th ed. Baltimore: Williams & Wilkins; in the dog are not specialized endings. Respir Phys-
1996. iol 1990;79:33–43.
8. Chamberlain WE, Young BR. Ossification (so-called 23. Bradley RM. Sensory receptors of the larynx. Am J
“calcification”) of normal laryngeal cartilages mistaken Med 2000;108 Suppl 4a:47–50.
for foreign body. Am J Roentgen Rad Ther 1935; 24. Sasaki CT. Physiology of the larynx. In: English GM,
33:441–50. editor. Otolaryngology. Vol 3. Philadelphia: JB Lip-
9. Hately W, Evison E, Samuel E. The pattern of ossifi- pincott; 1993.
cation in the laryngeal cartilages: a radiological 25. Sasaki CT, Suzuki M. The respiratory mechanism of
study. Br J Radiol 1965;38:585–91. aerosol inhalation in treatment of partial airway
10. Kirchner JA. What have whole organ sections con- obstruction. Pediatrics 1977;59:689–94.
tributed to the treatment of laryngeal cancer. Ann 26. Sasaki CT, Suzuki M. Laryngeal reflexes in cat, dog
Otol Rhinol Laryngol 1989;98:661–6. and man. Arch Otolaryngol 1976;102:400–2.
11. Sanders I, Jacobs I, Wu BL, Biller HF. The three bel- 27. Suzuki M, Sasaki CT. Laryngeal spasm: neurophysi-
lies of the canine posterior cricoarytenoid muscle: ologic redefinition. Ann Otol Rhinol Laryngol 1977;
implications for understanding laryngeal function. 86:150–7.
Laryngoscope 1993;103:171–7. 28. Suzuki M, Kirchner JA. The posterior cricoarytenoid
12. Sanders I, Rao F, Biller HF. Arytenoid motion evoked as an inspiratory muscle. Ann Otol Rhinol Laryngol
by regional electrical stimulation of the canine pos- 1969;78:849–64.
terior cricoarytenoid muscle. Laryngoscope 1994; 29. Suzuki M, Kirchner JA, Murakami Y. The cricothy-
104:456–62. roid as a respiratory muscle. Its characteristics in
13. Han Y, Wang J, Fischman DA, et al. Slow tonic mus- bilateral recurrent laryngeal nerve paralysis. Ann
cle fibers in the thyroarytenoid muscles of human Otol Rhinol Laryngol 1970;79:976–83.
Anatomy and Physiology of the Larynx 1109
30. Sasaki CT, Fukuda H, Kirchner JA. Laryngeal abduc- 35. Buchthal F, Faaborg-Anderson K. Electromyography
tor activity in response to varying ventilatory resist- of laryngeal and respiratory muscles: correlation
ance. Trans Am Acad Ophthalmol Otolaryngol 1973; with phonation and respiration. Ann Otol Rhinol
77:403–10. Laryngol 1964;73:118–23.
31. Sasaki CT. Electrophysiology of the larynx. In: 36. Hirano M, Koike Y, Joyner J. Style of phonation: an
Blitzer A, Brin MF, Sasaki CT, et al, editors. Neuro- electromyographic investigation of some laryngeal
logic disorder of the larynx. New York: Thieme Med- muscles. Arch Otolaryngol 1969;89:902–7.
ical Publishers; 1992. 37. Gay T, Strome M, Hirose H, et al. Electromyography
32. Hirano M. Clinical examination of voice. New York: of the intrinsic laryngeal muscles during phonation.
Springer-Verlag; 1981. Ann Otol Rhinol Laryngol 1972;81:401–9.
33. Gracco C. Vocal tract imaging. New York: Biomed- 38. Lovqvist A, McGarr N, Honda K. Laryngeal muscles
ical Communications; 1994. and articulatory control. J Acoust Soc Am 1984;76:
34. Kempster GB, Larson CR, Distler MK. Effects of 951–4.
electrical stimulation of cricothyroid and thyroary- 39. Woo P. Quantification of videostrobolaryngoscopic
tenoid muscles on voice fundamental frequency. J findings—measurements of the normal glottal
Voice 1988;2:221–9. cycle. Laryngoscope 1996;106 Suppl 79:1–27.
CHAPTER 48
Human prenatal life is divided into embryonic and piratory diverticulum that projects from the diges-
fetal periods. The embryonic period, which com- tive tube into the mesenchyme ventral to the foregut.
prises the first 8 weeks, is subdivided into 23 devel- Right and left lung buds are soon detectable
opmental stages, the details of which have been (stage 13), and the trachea becomes visible in the
described elsewhere.1 Prenatal age is postfertiliza- more advanced specimens. The bifurcation point of
tional. Postmenstrual weeks (which are not age) are the trachea then begins to descend.
useful clinically, but the term gestational age is
meaningless.2 A summary of the developing respira- THE TRACHEO-ESOPHAGEAL SEPTUM
tory system in relation to staging was published by
O’Rahilly and Boyden,3 and many further details The term tracheo-esophageal septum was used his-
were provided by O’Rahilly and Müller.4 Since the torically for a supposed fusion between medially
classic study of the larynx by Soulié and Bardier,5 the growing internal folds in the wall of the foregut,
development of this organ has been investigated by, which were believed to advance caudorostrally. Such
among others, O’Rahilly and Tucker6 and Müller et a septum, however, does not exist.10 In point of fact,
al,7,8 and there has been an excellent study in the as the respiratory primordium grows caudad, it
mouse.9 Many references to the earlier literature can becomes separated from the digestive primordium
be found in these publications. by tracheo-esophageal mesenchyme. The summit of
It is known that the hyoid bone is derived from this mesenchymal partition is the separation point
the cartilaginous elements of pharyngeal arches 2 and between the trachea and the esophagus, and it
3, and the thyroid and other cartilages of the larynx remains at a constant vertebral level during the first
are believed to be associated with the more caudally 6 postfertilization weeks (Figure 48–1).
situated arches. The details of the developing larynx
Four to Six Weeks At about 5 weeks (stages 14 and
have been identified stage by stage. A summary of the
15), the future larynx begins its differentiation. The
development of the larynx is provided in Table 48–1. lateral epithelial walls become apposed in the
median plane, thereby forming what is known as the
EMBRYONIC PERIOD epithelial lamina. This bilaminar plate is situated
between the arytenoid swellings, behind which the
In a certain sense, the larynx may be considered as a pharyngeal lumen still communicates with the tra-
diverticulum of the future laryngopharynx, with chea (pharyngoinfraglottic duct or canal). The
which (except for a temporary embryonic closure) it hypopharyngeal (formerly called hypobranchial)
communicates throughout life. eminence does not represent the epiglottis, which is
identifiable a little later.
The hyoid condensation begins to appear, and
THREE TO FOUR WEEKS
by 6 weeks, the cricoid can be identified in mes-
At 3 to 4 weeks, when the embryo is only about 3 mm enchyme (Figure 48–2). This is followed by the
long (stage 10), a median pharyngeal groove (inter- appearance of a single cartilaginous cricoid center.11
nally) and ridge (externally) are discernible, and the The larynx is clearly definable by 6 weeks
groove includes the laryngotracheal sulcus. Within a (stage 17) (see Figure 48–2, B). At this time, or a few
few days (stage 12), the “lung bud” appears as a res- days earlier, the front portion of the epithelial lam-
1110
Development of the Larynx 1111
TABLE 48–1. Initial Appearance of Features of the Larynx and Related Structures
mm 2 3 4 5 6 8 10 15 20 25 30
Weeks 4 5 6 7 8
Feature Stage 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Foregut appears
Laryngotracheal keel and sulcus (respiratory primordium)
Pharyngeal arches, clefts, and pouches
Lung bud and primary bronchi
Sagittal cleft of larynx
Arytenoid swellings; epithelial lamina of larynx; trachea;
superior laryngeal nerve
Pharyngoinfraglottic duct connects digestive and
respiratory tubes
Epithelial lamina is complete; coronal cleft (not vestibule)
of larynx identifiable
Hyoid and cricoid condensations
Skeleton of pharyngeal arches and larynx is dense mesenchyme;
infraglottic cavity; ansa cervicalis and recurrent laryngeal nerve
Hyoid chondrification begins; cricothyroid, posterior crico-
arytenoid, arytenoid, and “thyrocricoarytenoid” muscles
Epithelial lamina closes respiratory canal from pharynx
Mesenchymal epiglottis
Thyroarytenoid and lateral cricoarytenoid muscles
Solid primordium of ventricle of larynx begins to appear;
epithelial lamina begins to disintegrate
Perioral reflex responses ?
Aryepiglottic and thyroepiglottic muscles; ventricles that are
angulated to the coronal cleft; intraepithelial receptors in
laryngopharynx and nasal epithelium
Epiglottis and palate are not yet in contact; vestibule becomes
connected to infraglottic cavity; right and left leaves of
epithelial lamina begin to separate; infrahyoid and most
laryngeal muscles are present, eg, cricothyroid (oblique
and straight parts); adult pattern of motor innervation,
sensory incomplete
ina can be regarded as its vestibular part. Lateral a portion of the adult vestibule, which also includes
expansions of this portion soon form the embryonic the median cleft.
vestibule (coronal or transverse cleft) (see Figure The appearance of the epithelial lamina at 6
48–2, B). The laryngeal cavity is now T-shaped in weeks (stage 18) resembles type 1 congenital atresia,
transverse section, but the transverse cleft that con- which may be essentially a persistence of the embry-
stitutes the embryonic vestibule corresponds to only onic condition.4 The rostral end of the tracheal
1112 Ballenger’s Otorhinolaryngology
lumen is believed to represent the future infraglottic (base of the axis) by 6 weeks (see Figure 48–1). The
cavity. A tendency for the vestibule and the trachea pouch is then caudal to the epithelial lamina and
to communicate with each other (vestibuloinfra- does not represent the border between the pharynx
glottic duct or canal) is characteristic. Laryngeal and the larynx, as claimed.11 Indeed, it is as low as
muscles are beginning to develop, but acceptable the level of the future cricoid cartilage, and there is
evidence for the existence of one or two common no room for a fifth pharyngeal pouch, supposed to
sphincters initially is lacking.5,7 The hyoid condensa- correspond with the laryngeal ventricle.10 In con-
tion is undergoing chondrification, and condensa- trast, what we have termed the separation point
tion for the thyroid laminae begins to appear. between the trachea and esophagus, that is, the sum-
mit of the tracheoesophageal mesenchyme,4 is
IMPORTANCE OF VERTEBRAL LEVELS remarkably stable (see Figure 48–1), which is said to
be caused by its catenoid structure.13
In the assessment of levels, the only reliable land-
marks are first the somites and then, also postnatally, Seven to Eight Weeks The pharyngoinfraglottic
the vertebrae. Soft tissues, such as pharyngeal duct is largely, if not entirely, open in most embryos,
pouches and spinal ganglia, are unreliable because and the track of the vestibuloinfraglottic duct is vis-
they shift in position during development. Pharyn- ible (see Figure 48–2, C). The ventricles of the larynx
geal pouch 4, for example, used by several authors as begin to appear as right and left laterally projecting
a landmark,10–12 is initially at the level of somite 2 epithelial buds. The right and left leaves of the
(future basioccipital) but changes to somites 6 and 7 epithelial lamina are beginning to separate, but at
Development of the Larynx 1113
the end of the embryonic period (stage 23), areas of established, although most fibers do not yet reach
fusion generally persist rostrally and caudally. The the epithelium. In the laryngopharynx, however,
pharyngeal lumen, however, is continuous with the receptors are present.8
infraglottic cavity and hence with the trachea. Cavi-
tation is beginning in the ventricles.
By the end of the embryonic period (stage 23;
FETAL PERIOD
Figure 48–3), the hyoid cartilage consists of the body Much information concerning the fetal larynx is
and greater horns, the lesser horns being distinct available from Soulié and Bardier.5
nodules separated from the styloid processes. The During trimester 1 (Figure 48–4, A), the larynx
cartilaginous thyroid laminae, which may show a increases in size from about 3 to 7 mm. The thyroid
foramen, are united below by mesenchyme (“cop- laminae become fused, and the cricothyroid mem-
ula”). The superior horns may or may not be con- brane develops. The vocal ligaments begin to form
tinuous with the laminae, but they arise in common early (33 mm), and the ventricular ligaments and
with the greater horns of the hyoid. The cricoid car- glottis become increasingly apparent. The ventricles
tilage is a continuous ring that comprises an arch acquire their saccules. The cricoarytenoid joints
and a lamina. Each arytenoid cartilage possesses a undergo cavitation, in which they are followed by
cartilaginous muscular process and a mesenchymal the cricothyroid joints. By 90 mm, the laryngeal cav-
vocal process. ity has its adult form.5
Most of the major laryngeal muscles During trimester 2 (see Figure 48–4, C), the
(cricothyroid, posterior and lateral cricoarytenoids, larynx increases in size from about 8 to 15 mm. The
thyroarytenoid, transverse arytenoid) are now pres- thyroid cartilage becomes a single structure. The
ent (although not yet striated), and their innerva- epiglottis begins to chondrify. The hyoid cartilage
tion follows the adult pattern closely.7 Motor fibers commences ossification. The corniculate and
penetrate the muscles. The vocalis is beginning to cuneiform cartilages develop. The joints acquire lig-
differentiate. aments. Glands become well developed. Elastic fibers
The laryngeal cavity now comprises (as in the have been detected in the epiglottis.14
adult) the vestibule, the ventricles and the part During trimester 3, the larynx increases in size
between them, and the infraglottic cavity. The ven- to about 15 to 20 mm, and the inlet is about 5 mm
tricles are not at the level of the future glottis, which in diameter. Laryngeal connective tissue compart-
lies more caudally. The sensory innervation is well ments in trimesters 2 and 3 have been studied.15
1114 Ballenger’s Otorhinolaryngology
Measurements of the developing larynx are adulthood (Figure 48–5). Vertebral levels are avail-
available: embryonic and fetal,5 fetal and infantile,16 able: embryonic,4 fetal,20 fetal and child’s,21 and
infantile,17 infantile and child’s,18 and prepubertal child’s.22 The infantile larynx has been studied,23,24
and pubertal.19 The larynx, as indicated by the tip of and detailed views have been published.25
the epiglottis, the hyoid, and the lower border of the Ossification in the thyroid cartilage frequently
cricoid, descends from embryonic and fetal life to begins from about 20 years onward in the posterior
border of each lamina. It would be imprudent, how- such as anomalies of the limbs. Similarly, cleft larynx
ever, to attempt to estimate age from the extent of may be associated with a congenital cardiac defect
the ossific process.26 or cleft lip and palate and has been considered a
Function begins in the fetal larynx early in median developmental field defect that can occur in
trimester 2, when the larynx opens for the inhala- causally different syndromes.
tion of amniotic fluid into the lungs, and the Laryngomalacia, said to be the most frequent
diaphragm descends. Phonatory vibrations com- congenital laryngeal anomaly, produces partial
mence later in the trimester.27 obstruction of the supraglottic airway, but its
cause is unclear and cannot be merely immaturity
and alterations of the cartilaginous and muscular
CONGENITAL ANOMALIES components.28
Only some congenital anomalies of the larynx are Laryngeal clefts, which may extend to the tra-
currently amenable to interpretation in develop- chea and even to the carina, are rare.29 Interary-
mental terms. tenoid clefts develop as a consequence of lack of
Some laryngeal anomalies are part of a more development of the interarytenoid and aryepiglottic
widespread disturbance. Thus, congenital webs may muscles.30 Cricoid clefts, which may be partial or
be accompanied by subglottic stenosis, and struc- total, may arise from incomplete dorsal fusion of the
tures far removed are affected in some instances, limbs of the single ventral chondrific center.30 Com-
1116 Ballenger’s Otorhinolaryngology
plete clefts, those that involve the trachea, probably and a survey of the Carnegie Collection. Washington
develop during separation of the trachea and esoph- (DC): Carnegie Institution of Washington; 1987.
agus at 4 to 5 weeks (stage 13), as suggested by the 2. O’Rahilly R, Müller F. Prenatal ages and stages—
frequent association with tracheoesophageal fistulae. measures and errors. Teratology 2000;61:382–4.
Congenital laryngeal atresia probably arises 3. O’Rahilly R, Boyden EA. The timing and sequence of
between 6 and 10 postovulatory weeks, the more events in the development of the human respiratory
extensive examples representing embryonic stages system during the embryonic period proper. Z Anat
and the less severe forms being fetal. They are supra- Entwicklungsgesch 1973;141:237–50.
glottic rather than infraglottic.30 Complete atresia, 4. O’Rahilly R, Müller F. Respiratory and alimentary
which is probably the least frequent of congenital relations in staged human embryos. New embry-
laryngeal anomalies, is associated with polyhydram- ological data and congenital anomalies. Ann Otol
nios.28 It resembles closely the normal appearance of Rhinol Laryngol 1984;93:421–9.
the larynx at 6 weeks (stage 18) and may be basically 5. Soulié A, Bardier F. Recherches sur le développement
a persistence of the embryonic condition when the du larynx chez l’homme. J Anat Physiol 1907;43:
epithelial lamina has reached its full expansion (see 137–240.
Figure 48–2, C). Incomplete atresia arises later; 6. O’Rahilly R, Tucker JA. The early development of the
hence, the vestibule has already developed to a vari- larynx in staged human embryos. I. Embyros of the
able degree. Glottic atresia, the most frequent type, first five weeks (to stage 15). Ann Otol Rhinol
probably arises early during the fetal period, when Laryngol 1973;82:1–27.
the epithelial lamina has failed to undergo further 7. Müller F, O’Rahilly R, Tucker JA. The human larynx
delamination. at the end of the embryonic period proper. I. The
Congenital laryngeal webs, situated ventrally laryngeal and infrahyoid muscles and their innerva-
and extending dorsally to a variable degree, are also tion. Acta Otolaryngol (Stockh) 1981;91:323–36.
thought to result probably from a localized failure of 8. Müller F, O’Rahilly R, Tucker JA. The human larynx
splitting of the epithelial lamina into two walls, most at the end of the embryonic period proper. 2. The
likely early in the fetal period. A special instance is a laryngeal cavity and the innervation of its lining.
web at the vocal folds, namely at the lower border of Ann Otol Rhinol Laryngol 1985;94:607–17.
the epithelial lamina. It presents, early in the fetal 9. Henick DH. Three-dimensional analysis of murine
period, as a perforated membrane that obstructs the laryngeal development. Ann Otol Rhinol Laryngol
glottic opening.30 1993;102 Suppl 159:3–24.
Infraglottic (subglottic) stenosis is not associated 10. Zaw-Tun HA. The tracheo-esophageal septum—fact
with the persistence of the epithelial lamina, but or fantasy? Origin and development of the respira-
some instances seem to be produced by deformities tory primordium and esophagus. Acta Anat (Basel)
of the cricoid cartilage. Cartilaginous and membra- 1982;114:1–21.
nous types would differ in origin. 11. Zaw-Tun HA, Burdi AR. Reexamination of the ori-
Congenital laryngeal cysts may be ventricular or gin and early development of the human larynx.
infraglottic. They are usually in the region of the sac- Acta Anat (Basel) 1985;122:163–84.
cule but do not communicate with the laryngeal 12. Sanudo JR, Domenech-Mateu JM. The laryngeal pri-
lumen. They probably indicate disturbed develop- mordium and epithelial lamina. A new interpreta-
ment in fetal life. tion. J Anat 1990;171:207–22.
Nonrecurrent laryngeal nerve is associated with 13. Sutliff K, Hutchins GM. Septation of the respiratory
an abnormal origin of the right subclavian artery, and digestive tracts in human embryos: crucial role
usually from the dorsal aspect of the arch of the of the tracheoesophageal sulcus. Anat Rec 1994;
aorta. The condition is believed to arise from an 238:237–47.
embryonic failure of the right aortic arch 4, allowing 14. Patzelt V. Über die menschliche Epiglottis und die
the nerve to proceed directly to the larynx. Entwicklung des Epithela in den Nachbargebieten. Z
Anat Entwicklungsgesch 1924;70:1–178.
15. Tucker GF, Smith HR. A histological demonstration
REFERENCES of the development of laryngeal connective tissue
1. O’Rahilly R, Müller F. Developmental stages in human compartments. Trans Am Acad Ophthalmol Oto-
embryos, including a revision of Streeter’s “Horizons” laryngol 1962;66:308–18.
Development of the Larynx 1117
16. Schild JA. Relationship of laryngeal dimensions to 24. Wilson TG. Some observations on the anatomy of
body size and gestational age in premature neonates the infantile larynx. Acta Otolaryngol (Stockh)
and small infants. Laryngoscope 1984;94:1284–92. 1953;43:95–9.
17. Eckenhoff JF. Some anatomic considerations of the 25. Bosma JF. Anatomy of the infant head. Baltimore:
infant larynx influencing endotracheal anesthesia. Johns Hopkins University Press; 1986.
Anesthesiology 1951;12:401–40. 26. Keen JA, Wainwright J. Ossification of the thyroid,
18. Peter K, Wetzel G, Heiderich F, eds. Handbuch der cricoid and arytenoid cartilages. S Afr J Lab Clin
Anatomie des Kindes. Munich: Bergmann; 1938. Med 1958;4:83.
19. Kahane JC. A morphological study of the human 27. Ramón y Cajal CL. Description of human fetal
prepubertal and pubertal larynx. Am J Anat 1978; laryngeal functions: phonation. Early Hum Dev
151:11–9. 1996;45:63.
20. Magriples U, Laitman JT. Developmental change in 28. Willging JP, Cotton RT. Congenital anomalies of
the position of the fetal human larynx. Am J Phys the larynx. In: Tewfik TL, der Kaloustian VM, edi-
Anthropol 1987;72:463–72. tors. Congenital anomalies of the ear, nose, and
21. Noback GJ. The developmental topography of the throat. New York: Oxford University Press; 1997.
larynx, trachea and lungs in the fetus, new-born, p. 383–91.
infant and child. Am J Dis Child 1923;26:515–33. 29. Benjamin B, Inglis A. Minor congenital laryngeal
22. Roche AF, Barkla DH. The level of the larynx during clefts: diagnosis and classification. Ann Otol Rhinol
childhood. Ann Otol Rhinol Laryngol 1965;74: Laryngol 1989;98:417–20.
645–54. 30. Zaw-Tun HA. Development of congenital laryngeal
23. Tucker G. The infant larynx: direct laryngoscopic atresias and clefts. Ann Otol Rhinol Laryngol 1988;
observation. JAMA 1932;99:1899–902. 97:353.
CHAPTER 49
Disorders of voice, speech, and language comprise which air pulses are released through the glottic
an important category of problems faced by the aperture owing to vocal fold vibration, a rate deter-
physician because treatment of these disorders can mined primarily by the mass and elasticity of the
have a large influence on vocational, social, and vocal folds in relation to their length. Large folds
emotional adjustments of the patient. Many oto- produce a lower pitch than smaller folds because the
laryngologists are properly reluctant to provide greater mass causes them to vibrate more slowly.
rehabilitation for communicative disorders beyond This is why adults have lower vocal pitches than do
the treatment of disease because they believe they infants and young children; vocal pitch is inversely
are not qualified. Patients, however, inevitably seek related to the size of the vocal folds. However, each
answers to questions about communication disor- talker also has the ability to change the frequency of
ders and, while attempting to be helpful, the physi- vocal fold vibration. When the folds in any normal
cian often finds it necessary to play the role of a larynx are shortened, their cross-section becomes
part-time speech-language pathologist and coun- larger, and their myoelasticity is reduced. Such folds
selor. One of the purposes of this chapter is to pro- tend to move more slowly. Conversely, when the
vide current information about disorders of voice, vocal folds are elongated, they become thinner, and
speech, and language and their remediation. their elasticity is increased. As a result, when the air
This chapter is organized around three major stream pushes tightened and thinned vocal folds
categories of communication disorders: disorders of apart, they return to their approximated positions
voice, speech, and language. Each category will be more quickly. This reaction results in increased fre-
discussed separately. Communication disorders quency of vocal fold vibration (higher pitch). Fre-
stemming from hearing impairments are discussed quency of vibration may also be altered by isotonic
in Chapter 5. tension in the muscles of the vocal folds. This type of
contraction increases the stiffness of the folds and
consequently causes them to vibrate more rapidly.
VOICE DISORDERS
Loudness Loudness of the voice is related to the
NORMAL VOICE PRODUCTION sound pressure created by the released pulsations of
Voiced sound during speech production is called air through the glottis. Sound pressure is directly
phonation. Depending on the length, tension, and proportional to the volume-velocity of airflow in the
thickness adjustments of the vocal folds, the tone glottis. By increasing the thickness and stiffness of
produced by normal vibrating vocal folds can vary the vocal folds, increased resistance can be offered to
in frequency (perceived as variations of the pitch of the flow of air from the lung as the folds remain
the voice), intensity (loudness), duration, or quality. closed for a longer percentage of time during each
Such parameters contribute to changes in intonation cycle of vibration. The longer closed period allows
and stress during speech production and perception. greater subglottal air pressure to build up to over-
come the increased resistance offered by the folds.
Pitch The pitch of sound produced during normal With increased subglottal driving pressure on open-
phonation is directly related to the frequency at ing of the glottis, increased volume velocities of air-
1118
Disorders of Voice, Speech, and Language 1119
flow occur. Moreover, because increased stiffness vocal folds function to produce disordered voice. A
and thickness of the vocal folds increase the elastic- clinical appreciation of vocal fold vibration can
ity of the vocalis or internal thyroarytenoid muscles, begin with the concept of an ideal larynx. In such an
they snap back to the midline with increased veloc- organ, the two vocal folds would have the same
ity. The rapidly changing volume-velocity of the dimensions, they would move symmetrically and
escaping train of pressure pulses increases the ampli- regularly, and each vibratory cycle would include
tude of sound waves generated, causing greater three phases: glottal opening, glottal closing, and
excursions of the tympanic membrane in the ear of closed glottis. The vocal sound from this ideal larynx
a listener and a sensation of louder sound. would be judged “excellent”; it would be smooth and
free of all hoarseness, have an appropriate pitch
Quality Both vocal fold vibration and resonance range for the age and gender of the talker, and would
determine the quality of voice. The phonatory aspect be capable of wide pitch and loudness variation.
includes the manner of air pulse release at the glot- When vibration of the vocal folds varies from the
tis. Opening, closing, and closed phases of the glot- ideal, the characteristics of the voice also vary from
tal cycle can vary in relation to each other. For the ideal—the extent of vocal difference depending
example, laryngeal lesions can influence the pattern on the type and amount of alteration in the vibra-
of movement of the vocal folds, independently and tory pattern.
in combination (to be discussed later in this chap- The assumption that no two faces are exactly
ter). These factors can influence the number and rel- alike is commonly accepted. Observation of living
ative intensity of harmonic partials composing the and dissected larynges leads to a parallel assump-
complex vocal sound and, consequently, the quality tion that no two larynges are exactly alike. Each
of the voice. Modification of sound as it travels larynx reflects its uniqueness in its behavioral phys-
through the pharynx, mouth, and nose (resonance) iology, yet most larynges are capable of producing
results from selective emphasis and damping of the a normal voice that is judged to be within the
overtones and other partials in the complex sound accepted ranges of pitch, loudness, and quality
generated in the larynx. found in a majority of individuals of the same age
The contribution of voice to a normal com- and sex.
munication process is demonstrated succinctly by its Abnormal vocal fold vibration takes many
absence; speech without phonation is whispering. In forms, most of them not visible to the unaided eye.
whispered speech, the vocal folds do not vibrate, and Ultra–slow-motion films of abnormal voices reveal
the laryngeal sound is aphonic. When this condition that one fold may move faster than the other, one
is present, the speaker can produce speech and lan- may have a greater lateral excursion, vibration may
guage but has no vocal pitch in the musical sense. be limited to one vocal fold, there may be no glottal
The sound is a relatively weak noise composed of closure or incomplete glottal closure, closure may
breath sounds produced when the air becomes tur- occur at a paramedian position, vibratory patterns
bulent as it rushes past the irregularities that jut may be dissimilar at different regions along one or
from the walls of the respiratory tract (particularly both folds, and the vibratory periods and amplitudes
at the true and false vocal folds). This turbulent air may be randomly variable in consecutive glottal
noise constitutes a sound source that is acted on by openings.1 Acoustic indicators of such patterns may
the resonances of the mouth, pharynx, and nose include pitch period perturbations (jitter), ampli-
much as resonance occurs when vocal sound arises tude perturbations (shimmer), decreased signal-to-
at the glottis. When the vocal folds vibrate, there is noise ratio (more glottal noise), altered fundamental
vocal sound that has pitch and many of the distin- frequency (F0), increased standard deviations of F0,
guishing vocal qualities that identify individual and many others. The potential complexity of vibra-
voices, whereas in whisper they are absent. tory patterns resulting from combinations of these
cyclic abnormalities and sequential irregularities is
CAUSES OF VOICE DISORDERS almost endless.
Voice disorders always have causes. Something must Pitch Disorders Pitch disorders are present when
be abnormal or atypical in the way in which the the voice is consistently higher or lower (in relation
1120 Ballenger’s Otorhinolaryngology
to the musical scale) than would be expected for an UNDERDEVELOPED LARYNX. The underdeveloped lar-
individual of a given gender and age or when the ynx has small vocal folds that vibrate more rapidly
sound is tremulous, monotonous, or bizarre (eg, than larger folds and consequently create a high
when the pitch patterns do not convey the ideas pitch. The small larynx may accompany a general
being expressed). An involuntary, high-pitched structural retardation or may be part of a hereditary
voice in males does not necessarily interfere with familial body size. The clinician should be particu-
communication, and if a woman produced it, it larly sensitive to genetic syndrome effects from var-
would probably not be considered unpleasant. A ious forms of dwarfism, short neck, an abnormality
similar example could be provided for women with associated with syndromes of short stature, and
very low-pitched voices. The “voice disorder,” there- other possible syndromic effects when an underde-
fore, is not the sound itself, which may be quite veloped larynx is observed.3 The larynx may also fail
appropriate for the size and shape of the larynx that to develop as a result of hormonal imbalance, which
produced it, but the inappropriateness of the sound is usually revealed in simultaneous retardation of
to the circumstances (the age and gender of the other secondary sex characteristics.
talker). LARYNGEAL WEB. Another organic cause of high-
pitched voice is a laryngeal web, which may be con-
FUNCTIONAL PITCH PROBLEMS. In contrast to the fore- genital or cicatricial. When this structure is small
going example, high-pitched male voices frequently enough not to interfere with breathing or when it
have functional origins. Verdolini described muta- does not contribute to stridor, it may go undetected
tional falsetto as “the continued use of a high pitched until the voice is observed as abnormal. A web need
(falsetto) voice by a postpubertal male, without any not extend far along the borders of the vocal folds to
apparent physical basis. For some patients, psycho- create a voice problem. Its effect is to shorten the free
logical conflict is implied as a basis for the disorder. portions of the folds and thereby produce faster
In other patients, the disorder may simply reflect a vibration and a resulting higher pitch. The vocal
learned pattern.”2 To tell a person with this type of tone in children with webs resembles falsetto and
voice that he has nothing wrong with his larynx and tends to be weak. Hoarseness may be present also,
that he should go home and speak normally may accompanied by the audible evidence of vocal strain,
reassure him, but it does not help him, and usually particularly with men who have attempted to force
it serves only to increase his frustration. He is already a lower pitch.
speaking “normally” and needs to be taught how to
phonate in a way that is “abnormal” for him. Most of STRUCTURAL ASYMMETRY. A third organic cause for
these patients respond readily to voice therapy and chronic high pitch is abnormal approximation of the
adopt the new voice after a brief period of self-con- vocal folds. In this condition, a structural asymme-
sciousness. Those with normal structure who volun- try may cause the vocal process of one arytenoid car-
tarily maintain the high pitch reflect an abnormal tilage to slide on top of its opposite member in such
self-image and should be referred to a psychiatrist a manner that posterior parts of the membranous
or clinical psychologist. folds are pressed together, thereby effectively short-
Another form of functional pitch problem is ening their vibrating portions. The adjustment
ventricular phonation wherein the talker produces a approximates that which is often observed in the
low-pitched, gravely voice through vibration of the male larynx when a high-pitched, falsetto voice is
false vocal folds. This type of phonation most often produced.
develops as a compensatory mechanism. SWELLING OF THE ANTERIOR COMMISSURE. A fourth
condition, and one that may be overlooked or
ORGANIC HIGH-PITCH PROBLEMS. Although most ignored as a cause of excessively high pitch, is
abnormally high-pitched voices are probably caused enlargement of the glottal margin of one or both
by functional problems, cases with organic causes vocal folds adjacent to the anterior commissure. A
are not uncommon and may be classified into four localized protrusion no more than l mm high and
categories: underdeveloped larynx, laryngeal web, 2 mm long on the glottal margin is sufficient to
structural asymmetry, and swelling in the anterior shorten the vibrating length of the folds and to pro-
commissure. duce a higher than normal pitch. This lesion can be
Disorders of Voice, Speech, and Language 1121
seen only when the anterior commissure is visual- haps for some general enlargement of the vocal folds
ized, while the folds are widely abducted. During toward their glottal margins. The effects of compen-
adduction, the protruding areas are compressed satory vocal adjustments on size and condition of
into the underlying tissue and create the illusion of the folds are not known.
a prominent commissural attachment without sig-
GLOTTALIZATION OR “VOCAL FRY.” A form of exces-
nificance. The location of the offending lesion at the
sively low pitch characterized by a low-frequency
anterior attachment where the folds converge
popping or ticking sound is referred to as vocal fry
enables it to modify the vibratory pattern more
or glottalization. It is produced normally when only
extensively than it would if it were located more
a little breath pressure is exerted against the vocal
posteriorly. When a protruding mass is located
folds, such as during the ending of a phrase. This
where it is not pinched between the vocal folds, it
low-pitched voice is adopted occasionally by adoles-
usually does not shorten the vibrators and conse-
cent boys and young men in an effort to sound
quently does not raise vocal pitch; instead, it often
“more masculine.” Although glottalization is often
causes a lower pitch accompanied by hoarseness or
functional, it also has organic causes. Edematous
breathiness.
vocal folds from whatever cause are frequently asso-
ORGANIC LOW-P ITCH PROBLEMS. Defects of vocal ciated with this voice. Other alterations of the vocal
pitch can also encompass the abnormally low voice. folds, such as dry mucosa following irradiation ther-
Excessively low pitch in both men and women is apy, or absence of a flexible covering membrane,
usually associated with organic change; however, may be observed.
functional disorders are observed in persons who TREMULOUSNESS. Vocal pitch deviation such as per-
attempt to speak at a pitch below that which is opti- sistent tremulousness and its opposite, extreme
mum for the structures involved. The most com- monotony, are rare in young persons and are usu-
mon organic origins of low-pitched voices are ally considered psychogenic. In older individuals,
Reinke’s edema, virilization, glottalization or “vocal however, these vocal characteristics may be sympto-
fry,” and tremulousness. matic of deterioration or injury to the nervous sys-
REINKE’S EDEMA. Verdolini suggested that tem.7 In instances of brainstem involvement, such
vocal changes may appear among the early symp-
Reinke’s edema involves the widespread accumulation toms and consequently deserve careful considera-
of fluid or swelling, usually in both vocal folds, in the
tion in diagnosis.8,9 On the other hand, when either
layer of tissue right below the vocal fold epithelium.
Although the causes for this edema are not entirely tremulousness or monotony develops as a second-
clear, some clinicians think that chronic exposure to ary symptom, other impairments are usually so
irritants such as smoke may play a role in the develop- prominent that the voice, as an entity, is relatively
ment of the condition. The most obvious effect of unimportant as a priority in therapy.10,11 One of the
Reinke’s edema on voice typically is an extremely low most common diseases of the extrapyramidal sys-
speaking pitch (due to the increased mass of the folds) tem is Parkinson’s disease, in which chemical defi-
and loss of the ability to produce high notes. The voice ciencies (specifically a lack of dopamine) produce a
is also described as raspy.2 generalized movement disorder characterized by
small movements (hypokinesia) and slow move-
VIRILIZATION. An abnormally low pitch or masculine ments (bradykinesia) that impose low-frequency
type of voice in a woman is as distressing to the variations on voice production.2,12
woman possessing it as high pitch is in the male, and
for the same kinds of psychosocial reasons. Viriliza- Loudness Disorders Disorders of loudness may
tion of the female voice after hormone therapy in also be classified into categories that parallel those
young women has been reported with increasing used with pitch deviations; some are functional and
frequency.5,6 Recovery of normal pitch in these some are organic. The voice may be too loud or not
patients does not occur with interruption of med- loud enough in relation to the place and circum-
ication, and at present, no specific counteragent stances, or there may be loudness variations that are
seems to exist. The larynges of women with virilized not appropriate for conveying the meaning of the
voices appear to be normal in all aspects except per- utterance. Moreover, any generalized swelling of the
1122 Ballenger’s Otorhinolaryngology
glottal margins that improves approximation with- eral factors such as local trauma (including surgery),
out stiffening the folds contributes to glottal closure viruses, and heart disease; myasthenia gravis; arthri-
and sound generation. Patients whose voices become tis; or general debility from anemia or other diseases.
louder when they have laryngitis or mild edema In the larynx, peripheral paralyses and pareses usu-
illustrate this fact. ally affect only one vocal fold. The unaffected vocal
fold usually compensates to some degree by crossing
FUNCTIONAL LOUDNESS PROBLEMS. PERSONAL ADJUST- the midline of the glottal space to achieve closure
MENT. Atypical loudness is often an indicator of per- during phonation.2 When the disease and organic
sonality aberrations (eg, overly aggressive, shy, or conditions permit, direct therapy for voice improve-
socially insecure persons). Voices may be too loud or ment often produces good results. Suggestions about
too soft depending on the personality. Fortunately, therapy are presented later in this chapter.
these adjustment problems are amenable to coun- BOWED VOCAL FOLDS. This muscular deformation
seling procedures by a speech-language pathologist
stems from long-term heavy use of the voice, partic-
or clinical psychologist. Voice improvement is usu-
ularly in elderly patients. Patients produce a weak
ally enhanced by direct training of voice production
voice because of an impaired ability to develop clo-
along with counseling.
sure of the vocal folds during voicing.
ENVIRONMENTAL STRESS. Some persons are required SULCUS VOCALIS. A groove parallel to the vocal fold
to speak loudly in their occupations. This vocal margin may be present in one or both vocal folds as
requirement often creates laryngeal trauma, subse- a result of congenital or possibly developmental
quent changes in the vocal organs, and consequent causes. Although this condition is not well under-
voice disorders. Excessively loud speaking and loud stood because data are limited, the weak voice may
cheering at sports events are recognized as principal result from an inability to achieve adduction of the
types of vocal abuse. These causes create difficult vocal fold along its entire length.2
problems to manage when the basic occupational
conditions persist. Voices can be retrained, however, HEARING IMPAIRMENT. When a loss of hearing is suf-
if the patient is willing to learn how to use the voice. ficient to cause an individual to speak more loudly
An adjunct to voice training and a substitute when than circumstances warrant, a hearing problem is
circumstances are not conducive to such therapy is usually evident, and the offending vocal symptoms
the use of a speech aid. Small, portable amplifying (similar to those described above under the topic of
systems consisting of a clip-on microphone, ampli- functional loudness problems) are approached
fier, and loudspeaker are available and, when used through treatment of the hearing loss.
properly, can provide adequate loudness of voice in
noisy environments. The focal problem with the VOICE QUALITY DISORDERS
occupational voice disorder, when work requires
daily vocal abuse, is the lack of opportunity to Voice quality disorders encompass resonance and
recover from traumatic effects and to institute a phonatory components. The phonatory deviations
period of training to prepare the voice for unusual can be placed along an auditory continuum extend-
demands. Such patients benefit from periods of ing from aphonia to hoarseness, with such interven-
complete vocal rest (silence) prior to participating ing and intermixing qualities as breathiness and
in vocal retraining therapy. Ideally, it is helpful to the harshness. In this chapter, phonatory disorders are
professional speaker as well as to workers in noisy presented under five headings: aphonia, breathiness,
environments to acquire “big voices” during therapy. harshness, hoarseness, and spasmodic dysphonia.
Fortunately, amplification can satisfy the job needs Authors reporting in the medical literature tend to
and reduce the vocal abuse for some patients. classify all voice disorders under the headings of
aphonia and hoarseness. These terms are useful but
ORGANIC LOUDNESS PROBLEMS. PARALYSIS OR PARESIS. not adequate for a discussion of the variety of exist-
When a slowness, weakness, or absence of complete ing phonatory defects.
glottal closure occurs, the voice is weak and breathy.
The basic causes are as follows: impaired neural con- APHONIA AND ITS CAUSES. Aphonia, the absence of
trol from cerebral cortex lesions (stroke) or periph- phonated sound, is revealed as a whispered voice,
Disorders of Voice, Speech, and Language 1123
which indicates that the vocal folds are not vibrating. polyps, peduncular polyps, cysts, papillomas, ker-
One should be careful not to confuse aphonia with atosis, leukoplakias, cancers, contact ulcers, and
elective mutism, in which the patient has the poten- edema) can prevent the glottal borders from touch-
tial to phonate but simply chooses not to speak. ing firmly during the vibratory cycle. Even complete
Aphonia exists when the folds do not approximate closure of the muscular borders of the glottis can be
sufficiently to be activated by the air stream or when associated with a breathy voice if glottal resistance is
the folds themselves are not capable of vibrating markedly reduced (eg, when flaccid vocal folds result
even when approximated. Causal factors in aphonia from a lower motoneuron disease such as myasthe-
include lateral positioning of the arytenoid cartilages nia gravis), or in the presence of hypokinetic neuro-
with the associated open glottis, massive intrusion logic disorders such as Parkinson’s disease, or if a
of some neoplasm, atrophy or absence of vocal fold chronic posterior glottal chink (intercartilaginous
tissue, excessively stiff folds, or nonflexible mucosal portion) is observed.13
covering of the folds. Aphonia can also result from In many respects, the causes of a breathy voice
organic disease. The associated organic diseases are similar to, or may be the same as, those of apho-
range from paralyses and other neural impairments nia. This fact stresses the observation that the voice
to various tumors, inflammatory disease, scarring, is not a reliable indicator of the type or extent of
and other localized laryngeal lesions. Aphonia also laryngeal impairment or disease. At any given
may be indicative of a functional disorder of psy- moment, the degree of vocal fold approximation
chogenic origin, most commonly conversion apho- that can be achieved is influenced by the vowel
nia/dysphonia. Treatment of such functional sound that is being produced,14 the vocal effort used
disorders must be sensitive to the underlying psy- by the talker,15 and the muscle tension in the larynx.
chogenic bases of the disorders. Aphonia may be These factors can determine whether the voice is
present continuously but is more frequently inter- normal, aphonic, breathy, or hoarse. Although many
mittent. Intermittent aphonia varies considerably, attempts have been made to identify laryngeal dis-
sometimes even within the speech of a single ease based on acoustic measurements of the vocal
patient. Some persons whisper most of the time; signal-to-noise ratio, particularly by investigators in
others may be aphonic momentarily within words Japan, such measures appear to be more related to
or parts of sentences. perceived levels of breathiness than to specific dis-
eases of the larynx.16–20
BREATHINESS. Chronic breathiness can be recognized Breathy voice has been associated tradition-
by excessively audible breath-flow noise that is ally and sometimes exclusively with the availability
accompanied by a relatively low vocal loudness level of breath. This association is not valid apart from a
(a low vocal signal-to-noise ratio). The problem is consideration of the concurrent condition of the
common and varies from scarcely discernible levels larynx. Breath supply may be expressed in two
of breathiness in the voice to the almost aphonic. ways: the amount of air available and the force with
The vocal folds vibrate during the production of a which it is expelled. Observation reveals that a
breathy voice but do not impede the airflow suffi- reduced air supply, such as that resulting from the
ciently to allow much increase in subglottal pressure. removal of one lung, is not in itself a cause of
Air flows alternately more and less but is not com- breathiness. Substantial clinical evidence also indi-
pletely interrupted during the vibratory cycle. Sev- cates that reduced breath pressure alone is not a
eral organic conditions modify the glottal cause of breathiness. If low pressure produced the
configuration sufficiently to create incomplete glot- defect, a person with a normal voice would neces-
tal closure associated with a breathy voice. Muscular sarily have a breathy voice whenever a tone of low
tension dysphonia (simultaneous contraction of intensity was produced. Many persons with low
laryngeal adductor and abductors) can create vital capacity have normal voices.
incomplete closure during each glottal cycle and
produce a breathy voice.2 Moreover, various condi- HARSHNESS. Harshness is a physiologic opposite of
tions of paralysis (unilateral or bilateral) as well as breathiness. When the vocal folds remain in contact
growths protruding into the glottal space (these for a disproportionately long time in the vibratory
include discrete mass lesions such as nodules, sessile cycle, a voice quality known as harshness results.
1124 Ballenger’s Otorhinolaryngology
This vocal problem is usually functional. Harshness adductor muscles represent the kinds of changes to
is accompanied by increased air pressure and tighter which reference has been made. Under certain cir-
glottal closure. When the harsh voice is produced cumstances, swollen tissue or secretions above or on
loudly, as it is sometimes by hyperactive, aggressive the vocal folds may be set into more or less inde-
individuals, the speech is staccato, and the listener pendent vibration and may thereby create hoarse or
perceives hyperactive contraction in the entire respi- rough sounds. Descriptions of the many laryngeal
ratory, phonatory, and articulatory musculature. diseases and anomalies potentially related to hoarse-
This behavior is called hyperfunctional voice pro- ness occupy much of this volume. The possible
duction. Organic causes of harshness include ede- effects of some of these conditions are summarized
matous vocal folds, neoplasms, and any other in a later section on voice therapy.
structural alteration that may prolong the closed
phase of the vibratory cycle. SPASMODIC DYSPHONIA. The term spasmodic dyspho-
nia (sometimes called spastic dysphonia) designates
HOARSENESS. Hoarseness and harshness are often one of the most disabling of communication disor-
confused with each other, partly because both terms ders. It is probably an organic movement disorder
are relatively imprecise. Hoarseness varies from mild with an unknown cause. It prevents or seriously lim-
to severe and is so common in the population as a its the person who has it from holding positions in
result of acute upper respiratory infections that it which speaking is required. The problem originates
evokes little concern unless it is severe or chronic. in the larynx and is heard most frequently as a sud-
The differentiating, audible feature of hoarseness is den, momentary interruption of the voice caused by
a roughness that results from random variations in brief, spasmodic glottal closure. In some patients,
the periodicity of the glottal waveform and/or ran- instead of closing, the glottis spasmodically opens to
dom variations in the intensity of consecutive allow air to escape, as in a whisper.21 The closure
sound. Such variations may contribute to, or be form of the disorder is often referred to as adductor
accompanied by, noise in the phonation. Conse- spasmodic dysphonia and the open form as abduc-
quently, it is understandable that the perceptual con- tor spasmodic dysphonia.22 In addition to these
ditions of hoarseness and breathiness often coexist. symptoms, some patients describe difficulty with
Normal vocal sound results from repetitive breathing in the adductor type. Also, as patients
vibrations that are similar to each other in time and attempt to “speak through” the spasmodic closure,
intensity or that vary progressively as pitch or inten- the voice may be described as “squeezed,”“effortful,”
sity shifts upward or downward. Vocal sound is gen- or “struggle strained.” Occasionally, when a vowel
erated by the motions of the folds in conjunction sound is prolonged, as in singing, a prominent
with the breath stream that activates them, and any intermittent pulsing occurs, suggesting a tremor.
condition that alters their regular, repetitive, syn- The adductor form is more common than the
chronous vibration, causing randomly timed or ran- abductor, but both may be heard in a single patient.
domly intense pressure pulses, creates a voice quality The spasmodic episodes occur most frequently on
called hoarseness. Physical conditions that cause vowel sounds, particularly at the beginning of
random aperiodicity probably result from a combi- words. The abductor form is most prominent on
nation of transient and interference factors and may vowels that follow unvoiced fricative sounds. Almost
include any disease or condition in the larynx that without exception, persons with spasmodic dyspho-
changes the size, stiffness, or surface characteristics nia can whisper normally without interruption in
of one or both vocal folds (laryngitis or any of the the flow of speech. Superficially, spasmodic dyspho-
discrete mass lesions, eg, nodules, polyps, cysts, papil- nia resembles stuttering, but significant differences
lomas) or that causes excessive squeezing of one fold exist between these disorders. One of the puzzling
against the other (eg, pressed phonation by a patient features of this type of dysphonia is that the severity
with contact ulcers). Any of these factors may create and type of symptoms can vary within as well as
the conditions for hoarseness. Enlargements caused among patients. Inconsistency of symptoms
by tumor or edema, reductions resulting from sur- undoubtedly contributes to the traditional assump-
gery or atrophy, flaccidity subsequent to neural tion that spasmodic dysphonia is psychogenic.23,24
involvement, and functional hypercontraction of the Indeed, it may be, but research evidence indicates
Disorders of Voice, Speech, and Language 1125
the possibility of a neural etiologic component.25–27 paralysis. Unfortunately, the speech symptoms tend
A discussion of the several theories is not appropri- to recur with return of function. When unilateral
ate here but may be explored through references at paralysis is permanent after section of one recurrent
the end of the chapter.28–31 Differing concepts are nerve, the voice is almost always normally fluent for
mentioned simply because the neurogenic theory at least the first year, but as time passes, more and
has led to surgical therapeutic procedures that have more patients report recurrence of their symp-
been more successful in treating the adductor type toms.39–41 The several reported failures signal the
than other approaches.32 The tenacious persistence need for increased caution with the surgical
of spasmodic dysphonia has caused patients to seek approach and careful assessment of the conditions
help from psychiatry, clinical psychology, speech associated with the occurrences.42 In contrast, some
therapy, hypnosis, drugs of many varieties, and patients are known to have maintained normal flu-
bizarre remedies of every type, all unsuccessfully.33 ency for more than 10 years. These varying results
The observed freedom from spasmodic dys- lead to the speculation that spasmodic dysphonia
phonia during whispering, and almost complete flu- symptoms are probably the result of multiple causes.
ency by patients when they produce a breathy voice, The abductor type of spasmodic dysphonia is
demonstrates that the spasmodic adductory speech not helped by intentional unilateral vocal fold paral-
symptom is absent when glottal closure does not ysis. This procedure simply exaggerates the unde-
occur. Short-term clinical relief of the dysphonia can sired glottal opening. Patients with this problem
be achieved by chemically blocking one recurrent report considerable variation in symptoms, with the
laryngeal nerve to create a temporary unilateral disorder worsening with anxiety and worry.43 Psy-
vocal fold paralysis. This injection procedure is also chiatry, clinical psychology, speech-language pathol-
useful in diagnosis because it demonstrates the effect ogy, medicine, and many exotic approaches have
of a unilateral paralysis on the speech symptoms. been as unsuccessful with this form of spasmodic
When the injected anesthetic results in immediate dysphonia as with the adductor form. Unfortunately,
elimination of both the tight glottal closure and the there is no known temporary alleviation of the
symptoms of spasmodic dysphonia, the diagnosis of abductor symptoms that parallels the anesthetic
the disorder is strongly supported. The resulting blocking of one recurrent laryngeal nerve used with
voice is not normal, although it is useful for com- the adductor form of the disorder. There is substan-
munication purposes. tial evidence of neurogenic disorder with the abduc-
Patients with spasmodic dysphonia usually tor as well as the adductor form of the dysphonia.
have had the disorder for many years and have Support for neural involvement has been found in
become frustrated with the uniform lack of assis- electromyography,44 electroencephalography,45 mag-
tance from various therapies. They are generally netic resonance imaging,46 auditory brainstem
eager to prolong the fluent speaking they experience response,47 and various clinical neurologic tests.
during the nerve block and request some way to
accomplish that end. The three options that are Resonance and Resonance Disorders When the
available are (1) the creation of a permanent unilat- shapes and adjustments of the resonance spaces do
eral paralysis by sectioning of one of the recurrent not conform to the customary configurations, reso-
laryngeal nerves, a therapy that has become rather nance disorders are apt to be present. The two most
widely used34–36; (2) the establishment of a tempo- common resonance defects are too much nasal res-
rary unilateral paralysis by crushing one recurrent onance (hypernasality) and insufficient nasal reso-
laryngeal nerve37; and (3) the production of another nance (hyponasality). The first is caused by
temporary laryngeal nerve paralysis by the injection incomplete closure of the velopharyngeal valve or by
of botulinum toxin.38 The crushing and toxin proce- a fistula in the structures separating the oral and
dures are usually followed in 3 to 6 months by a nasal spaces, and the second is caused by blockage of
return to pretreatment function. The underlying the nasal passageway. Incomplete velopharyngeal
rationalization for the temporary paralysis proce- closure results from one or more of five possible
dures is that if spasmodic dysphonia is psychogenic, causes: (1) congenital deformity, such as cleft palate,
the fluent speech practiced during the period of submucous cleft, excessively deep pharynx, or short
paralysis should persist after recovery from the palate; (2) paralysis of pharyngeal or palatal mus-
1126 Ballenger’s Otorhinolaryngology
cles; (3) destructive disease; (4) surgical procedure in a voice disorder is probably redundant. Otolaryn-
which adenoidal tissue vital to velopharyngeal clo- gologists, particularly, are aware that voice problems
sure has been removed; and (5) imitation of hyper- are among humankind’s most subtle disorders; they
nasal speech. reflect certain aspects of the patient’s thinking,
The second general condition, blockage of the behavior, health, and diseases. The causes of voice
nasal passageway, causes denasality (cold-in-the- disorders may be arbitrarily grouped into the fol-
head speech), which also results from one or more of lowing nine categories:
five causes: (1) growths such as adenoid tissue, papil-
1. Structural modifications that result from misuse
lomas, polyps, and nasal spurs; (2) hypertrophy
of the voice, such as thickened vocal fold tissue,
resulting from chronic disease; (3) swollen mucosa
myasthenia laryngis, vocal nodules, and contact
associated with allergies; (4) trauma to the nose; and
ulcer. Furthermore, vocal abuse combined with
(5) imitation. A blockage situated anteriorly in the
infection may cause such chronic conditions as
nasal passageway may contribute to hypernasality
laryngitis, corditis with hypertrophic and hyper-
instead of hyponasality because the posterior nasal
plastic laryngitis, and atrophic laryngitis.
areas act as resonators if an opening is present at the
2. Anxiety, emotional turmoil, frustration, and sim-
velopharyngeal valve. This form of hypernasality can
ilar psychogenic problems that cause excessive
be demonstrated by pinching the nose closed and
contraction of the laryngeal, thoracic, and associ-
trying to speak “through the nose.”
ated musculature during speech but do not cause
A resonance disorder identified as muffled
observable organic disease
quality or “hot potato speech” is often difficult to
3. Diseases and growths, including infections not
identify because it is similar to some rural dialects. It
related to vocal abuse; paralyses of central,
results from space-occupying lesions such as masses
peripheral, and myopathic origin; cysts; and both
of lymph tissue or tumors in the valleculae between
benign and malignant tumors
the epiglottis and the base of the tongue. Confusion
4. Mechanical and chemical irritants affecting the
with dialects occurs because some speakers habitually
mucosa: fumes, irritating vapors and gases, dry
retract the base of the tongue into the pharynx on
air, dusts, allergens, caustic fluids, and gastric
sounds that customarily do not use that adjustment.
reflux
5. Substances causing noninflammatory edema,
COMBINED SOURCES OF VOICE QUALITY DISORDERS.
such as internal medicaments, mechanical com-
The two separate sources of voice quality disorders,
pression of venous blood flow, endocrine imbal-
the larynx and resonance cavities, are capable of
ance, and allergy
functioning independently; consequently, quality
6. Irradiation therapy, antihistamines, and other
deviations can be generated in either one separately
medications that cause drying of the mucosa
or in both concurrently. This possibility provides the
7. Congenital anomalies
means by which many combinations of phonatory
8. Destruction of laryngeal tissue by surgery,
and resonance problems may be produced simulta-
trauma, or disease
neously and presents a basis for the variety of voice
9. Systemic disorders leading to chronic fatigue,
quality disorders that exist. The potential array of
such as anemia, metabolic disturbances, malnu-
vocal problems may be compounded by the simul-
trition, and inadequate rest, can also affect the
taneous presence of both organic and functional
voice adversely
deviations. It is apparent that vocal disorders deserve
careful evaluation and diagnosis; it is equally clear
that vocal rehabilitation may require more than one
type of therapy.
THERAPY FOR VOICE DISORDERS
The long history of medicine has demonstrated that
medical and surgical treatment may eliminate some
SUMMARY OF CONDITIONS AFFECTING
types of voice disorders, but such treatment cannot
LARYNGEAL HEALTH AND FUNCTION always restore normal function. Nonmedical reha-
To stress the need for careful and complete medical bilitative measures may be necessary to help com-
evaluation and treatment of the individual who has pensate for altered anatomic and physiologic
Disorders of Voice, Speech, and Language 1127
conditions, and re-educative procedures are usually vocal elements as the rate of speaking, choice of
indicated in the treatment of habitual or functional words, vocal pitch, loudness of the voice, and vocal
disorders. The preceding descriptions of voice dis- quality.48 These factors often indicate the degree of
orders and their causes have indicated the potential poise, anxieties, emotional states, feelings of friend-
complexity of voice problems. Rehabilitative meas- ship or hostility, and belief about acceptance or
ures used in the management of such problems fol- rejection. When these concepts cause the individual
low the approved convention of adapting the to use an unpleasant, inadequate, or defective voice,
therapy to the specific patient and his or her disor- any successful modification of the problem must
der. Because this presentation must play a relatively include a consideration of the person’s concepts
minor role in a volume on otorhinolaryngology, about self, the environment, and his or her speech.
suggestions for therapy have been limited to basic or In Western culture, the low-pitched male voice
universal recommendations that can be used by the seems to be identified strongly with concepts of
physician who cannot devote much time to vocal masculinity, and unless the young man realizes that
rehabilitation. When greater depth is needed, one a tenor voice is just as masculine as a bass one, he is
should refer to detailed books and extensive reports apt to develop detrimental vocal habits that are car-
in the periodical literature to support systematic ried into adulthood. Children as well as adults some-
therapy. The purpose of this volume is best served by times use loud voices or rough-sounding, hoarse
directing the physician’s attention to the following voices to dominate, control, or compete in their fam-
four aspects of diagnosis and voice therapy: (1) con- ily or social groups. The focus of attention here is on
ditions affecting the patient’s general health and the the fact that the attitudes and needs of the individ-
function of the larynx, (2) environment, (3) psycho- ual that led to vocal nodules or thickened vocal fold
logical adjustment, and (4) voice. tissue must be considered in any program of vocal
rehabilitation. Individuals occasionally demonstrate
Environmental Factors A program of voice ther- overwhelming anxieties in vocal disorders (eg, hys-
apy that does not recognize the demands of the envi- terical aphonia, intermittent dysphonia, and tremu-
ronment on the communication needs of the patient lousness). In these conditions, psychiatric assistance
is incomplete and may be doomed to failure. The is usually desirable, and if any work on the voice is
person who must talk more or less continuously in recommended, it is carried on as a supporting activ-
a noisy environment may develop detrimental vocal ity in close cooperation with the psychiatrist. The
habits and may also abuse the larynx and create tis- preceding paragraphs have suggested that psy-
sue changes. In some families, excessive and harmful chogenic factors of many degrees of severity may
use of the voice is so common or so subtle that the cause voice disorders. It follows that successful vocal
persons involved are not aware of the excess and do rehabilitation must include appropriate psychother-
not associate the behavior with the voice problem. apeutic procedures when indicated.
Therapy for a voice disorder that is generated and
nourished within an environment often encom- Analysis of the Voice Problem Defective voices
passes complex personal management problems. are usually not consistently abnormal in the same
Frequently, the patient cannot move to another job degree under all circumstances. A voice that is
or otherwise modify his/her living situation; when hoarse at a low pitch may be completely clear in
such changes can be made, however, the restoration falsetto. The vocal sound may vary during the pro-
of the voice is simplified. When the environmental duction of different vowels, and the characteristics of
conditions cannot be altered, the voice therapy must vocal defects often change with loudness or vocal
include a review of the situation with the patient, or effort. The individual who provides voice therapy
with the parents if children are involved, to provide must know the capacities and limitations of the
insight and a rationale for adjustment to the envi- patient’s voice because this information not only
ronment. To ignore the patient’s work setting, recre- provides diagnostic data but also determines the
ation routines, and living patterns is to invite failure. pattern of rehabilitation. To determine the dimen-
sions of a voice disorder, the clinician should evalu-
Psychological Factors An individual’s attitude ate systematically and individually the pitch,
toward self and the environment is reflected in such loudness, and quality characteristics of the voice.
1128 Ballenger’s Otorhinolaryngology
The patient should be asked to sing a vowel, such as “ear training.” Samples of the patient’s voice should be
/a/, up and down a musical scale to the limits of the recorded at appropriate intervals during therapy, and
individual’s range. It may be necessary to provide a these should be studied carefully with frequent com-
tone to imitate because many patients with voice dis- parison of the changing vocal features over time. The
orders have poor pitch discrimination. The ade- clinician should choose one vocal element at a time
quacy of the pitch range should be noted, as well as for special attention and must avoid both discourag-
any changes in vocal quality that occur at different ing and overwhelming the patient with the re-educa-
positions on the scale. The patient should also be tive task. This purposeful listening requires great
required to read a few paragraphs of simple material clinical skill to make it meaningful and to keep the
to reveal typical vocal habits. Generous samples of patient motivated. Inexperienced listeners do not hear
the patient’s vocal production should be recorded many of the elements of vocal sound, particularly
during the evaluation process. Recordings are essen- their own, until they are instructed; this is the func-
tial for objective listening to the voice and serve as a tion of the clinician. The temptation to send the
basis for determining improvement or regression patient home to listen to a voice recording as a thera-
during the course of therapy. The vocal evaluation peutic measure should be resisted until one is assured
should answer the following questions: Is the pitch that the patient can identify specific faults. Another
of the voice that the patient uses in conversation and aspect of evaluative listening is detailed analytic study
while reading aloud normal for a person of that age, of the vocal characteristics of other persons with both
sex, and size? Are there any unusual inflections or good and poor voices. This exercise improves the
atypical pitch variations? Is the pitch range satisfac- patient’s ability to identify specific vocal features and
tory, such as a minimum of five to six tones? Can the use them in production through imitation and exper-
patient match the pitch of a given tone and volun- imental variations.
tarily go up and down a scale? Is the loudness of the
voice appropriate to the circumstances? Is there any Voice Therapy DIRECT VOICE THERAPY. Two types of
evidence of a hearing loss? Is the quality of the voice instruction relate specifically to direct voice therapy:
predominantly normal? Is it aphonic? Breathy? the first can be classified as recovery, the second as
Harsh? Mildly hoarse? Severely hoarse? Does the training. Recovery procedures presume a need for
quality change when the pitch is high or low? Does healing, for a return of the structures to normal. They
the speaker appear to be using too much or too lit- are based on the premise that the vocal organs will
tle effort during speaking? Does too much sound restore themselves if abusive behavior is discontinued.
seem to come out through the nose? Does too little Recommendations commonly given to achieve these
sound pass through the nose on the /m/, /n/, and goals include complete vocal silence for a week or two
/ng/ sounds? Is there any tremulousness? Is the (or sometimes longer) with no whispering, limited
speech commensurate with the socioeconomic back- vocal use in which speaking is allowed only when
ground of the patient? Under what conditions of absolutely necessary, reduced vocal intensity, elimina-
pitch, vowel sounds, and loudness levels does the tion of all singing, limitation of physical exercises and
subject produce the best vocal sound? activities that cause the breath to be impounded by the
closure of the glottis, and avoidance of coughing and
Patient’s Evaluation of the Voice Problem Two clearing of the throat whenever possible. These rec-
basic premises support the concept that one must ommendations are essentially passive but are often
evaluate one’s own voice problem if one wishes to desirable early in therapy. However, if recovery proce-
modify it. First, an individual does not hear his or her dures have allowed the larynx to become more nor-
own voice as others hear it; second, the clearer and mal, the resumption of habitual patterns of phonation
more specific a goal or task can be made, the faster it ordinarily causes a relapse. To be successful with these
will be reached. A corollary to these concepts is that patients, voice therapy must include a period of train-
unless an individual can recognize the voice problem ing that modifies previous habit patterns and replaces
and can form a clear concept of the improved vocal them with more efficient phonatory behavior.
sound, remedial efforts will be relatively ineffective.
The process by which a person evaluates his or her IMITATION AND EXPERIMENTATION. Soon after learning
own voice is systematic listening, sometimes called to hear specific flaws in the voice, the patient should
Disorders of Voice, Speech, and Language 1129
be encouraged to experiment with voice production between disorders of articulation and certain voice
in an effort to modify specific faults and also to problems that need attention in a discussion of voice
develop greater control over the voice. It is often therapy. Two types of phonatory problems are effec-
helpful to use computer software that permits two tively treated through the management of articula-
voice samples to be displayed at once. One channel tion. One of these is observed when generalized
can display a previously recorded voice sample or excessive muscle tension is chronic during speaking,
the clinician’s live voice sample and the other dis- and the other is found in indistinct speech caused
plays the patient’s efforts to match the model. by imprecise or inaccurate movements of the lips
and tongue. Where excessive muscle tension exists,
RELAXATION. With voice disorders in which vocal mouth opening is usually minimal, talking is of the
abuse is present, the patient usually has excessive “clenched jaw” variety, and the vocal sound may be
tension in the muscles of the larynx as well as else- hoarse, harsh, or hypernasal. Easier, more efficient
where throughout the body. Unless this tension can speaking usually accompanies increased opening of
be controlled, vocal therapy cannot progress. The the mouth, reduction of rate, and relaxation of the
patient needs to relax. The term relaxation com- muscles of the head and neck. When imprecise, inac-
monly has two meanings: it may refer to the absence curate, or lax speech exists, the tongue and lips do
of muscle contraction, or it may signify coordina- not make firm contact with their opposing struc-
tion in which the opposing sets of muscles exert just tures, that is, movements are often incomplete in a
enough reciprocal tension on each other to accom- phonetic sense. The speech is frequently called
plish a desired movement with perfect control. Both “slurred” or “careless.” Actually, the atypical sounds
types of relaxation can be, and sometimes must be, are usually learned in an environment where such
learned for the successful alleviation of a voice dis- speech is typical. When speakers with these habits
order. Learning to relax involves both muscle train- are requested to talk so that they can be more easily
ing, which can be approached directly through understood, they attempt to comply by speaking
exercise, and emotional control, which is managed more loudly and by increasing laryngeal and respi-
through modification of attitudes, anxiety, worry, ratory muscle contraction. Training in more appro-
and comparable problems. priate production of speech sounds usually increases
intelligibility and reduces the detrimental, excessive
PITCH ADJUSTMENT. Many persons, particularly men, effort.
attempt to use a vocal pitch that is lower than that
which is normal for their laryngeal structures. This VOCAL PRACTICE. If the physician finds it necessary
behavior not only produces an unpleasant voice but or desirable to direct the vocal practice of a patient,
also traumatizes the laryngeal structures. If this vocal the focus should be on the use of a quiet voice. More
tendency is observed, its inadequacy should be specifically, practice sessions of 5 to 10 minutes
explained and assurance provided that a more nor- should be advised in which vowel sounds are pro-
mal pitch will supply a satisfactory masculine image. longed gently at various pitches, and short selections
Subsequently, direct instruction can be given to from magazine stories and other sources are read
establish a habitual pitch that averages four or five aloud. If the subject has experimented successfully
musical notes above the lowest tone that the patient with various voice qualities and is able to relax ade-
can produce. An average shift of as little as one tone quately, such practice will prove beneficial. If the
upward “feels” much higher to the patient and patient uses detrimental vocal behavior when he/she
causes reluctance to accept the change. Furthermore, reads aloud, however, this practice should be post-
the patient is usually surprised to discover little poned. Vocal practice requires patience and con-
change in the recording and is startled when the stancy. Patients are often disturbed when they are
average listener does not recognize a change of as told that they may not detect much improvement in
much as several tones in his speaking pitch. 3 months or more and that 6 months may be
required to achieve some skill in the use of new vocal
SPEECH ARTICULATION IN PATIENTS WITH VOICE DISOR- habits. Persons preparing their voices for singing or
DERS. Although articulatory disorders are discussed acting accept the concept of lengthy training, but
later in this chapter, a close relationship exists those correcting voice defects seem to expect a mag-
1130 Ballenger’s Otorhinolaryngology
ical change. Consequently, one of the most difficult rehabilitation. Training in communication skills is
and important aspects of voice therapy is motiva- almost always desirable for patients who have had a
tion of the patient. total laryngectomy.
self-assuredness, and absence of denial.”57 The latter laryngectomized person. Without the larynx (voice
four factors are amenable to counseling and reflect generator), the patient can simply mouth the words.
the importance of this process in both the pre- and The removal of the larynx usually leaves the articu-
postsurgical periods. latory mechanism intact. Consequently, when the
patient substitutes some other sound for the missing
Presurgical Speech Training Some laryngeal sur- laryngeal tones, speech is possible. The options open
geons regularly introduce a skilled laryngectomized to the laryngectomized person to develop a new
speaker to the patient before surgery. Others believe voice are discussed later in this chapter. If the person
this practice to be unwise. Gates and associates who loses the larynx could resume talking immedi-
stated that “… a preoperative visit by a laryngec- ately after the laryngectomy, concern would be no
tomee is not associated with success in learning greater than that associated with any other major
esophageal speech or in rehabilitation and in fact, is surgery. Unfortunately, when the means of commu-
statistically significantly correlated with a poorer nication is disrupted, the patient feels isolated and at
outcome.”56 a great disadvantage. The early restoration of the
Reliable estimates of the prevalence of presur- ability to communicate is a major consideration in
gical speech training are not available, but few successful rehabilitation. Every possible effort should
speech-language pathologists currently seem to be made while the patient is still in the hospital to
advise this practice. Perhaps the most satisfactory establish communication by computer, writing, pic-
way to plan for postsurgical speech in the presurgi- ture boards, signing, or the use of an artificial larynx.
cal period and to handle the many questions about In addition, plans should be made during this period
work, family, and social relationships is to introduce for instruction at home. This program should
a mature speech-language pathologist who has had include direct work with the patient. Of equal
extensive experience with laryngectomized persons. importance is instruction of the spouse and other
The speech-language pathologist’s function is to family members. Because individuals vary greatly in
encourage and to motivate the patient to make plans their ability to understand alaryngeal speech, the
for the postsurgical period. The speech-language problem listeners in the family group should be
pathologist does not promise fluent speech or that identified and taught to comprehend. Some of the
the learning will be easy but expresses confidence instruction will include speech reading skills and the
that verbal communication is usually possible with use of hearing aids where indicated.58
esophageal speech, a tracheoesophageal prosthesis, Hospital care of laryngectomees, whether in
or an artificial larynx. the immediate postsurgical period or at some later
admission for any reason, deserves special attention
Early Postsurgical Period Within a few days after from all service levels. The inability of the patient to
surgery, the patient begins to assess the new condi- communicate creates serious problems, especially
tion. The patient is relieved that the operation is suc- when specialized nursing care is not available. Many
cessfully past and is glad to be alive but discovers horror stories have been related by laryngectomized
new problems and fears to add to those that linger. persons, ranging from aides splashing water into the
The patient is bothered somewhat by breathing and stoma during bathing and application of oxygen to
coughing through the stoma and is dismayed by the the nose to failure to open a plugged stoma. The
reality of voicelessness. Attempts to whisper are frus- International Association of Laryngectomees recom-
trating. During convalescence, anxieties often grow mends that a special “warning” sign at the bed and
about employment, personal appearance, family on the patient’s chart identify every hospitalized
relationships, and association with friends. If the laryngectomee and that the care providers be given
patient or the patient’s associates have impaired specific instructions.59
hearing, communication becomes doubly difficult.
The inability to talk leads to depression and with- Restoring Speech Communication Following
drawal from social situations, a condition that Laryngectomy It is a truism that any form of sub-
becomes progressively more difficult to reverse. The stitute voice is inferior to that produced normally.
distinction between vocal tone production and Similarly, any usable speech is superior to mutism,
speech sound formation is clearly illustrated by the whispering, writing, or signing. Clinicians must
1132 Ballenger’s Otorhinolaryngology
search for the best substitute voice sources in rela- because it must be transported by the user and kept
tion to the needs and capacities of the individual readily available for speaking, it becomes a nuisance.
patient. Because structural adjustments above the
ELECTRICAL ARTIFICIAL LARYNGES. Two major types of
larynx regulate the acoustic filtering of the laryngeal
electrical instruments are in common use. In one,
sound source, they are primarily responsible for cre-
the sound is generated by a battery-powered buzzer,
ating the sounds of spoken language. Thus, any
about the size of a hearing aid phone, that is held in
complex sound that can be put into the upper air-
the hand and from which the sound travels by way
way can be substituted for the laryngeal sound
of a tube into the mouth. The sound is formed into
source and molded into speech. The need to restore
speech by articulatory movements as it is with the
speech to the laryngectomized patient has enabled
breath-powered unit. The second type of instrument
engineers, surgeons, speech-language pathologists,
has several forms, but basically it is a handheld unit,
and others to devise various means for producing
about the size of a two-cell flashlight, that transmits
sound that can substitute for the normal voice.
a buzzer type of sound through the tissues of the
neck into the pharynx, mouth, and nose, where the
ENGINEERING APPROACH. The engineering approach
sound is articulated into speech in the customary
involves the development of artificial sound genera-
manner. The vibrating element of these units is a
tors. These can be separated into two general types
disk that is placed against the skin of the neck. It is
according to the driving force used in the produc-
activated by a battery and controlled by a switch
tion of sound: one is powered by the breath stream,
similar to that on a flashlight. Battery-powered arti-
the other by electricity from batteries.
ficial larynges share with the breath-activated units
BREATH-ACTIVATED INSTRUMENTS. The various forms such advantages as low cost, early and easy restora-
of breath-activated instruments have three elements tion of speech, and good intelligibility. The electrical
in common: (1) a flexible tube that conveys the tissue-vibrating instruments have the additional
breath from the tracheal stoma to a small capsule positive features of freedom from hygienic prob-
held in one hand; (2) the capsule, which contains a lems, moisture condensation, and instrument care
reed or membrane that is vibrated by the breath, that accompany the breath-powered units. On the
thereby generating the sound; and (3) a second, negative side, electrical artificial larynges require one
smaller tube that carries the sound from the capsule hand for operation and must be carried continu-
into the mouth, where it is articulated into speech. ously by the user. Furthermore, the vibrating disk
Breath-powered, handheld artificial larynges are models generate a field noise that is transmitted
inexpensive and offer the patient an early means of directly to the surrounding air, where it competes
talking with little or no special instruction. The with the sound that comes from the speaker’s
speech sound can be relatively loud, phrasing and mouth. The ambient noise and the monotonous
sentence length are normal, and speech is intelligi- speech sound produce an artificial, machine-like
ble, even though it has a monotonous pitch. Unfor- utterance. Breathing and phrasing are interrelated in
tunately, the disadvantages attending the use of these normal speech. When the basic sound is produced
simple instruments are substantial; consequently, more or less continuously, as with the electrical
few of them are currently in use. The problems can instruments, utterance tends to become “mechani-
be listed as follows: moisture from the exhaled cal.” Experienced users of these units, however, learn
breath condenses relatively quickly at the vibrator, to start and stop the sound to approximate the
causing malfunction and the necessity of draining appropriate phrasing of the sentences.
or drying it; the tube conveying air from the stoma
to the vibrator becomes congested with mucus from SURGICAL APPROACH. Surgical efforts to produce sub-
the trachea, causing both hygienic and esthetic prob- stitute vocal sound have extended over many years
lems; and saliva seeps into the sound-conducting and can be classified into three forms.
tube, contributing to vibrator problems and necessi- TRACHEOESOPHAGEAL SHUNTS. A primary surgical ap-
tating frequent changes and washing of the tube to proach to the construction of a substitute sound source
keep it clean. Because the unit is held by one hand, is the formation of a tracheoesophageal shunt.60,61
it interferes with two-handed activities; furthermore, Basically, the shunt is a small channel extending from
Disorders of Voice, Speech, and Language 1133
the upper, posterior wall of the trachea through the diseases. In patients with whom the procedure has
anterior wall of the esophagus. When the tracheal been successful, the voice has been good. When a
stoma is closed with a finger, exhaled air passes tracheal stoma has been maintained, however, the
through the shunt into the esophagus, where it patient has the disadvantage of using a finger to
vibrates the pharyngoesophageal sphincter or other cover the opening to divert the air stream.
esophageal tissue to create a sound. At least four
COMBINED SURGICAL AND ARTIFICIAL DEVICES. In this
advantageous features are associated with the surgi-
approach, an artificial, breath-powered, sound-gen-
cal creation of a shunt for the production of voice.
erating reed is mounted in a small box and is acti-
When the air resistance in the shunt is relatively
vated by air conducted through a tube from the
small, the manner of speaking is almost effortless; the
tracheal stoma to the box. The sound is discharged
voice is produced on the exhalation of pulmonary air
through a second tube that extends from the gener-
as in ordinary speaking; phrases and pauses occur at ator to a surgically created fistula that passes through
linguistically appropriate places; occasionally, slight the skin and deeper structures at the side of the neck
pitch variation is achieved; and little training in the into the pharynx. The small enclosure containing the
use of the method is needed. The Blom-Singer and sound source lies on the patient’s chest just below
Panje prostheses are comfortable, reliable, and rela- the stoma.67 The surgical creation of a fistula into the
tively unobtrusive.62 Detailed descriptions of these pharynx, permitting the connection of an external,
prostheses and the procedures for placing them are artificial sound source, appeals to some laryngec-
presented in Chapter 54. Additional information tomized persons, particularly those who have been
appears in the literature.63,64 The major limitation, unable to learn esophageal speech and who do not
from a speech standpoint, is that a finger must be want to use one of the handheld artificial larynges.
used to close the tracheal stoma whenever sound is The advantages of the surgical fistula and attached
produced unless the patient is able to wear a tra- mechanical device include the capacity to produce
cheostoma valve.65 Vocal intensity is usually reduced highly intelligible, fluent speech with customary
from that of normal speech, and the prosthesis must phrasing and the utterance of sentences of normal
be removed, cleaned, and reinserted. The new pros- length. Both hands are freed for normal activity. The
theses have greatly reduced problems of leakage, disadvantages of this system are (1) the obvious
infection, and stenosis.66 Patients must be selected esthetics, the hygienic and clothing annoyances
carefully and motivated to want to improve their caused by a device attached at both the tracheal
speech and must be capable of managing the stoma and the fistula; (2) the special surgical proce-
hygienic care of the prosthesis as well as having the dure that is necessary to create the fistula; (3) occa-
dexterity to remove and replace it. sional rupture of a neck artery when the fistula is
located incorrectly; (4) the hygienic care of the fis-
CONSTRUCTION OF A PSEUDOGLOTTIS. Theoretically, tula and instrument; and (5) the need to insert a
the ideal solution to the loss of voice through the stopper into the fistula to prevent leakage when the
removal of the larynx would be the construction of tube that passes through the fistula is removed for
a living tissue substitute that would produce sound sleeping or other reasons.
and have no detrimental sequelae. In this approach,
the surgeon constructs a pseudoglottis at approxi- ESOPHAGEAL SPEECH APPROACH. The third approach
mately the location of the original larynx. Muscle to speech recovery for laryngectomees is the devel-
and cartilage that can be spared are formed into an opment of esophageal speech. This procedure allows
airway continuous with the trachea. At the junction the patient to control and refine the natural eructa-
with the pharynx or esophagus, a vibrator “button- tion sound as the basis for speech. The advantages of
hole” is formed that can generate a sound when the esophageal speech are that (1) natural physiologic
breath is exhaled through it. Some success has been structures and functions are used, thereby obviating
achieved through this approach by highly skilled the need for an artificial device; (2) both hands are
surgeons with carefully selected patients. Unfortu- free for normal activities during speech; and (3) the
nately, the pseudoglottis is usually not a liquid-tight good esophageal speaker presents a relatively normal
valve. Fluids leak from the pharynx or esophagus appearance and speaking manner. The disadvan-
into the trachea, leading to pneumonia and other tages of esophageal speech are that (1) it is often dif-
1134 Ballenger’s Otorhinolaryngology
ficult to learn (according to Gardner, approximately and thereby allow air to be pulled into the esopha-
30% of laryngectomized patients do not learn to gus. In the initial stages of learning this procedure,
speak well with esophageal speech68), and frequently, however, before the laryngectomee is able to relax
3 months or more are required to achieve fluency; the esophageal valve readily, he or she can facilitate
(2) phrasing is usually changed, so fewer words than the intake of air by momentarily covering the stoma
normal are uttered in a sequence without pause for with a finger. This action suddenly decreases the
phonatory air; and (3) the voice lacks sufficient pressure in the thorax, causing the air in the pharynx
loudness to be heard easily over common environ- to be drawn into the esophagus. As soon as the air
mental noise. All of the substitute methods of creat- has been taken in, it can be expelled by increasing
ing voice, except the battery-powered, disk-type the thoracic pressure, as in exhalation. This return
artificial larynges, encounter maximal problems flow is interrupted intermittently by the vibration of
when the patient eats. Swallowing food and the stim- the tissues of the pseudoglottis, thereby producing
ulation of salivary secretion complicate speaking sound.
and frequently embarrass the patient in social situa-
INJECTION METHOD. The “injection” method of put-
tions. Esophageal voice production and the artificial
ting air into the esophagus uses a different principle
larynges with oral tubes are probably more adversely
from that used in the inhalation procedure just
affected while eating than with the other methods
described. In injection, the air is forced, pumped, or
discussed.
squeezed from the mouth and pharynx into the
The air used in ordinary eructation comes
esophagus. Injection is accomplished by closing the
from the stomach, and the sound usually does not
lips and the velopharyngeal valve to provide an air-
result from voluntary acquisition and expulsion of
tight oropharyngeal area while simultaneously
air. Many persons, however, can learn to take air into
thrusting the back of the tongue upward from the /d/
the esophagus and expel it without allowing it to
position. This movement pumps the air out of the
reach the stomach. In this method, air in the esoph-
mouth (oral cavity) into the pharynx, and because it
agus is put under slight pressure by respiratory
is not permitted to escape through the nose and no
movements and escapes in vibratory pulses through
longer has access to the larynx and trachea, it passes
the sphincter mechanism at the upper end of the
into the esophagus. Squeezing the air from the
esophagus. This organ does not produce sound as
mouth into the esophagus can also be achieved by
effectively as the larynx, but its phonation function
compressing the lips and buccal spaces, as in making
is similar, and it is subject to considerable regulation.
a /b/ sound, and simultaneously lifting the mandible.
The ability to control the air charge and conse-
Several manuals and instructional booklets are
quently the moment of sound production is the pri-
also available through local cancer societies. It is
mary problem in learning esophageal speech. Before
often necessary for the person working with a laryn-
air can be expelled from the esophagus, it must be
gectomee to help with suggestions about everyday
taken in. If it is allowed to enter the stomach, it can- hygiene and appearance. The instructor should be
not be returned readily for voice; consequently, the able to advise on such items as care of the tracheal
air charge must not be swallowed in the sense that tube and prostheses, cleanliness, coverings for the
water is swallowed. Instead, it must either be stoma, suitable neckwear for men and women, pre-
“inhaled” or “injected” into the esophagus. Experi- cautions related to bathing, difficulties of speaking
ence proves that either of these procedures is serv- while eating, and similar personal problems. The cli-
iceable for each has been used by good esophageal nician should also be able to help the laryngectomee
speakers. Indeed, many of these speakers use both join a “Lost Cord Club” for instruction, practice, and
methods interchangeably. recreation. Addresses can be obtained from the
International Association of Laryngectomees* or
INHALATION METHOD. If the esophagus were held from a local chapter of the American Cancer Society.
open as the trachea is, the ordinary respiratory
expansion of the thorax would draw air into the
esophagus as readily as into the lungs. Many laryn-
gectomized persons can learn to relax the upper *International Association of Laryngectomees, 8900
esophageal sphincter at the moment of inhalation Thornton Road, Box 99311, Stockton, CA 95209, USA.
Disorders of Voice, Speech, and Language 1135
SELECTING A METHOD OF SPEECH REHABILITATION lation, however, with its associated communication
The welfare of the patient is, of course, the first con- disorders, may require us to change that assumption.
sideration in the rehabilitation process. The laryn- In addition, many neurogenic speech and language
gologist, speech-language pathologist, and others disorders, unlike stuttering and many articulatory
involved in restoration of communication should disorders, develop in adulthood.
assess the patient’s needs and potential for rehabili- Speech and language disorders can be divided
tation as early as possible, preferably while the into three major categories. First and most common
patient is still in the hospital. If the team determines are the articulation disorders. These problems involve
that a shunt with a Blom-Singer or Panje prosthesis the production of defective speech sounds and
is appropriate, the steps toward spoken communica- sound combinations that may be distorted, omitted,
tion are clearly evident. When surgery is not indi- substituted, or added as accessory sounds. Some-
cated, attention can be given immediately to the use times articulatory disorders are the result of neuro-
of an artificial larynx. Subsequently, when healing genic disorders, the dysarthrias. A second type of
and the effects of postsurgical irradiation have pro- disorder is the impairment of speech fluency, called
gressed satisfactorily, esophageal speech instruction stuttering or stammering. Repetition of sounds, syl-
can be introduced. Most clinicians agree that good lables, words, or phrases; sound prolongations; atyp-
esophageal speech is more desirable than speech ical pauses (hesitations); word substitution; and use
with artificial devices. The rehabilitation team, how- of word fillers characterize dysfluent behavior. A
ever, can determine when or whether such instruc- third category is variously labeled language impair-
tion should be introduced. If the decision is made to ment, linguistic disability, or faulty symbolization,
use an artificial larynx, either temporarily or perma- which refers to disorders in both expression of
nently, the patient should be taught how to manip- thought through verbal language and its compre-
ulate it most effectively and how to care for it.69 hension. The category includes various disorders,
Manufacturers customarily include printed instruc- ranging from delayed/deviant language development
tions, but usually these need to be supplemented by to neurogenic disorders known as aphasia.
demonstration and personal experimentation.
NORMAL SPEECH DEVELOPMENT IN CHILDREN
DISORDERS OF SPEECH
The normal acquisition of speech may be expected to
Speech-language pathologists recognize that sub- follow much the same pattern as the motor, adaptive,
stantial segments of the adult population as well as and personal-social behavior of the child. As in all
younger groups have serious speech, language, and other types of learned behavior, speaking depends on
voice defects, the problems that involve otolaryngol- the process of maturation. A “speech readiness
ogists most directly. Prevalence of communication period” extends from birth to the fifth year of life,
disorders in children is high, with a gradual decline when the child acquires the ability to develop speech
through adolescence. At least 5% of school-age chil- as a method of communication. This capacity, how-
dren (up to age 17) have significant speech impair- ever, represents the cumulative learning of many bits
ment, although most professionals consider this and pieces of language that begin within the first few
estimate extremely conservative. Some researchers weeks of life.71 Although endowed by nature with the
have reported a prevalence as high as 10% for certain capability of learning language, it appears that a child
samples of children.70 Most of these difficulties in learns to talk only because people in the immediate
children involve functional articulation disorders; environment speak to each other and to the infant. In
faulty language formulation and dysfluency (stutter- the first few months of life, infants are capable of per-
ing) comprise the remainder. The presence of com- ceptually differentiating a wide variety of speech
munication problems appears to stabilize during sound contrasts, giving children the capability of
adulthood and tends to increase after the age of 40 learning any of the languages of the world.72,73 How-
years. There seems to be a higher percentage of dis- ever, by 6 months of age, children have already begun
orders in men than women. Fewer disorders are to lose some of the capability of perceptually differ-
assumed to occur among adults than among chil- entiating among sound contrasts that are not used by
dren. The ever-increasing size of our geriatric popu- talkers within their immediate language environ-
1136 Ballenger’s Otorhinolaryngology
ment.74 Also, by 6 months of age, infants show an Reduplicated Babbling Reduplicated babbling
enhanced ability to distinguish perceptually those (repeated syllables such as pa, pa, pa, ba, ba, ba, ku, ku,
sounds used by talkers within their native language ku, etc) begins during the second 6 months. At first,
environment.75 Infants and young children are typi- the sounds produced are carried over from babbling,
cally “bathed in language” by their caregivers during but later the infant appears to be responding more
the first months of life. Such stimulation, often called selectively to the sounds of others, as well as to those
motherese, serves to nurture proper language devel- he or she has just produced. Reduplicated babbling
opment.76 This potential for language learning is appears to be a good index of normal development.
graphically highlighted by cases of abandoned, non- Virtually all normal-hearing children produce redu-
stimulated children who manifest severe language plicated babbling before 12 months of age, whereas
impairments. Before the child can learn to use oral children with significant hearing impairments rarely
symbols as a form of social behavior, he or she nor- do.81 The speech development of the congenitally deaf
mally lives through a series of prelinguistic overlap- child differs from that of the child with normal hear-
ping stages of sound production. The child’s physical, ing beyond the babbling stage. The deaf child does
emotional, and intellectual needs are served and not continue babbling for as long as the hearing child,
expressed in each stage.77 Furthermore, the emer- and speech development usually follows a different
gence of speech in the “normal” child serves as an pattern from that of a hearing child.82
excellent index of his or her physical, intellectual, and
emotional status. From a body systems perspective, Echolalia Echolalia, the name given to the fourth
the general sequence of speech development involves stage, begins somewhere around the ninth to tenth
attaining proficiency with breath control, then laryn- month, when the baby repeats sounds that he or
geal control, and finally articulatory control.78 The she hears in the environment. The child seems to
development of speech can be classified into a produce sounds that are pleasurable and repeats
sequence of five stages, each of which has distinctive sounds that another individual produces. This is
characteristics that blend cumulatively. the stage when the child demonstrates that speech
and language comprehension are emerging. Up to
The Cry The first stage is crying, which includes this stage, the baby has been acquiring an inventory
both undifferentiated and differentiated cry. During of sound complexes that later will be used in learn-
the first month or two, the cry does not differentiate ing to speak and in developing a vocabulary. The
sensations of hunger or pain, heat, cold, or other ages at which children typically master the sounds
kinds of discomfort. Differentiated crying appears of English are shown in Table 49–1 (after Sander83).
within the first few months, and the mother soon
learns to interpret variations in the cry as signals of Intentional Speech The fifth stage is the acquisi-
immediate needs or desires.79 tion of speech as a practical tool for communication.
Before entering this final but ever-expanding stage,
Babbling In the second stage, babbling, the infant the child must have established a functional under-
does not abandon differentiated crying but usually standing of conventionalized speech patterns. Pro-
by the third or fourth month produces a variety of viding meaningful time sequences for the mastery of
sounds at random and may appear to be “listening” speech sounds is difficult because many factors
as well as responding to sounds in the environment. influence and regulate their acquisition. Girls gener-
Most of these are “cooing” sounds that are like vow- ally surpass boys in learning speech sounds and tend
els. Prosodic features (pitch, stress, and duration) to be accelerated in articulation skill from about 41/2
begin to develop. Later the child begins to use the years on. Girls normally approximate mature artic-
lips and tongue to make consonant-like sounds that ulation by the age of 7, whereas boys usually take an
combine with those vowels, producing what we call additional year to reach the same degree of profi-
babbling.80 Because the child’s sensory feedback loop ciency. Whereas development of articulation skills is
(primarily auditory) is beginning to develop now, nearly complete for most normal children by age 8
the child’s babbling becomes progressively imitative years, subtle performance differences still exist for
of the prosodic and phonemic aspects of the input several years. Research evidence emphasizes that the
(adult) language. Children at 3 to 10 months of age accuracy of speech motor control continues to
progressively play with adult forms of speech. improve until age 11 or 12 years, at which point,
Disorders of Voice, Speech, and Language 1137
and inappropriate behavior. Applied to speech, The traditional way of describing the nature of
habits can account for the persistence of a problem articulation disorders is in terms of the following
and the resistance to its successful treatment. four classic error types:
The child’s mental age or intelligence must
also be considered when articulation is being eval- SUBSTITUTIONS. One standard sound is substituted
uated. Intelligence, reflected in cognitive function- for another in the initial, medial, or final position
ing, underlies one’s ability to learn. Because learning within the word. For example, the sound w is
is fundamental to speech and language acquisition, frequently substituted for r, producing wed for red;
intelligence factors can influence speech perform- t or d may replace th, and mother becomes mudder
ance. It is not surprising, then, that numerous stud- and something changes to someting; th may substi-
ies have demonstrated that children of low tute for s, and miss becomes mith. The most
mentality produce more articulation errors than frequently misarticulated sounds are often those
children of normal intelligence. Moreover, children that are mastered later in the course of speech
with severe articulation defects frequently have development: /s, z, r, 1, th, ch, sh, zh/.
depressed scores in reading and spelling, which may
help to explain their low scores on verbal intelli- OMISSIONS. Sounds are omitted in a word and are not
gence tests. replaced by a substitute. The child may produce tep
The word delay implies normal sound devel- for step, air for where, or daw for dog.
opment as a reference, and impairment of this type
is manifested as (1) a delay in onset, (2) slowness of DISTORTIONS. The target sounds are produced but
development, and/or (3) termination of develop- are modified so that the perceptual result is inaccu-
ment before the average adult skills are achieved.78,89 rate. A distortion might be considered a special case
Furthermore, delay assumes that between the onset of substitution error in that a standard sound is
and termination of a particular child’s development, replaced by a nonstandard sound. The /s/ and /z/
the course of events will follow the developmental are among the most misarticulated speech sounds
sequence observed with children who are acquiring because adjustments of the tongue, teeth, and bite
speech normally.90 relationships during normal growth and develop-
Answers to the following questions may supply ment during the preschool and primary years are so
useful insight into the problems: Did the child follow exacting that minor deviations easily occur. A com-
a normal pattern in sitting, walking, eating, talking, mon form is lisping, when one or more of the sibi-
and using the toilet? Did the child have any periods lant consonants /s, z, sh, zh/ is distorted.
of extreme illness or temporary hearing loss? Did the
child have extended absences from the family envi- ADDITIONS. Extra sounds are added that are not part
ronment? Did emotional conflicts arise between the of the word: examples are warsh for wash or plass for
mother and father or between the parents and the pass. Additions are not as common as substitutions,
child? Did any undue penalties and frustrations omissions, and distortions.
occur that may have been associated with the speech
readiness period? Did or do persons in the environ- Organic Articulation Disorders in Children
ment have similar speech problems that could have Many speech-language pathologists now approach
been imitated? the subject of organic articulation disorders cau-
In summary, a child with a delay profile tiously. As Bernthal and Bankson stated,
demonstrates performance similar to that of a nor- Although individuals with oral structural devi-
mal but younger speaker. In contrast, deviant speech ations frequently experience articulation problems,
refers to an articulation profile unlike that of a nor- the relationship between structural deficits and artic-
mally developing child, even a younger one.78 ulation skills is not very predictable. The literature
Although both appropriate and delayed characteris- cites many instances of individuals with structural
tics may still persist in the speech of these children, anomalies who have developed appropriate compen-
the deviant speaker’s articulation reveals error pat- satory gestures to produce acoustically acceptable
terns that cannot be accounted for on the basis of a speech. Why some individuals are able to compensate
“delayed” concept. for relatively gross abnormalities and others are
Disorders of Voice, Speech, and Language 1139
unable to compensate for lesser deficits has not been shaped cleft palate, and upper airway obstruction),
resolved.91 and Stickler’s syndrome (clefting of palate, micro-
These observations clearly emphasize that the gnathia, and perhaps Robin sequence). Other ter-
relationship between oral structure and articulation atogenic disorders are associated with multiple
proficiency is neither simple nor automatic. The anomalies. Examples include the effects of thalido-
remarkable compensatory potential of the oral- mide, German measles virus, and fetal alcohol syn-
drome. Myotonic dystrophy (Steinert’s disease),
peripheral mechanism seems to account for the clin-
neurologic diseases associated with lysosomal stor-
ically observed inconsistencies in speakers whose
age diseases (Hunter’s syndrome), cleft of the larynx
performance is relatively better than would be
(Opitz syndrome), and vocal cord atrophy (owing to
expected from the individual’s structural status. In
Werner’s syndrome) can have specific consequences
general, structural deviations can affect articulation
on the voice and speech production capabilities of
by interfering with articulatory contact points,
the patient. Although a discussion of these syn-
breath stream flow (force and direction), oral breath
dromes is well beyond the scope of this chapter,
pressure, and oral-nasal cavity coupling. Disorders
interested readers should consult the excellent refer-
such as cleft lip and palate can involve all of these
ences provided.3,93–95
aspects, whereas the normal loss of front teeth in a
growing child might create involvement of only the
TONGUE-TIE (ANKYLOGLOSSIA). Parents frequently
first two factors. As Carrell pointed out, a good rule
take children with articulatory defects to physicians
of thumb is to “consider any structural deviation a
to determine whether the child is “tongue-tied.” The
possible cause of misarticulation provided the
term “tongue-tied” (ankyloglossia) is used when the
nature of the speech defect is consistent with the
lingual frenum appears to be abnormally short or
deviation.”92
taut, restricting the movement of the tongue so that
it cannot move upward to the alveolar ridge.
STRUCTURAL AND SYNDROME-RELATED SPEECH DISOR-
Although this condition is known to exist, its inter-
DERS. Many structural deviations (eg, clefts of the lip
ference with articulation is considered compara-
and/or palate) are associated with speech, hearing,
and language disorders. The physician should be tively rare. McEvery and Gaines examined 1,000
sensitive to the possibility that structural anomalies children who had short frenums and found only 4
concomitant to speech disorders can result from with articulatory defects.96 They recommended that
dysmorphisms of genetic origin, commonly referred the frenum not be clipped because of possible infec-
to as syndromes, or a “pattern of things that run tion, hemorrhage, and residual scar tissue. A more
together.”3 When multiple dysmorphisms appear recent study confirmed the minimal relationship
in the same patient, consultation with a medical between ankyloglossia and articulation disorders,
geneticist is prudent to determine whether evalua- finding that an individual who presents a tongue-tie
tion and treatment of the family as well as the and an associated articulatory problem can usually
patient are necessary. Shprintzen identified some be re-educated successfully without surgical removal
syndromic patterns commonly associated with lan- or clipping of the frenum.97 The exception is when
guage and speech disorders. Contiguous gene disor- the tip of the tongue is almost completely immobi-
ders give rise to Prader-Willi, Beckwith-Wiedemann, lized. Even in these cases, however, surgical inter-
velocardiofacial, and Rubinstein-Taybi syndromes.3 vention does not independently remedy the speech
Mechanically induced syndromes that cause defor- problem. The freedom of the tongue that results
mations from tearing or mutilation of the embryo from clipping the frenum provides a potential for
include sequences in which multiple anomalies stem improvement, but the tongue habits that have devel-
from a single factor. Such sequences that result in oped will persist during speaking until the individ-
speech and language disorders include ADAM ual has been retrained.
sequence (amniotic deformations, adhesions, and
mutilations—the craniofacial complex and limbs are DENTAL ABNORMALITIES AND TONGUE THRUST. Nor-
particularly susceptible to amniotic adhesions mally, the teeth serve an important function in the
resulting in cleft lip, facial clefts, and anencephaly), production of speech sounds. Research and clinical
Pierre Robin syndrome (micrognathia, large U- observations have indicated, however, that many
1140 Ballenger’s Otorhinolaryngology
individuals with dental abnormalities are able to setting. The last three stages are really designed to
make compensatory adjustments that produce habituate the new response.78 Although the steps are
acceptable speech. Professional debate related to the straightforward, the complexity of the behavior and
developmental nature of swallowing (normal and the clinical process dictate that treatment be guided
abnormal), the impact of tongue thrust on dentition by a professional speech-language pathologist rather
and articulation, and the efficacy of speech and/or than by the client or parents attempting a self-
myofunctional therapy has created an ongoing con- improvement program. Additionally, the parents
troversy that is still unresolved. Review of the vari- should guard against continually correcting the child
ous positions in the literature led Bernthal and in his or her speech production. When proper ther-
Bankson to the following conclusions91: apy for articulatory problems is administered, the
prognosis is good.
1. Currently, no data support the existence of a
distinct clinical entity sometimes referred to
as “tongue thrust.” Behavior so identified is DISORDERS OF SPEECH MOTOR CONTROL
probably “normal,” especially in preadolescent
“Neuromotor speech disorders are disturbances of
children.
movement of the speech production system that
2. Speech sound errors, particularly sibilant distor-
result in someone being imperfectly understood or
tions, are present in greater number in those who
creating the impression that something is unusual or
evidence reverse swallow patterns than in those
bizarre about his or her speech pattern.”98 The two
who do not.
major types of neuromotor speech disorders are
3. The speech-language pathologist should focus on
dysarthria and apraxia.
the correction of speech sound errors. On the
basis of developmental data, techniques designed Dysarthria Dysarthria may be defined as a defect
to change swallow patterns as part of an overall of articulation resulting from a lesion in the central
remediation program appear ill advised before a or peripheral nervous system, which directly regu-
client has reached adolescence. lates the muscles used for speaking. It involves an
impairment in the control and execution of speech
Treatment of Articulation Disorders in Children movements because of muscle weakness, slowness,
The complexity of speech production requires incoordination, or altered muscle tone.98 Depending
awareness of many factors that could influence on the type of damage to the neuromuscular control
speech sound learning/monitoring/modification system, dysarthria can result in impaired respiration,
and performance. One must evaluate the articula- phonation, articulation, resonance, and prosodic
tion problem in terms of (1) the degree of sound aspects of speech. Largely through the work of Dar-
variation, (2) the consistency of misarticulation, (3) ley and his colleagues at the Mayo Clinic in the
the effect of the disorder on intelligibility, and (4) 1970s, differential diagnosis of the types of
the total number of sounds affected. This clinical dysarthrias can now be made.99 Table 49–2 presents
strategy naturally results in capturing an essential a list of recognizable dysarthria types along with the
component of any treatment plan; it must be pre- neurologic conditions or level of brain damage asso-
scriptive. The goal in treating articulation disorders ciated with them. Dysarthrias associated with
is to identify and correct defective sounds. Most Parkinson’s disease7,9,11–13,100,101 and amyotrophic lat-
treatment is directed at improving performance eral sclerosis10,102–106 have probably received more
accuracy and consistency. The four general steps of research attention during the past 5 years than other
remediation are (1) training the speaker’s perceptual types of speech disorders.107,108
skills (phonologic process or sound identification
and discrimination), (2) establishing the new Apraxia In contrast, apraxia of speech represents an
response (correct sound production), (3) strength- impairment in the programming of speech move-
ening and generalizing the correct sound production ments in the absence of muscle impairments associ-
or phonologic process to connected speech levels, ated with dysarthria.98 Apraxia is considered to involve
and (4) carrying over the new response to conversa- damage to the speech programming area of the brain
tional speech both within and outside the clinical in the left frontal lobe (Broca’s area).109 With both
Disorders of Voice, Speech, and Language 1141
conditions, dysarthria and apraxia, articulation profi- ates,99 any treatment program should incorporate
ciency of the speaker is adversely affected. As would be five fundamental principles: (1) the patient must be
expected, the degree to which speech intelligibility is assisted to develop functional compensation from
compromised depends on the type and severity of the the healthy body systems; (2) the patient must
underlying neuromuscular impairment. Darley and develop the perspective that speech production must
associates suggested that a comparison of dysarthria now become a highly conscious, deliberate effort; (3)
and apraxia of speech reveals distinctive performance the patient must develop the ability to monitor
profiles.99 According to their extensive study of these speech performance continuously; (4) remediation
clinical entities, the “most characteristic error made must begin as soon as possible because waiting is not
by dysarthric patients is imprecise production of con- beneficial; and (5) the patient must receive contin-
sonants, usually in the form of distortions and omis- ued support and reassurance. In an attempt to enu-
sions.” These are considered errors of “simplification.” merate various treatment options with neurogenic
In contrast, the patient demonstrating apraxia of speech disorders, LaPointe and Katz included med-
speech reveals errors of “complication” and relatively ical (alleviate cause), behavioral (modify neuromus-
few simplification errors. These complication errors cular and aerodynamic events), palliative (make the
include “substitutions of other phonemes, often unre- behavior, as well as the reaction to it, more moder-
lated substitutions, as well as additions of phonemes, ate), and alternate mode (implement alternative
repetitions of phonemes, and prolongations of communication systems) intervention strategies.111
phonemes.” Typically, the speech-language pathologist uses one
or all of the final three options in conjunction with
Treatment of the Motor Speech Disorders the appropriate medical intervention.
Although distinctive articulation profiles can be
described for both motor speech disorders, differen-
tial diagnosis between these two clinical entities is DEFECTS OF FLUENCY (STUTTERING)
usually difficult to make with confidence. The prog- The terms stuttering and stammering are used syn-
nosis for improvement with therapy for both of onymously around the world, although the term
these motor speech disorders should be guarded, but stuttering is preferred in the United States. Stuttering
judgment varies with the type and severity of the is one of the most enigmatic speech defects encoun-
underlying neuromuscular impairment.110 Because tered by the speech-language pathologist. This phe-
patients with either disorder may benefit from a for- nomenon is difficult to define because “no two
mal, structured remediation program, rehabilitation stutterers are alike” and no single stutterer is the
should be provided. According to Darley and associ- same from one time until the next. A workable def-
1142 Ballenger’s Otorhinolaryngology
inition of stuttering that has been acceptable to terers.115–117 In fact, research into the nature of stut-
all speech-language pathologists has not yet been terers’ fluent utterances indicates subtle motoric dif-
formulated. Wingate, however, provided a useful ferences (not auditorily perceptible) that suggest
description of the disorder that enumerates behav- some underlying difficulty with motor control and
iors common to all stutterers and indicates kinds of timing.118 Substantial agreement exists on the gen-
accessory behaviors shown only by some: eral “facts” regarding the onset and development of
I. (a) Disruption in the fluency of verbal expression, stuttering. The typical onset occurs during the pre-
which is (b) characterized by involuntary, audible or school years, usually 1 or 2 years after the child first
silent, repetitions or prolongations in the utterance learns to speak (onset is rare in adulthood). The
of short speech elements, namely: sounds, syllables, onset is usually gradual and most often character-
and words of one syllable. These disruptions (c) usu- ized by an excessive amount of repetitive speech
ally occur frequently or are marked in character and (sounds or syllables), usually without tension or
(d) are not readily controllable. II. Sometimes the effort. Although the exact nature of development
disruptions are (e) accompanied by accessory activ- varies among stutterers, virtually all demonstrate a
ities involving the speech apparatus, related or unre- change of behavior as long as the disorder persists.
lated body structures, or stereotyped speech The initial speech characteristics of part-word
utterances. These activities give the appearance of repetitions are often supplemented with sound
being speech-related struggles. III. Also, there are not
prolongations and hesitations, usually associated
infrequently (f) indications or report of the presence
with increasing struggle and avoidance behavior.
of an emotional state, ranging from a general condi-
tion of “excitement” or “tension” to more specific Reactions by listeners, important “others,” and the
emotions of a negative nature such as fear, embar- stutterer tend to create fear, anxiety, and self-doubt.
rassment, irritation, or the like. (g) The immediate These observations tend to confirm the accuracy
source of stuttering is some incoordination and utility of Wingate’s “definition” presented
expressed in the peripheral speech mechanism; the earlier. Moreover, the stability of these behaviors is
ultimate cause is presently unknown and may be not observed until the advanced stage of the disor-
complex or compound.112 der. Until that time, the severity of stuttering has
Although no conclusive prevalence figures currently been described as cyclic, changing from better to
exist, it has been estimated that stuttering has its worse with no apparent logic. Despite differences in
highest occurrence in the preschool years (above severity and symptom profile, there is clear evidence
4%), declining thereafter to an unstable value of less that as long as the disorder persists, the stutterer
than 1%. This declining pattern appears to relate to must face exposure of the disability to an ever-
two factors, successful therapy and spontaneous growing number of situations that come with social
recovery. Research has confirmed the clinical obser- and professional growth in adulthood. Stuttering is
vation that stuttering is more common among boys truly a disorder of social living, not just a speech
than girls in a ratio of approximately 3 to 1.113 The impediment.
literature presents a variety of theories regarding the Research regarding the development of speech
origin of stuttering; unfortunately, none represent and language skills makes it clear that most children
professional consensus. Based on extensive case experience periods of “normal nonfluency” during
study, Van Riper concluded that one cannot deter- their early years that look and sound similar to the
mine or account for the onset of stuttering in terms behaviors described as onset characteristics of stut-
of the conditions surrounding it for the vast major- tering. The number and duration of such episodes
ity of cases studied soon after onset.114 At a basic vary among children, but their occurrence does not
physiology level, however, Van Riper stated that it automatically confirm the existence of stuttering.
seems reasonable to attribute stuttering to the “dif- Therefore, great caution should be exercised to
ficulty some children are bound to experience in avoid the unnecessary stigmatizing effect of labeling
mastering the synchronized timing of the motor a child’s nonfluencies as clinically significant (stut-
coordinations required for speech.” Van Riper’s con- tering) when they could be variations of normal
clusion has current consensus in light of the emerg- speech development. Although differentiation
ing research evidence that differences in speech between normal nonfluencies and those reflective of
physiology do exist between stutterers and nonstut- incipient stuttering is difficult, research has gener-
Disorders of Voice, Speech, and Language 1143
ated behavior guidelines to assist the speech-lan- muscular control system for speech in boys, at least
guage pathologist in making these clinical distinc- during the early years of development.
tions.114,119,120 Almost all stutterers have periods of
relative freedom from hesitancies, repetitions, Treatment of Stuttering Parents of a young child
blocks, or prolongations. Stutterers can usually sing who demonstrates minor hesitations and repetitions
or speak in unison without disruption in their flow in his or her speech should remain unemotional
of speech and usually have no difficulty when about these speech patterns to prevent the develop-
speaking aloud to themselves or to a pet. The degree ment of undue awareness and concern on the part of
of communicative stress in a speaking situation the child. Being an attentive, thoughtful listener is
appears to govern the degree of stuttering severity. the best response. The young child with incipient
stuttering should not be subjected to direct speech
Common Questions about Stuttering What is therapy or any type of therapy related to speech pro-
primary stuttering? This term is sometimes used to duction. According to Shames, the family is a critical
describe a child’s speech when it is marked by effort- factor in dealing with the young child because “the
less repetitions or prolongations of words, phrases, family can either reinforce or counteract the efforts
or syllables without an awareness on the child’s part of the speech-language pathologist.”122 An advanced,
that these mannerisms are different or abnormal. or secondary, stutterer should seek the assistance of
Johnson stated that “practically all stutterers are a qualified speech-language pathologist. The stut-
originally diagnosed (regarded as “stutterers,” “not terer or the family should be warned against treat-
talking right,” or “having difficulty saying words,” ment employing unethical procedures, such as
and so forth) by … their parents, more often than gimmicks, devices, pills, or the guarantee of a “cure
not the mother being the first to become con- for stuttering.” The treatment should always be con-
cerned.”121 Is stuttering hereditary? No clear evidence ducted by individuals who have had academic train-
supports the view that stuttering is a characteristic ing and experience in the areas of speech-language
that can be transmitted, in a biologic sense, from one pathology, clinical psychology, or psychiatry. A mul-
generation to another. Does stuttering run in fami- titude of different therapy strategies are currently
lies? Research studies pertaining to the families of available, and each reflects a theoretic view of the
stutterers and nonstutterers indicate that, to a lim- cause and nature of stuttering. Recent theories and
ited extent, stuttering does tend to run in families. treatment strategies have centered on fluency disor-
The reason appears to involve tradition more than ders as a motor speech disorder. In general, however,
heredity. When parents have had a background of clinical management of stuttering involves changing
experience with stuttering, they appear to react to the stutterer’s attitude, method of talking, and/or
the speech imperfections of their children differently environment. The advanced or secondary stutterer
from parents who are unfamiliar with the condition. must perceive the need for therapy. Frequently, the
Parents with stuttering in their background may be family of the secondary stutterer is also in need of
so conditioned in attitude, policies, and concern that appropriate treatment.
they view their child’s normal speech imperfections
as stuttering. Is stuttering caused by imitation? Par- DISORDERS OF SYMBOLIZATION
ents are frequently concerned about the possibility
of a child becoming a stutterer if their child associ-
(LANGUAGE)
ates with a stuttering child. Imitation in and of itself Language may be defined as an organized symbolic
does not cause stuttering. If this were true, the inci- representation of thought and action used as a means
dence of stuttering would be considerably higher of communication on an abstract level by human
than that currently reported. Children have been beings. Therefore, preceding the act of speaking is the
exposed to stuttering for years in public and private process of symbolization, which involves the com-
schools, and no “epidemic” has ever been recorded. prehension and formulation of language. When this
Why do more boys stutter than girls? Studies process is disturbed, the result may be classified as a
have shown that male stutterers outnumber female communication disorder that is manifested in the
stutterers by about 3 to 1. From a physical stand- inability, or limited ability, to use linguistic symbols
point, the sex ratio might reflect a less stable neuro- as a means of oral communication. This difficulty is
1144 Ballenger’s Otorhinolaryngology
common to many different types of children (includ- integration, comprehension, and expression. The
ing children with “specific language impairment,” deficits referred to are not the result of sensory, motor,
children with aphasia, mentally retarded children, intellectual, or emotional impairment, or of the lack
children with autistic-like characteristics, and hear- of opportunity to learn. They are assumed to derive
ing-impaired children) and markedly influences from dysfunctions in the brain, though the evidence
normal language acquisition. Language disorders are for such dysfunctioning may be mainly behavioral,
also central to the adult aphasic patient. rather than neurological, in nature.124
nostic approach, will the child be led to a more pre- 3. There is a continuum of severity within each
scriptive type of educational training. syndrome.
Because many aphasic children recover quickly
The linguistic disturbances of the aphasic have
after head injury or illness, the role of the speech-lan-
been classified in numerous ways that reflect the
guage pathologist and other professionals may be
clinical experience of the classifiers and their con-
minimal. When residual deficits persist, however, a
cepts of cortical function related to language.128
formal remediation program appears justified.126
These classifications have also attempted to recog-
Holland and Reinmuth remind us that for an unfor-
nize the major types and specific forms of language
tunate minority of these children, the prognosis is
disturbance. One classification system presently in
not good.127 Extensive residual problems require
wide use is the one developed by a Boston-based
intensive, specialized, interdisciplinary remediation
group of professionals that highlights fluent versus
available only through special rehabilitation centers
nonfluent types.129 The six options were summarized
or special schools. In those settings, “restitution of
by Boone as follows70:
linguistic, cognitive and physical skills is the primary
goal.” The diagnosis and prescribed training program 1. Broca’s or motor aphasia—marked reduction in
for the aphasic child would be woefully incomplete if speech output, common oral-verbal apraxia, rel-
the emotional factors of the family environment were atively good speech comprehension, word
not considered. The family may protect or shield the retrieval problem, writing performance matches
child excessively, or else coerce or reject the child. The speech output
presence of an aphasic child in the family unit may be 2. Transcortical motor aphasia—a fairly rare type
deeply disturbing; the situation requires a thorough with significant struggle in producing an utter-
appraisal of both the family structure and the need ance, telegraphic speech is common, relatively
for therapeutic counseling. good speech comprehension, impaired writing
skills
3. Anomic aphasia—word retrieval problems pre-
APHASIA (DYSPHASIA) IN ADULTS dominate for both speech and writing, nearly
Aphasia is associated with cortical disturbances or normal comprehension for speech and reading
lesions resulting from vascular impairment (throm- 4. Wernicke’s or jargon aphasia—significant com-
bosis, embolism, and hemorrhage), tumors, degen- prehension deficit for speech and reading, fluent
erating and infectious disease, and trauma. Holland but jargon-like verbal output, writing parallels
and Reinmuth stated that aphasia is a general term speech patterns
applied to different but related syndromes that 5. Conduction aphasia—nearly normal compre-
impair the ability to formulate, retrieve, and/or hension for speech and reading, marked deficit
decode the symbols of language.127 As a common in speech repetition, fluent speech output with
adult disorder of communication, it disrupts speech numerous sound and word errors
and verbal output, comprehension of speech, and 6. Global aphasia—the most severe and most com-
reading and writing skills. The onset of aphasia is mon type; profound problems with both verbal
usually abrupt and typically occurs in adults with no output and comprehension, and both reading
previous speech or language difficulty. According to and writing functions are poor
Holland and Reinmuth, most syndromes of aphasia
The emotional language of the adult aphasic is usu-
share several concepts:
ally better than his or her propositional language.
1. Aphasic symptoms are not bizarre but rather are The patient may find it easier to swear, count, or use
extreme extensions of language problems demon- other forms of automatic speech or nonproposi-
strated daily by normal speakers (ie, losing one’s tional forms of speech but is at a loss when requested
train of thought, forgetting how to spell a word, to develop this emotional language into abstract or
not understanding a spoken word or concept). propositional language situations. The patient expe-
2. All aphasics have some fundamental difficulty riences difficulty in combining simple linguistic
with both comprehension and word retrieval, symbols into more complex linguistic units. The
regardless of the presence of other deficits. patient is not without words but rather cannot
1146 Ballenger’s Otorhinolaryngology
quickly command the response that is appropriate 5. Damste PH. Virilization of the voice due to anabolic
to the situation. Boone emphasized that the brain steroids. Folia Phoniatr Logop 1964;16:10.
damage (regardless of its cause) can produce other 6. Damste PH. Voice change in adult women caused by
deficits or symptoms.70 These include hemiplegia virilizing agents. J Speech Hear Disord 1967;32:126.
(gross motor paralysis), hemianopsia (visual field 7. Ramig LO, Scherer RC, Klasner ER, et al. Acoustic
defect), intellectual deficits, seizures, dysarthria analysis of voice in amyotrophic lateral sclerosis. J
(motor speech impairment), and apraxia (inability Speech Hear Disord 1990;55:2–14.
to execute voluntary movement). 8. Hanson K, Gerratt B, Ward R. Cinegraphic observa-
Prognosis for the recovery of the aphasic tions of laryngeal function in Parkinson’s disease.
patient must be based on many factors, including the Laryngoscope 1984;94:348.
site and extent of the lesion, general health, attitude 9. Coutryman MA, Ramig LO, Pawlas AA. Speech and
toward self and environment, age and educational voice deficits in parkinsonism plus syndromes: can
attainment, vocation and avocations, family attitude, they be treated? In: NCVS Status and Progress
and degree of cooperation. Assuming that these and Report 1994;6:99.
other factors are relatively positive, considerable 10. Ramig LA, Scherer RC, Titze IR, Ringel SP. Acoustic
recovery may be expected from the overall linguistic characteristics of voice in amyotrophic lateral scle-
and physical impairments. Spontaneous improve- rosis: a longitudinal study. Ann Otol Rhinol Laryn-
ment may be noted during the first few months after gol 1988;97:164–72.
the onset without structured training. This may give 11. King JB, Ramig LO, Lemke JH, Horii Y. Parkinson’s
false hope to the patient and family for additional disease: longitudinal changes in acoustic parame-
recovery without seeking professional assistance. ters of phonation. J Med Speech Lang Pathol [In
Depending on the degree of involvement, the family, press].
with the physician’s guidance, should enlist the serv- 12. Strand E, Yorkston K. Description and classification
ices of a physical therapist, occupational therapist, of dysarthric individuals: toward a new taxonomy.
speech-language pathologist, psychologist, and voca- In: Till J, Beukelman D, Yorkston K, editors. Clini-
tional counselor in formulating a personalized reha- cal dysarthria. Baltimore (MD): Paul H. Brookes;
bilitation program. Ideally, the adult aphasic should 1994.
be started on a program of rehabilitation as soon 13. Ramig LO. Speech therapy for Parkinson’s disease.
after the traumatic episode as possible. In: Koller W, Paulson G, editors. Therapy of Parkin-
son’s disease. New York: Marcel Dekker; 1994.
14. Orlikoff RF, Huang ZD. Influence of vowel production
REFERENCES on acoustic and electroglottographic perturbation
1. Ludlow CL. Research needs for the assessment of measures. Presented at the American Speech-Language-
phonatory function. In: Ludlow CL, Hart MO, edi- Hearing Association Convention, Atlanta, GA, 1991.
tors. Proceedings of the Conference on the Assess- 15. Huang ZD, Minifie FD, Kasuya H, Lin XS. Measures
ment of Vocal Pathology. ASHA Reports No. 11. of vocal function during changes in vocal effort
Rockville (MD): American Speech-Language-Hear- level. J Voice 1995;9:429–38.
ing Association; 1981. 16. Koike Y. Application of some acoustic measures for
2. Verdolini K. Voice disorders. In: Tomblin JB, Morris the evaluation of laryngeal dysfunction. Studia
HL, Spriestersbach DC, editors. Diagnosis in speech- Phonol 1973;7:17.
language pathology. San Diego (CA): Singular Pub- 17. Yoshida M. Study on perceptive and acoustic classi-
lishing Group; 1994. p. 253–4. fication of pathological voices. Pract Otol (Kyoto)
3. Shprintzen RJ. Syndrome delineation and communi- 1979;72:249.
cative impairment. In: Minifie FD, editor. Introduction 18. Sawashima M, Hirano M. Clinical evaluation of
to communication sciences and disorders. San Diego voice disorders. Ann Bull Res Inst Logop Phoniatr
(CA): Singular Publishing Group; 1994. p. 439–80. 1981;15:164.
4. Bastian RW, Keidar AK, Verdolini-Marston K. Sim- 19. Yumoto E, Gould WJ, Baer T. Harmonics-to-noise
ple vocal tasks for detecting vocal fold swelling. J ratio as an index to harshness. J Acoust Soc Am
Voice 1990;4:172–83. 1982;71:1544–9.
Disorders of Voice, Speech, and Language 1147
20. Yumoto E, Sasaki Y, Okamura H. Harmonics-to- 36. Levine HL, Wood BG, Batza E, et al. Recurrent laryn-
noise ratio and psychophysical measurement of the geal nerve section for spasmodic dysphonia. Ann
degree of hoarseness. J Speech Hear Res 1984;27:2–6. Otol Rhinol Laryngol 1979;88:527–30.
21. Zwitman DH. Bilateral cord dysfunctions: abduction 37. Biller HF, Som MI, Lawson W. Laryngeal nerve crush
type spastic dysphonia. J Speech Hear Disord for spastic dysphonia. Ann Otol Rhinol Laryngol
1979;44:373–8. 1979;88:531–2.
22. Freeman F, Cannito M, Finitzo-Hieber T. Classifica- 38. Miller RH, Woodson GE, Jankovic J, Izdebski R. Bot-
tion of spasmodic dysphonia by perceptual-acoustic ulinum toxin injection of the vocal fold for spas-
means. In: Gates GA, editor. Spastic dysphonia: state of modic dysphonia. Arch Otolaryngol Head Neck Surg
the art 1984. New York: The Voice Foundation; 1985. 1987;113:603–5.
23. Brodnitz FS. Spastic dysphonia. Ann Otol Rhinol 39. Dedo HH, Izdebski K. Intermediate results of 306
Laryngol 1975;85:210–4. recurrent laryngeal nerve sections for spastic dys-
24. Spiegel H. Psychiatric aspects of spasmodic dyspho- phonia. Laryngoscope 1983;93:9–16.
nia. In: Gates GA, editor. Spastic dysphonia: state of 40. Aronson AE, DeSanto LW. Adductor spasmodic dys-
the art 1984. New York: The Voice Foundation; 1985. phonia: three years after recurrent nerve section.
25. Aronson AE, Brown JP, Litin EM, Pearson JS. Spastic Laryngoscope 1983;93:1–8.
dysphonia: I. Voice, neurologic and psychiatric 41. Wilson FB, Oldring DJ, Mueller K. Recurrent laryn-
aspects. J Speech Hear Disord 1968;33:203–18. geal nerve dissection: a case report involving return
26. Feldman M, Nixon J, Finitzo-Hieber T, Freeman F. of spastic dysphonia after initial surgery. J Speech
Abnormal parasympathetic vagal function in Hear Disord 1976;45:112–8.
patients with spasmodic dysphonia. Ann Intern Med 42. Fritzell B, et al. Experiences with recurrent laryngeal
1984;100:491–5. nerve section for spastic dysphonia. In: Phoniatric
27. Dedo HH, Townsend JJ, Izdebski K. Current evi- and logopedic progress report no. 3. Stockholm:
dence for the organic etiology of spastic dysphonia. Department of Logopedics and Phoniatrics, Hud-
Otolaryngology 1978;86:875–80. dinge University Hospital, Karolinska Institute; 1981.
28. Izdebski K, Shipp T. Model of spastic dysphonia. In: 43. Hartman DE, Aronson AE. Clinical investigations of
Gates GA, editor. Spastic dysphonia: state of the art intermittent breathy dysphonia. J Speech Hear Dis-
1984. New York: The Voice Foundation; 1985. ord 1981;46:428–32.
29. Fink M. Neurobiology of spastic disorders. In: Gates 44. Blitzer A. Electromyographic findings in spastic dys-
GA, editor. Spastic dysphonia: state of the art 1984. phonia. In: Gates GA, editor. Spastic dysphonia: state
New York: The Voice Foundation; 1985. of the art 1984. New York: The Voice Foundation;1985.
30. Malmgran L. Neuromuscular anatomy of the larynx. 45. Robe E, Brumlik J, Moore P. A study of spastic dys-
In: Gates GA, editor. Spastic dysphonia: state of the phonia: neurologic and electroencephalographic
art 1984. New York: The Voice Foundation; 1985. abnormalities. Laryngoscope 1960;70:219.
31. Bocchino JV, Tucker HM. Recurrent laryngeal nerve 46. Schaefer S, Freeman F, Finitzo T, et al. Magnetic res-
pathology in spasmodic dysphonia. Laryngoscope onance imaging findings and correlations in spas-
1978;88:1274–8. modic dysphonia patients. Ann Otol Rhinol
32. Dedo HH, Shipp T. Spastic dysphonia—a surgical Laryngol 1985;94:595–601.
and voice therapy treatment program. Houston: 47. Finitzo-Hieber T, Freeman FJ, Gerling IJ, et al. Audi-
College-Hill Press; 1980. tory brain stem response abnormalities in adductor
33. Freeman F, Cannito MP, Finitzo-Hieber T, Ross E. spasmodic dysphonia. Am J Otolaryngol 1982;3:
Spasmodic dysphonia: myths and facts. In: Rosen- 26–30.
field D, editor. Speech news. Houston: Baylor Col- 48. Boone DR, McFarland SC. The voice and voice ther-
lege of Medicine; 1984. apy. Englewood Cliffs (NJ): Allyn & Bacon; 1999.
34. Dedo HH. Recurrent laryngeal nerve section for spastic 49. Lowry LD, Marks JE, Powell WJ. 260 laryngeal carci-
dysphonia. Ann Otol Rhinol Laryngol 1976;85:451–9. nomas. Arch Otolaryngol 1973;98:147–53.
35. Barton TT. Treatment of spastic dysphonia by recur- 50. Silverberg E. Cancer statistics, 1981. Reprinted by
rent laryngeal nerve section. Laryngoscope 1979; American Cancer Society from CA Cancer J Clin
89:244. 1981;37:13–28.
1148 Ballenger’s Otorhinolaryngology
51. Cancer facts and figures. New York: American Can- 67. Sisson G, McConnell FM, Logemann JA, Yeh S. Voice
cer Society; 1988. rehabilitation after laryngectomy. Arch Otolaryngol
52. Cancer facts and figures. Atlanta: American Cancer 1975;101:178.
Society; 1994. 68. Gardner WH. Laryngectomee speech and rehabilita-
53. American Cancer Society. Cancer facts and figures. tion. Springfield (MA): Charles C. Thomas; 1971.
Year 2000. Available at: www3.cancer.org (accessed 69. Lauder E. The laryngectomee and the artificial larynx
Nov 2000). —a second look. J Speech Hear Disord 1970;35:62–5.
54. Gates GA, Ryan W, Cooper JC, et al. Current state of 70. Boone D. Human communication and its disorders.
laryngectomee rehabilitation: I. Results of therapy. Englewood Cliffs (NJ): Prentice Hall; 1987.
Am J Otolaryngol 1982;3:1–7. 71. Eimas PD, Siqueland ER, Jusczyk P, Vigorito J. Speech
55. Snidecor JC. The family of the laryngectomee. In: perception in infants. Science 1971;171:303–6.
The family as supportive personnel in speech and 72. Kuhl PK. Speech perception. In: Minifie FD, editor.
hearing remediation. Proceedings of a postgraduate Introduction to communication sciences and disor-
short course. Santa Barbara (CA): University of Cal- ders. San Diego (CA): Singular Publishing Group;
ifornia, Santa Barbara, US Department of Health, 1994. p. 77–148.
Education and Welfare; 1971. p. 12–24. 73. Gopnik A, Meltzoff AN, Kuhl PK. The scientist in the
56. Gates GA, Ryan W, Lauder E. Current status of crib: minds, brains, and how children learn. New
laryngectomee rehabilitation: IV. Attitudes about York: William Morrow; 1999.
laryngectomee rehabilitation should change. Am J 74. Werker JF, Tees RC. Cross-language speech percep-
Otolaryngol 1982;3:97–103. tion: evidence for perceptual reorganization during
57. Gates GA, Ryan W, Cantu E, Hearne E. Current sta- the first year of life. Infant Behav Dev 1984;7:49.
tus of laryngectomee rehabilitation: II. Causes of 75. Kuhl PK, Williams KA, Lacerda F, et al. Linguistic
failure. Am J Otolaryngol 1982;3:8–14. experience alters phonetic perception in infants by 6
58. Ryan W, Gates GA, Cantu E, Hearne E. Current sta- months of age. Science 1992;255:606–8.
tus of laryngectomee rehabilitation: III. Understand- 76. Greiser DL, Kuhl PK. Maternal speech to infants in a
ing of esophageal speech. Am J Otolaryngol 1982; tonal language: support for universal prosodic fea-
3:91–6. tures in motherese. Dev Psychol 1988;24:14.
59. Ignorance of laryngectomee care confirmed by med- 77. Bloom L. Language development. In: Minifie FD,
ical authorities. The IAL News 1982;27:June. editor. Introduction to communication sciences and
60. Singer MI, Blom ED. An endoscopic technique for disorders. San Diego (CA): Singular Publishing
restoration of voice after laryngectomy. Ann Otol Group; 1994. p. 189–235.
Rhinol Laryngol 1980;89:529–33. 78. Stone JR, Stoel-Gammon C. Phonological develop-
61. Zwitman DH, Calcaterra TC. Phonation using the ment and disorders in children. In: Minifie FD, edi-
trachea-esophageal shunt after total laryngectomy. J tor. Introduction to communication sciences and
Speech Hear Disord 1973;38:368–73. disorders. San Diego (CA): Singular Publishing
62. Weinberg B. Airway resistance to the voice button. Group; 1994. p. 149–87.
Arch Otolaryngol 1982;108:498–500. 79. Lewis MM. How children learn to speak. New York:
63. Singer MI, Blom ED, Hamaker RC. Further experi- Basic Books; 1957.
ence with voice restoration after total laryngectomy. 80. Locke JL. Phonological acquisition and change. New
Ann Otol Rhinol Laryngol 1981;90:498–502. York: Academic Press; 1983.
64. Singer MI, Blom ED. A selective myotomy for voice 81. Oller DK, Eilers RE. The role of audition in infant
restoration after total laryngectomy. Arch Otolaryn- babbling. Child Dev 1988;59:441–9.
gol 1981;107:670–3. 82. Yoshinaga-Itano C. Language development of deaf
65. Blom ED, Singer MI, Hamaker RC. Tracheostoma and hard of hearing children. San Diego (CA): Sin-
valve for postlaryngectomy voice rehabilitation. Ann gular Publishing Group; 1999.
Otol Rhinol Laryngol 1982;91:576–8. 83. Sander EK. When are speech sounds learned? J
66. Andrews J, Mickel RA, Hanson DG, et al. Major Speech Hear Disord 1972;37:55–63.
complications following tracheoesophageal punc- 84. Kent RD. Anatomical and neuromuscular matura-
ture for voice rehabilitation. Laryngoscope 1987; tion of the speech mechanism: evidence from
97:562–7. acoustic studies. J Speech Hear Res 1976;19:421–47.
Disorders of Voice, Speech, and Language 1149
85. Ingram D. Phonological disability in children. Lon- 103. Kent JF, Kent RD, Rosenbek JC, et al. Quantitative
don: Edward Arnold; 1976. description of the dysarthria in women with amy-
86. Dyson AT. Phonetic inventories of 2- and 3-year- otrophic lateral sclerosis. J Speech Hear Res 1992;35:
old children. J Speech Hear Disord 1988;53:89–93. 723–33.
87. Crary MA, Fokes J. Phonological processes in apraxia 104. Kent RD, Kent JF, Weismer G, et al. Impairment of
of speech: a systemic simplification of articulatory speech intelligibility in men with amyotrophic lat-
performance. Aphasia Apraxia Agnosia 1980; 4:1. eral sclerosis. J Speech Hear Disord 1990;55:721–8.
88. Grumwell P. Clinical phonology, 2nd ed. Balti- 105. Kent RD, Sufit RL, Rosenbek JC, et al. Speech dete-
more: Williams & Wilkins; 1987. rioration in amyotrophic lateral sclerosis: a case
89. Smit AB. Speech sound disorders. In: Tomblin JB, study. J Speech Hear Res 1991;34:1269–75.
Morris HL, Spriestersbach DC, editors. Diagnosis 106. Weismer G, Martin R, Kent RD, Kent JF. Formant
in speech-language pathology. San Diego (CA): trajectory characteristics of males with amyotrophic
Singular Publishing Group; 1994. p. 179–99. lateral sclerosis. J Acoust Soc Am 1992;91:1085–98.
90. Stoel-Gammon C, Dunn C. Normal and disordered 107. Cannito MP, Marquardt TP. Ataxic dysarthria. In:
phonology in children. Austin (TX): Pro-Ed; 1985. McNeil MR, editor. Clinical management of senso-
91. Bernthal JE, Bankson NW. Articulation and rimotorspeech disorders. New York: Thieme; 1997.
phonological disorders. 2nd ed. Englewood Cliffs 108. Kent RD, Kent JF, Duffy JR, et al. Ataxic dysarthria.
(NJ): Prentice-Hall; 1988. J Speech Lang Hear Res 2000;43:1275–89.
92. Carrell J. Disorders of articulation. Englewood 109. Kent RD. Neurological bases of communication
Cliffs (NJ): Prentice-Hall; 1968. disorders. In: Minifie FD, editor. Introduction to
93. Cohen MM. The child with multiple birth defects. communication sciences and disorders. San Diego
New York: Raven Press; 1982. (CA): Singular Publishing Group; 1994. p. 313–50.
94. Fraser FC. The genetics of cleft lip and cleft palate. 110. Duffy JR. Motor speech disorders: substrates, dif-
Am J Hum Genet 1970;22:336–52. ferential diagnosis, and management. St. Louis:
95. Siegel-Sadewitz VL, Shprintzen RJ. The relation- Mosby Year Book; 1995.
ship of communication disorders to syndrome 111. LaPointe LL, Katz RC. Neurogenic disorders of
identification. J Speech Hear Disord 1982;47: speech. In: Shames G, Wiig E, Secord WB, editors.
338–54. Human communication disorders. 4th ed. Colum-
96. McEvery ET, Gaines FP. Tongue-tie in infants and bus (OH): Charles E. Merrill; 1994. p. 480–518.
children. J Pediatr 1941;18:252. 112. Wingate M. A standard definition of stuttering. J
97. Fletcher SG, Meldrum JR. Lingual function and Speech Hear Disord 1964;29:484.
relative length of the lingual frenulum. J Speech 113. Prins D. Fluency and stuttering. In: Minifie FD,
Hear Res 1968;11:382–90. editor. Introduction to communication sciences
98. LaPointe LL. Neurogenic disorders of communica- and disorders. San Diego (CA): Singular Publishing
tion. In: Minifie FD, editor. Introduction to com- Group; 1994. p. 521–59.
munication sciences and disorders. San Diego 114. Van Riper C. The nature of stuttering, 2nd ed.
(CA): Singular Publishing Group; 1994. Englewood Cliffs (NJ): Prentice-Hall; 1982.
99. Darley F, Aronson A, Brown J. Motor speech disor- 115. Starkweather CW. Fluency and stuttering. Engle-
ders. Philadelphia (PA): WB Saunders; 1975. wood Cliffs (NJ): Prentice-Hall; 1987.
100. Hartelius L, Svensson P. Speech and swallowing 116. Hillman RE, Gilbert HR. Voice onset times for voice-
symptoms associated with Parkinson’s disease and less stop consonants in fluent reading of stutterers
multiple sclerosis: a survey. Folia Phoniatr Logop and nonstutterers. J Acoust Soc Am 1977;61:610–1.
1991;46:9–17. 117. Metz DE, Conture EG, Caruso A. Voice onset time,
101. Yorkston KM, Hammon VL, Beukelman DR, frication and aspiration during stutterers’ fluent
Traynor CD. The effect of rate on the intelligibility speech. J Speech Hear Res 1979;22:649–56.
and naturalness of dysarthric speech. J Speech 118. Zimmerman G. Articulatory dynamics of fluent
Hear Disord 1990;55:550–60. utterances of stutterers and nonstutterers. J Speech
102. Hartelius L, Nord L, Buder EH. Acoustic analysis Hear Res 1980;23:95.
of dysarthria associated with multiple sclerosis. 119. Ingham RJ. Stuttering and behavior therapy. San
Clin Linguist Phonet 1994;8:143. Diego (CA): College Hill Press; 1984.
1150 Ballenger’s Otorhinolaryngology
120. Adams MR. A clinical strategy for differentiating the 125. Chase R. Neurological aspects of language disorders
normal nonfluent child and the incipient stutterer. J in children. In: Irwin J, Marge M, editors. Principles
Fluency Disord 1977;2:141. of childhood language disabilities. Englewood Cliffs
121. Johnson W. People in quandaries. New York: Harper (NJ): Prentice-Hall; 1972.
and Row; 1946. 126. Wood NE. Delayed speech and language develop-
122. Shames G. Disorders and fluency. In: Shames G, ment. Englewood Cliffs (NJ): Prentice Hall; 1964.
Wiig E, editors. Human communication disorders. 127. Holland A, Reinmuth O. Aphasia in adults. In:
3rd ed. Columbus (OH): Charles E. Merrill; 1990. Shames G, Wiig E, editors. Human communication
123. Leonard L. Early language development and lan- disorders. 2nd ed. Columbus (OH): Charles E.
guage disorders. In: Shames G, Wiig E, editors. Merrill; 1986.
Human communication disorders. 2nd ed. Colum- 128. Chapey R. Language intervention strategies in adult
bus (OH): Charles E. Merrill; 1986. aphasia. 3rd ed. Baltimore: Williams & Wilkins;
124. Myklebust H. Childhood aphasia: an evolving con- 1994.
cept. In: Travis LE, editor. Handbook of speech 129. Goodglass H, Kaplan E. The asssessment of aphasia
pathology and audiology. Englewood Cliffs (NJ): and related disorders. 2nd ed. Philadelphia: Lea &
Prentice-Hall; 1971. Febiger; 1983.
CHAPTER 50
The successful management of the airway is of para- which are synovial and allow a hinge motion
mount importance. Airway control requires a logical between the cartilages.
and systematic approach guided by the principles of The cricoid cartilage is the only complete ring
basic and advanced life support techniques and a of the airway, which accounts for the association
working knowledge of relevant pharmacology. Most between prolonged or traumatic endotracheal intu-
importantly, the health professional must possess a bation and subglottic stenosis occurring in this area.
mastery of the anatomy and physiology of the upper The cricoid is composed of hyaline cartilage that
aerodigestive tract. The airway surgeon is also often calcifies later in adult life. It tends to be
uniquely responsible for the diagnosis and treatment broader posteriorly and tapers to a smaller arch
of airway lesions such as laryngotracheal stenosis anteriorly, mimicking the shape of a signet ring. The
and arytenoid fixation. thyroid and cricoid cartilages are attached anteriorly
by the cricothyroid membrane.
ANATOMY
Successful airway intervention necessitates an
understanding of the anatomy of the laryngotra-
cheal complex (Figure 50–1). The hyoid bone allows
muscular attachment from the lingual muscles and
mandible as well as the extrinsic muscles of the lar-
ynx and serves as a laryngeal anchor via the thyro-
hyoid membrane. This membrane is pierced
bilaterally by the superior laryngeal neurovascular
bundles. Embryologically, the hyoid bone is derived
from mesodermal cells in the second and third
branchial arches. The greater horn of the hyoid bone
is derived from the third branchial arch, whereas the
lesser horn is of second branchial arch origin.
The major cartilages of the larynx include the
thyroid, cricoid, epiglottis, and paired arytenoids
(Figure 50–2). These cartilages develop from mes-
enchymal tissue originating in the fourth, fifth, and
sixth branchial arches. The thyroid cartilage is a
shield-shaped structure whose central prominence FIGURE 50–1. Lateral view of the larynx. Reproduced
tends to be more acutely angled in men than in with permission from Graney DO, Flint PW. Anatomy.
women. The inferior horns of the thyroid cartilage In: Cummings CW, et al, editors. Otolaryngology-head
articulate with the posterior facets of the cricoid car- and neck surgery. 2nd ed. St. Louis: Mosby Year Book;
tilage and form the important cricothyroid joints, 1993. p. 1693.
1151
1152 Ballenger’s Otorhinolaryngology
The epiglottis serves a protective function for obliquely angled left bronchus while preserving
the airway and is composed of elastic cartilage. It visualization into the right bronchus.1
attaches to the thyroid cartilage via the thyroepiglot-
tic ligament (Figure 50–3). The arytenoid cartilages CLINICAL EVALUATION OF THE
provide the posterior attachments of the vocal cords,
the anterior attachment being on the thyroid carti-
AIRWAY
lage at Broyle’s ligament. The arytenoids articulate The clinical evaluation of the airway must begin with
with facets on the posterosuperior aspect of the a rapid assessment of the patient’s ventilatory and
cricoid cartilage and form synovial joints. respiratory status. If the patient is in impending air-
The trachea begins at the lower border of the way distress, prophylactic measures to prevent dete-
cricoid cartilage and is composed of incomplete, C- rioration of the airway must be employed. If the
shaped “rings” of hyaline cartilage. The rings are patient does not appear to be ventilating adequately,
open posteriorly and connected on this aspect by the airway must be definitively secured through
fibroareolar connective tissue and smooth muscle either medical or surgical techniques. If medical con-
fibers. The larynx and trachea are lined with a pseu- trol of the airway fails and intubation is impossible
dostratified, ciliated columnar epithelium inter- owing to an airway injury or upper airway obstruc-
spersed with mucus-secreting cells, except at the tion, an urgent tracheostomy or cricothyroidotomy
glottis, which is lined with a stratified squamous must be performed. The technique and advantages
epithelium. The trachea bifurcates at approximately of each are discussed in this chapter. The symptoms
the sternal angle, forming the two bronchi. The right and signs that indicate upper respiratory obstruction
bronchus is wider, shorter, and more vertically ori- include hoarseness; dyspnea; stridor; intercostal,
ented than the left bronchus. When using an open suprasternal, and supraclavicular retractions; rest-
bronchoscope, one may most easily examine both lessness; cyanosis; and drooling. The signs of trauma
bronchi by passing the instrument through the right to the airway include bloody sputum, subcutaneous
side of the mouth, thus allowing the best view of the emphysema, and palpable laryngotracheal fractures.
Airway Control and Laryngotracheal Stenosis in Adults 1153
If the patient does not require an immediate tracheoscopy. This mission must be accomplished
airway intervention, the caregiver may proceed with while respecting the possibility of other injuries such
a diagnostic assessment. This assessment should as cervical spine dislocation, vascular injuries, or
include a complete history and a physical examina- other associated medical conditions.
tion of the upper aerodigestive tract. If the patient is
seen in the clinic setting, a mirror indirect laryn-
goscopy may be performed. Perhaps the most valu-
AIRWAY MANAGEMENT
able study is a direct fiber-optic examination via Although the management of the airway in the con-
nasopharyngoscopy. This technique allows unparal- trolled environment of the operating room is
leled visualization of the upper airway and larynx straightforward, patients presenting in the emer-
and may allow for video documentation (Figure gency department pose unique problems such as
50–4). The fiber-optic endoscopes and light sources cervical spine injuries, closed head injuries with the
are now portable and may be used in the emergency possibility of increased intracranial pressure, laryn-
department, intensive care unit, and nursing unit. A gotracheal disruption, airway hemorrhage, and facial
blood gas determination, chest radiograph, and air- deformities. The intensive care unit setting also
way evaluation with radiography or computed offers challenges such as confounding medical
tomography may also be indicated. issues. These complicating factors can be handled
While remaining cognizant of the general sta- only through an individualized approach that is
tus of the patient, the surgeon must accurately assess guided by a stepwise progression of techniques
the nature and level of the airway obstruction and aimed at controlling the increasingly difficult airway.
establish airway control below the lowest level of the Supplemental oxygen is the most simple meas-
obstruction. Once the airway has been controlled, a ure of airway support and should be given almost
complete airway evaluation may be performed in the universally to patients with airway distress. After this
operating room through direct laryngoscopy and intervention, the clinician should evaluate for airway
1154 Ballenger’s Otorhinolaryngology
obstruction from foreign bodies such as displaced (trumpet) may be placed transnasally into the pos-
teeth or tongue and soft tissue collapse into the terior hypopharynx, thus relieving soft tissue
pharynx. Because of its efficacy and lack of cervical obstruction of the posterior oropharynx. Nasopha-
movement, the jaw thrust is the most appropriate ryngeal airways tend to be less stimulating than oral
positioning maneuver.2 Lifting the chin and extend- airways in awake patients but risk epistaxis.
ing the neck may be successful in improving the air- Nasopharyngeal trumpets should not be used in
way but risks cervical spinal cord injury in a trauma patients with known or suspected basilar skull frac-
patient. An oropharyngeal airway may relieve soft tures owing to the risk of inadvertent intracranial
tissue obstruction of the airway (Figure 50–5). It placement.3
serves to displace the tongue anteriorly, providing an A laryngeal mask airway is a nondefinitive
unobstructed airway. A nasopharyngeal airway technique sometimes employed by emergency med-
toward tracheostomy changed in 1909, when Cheva- strap muscles. After identifying the strap muscles, the
lier Jackson described the modern tracheostomy.12 sternohyoid and sternothyroid muscles are separated
Jackson then addressed the high rate of laryngeal and in the midline by incising the fascia that connects
tracheal damage and stenosis that had previously them. Retractors are used to pull the muscles laterally,
been associated with tracheostomies in his landmark revealing the thyroid isthmus. The cricoid cartilage is
article of 1921, “High Tracheotomy and Other Errors: palpated and identified at this point. The isthmus of
The Chief Cause of Chronic Laryngeal Stenosis.”13 In the thyroid gland is dissected off of the trachea in a
this treatise, the author hypothesized that the unac- bloodless fascial plane just superficial to the trachea.
ceptably high rates of laryngeal and tracheal stenosis The thyroid isthmus is transected and suture-ligated.
associated with tracheostomies preceding his descrip- A cricoid hook is used to pull the trachea superiorly
tion were attributable to damage to the thyroid and to stabilize the airway and improve exposure of the
cricoid cartilages incurred during the performance of anterior tracheal wall (Figure 50–6). The fine fascia
“high” tracheostomies. Jackson implored that tra- overlying the trachea is carefully separated.
cheostomies be performed below the second tracheal Although horizontal and vertical incisions into
ring, thereby avoiding these dreaded complications. the tracheal wall have been proposed, an inferiorly
This dictum has been followed to the present day. based Bjork flap consisting of several tracheal rings
is a superior option for adults. Following Jackson’s
Technique A tracheostomy is generally begun with principle, a horizontal incision is made between the
a horizontal skin incision approximately midway second and third tracheal rings and carried inferi-
between the sternal notch and cricoid cartilage, orly with Mayo scissors to fashion an inferiorly
although some surgeons prefer a vertical skin inci- based flap. The space between the rings may be cal-
sion. The incision is carried down through the skin, cified in older patients. The Bjork flap is sewn to the
subcutaneous tissue, and platysma to the level of the subcutaneous tissue of the inferior skin margin with
an absorbable suture (Figure 50–7). This tracheal air from the wound to prevent subcutaneous
flap makes reintubation safer in the event of acci- emphysema, which could potentially lead to pneu-
dental extubation but does lead to a slightly momediastinum, pneumothorax, or infection.
increased risk of tracheocutaneous fistula. For this
reason, a horizontal H incision based on the third Complications of Tracheostomy The complica-
tracheal ring or the removal of an anterior section of tions of tracheostomy are often divided into two
a single tracheal ring may be preferable in patients main categories: early and late. Early complications
who are expected to require a tracheostomy only for include hemorrhage, tube obstruction, tube dis-
a short period of time. placement, subcutaneous emphysema, and pneu-
When a tracheostomy is permanent or of long mothorax. Late complications include innominate
duration, the surrounding skin may be surgically artery rupture, infection, aspiration, granuloma for-
defatted and sutured to the tracheostoma circum- mation, and laryngeal or subglottic stenosis.14
ferentially. This is particularly useful in obese
patients, in whom a semipermanent tracheostoma EARLY COMPLICATIONS. HEMORRHAGE. Mild bleeding is
can be fashioned that is less prone to maceration or the most common early complication of tra-
the formation of granulation tissue and stenosis cheostomy, occurring in about 5% of cases. The hem-
because the skin directly abuts the respiratory orrhage is usually from veins or the incised thyroid
mucosa of the trachea. The creation of a semiper- isthmus. Mild bleeding can generally be controlled by
manent tracheostoma in this fashion also serves to raising the head of the patient to decrease venous
decrease the length of the tract of the tracheostomy, pressure or by placing hemostatic gauze over oozing
thereby facilitating removal and reinsertion of the areas. Major hemorrhage is unusual and most often
tracheostomy tube. involves a branch of the superior thyroid artery. Arte-
The tracheostomy incision should never be rial bleeding is an indication for immediate surgical
closed tightly and must allow the passive egress of exploration for bleeding control and vessel ligation.
TUBE OBSTRUCTION. Tube obstruction is the most
common cause of ventilatory insufficiency in a post-
tracheostomy patient and most often results from a
mucous plug. Dried mucus and secretions in and
around the tracheostomy tube can form crusts that
may become large enough to obstruct the lumen of
the tube. Audible airflow and difficulty passing a
suction catheter through the tube are signs of
impending tube obstruction. Adequate humidifica-
tion, irrigation, frequent suctioning, and cleaning of
the inner cannula help to reduce the risk of plugging
and obstruction. If the tracheostomy tube becomes
obstructed and cannot be recannulized, the patient
and care staff should be instructed to remove the
entire tube.
TRACHEOSTOMY TUBE DISPLACEMENT. Displacement of
the tracheostomy tube or dislocation of the tube
from the tracheostomy tract poses a considerable
risk to the patient who has recently undergone a tra-
cheostomy. Displacement of the tube is most likely
FIGURE 50–7. Creation of an inferiorly based Bjork to occur in the early postoperative period before a
flap. Reproduced with permission from Bailey BJ, et al, stable tract has matured between the tracheal lumen
editors. Head and neck surgery-otolaryngology. Philadel- and the skin. Displacement most often occurs owing
phia: JB Lippincott; 1993. Copyright Lippincott Williams to the tube being inadequately secured to the patient
& Wilkins. p. 716. with sutures or ties. Excessive tension applied on the
1158 Ballenger’s Otorhinolaryngology
tube from the ventilatory apparatus also poses a risk pressure is applied to compress the innominate
of tube dislodgment. artery against the manubrium. The patient should be
Tracheostomy tube replacement in the early taken immediately to the operating room for median
postoperative period and during the first tube sternotomy and vessel ligation. Many surgeons feel
change should be done under direct vision with the that the Bjork flap technique of tracheostomy lessens
surgeon in attendance. Blind reinsertion risks creat- the risk of this potentially fatal complication.
ing a false passage into the paratracheal tissues.
INFECTION. Although bacterial colonization of the
SUBCUTANEOUS EMPHYSEMA. Subcutaneous emphy- trachea and peristomal area is unavoidable owing to
sema results from the forced entrance of air into the the moist, open nature of the tracheostomy wound,
fascial planes of the neck and usually results from significant infections rarely occur after a tra-
closing the tracheostomy incision too tightly. Tube cheostomy. Local cellulitis can generally be managed
obstruction or displacement can also lead to the with aggressive local cleaning measures and topical
escape of air into the fascial planes. Crepitus and soft antibiotics. Uncontrolled local infection can rarely
tissue swelling can involve the neck, face, and upper lead to serious complications such as mediastinitis
torso. Minor amounts of subcutaneous emphysema or predispose a patient for innominate artery rup-
usually resolve spontaneously without significant ture or peristomal tissue loss. Local infection that
sequelae, whereas massive amounts may progress to does not respond to aggressive local wound care
pneumomediastinum and pose an increased risk of should be treated with systemic antibiotics.
infection through bacterial contamination.
ASPIRATION. Aspiration following tracheostomy is a
PNEUMOTHORAX. Pneumothorax occurs in less than phenomenon that is often overlooked. Although a
5% of tracheostomies and can result from damaging tracheostomy is generally thought to “protect” the
the pleural apices during dissection that veers away airway, tracheostomies have actually been shown to
from the midline. Pneumothorax may also be caused decrease the protective glottic closure reflexes of
by excessively forceful ventilation that prevents the both the true and false vocal cords.16 Loss of this
passive exhalation of air. This air trapping can lead to protective mechanism does predispose the tra-
alveolar rupture and the entrance of air into the pleu- cheostomized patient to aspiration and concomitant
ral space. A misplaced tracheostomy tube can also pneumonia. Prophylactic measures include a soft,
introduce air into the pleural space or mediastinum. solid diet, which poses a decreased risk of aspiration
Decreased breath sounds may indicate a pneumoth- when compared to liquids, and maintaining the
orax, although this complication is usually asympto- patient in a somewhat upright position. Although
matic and noted incidentally on the postoperative inflating the tracheostomy tube cuff can afford tem-
chest radiograph. A small pneumothorax is generally porary airway protection, hyperinflation of the cuff
observed with serial chest radiographs, whereas a actually exacerbates aspiration owing to compres-
large or symptomatic pneumothorax may require a sion of the esophagus. Consultation with a speech
chest tube for lung re-expansion. and swallowing therapist is advisable for any patient
who requires a tracheostomy.
LATE COMPLICATIONS. INNOMINATE ARTERY RUPTURE.
GRANULOMA FORMATION. Granulation tissue may
Innominate artery rupture is perhaps the most
form in the peristomal area owing to chronic
dreaded tracheostomy complication and, although
mucosal and skin irritation by an inadequately fixed
rare, results in only a 10 to 25% survival rate.15
or improperly fitted tracheostomy tube. Granulation
Innominate artery rupture is heralded by a “sentinel
tissue may also form inside the tracheal lumen. Early
bleed,” which is a brief episode of bleeding occurring
and small granulomas may be managed with local
minutes to hours prior to a massive hemorrhage.
débridement. Mature, fibrotic lesions generally
Rapid peristomal bleeding, even when it resolves,
require endoscopic laser excision.
should trigger a fiber-optic examination of the tra-
chea to rule out innominate artery involvement. SUBGLOTTIC STENOSIS. Tracheostomies may con-
When massive bleeding does occur, the tracheostomy tribute to subglottic stenosis by causing chronic irri-
tube should be rapidly replaced with a longer cuffed tation to the tracheal mucosa while also providing a
endotracheal tube to allow oxygenation while digital route of bacterial contamination that causes
Airway Control and Laryngotracheal Stenosis in Adults 1159
increased inflammation in the damaged area. This standard tracheostomy performed in the controlled
inflammation results in the formation of scar tissue environment of the operating room.
and subsequent subglottic stenosis. Gastroeso- An additional disadvantage of percutaneous
phageal reflux is also felt to increase the risk of sub- tracheostomy is the risk of tracheal or subglottic
glottic stenosis by providing additional mucosal stenosis. Unlike soft tissue, cartilage is rigid and
irritation that contributes to granulation and scar incapable of changing shape and conforming to the
tissue formation. The risk of this complication shape of a dilator. Because of the progressive dila-
underscores the importance of minimizing extrane- tions performed during percutaneous tracheos-
ous motion of the tracheostomy tube, managing tomies, the tracheal cartilages are at high risk for
gastroesophageal reflux, and removing a tra- crush injury during the procedure. Damaged carti-
cheostomy tube when it is no longer required for air- lage poses a risk of scar tissue formation and subse-
way support and protection. quent tracheal or subglottic stenosis.
Since a percutaneous tracheostomy must
sometimes be converted to a standard open tra-
PERCUTANEOUS TRACHEOSTOMY cheostomy, a surgical tracheostomy tray and someone
Although percutaneous tracheotomy was first with the ability to perform a standard tracheostomy
described in 1955,17 it experienced a resurgence in should be present at the time of the percutaneous
popularity after its reintroduction by Ciaglia and procedure. With these precautions and adequate
colleagues in 1985.18 The technique involves the training, percutaneous tracheostomy can be a safe
transcervical insertion of a guidewire into the air- and efficient procedure.
way followed by blunt dilation of the guidewire
tract. The tracheostomy tube is inserted over the
guidewire using a modified Seldinger technique. The
OPEN BEDSIDE TRACHEOSTOMY
advantage of the procedure is that it can be per- A tracheostomy can also be performed in the intu-
formed at the bedside in the intensive care unit.19 bated patient as an open procedure at the bedside
Visualization of the guidewire insertion, dilation, in the intensive care unit setting.23 The only advan-
and tracheostomy tube placement may be achieved tage of performing a tracheostomy at the bedside is
via a flexible fiber-optic laryngoscope inserted at the that operating room costs are defrayed and the
time of the procedure. This improved visualization procedure is generally less expensive than a percu-
decreases airway complications by preventing taneous tracheostomy. Obvious disadvantages are
improper placement of the guidewire or esophageal that lighting, surgical assistance, and equipment are
perforation by the inserting device or guidewire inferior to that available in a standard operating
itself.20 The proper level of tracheostomy placement room. Patients with unfavorable anatomy such as
may also be confirmed with airway visualization at cervical mass lesions or morbid obesity are not
the time of the procedure. good candidates for an open bedside tracheostomy
One major disadvantage of percutaneous tra- and should proceed to the operating room for a
cheostomy is that only a narrow, dilated tract, rather standard tracheostomy.
than a formal stoma, is created during the proce-
dure. This results in an increased rate of tube dis- LARYNGEAL AND TRACHEAL
placement and difficult tube reinsertion with
percutaneous tracheostomy as compared with a
STENOSIS IN THE ADULT
standard tracheostomy.21 An increased rate of post- The management of laryngeal and tracheal stenosis
operative death owing to tube dislodgment has been in adults is both challenging and intriguing. The
described with the percutaneous technique.22 The diagnosis and evaluation of these lesions requires a
surgeon may wish to consider this factor in planning complete mastery of the anatomy and physiology of
a tracheostomy procedure on a patient who is the upper aerodigestive tract. The incredible vari-
known to be difficult to intubate translaryngeally. ability of stenotic areas in the adult larynx and tra-
Likewise, a patient with morbid obesity or cervical chea requires the head and neck surgeon carefully to
anatomic anomalies is not a good candidate for per- individualize treatment and provide unique strate-
cutaneous tracheostomy and should likely undergo a gies for the management of these diverse lesions.
1160 Ballenger’s Otorhinolaryngology
the tube may be plugged. Symptoms of aspiration, trapdoor technique, or serial dilation with radial
voice change, or dysphagia may indicate the degree incisions of the stenotic segment. Intralesional cor-
of glottic involvement. ticosteroids may also be injected under endoscopic
The entire upper aerodigestive tract must be guidance.25 Lasers allow the precise treatment of tis-
carefully examined in a patient with suspected LTS. sue throughout the airway while avoiding external
Indirect laryngoscopy and flexible fiber-optic laryn- incisions and providing an excellent method of cut-
goscopy offer critical information regarding the ting, coagulating, or vaporizing tissue. Hemostasis
supraglottic airway and mobility of the true vocal may be achieved, and perioperative edema is often
folds. In extreme abduction, areas of subglottic decreased with the use of lasers owing to smaller
stenosis may be visible using these techniques. amounts of tissue sustaining thermal damage when
Video documentation of these procedures offers a compared to electrocautery.
valuable method of treatment planning and patient The ideal laser for any particular case depends
education.24 on the type of tissue and lesion that requires treat-
Although imaging studies such as airway ment. Owing to its precision (the small spot size)
radiographs, computed tomography, and magnetic and availability, the carbon dioxide laser, which pro-
resonance imaging occasionally provide useful duces light in the mid-infrared region, remains the
information, the most valuable diagnostic assess- instrument of choice in the endoscopic management
ment stems from the examination of the patient by of LTS. Although the carbon dioxide laser is very
endoscopy. After the patient has been examined by precise, it is not a good instrument for coagulation
indirect laryngoscopy and flexible fiber-optic tech- and can only be used to coagulate vessels up to
niques, rigid endoscopic evaluation under general 0.5 mm in diameter. If the area of stenosis is thought
anesthesia should be performed in all patients with to be very vascular, a laser with better hemoglobin
symptomatic airway abnormalities. Direct measure- absorption, such as a KTP or Nd:YAG laser, would
ment and documentation of the diameter and length be recommended. One further disadvantage of the
of stenotic areas are critical steps in the management carbon dioxide laser is that it lacks a good fiber-
of these lesions. Measurement of the diameter of optic delivery system and must generally be con-
stenotic segments is best evaluated by passing an trolled via a micromanipulator system mounted on
endoscope, with a known diameter, that just fits a microscope.
through the stenotic area. Measurement of stenosis Laser ablation of stenosis is a useful technique
length may be performed by placing the endoscope that may be combined with dilation of the stenotic
at the distal end of the stenotic segment and mark- segment or placement of an intraluminal stent. This
ing the instrument at the incisors. The endoscope is procedure is most successful in the management of
withdrawn to the proximal aspect of the stenosis and early lesions composed mostly of granulation tissue
remarked. The length of stenosis may be measured that have not yet evolved into a mature scar. Stenotic
on the endoscope. segments less than 1 cm in length may also be
addressed with this method.
The microtrapdoor technique is used to debulk
TREATMENT OF LARYNGOTRACHEAL STENOSIS stenotic areas confined to a single quadrant of the
airway. The procedure is somewhat more technically
Medical Most surgeons who treat LTS recommend demanding than simple ablation of the stenosis.
the use of antibiotics, local and/or systemic corticos- First, a laser incision is made on the superior aspect
teroids, and histamine2 antagonists or omeprazole of the stenotic shelf (Figure 50–8). Once the incision
when treating mild or acute subglottic injuries. In has been made, a microelevator is used to elevate a
mature areas of laryngotracheal fibrosis and scar- mucosal flap over the area of scar tissue. The laser
ring, these medical treatments are unlikely to result may be used to vaporize the scar tissue forming the
in any clinical improvement. stenosis. Once the scar tissue has been adequately
vaporized, the flap is repositioned into its original
Endoscopic Some areas of LTS are amenable to location. The laser may be defocused and milliwatt
endoscopic treatment techniques such as laser power settings used to weld the edges of the incision
vaporization and dilation, excision using a micro- together.
1162 Ballenger’s Otorhinolaryngology
resection of scar tissue, however, is generally safe and used source of grafts. The fifth or sixth costal carti-
does not increase the risk of restenosis. lage is harvested with the anterior perichondrium
A posterior graft, if it must be used, is placed intact. The grafts are carved to the appropriate
next. Posterior grafts usually contain a flange that is shape, with the perichondrium facing the airway
tucked behind the posterior lamina of the cricoid lumen. The hyoid bone may also be harvested
cartilage bilaterally to prevent extrusion into the air- through the existing cervical incision and used as an
way. An airway stent, if one is to be placed, is interposition graft, which offers the advantage of
inserted after placement of the posterior cricoid avoiding the need to prepare a second operative area.
graft. The anterior cartilage graft is generally cut in The central portion of the hyoid bone between the
a fusiform or boat-shaped fashion with beveled lesser cornua may be used as a free graft and fixed
edges to prevent the graft from slipping into the air- into place. The hyoid bone has also been used as a
way. The graft is sutured into place while taking pedicled graft based inferiorly on the sternohyoid
great care to ensure that the sutures remain extralu- muscle.28
minal. The strap muscles are reapproximated in the
midline, and the platysma and skin are closed over a Tracheal Resection and Reanastomosis Areas of
passive drain to allow air egress and prevent subcu- cervical tracheal stenosis up to about 5 cm can
taneous emphysema. The success rate of primary generally be excised, and the proximal and distal tra-
laryngotracheal reconstruction in adults is in the 60 cheal segments reanastomosed primarily. A suprahy-
to 70% range.27 oid laryngeal release may be required to allow for
Cartilage grafts for laryngotracheoplasty may closure under minimal tension. When performing
be harvested from the costal cartilage or nasal septal this procedure, the surgeon must keep in mind the
cartilage. Costal cartilage is the most commonly age and body habitus of the patient. Older patients
1164 Ballenger’s Otorhinolaryngology
reconstruction of a complex LTS.31 At this point, the vocal folds on phonation or normal abduction with
usefulness of microvascular free flaps appears to be inspiration. However, denervation of the larynx may
limited to a subset of complex cases not amenable to also limit the normal mobility of the arytenoids.
more conventional surgical techniques. In the patient with suspected cricoarytenoid
joint dysfunction, the differential diagnosis is three-
fold. First, the posterior cricoarytenoid muscle may
CRICOARYTENOID JOINT FIXATION be denervated. Second, the arytenoid cartilage may
The cricoarytenoid joint is a synovial joint formed be dislocated. A history of trauma should be care-
by the articulation of the arytenoid cartilage with fully elicited in this group of patients. Finally, the
the posterosuperior aspect of the cricoid cartilage. joint may be fixed because of an inflammatory con-
The vocal process of the arytenoid cartilage is usu- dition. The proper location and mobility of the
ally free to rotate in three dimensions to allow cricoarytenoid joint are best assessed under general
proper apposition of the true vocal folds. This nor- anesthesia by gently rocking the arytenoid cartilage
mal mobility of the arytenoids can be impaired by back and forth. A “fixed” cricoarytenoid joint can be
several factors. Dislocation of the arytenoid cartilage diagnosed with this method. An electromyogram of
may occur due to either external trauma or intuba- the intrinsic laryngeal musculature can determine if
tion. The arytenoid may be dislocated anteriorly or the immobility is caused by denervation or is sec-
posteriorly, with anterior dislocation being slightly ondary to fixation of the cricoarytenoid joint. A
more common owing to the force vector exerted by careful history aids in the diagnosis of a systemic
the blade of a laryngoscope. Several inflammatory inflammatory condition.
disorders such as rheumatoid arthritis and gout may The treatment of cricoarytenoid joint dysfunc-
also involve the cricoarytenoid joint and result in an tion must be carefully individualized to the patient
abnormal “fixation” of the joint. Inflammatory dis- and the disease process. A patient with an inflamma-
orders can result in unilateral or bilateral cricoary- tory disease should be treated medically with the aid
tenoid joint dysfunction. With cricoarytenoid of a rheumatologist. Stable patients who are able to
arthritis, the patient generally presents with symp- phonate, breathe, and swallow well without aspira-
toms of stridor and dyspnea with a variable degree tion may be safely observed. Unstable patients or
of dysphonia.32 The dysfunction results from fixing patients who do not improve on medical and reha-
of the vocal cords in the paramedian position and bilitative strategies must be treated surgically. Patients
the inability to achieve normal apposition of the true with inadequate ventilation may undergo a tra-
1166 Ballenger’s Otorhinolaryngology
11. American College of Surgeons. Advanced trauma 24. Duncavage JA, Koriwchak MJ. Open surgical tech-
life support for doctors 1997. 6th ed. Chicago: First niques for laryngotracheal stenosis. Otolaryngol Clin
Impression; 1997. North Am 1995;28:785–95.
12. Jackson C. Tracheotomy. Laryngoscope 1909;18:285. 25. Coleman JA, Van Duyne JA, Ossoff RH. Laser treat-
13. Jackson C. High tracheotomy and other errors: the ment of lower airway stenosis. Otolaryngol Clin
chief causes of chronic laryngeal stenosis. Surg North Am 1995;28:771–83.
Gynecol Obstet 1921;32:382–98. 26. McCaffrey TV. Management of subglottic stenosis
14. Reilly H, Sasaki CT. Tracheotomy complications. In: in the adult. Ann Otol Rhinol Laryngol 1991;100:
Complications in head and neck surgery. Philadel- 90–4.
phia: WB Saunders; 1993. p. 257–74. 27. Lano CF, Duncavage JA, Reinisch L, et al. Laryngo-
15. Jones JW, Reynolds M, Hewitt RL, Drapanas T. Tra- tracheal reconstruction in the adult: a ten year
cheoinnominate artery erosion: successful surgical experience. Ann Otol Rhinol Laryngol 1998;107:
management of a devastating complication. Ann 92–7.
Surg 1977;184:194–204. 28. Ward PH, Canalis R, Fee W. Composite hyoid ster-
16. Sasaki CT, Suzuki M, Horiuchi M, Kirchner JM. The nohyoid muscle grafts in humans. Arch Otolaryngol
effect of tracheostomy on the laryngeal closure 1977;103:531–4.
reflex. Laryngoscope 1977;87:1428–33. 29. Laccourreye O, Brasnu D, Cauchois R, et al. Tra-
17. Sheldon CH, Pudenz RH, Freshwater DB. A new cheal resection with end-to-end anastomosis for
method of tracheotomy. J Neurosurg 1955;12:428. isolated postintubation cervical trachea stenosis:
18. Ciaglia P, Firsching R, Syniec C. Elective percuta- long-term results. Ann Otol Rhinol Laryngol 1996;
neous dilatational tracheostomy. A new simple bed- 105:944–8.
side procedure; preliminary report. Chest 1985; 30. Kunachak S, Kulapaditharom B, Vajaradul Y,
87:715–9. Rochanawutanon M. Cryopreserved, irradiated tra-
19. Massick DD, Powell DM, Price PD, Chang SL. Quan- cheal homograft transplantation for laryngotracheal
tification of the learning curve for percutaneous reconstruction in human beings. Otolaryngol Head
dilatational tracheotomy. Laryngoscope 2000;110: Neck Surg 2000;122:911–6.
222–8. 31. Esclamado RM, Carroll WR. Repair of a complete
20. Donaldson DR, Emami AJ, Wax MK. Endoscopically glottic-subglottic stenosis with a fibular osseocuta-
monitored percutaneous dilational tracheotomy neous free flap. Arch Otolaryngol Head Neck Surg
in a residency program. Laryngoscope 2000;110: 1997;123:877–9.
1142–6. 32. Gacek RR, Gacek MR, Montgomery WW. Evidence
21. Graham JS, Mullory RH, Sutherland FR, Rose S. Per- for laryngeal paralysis in cricoarytenoid joint arthri-
cutaneous versus open tracheostomy: a retrospective tis. Laryngoscope 1999;109:279–83.
cohort outcome study. J Trauma 1996;42:245–50. 33. Laccourreye O, Paz Escovar MI, Gerhardt J, et al.
22. Dulguerov P, Gysin C, Perneger TV, Chevrolet JC. CO2 laser endoscopic posterior partial transverse
Percutaneous or surgical tracheostomy: a meta- cordotomy for bilateral paralysis of the vocal fold.
analysis. Crit Care Med 1999;27:1617–25. Laryngoscope 1999;109:415–8.
23. Wang SJ, Sercarz JA, Blackwell KE, et al. Open bed- 34. Ossoff RH, Duncavage JA, Shapshay SM, et al. Endo-
side tracheotomy in the intensive care unit. Laryn- scopic laser arytenoidectomy revisited. Ann Otol
goscope 1999;109:891–3. Rhinol Laryngol 1990;99:764–71.
CHAPTER 51
ETIOLOGY and neck are pulled forward while the thorax is held
in restraint. The larynx is decelerated against blunt
The position of the larynx in the neck, protected by
objects, such as the steering wheel and dashboard,
the mandible superiorly and the clavicles and ster-
and is crushed against the vertebral column. Similar
num below, shields it from falls and blows. The lateral
mechanisms of injury may occur in sporting acci-
mobility of the larynx within the neck also serves to
dents (ie, karate, hockey, basketball, Frisbee throw-
prevent the severe effects of compression injuries.
ing, water skiing). In laryngeal trauma, the severity
The ossification centers of the larynx do not develop
of the injury is dependent on the velocity and site of
until young adulthood and are more pronounced in
injury. In mild cases, the patient may not report the
the male. This makes laryngeal fractures a rare con-
injury for many days. Severe injuries may result in
dition, one more often seen in men than in women.
catastrophic asphyxia in the field.
Although the cartilaginous framework pro-
The other major causes of blunt trauma to the
vides protection to the larynx, once this framework
larynx are of the “clothesline” type. The injury may
has been violated by trauma, the tight space defined
be caused by a clothesline, chain, or tree branch.
by the laryngeal skeleton makes rapid airway com-
Injures of this type occur when the anterior part of
promise possible. The tight adherence of the soft tis-
the neck strikes one of these objects while bicycling,
sue to the laryngeal framework and the potential
snowmobiling, or riding in all terrain vehicles.
spaces that can be easily expanded at the expense of
Clothesline injuries tend to be more severe because
the airway make rapid changes in the airway status
of the high impact of the force and therefore require
possible in patients with laryngeal trauma.
special attention. In clothesline injuries, the possi-
External laryngeal trauma is a relatively
bility of cricotracheal separation is a special concern.
uncommon injury. Jewett et al reported an incidence
It appears that the larynx cannot be fractured
of blunt trauma to the larynx of 1 in 137,000 in an
by concussion unless it is supported to some extent
analysis of 54 million inpatients over a 5-year period
by the vertebral column. Furthermore, a blow to the
in 11 US states.1 Laryngeal trauma accounts for
neck will do relatively little damage to the laryngeal
about 1 in every 25,000 emergency department vis-
skeleton if the laryngeal cartilage is soft and pliable.
its. In addition to the obvious possibility of acute
The cartilage may spring back into position without
airway obstruction, the complications of late diag-
fracture. Such injury will result in soft tissue edema
nosed or undiagnosed laryngeal injuries can be
and hematoma. Soft tissue disruption may result in
severe, including glottic insufficiency, aspiration, and
edema and hematoma severe enough to interrupt
laryngeal stenosis. Furthermore, studies have
the airway or cause dysphonia and stridor. Rapid
demonstrated that early diagnosis and surgical man-
acceleration and deceleration of the soft tissue of the
agement result in improved functional outcomes.1,2
larynx may result in arytenoid ca