4

Disturbances of
Vision
CONTENTS
Approach to diagnosis,
125
Functional anatomy of the
visual system, 126
Functional anatomy of the
ocular motor system,
127
History, 130
Neuroophthalmologic examination, 131

Disorders of the visual system,

144
Monocular disorders, 144
Binocular disorders, 145
Disorders of ocular motility,
146
Gaze palsy, 146
Internuclear ophthalmoplegia, 147
Oculomotor (III) nerve
lesions, 148

Trochlear (IV) nerve lesions,

148
Abducens (VI) nerve lesions,
148
Diabetic ophthalmoplegias,
150
Painful ophthalmoplegias,
150
Myasthenia gravis, 150
Ocular myopathies, 150

KEY CONCEPTS
Examination of the visual system should be part
of even the briefest neurologic examination as it
tests the function of much of the brainstem and
cerebral hemispheres.

Ptosis (drooping of the eyelid) from oculomotor

(III) nerve palsy is complete, but ptosis from sympathetic denervation of the eyelid (Horner syndrome) is only partial.

Test extraocular muscle function (eye movements) in the direction of action of the individual
muscles.

Transient monocular blindness is associated with

an increased risk of subsequent stroke.

In assessing a swollen optic disk, papilledema (a

sign of increased intracranial pressure) is bilateral
and painless, whereas papillitis (a sign of optic
nerve inammation, as in multiple sclerosis) is
unilateral and painful.

Gaze preference is directed toward the lesion

(and away from the hemiparesis) when caused by
a hemispheric lesion, but away from the lesion
(and toward the hemiparesis) when caused by a
brainstem lesion.

Because the anatomic pathways of the visual

and ocular motor systems traverse major porAPPROACH TO DIAGNOSIS
tions of the brainstem and cerebral hemispheres, neuroophthalmologic signs are often of great
Disorders that affect the ocular muscles, cranial value in the anatomic localization of neurologic
nerves, or visual or ocular motor pathways in the disease,
brain produce a wide variety of neuroophthalmologic
which in turn suggests possible etiologies. Symptoms
most commonly involve vision (disorders of visual
disturbances.
125
Copyright 2005, 2002 by The McGraw-Hill Companies, Inc. Click here for terms of use.

126 / CHAPTER 4
pathways) or eye movements (disorders of ocular
motility) or both.

FUNCTIONAL ANATOMY
OF THE VISUAL SYSTEM
Reception of Visual Information

Posterior

Optic tract

Optic chiasm

Visual information enters the nervous system when

Optic nerve
light, refracted and focused by the lens, creates a
Anterior
visual
image on the retina at the posterior pole of the eye
(Figure 41). The action of the lens causes this image
to be reversed in the horizontal and vertical planes.
Retina
Thus, the superior portion of the visual image falls on
the inferior retina and vice versa, and the temporal
(latST
SN
eral) and nasal (medial) elds are likewise reversed
(FigVisual fields
ure 42). The center of the visual eld is focused at
the
fovea,
where the retinas
sensitivity is IT
Pointperceptual
of fixation
IN
Physiologic
greatblind spot
Figure 42. Representation of the visual eld at the
est. Within the retina, photoreceptor cells (rods and
18

Temporal
visual
field

Nasal
visual
field

13

Temporal
retina

Nasal
retina

level of the optic nerve, chiasm, and tract. Quadrants of

the visual eld are designated ST (superior temporal), IT
(inferior temporal), SN (superior nasal), and IN (inferior
nasal).

cones) transduce incident light into neuronal

impulses,
which are transmitted by retinal neurons to the optic
(II) nerve. At this and all other levels of the visual system, the topographic relations of the visual eld are
preserved.

Peripheral Visual Pathways

Each optic nerve contains bers from one eye, but as
shown in Figure 42, the nasal (medial) bers,
conveying information from the temporal (lateral) visual
elds, cross in the optic chiasm. As a result, each
optic
tract contains bers not from one eye but from one
half of the visual eld. Because of this arrangement,
prechiasmal lesions affect vision in the ipsilateral eye
Fovea
and retrochiasmal lesions produce defects in the conOptic disk
The
opticVisual
tracts
terminate
theoflateral
geniculate
tralateral
half
ofPathways
the visual in
eld
both eyes.
Central
Optic nerve
nuclei, where their neurons synapse on neurons that
Figure 41. Representation of the visual eld at the
projlevel of the retina.The point of xation is focused on
ect through the optic radiations to the primary visual
the fovea, the physiologic blind spot on the optic disk,
the temporal half of the visual eld on the nasal side of or calcarine cortex (area 17), located near the
the retina, and the nasal half of the visual eld on the posterior
poles of the occipital lobes, and visual association
temporal side of the retina.
areas
(areas 18 and 19). Here, too, the visual image is
represented in such a way that its topographic
organization

DISTURBANCES OF VISION / 127

is preserved (Figure 43). The central region of theC.vi-OPTIC RADIATIONS
sual eld (macula) projects to the most posterior porAs the optic radiations course backward toward the
tion of the visual cortex, while the inferior and
visuperior
sual cortex, they are supplied by branches of the
parts of the eld are represented above and belowmiddle
the
cerebral artery. Ischemia or infarction in the distribucalcarine
ssure,
respectively.
tion of the middle cerebral artery may thus cause loss
Vascular Supply
D.
of PRIMARY VISUAL CORTEX
The vascular supply of the visual system is derivedThe
principal
source of arterial
vision
in the contralateral
visualblood
eld.for the primary
from
visual cortex is the posterior cerebral artery.
the ophthalmic, middle cerebral, and posterior
Occlusion
cerebral
of one posterior cerebral artery produces blindness in
arteries (Figure 44); thus, ischemia or infarction inthe contralateral visual eld, although the dual
the
A.
RETINA of any of these vessels can produce visual(middle
territory
and
The
a posterior cerebral) arterial supply to the macular
eldretina is supplied by the central retinal artery,rebranch
defects.of the ophthalmic artery that, in turn,
gion of the visual cortex (Figures 43 and 44) may
branches
spare central (macular) vision. Because the posterior
from the internal carotid artery. Because the central
cerebral arteries arise together from the basilar
retinal artery subsequently divides into superior and
artery,
inocclusion at the tip of the basilar artery can cause
ferior retinal branches, vascular disease of the retina
FUNCTIONAL
ANATOMY OF THE OCULAR
bilattends to produce altitudinal (ie, superior or inferior)
MOTOR
SYSTEM
eral occipital
infarction and complete cortical blindB.
vi- OPTIC NERVE
Extraocular
Muscles
nessalthough,
in some cases, macular vision is
The optic
nerve receives arterial blood primarily from
sual
eld decits.
spared.
the ophthalmic artery and its branches.
Movement of the eyes is accomplished by the
action of six muscles attached to each globe
(Figure 45A). These muscles act to move the
eye into each of six cardinal positions of gaze (Figure
45B and C). Equal and opposed actions of these six
muscles in the resting state place the eye in mid or
primary position, ie, looking directly forward. When the
function of one extraocular muscle is disrupted, the
eye
is unable to move in the direction of action of the affected muscle (ophthalmoplegia) and may deviate in
the opposite direction because of the unopposed
action
of other extraocular muscles. When the eyes are thus
misaligned, visual images of perceived objects fall on
Cranial Nerves
a
different region of each retina, creating the illusion of
The extraocular muscles are innervated by the oculodouble vision, or diplopia.
motor (III), trochlear (IV), and abducens (VI) nerves.
Upper peripheral quadrant of retina
Because of this differential innervation of the ocular
muscles, the pattern of their involvement in
Upper quadrant of macula
pathologic
conditions can help to distinguish a disorder of the
Lower quadrant of macula
ocLower peripheral quadrant of retina
ular muscles per se from a disorder that affects a
cranial
Figure 43. Representation of the visual eld at the nerve. Cranial nerves that control eye movement tralevel of the primary visual cortex, midsagittal view,
verse long distances to pass from the brainstem to
shows the medial surface of the right occipital lobe,
A.
theNERVE III
which receives visual input from the left side of the
The
nerve rendered
supplies the
medial rectus,
eye;oculomotor
they are thereby
vulnerable
to injury
visual eld of both eyes.
supeby a
rior
andof
inferior
rectus,
and inferior oblique muscles
variety
pathologic
processes.

128 / CHAPTER 4

Optic nerve

Left eye

Ciliary arteries
Central retinal artery
Ophthalmic artery
Optic chiasm
Internal carotid artery

Middle cerebral artery

Optic tract

Anterior choroidal artery

Basilar artery
Posterior cerebral artery
Lateral geniculate body

Optic radiations

Deep branch of
middle cerebral artery

Occipital cortex

Figure 44. Arterial supply of the visual system, viewed from below.
and carries bers to the levator palpebrae (which aqueduct (of Sylvius), while the abducens nerve nuraises
cleus occupies a similarly dorsal and periventricular
the eyelid). It also supplies the parasympathetic pobers
sition in the pons.
responsible for pupillary constriction. With a complete
Lesions involving these nuclei give rise to clinical
nerve III lesion, the eye is partially abducted and abnormalities similar to those produced by involvethere
ment of their respective cranial nerves; in some
B.
N
ERVE IV
is an inability to adduct, elevate, and depress the cases,
The
eye;trochlear nerve innervates the superior oblique
nuclear
nerve lesions can be distinguished.
A.
NERVE and
III NUCLEUS
muscle.
Lesions
this nerve
in defective
the eyelid
droopsof(ptosis),
andresult
the pupil
is
While each oculomotor nerve supplies muscles of the
depresnonreactive.
ipsilateral eye only, bers to the superior rectus origision of the adducted eye.
nate in the contralateral oculomotor nerve nucleus,
C. NERVE VI
Lesions of the abducens nerve cause lateral rectusand the levator palpebrae receives bilateral nuclear
inpalsy,
nervation. Thus, ophthalmoplegia affecting only one
with impaired abduction of the affected eye.
eye with ipsilateral ptosis or superior rectus palsy
Cranial Nerve Nuclei
sugThe nuclei of the oculomotor and trochlear nerves gests
are oculomotor nerve disease, whereas ophthalmoplegia
accompanied by bilateral ptosis or a contralatlocated in the dorsal midbrain, ventral to the cerebral
eral superior rectus palsy is probably due to a nuclear
lesion.

DISTURBANCES OF VISION / 129

Trochlea
Superior oblique
Superior rectus
Levator

51

23

External rectus
Inferior rectus
A

Inferior oblique

Superior
rectus

Inferior
oblique

Lateral
rectus

Medial
rectus

Inferior
rectus

Superior
oblique

Figure 45. A: The origin and insertions of the extraocular muscles in the right orbit. B: An illustration of the right
eye viewed from above in the primary position (center gure) showing the angle of attachment of the superior
and
inferior rectus muscles and the superior and inferior oblique muscles. With the eye directed to the right, the
superior
and inferior rectus muscles can now be examined as pure elevators and depressors of the globe (right image) and
with the eye deviated to the left, the oblique muscles can now be examined as pure elevators and depressors of
the
globe as illustrated in C. C: The six cardinal positions of gaze for testing the function of the extraocular
muscles.The
eye is adducted by the medial rectus and abducted by the lateral rectus.The adducted eye is elevated by the
inferior
oblique
depressed
by the superior oblique; the abducted
eye
is elevated
by the
superior
rectus and
B.
NERVEand
IV N
UCLEUS
center,
and
ascending
reticular
activating
system, redepressed
It is not possible to distinguish clinically between lespectively.
by theof
inferior
rectus. nerve and those of its nucleus.
sions
the trochlear

C. NERVE VI NUCLEUS
Supranuclear Control of Eye Movements
In disorders affecting the abducens nerve nucleus
Supranuclear control of eye movements enables the
rather
than the nerve itself, lateral rectus paresis is oftentwo
eyes to act in concert to produce version (conjugate
associated with facial weakness, paresis of ipsilateral gaze)
A.
RAINSTEM GAZE CENTERS
or B
vergence
(convergence and divergence)
conjuCenters that control horizontal and vertical gaze are
gate gaze, or a depressed level of consciousness. movements.
loThis is
cated in the pons and in the pretectal region of the
because of the proximity of the abducens nerve
nucleus
to the facial (VII) nerve fasciculus, pontine lateral
gaze

130 / CHAPTER 4
midbrain, respectively, and receive descending inputs
terferes with the mechanism for contralateral
from the cerebral cortex that allow voluntary control
horizontal
of
gaze and may result in a gaze preference toward the
gaze (Figure 46). Each lateral gaze center, located
side
in
the paramedian pontine reticular formation (PPRF)of the lesion (and away from the side of associated
adhemiparesis). By contrast, an irritative (seizure) focus
jacent to the abducens nerve nucleus, mediates in
ipsilatthe frontal lobe may cause gaze away from the side
HISTORY
eral conjugate horizontal gaze via its connections to
of
Nature
of(see
Complaint
the
the focus
Figure 419).
ipsilateral abducens and contralateral oculomotor
The rst step in evaluating a neuroophthalmologic
nerve
B.
CORTICAL
INPUT in the pons affecting the PPRF theredisnucleus.
A lesion
The
PPRF
receives
cortical
input
from
the
order is to obtain a clear description of the complaint.
fore produces a gaze preference away from the side
contralateral
Patients often complain only of vague symptoms,
of
frontal
lobe,
which
regulates
rapid
eye
movements
the lesionand toward the side of an associated such
(sacas blurred vision, which provide little diagnostic inforhemicades),
and
from
the
ipsilateral
parietooccipital
lobe,
mation. An attempt must be made to determine
paresis, if present.
which regulates slow eye movements (pursuits). exactly
Therewhat the patient means to conveydecreased visual
fore, a destructive lesion affecting the frontal cortex
acuity in one or both eyes, loss of vision in part of the
Left frontal
in- eye field
Voluntary gaze
to right

Medial rectus

Lateral rectus

Oculomotor (III) nerve

Oculomotor (III) nucleus

Medial longitudinal
fasciculus
Paramedian pontine
reticular formation

Abducens (VI)
nerve
Abducens (VI)
nucleus

Figure 46. Neuronal pathways involved in horizontal gaze.

DISTURBANCES OF VISION / 131

visual eld, diplopia, an unstable visual image, pain
NEUROOPHTHALMOLOGIC
in
EXAMINATION
or about the eye, or some other problem.
Visual Acuity

Temporal Pattern of Symptoms

A. ASSESSMENT
Once the nature of the complaint has been
To assess visual acuity from a neurologic standpoint,
established,
viinquiries regarding its temporal pattern can provide
sion is tested under conditions that eliminate
clues to the underlying pathologic process.
A. SUDDEN ONSET
refractive
Vascular disorders that affect the eye or its
errors. Therefore, patients who wear glasses should
connections
be exin the brain tend to produce symptoms of sudden amined while wearing them (a pinhole can be
onset.
substituted
B. SLOW ONSET
if the corrective lenses usually worn are not available
With inammatory or neoplastic disease, symptoms
at
usually evolve over a longer period.
the time of testing). Visual acuity must be assessed
for
C. TRANSIENT, RECURRENT SYMPTOMS
B.
RECORDING
each
eye separately. Distant vision is tested using a
Symptoms that are transient and recurrent suggest
a
Visual
acuity is expressed as a fraction (eg, 20/20,
Snellen
se20/40,
eye chart, with the patient 6 m (20 ft) away. Near
lect group of pathologic processes, including
20/200).
The numerator is the distance (in feet) from
vision
ischemia,
the
test
gures
at Rosenbaum
which the examination
is tested with the
pocket eye is
chart held
multiple sclerosis, and myasthenia gravis.
performed,
about
Associated Neurologic Abnormalities
and
the(14
denominator
the distance
(incase,
feet) the
at which
36 cm
in) from theispatient.
In each
The nature of any associated neurologic
gures
of
a
given
size
can
be
correctly
identied
by
smallest
abnormalities,
perline of print that can be read is noted.
suchhistory
as impaired
sensation,for
weakness,
ataxia,
The
shouldfacial
be scrutinized
conditions
sons with normal vision. For example, if a patient
or predispose the patient to neuroophthalmologic
that
standaphasia,
problems.can be valuable in localizing the anatomicing 20 ft away from the eye chart is unable to identify
site
Multiple
sclerosis often involves the optic nerve gures
or
that can normally be seen from that distance
Medical
History
of
involvement.
brainstem,
leading to a variety of
but
neuroophthalmologic
can identify the larger gures that would be visible 40
disorders. A history of disturbances that also involve
ft
other parts of the central nervous system should away with normal acuity, the visual acuity is recorded
suggest
as
this diagnosis.
20/40. If the patient can read most of a given line but
Atherosclerosis, hypertension, and diabetes canmakes
be
some errors, acuity may be recorded as
complicated by vascular disorders of the eye, cranial
20/401,
ED-GREEN C
OLOR VISION
nerves, or visual or ocular motor pathways in the C.
forRexample,
indicating
that all but one letter on the
Red-green
color correctly
vision is often
disproportionately
brain.
20/40 line were
identied.
When visual imEndocrine disorders (eg, hyperthyroidism) can paired
acuity in optic nerve lesions and can be tested with
colcause
is markedly reduced, it can still be quantied, though
ored
objects such
as pens
or hatpins
orat
with
color
viocular myopathy.
less precisely,
in terms
of the
distance
which
the
plates.
Connective tissue disease and systemic cancer sion
can
paaffect the visual and ocular motor systems at a
tient
can
count ngers (CF), discern hand movement
Visual
Fields
variety
(HM), or perceive light. If an eye is totally blind, the
Evaluating
the visual elds can be a lengthy and
of sites in the brain or subarachnoid space.
extedious
Patients with nutritional deciencies may present
amination will reveal no light perception (NLP).
procedure if conducted in an undirected fashion. Fawith neuroophthalmologic symptoms, as in the
miliarity with the common types of visual eld
amblydefects
opia (decreased visual acuity) associated with
is important if testing is to be reasonably rapid and
malnutriyield useful information. The most common visual
tion and the ophthalmoplegia of Wernicke enA.
EXTENT
OF VISUAL FIELDS
eld
abnormalities
are illustrated in Figure 47.
cephalopathy.
The normal monocular visual eld subtends an angle
Numerous drugs (eg, ethambutol, isoniazid, digiof
talis, clioquinol) are known to be toxic to the visual
about 160 degrees in the horizontal plane and about
system, and others (sedative drugs, anticonvulsants)
commonly produce ocular motor disorders.

132 / CHAPTER 4
Visual fields
Left
L

Temporal

Right
Nasal

Nasal

Temporal

Retina

1
Optic nerve

6
4
5

Optic tract

6
7

8
Lateral
geniculate
nucleus
7

Optic radiation

Occipital lobe
9

Figure 47. Common visual eld defects and their anatomical bases. 1. Central scotoma caused by
inammation
of the optic disk (optic neuritis) or optic nerve (retrobulbar neuritis). 2. Total blindness of the right eye from a complete lesion of the right optic nerve. 3. Bitemporal hemianopia caused by pressure exerted on the optic chiasm by
a
apituitary tumor. 4. Right nasal hemianopia caused by a perichiasmal lesion (eg,
calcied internal carotid artery).
5. Right homonymous hemianopia from a lesion of the left optic tract. 6. Right homonymous superior quadrantanopia caused by partial involvement of the optic radiation by a lesion in the left temporal lobe (Meyer loop).
i7. Right homonymous inferior quadrantanopia caused by partial involvement of the optic
radiation by a lesion in
the left parietal lobe. 8. Right homonymous hemianopia from a complete lesion of the left optic radiation. (A similar defect may also result from lesion 9.) 9. Right homonymous hemianopia (with macular sparing) resulting from
posterior cerebral artery occlusion.

DISTURBANCES OF VISION / 133

135 degrees in the vertical plane (Figure 48). With
iner uses the index ngers of either hand to locate
binocular vision, the horizontal range of vision
the
exceeds
boundaries of the patients eld, moving them slowly
180 degrees.
inB. PHYSIOLOGIC BLIND SPOT
ward from the periphery in all directions until the paWithin the normal eld of each eye is a 5-degree tient detects them. The boundaries are then dened
blind
more carefully by determining the farthest peripheral
spot, corresponding to the optic disk, which lacks resites at which the patient can detect slight
ceptor cells.
movements of
C. MEASUREMENT TECHNIQUES
the ngertips or the white head of a pin. The patients
Numerous techniques exist for measuring the visual
blind spot can be located in the region of the
eldwhich, like visual acuity, must be examined examiners
sepown blind spot, and the sizes of these spots can be
arately for each eye.
com1. The simplest method for visual eld testing ispared using a pin with a white head as the target.
the
The
confrontation technique (Figure 49). The examiner
procedure is then repeated for the other eye.
stands at about arm length from the patient, with the2. Subtle eld defects may be detected by asking
eyes of both patient and examiner aligned in the horithe
zontal plane. The eye not being tested is covered by
patient to compare the brightness of colored objects
the
presented at different sites in the eld or by
patients hand or an eye patch. The examiner closes
measuring
the
the elds using a pin with a red head as the target.
eye opposite the patients covered eye, and the
3. In young children, the elds may be assessed by
patient is
standing behind the child and bringing an attentioninstructed to x on the examiners open eye. Now getting
the
object, such as a toy, forward around the
monocular elds of patient and examiner are
childs
superimhead in various directions until it is rst noticed.
posed, which allows comparison of the patients eld4. A gross indication of visual eld abnormalities
with the examiners presumably normal eld. The may be obtained in obtunded patients by determining
examwhether they blink in response to a visual threat
60
Superior

typically the examiners ngerbrought toward the patients eye in various regions of the eld.

75
Inferior

100
Tempora

Figure 48. Normal limits of the visual eld.

60al
Nas

134 / CHAPTER 4

Figure 49. Confrontation testing of the visual eld. A: The left eye of the patient and the right eye of the
examiner
are aligned. B: Testing the superior nasal quadrant. C: Testing the superior temporal quadrant. D: Testing the
inferior
nasal quadrant.The procedure is then repeated for the patients other eye. E: Testing the inferior temporal
quadrant.

5. Although many visual eld decits are detectable

mologic disorders that affect the retina or optic disk
by these screening procedures, more precise
and in the evaluation of patients with a suspected inmapping of
crease in intracranial pressure. The examination
the elds requires the use of one of many perimetry
should be conducted in a dark room so that the
techniques: standard tangent screen testing or autopupils are dilated; in some patients, the use of mydrimated perimetry techniques.
atic (sympathomimetic or anticholinergic) eye drops
is necessary. In the latter case, visual acuity and
Ophthalmoscopy
pupillary reexes should always be assessed before
A. PREPARATION OF THE PATIENT
inOphthalmoscopic examination of the optic fundus stilling
is
the drops. Mydriatic agents should be avoided
particularly important in evaluating neuroophthal- in patients with glaucoma and in situationssuch as
impending or ongoing transtentorial herniationin

DISTURBANCES OF VISION / 135

which the state of pupillary reactivity is an important
communicates with the subarachnoid space,
guide to management.
disorders
associated with increased intracranial pressure that
B. EXAMINATION OF THE FUNDUS
also
Familiarity with the normal appearance of the opticobstruct the subarachnoid space, such as meningitis,
fundus (Figure 410) is necessary if abnormalities are
are less likely to cause papilledema. The ophthalmoto be appreciated.
scopic changes in papilledema typically develop over
1. Optic disk
days or weeks but may become apparent within
a. Normal appearanceThe optic disk is usuallyhours
easily recognizable as a yellowish, slightly oval
following a sudden increase in intracranial pressure
structure
as, for example, following intracranial hemorrhage. In
situated nasally at the posterior pole of the eye. The
early papilledema (Figure 411), the retinal veins aptemporal side of the disk is often paler than the nasal
pear engorged and spontaneous venous pulsations
side. The disk margins should be sharply demarcated,
are
though the nasal edge is commonly somewhat lessabsent. The disk may be hyperemic, and linear
dishemortinct than the temporal edge. The disk is normally rhages
in
may be seen at its borders. The disk margins
the same plane as the surrounding retina.
beb. Optic disk swellingAmong the many
come blurred, with the temporal edge last to be afophthalmoscopic ndings that provide useful
fected. In fully developed papilledema, the optic disk
diagnostic information, the abnormality thatis
most often requires prompt interpretation and attenelevated above the plane of the retina.
tion is optic nerve swelling (papilledema). Although c. Optic disk pallorOptic disk pallor with imthis condition implies increased intracranial pressure,
paired visual acuity, visual elds, or pupillary
it
reactivity
must be differentiated from swelling that is due tois associated with a wide variety of disorders that
other causes, such as local inammation (papillitis)
affect
and
the optic nerve, including inammatory conditions,
ischemic optic neuropathy. In making this distinction,
nutritional deciencies, and heredodegenerative disit is most helpful to bear in mind that papilledema eases.
is
Note that a pale optic disk with normal visual
almost always bilateral; it does not typically impairfunction
vican occur as a congenital variant.
sion, except for enlargement of the blind spot, and it 2. Arteries and veinsTo determine the caliber of
is
the retinal arteries and veins, they are observed at
not associated with eye pain. Papilledema can alsothe
be
simulated by disk abnormalities such as drusen point where they arise from the disk and pass over its
(colloid
edges onto the retina. Observations include whether
or hyaline bodies).
they are easily visible throughout their course,
Increased intracranial pressure is thought to cause
whether
papilledema by the increased pressure blocking they appear engorged, and whether spontaneous veaxonal
nous pulsations are present. The remainder of the
transport in the optic nerve. Because this
visicompartment
ble retina is inspected, noting the presence of hemorrhages, exudates, or other abnormalities.
3. MaculaThe macula, a somewhat paler area
than the rest of the retina, is located about two disk
diameters temporal to the temporal margin of the optic
Optic disk

Fovea

Arteriole

Macula
Vein

Figure 410. The normal fundus.The diagram shows landmarks corresponding to the photograph. (Photoby
DianeBeeston;reproducedwithpermission,fromVaughanD,AsburyT,RiordanEvaP:Gen
eralOphthalmology,15thed.Appleton&Lange,1992.)

136 / CHAPTER 4

Figure 411. Appearance of the fundus in papilledema. A: In early papilledema, the superior and inferior
margins
of the optic disk are blurred by the thickened layer of nerve bers entering the disk. B: Swollen nerve bers (white
patches) and hemorrhages can be seen. C: In fully developed papilledema, the optic disk is swollen, elevated, and
congested, and the retinal veins are markedly dilated. D: In chronic atrophic papilledema, the optic disk is pale
and
slightly elevated, and its margins are blurred.The white areas surrounding the macula are reected light from the
vitreoretinal interface.The inferior temporal nerve ber bundles are partially atrophic (arrows). (Photoscourtesy
ofWFHoyt.)

DISTURBANCES OF VISION / 137

disk. It can be visualized quickly by having the
tic nerve to the midbrain (Figure 412). The normal
patient
pupil is round, regular, and centered within the iris;
look at the light from the ophthalmoscope. Ophthalits
moscopic examination of the macula can reveal size varies with age and with the intensity of ambient
abnorlight. In a brightly illuminated examining room, normalities related to visual loss from age-related
mal pupils are about 3 mm in diameter in adults.
macular
They
degeneration,
from
macular
holes,
or
from
hereditary
are often smaller in the elderly and commonly 5 mm
Pupils
cerebromacular degenerations.
or
A. SIZE
more in diameter in children. Pupillary size may be
Assessing the size and reactivity of the pupils
asymmetric in as much as 20% of the population
provides
(physiologic anisocoria), but the difference in size is
an evaluation of nervous system pathways from the
not more than 1 mm. Symmetrically rapid
opconstriction
in response to a bright light indicates that the size difLight
ference
is not due to oculomotor nerve compression.

Pupillary constrictor muscle

Optic
nerve
Ciliary ganglion

Optic tract
Oculomotor nerve

Edinger-Westphal nucleus

Lateral geniculate nucleus

Pretectal nucleus

Figure 412. Anatomic basis of the pupillary light reex.The afferent visual pathways from the retina to the
pretectal nuclei of the midbrain are represented by dashed lines and the efferent pupilloconstrictor pathways from
the
midbrain to the retinas by solid lines. Note that illumination of one eye results in bilateral pupillary constriction.

138 / CHAPTER 4
B. REACTION TO LIGHT
and reacts sluggishly to changes in illumination or acDirect (ipsilateral) and consensual (contralateral) commodation. Because the tonic pupil does
pupillary constriction in response to a bright light eventually
shined in one eye demonstrates the integrity of the
react, anisocoria becomes less marked during the
pathways shown in Figure 412. Normally, the direct
time
response to light is slightly brisker and more pro- of the examination. This abnormality is most comnounced than the consensual response.
monly a manifestation of a benign, often familial
disorC. REACTION TO ACCOMMODATION
der that frequently affects young women (HolmesWhen the eyes converge to focus on a nearer object,
Adie
the
syndrome) and may be associated with depressed
pupils normally constrict. The reaction to
deep
accommodatendon reexes (especially in the legs), segmental
tion is tested by having the patient focus alternately
anon
hidrosis (localized lack of sweating), orthostatic hyD.
PUPILLARY
ABNORMALITIES
a distant
object
and a nger held just in front of his
or
potension,
or cardiovascular autonomic instability.
1. nose.
Nonreactive pupilsUnilateral disorders of
her
The
pupillary constriction are seen with local disease ofcondition may be bilateral. The pupillary abnormality
the
may be caused by degeneration of the ciliary
iris (trauma, iritis, glaucoma), oculomotor nerve comganglion,
pression (tumor, aneurysm), and optic nerve
followed by aberrant reinnervation of the pupillocondisorders
strictor muscles.
(optic neuritis, multiple sclerosis).
5. Horner syndromeHorner syndrome (Table
2. Light-near dissociationImpaired pupillary re41 and Table 42) results from a lesion of the central
activity to light with preserved constriction during or
ac-peripheral sympathetic nervous system and
commodation (light-near dissociation) is usually bilatconsists
eral and may result from neurosyphilis, diabetes, of a small (miotic) pupil associated with mild ptosis
optic
(Figure 413A) and sometimes loss of sweating (annerve disorders, and tumors compressing the
hidrosis).
midbrain
a. Oculosympathetic pathwaysThe sympathetic
tectum.
pathway controlling pupillary dilation (Figure 413B)
3. Argyll Robertson pupilsThese pupils are small,
consists of an uncrossed three-neuron arc: hypothalapoorly reactive to light, often irregular in shape, and
mic neurons, the axons of which descend through the
frequently unequal in size; they show light-near brainstem to the intermediolateral column of the
dissocispinal
ation (Table 41). Neurosyphilis is the classic causecord at the T1 level; preganglionic sympathetic neubut
rons projecting from the spinal cord to the superior
other lesions in the region of the Edinger-Westphalcervical ganglion; and postganglionic sympathetic
Table 41. Common pupillary abnormalities.
nuneucleus (eg, multiple sclerosis) are now more common.
rons that originate in the Differential
superior cervical
ganglion,
Diagnosis
4. Tonic pupilThe tonicAppearance
(Adie) pupil (see Table as- Response
41)
larger
than the
contralateral
unaffected
pupil
cend
in the neck
along
the internal
carotid artery,
Tonic is
(Adie)
pupil
Unilateral
(rarely bilateral)
dilated
Reacts
sluggishly
and only
toHolmes-Adie
syndrome,
ocular and
enterbright
the orbit
the
rst (ophthalmic)
division of
pupil
persistent
lightwith
or 0.125%
trauma,
autonomic neuropathy
pilocarpine
eye drops;
the trigeminal
(V) nerve. Horner syndrome is caused
accommodation
less affected
by interruption
of these pathways at any site.
b. Clinical featuresThe lesionsand the pupilHorner syndrome
Unilateral small pupil and slight
Normal response to light and Lateral medullary infarcts,
lary
abnormality producedare
usually unilateral.
ptosis
accommodation
cervical cord lesions, pulmonary
The
apical or mediastinal tumors,
neck trauma or masses, carotid
artery thrombosis, intrapartum
brachial plexus injury, cluster
headache
Argyll Robertson pupilUnequal irregular pupils less Poorly reactive to light; more Neurosyphilis; mimicked by
than 3 mm in diameter (usually
responsive to accommodationdiabetes, pineal region tumors
bilateral)

DISTURBANCES OF VISION / 139

Table 42. Causes of Horner syndrome in 100
hospitalized patients.
Percentage
Central (rst) neuron
Brainstem infarction
Cerebral hemorrhage/infarction
Multiple sclerosis
Intracranial tumor
Trauma (including surgery)
Syrinx
Transverse myelopathy
Other or unknown

63
36
12
3
2
2
2
2
4

the direct response is greater than the consensual response. The abnormality is detected by rapidly
moving
a bright ashlight back and forth between the eyes
while continuously observing the suspect pupil (Gunn
pupillary test). Relative afferent pupillary defect is
commonly associated with disorders of the ipsilateral
optic nerve, which interrupt the afferent limb and affect the pupillary light reex (Figure 412). Such
disorders also commonly impair vision (especially color vision)
in the involved
eye.
Optokinetic
Response

Optokinetic nystagmus consists of eye movements

elicited by sequential xation on a series of targets
Preganglionic (second) neuron
21
passThoracic and neck tumor
14
ing in front of a patients eyes, such as telephone
Trauma
poles
Nonsurgical
4
seen from a moving train. For clinical testing, a
Surgical
3
revolvOther or unknown
0
ing drum with vertical stripes or a vertically striped
Postganglionic (third) neuron
13
strip of cloth moved across the visual eld is used to
Intracranial tumor (cavernous sinus)
7
generate these movements. Testing produces a slow
Trauma (including surgical)
2
folVascular headache
2
lowing phase in the direction of the targets
Other or unknown
2
movement,
followed by a rapid return jerk in the opposite direcUnknown localization
3
pupillary diameter on the involved side is typicallytion.
re- The slow (pursuit) phase tests ipsilateral pariduced
by
0.51
mm
compared
with
the
normal
side.
DatafromKeaneJR:ArchNeurol1979;36:1316.
etooccipital pathways; the rapid (saccadic)
This inequality is most marked in dim illumination movement
and in other situations in which the pupils are
tests pathways originating in the contralateral frontal
normally
lobe. The presence of an optokinetic response reects
dilated, such as during a painful stimulus or startle.
the ability to perceive movement or contour and is
The pupillary abnormality is accompanied by mild sometimes
to
useful for documenting visual perception
moderate ptosis (see below) of the upper lid (as opin
posed to the pronounced ptosis with oculomotor The
eyelids
should
be examined
the
Eyelids
newborns
or(palpebrae)
in psychogenic
blindness.
Visualwith
acuity
nerve
patients
eyes
open.
The
distance
between
the
upper
relesions), often associated with elevation of the lower
and
quired to produce the optokinetic response is
lid.
lower
lids (interpalpebral ssure) is usually about 10
minimal,
When Horner syndrome has been present since in-mm
and
in both
eyes,counting
though physiologic
however equal
(20/400,
or nger
at 35 ft). Unilatfancy, the ipsilateral iris is lighter and blue
asymeral impairment of the optokinetic response may be
(heterochrometries
do occur.
The
position
the inferior
margin
found when
targets
are
movedof
toward
the side
of a
mia iridis).
of
parietal lobe lesion.
Decits in the pattern of sweating, which are most
the upper lid relative to the superior border of the iris
prominent in acute-onset Horner syndrome, can help
should be noted in order to detect drooping (ptosis)
localize the lesion. If sweating is decreased on an or
entire
abnormal elevation of the eyelid (lid retraction). The
half of the body and face, the lesion is in the central
upper lid normally covers 12 mm of the iris.
nervous system. Cervical lesions produce anhidrosis
Unilateral ptosis is seen with paralysis of the leof
vator palpebrae muscle itself, lesions of the
the face, neck, and arm only. Sweating is unimpaired
oculomotor nerve or its superior branch, and
if
Horner syndrome. In the last condition, ptosis is custhe lesion is above the bifurcation of the carotid tomarily associated with miosis and may be
artery.
momentarThe differential diagnosis of Horner syndrome is preily overcome by effortful eye opening.
sented in Table 42.
Bilateral ptosis suggests disease affecting the
6. Relative afferent pupillary defect (Marcus Gunn
oculopupil)In this condition, one pupil constricts less motor nerve nucleus; a disorder of the neuromuscular
markedly in response to direct illumination than tojunction,
ilsuch as myasthenia gravis; or a disorder of
lumination of the contralateral pupil, whereas
muscle, such as myotonic, ocular, or oculopharyngeal
normally
dystrophy.

140 / CHAPTER 4

A
Hypothalamus
Ophthalmic division
of trigeminal nerve
Long ciliary nerve

To sweat glands of forehead

To smooth muscle of eyelid
To pupil

Internal carotid artery

To sweat glands of face

External carotid artery
C2
Third neuron

Superior cervical ganglion

First neuron

T1
Second neuron

Spinal cord
B

Figure 413. A: Left Horner syndrome (ptosis and myosis) after an attempted intercostal nerve block
complicated
by pneumothorax. (CourtesyofJRKeane.)B: Oculosympathetic pathway involved in Horner syndrome.This
three-neuron pathway projects from the hypothalamus to the intermediolateral column of the spinal cord, then to
the superior cervical (sympathetic) ganglion, and nally to the pupil, smooth muscle of the eyelid, and sweat
glands
of the forehead and face.

A. OCULAR EXCURSION AND GAZE

Ocular palsies and gaze palsies are detected by
having the
patient gaze in each of the six cardinal positions (see
DISTURBANCES OF VISION / 141
Figure 45). If voluntary eye movement is impaired or
Lid retraction (abnormal elevation of the upper lid)
neuromuscular junction, or muscle) lesions. An ocular
the
is seen in hyperthyroidism; in Parinaud syndrome, palsy
it
cannot be overcome by caloric stimulation of
patient is unable to cooperate with the examination
is
re(eg,
caused by tumors in the pineal region.
ex eye movement. Nerve lesions produce distinctive
is comatose), reex eye movements can be induced
patterns of ocular muscle involvement.
Exophthalmos
by
a. Oculomotor (III) nerve palsyA complete leone
of twoprotrusion
maneuvers
Figure
103).
The dolls
Abnormal
of(see
the eye
from
the orbit
(exophsion of the oculomotor nerve produces closure of the
head
thalmos or proptosis) is best detected by standingaffected
beeye because of impaired levator function.
oculocephalic)
is performed
by rotating
the
hind the seatedmaneuver
patient and
looking down
at his orPashead
her horizontally, to elicit horizontal eye movements,
sively elevating the paralyzed lid (Figure 414) shows
and
to elicit
vertical
movements.orbital
The eyes
eyes.vertically,
The causes
include
hyperthyroidism,
tu- involved eye to be laterally deviated because of
the
should
in the direction
opposite
to that of head
mor or move
pseudotumor,
and carotid
artery-cavernous
sithe
ronus stula. A bruit may be audible on auscultationunopposed action of the lateral rectus muscle, which
tation.
over This may be an inadequate stimulus for
is
inducing
the proptotic eye in patients with carotid artery-cavnot innervated by the oculomotor nerve. Diplopia is
eye
movements,
however,
the reex
may be
ernous
sinus stula
or otherand
vascular
anomalies.
present in all directions of gaze except for lateral
Eye
Movements
overridgaze
den in conscious patients. Caloric (oculovestibular)
toward the side of involvement. The pupils function
stimulation is a more potent stimulus and is
may be normal (pupillary sparing) or impaired.
performed
b. Trochlear (IV) nerve palsyWith trochlear
by irrigating the tympanic membrane with cold
nerve lesions, which paralyze the superior oblique
(30C)
musor warm (44C) water. Otoscopic examination should
cle, the involved eye is elevated during primary (foralways be undertaken before this maneuver is
ward) gaze; the extent of elevation increases during
attempted:
adit is contraindicated if the tympanic membrane is
duction and decreases during abduction. Elevation is
perfogreatest when the head is tilted toward the side of
rated. In conscious patients, unilateral cold water
the
irrigainvolved eye and abolished by tilt in the opposite
tion produces nystagmus with the fast phase directed
direcaway from the irrigated side. Because this procedure
tion (Bielschowsky head-tilt test; Figure 415).
may
Diplopia is most pronounced when the patient looks
produce discomfort and nausea or vomiting, only
downward with the affected eye adducted (as in looksmall
ing at the end of ones nose). Spontaneous head
volumes (eg, 1 mL) of water should be used in
tilting,
conscious
intended to decrease or correct the diplopia, is
patients. In comatose patients with intact brainstem
present
function, unilateral cold water irrigation results in
in about half the patients with unilateral palsies and
tonic
in
deviation of the eyes toward the irrigated side.
an even greater number with bilateral palsies.
Bilateral
c. Abducens (VI) nerve palsyAn abducens nerve
irrigation with cold water causes tonic downward
lesion causes paralysis of the lateral rectus muscle,
deviaretion, whereas bilateral stimulation with warm water
sulting in adduction of the involved eye at rest and
infailduces tonic upward deviation. An absent or impaired
ure of attempted abduction (Figure 416). Diplopia
reoccurs on lateral gaze to the side of the affected eye.
sponse to caloric stimulation with large volumes (eg,
2. Gaze palsyGaze palsy is the diminished ability
50
of a pair of yoked muscles (muscles that operate in
mL) of cold water is indicative of peripheral vestibular
condisease, a structural lesion in the posterior fossa Figure 414. Clinical ndings with oculomotor (III)
cert to move the two eyes in a given direction) to
(cerebelnerve lesion. With the ptotic lid passively elevated, the
move
lum or brainstem), or intoxication with sedative affected (right) eye is abducted. On attempted
the eyes in voluntary gaze; it is caused by
drugs. If
downgaze,
the unaffected superior oblique muscle,
supranuclear
limitations in movement are observed, the muscles
which
is
innervated
by the trochlear
(IV)hemisphere.
nerve, causesGaze
lesions in the brainstem
or cerebral
inthe eye to turn inward.
palsy, unlike ocular palsies, affects both eyes and
volved are noted and the nature of the abnormality is
usually
determined according to the following scheme.
1. Ocular palsyThis weakness of one or more eye
muscles results from nuclear or infranuclear (nerve,

142 / CHAPTER 4

3. Internuclear ophthalmoplegiaThis disorder results from a lesion of the medial longitudinal

C
fasciculus,
an ascending pathway in the brainstem that projects
Figure 415. Clinical ndings with trochlear (IV) nerve lesion.The affected (right) eye is elevated on forward
from the abducens to the contralateral oculomotor
gaze
(A).The extent of elevation is increased with adduction (B) and decreased with abduction (C). Elevation
nerve nucleus. As a consequence, the actions of the
increases
with head tilting to the affected side (D) and decreases abwith head tilting in the opposite direction (E).
ducens and oculomotor nerves during voluntary gaze
or caloric-induced movement are uncoupled.
Excursion
can be overcome by caloric stimulation. Its
of the abducting eye is full, but adduction of the conpathophysitralateral eye is impaired (Figure 417). Internuclear
ology and causes are discussed more fully in the ophthalmoplegia cannot be overcome by caloric
section
stimuon gaze palsy. Mild impairment of upgaze is not unlation; it can be distinguished from oculomotor nerve
common in asymptomatic elderly subjects.
palsy by noting preservation of adduction with
convergence. Its causes are discussed later (see
Internuclear
Ophthalmoplegia).
4. One-and-a-half syndromeA pontine lesion affecting
both the medial longitudinal fasciculus and
A
the
ipsilateral paramedian pontine reticular formation
(lateral
gaze center) produces a syndrome that combines
internuGaze
clear ophthalmoplegia with an inability to gaze
toward
B
the side of the lesion (Figure 418). The ipsilateral
eye is
Figure 416. Clinical ndings with abducens (VI)
immobile in the horizontal plane and movement of
nerve lesion.The affected (right) eye is adducted at restthe
(A) and cannot be abducted (B).
contralateral eye is restricted to abduction, which
may be
associated with nystagmus. The causes include
pontine
infarct, multiple sclerosis, and pontine hemorrhage.

DISTURBANCES OF VISION / 143

B. DIPLOPIA TESTING
When the patient complains of diplopia, maneuvers
to
Gaze
Left
test eye movement should be used to determine its
INO
anatomic basis. The patient is asked to x his or her
viNystagmus
Impaired adduction
sion on an object, such as a ashlight, in each of the
six
cardinal positions of gaze (see Figure 45). With normal conjugate gaze, light from the ashlight falls at
the
Gaze
Right
same spot on both corneas; a lack of such
INO
congruency
conrms that gaze is disconjugate. When the patient
Impaired adduction
Nystagmus
notes diplopia in a given direction of gaze, each eye
Figure 417. Eye movements in internuclear ophthal- should be covered in turn and the patient is asked to
remoplegia (INO) resulting from a lesion of the medial
port which of the two images disappears. The image
longitudinal fasciculus bilaterally.
displaced farther in the direction of gaze is always
referable to the weak eye, because that image will not fall
on B
A
R
L
R variation of this procedure
L
the fovea. A
is the red
glass
test, in which one eye is covered with translucent red
Gaze
Gaze
glass, plastic, or cellophane;
this allows the eye
responL
R
sible for each image to be identied.
To left medial rectus

To right
lateral rectus

To right
medial rectus
To left
lateral
rectus
muscle

Oculomotor (III)
nucleus
Abducens (VI)
nucleus
Medial
longitudinal
fasciculus
Paramedian
pontine
reticular
formation
Pons

Pons
L

Figure 418. One-and-a-half syndrome.This results from a pontine lesion (shaded area) involving the paramedian
pontine reticular formation (lateral gaze center) and medial longitudinal fasciculus, and sometimes also the
abducens (VI) nucleus, and affecting the neuronal pathways indicated by dotted lines. Attempted gaze away from
the lesion (A) activates the uninvolved right lateral gaze center and abducens (VI) nucleus; the right lateral rectus
muscle contracts and the right eye abducts normally. Involvement of the medial longitudinal fasciculus interrupts
the pathway to the left oculomotor (III) nucleus, and the left eye fails to adduct. On attempted gaze toward the
lesion
(B), the left lateral gaze center cannot be activated, and the eyes do not move.There is a complete (bilateral) gaze
palsy in one direction (toward the lesion) and one-half (unilateral) gaze palsy in the other direction (away from the
lesion), accounting for the name of the syndrome.

C. NYSTAGMUS
Nystagmus is rhythmic oscillation of the eyes. Pendular nystagmus, which usually has its onset in infancy,
occurs with equal velocity in both directions. Jerk
144 / CHAPTER 4
nystagmus is characterized by a slow phase of movement followed by a fast phase in the opposite direction; the direction of jerk nystagmus is specied by
DISORDERS OF THE VISUAL
stating the direction of the fast phase (eg, leftwardbeating nystagmus). Jerk nystagmus usually
SYSTEM
increases
in amplitude with gaze in the direction of the fast
phase.
MONOCULAR DISORDERS
Nystagmus, a normal component of both the optoCommon syndromes of monocular visual loss include
kinetic response and the response to caloric
two reversible and two irreversible disorders.
stimulation
Transient
of reex eye movements, can also occur at the
monocular blindness caused by optic nerve or retinal
extremes
ischemia is sudden in onset and resolves rapidly.
of voluntary gaze in normal subjects. In other
Subasettings,
cute, painful, unilateral visual loss with partial resoluhowever, it is commonly due to anticonvulsant or
tion is associated with optic neuritis. Less reversible
sedavitive drugs or is a sign of disease in the peripheral
1.
TRANSIENT
MONOCULAR
BLINDNESS
sual
loss of sudden
onset
occurs in idiopathic
vestibular apparatus, central vestibular pathways, or
This condition, sometimes called amaurosis
ischemic
cerebellum.
fugax, is characterized
by unilateral
transient
optic neuropathy
and in giant cell
(temporal)
arteritis.
To detect nystagmus, the eyes are observed in the
diminution or loss of vision that develops over
primary position and in each of the cardinal positions
seconds, remains maximal for 15 minutes, and reof gaze (see Figure 45). Nystagmus is described in
solves over 1020 minutes. Although the cause of
terms of the position of gaze in which it occurs, its dithese
rection and amplitude, precipitating factors such as
episodes often remains uncertain, the presence of
changes in head position, and associated symptoms,
what
such as vertigo.
appears to be embolic material in retinal arteries
Many forms of nystagmus and related ocular
during
oscillaepisodes suggests that emboli are the cause. The
tions have been described, but two syndromes of acmajor
quired pathologic jerk nystagmus are by far the most
site of origin of such emboli appears to be atherosclecommon.
rotic lesions at the carotid bifurcation. Mitral valve
1. Gaze-evoked nystagmusAs its name implies,
progaze-evoked nystagmus occurs when the patient atlapse and other cardiac sources of emboli can
tempts to gaze in one or more directions away from
produce a
the
similar syndrome. The risk for subsequent
primary position. The fast phase is in the direction of
hemispheric
gaze. Nystagmus evoked by gaze in a single direction
infarction is increased (14% within 7 years) in
is
patients
a common sign of early or mild residual ocular palsy.
with a history of transient monocular blindness but is
Multidirectional gaze-evoked nystagmus is most often
only about one-half that in patients with hemispheric
an adverse effect of anticonvulsant or sedative drugs,
transient ischemic attacks (TIAs).
but it can also result from cerebellar or central
Diagnostic evaluation and treatment of patients
vestibuwith transient monocular blindness resemble that reclar dysfunction.
ommended
for patients with hemispheric TIAs (see
2. OPTIC NEURITIS
2. Vestibular nystagmusVestibular nystagmus
Chapter
9).
Recent
have produces
shown that
Inammation of thestudies
optic nerve
theinsynincreases with gaze toward the fast phase and is usupatients
drome of optic neuritis. The most common cause is
ally accompanied by vertigo when caused by a lesion
with
de- transient monocular blindness or TIAs and highof the peripheral vestibular apparatus. Vestibular nysgrade (>70%)
stenosis
of the
carotid
arteryparaat
myelination.
Less
common
causes
include
tagmus is characteristically unidirectional, horizontal,
angiogra- meningeal, or intraocular inammation
meningeal,
or horizontal and rotatory and is associated with sephy (but not
transient
monocular
associated
with
viral infections
or blindness
post-viral alone),
vere vertigo. In contrast, central vestibular
the
syndromes.
nystagmus
combination
of optic
aspirin
plus surgical
removal
of (eg,
plaque
Rare
causes of
neuropathy
include
toxins
may be bidirectional and purely horizontal, vertical,
(endarterectomy)
is superior
to aspirin and
alone.
methanol,
ethambutol),
neurosyphilis,
vitamin
or rotatory, and the accompanying vertigo is typically
B12
mild. Positional nystagmuselicited by changes in
deciency. Unilateral impairment of visual acuity ochead positioncan occur with either peripheral or
curs over hours to days, becoming maximal within
central vestibular lesions. The most helpful distin1 week. The visual loss is associated with headache,
guishing features are the presence of hearing loss or
globe tenderness, or eye pain in over 90% of cases;
tinnitus with peripheral lesions and of corticospinal
the
tract or additional cranial nerve abnormalities with
pain is typically exacerbated by eye movement.
central lesions.

DISTURBANCES OF VISION / 145

On visual eld testing, there is usually a centralor temporal, arteritis. This disorder is usually
scoaccompatoma (blind spot) associated with decreased visualnied by systemic symptoms such as fever, malaise,
acunight
ity. Examination of the fundus shows unilaterial disk
sweats, weight loss, and headache (see Chapter 2)
swelling when the nerve head is involved, but is and
normal
often by polymyalgia rheumatica. Transient retinal iswhen the inammatory process is posterior to the chemia, mimicking embolic events, may precede
optic
optic
disk (retrobulbar neuritis). The pupils are equal in size
nerve infarction. The visual loss is sudden and often
but show a diminished reaction to illumination of the
toaffected eye (relative afferent pupillary defect;
tal. On examination, the optic disk appears swollen
discussed
and
above).
pale. Immediate treatment with corticosteroids
In demylinating disease, visual acuity usually but
(methylprednisolone, 1000 mg/d intravenously, then
not
prednisone, 6080 mg/d orally) is urgently required to
invariably improves over 23 weeks to normal. Intraprotect what vision remains. Prednisone may be
venous methylprednisolone, 1 g/d for 3 days,
gradufollowed by
ally
reduced over many months while monitoring the
1. PAPILLEDEMA
oral prednisone, 1 mg/kg/d for 11 days, has been erythrocyte
Papilledemasedimentation
is the painless,rate.
passive bilateral disk
shown
Because
giant
cell arteritis
is increased
treatable, intracranial
it is most
swelling that is associated
with
to hasten recovery but does not alter the nal
impressure. Less common causes include congenital
outcome.
portant
cyan- to distinguish it from idiopathic or nonarteritic
Oral prednisone alone in lower doses was associated
anterior
ischemic
optic
neuropathy
as the cause
of
BINOCULAR
DISORDERS
otic
heart
disease
and disorders
associated
with inwith
monocular
visual
loss.
Patients
with
giant
cell
arteritis
3. ANTERIOR ISCHEMIC OPTIC NEUROPATHY (AION)
creased cerebrospinal uid (CSF) protein content, ina
higher recurrence
than
occurred
in patients
tend
to be
older
(aged
7080
and they may
Idiopathic
infarction rate
of the
anterior
portion
of the opcluding
spinal
cord
tumor
andyears),
idiopathic
treated
have
tic nerve is termed anterior ischemic optic
inammatory
with
placebo. The frequency with which optic neuritis
premonitory
symptoms.
The most
helpful differential
neuropathy.
polyneuropathy
(Guillain-Barr
syndrome).
is
features
are
the
erythrocyte
sedimentation
rate,
It occurs after the age of 50. Such visual loss is
The speed with which papilledema develops
is dicthe
rst sign of more widespread central nervous which
is the underlying cause. When intracranial
sudden
tated by
system
in onset, usually painless, always monocular, and greater
pres- than 50 mm/h (Westergren) in most patients
demyelination
(multiple
sclerosis)
remains
uncertain
with
cell arteritis,
C-reactive
withsure giant
increases
suddenly,and
as elevated
in subarachnoid
or
and
protein.
out premonitory ocular symptoms. Visual loss is usuintracerevaries
with the
of follow-up
studies.
Most bral hemorrhage, disk swelling may be seen within
ally maximal
atlength
onset and
frequently
subtotal,
prospecproduchours, but it most often evolves over days.
tive
retrospective
series,
however,
report
ing aand
eld
defect that is
typically
altitudinal
(superior
Papilledema
progression
or inferior) in conguration; in one-third of cases the
may require 23 months to resolve following restorato
denite
multiple sclerosis
in many
of these
course
is stuttering
or progressive.
Examination
tion of normal intracranial pressure. Associated
patients
reveals
nonspe(74%
of women
and 34%
of men)
the
ipsilateral
disk swelling
often
with over
peripapillary
cic symptoms of raised intracranial pressure include
subsequent
hemorheadache, nausea, vomiting, and diplopia from ab15
years.
dataof
support
immunomodulatory
rhages.
InEvolving
the absence
this nding,
the diagnosis
ducens
is
nerve palsy. Funduscopic examination (Figure
treatment
for other
optic neuritis
presumed
multiple 411) reveals (in order of onset) blurring of the nerve
tenuous, and
causes, as
such
as a rapidly
sclerosis
expanding
ber layer, absence of venous pulsations (signifying
if
demyelinating
lesions
are
seen
on
a
brain
magnetic
intracranial mass or neoplastic meningitis, should inbe
ressought. Although ischemic optic neuropathy is often
tracranial pressure greater than approximately 200
onance
imaging
(MRI) scan (see
5). is nomm
assumed
to be atherosclerotic
inChapter
origin, there
conHg), hemorrhages in the nerve ber layer, elevation
sistent association with other risk factors for
of
cerebrovasthe disk surface with blurring of the margins, and disk
cular disease, such as hypertension, diabetes, or hyperemia.
atheroPapilledema requires urgent evaluation to search
sclerotic carotid artery disease. Patients with AIONfor
4. GIANT CELL (TEMPORAL) ARTERITIS
have a structurally smaller than normal disk; 25% an
willintracranial mass and to exclude papillitis from
Arteritic infarction of the anterior portion of the optic
go on to have the other eye affected within 24 meningeal carcinoma, sarcoidosis, or syphilis, which
nerve is the most devastating complication of giant
years.
may produce a similar ophthalmoscopic appearance.
cell,
Attempts at treatment have been uniformly unsucIf
cessful. As disk swelling resolves, ophthalmoscopican intracranial mass lesion and the disorders listed in
evalTable 24 are excluded by the history, examination,
uation shows optic atrophy.
and computed tomography (CT) scanning or MRI; if

146 / CHAPTER 4
inammatory meningeal processes are excluded by
lobe may be due to tumor or vascular disease and are
CSF
usually associated with contralateral weakness and
examination; and if CSF pressure is elevated, a
sendiagnosory loss. A gaze preference is common in the acute
sis of idiopathic intracranial hypertension is estab-phase, with the eyes conjugately deviated to the side
lished by exclusion. The idiopathic form, which is the
of
most common, occurs most often in obese womenthe parietal lesion. The visual eld abnormality is
dureither
ing the childbearing years. Although this disorder is
complete homonymous hemianopia or inferior quadusually self-limited, prolonged elevation of
rantanopia (see Figure 47). The optokinetic response
2.
CHIASMAL LESIONS
intracranial
to a visual stimulus moved toward the side of the
The
majorcan
lesions
produce visual
at
pressure
lead that
to permanent
visualimpairment
loss (see lesion
Occipital Cortex
the
discusis impaired, which is not the case with pure temporal
level
of
the
optic
chiasm
are
tumors,
especially
those
Lesions
in the
occipital
sion in Chapter 2).
or occipital
lobe
lesions.cortex usually produce
of
homonymous hemianopias affecting the contralateral
pituitary origin. Other causes include trauma,
visual eld. The patient may be unaware of the visual
multiple
decit. Because the region of the occipital cortex in
sclerosis or other demyelinating diseases, and
which the macula is represented is often supplied by
expanding
branches of both the posterior and middle cerebral
berry aneurysms. The classic pattern of visual decit
arcaused by lesions of the optic chiasm is bitemporalteries (see Figure 44), visual eld abnormalities
hemianopia (Figure 47). With the exception of pitucaused
itary apoplexy due to acute intrapituitary
by vascular lesions in the occipital lobe may show
hemorrhage,
sparchiasmal visual loss is gradual in onset, and the ing of macular vision (see Figure 47). Macular sparresulting
ing may result from bilateral cortical representation
impairment in depth perception or in the lateral of
visual
the macular region of the visual eld.
elds may not be noted for some time. Associated in-The most common cause of visual impairment in
volvement of the oculomotor, trochlear, trigeminal,
or
the
abducens nerve suggests tumor expansion laterally
occipital lobe is infarction in the posterior cerebral
into
artery
the cavernous sinus. Nonophthalmologic
territory (90% of cases). Occipital lobe arteriovenous
manifestations
malformations (AVMs), vertebral angiography, and
of pituitary tumors include headache, acromegaly,waamenorrhea, galactorrhea, and Cushing syndrome.tershed infarction following cardiac arrest are less
3. R
ETROCHIASMAL
LESIONS abnormalities, and occasionHeadache,
endocrine
comally blurred or double vision may occur in patients mon causes. Additional symptoms and signs of
with
basilar arOptic Tract & Lateral Geniculate Body
an enlarged sella turcica (shown on radiographic tery ischemia may occur. Tumors and occipital lobe
Lesions
exami- of the optic tract and lateral geniculate body
AVMs are often associated with unformed visual
are
usually
to infarction.
The resulting
visual eld
nation)
but due
in whom
neither tumor
nor increased
inhalluciabnormality
is typically
a noncongruous
homonymous
tracranial pressure
is found.
This empty sella
nations
that are typically
unilateral, stationary or
DISORDERS
OF OCULAR
hemianopia,
ie, the eld defect is not the same in moving,
the
syndrome
two
eyes.
Associated
hemisensory
loss mainly
may occur MOTILITY
is most
common
in women
and occurs
brief or ickering; they can be colored or not colored.
with
between
Bilateral occipital lobe involvement produces cortithalamic
the fourthlesions.
and seventh decades of life. Treatment is
cal
blindness.
GAZE
PALSY Pupillary reactions are normal, and
Optic
Radiations
symptomatic.
bilatLesions
in thesparing
cortex may
or brainstem
the
level of
eral macular
preserveabove
central
(tunnel)
Lesions of the optic radiations produce eld decits
the
vithat
oculomotor
nuclei
may impair
conjugate
sion. With more
extensive
lesions,
denial (yoked)
of blindness
are congruous and homonymous (bilaterally symmetmovement
of
the
eyes,
producing
gaze
disorders.
may
occur
(Anton
syndrome).
ric). Visual acuity is normal in the unaffected portion

Hemispheric Lesions

of
the eld. With lesions in the temporal lobe, where tumors are the most common cause, the eld decit is
denser superiorly than inferiorly, resulting in a
superior
quadrantanopia (pie in the sky decit; Figure 47).
Lesions affecting the optic radiations in the parietal

Acutely, hemispheric lesions produce tonic

deviation of both eyes toward the side of the lesion and away from the side of the hemipare-

DISTURBANCES OF VISION / 147

sis (Figure 419A). This gaze deviation may last forvolvement (unlike those from hemispheric lesions)
sevcause eye deviation towardrather than away from
eral days in alert patientssomewhat longer in comathe side of the hemiparesis (Figure 419C) because
tose patients. Seizure discharges involving the frontal
the
gaze centers can also produce gaze deviation by corticobulbar pathways that regulate gaze have
driving
decusthe eyes away from the discharging focus. When the
sated but the descending motor pathways have not
ipyet
silateral motor cortex is also involved, producing focal
crossed. Brainstem gaze pareses are
motor
seizures,
the
patient
gazes
toward
the
side
characteristically
of
far
Midbrain Lesions
the
more resistant to attempts to move the eyes (via the
Lesions
of the dorsal
motor activity
(Figuremidbrain
419B). affect the center dolls eye maneuver or caloric stimulation) than are
responsupratentorial gaze pareses and are commonly
sible for voluntary upward gaze and may thereforeINTERNUCLEAR
OPHTHALMOPLEGIA
associproated
with abducens
nerve dysfunction
because
Internuclear
ophthalmoplegia
(INO) results
fromof
le-the
duce upgaze paralysis. In addition, all or some of the
involvement
of
the
abducens
nerve
nucleus.
sions of the medial longitudinal fasciculus between
features of Parinaud syndrome may occur: preserved
reex vertical eye movements with the dolls headthe
midpons and the oculomotor nerve nucleus resulting
main
neuver or Bell phenomenon (elevation of the eye with
disconnection of the abducens nerve nucleus from
eyelid closure), nystagmus (especially on downward
gaze and typically associated with retraction of thethe
contralateral oculomotor nucleus (see Figure 46).
eyes),
paralysis
Pontine
Lesionsof accommodation, midposition
The
pupils,
site of the internuclear ophthalmoplegia is named acBrainstem
lesions
at
the
level
of
the
pontine
and light-near dissociation.
cording to the side on which oculomotor nerve funcgaze centers produce disorders of conjugate
horizontal gaze. Gaze palsies from pontinetion
in- is impaired. There is a characteristic abnormality
consisting of disconjugate gaze with impaired adduction and nystagmus of the abducting eye (Figure 4
A
B
C
17).
Such a nding strongly supports a diagnosis of
intrinsic
brainstem disease. The most common cause,
especially

Figure 419. Disorders of gaze associated with hemispheric and brainstem lesions. A: Destructive lesion in
the
frontal lobe of the right cerebral hemisphere. B: Seizure arising from the frontal lobe of the right cerebral hemisphere. C: Destructive lesion in the right pons. Arrows indicate the direction of gaze preference (away from the
hemiparetic side in A and toward the convulsing or hemiparetic side in B and C).

148 / CHAPTER 4
in young adults or in patients with bilateral involveBrainstem
ment, is multiple sclerosis. In older patients and those
Within the brainstem, associated neurologic signs
with unilateral involvement, vascular disease is likely.
perThese two diagnoses encompass 80% or more of all
mit localization of the lesion; associated contralateral
cases. Rarer causes include brainstem encephalitis,
hemiplegia (Weber syndrome) and contralateral
intrinsic brainstem tumors, syringobulbia, sedative ataxia
(Benedikt syndrome) are the most common vascular
drug
syndromes.
Subarachnoid
Space
intoxication, and Wernicke encephalopathy. Because
the oculomotor abnormalities of myasthenia gravisAs the oculomotor nerve exits the brainstem in the incan
terpeduncular space, it is susceptible to injury from
closely mimic a lesion of the medial longitudinal fascitrauma and from aneurysms of the posterior
culus,
myasthenia(III)
must
be ruled
out in patients with
communiOCULOMOTOR
NERVE
LESIONS
isolated internuclear ophthalmoplegia.
cating artery. The latter often cause acute oculomotor
Lesions of the oculomotor nerve can occur at any of
palsy from aneurysmal expansion with a
several levels. The most common causes are listedcharacteristic
in
Table 43; oculomotor disorders resulting from dia-impairment of the pupillary light reex.
Cavernous Sinus
betes are discussed separately below.
In the cavernous sinus (Figure 420), the oculomotor
nerve is usually involved along with the trochlear and
abducens nerves and the rst and sometimes the
Table 43. Causes of oculomotor (III), trochlear
second
(IV), and abducens (VI) nerve lesions.1
division of the trigeminal nerve. Horner syndrome
may
occur. Oculomotor nerve lesions in the cavernous
Nerve III Nerve IV Nerve VI
(%)
(%)
(%)
sinus
Cause
tend to produce partial decits that may or may not
Orbit
Unknown
23
29
26
spare the pupil.
Unlike cavernous sinus lesions, orbital lesions that afVasculopathy2
20
21
17
fect the oculomotor nerve are often associated with
opAneurysm
19
1
3
tic nerve involvement and exophthalmos; however,
Trauma
14
32
14
disorders of the orbit and cavernous sinus may be
Neoplasm3
12
7
20
clinically indistinguishable except by CT scanning or
Syphilis
2

1
MRI.
TROCHLEAR (IV) NERVE LESIONS
Multiple sclerosis

Other

104

105

Head trauma, often minor, is the most common cause

of an isolated trochlear nerve palsy (Table 43). Although trochlear palsies in middle-aged and elderly
1 Data are from several series, as compiled in Burde RM,
Savino PJ, Trobe JD: Clinical Decisions in Neuro-ophthalmol-patients are also frequently attributed to vascular disease or diabetes, they often occur without obvious
ogy, Mosby, 1984.
2 Includes diabetes, hypertension, and atherosclerosis.
cause. For patients with isolated trochlear nerve
3 Includes pituitary and parapituitary tumors, cavernous si-palsies without a history of trauma, in whom
nus meningioma, and primary and metastatic tumors of diabetes,
the brainstem.
myasthenia, thyroid disease, and orbital mass lesions
4 Includes sinusitis, Hodgkin disease, herpes zoster, giant
have been excluded, observation is the appropriate
cell arteritis, meningitis, encephalitis, collagen vascular disclinical approach.
eases, Paget disease, and postoperative neurosurgical com136

plications.
ABDUCENS (VI) NERVE LESIONS
5 Includes herpes zoster, collagen vascular disease, hypoxia,
hydrocephalus, postoperative complications, and enPatients with abducens nerve lesions complain of
cephalitis.
hori6 Includes raised intracranial pressure from any cause, Werzontal diplopia due to weakness of the lateral rectus
nicke encephalopathy, cervical manipulation, meningitis,
sarcoidosis, post-lumbar-puncture complications, postop- muscle (Figure 416). Lateral rectus palsies can occur
as a result of disorders of either the muscle itself or
erative complications, migraine, and sinusitis.

the
abducens nerve, and each of these possibilities
should
be investigated in turn. The causes of abducens
nerve
lesions are summarized in Table 43. In elderly pa-

DISTURBANCES OF VISION / 149

A
Optic (II) tract
Middle cerebral artery

Pituitary
Cavernous sinus
Oculomotor (III) nerve
Trochlear (IV) nerve
Sphenoidal sinus
Ophthalmic (V1) nerve
Maxillary (V2) nerve
Abducens (VI) nerve
Internal carotid artery
Subarachnoid space
Mandibular (V3) nerve

Blood

CSF

Air

II
III
IV
VI
V1
V2
V3

Cavernous sinus

Superior orbital fissure

Orbital apex

Figure 420. Position of cranial nerves in the cavernous sinus and adjacent structures. A: Coronal view through
the
cavernous sinus, with the midline at left and the temporal lobe at right. B: Location of cranial nerves as they
course
anteriorly (left to right) in relation to the cavernous sinus, superior orbital ssure, and orbital apex. Note that a
lesion
in the cavernous sinus spares the optic (II) and mandibular (V3) nerves, a lesion in the superior orbital ssure additionally spares the maxillary (V2) nerve, and a lesion in the orbital apex spares both V2 and V3 but may involve II.

tients, abducens nerve involvement is most often symptoms are absent, and intracranial pressure is not
idioelevated) patients can be followed conservatively. A
pathic or caused by vascular disease or diabetes, but
trial
the
of prednisone (60 mg/d orally for 5 days) may
erythrocyte sedimentation rate should be determined
produce
to
dramatic relief in painful abducens nerve palsy,
exclude a rare presentation of giant cell arteritis. giving
Radisupport to a tentative diagnosis of idiopathic
ographic investigation of the base of the skull is indiinammacated to exclude nasopharyngeal carcinoma or other
tion of the superior orbital ssure (superior orbital stusure syndrome) or cavernous sinus (Tolosa-Hunt synmors. In painless abducens palsy (when the abovedrome). Persistent pain despite treatment with
studies are normal, other systemic and neurologic steroids

150 / CHAPTER 4
should prompt investigation of the cavernous sinusTable 44. Causes of painful ophthalmoplegia.
by
CT scanning or MRI, followed, in some cases, by anOrbit
giography.
Orbital pseudotumor
Sinusitis
Tumor (primary or metastatic)
Infections (bacterial or fungal)
An isolated oculomotor, trochlear, or abducens nerve

DIABETIC OPHTHALMOPLEGIAS

lesion may occur in patients with diabetes mellitus;

Cavernous sinus
noninvasive imaging procedures (CT scanning or MRI)
Tolosa-Hunt syndrome (idiopathic granulomatous
reveal no abnormality. Such oculomotor nerve lesions
inammation)
are characterized by pupillary sparing, commonly atTumor (primary or metastatic)
tributed to infarction of the central portion of the Carotid arterycavernous sinus stula or thrombosis
nerve with sparing of the more peripherally situatedAneurysm
bers that mediate pupillary constriction. PupilSella and posterior fossa
sparing
Pituitary tumor or apoplexy
oculomotor palsies also can be seen with
Aneurysm
compressive,
Metastatic tumor
inltrative, or inammatory lesions of the oculomotor
nerve or with infarcts, hemorrhages, or tumors that
Other
afDiabetes
fect the oculomotor nucleus or fascicle within the Migraine
Giant cell arteritis
midbrain. Pain, when present, may be severe enough to
suggest aneurysmal expansion as a likely diagnosis.
In known diabetics, painful ophthalmoplegia with
exophthalmos and metabolic acidosis requires urgent
ent with ocular muscle involvement. The syndrome is
attention to determine the possibility of fungal infecpainless; pupillary responses are always normal, and
tion in the paranasal sinus, orbit, or cavernous sinus
there are no sensory abnormalities. The diagnosis is
by
conrmed by a positive response to intravenous edromucormycosis (see Chapter 1). The diagnosis is phonium (Tensilon). Details of this disorder are disPAINFUL
OPHTHALMOPLEGIAS
usually
cussed in Chapter 5.
made by biopsy
of the
nasalofmucosa.
Urgent
Dysfunction
of one
or more
the ocular
motor
treatment
nerves
Ocular myopathies
are painless syndromes that spare
MYOPATHIES
amphotericin Bpain
and may
surgical
debridement
of OCULAR
with accompanying
be produced
by lesions
pupillary function and are usually bilateral. The most
necroticanywhere
tissue is required.
located
from the posterior fossa to the common is the myopathy of hyperthyroidism, a comorbit
mon cause of double vision beginning in midlife or
(Table 44). The evaluation should consist of careful
later. Many patients are otherwise clinically euthyroid
documentation of the clinical course, inspection and
at the time of diagnosis. Double vision on attempted
palpation of the globe for proptosis (localizing the elevation of the globe is the most common symptom,
process to the orbit or anterior cavernous sinus), ausbut in mild cases there is lid retraction during staring
cultation over the globe to detect a bruit (supporting
or lid lag during rapid up-and-down movements of the
a
eye. Exophthalmos is a characteristic nding,
diagnosis of carotid artery-cavernous sinus stula especially
or
anin advanced cases. The diagnosis can be conrmed
other vascular anomaly), and evaluation for diabetes.
by
Useful laboratory studies include an orbital CT scan
orforced duction test, which detects mechanical rethe
MRI, carotid arteriography, and orbital venography.sistance to forced movement of the anesthetized
Therapy for these disorders is dictated by the speglobe
cic diagnosis. Idiopathic inammation of the orbitin the orbit. This restrictive ocular myopathy is
(orbital pseudotumor) or cavernous sinus (Tolosa- usually
Hunt
self-limited. The patient should be referred for testing
syndrome) responds dramatically to corticosteroids
of thyroid function and treated for hyperthyroidism as
(prednisone, 60100 mg/d orally). However, the pain
appropriate.
MYASTHENIA
GRAVIS
and ocular signs of some neoplasms may also
The progressive external ophthalmoplegias are a
improve
Myasthenia
eventually involves the ocular musclesgroup
in
of syndromes characterized by slowly
transiently during
corticosteroid
therapy
so60%
thatpresa progressive,
approximately
90%
of patients; more
than
spesymmetric impairment of ocular movement that cancic etiologic diagnosis may depend on biopsy.
not be overcome by caloric stimulation. Pupillary
function is spared, and there is no pain; ptosis may be

DISTURBANCES OF VISION / 151

prominent. This clinical picture can be produced byBennett JL, Pelak VS. Palsies of the third, fourth, and sixth cranial
ocular or oculopharyngeal muscular dystrophy. Pro- nerves. Ophthalmol Clin North Am. 2001;14:169185.
Buono LM et al: Nonarteritic anterior ischemic optic neuropathy.
gressive external ophthalmoplegia associated with Curr Opin Ophthalmol 2002;13:357361.
myDigre KB et al: Selective MR imaging approach for evaluation of
otonic contraction on percussion of muscle groups patients with Horners syndrome. AJNR Am J Neuroradiol
(classically, the thenar group in the palm) suggests 1992;13:223227.
Fisher CM: Some neuroophthalmological observations. J Neurol
the
Neurosurg Psychiatry 1967;30:383392.
diagnosis of myotonic dystrophy. In Kearns-Sayre- Foroozan R et al: Acute demyelinating optic neuritis. Curr Opin
Ophthalmol 2002;13:375380.
Daroff syndrome, which has been associated with
Glaser JS: Neuro-ophthalmology, 2nd ed. Lippincott, 1990.
deleHall JK, Balcer LJ. Giant cell arteritis. Curr Treat Options Neurol
tions in muscle mitochondrial DNA, progressive exter-2004;6:4553.
nal ophthalmoplegia is accompanied by pigmentary
Keane JR: Acute bilateral ophthalmoplegia: 60 Cases. Neurology
1986;36:279281.
degeneration of the retina, cardiac conduction
Keane
JR: The pretectal syndrome: 206 patients. Neurology
defects,
1990;40:684690.
cerebellar ataxia, and elevated CSF protein. The Keane JR: Fourth nerve palsy: historical review and study of 215
muscle
inpatients. Neurology 1993;43:24392443.
biopsy shows ragged red bers that reect the
Keane JR: Cavernous sinus syndrome. Analysis of 151 cases. Arch
Neurol 1996;53:967971.
presence
Kline LB, Hoyt WF: The Tolosa-Hunt syndrome. J Neurol Neuroof abnormal mitochondria. Disorders that simulate
surg Psychiatry 2001;71:577582.
progressive
external ophthalmoplegia include
Salvarani C et al: Laboratory investigations useful in giant cell arREFERENCES
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Barnett
HJ et al:The appropriate
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these
conditions
the impairment
of (usually
vertical)
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the
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17641769.

Motor Decits
CONTENTS
Approach to diagnosis, 153
History & examination, 153
Clinical localization of the
lesion, 159
Investigative studies, 162
Spinal cord disorders, 163
Traumatic myelopathy, 163
Demyelinating myelopathies,
164
Other infective or inammatory myelopathies, 168
AIDS, 168
Vascular myelopathies, 170
Deciency disorders, 171
Cervical spondylosis, 171
Congenital anomalies, 172
Tumors & cord compression,
172
Anterior horn cell
disorders, 173
Idiopathic anterior horn cell
disorders, 173
Other noninfective disorders
of anterior horn cells, 176

Infective disorders of anterior

Myasthenic syndrome
horn cells, 176
(Lambert-Eaton synNerve root and plexus lesions,
drome), 185
177
Botulism, 185
Acute intervertebral disk proAminoglycoside antibiotics,
lapse, 177
186
Cervical spondylosis, 177
Myopathic disorders, 186
Traumatic avulsion of nerve
Muscular dystrophies, 186
roots, 177
Congenital myopathies, 189
Neuralgic amyotrophy (idioMyotonic disorders, 189
pathic brachial plexopaInammatory myopathies,
thy), 177
190
Cervical rib syndrome, 179
AIDS, 191
Other causes of brachial plex- Metabolic myopathies, 192
opathy, 179
Endocrine myopathies, 192
Lumbosacral plexopathy, 179
Alcoholic myopathies, 192
Disorders of peripheral nerves,
Drug-induced myopathies,
179
193
Polyneuropathy, 180
Myoglobinuria, 193
Mononeuropathy multiplex,
Motor-unit hyperactivity
181
states, 193
Mononeuropathy simplex, 182 Central disorders, 193
Disorders of neuromuscular
Peripheral nerve disorders, 193
transmission, 183
Muscle disorders, 195
Myasthenia gravis, 183

KEY CONCEPTS
The cause of weakness is best determined after
the disorder has been localized to a particular
level of the neuromuscular system by any associated symptoms and signs.
It is important to record all medication that have
been taken, as motor disorders at all levels of the
neuromuscular system may be drug-related.
Hereditary causes of weakness must be excluded,
if necessary, by examination of other family
members. A number of hereditary disorders have

variable clinical expression and can be identied

by genetic testing.
The distribution of weakness is helpful in distinguishing between a radiculopathy, plexopathy,
and peripheral neuropathy, and between neurogenic and myopathic disorders.
Weakness that is patchy, varies in severity with
activity, and does not conform in distribution to
the territory of a nerve or nerve root suggests a
disorder of neuromuscular transmission.

152
Copyright 2005, 2002 by The McGraw-Hill Companies, Inc. Click here for terms of use.

MOTOR DEFICITS / 153

muscular control, or difculty in executing
movements.
APPROACH TO DIAGNOSIS
The term weakness is sometimes used in a
nonspecic
Motor function can be impaired by a lesion that in-way to denote fatigue or loss of energy, drive, or
enthuvolves the nervous system either centrally or
siasm, and care must be taken to clarify what the paperiphertient means. The word is properly used to mean loss
ally. Several parts of the central nervous system are
of
inHistory of Present Illness
volved in the regulation of motor activity; these muscle power, and it is in this sense that it is
Several
aspects of the present complaint must be
employed
include
docuthe pyramidal and extrapyramidal systems, the here.
mented.
cerebelA. MODE OF ONSET
lum, and the lower motor neurons of the brainstem
An abrupt onset suggests a vascular disturbance,
and spinal cord.
such as
The pyramidal system consists of bers that de-a stroke, or certain toxic or metabolic disturbances,
scend from the cerebral cortex through the internal
whereas subacute onset of days to weeks is
capsule, traverse the medullary pyramid, and thencommonly
mostly decussate, to descend in the lateral
associated with a neoplastic, infective, or
corticospinal
inammatory
tract on the side opposite that of their origin, where
process (Table 51). Weakness that evolves slowly
they synapse on lower motor neurons in the spinalB.
COURSE
over
cord. All other descending inuences on lower motor
A
progressive
increase
the motor
from its
several months
or yearsinoften
has a decit
hereditary,
neurons belong to the extrapyramidal system and onset
degenerorigsuggests
continuing activity
of the underlying
ative, endocrinologic,
or neoplastic
basis.
inate primarily in the basal ganglia and cerebellum.
process.
Disorders of the basal ganglia (see Chapter 7) andEpisodic progression suggests a vascular or
cereinammatory
bellum (see Chapter 3) are considered separately. origin; a steadily progressive course is more
The motor bers that make up the cranial and pesuggestive
of
Table 51. Causes
of weakness of acute
ripheral nerves have their origin in the lower motor
neoplastic
disorder
or subacute onset. or such degenerative conditions
neurons
51). A disturbance of function at as
HISTORY(Figure
& EXAMINATION
any point in the peripheral nervous system (anterior
Patients
motor
generally
complain
of Supraspinal lesions
horn cell,with
nerve
root,decits
limb plexus,
peripheral
nerve,
weakness,
heaviness,
stiffness,
clumsiness,
impaired
or neuromuscular
junction)
can disturb
motor
func- Stroke
Other structural lesions
tion, as can disease that primarily affects the muscles
Spinal cord lesions
themselves.
Infective: polio virus infection, coxsackievirus

Motor neuron
Nerve root
Peripheral nerve

Neuromuscular
junction

Muscle fiber

Figure 51. Anatomic components of the motor unit.

infection,
West Nile virus infection
Inammatory: transverse myelitis, multiple sclerosis
Compressive: tumor, disk protrusion, abscess
Vascular: infarction, hematomyelia
Peripheral neuropathy
Guillain-Barr syndrome
Diphtheria
Shellsh poisoning
Porphyria
Arsenic poisoning
Organophosphate toxicity
Disorders of neuromuscular transmissionn
Myasthenia gravis
Botulism
Aminoglycoside toxicity
Muscle disorders
Necrotizing myopathies
Acute hypo- or hyperkalemia
Periodic paralyses

154 / CHAPTER 5
motor neuron disease. Rapid uctuation of symptoms
Medical History
over short periods (eg, activity leads to fatigue and
The importance of the history depends upon the paan extients present complaint and the nature of any
acerbation of weakness; rest is followed by recovery
previous
of
C.
A
SSOCIATED
S
YMPTOMS
strength) is characteristic of myasthenia gravis. illnesses. For example, in a patient with known carcinoma of the lung, limb weakness may be due to
The distribution of weakness and the presence
metasof associated symptoms may indicate the approximate site of the lesion. For example, tasis or to a remote (nonmetastatic) complication of
Leg weakness in a diabetic may reect
weakness in the right arm and leg may result fromcancer.
a
periphlesion of the contralateral motor cortex or the corti- eral nerve, plexus, or multiple root involvement, and
hand weakness in a myxedematous patient may be
cospinal pathway at any point above the fth cervical
segment of the spinal cord. Associated right facial assowith carpal tunnel syndrome.
weakness indicates that the lesion must be above ciated
the
The history should include careful note of all
level of the facial (VII) nerve nucleus in the
drugs taken
by the patient. Drugs can cause
brainstem,
Developmental
History
and an accompanying aphasia (see Chapter 1) or peWhen symptoms
develop during
infancy,
childhood,
ripheral neuropathy,
impair
neuromuscular
visual
or
transmission, or lead to myopathy (Table 52).
eld defect (see Chapter 4) localizes it to the cerebral
early adult life, it is particularly important to obtain a
D.
SEVERITY OF SYMPTOMS
hemisphere.
full developmental history, including details of the deAnThe
attempt
must
be
made
to
evaluate
the
functional
character of the associated symptoms may
livery, birth weight, the patients condition in the
severity
of
any
motor
decit
by
determining
whether
sugneonatal period, and the dates at which motor milethere
has
been
any
restriction
of
daily
activities,
difgest the nature of the lesion at any given site in the
stones were attained. Congenital or perinatal cerebral
culty
in
performing
previously
easy
tasks,
or
nervous system. Thus, progressive leg weakness
disease accounts for most causes of infantile diplegia
reduction
caused
(weakness
of all four limbs, with the legs more
in
exercise
tolerance.
The
nature
of
the
functional
disby myelopathy is often preceded or accompanied by
severely
turbance
depends
on
the
muscles
involved.
pain in the back or legs when the myelopathy is due
affected than the arms).
to Weakness of proximal muscles in the legs leads to
difculty
in climbing
or descending
Table 52. Motor disorders associated with drugs.
a compressive
lesionbut
not whenstairs
it hasora in getting
up
from
a
squatting
position,
whereas
weakness
in
metabolic
the
Drugs that cause motor (or predominantly motor)
or hereditary basis.
arms leads to difculty with such tasks as combingperipheral neuropathy1
the
Dapsone
Imipramine
hair. Distal weakness in the arms may lead to clumsiCertain sulfonamides
ness, difculty with such ne motor tasks as doing up
buttons or tying shoelaces, and eventually the
Drugs that can impair neuromuscular transmission
inability
ACTHPenicillamine
to pick up or grasp objects with the hands, so that Aminoglycoside antibioticsPhenothiazines
even

Phenytoin
eating becomes difcult or impossible.
ChloroquinePolymyxin
Involvement of the muscles supplied by the cranial
ColistinProcainamide
nerves may lead to diplopia (oculomotor [III],
CorticosteroidsQuinidine, quinine
trochlear
LithiumTetracycline
[IV], and abducens [VI] cranial nerves; see Chapter Magnesium-containing
cathartics
4);
difculty in chewing (trigeminal [V] nerve) or sucking,
Drugs associated with myopathy
blowing, or using the facial muscles (facial [VII]
acid

nerve);
HMG-CoA reductase
Chloroquine
and difculty in swallowing, with nasal regurgitation
inhibitors
Clobrate
and dysarthria (glossopharyngeal [IX], vagus [X], and
Zidovudine
Corticosteroids
hypoglossal [XII] nerves).
Drugs causing hypokalemia Penicillamine
Weakness of the respiratory muscles leads to
Emetine
tachyp1A number of drugs cause mixed sensory and motor neunea, the use of accessory muscles of respiration, and
anxiety at a stage when arterial blood gases are ropathies, as shown in Table 62.
usually
still normal. A vital capacity of less than 1 L in an
adult
generally calls for ventilatory support, especially if
weakness is increasing.

sion of the ipsilateral lower limbof many patients

who have had a stroke. To assess resistance to
passive
movement, the patient is asked to relax while each
MOTOR DEFICITS / 155
limb
is examined in turn by passively taking the major
Family History
joints
through their full range of movement at different
Hereditary factors may be important, and the
and estimating whether the force required is
patients family background therefore must speeds
be
more or less than normal.
explored. Some types of myopathy, motor neu1. HypertoniaTwo types of increased tone can be
ron disease, and peripheral neuropathy have a
distinguished.
genetic
a. Spasticityconsists of an increase in tone that
basis, as do some spinocerebellar degenerations,
afheredifects different muscle groups to different extents. In
tary spastic paraparesis, and certain other neurologic
the
disorders. In certain instances, it may be necessary
to
arms, tone is increased to a greater extent in the
examine other family members to determine whether
exor
the
patients disorder
has a hereditary
Examination
of the Motor
System basis.
muscles than in the extensors; in the legs, tone is inIn examining the motor system, a systematic
creased to a greater extent in the extensor muscles
approach
than
will help to avoid overlooking important
in the exors. Moreover, the resistance of affected
abnormalities.
musA sequential routine for the examination should becle is not the same throughout the range of
A.
de-MUSCLE APPEARANCE
movement
Wasting,
veloped. or muscle atrophy, suggests that weakness
but tends to be most marked when passive
is
movement
due to a lesion of the lower motor neurons or of the
is initiated and then diminishes as the movement
muscle itself.
conThe distribution of wasting may help to localtinues (the clasp-knife phenomenon). The increase in
ize the underlying disorder. Upper motor neutone is velocity dependent, so that passive
ron disorders are not usually accompanied by
movement at
muscle wasting, though muscle atrophy may
a high velocitybut not at lower velocitiesmay be
occasionmet with increased resistance. Spasticity is caused by
ally occur with prolonged disuse. Pseudohypertrophy
an
of muscles occurs in certain forms of myopathy, but
upper motor neuron lesion, such as a stroke that inthe
apparently enlarged muscles are weak and abby.volves the supplementary motor cortex or
The presence of fasciculationsvisible irregularcorticospinal
ickerings over the surface of the affected muscle tract. Spasticity may not become apparent for several
days following the onset of an acute lesion, however.
caused by spontaneous contractions of individual motor unitssuggests that weakness is due to a lower b. Rigidityconsists of increased resistance to passive movement that is independent of the direction of
motor
lesion. Fasciculations are most apt to bethe movementie, it affects agonist and antagonist
B. Mneuron
USCLE TONE
muscle
groups equally. The term lead-pipe rigidity is
seen
in anterior
horn cell
but also
in
For clinical
purposes,
tonedisorders,
can be dened
as occur
the sometimes
used for descriptive purposes, whereas
normal
resist- individuals. Although such activity does notcogocance of muscle to passive movement of a joint. Tone
wheel rigidity is used when there are superimposed
cur
with upper
neuron
disorders,
exor and
or exdepends
on themotor
degree
of muscle
contraction
on
tensor
spasms of
the limbsof
are
sometimes
seen inratchetlike interruptions in the passive movement,
the mechanical
properties
muscle
and connective
which probably relate to underlying tremor. In
these
tisgeneral,
latter
conditions
as muscle
a resultcontraction
of impaireddepends,
supraspinal
sue. The
degree of
inrigidity indicates extrapyramidal dysfunction and is
control
turn, of reex activity.
due
on the activity of anterior horn cells, which is
to a lesion of the basal ganglia (eg, Parkinson
governed
disease).
by spinal and supraspinal mechanisms. Tone is
2. Hypotonia (accidity)This is characterized by
assessed
excessive oppinessa reduced resistance to passive
by observing the position of the extremities at rest,
movementso that the distal portion of the limb is
by
easily waved to and fro when the extremity is
palpating the muscle belly, and particularly by deterpassively
mining the resistance to passive stretch and
shaken. In hypotonic limbs it is often possible to hymovement.
perextend the joints, and the muscle belly may look
Postural abnormalities may result from the increased
attened and feel less rm than usual. Although
activity of certain muscle groups caused by
hypodisturbances
tonia usually relates to pathologic involvement of the
of reex function, as exemplied by the typical hemilower motor neuron supply to the affected muscles, it
plegic postureexion of the upper limb and extencan also occur with primary muscle disorders, disrup-

C. MUSCLE POWER
When muscle power is to be tested, the patient is
asked
to resist pressure exerted by the examiner. Selected
156 / CHAPTER 5
individual muscles are tested in turn, and strength on the
phenomenonparatoniais particularly apt to occur
Table 53. Grading of muscle power according to
two sides is compared so that minor degrees of weakin patients with frontal lobe or diffuse cerebral
the system suggested by the Medical Research
ness can be recognized. Weakness can result from a
disease.
Council.
disturbance in function of the upper or the lower motor
Grade
Muscle Power
neurons; the distribution of weakness is of paramount
importance in distinguishing between these two
5
Normal power
possibilities. Upper motor neuron lesions (eg, stroke) lead 4
Active movement against resistance and
to
gravity
3
Active movement against gravity but not
weakness that characteristically involves the
resistance
extensors
and abductors more than the exors and adductors of2
Active movement possible only with gravity
the armsand the exors more than the extensors of
eliminated
the legs. Lower motor neuron lesions produce
1
Flicker or trace of contraction
weakness
of the muscles supplied by the affected neurons; the 0
No contraction
particular distribution of the weakness may point to
Reproduced,withpermission,fromAidstotheIn
D.
COORDINATION
lower motor neuron involvement at the spinal cord,
vestigationofPeripheralNerveInjuries.HMSO,
The
coordination of motor activity can be impaired by
nerve root, plexus, or peripheral nerve level.
1943.
weakness,
sensory disturbances, or cerebellar
On the basis of the history and other ndings, musdisease
cles that are particularly likely to be affected are selected for initial evaluation, and other muscles areand requires careful evaluation.
(also
tetraplegia,
tetraparesis)
is with
weakness
Voluntary
activity
is observed
regardoftoall
itsfour
acsublimbs.
curacy,
velocity,
range,
and
regularity,
and
the
sequently examined to determine the distribution of
the weakness more fully and to shorten the list of manner
in which individual actions are integrated to produce
diagnostic possibilities. For instance, if an upper motora
smooth complex movement. In the nger-nose test,
neuron (pyramidal) lesion is suspected, the extensors
the
and abductors of the upper extremity and the exors
patient moves the index nger to touch the tip of his
of
the lower extremity are tested in the most detail, or
her nose and then the tip of the examiners index nsince
ger; the examiner can move his or her own nger
these muscles will be the most affected.
about
Weakness may also result from a primary muscle
during the test to change the location of the target
disorder (myopathy) or from a disorder of neuromuscular transmission. In patients with a motor decitand
in
position it so that the patients arm must
all limbs that is not due to an upper motor neuron should
leextend
sion, proximal distribution of weakness suggests a
fully to reach it. In the heel-knee-shin test, the recummyobent patient lifts one leg off the bed, exes it at the
pathic disorder, whereas predominantly distal
knee, places the heel on the other knee, and runs the
involvement suggests a lower motor neuron disturbance. heel down the shin as smoothly as possible.
Marked variability in the severity and distribution of The patient should also be asked to tap repetitively
with one hand on the back of the other; to tap alterweakness over short periods of time suggests
nately with the palm and back of one hand on the
myastheback
nia gravis, a disorder of neuromuscular transmission.
of the other hand or on the knee; to screw an imagiApparent weakness that is not organic in nature also
shows a characteristic variability; it is often more nary light bulb into the ceiling with each arm in turn;
and to rub the ngers of one hand in a circular polishsevere
ing movement on the back of the other hand. Other
on formal testing than is consistent with the patients
daily activities. Moreover, palpation of antagonist tests of rapid alternating movement include tapping
on
musthe ball of the thumb with the tip of the index nger
cles commonly reveals that they contract each time
or
the
tapping the oor as rapidly as possible with the sole
patient is asked to activate the agonist.
keeping the heel of the foot in place. During all
For practical and comparative purposes, power while
is
these
best graded in the manner shown in Table 53. Mono- tests, the examiner looks for irregularities of
plegia denotes paralysis or severe weakness of therate,
amplitude, and rhythm and for precision of movemusments. With pyramidal lesions, ne voluntary movecles in one limb, and monoparesis denotes less

MOTOR DEFICITS / 157

ments are performed slowly. With cerebellar lesions,
may be lost or depressed by any lesion that
the
interrupts
rate, rhythm, and amplitude of such movements are
the structural or functional continuity of its reex arc,
iras
regular.
in a root lesion or peripheral neuropathy. In addition,
If loss of sensation may be responsible for impaired
reexes are often depressed during the acute stage
coordination, the maneuver should be repeated both
of an
with eyes closed and with visual attention directedupper
to
motor neuron lesion, in patients who are
the limb; with visual feedback the apparent weakness
deeply
or
comatose, and in patients with cerebellar disease.
incoordination will improve. In patients with
2. HyperreexiaIncreased reexes occur with upcerebellar
per motor neuron lesions, but they may also occur
disease, the main complaint and physical nding are
with
ofsymmetric distribution in certain healthy subjects and
E.
REFLEXES
tenTENDON
of incoordination,
and examination may revealinlitpatients under emotional tension. The presence of
Changes
in the tendon
reexes
may
accompany
tle else. Further
discussion
of the
ataxia
of cerebellar
reex asymmetry is therefore of particular clinical sigdisturdisease and the various terms used to describe nicance. Clonus consists of a series of rhythmic
bances
a
aspects in
ofmotor (or sensory) function and provide reex
guide
to
the
cause
of
the
motor
decit.
The
tendon
is
it will be found in Chapter 3.
contractions
of a muscle that is suddenly subjected to
tapped with a reex hammer to produce a suddensustained stretch, with each beat caused by renewed
brisk
stretch of the muscle during relaxation from its previstretch of the muscle and its contained spindles. The
ous contracted state. Sustained clonusmore than
clinically important stretch reexes and the nerves,
three or four beats in response to sudden sustained
roots, and spinal segments subserving them are indistretchis always pathologic and is associated with
cated in Table 54. When the reexes are tested, the
an
limbs on each side should be placed in identical posiabnormally brisk reex. In hyperreexic states, there
tions and the reexes elicited in the same manner.may be spread of the region from which a particular
1. AreexiaApparent loss of the tendon reexes
rein
ex response can be elicited. For example, elicitation
a patient may merely reect a lack of clinical
of
expertise
the biceps reex may be accompanied by reex
on the part of the examiner. Performance of
nger
Jendrassik
exion, or eliciting the nger exion reex may cause
maneuver (an attempt by the patient to pull apartexion
the
of the thumb (Hoffmann sign).
ngers of the two hands when they are hooked to- 3. Reex asymmetryAlthough the intensity of
gether)
or Muscle
some similar
action
(such1 as making a st
reex responses varies considerably among subjects,
Table 54.
strength
reexes.
with the hand that is not being tested) may elicit the
reexes should be symmetric in any individual. Sevreeral general points can be made regarding reex
Segmental
ex response when
it is otherwise unobtainable. Aasymmetries.
Innervation
Reex
Nerve
reex
a. Lateralized asymmetries of responseie,
Jaw
Pons
Mandibular branch, reexes
trigeminal
that are brisker on one side of the body than on the
F. SUPERFICIAL REFLEXES
Biceps
C5, C6
Musculocutaneous otherusually indicate an upper motor neuron distur1. Thebut
polysynaptic
abdominal
bance,
sometimessupercial
reect a lower
motor reexes,
neuron
which
depend on the integrity of the T812 spinal
Brachioradialis
C5, C6
Radial
lecord
segments,
by gentlyreexes.
stroking each
sion on
the side are
withelicited
the depressed
Triceps
C7, C8
Radial
quadrant
of
the
abdominal
wall
with
a
b. Focal reex decits often relate toblunt
root,object
plexus,
such
as
a
wooden
stick.
A
normal
response
consists
Finger
C8,T1
Median
or
of
peripheral nerve lesions. For example, unilateral
Knee
L3, L4
Femoral
contraction
of the muscle in the quadrant stimulated,
depreswith
a
brief
movement
of the umbilicus
the
Ankle
S1, S2
Tibial
sion of the ankle jerk commonly
reectstoward
an S1 radicustimulus.
Asymmetric
loss
of
the
response
may
lopathy resulting from a lumbosacral disk lesion.be of
1 At the National Institutes of Health, the reexes are
di-c. Loss of distal tendon reexes (especially ankle
graded on the following scale: 0, absent; 1, reduced, trace
agnostic signicance.
response, or present only with reinforcement; 2 and 3, in jerks), with preservation of more proximal ones, is
a. The in
response
may be depressed or lost on one
polyneuropathies.
lower and upper half of normal range, respectively; 4, en- common
side
in
patients
with
an upper motor neuron disturhanced, with or without clonus.
bance from a lesion of the contralateral motor cortex
or
its descending pathways.

tients with disturbances, usually bilateral, of frontal

lobe function, such as may occur in hydrocephalus or
progressive dementing disorders. There is no
weakness
158 / CHAPTER 5
or incoordination of the limbs, but the patient is unable to stand unsupported or to walk properlythe
b. Segmental loss of the response may relate to
feet seem glued to the ground. If walking is possible
local
at
disease of the abdominal wall or its innervation, as in
all, the gait is unsteady, uncertain, and shorta
stepped,
radiculopathy.
with marked hesitation (freezing), and the legs are
c. The cutaneous abdominal reexes are frequently
moved in a direction inappropriate to the center of
absent bilaterally in the elderly, in the obese, in
gravity.
multi2. Corticospinal lesionsA corticospinal lesion, irparous women, and in patients who have had
respective of its cause, can lead to a gait disturbance
abdomithat varies in character depending on whether there
nal surgery.
is
2. The cremasteric reex, mediated through the L1
unilateral or bilateral involvement. In patients with
and L2 reex arcs, consists of retraction of the ipsilathemiparesis, the selective weakness and spasticity
eral testis when the inner aspect of the thigh is lightly
lead
stroked; it is lost in patients with a lesion involving
to a gait in which the affected leg must be circumthese nerve roots. It is also lost in patients with conducted to be advanced. The patient tilts at the waist
tralateral upper motor neuron disturbances.
to3. Stimulation of the lateral border of the foot in a
ward the normal side and swings the affected leg outnormal adult leads to plantar exion of the toes and
ward as well as forward, thus compensating for any
dorsiexion of the ankle. The Babinski response contendency to drag or catch the foot on the ground besists of dorsiexion of the big toe and fanning of the
cause of weakness in the hip and knee exors or the
other toes in response to stroking the lateral border
anof
kle dorsiexors. The arm on the affected side is
the foot, which is part of the S1 dermatome; exion
usually
at
held exed and adducted. In mild cases, there may
the hip and knee may also occur. Such an extensor
be
plantar response indicates an upper motor neuron leno more than a tendency to drag the affected leg, so
sion involving the contralateral motor cortex or the
that the sole of that shoe tends to be excessively
corticospinal tract. It can also be found in
worn.
anesthetized
With severe bilateral spasticity, the legs are
or comatose subjects, in patients who have had a
brought
seizure, and in normal infants. An extensor plantar restify forward and adducted, often with
sponse
G. GAIT can also be elicited, though less reliably, by
compensatory
such
In evaluating gait, the examiner rst observes the movements
paof the trunk. Such a gait is commonly demaneuvers
asatpricking
the dorsal
surface
of the
tient walking
a comfortable
pace.
Attention
is big
discribed as scissorslike. This gait is seen in its most
toe
rected at the stance and posture; the facility with exwith
whicha pin (Bing sign), rmly stroking down the antetreme form in children with spastic diplegia from peririor
border of
the tibia
from knee
to ankle
the patient
starts
and stops
walking
and turns to natally acquired static encephalopathy. In patients
(Oppenheim
either
with
maneuver),
squeezing
the calfthe
muscle
(Gordon
side; the length
of the stride;
rhythm
of walking;
mild spastic paraparesis, the gait is shufing, slow,
maneuthe presence of normally associated movements, stiff,
ver)
suchor
asAchilles tendon (Schafer maneuver), icking
and awkward, with the feet tending to drag.
the
swinging of the arms; and any involuntary
3. Frontal disordersSome patients with frontal
little
toe (Gonda maneuver), or stroking the back of
movements.
lobe or white matter lesions have a gait characterized
the
footgait
justdisorders
below the
lateral apparent
malleolusonly
(Chaddock
Subtle
become
when by
the
mapatient is asked to run, walk on the balls of the feet
short, shufing steps; hesitation in starting or turning;
neuver).
In interpreting responses, attention must be
or
unsteadiness; and a wide or narrow base. Sometimes
focused
only
direction
the big toe rst
the heels, hopononthe
either
foot, in
or which
walk heel-to-toe
removes.
along
ferred to as marche petit pas, this abnormality may
a straight line. Gait disorders occur in many
be mistaken for a parkinsonian gait, but the wide
neurologic
base,
disturbances and in other contexts that are beyond
preserved arm swing, absence of other signs of
the
parkinscope of this chapter. A motor or sensory disturbance
sonism, and accompanying ndings of cognitive immay lead to an abnormal gait whose nature depends
pairment, frontal release signs, pseudobulbar palsy,
upon the site of pathologic involvement. Accordingly,
pythe causes and clinical types of gait disturbance are
ramidal decits, and sphincter disturbances are
best
helpful
considered together.
in indicating the correct diagnosis. In patients with
1. Apraxic gaitApraxic gait occurs in some pa-frontotemporal dementia, however, a parkinsonian

by loss of the arm swinging that normally

accompanies
locomotion. In mild parkinsonism, a mildly slowed or
unsteady gait, exed posture, or reduced arm
MOTOR DEFICITS / 159
swinging
may be the only abnormality found.
8. Unsteady gait in the elderlyMany elderly perb. Abnormal posturing of the limbs or trunk is a
sons complain of unsteadiness when walking and a
feature of dystonia; it can interfere with locomotion
fear
or
of falling, but neurologic examination reveals no
lead to a distorted and bizarre gait.
abnorc. Chorea can cause an irregular, unpredictable,
mality. Their symptoms have been attributed to reand
duced sensory input from several different afferent
unsteady gait, as the patient dips or lurches from side
systo side. Choreiform movements of the face and
tems and impaired central processing of sensory
extreminput;
ities are usually well in evidence.
an
impairment
of vestibular OF
function
also be imCLINICAL
LOCALIZATION
THE may
LESION
d. Tremor that occurs primarily on standing (orthoportant.
static tremor) may lead to an unsteady, uncertain The ndings on examination should indicate whether
gait,
the weakness or other motor decit is due to an
with hesitancy in commencing to walk.
upper
5. Cerebellar disordersIn cerebellar disorders or lower motor neuron disturbance, a disorder of neu(see
romuscular transmission, or a primary muscle
Chapter 3), the gait may be disturbed in several disorder.
ways.
In the case of an upper or lower motor neuron distura. Truncal ataxia results from involvement of midbance, the clinical ndings may also help to localize
line cerebellar structures, especially the vermis. The
the
gait
lesion more precisely to a single level of the nervous
is irregular, clumsy, unsteady, uncertain, and broadsystem.
Such localization
helps to reduce the number
Upper Motor
Neuron Lesions
based, with the patient walking with the feet wide of
apart
A.
SIGNS
diagnostic
possibilities.
for additional support. Turning and heel-to-toe
Weakness or paralysis.
walking
Spasticity.
are especially difcult. There are often few
Increased tendon reexes.
accompany An extensor plantar (Babinski) response.
ing signs of a cerebellar disturbance in the limbs. Loss of supercial abdominal reexes.
Causes include midline cerebellar tumors and the Little, if any, muscle atrophy.
cereSuch
signs occur
OF U
with
NDERLYING
involvement
LESION of the upper
bellar degeneration that can occur with alcoholismB.
orLOCALIZATION
motor
1. A parasagittal intracranial lesion produces an uphypothyroidism, as a nonmetastatic complication of
neuron
per
motor
at any
neuron
point,
decit
but further
that characteristically
clinical ndingsaffects
decancer, and with certain hereditary disorders.
pend legs
uponand
themay
actual
site
of the the
lesion.
Note that it
later
involve
arms.
b. In extreme cases, with gross involvement of both
may
2. not
A discrete
be possible
lesiontooflocalize
the cerebral
a lesion
cortex
by itsormotor
its promidsigns
alone.
jections
may
produce
a
focal
motor
decit
involving,
line cerebellar structures (especially the vermis), the
for
paexample, the contralateral hand. Weakness may be
tient cannot stand without falling.
c. A lesion of one cerebellar hemisphere leads torestricted to the contralateral leg in patients with
an
anterior
unsteady gait in which the patient consistently falls
cerebral artery occlusion or to the contralateral face
or
and
lurches toward the affected side.
arm if the middle cerebral artery is involved. A more
6. Impaired sensationImpaired sensation, espeexcially disturbed proprioception, also leads to an unsteady gait, which is aggravated by walking in thetensive cortical or subcortical lesion will produce
weakdark
or with the eyes closed, since visual input cannot ness or paralysis of the contralateral face, arm, and
leg
then
compensate for the sensory loss. Because of their and may be accompanied by aphasia, a visual eld
dedefective position sense, many patients lift their feet fect, or a sensory disturbance of cortical type.
3. A lesion at the level of the internal capsule,
higher
where
than necessary when walking, producing a steppage
gait. Causes include tabes dorsalis, sensory neu- the descending bers from the cerebral cortex are
closely packed, commonly results in a severe
ropathies, vitamin B12 deciency, and certain
hemiparehereditary
sis that involves the contralateral limbs and face.
disorders (discussed in Chapter 6).
7. Anterior horn cell, peripheral motor nerve, or 4. A brainstem lesion commonlybut not invari-

160 / CHAPTER 5
ablyleads to bilateral motor decits, often with acLower Motor Neuron Lesions
companying sensory and cranial nerve disturbances,
and disequilibrium. A more limited lesion involvingA. SIGNS
the brainstem characteristically leads to a cranial Weakness or paralysis.
Wasting and fasciculations of involved muscles.
nerve
Hypotonia (accidity).
disturbance on the ipsilateral side and a contralateral
Loss of tendon reexes when neurons subserving
hemiparesis; the cranial nerves affected depend on
them are affected.
the

Normal abdominal and plantar reexesunless the

level at which the brainstem is involved.
neurons
subserving them are directly involved, in
5. A unilateral spinal cord lesion above the fth cerwhich
case
reex responses are lost.
vical segment (C5) causes an ipsilateral hemiparesis
that spares the face and cranial nerves. Lesions beB. LOCALIZATION OF THE UNDERLYING LESION
tween C5 and the rst thoracic segment (T1) affect
In distinguishing weakness from a root, plexus, or pethe ipsilateral arm to a variable extent as well as the
ripheral nerve lesion, the distribution of the motor
ipdecit is of particular importance. Only those muscles
silateral leg; a lesion below T1 will affect only the ipsilateral leg. Because, in practice, both sides of the supplied wholly or partly by the involved structure are
weak (Tables 55 and 56). The distribution of any accord
companying sensory decit similarly reects the locaare commonly involved, quadriparesis or paraparesis
tion of the underlying lesion (see Figure 61). It may
usually results. If there is an extensive but unilateral
be impossible to distinguish a radicular (root) lesion
cord lesion, the motor decit is accompanied by ipsilateral impairment of vibration and position sense from discrete focal involvement of the spinal cord. In
the latter situation, however, there is more often a
and
bilatby contralateral loss of pain and temperature
eral motor decit at the level of the lesion, a cortiappreciation (Brown-Squard syndrome). With compressivecospinal or sensory decit below it, or a disturbance
of
and other focal lesions that involve the anterior horn
bladder, bowel, or sexual function. Certain disorders
cells in addition to the ber tracts traversing the cord,
sethe muscles innervated by the affected cord segment
lectively affect the anterior horn cells of the spinal
weaken and atrophy. Therefore, a focal lower motor
Table
55.
Innervation
of
selected
muscles
of
upper
limbs.
cord
neuron decit exists at the level of the lesion and an
upper motor neuron decit exists below itin addiRoot
Peripheral Nerve
Main Action
tion toMuscle
any associated sensoryMain
disturbance.
Supraspinatus

C5

Suprascapular

Abduction of arm

Infraspinatus

C5

Suprascapular

External rotation of arm at shoulder

Deltoid

C5

Axillary

Abduction of arm

Biceps

C5, C6

Musculocutaneous

Elbow exion

Brachioradialis

C5, C6

Radial

Elbow exion

Extensor carpi radialis longus

C6, C7

Radial

Wrist extension

Flexor carpi radialis

C6, C7

Median

Wrist exion

Extensor carpi ulnaris

C7

Radial

Wrist extension

Extensor digitorum

C7

Radial

Finger extension

Triceps

C8

Radial

Extension of elbow

Flexor carpi ulnaris

C8

Ulnar

Wrist extension

Abductor pollicis brevis

T1

Median

Abduction of thumb

Opponens pollicis

T1

Median

Opposition of thumb

First dorsal interosseous

T1

Ulnar

Abduction of index nger

Abductor digiti minimi

T1

Ulnar

Abduction of little nger

MOTOR DEFICITS / 161

Table 56. Innervation of selected muscles of lower limbs.
Muscle

Main Root

Peripheral Nerve

Main Action

Iliopsoas

L2, L3

Femoral

Hip exion

Quadriceps femoris

L3, L4

Femoral

Knee extension

Adductors

L2, L3, L4

Obturator

Adduction of thigh

Gluteus maximus

L5, S1, S2

Inferior gluteal

Hip extension

Gluteus medius and minimus, tensor fasciae

latae
Hamstrings

L4, L5, S1

Superior gluteal

Hip abduction

L5, S1

Sciatic

Knee exion

Tibialis anterior

L4, L5

Peroneal

Dorsiexion of ankle

Extensor digitorum longus

L5, S1

Peroneal

Dorsiexion of toes

Extensor digitorum brevis

S1

Peroneal

Dorsiexion of toes

Peronei

L5, S1

Peroneal

Eversion of foot

Tibialis posterior

L4

Tibial

Inversion of foot

Gastrocnemius

S1, S2

Tibial

Plantar exion of ankle

Soleus

S1, S2

Tibial

Plantar exion of ankle

diffusely (see Anterior Horn Cell Diseases) or the patient may rst ex the elbow and then bring the
motor
hand up to the nose instead of combining the maneunerves; the extensive lower motor neuron decit vers into one action. Intention tremor occurs during
withactivity and is often most marked as the target is
out sensory changes helps to indicate the site andneared. The rebound phenomenon is the
naovershooting
Cerebellar Dysfunction
ture of the pathologic involvement.
of the limb when resistance to a movement or
A. SIGNS
posture
Hypotonia.
is suddenly withdrawn.
Depressed or pendular tendon reexes.
The gait becomes unsteady in patients with distur Ataxia.
bances of either the cerebellar hemispheres or
Gait disorder.
midline
Imbalance of station.
structures, as discussed in Chapter 3.
Disturbances of eye movement.
Jerk nystagmus, which is commonly seen in
Dysarthria.
patients
with a unilateral lesion of the cerebellar hemisphere,
Ataxia is a complex movement disorder caused, at
is
least
slowest and of greatest amplitude when the eyes are
in part, by impaired coordination. It occurs in the
turned to the side of the lesion. Nystagmus is not
limbs on the same side as a lesion affecting the
present
cerebelin patients with lesions of the anterior cerebellar
lar hemisphere. With midline lesions, incoordination
B.
LOCALIZATION OF THE UNDERLYING LESION
vermis.
may not be evident in the limbs at all, but there is The relationship of symptoms and signs to lesions of
Speech becomes dysarthric and takes on an irregumarked truncal ataxia that becomes evident on walkdiflar and explosive quality in patients with lesions that
ing. The term dysmetria is used when movementsferent
are
of the cerebellum
is considered
involveparts
the cerebellar
hemispheres.
Speech in
is usually
not adjusted accurately for range, so thatfor examChapter
3.
unremarkable when only the midline structures are
plea moving nger overshoots a target at which Neuromuscular-Transmission
it
Disorders
involved.
is
A. SIGNS
aimed. Dysdiadochokinesia denotes rapid alternating
movements that are clumsy and irregular in termsofNormal or reduced muscle tone.
Normal or depressed tendon and supercial
rhythm and amplitude. Asynergia or dyssynergia dereexes.
notes the breakdown of complex actions into the individual movements composing them; when asked to
touch the tip of the nose with a nger, for example,
the

162 / CHAPTER 5
No sensory changes.
B. DIFFERENTIATION
Weakness, often patchy in distribution, not
In distinguishing the various myopathic disorders, it is
conformimportant to determine whether the weakness is
ing to the distribution of any single anatomic struccongenture; frequently involves the cranial muscles andital or acquired, whether there is a family history of a
may
similar disorder, and whether there is any clinical eviuctuate in severity over short periods, particularly
dence that a systemic disease may be responsible.
in
The
relation to activity.
distribution of affected muscles is often especially
B. LOCALIZATION OF THE UNDERLYING LESION
imporPathologic involvement of either the pre- or
tant
in distinguishing
the various hereditary
INVESTIGATIVE
STUDIES
postsynapmyopathies
Investigative
studies
of patients
with514,
weakness
tic portion of the neuromuscular junction may impair
(see Myopathic
Disorders
and Table
later).from
Myopathic
Disorders
focal
neuromuscular transmission. Disorders affecting
cerebral decits are considered in Chapter 11. The
neuroA.
SIGNS
invesmuscular
transmission
aremarked
discussed
later.

Weakness,
usually most
proximally
rather
tigations discussed here may be helpful in evaluating
than distally.
Imaging
pa No muscle wasting or depression of tendon reexes
with
A. PLAIN
X-Rweakness
AYS OF THE Sfrom
PINE other causes (Table 57).
until at least an advanced stage of the disorder. tients
Congenital abnormalities and degenerative,
Normal abdominal and plantar reexes.
inamma No sensory loss or sphincter disturbances.
tory, neoplastic, or traumatic changes may be
revealed
Table 57. Investigation of patients with weakness.

Test

Spinal Cord
Disorders

Serum enzymes Normal

Anterior Horn Cell

Disorders
Normal or mildly
increased

Peripheral Nerve
or Plexus
Disorders
Normal

Neuromuscular
Junction
Disorders
Normal

Myopathies
Normal or increased

ElectromyographyReduced number of motor units under voluntary control;

Often normal, but Small, short,
with lesions causing axonal degeneration, abnormalindividual motor
abundant
spontaneous activity (eg, fasciculations, brillations)
units
maymay show
polyphasic motor
be
abnormal variabilityunit potentials;
present if sufcient time has elapsed after onset; with
in size
abnormal
reinnervation, motor units may be large, long, and
spontaneous activity
polyphasic
may be conspicuous
in myositis
Nerve conduction Normal
velocity

Normal

Muscle response Normal

to repetitive
motor nerve
stimulation

Normal, except in Normal

rapidly progressive
disease

Muscle biopsy
Myelography
or spinal MRI

Slowed, especially
Normal
in demyelinative
neuropathies.
May be normal
in axonal
neuropathies

May be normal in acute stage but subsequently

suggestive
of denervation
May be helpfulHelpful in excludingNot helpful
other disorders

Normal

Abnormal decrement
Normal
or increment
depending on
stimulus frequency
and disease
Normal

Changes suggestive
of myopathy

Not helpful

Not helpful

MOTOR DEFICITS / 163

by plain x-rays of the spine, which therefore should
trauma, surgery, intramuscular injections, EMG, or
be
vigorous activity.
undertaken in the evaluation of patients with
suspected
Muscle Biopsy
B.
CTor
SCAN
MRI
cord
rootORlesions.
A computed tomography (CT) scan of the spine, espeHistopathologic examination of a specimen of weak
cially when performed after instilling water-solublemuscle can be important in determining whether the
contrast material into the subarachnoid space, may
unalso
derlying weakness is neurogenic or myopathic in
reveal disease involving the spinal cord or nerve origin.
roots.
With neurogenic disorders, muscle biopsy specimens
Magnetic resonance imaging (MRI) is superior to CT
show atrophied bers occurring in groups, with
C.
MYELOGRAPHY
scanning
in this regard (see Chapter 11).
adjacent
Radiologic study of the spinal subarachnoid space groups of larger, uninvolved bers. In myopathies,
with
atroinjection of a contrast medium is an important means
phy occurs in a random pattern; nuclei of muscle cells
of visualizing intramedullary tumors and exmay be centrally situated, in contrast to their normal
tramedullary lesions that compress the spinal cordpeor
nerve roots, and certain vascular malformations. Itripheral location; and brosis or fatty inltration may
can
be
also permit detection of congenital or acquired strucseen. In addition, examination of a muscle biopsy
tural abnormalities, especially in the region of the speciforaSPINAL
CORD
DISORDERS
men may permit
recognition
of certain inammatory
men magnum. For most purposes, however, spinalmuscle diseases (eg, polymyositis) for which specic
Electrodiagnostic Studies
MRI is superior to myelography (see Chapter 11). treatment is availablehelping to differentiate them
Cord lesions can lead to motor, sensory, or sphincter
The function of the normal motor unit, which consists
from muscle disorders that have no specic
disturbances
or to some combination of these
of a lower motor neuron and all of the muscle bers
it
treatment.
decits.
innervates, may be disturbed at any of several sites
Depending upon whether it is unilateral or bilateral, a
in patients with weakness. A lesion may, for example, lesion above C5 may cause either an ipsilateral hemiparesis or quadriparesis. With lesions located lower in
affect
the cervical cord, involvement of the upper limbs is
the anterior horn cell or its axon, interfere with neuropartial, and a lesion below T1 affects only the lower
muscular transmission, or involve the muscle bers
limbs on one or both sides. Disturbances of sensation
diare considered in detail in Chapter 6, but it should be
rectly so that they cannot respond normally to neural
noted here that unilateral involvement of the
acposterior
tivation. In each circumstance, characteristic changes
columns of the cord leads to ipsilateral loss of
Damage
to muscle bers may lead to the release of
in
position
certhe electrical activity can be recorded from affected
tain
mus-enzymes [creatine kinase (CK), aldolase, lacticand vibration sense. In addition, any disturbance in
function of the spinothalamic tracts in the
acid
cle
by aEnzymes
needle electrode inserted into it and
Serum
dehydrogenase,
and the transaminases] that can anterolateral
connected
impairs contralateral pain and temperature
then
to an be
oscilloscope (electromyography). Dependingcolumns
on
apdetected
in
increased
amounts
in
serum.
Serum
CK
the site of pathology, nerve conduction studies or the
preciation below the level of the lesion.
shows
greatesttoincrease
and
is thestimulation
most useful
musclethe
responses
repetitive
nerve
may
Spasticity is a common accompaniment of upper
for
also
motor
neuron lesions and may be especially troublefollowing
the course
of muscle
disease.
is also
be abnormal.
See Chapter
11 for
furtherItdetails.
some
below
the level of the lesion in patients with
present
myelopathies.
When the legs are weak, the increased
in high concentrations in the heart and brain,
tone
of
spasticity
may help to support the patient in
however,
the
and damage to these structures can lead to increased
serum CK levels. Fractionation of serum CK into upright position. Marked spasticity, however, may
lead
isoenzyme forms is useful for determining the tissue
to
deformity, interfere
with toilet functions, and cause
of
TRAUMATIC
MYELOPATHY
exor or extensor spasms. Pharmacologic
origin. In patients with weakness, elevated serum painful
CK
Although
cord damage may result from whiplash (remanlevels are generally indicative of a primary myopathy,
coil)
injury,
severetreatment
injury to the
cord
usually relates
to
agement includes
with
diazepam,
baclofen,
especially one that is evolving rapidly. A moderately
dantrolene, or tizanidine, as discussed below under
eleTraumatic Myelopathy, but reduction in tone may lead
vated serum CK may also occur in motor neuron disease, however, and more marked elevations can to
increased disability from underlying leg weakness.
follow

164 / CHAPTER 5
fracture-dislocation in the cervical, lower thoracic, 5.4
or mg/kg/h for 24 hours) can improve motor and
upper lumbar region.
sensory function at 6 months when treatment is begun
within 8 hours of traumatic spinal cord injury. The
Clinical Findings
mechanism of the action is unknown, but it may involve the inhibition of lipid peroxidation and the imA. TOTAL CORD TRANSECTION
Total transection results in immediate permanent provement of blood ow to the injured spinal cord.
C. PAINFUL SPASMS
paralysis and loss of sensation below the level of the
Painful exor or extensor spasms can be treated with
ledrugs that enhance spinal inhibitory mechanisms (basion. Although reex activity is lost for a variable period after the injury, a persistent increase in reexclofen, diazepam) or uncouple muscle excitation from
contraction (dantrolene). Baclofen should be given
function follows.
5 mg orally twice daily, increasing up to 30 mg four
1. In the acute stage, there is accid paralysis with
times daily; diazepam, 2 mg orally twice daily up to
loss of tendon and other reexes, accompanied by
as
senhigh as 20 mg three times daily; and dantrolene,
sory loss and by urinary and fecal retention. This is
25 mg/d orally to 100 mg four times daily. Tizanidine,
the
a central 2-agonist, may also be helpful but its
stage of spinal shock.
precise
2. Over the following weeks, as reex function returns, the clinical picture of a spastic paraplegia ormechanism of action is unclear. The daily dose is built
up gradually, usually to 8 mg three times daily. Side
quadriplegia emerges, with brisk tendon reexes and
extensor plantar responses; however, a accid, effects include dryness of the mouth, somnolence, and
atrophic
but the drug is usually well tolerated.
(lower motor neuron) paralysis may affect muscleshypotension,
inPanervated by spinal cord segments at the level of the
tients who fail to benet from or who cannot tolerate
lesion, where anterior horn cells are damaged. The sufcient doses of oral medications may respond to
inbladder and bowel now regain some reex function, sotrathecal infusion of baclofen.
D. All
SKIN
CARE drugs may increase functional disability
these
that
Particular
attention must be given to skin care, avoidby
urine and feces are expelled at intervals.
ing
continued
on any
area.
reducing tone.pressure
Dantrolene
maysingle
also increase
3. Flexor or extensor spasms of the legs may beB.
LESSincreasingly
SEVERE INJURYtroublesome and are ultimately weakness
come
E. BLADDER
AND BOWEL DISORDERS
With
lesser
degrees
injury, cutaneous
the neurologic
decitand
is should be avoided in patients with severely comelicited by even
the of
slightest
stimulus,
Depending
on the severity
of the injury,
promised respiratory
function.
less severe and less complete, but patients may be
especatheterization
left
cially in the presence of bedsores or a urinary tractmay be necessary initially. Subsequently, the urgency
with
in- a mild paraparesis or quadriparesis or a distaland frequency of the spastic bladder may respond to
senfection. Eventually, the patient assumes a posturea
sory
with disturbance. Sphincter function may also be imparasympatholytic drug such as oxybutynin, 5 mg
pairedurinary
urgency
and urgency
incontinence
the legs in exion
or extension,
the former
being three
are
espetimes daily. Suppositories and enemas will help mainespecially
Hyperextension
of the
cially likelycommon.
with cervical
or completeinjuries
cord lesions.
tain regular bowel movements and may prevent or
neck can lead to focal cord ischemia that causes conbibrachial paresis (weakness of both arms) with DEMYELINATING MYELOPATHIES
trol fecal incontinence.
Treatment
sparing
1. MULTIPLE SCLEROSIS
of the
legs and variable sensory signs.
A.
IMMOBILIZATION
Initial treatment consists of immobilization until the
Epidemiology
nature and extent of the injury are determined. If
there
Multiple sclerosis is one of the most common neurois cord compression, urgent decompressive surgery
logic disorders, affecting about 300,000 patients in
will
the
be necessary. An unstable spine may require surgical
United States, and its highest incidence is in young
xation, and vertebral dislocation may necessitateadults. It is dened clinically by the involvement of
B.
CORTICOSTEROIDS
spinal
traction.
difCorticosteroids (eg, methylprednisolone, 30 mg/kgferent
in- parts of the central nervous system at different
travenous bolus, followed by intravenous infusion timesprovided
at
that other disorders causing multifocal central dysfunction have been excluded. Initial
symptoms generally commence before the age of

MOTOR DEFICITS / 165

55 years, with a peak incidence between ages 20 and
Table 58. Symptoms and signs of multiple
40; women are affected nearly twice as often as men.
sclerosis.
Epidemiologic studies show that the prevalence of
the disease rises with increasing distance from the
Percentage
equaof Patients
tor, and no population with a high risk for the disease
exists between latitudes 40N and 40S. A geneticSymptoms (at presentation)
Paresthesia
37
preGait disorder
35
disposition is suggested by twin studies, the
Lower extremity weakness or
occasional
incoordination
17
familial incidence, and the strong association
Visual loss
15
between
Upper extremity weakness or
the
disease
and
specic
HLA
antigens
(HLA
DR2).
incoordination
Pathology
10
Present evidence supports the belief that the disease
Diplopia
10
The
disorder
is
characterized
pathologically
by
the
has
dean autoimmune basis.
Signs
velopment of focaloften perivenularscattered Absent abdominal reexes
81
areas
Hyperreexia
76
of demyelination followed by a reactive gliosis; thereLower extremity ataxia
57
54
may be axonal damage as well. These lesions occur Extensor plantar responses
Impaired
rapid
alternating
movements
49
in
Impaired
vibratory
sense
47
the
white matter of the brain and cord and in the
Pathophysiology
Optic neuropathy
38
optic
Nystagmus
35
The
cause
of
multiple
sclerosis
is
unknown,
but
tissue
(II) nerve.
Impaired joint position sense
33
damage and neurologic symptoms are thought to
Intention tremor
32
result
Spasticity
31
from an immune mechanism directed against myelinImpaired pain or temperature sense
22
antigens. Viral infection or other inciting factors mayDysarthria
19
promote the entry of T cells and antibodies into the Paraparesis
17
Internuclear ophthalmoplegia
central nervous system by disrupting the bloodbrain
11
barrier. This leads to increased expression of celladheAdaptedfromSwansonJW:Multiplesclerosis:Up
sion molecules, matrix metalloproteinases, and proindateindiagnosisandreviewofprognosticfactors.
ammatory cytokines, which work in concert to MayoClinProc1989;64:577586.
attract
additional immune cells, break down the extracellular
tients present with an acute or gradually progressive
matrix to aid their migration, and activate
spastic paraparesis and sensory decit; this should
autoimmune
raise
SUBSEQUENT COURSE
responses against antigens such as myelin basic B.
concern
about
theinterval
possibility
of an underlying
strucThere
may
be an
of months
or years after
the
protein,
tural
lesion
unless
there
is
evidence
on
clinical
initial
episode
before
further
neurologic
symptoms
myelin-associated glycoprotein, myelin
examinaapoligodendrocyte
tion ofNew
more
widespread
disease.
pear.
symptoms
may
then develop, or the
glycoprotein, proteolipid protein, B-crystallin, phosoriginal
phodiesterases, and S-100. Binding of these target
ones may recur and progress. Relapses may be
antiClinical Findings
triggered
gens by antigen-presenting cells triggers an autoimA. INITIAL OR PRESENTING SYMPTOMS
by infection and, in women, are more likely in the
mune response that may involve cytokines,
Patients can present with any of a variety of
3 months or so following childbirth. A rise in body
macrophages, and complement. Immune attack on
symptoms
temmyelin denudes axons, which slows nerve conduction
(Table 58). Common initial complaints are focal perature can cause transient deterioration in patients
and leads to neurologic symptoms.
weakness, numbness, tingling, or unsteadiness in with
a
a xed and stable decit. With timeand after a
limb; sudden loss or blurring of vision in one eye number of relapses and usually incomplete
(optic
remissions
neuritis); diplopia; disequilibrium; or a bladder-functhe patient may become increasingly disabled by
tion disturbance (urinary urgency or hesitancy). Such
weaksymptoms are often transient, disappearing after aness, stiffness, sensory disturbances, unsteadiness of
few
the
days or weeks, even though some residual decit limbs, impaired vision, and urinary incontinence.
may
Based on its course, the disease is divided into a
be found on careful neurologic examination. Otherrepalapsing-remitting form (85% of cases) in which pro-

In patients with relapsing-remitting disease,

treatment
with
interferon

given
intramuscularly
once
gression does not occur between attacks; a
In patients
presenting
with
the spinal form
of the
weekly
secondary
disorder and no evidence of disseminated disease,
or
interferon
given subcutaneously
on alternate
progressive form (80% of cases after 25 years)
spinal
MRI or myelography
may be necessary
to exdays
the relapse
rate. Glatiramer
characcludereduces
the possibility
of a single
congenital acetate
or acquired
terized by a gradually progressive course after an (forsurgically treatable lesion. The region of the foramen
merly
copolymer
a mixturetoofexclude
randomthe
polymers
initial
magnum
must be1,
visualized
possibility
simrelapsing-remitting pattern; and a primary
of a lesion such as Arnold-Chiari malformation, in
ulating
the of
amino
acid composition
oflower
myelin
basic
progressive
which part
the cerebellum
and the
brainstem
protein)
giveninto
by daily
subcutaneous
injection ismixed
also
form (10% of cases) in which there is gradual
are displaced
the cervical
canal, producing
effective.
addition
to their
effect
progrespyramidalIn
and
cerebellar
decits
in on
therelapses,
limbs. interferon
and glatiramer acetate may also delay the
sion of disability from clinical onset. A progressive-reonset of signicant disability in patients with
lapsing form occurs rarely, with acute relapses being
Treatment
relapsing
sudisease. Intravenous immunoglobulin (IVIg) infusions
perimposed on a primary progressive course.
may also reduce the relapse rate in relapsingExamination in advanced cases commonly reveals
remitting
opdisease, but treatment recommendations are
tic atrophy, nystagmus, dysarthria, and upper motor
Diagnosis
premature.
neuron, sensory, or cerebellar decits in some or all
The
of diagnosis of multiple sclerosis requires evidence The most common side effects of interferons are a
that
at least
two
different
of the
the diagnosis
central white
the limbs
(see
Table
58). regions
Note that
u-like syndrome and (in the case of interferon
matter
cannot have been affected at different times.
injection site reactions. Glatiramer acetate is
Clinically
be based on any single symptom or sign but only on
generally
denite
disease can be diagnosed in patients with tolerated
a
a
well, but it may produce erythema at the
retotal clinical picture that indicates involvement of sites
lapsing-remitting
course and signs of at least two ledifferof injection, and about 15% of patients experience
sions
involving
regions system
of the central
white
ent parts
of thedifferent
central nervous
at different
transient episodes of ushing, dyspnea, chest
matter.
times. Probable multiple sclerosis is diagnosed when
tightness,
patients have evidence of multifocal white matter palpitations,
disand anxiety after injections. All three of
ease
but
have
had
only
one
clinical
attack,
or
have
a
these
agents
are approved for use in relapsingThese may help to support the clinical diagnosis and
history
of
at
least
two
clinical
episodes
but
signs
of
remitting
exclude other disorders but do not themselves justify
only
multiple sclerosis and are available by prescription.
a
Investigative Studies
a
single
lesion.
They are expensive, but their cost must be balanced
denitive diagnosis of multiple sclerosis.
against the reduced need for medical care and
The cerebrospinal uid (CSF) is commonly abnorreduced
mal, with mild lymphocytosis or a slightly increased
protein concentration, especially if examined soontime lost from work that follows their use.
Corticosteroids may hasten recovery from acute reafter
lapses,
but the extent of the recovery itself is
an acute relapse. CSF protein electrophoresis shows
unchanged.
the
steroid administration does not prevent represence of discrete bands in the immunoglobulin Long-term
G
lapses
and
should not be used because of
(IgG) region (oligoclonal bands) in 90% of patients.
unacceptable
The antigens responsible for these antibodies are not
side effects. There is no standard schedule of
known.
If clinical evidence of a lesion exists at only one treatment
with corticosteroids, but the regimen most commonly
site
used is intravenous methylprednisolone (1 g daily) for
in the central nervous system, a diagnosis of multiple
sclerosis cannot properly be made unless other 35 days, followed by an oral prednisone taper (1
mg/kg/d for 1 week, with rapid reduction over the
regions
ensuing 12 weeks). For mild attacks, some clinicians
have been affected subclinically, as detected by the
prefer oral treatment with prednisone 60 or 80 mg/d,
elecor
trocerebral responses evoked by one or more of the
dexamethasone 16 mg/d, given for a week and
foltapered
lowing: monocular visual stimulation with a checkerboard pattern (visual evoked potentials); monauralrapidly over the following 2 weeks. ACTH (corticotropin) is no longer used.
stimulation with repetitive clicks (brainstem auditory
evoked potentials); and electrical stimulation of a pe-Appropriate treatment of primary or secondary proripheral nerve (somatosensory evoked potentials).gressive multiple sclerosis is less well established.
MRI may also detect subclinical lesions and has Recent
bestudies suggest that interferon
(and probably income nearly indispensable in conrming the
terferon
are effective in reducing the
diagnosis
(Figure 52A,B).
progression
166 / CHAPTER 5

MOTOR DEFICITS / 167

Figure 52. A: A mid-sagittal T2-weighted MRI of the cervical spinal cord in a young woman with multiple sclerosis. An abnormal region of high signal intensity (arrow) is seen. (Courtesy of RA Heyman.) B: Axial T2-weighted
MR
rate
determined
clinically
and bysclerosis
MRI in secondary
brainas
images
of a patient
with multiple
showing multiple, primarily punctate, white matter plaques
progressive
butlocation
there is
limited
(arrows); notedisease,
the typical
in only
the periventricular
region (arrowheads). (CourtesyofRAHeyman.)

experience
with glatiramer acetate in this setting. Mitoxantrone
selective serotonin reuptake inhibitor
probably reduces the clinical attack rate and may
antidepressants.
help
Treatment for spasticity (discussed earlier) is often
to reduce disease progression in patients whose
needed, as is aggressive bladder and bowel manageclinical
ment. Treatment for other aspects of advanced
condition is worsening. Treatment with cyclophosphamide, azathioprine, methotrexate, or cladribinemultiple
sclerosis such as cognitive decits, pain, tremor, and
may
is generally less successful.
help to arrest the course of secondary progressiveataxia
Prognosis
disAt least partial recovery from an acute episode can
ease, but studies are inconclusive. Pulse therapy with
high-dose intravenous methylprednisolone (1 g/d be
anticipated, but it is impossible to predict when the
once
next
a month) is also sometimes effective and may carry
a relapse will occur. Features that tend to imply a
more
favorable prognosis include female sex, onset
lower risk of long-term complications than the cytobefore
age 40, and presentation with visual or
toxic drugs.
somatosensory,
rather than pyramidal or cerebellar,
No specic immunomodulatory therapy has been
dysfunction.
Although
some degree of disability is
shown to be effective in primary progressive multiple
likely
to
result
eventually,
about half of all patients
sclerosis, and management is with symptomatic
are
measures.
mildly or moderately disabled 10 years after the
Maintenance of general health and symptomaticonly
2.
ACUTE
ISSEMINATED ENCEPHALOMYELITIS
onset
of D
symptoms.
treatment should not be neglected in the comprehenThis occurs as a single episode of neurologic
sive management of multiple sclerosis. Exercise and
symptoms
physical therapy are important, but excessive
and signs that develop over a few days in association
exertion
with a viral infection, especially measles or
must be avoided, particularly during periods of acute
chickenpox.
relapse. Fatigue is a serious problem for many
patients,
and sometimes responds to amantadine or one of the

168 / CHAPTER 5
The neurologic decit resolves, at least in part, over
or vancomycin is administered to cover
the
staphylococcal
succeeding few weeks. Pathologically, perivascularor streptococcal infection, and other agents are
areas
added
of demyelination are scattered throughout the brain
or substituted based on the clinical context and
and spinal cord, with an associated inammatory results
reacof Gram stain of excised material. The results of
tion. A similar disorder may also occur independently,
culture
with no apparent infection; it may then represent the
of the necrotic material that makes up the abscess
initial manifestation of multiple sclerosis.
may
The initial symptoms often consist of headache,subsequently alter the antibiotic regimen. The antibifever, and confusion; seizures may also occur, andotic
dosages are those used to treat bacterial
Syphilis
exmeningitis,
Syphilis
produce1.meningovasculitis
of the are
cord,
amination reveals signs of meningeal irritation.
as givencan
in Chapter
Intravenous antibiotics
reFlaccid
ususulting
in spinalfor
cord
Vascular
weakness and sensory disturbance of the legs,
ally continued
34infarction.
weeks, but
longer treatment is
myelopathies
extensor
required in the presence of vertebral osteomyelitis.
are discussed later in this chapter.
Tuberculosis
plantar responses, and urinary retention are common
manifestations of cord involvement. Other neurologic
Tuberculosis may lead to vertebral disease (Pott
signs may indicate involvement of the optic nerves,
disease) with secondary compression of the cord, to
cerebral hemispheres, brainstem, or cerebellum. meningitis with secondary arteritis and cord
Examination of the CSF may show an increased infarction,
mononuclear cell count, with normal protein and gluor to cord compression by a tuberculoma. Such
cose concentrations.
compliCorticosteroids
are often
prescribed,
but
there
iscations assume great importance in certain parts of
Epidural
abscess
may
occur
as
a
sequel
to
skin
infecOTHER
INFECTIVE OR INFLAMMATORY
littion, septicemia, vertebral osteomyelitis, intravenous
the
MYELOPATHIES
tle
evidence
of benet.
Treatment
with
drug
abuse, back
trauma
or surgery,
orintravenous
lumbar puncworld, especially Asia and Africa, and among such
Epidural
Abscess factors include acquired
imture. Predisposing
groups as the homeless and intravenous drug users.
munoglobulins
or
plasmapheresis
has
been
helpful
in
immunodeTuAIDS
small
series
of cases.
A mortality
rate of immunosup530% is A
re-disorder meningitis
ciency
syndrome
(AIDS)
and iatrogenic
of the spinal
cord, vacuolar
myelopathy,
berculous
is considered
in more
detail in is
ported,
and
survivors
often
have
severe
residual
pression. The most common causative organisms are
Chapter
found
at 1.
autopsy in about 20% of patients with AIDS.
decits.
Staphylococcus aureus, streptococci, gram-negative
This disorder is characterized by vacuolation of white
bacilli, and anaerobes. Fever, backache and
matter in the spinal cord, which is most pronounced
tenderness,
in
pain in the distribution of a spinal nerve root,
the lateral and posterior columns of the thoracic cord.
headache, and malaise are early symptoms, followed
Direct involvement of the spinal cord by human imby
munodeciency virus-1 (HIV-1), the etiologic agent in
rapidly progressive paraparesis, sensory disturbances
AIDS, is thought to be the cause, but the correlation
in
between presence and extent of HIV-1 infection and
the legs, and urinary and fecal retention.
spinal pathology is poor. A metabolic basis therefore
Spinal epidural abscess is a neurologic emergency
has been suggested. Vacuolar myelopathy in AIDS rethat requires prompt diagnosis and treatment. MRIsembles myelopathy caused by vitamin B12
with gadolinium enhancement is the imaging study
deciency,
of
choice and should be sufcient to determine the but it tends to produce earlier incontinence and less
extent
conspicuous sensory abnormalities. Myelopathy in paof the abscess. A block may be found at myelography.
tients with AIDS also may be caused by lymphoma,
Laboratory investigations reveal a peripheral
cryptococcal infection, or herpesviruses.
leukocytoMost patients with vacuolar myelopathy have coexsis and increased erythrocyte sedimentation rate. isting
A
AIDS dementia complex (see Chapter 1). Sympspinal tap should not be performed at the site of atoms progress over weeks to months and include leg
susweakness, ataxia, incontinence, erectile dysfunction,
pected abscess as it may disseminate the infectionand paresthesias. Examination shows paraparesis,
from
lower
the epidural to subarachnoid space. Typically the CSF
extremity monoparesis, or quadriparesis; spasticity;
shows a mild pleocytosis with increased protein but
innormal glucose concentrations.
creased or decreased tendon reexes; Babinski signs;
Treatment involves surgery and antibiotics. In the
and diminished vibration and position sense.
absence of cord compression, treatment with intraSensation
venous antibiotics alone has been successful.
over the trunk is usually normal and a sensory level is
Nafcillin
difcult to dene. MRI of the spinal cord is typically

ity or absence of the normal silent period in the masseter muscle following elicitation of the jaw-jerk reex
is a helpful electromyographic nding. The serum CK
may be elevated, and myoglobinuria may occur. The
MOTOR DEFICITS / 169
organisms can be cultured from a wound in only a minority of cases.
normal. Therapy is generally with antiretroviral drug
Tetanus is preventable through immunization with
combinations, but whether this helps to arrest the
tetanus toxoid. Tetanus toxoid is usually administered
myelopathy is not clear.
routinely to infants and children in the United States,
in combination with pertussis vaccine and diphtheria
Other Viral Infections
toxoids. In children under age 7 years, three doses of
tetanus toxoid are administered at intervals of at
A retrovirus, human T-lymphotropic virus type I
least
(HTLV-I), appears to be the cause of tropical spastic
1 month, followed by a booster dose 1 year later. For
paraparesis, a disorder found especially in the
Caribbean, off the Pacic coast of Colombia, and inolder children and adults, the third dose is delayed
the Seychelles. Transmission of the virus occurs infor
at least 6 months after the second, and no fourth
breast milk, during sexual intercourse, and by
dose
exposure
is required. Immunization lasts for 510 years.
to contaminated blood products. Clinical features of
the disorder include spastic paraparesis, impaired Debridement of wounds is an important preventive
measure. Patients with open wounds should receive
vibraan
tion and joint position sense, and bowel and bladder
additional dose of tetanus toxoid if they have not redysfunction. Recent reports indicate that a clinically
ceived a booster dose within 10 yearsor if the last
similar myelopathy may also follow infection with human T-lymphotropic virus type II (HTLV-II). Specicbooster dose was more than 5 years ago and the risk
therapy is lacking, and treatment is symptomatic. of
infection with C tetani is moderate or high. A
Herpesviruses can also produce myelopathy, which
commonly affects spinal nerve roots as well as themoderate
likelihood of infection is associated with wounds that
cord
penetrate muscle, those sustained on wood or pave(radiculomyelopathy), especially in immunocomproment, human bites, and nonabdominal bullet wounds.
mised patients, such as those with AIDS. Cywounds include those acquired in
tomegalovirus causes a myelopathy characterizedHigh-risk
by
barnyards,
demyelination of the posterior columns of the spinal near sewers or other sources of waste material, and
abcord
Tetanus
is a disordercells
of neurotransmission
associated
bullet wounds. Patients with moderate- or
and by cytomegalic
that contain Cowdry
typedominal
A
with
infection
by Clostridium
The organism
high-risk wounds should also be given tetanus
inclusion
bodies.
The value oftetani.
treatment
with antiviral
typimmune
drugs
such as ganciclovir and foscarnet is still uncerTetanus
ically
becomes
established
in a simplex
wound, where
globulin.
tain. Herpes
zoster
and herpes
types 1itand
2
elabocan also cause myelopathy, which may respond to The treatment of tetanus includes hospitalization in
rates
treat- a toxin that is transported retrogradely alongan intensive care unit to monitor respiratory and
mocirculament with acyclovir (see Chapter 1).
tor nerves into the spinal cord or, with wounds to the
tory function, tetanus immune globulin to neutralize
face or head, the brainstem. The toxin is also
the
dissemitoxin, and penicillin or metronidazole for the infection
nated through the bloodstream to skeletal muscle,itwhere it gains access to additional motor nerves. In
self. Intrathecal administration of tetanus immune
the
globuspinal cord and brainstem, tetanus toxin interfereslin has been associated with better clinical
with
progression
the release of inhibitory neurotransmitters, including
than intramuscular administration. Diazepam, 1030
glycine and GABA, resulting in motor nerve hyperacmg
tivity. Autonomic nerves are also disinhibited.
intravenously or intramuscularly every 46 hours, and
After an incubation period of up to 3 weeks,
chlorpromazine, 2550 mg intravenously or
tetanus
intramuscuusually presents with trismus (lockjaw), difculty in
larly every 8 hours, are useful for treating painful
swallowing, or spasm of the facial muscles that spasms
resemand rigidity. Baclofen also has been used, with
bles a contorted smile (risus sardonicus). Painful musintrathecal
Chronic Adhesive Arachnoiditis
cle spasms and rigidity progress to involve both axial
administration. Neuromuscular blockade with vecuroThis
disorder
is usually
idiopathic
but
and limb musculature and may give rise to hyperexniuminammatory
or pancuronium
may be
required
when these
can
follow
subarachnoid
hemorrhage;
meningitis;
intended posturing (opisthotonos). Laryngospasm and
meaautonomic instability are potential life-threateningsures fail; if so, mechanical ventilation must be used.
complications.
Fatality rates of 1060% are reported. Lower
Although the diagnosis is usually made on clinical
fatality
grounds, the presence of continuous motor unit activrates are most likely to be achieved by early

170 / CHAPTER 5
Posterior
trathecal administration of penicillin, radiologic conspinal arteries
trast materials, and certain forms of spinal
anesthetic;
Lateral
trauma; and surgery.
column
The usual initial complaint is of constant radicular
pain, but in other cases there is lower motor neuron
weakness because of the involvement of anterior
nerve
roots. Eventually, a spastic ataxic paraparesis
develops,
with
sphincter
CSF only
protein
is elevated,
This rare
eventinvolvement.
generally occurs
in the
territory
and
the
cell
count
may
be
increased.
Myelography
of
shows
a characteristic
fragmentation
theartery,
contrast
the anterior
spinal artery
(Figure 53).ofThis
material
into pockets; MRI may disclose inammation.
Leg
which
Treating
aseptic
inammatory
supplies thethis
anterior
two-thirds
of theleptomeningeal
cord, is itself
Corticospinal
Arm
process
with steroids or with nonsteroidal antiinamsuptract
Anterior
matory
maynumber
be helpful.
Surgery
may be
plied byanalgesics
only a limited
of feeding
vessels,
Hand
spinal artery
indiVASCULAR
whereas
the MYELOPATHIES
paired posterior spinal arteries are
cated
in cases with localized cord involvement.
Figure 53. Blood supply to the cervical spinal cord
supplied
Infarction
of feeders
the Spinal
Cord different levels. Thus,
by numerous
at many
(shown in transverse section). Left: Major territories
supplied by the anterior spinal artery (dark shading)
anteand the posterior spinal artery (light shading). Right:
rior spinal artery syndrome usually results from interrupted ow in one of its feeders. Causes include Pattern of supply by intramedullary arteries. From the
pial vessels (around the circumference of the cord),
trauma,
radially oriented branches supply much of the white
dissecting aortic aneurysm, aortography, polyarteritis
matter and the posterior horns of the gray matter.The
noremaining gray matter and the innermost portion of
dosa, and hypotensive crisis. Since the anterior spinal
the white matter are supplied by the central artery
ar(located in the anterior median ssure), which arises
tery is particularly well supplied in the cervical region,
from the anterior spinal artery.The descending corticospinal tract is supplied by both the anterior and posinfarcts almost always occur more caudally.
terior spinal arteries.
The typical clinical presentation is with the acute
onset of a accid, areexic paraparesis that, as spinal
shock
wears off after a few days or weeks, evolves into a
spastic
ticoagulant therapy. A severe cord syndrome
paraparesis with brisk tendon reexes and extensor
develops
planacutely and is usually associated with blood in the
tar responses. In addition, there is dissociated
CSF.
sensory
The prognosis depends on the extent of the hemorimpairmentpain and temperature appreciation are
Spinal
epidural
or subdural
hemorrhage
can occur in
rhage
and
the
rapidity
with
which it occurs.
Epidural
or
Subdural
Hemorrhage
lost, but there is sparing of vibration and position resense
lation to trauma or tumor and as a complication of
because the posterior columns are supplied by theantipostecoagulation, aspirin therapy, thrombocytopenia,
rior spinal arteries. Treatment is symptomatic.
coaguA subacute, asymmetric myelopathy sometimeslopathy, epidural catheters, or lumbar puncture. It
deoccasionally occurs spontaneously. The likelihood of
velops as a consequence of a vasculitic process; the
hemorrhage following lumbar punctureusually
cereepidural in locationis increased when a disorder of
brospinal uid shows a pleocytosis and clinical benet
coagulation is present. Therefore, the platelet count,
may follow steroid therapy. An even more insidious,
prothrombin time, and partial thromboplastin time
asymmetric
ischemic
myelopathy
may
relate
to
comshould be determined before lumbar puncture is perHematomyelia
pression of the anterior spinal artery or its major formed, and if anticoagulant therapy is to be
Hemorrhage
into the spinal cord is rare; it is caused
feeder,
instituted,
by
as by degenerative disease of the spine. The resulting
it should be delayed for at least 1 hour following the
trauma,
vascular
anomaly,
a bleeding
disorder,
or
disorder amay
simulate
amyotrophic
lateral
sclerosis
procedure. Patients with less than 20,000
anwhen there is a combined upper and lower motor platelets/mm3
neuor those with rapidly falling counts (as high as
ron decit, without sensory changes.
50,000)

MOTOR DEFICITS / 171

should be transfused prior to lumbar puncture. Spinal
eration, with herniation of disk material, secondary
epidural hemorrhage usually presents with back pain
calthat may radiate in the distribution of one or morecication, and associated osteophytic outgrowths. It
spinal nerve roots; it is occasionally painless.
can lead to involvement of one or more nerve roots
Paraparesis
on
or quadriparesis, sensory disturbances in the lowereither or both sides and to myelopathy related to
limbs, and bowel and bladder dysfunction may
comClinical
develop
pression,Findings
vascular insufciency, or recurrent minor
rapidly, necessitating urgent CT scan, MRI, or myelogtrauma to the cord.
Patients often present with neck pain and limitation of
raphy, and surgical evacuation of the hematoma.
head movement or with occipital headache. In some
Arteriovenous Malformation (AVM)
cases, radicular pain and other sensory disturbances
or Fistula
ocThis may present with subarachnoid hemorrhage or
cur in the arms, and there may be weakness of the
with myelopathy. Most of these lesions involve thearms
lower part of the cord. Symptoms include motor and
or legs. Examination commonly reveals restricted
sensory disturbances in the legs and disorders of lateral
sphincter function. Pain in the legs or back is oftenexion and rotation of the neck. There may be a segconspicuous. On examination, there may be an
mental pattern of weakness or dermatomal sensory
upper,
loss
a lower, or a mixed motor decit in the legs, whilein one or both arms, along with depression of those
sentensory decits are usually extensive but occasionallydon reexes mediated by the affected root(s).
radicCervical
ular; the signs indicate an extensive lesion in the spondylosis tends to affect particularly the C5 and C6
longinerve roots, so there is commonly weakness of
tudinal axis of the cord. In patients with cervical muscles
lesions, symptoms and signs may also be present (eg,
in deltoid, supra- and infraspinatus, biceps,
the
brachioraarms. A bruit is sometimes audible over the spine,Investigative
dialis) suppliedStudies
from these segments, pain or sensory
and
loss about the shoulder and outer border of the arm
there may be a cutaneous angioma. The diagnosisPlain
is x-rays show osteophyte formation, narrowing of
and
spaces, and encroachment on the intervertebral
suggested by the MRI appearance and the myelo- disk
forearm, and depressed biceps and brachioradialis reforamina. MRI, CT scanning, or even myelography
graphic nding of serpiginous lling defects caused
exes. If there is an associated myelopathy, upper
may be necessary to conrm the diagnosis and
by
motor
enlarged vessels, and it is conrmed by selective exclude
neuron weakness develops in one or both legs, with
other structural causes of myelopathy. The CSF obspinal
contained at the time of myelography is usually normal,
arteriography. Spinal MRI is sometimes normal
comitant changes in tone and reexes. There may
but the protein concentration may be increased,
despite
also
the presence of an AVM and therefore cannot be espebe posterior column or spinothalamic sensory
cially if there is a block in the subarachnoid space.
relied
decits.
DEFICIENCY
DISORDERS
Elecupon to exclude this diagnosis.
studies, especially needle
Most lesions
are extramedullary
and
Subacute
combined
degeneration of
theposterior
cord as atotrophysiologic
reelectromyograthe of vitamin B12 deciency is characterized by an
sult
are helpful
in identifying a radiculopathy and in
Differential
Diagnosis
cord; they can be treated by embolization or by phy,
updetermining
whether
degenerative anatomic
ligation
per
motor neuron decit in the limbs that is usually
Spondylotic
myelopathy
may resemble myelopathy
of feedingby
vessels
andsymptoms
excision of
thesigns
anomalous
preceded
sensory
and
caused abnormaliby
caused
by
such
disorders
as multiple
sclerosis,
motor
of the cervical spine are
of any clinical
relevance.
arteriposterior
column involvement (see Chapter 6). In ties
neuron disease, subacute combined degeneration,
ovenous nidus of the malformation, which is usually
addicord
duraltointhe
location.
Left untreated,
the
is likely
tion
myelopathy,
there may
bepatient
optic atrophy,
tumor, syringomyelia, or hereditary spastic
to
mental
changes, or peripheral neuropathy.
paraplegia.
CERVICAL
SPONDYLOSIS
become increasingly disabled until chair-bound or
Moreover, degenerative changes in the spine are
bedCervical
spondylosis is characterized by any or all comof
bound.
the
mon in the middle-aged and elderly and may coincide
Treatment
following: pain and stiffness in the neck; pain in the
with one of these other disorders.
Treatment with a cervical collar to restrict neck movearms, with or without a segmental motor or sensory
ments may relieve any pain. Operative treatment
decit in the arms; and an upper motor neuron decit
may
in the legs. It results from chronic cervical disk degen-

172 / CHAPTER 5
be necessary to prevent further progression if there is
Pain is a conspicuous featureand usually the inia
tial abnormalityin many patients with extradural
signicant neurologic decit; it may also be required
lesions; it can be radicular, localized to the back, or
if
experienced diffusely in an extremity and is
the root pain is severe, persistent, and unresponsive
characteristo
tically aggravated by coughing or straining (Table 5
CONGENITAL ANOMALIES
conservative measures.
9).
A combination of corticospinal and cerebellar signs Motor symptoms (heaviness, weakness, stiffness,
may be found in the limbs of patients with congenital
or
skeletal abnormalities such as platybasia (attening
focal wasting of one or more limbs) may develop, or
of
there may be paresthesias or numbness, especially in
B.
IGNS
the base of the skull) or basilar invagination (an uptheSlegs.
When sphincter disturbances occur, they
Examination
sometimes reveals localized spinal
ward bulging of the margins of the foramen
usutendermagnum).
ally are particularly disabling.
ness. Involvement of anterior roots leads to an approSyringomyelia (cavitation of the cord), which can be
congenital or acquired, may lead to a lower motor priate lower motor neuron decit, and involvement of
posterior roots leads to dermatomal sensory changes
neuron decit, a dissociated sensory loss in the arms, at
the level of the lesion. Involvement of pathways
and
upper motor neuron signs in the legs. Because thetraversing the cord may cause an upper motor neuron decit
senTUMORS & CORD COMPRESSION
sory ndings are so characteristic, this disorder, below the level of the lesion and a sensory decit
with
Common
causes of cord compression are disk protruwhich
sion,
trauma,associated
and tumors;
in certain
parts of
the an upper level on the trunk. The distribution of signs
is frequently
with
Arnold-Chiari
malformavaries with the level of the lesion and may take the
world,
tion, is discussed in detail in Chapter 6.
Investigative Studies
tuberculous disease of the spine is also a frequentform of Brown-Squard or central cord syndrome (see
The
CSF65
is often
xanthochromic, with a greatly inFigures
and 67).
cause.
creased
protein
concentration,
a normal or elevated
Rare but important causes include epidural abscess
white
blood
cell
count,
and
normal
or depressed gluand
cose
concentration;
Queckenstedt
test
at lumbar
hematoma. The present section will be restricted to a
puncconsideration
Classicationof tumors, and other causes will be
ture may reveal a partial or complete block. A plain xconray of the spine may or may not be abnormal, and
Tumors
can
be
divided
into
two
groups:
sidered elsewhere.
intramedullary
CT scanning, MRI, or myelography is necessary to delineate the lesion and localize it accurately.
(10%) and extramedullary (90%). Ependymomas are
the most common type of intramedullary tumor, and
Treatment
the various types of gliomas make up the remainder.
Treatment depends upon the nature of the lesion.
Extramedullary tumors can be either extradural or in-Extradural metastases must be treated urgently. Depending upon the nature of the primary neoplasm,
tradural in location. Among the primary
extramedullary
tumors, neurobromas and meningiomas are
relatively
common and are benign; they can be intra- or ex- Table 59. Clinical features of spinal cord
compression by extradural metastasis.
tradural.
Carcinomatous metastases (especially from
Clinical Findings
bronchus, breast, or prostate), lymphomatous or
Irrespective
of its nature,
a tumorare
canusually
lead to cord
Initial
Present at
leukemic deposits,
and myeloma
dysFeature (%) Diagnosis (%)
Sign or Symptom
extradural.
function and a neurologic decit by direct compresPain
96
96
sion, ischemia secondary to arterial or venous
obstrucWeakness
2
76
tion, or, in the case of intramedullary lesions, by
A.
S
YMPTOMS
Sensory disturbance
0
51
invasive inltration.
Symptoms may develop insidiously and progress
Sphincter dysfunction
0
57
gradually oras is often the case with spinal cord compresAdaptedfromByrneTN,WaxmanSG:SpinalCord
sion from metastatic carcinomaexhibit a rapid Compression.Vol33of:ContemporaryNeurology
course.

MOTOR DEFICITS / 173

they are best managed by analgesics, corticosteroids,
hibitory protein (NAIP) gene, and the BTF2p44 gene.
radiotherapy, and hormonal treatment; decompresAbnormalities of the SMN gene have been identied
sive laminectomy is often unnecessary. Intradural in
(but extramedullary) lesions are best removed if pos95% of all patients with SMA, and of the NAIP gene
sible. Intramedullary tumors are treated by decomin 45% of patients with SMA-I and 18% of those with
pression and surgical excision when feasible and by
SMA-II and SMA-III. The NAIP gene may modify disradiotherapy.
ease severity.

Prognosis

Infantile Spinal Muscular Atrophy

(Werdnig-Hoffmann Disease or SMA-I)

The prognosis depends upon the cause and severity

This autosomal recessive disorder usually manifests
of
itthe cord compression before it is relieved. Cord comself within the rst 3 months of life. The infant is
pression by extradural metastasis is usually
oppy and may have difculty with sucking, swallowmanifested
ing, or ventilation. In established cases, examination
rst by pain alone and may progress rapidly to cause
repermanent impairment of motor, sensory, and
veals impaired swallowing or sucking, atrophy and
sphincfaster function. Therefore, the diagnosis must be susciculation of the tongue, and muscle wasting in the
pected early in any patient with cancer and spinal or
limbs that is sometimes obscured by subcutaneous
radicular pain, who must be investigated
fat.
immediately.
The tendon reexes are normal or depressed, and the
Reliance on motor, sensory, or sphincter disturbances
plantar responses may be absent. There is no sensory
to make the diagnosis will unnecessarily delay treatdecit. The disorder is rapidly progressive, generally
ANTERIOR
HORN
CELL
ment and worsen
the outcome.
leading to death from respiratory complications by
DISORDERS
about
age 3 years.
Intermediate
Spinal Muscular Atrophy
The cause is unknown, and there is no effective
(Chronic Werdnig-Hoffmann Disease
treatment.
Disorders that predominantly affect the anterior horn
or SMA-II)
cells are characterized clinically by wasting and
This also has an autosomal recessive mode of inheriweaktance but usually begins in the latter half of the rst
ness of the affected muscles without accompanying
year of life. Its main clinical features are wasting and
senweakness of the extremities; bulbar weakness occurs
sory changes. Electromyography shows changes that
less
are
commonly. The disorder progresses slowly, ultimately
characteristic of chronic partial denervation, with abto severe disability with kyphoscoliosis and
normal spontaneous activity in resting muscle andleading
a
contractures, but its course is more benign than the
reinduction in the number of motor units under voluntary
fantile variety described above, and many patients
control; signs of reinnervation may also be present.
surMotor conduction velocity is usually normal but may
vive into adulthood.
be slightly reduced, and sensory conduction studies
Treatment is essentially supportive and directed
are
parnormal.
Muscle
biopsy
shows
the
histologic
changes
Juvenile Spinal Muscular Atrophy
IDIOPATHIC ANTERIOR HORN
ticularly at the prevention of scoliosis and other
of
(Kugelberg-Welander Disease or SMA-III)
CELL DISORDERS
defordenervation. Serum CK may be mildly elevated, but
it
mities.
this disorder develops in childhood or early
never
reaches
the extremely
highdepend
values in
seen
The
clinical
features
and outlook
partinonGenerally
adolescence, on either a hereditary or sporadic basis.
some
the
The
muscular age
dystrophies.
patients
at onset. The cause of these disorders
is usual mode of inheritance is autosomal
recessive. It
unknown, but the genetic basis for some of them is
particularly tends to affect the proximal limb muscles,
be1.
OTOR NEURON DISEASE IN CHILDREN
with generally little involvement of the bulbar
ingMclaried.
Three forms of spinal muscular atrophy (SMA- I, II, musculaand III) have been described in infants and children,
ture. It follows a gradually progressive course, leading
and the responsible gene has been mapped to
to disability in early adult life. The proximal weakness
chromomay lead to a mistaken diagnosis of muscular dystrosome 5q11.1213.3, an area that contains the
phy, but serum CK determination, electromyography,
survival
and muscle biopsy will differentiate the disorders.
motor neuron (SMN) gene, the neuronal apoptosis inThere is no effective treatment.

174 / CHAPTER 5
2. MOTOR NEURON DISEASE IN ADULTS
the sporadic disorder is unknown but no robust enviMotor neuron disease in adults generally begins beronmental risk factors have emerged.
tween the ages of 30 and 60 years and has an annual
The pathophysiologic basis of hereditary or
insporadic
cidence in the order of 2 per 100,000, with a malemotor neuron disease is uncertain, but one or more of
prefour proposed mechanisms may be involved. These
dominance. It is characterized by degeneration of inanterior horn cells in the spinal cord, motor nuclei clude
of
oxidative injury by reactive oxygen species that
the lower cranial nerves in the brainstem, and cortiescape scavenging by defective copper/zinc
cospinal and corticobulbar pathways. The disordersuperoxide
usudismutase, aggregation of abnormal superoxide
ally occurs sporadically but may be familial in 510%
dismuof cases. An autosomal dominant familial motor neutase proteins, strangulation of axonal transport by
ron disease (with upper and lower motor neuron prosigns)
tein aggregates or mutant neurolament proteins,
has been related in some cases to mutations of the
and
copexcitotoxicity due to defective glutamate uptake into
per/zinc superoxide dismutase (SOD) gene on the astrocytes through the excitatory amino acid (glutalong
mate) transporter, EAAT2.
Classication
arm of chromosome 21 (21q22.122.2) whereas autoFive varieties of the disorder can be distinguished
somal recessive forms map to 2q33q35 and to by
A. PROGRESSIVE BULBAR PALSY
15q1522. Another autosomal dominant form has their
predominant
(limb
or is
bulbar
muscuBulbar
involvementdistribution
predominates
and
due to
been mapped to 9q34,and a form associated with lature)
and
the
nature
of
their
clinical
decits
(upper
lesions
fronor
affecting the motor nuclei of cranial nerves (ie, lower
totemporal dementia maps to 9q2122. Additionallower
neuron).
motor motor
neurons)
in the brainstem.
loci
B. PSEUDOBULBAR PALSY
for autosomal dominant, autosomal recessive, andThis
X- term is used when bulbar involvement predomilinked forms have been identied (Table 510), as nates and is due primarily to upper motor neuron dishave
sporadic cases with apparently new mutations in
neuro-510. Hereditary forms of ALS.
Table
lament heavy chain (22q12). More than 100 mutationsSyndrome
of the SOD gene
have
been described
Gene
or Locus
Protein in
Inheritance
Distinctive Features
heterozygotes
Vascular Dominant
SOD1 lateral sclerosis.
ALS
1 with amyotrophic
Cu/Zn-superoxide

endothelial growth factor (VEGF)dismutase

protects motor neurons in mouse models of motor neuron disease, and
ALS2
ALS 2
Alsin
Recessive
Childhood onset, slow progression
polymorphisms in the VEGF gene may increase the
risk 3of motor neuron
disease in humans.
of
ALS
18q21
UnknownThe causeDominant

ALS 4

9q34

Unknown

Dominant

Juvenile onset

ALS 5

15q15

Unknown

Recessive

Teenage onset, LMN predominant

ALS 6

16q

Unknown

Dominant

ALS 7

20p

Unknown

Dominant

ALS FTD

9q21q22

Unknown

Dominant; sporadic Frontotemporal dementia, posterior

column defect

ALS X

Xp11q12

Unknown

X-linked dominant

Unknown

Dominant

Face and tongue atrophy, dysarthria

Neurolament
heavy chain

Dominant or sporadic
Dementia, single limb involvement

Unknown

Unknown

ALS with bulbar onset

Unknown
NF heavy chain

NFH

Western Pacic ALS Unknown

Dementia, parkinsonism

AdaptedfromSwashM.Neurology2002;59:967,andwww.wustl.neuro.edu.

MOTOR DEFICITS / 175

ease, ie, to bilateral involvement of corticobulbar Table 511. Clinical diagnosis of amyotrophic latpatheral sclerosis: El Escorial Criteria of the World Fedways. A pseudobulbar palsy can occur in any disorder
eration of Neurology.
that causes bilateral corticobulbar disease, however,
and
Diagnostic
the use of the term must not be taken to imply that Certainty
Clinical Features
C.
P
ROGRESSIVE SPINAL MUSCULAR ATROPHY
the
There
is primarily
a lower
motormotor
neuron
decit in the
underlying
cause is
necessarily
neuron
Upper and lower motor neuron signs in the
limbs,
caused
by
anterior
horn
cell
degeneration
inDenite
disease.
bulbar and two spinal regions or in three
the
spinal regions
spinal cord. Familial forms have been recognized.
D. PRIMARY LATERAL SCLEROSIS
Probable
Upper and lower motor neuron signs in two
In this rare disorder, a purely upper motor neuron
or more regions; the regions may differ, but
some upper motor neuron signs must be
(corrostral to the lower motor neuron decit
ticospinal) decit is found in the limbs.
E. AMYOTROPHIC LATERAL SCLEROSIS
Upper and lower motor neuron signs in only
A mixed
lower with
motor
neuron decit
is Possible
In
about upper
20% ofand
patients
amyotrophic
lateral
one region or upper motor neuron signs
found
sclealone in two or more regions or lower motor
in the the
limbs.
There
may also
berelated
bulbarto
involvement
of
rosis,
initial
symptoms
are
weakness of
neuron signs rostral to upper motor neuron
the upper
or lower
motor
neuron type.
Both primary
bulbar
muscles.
Bulbar
involvement
is generally
signs
lateral sclerosis and progressive spinal muscular
characatrophyby difculty in swallowing, chewing, coughing,
Suspected
Lower (but not upper) motor neuron signs in
terized
at least two regions
are considered
to be variants
of amyotrophic
lateral
breathing,
and speaking
(dysarthria).
In progressive
sclerosis
because,
at autopsy,
of both
bulbar
palsy,
examination
mayabnormalities
reveal drooping
of the
uppalate,
a depressed gag reex, a pool of saliva in the
per
and
motor
neurons
likely.and
pharynx,
a weak
cough,
and aare
wasted
Clinical lower
Findings
Differential Diagnosis
fasciculating
tongue. The tongue is contracted and spastic in Other noninfective disorders of anterior horn cells
pseudobulbar palsy and cannot be moved rapidly (disfrom
cussed separately) must be excluded: they have
side to side.
different
Weakness of the upper extremity muscles is theRiluzole
(100
mg
daily) mayimplications.
reduce mortality
and
prognostic
and
therapeutic
Multifocal
preslow
motor neuropathy is also an important consideration;
senting complaint in about 40% of patients; lower progression
ex-clinical features
of amyotrophic
lateralare
sclerosis,
possibly
its
and treatment
discussed
on
tremity muscles are rst affected in a similar
because
it blocks glutamatergic transmission in the
page
Treatment
proportion
cen182.
of patients. Limb involvement is characterized by tral nervous system (CNS). It probably prolongs sureasy
vival by about 2 or 3 months. Adverse effects include
fatigability, weakness, stiffness, twitching, wasting,
fatigue, dizziness, gastrointestinal disorders, reduced
and
pulmonary function, and a rise in liver enzymes.
muscle cramps, and there may be vague sensory Sympcomtomatic measures may include anticholinergic drugs
plaints and weight loss. Examination reveals no (eg, glycopyrrolate, trihexyphenidyl, amitriptyline,
sensory
transdermal hyoscine, atropine) if drooling of saliva is
decit but only upper or lower motor neuron signs,troublesome.
as
Braces or a walker may improve
indicated above.
mobility,
Diagnostic criteria for amyotrophic lateral sclerosis
and physical therapy may prevent contractures.
have been established by the World Federation of
A semiliquid diet or feeding via nasogastric tube
Neumay be required for severe dysphagia. Percutaneous
rology. Criteria vary depending on the level of
encertainty
doscopic gastroscopy (PEG) is indicated for dysphagia
of the diagnosis, as shown in Table 511. Denitivewith
di- accelerated weight loss due to insufcient
agnosis requires the presence of upper and lower caloric
motor
intake, dehydration, or choking on food. For optimal
neuron signs in the bulbar region and at least two safety, it should be offered when the patients vital
other
caspinal regions (cervical, thoracic, or lumbosacral), pacity
or
is more than 50% of predicted. Noninvasive or
in
invasive ventilation may be necessary as
three spinal regions.
hypoventilaThere is generally no involvement of extraoculartion develops. In these circumstances, however,
muscles or sphincters. The CSF is normal.
pallia-

176 / CHAPTER 5
tive care to relieve distress without prolonging life picornavirus
begroup. The usual route of infection is fecomes an important consideration and requires cal-oral, and the incubation period varies between 5
detailed
and 35 days.
discussion with the patient and family. Such
Neurologic involvement follows a prodromal phase
discussions
of fever, myalgia, malaise, and upper respiratory or
are best initiated early in the course of the disease,
gaswith
trointestinal symptoms in a small number of cases.
Prognosis
continuing discussion as the disease advances. This
Motor neuron disease is progressive and usually has
a
involvement
may consist merely of aseptic meningitis
fatal outcome within 35 years, most commonly from
but in some instances leads to weakness or paralysis.
pulmonary infections. In general, patients with bulbar
Weakness develops over the course of one or a few
involvement have a poorer prognosis than those indays,
whom dysfunction is limited to the extremities.
sometimes in association with recrudescence of
fever,
OTHER NONINFECTIVE DISORDERS
and is accompanied by myalgia and signs of
meningeal
OF ANTERIOR HORN CELLS
irritation. The weakness is asymmetric in distribution
Bulbospinal neuronopathy (Kennedy syndrome) is and
a
can be focal or unilateral; the bulbar and respirasex-linked recessive disorder associated with an extory muscles may be affected either alone or in
panded trinucleotide repeat sequence on the
associaandrogen
tion with limb muscles. Tone is reduced in the
receptor gene. It has a more benign prognosis than
affected
the
muscles, and tendon reexes may be lost. There is no
other motor neuron diseases. Its clinical
sensory decit.
characteristics
CSF pressure is often mildly increased, and spinal
include tremor (resembling essential tremor), cramps,
uid analysis characteristically shows an increased
fasciculations, proximal weakness, and twitching number of cells, a slightly elevated protein concentramovetion, and a normal glucose level. Diagnosis may be
ments of the chin that are precipitated by pursing conrmed
of
by virus isolation from the stool or
the lips.
nasopharyngeal secretionsand less commonly from
Juvenile spinal muscular atrophy can occur in pathe CSF. A rise in viral antibody titer in convalescenttients with hexosaminidase deciency. Rectal biopsy
phase serum, compared with serum obtained during
may be abnormal, and reduced hexosaminidase A the
is acute phase of the illness, is also diagnostically
found in serum and leukocytes.
helpful. A clinically similar disorder is produced by
Patients with monoclonal gammopathy may prescoxsackievirus infection.
ent with pure motor syndromes. Plasmapheresis and There is no specic treatment, and management is
immunosuppressive drug treatment (with
purely supportive, with attention directed particularly
dexamethato the maintenance of respiratory function. With time,
sone and cyclophosphamide) may be benecial in there is often useful recovery of strength even in sesuch
verely weakened muscles.
cases.
The postpolio syndrome is characterized by the ocAnterior horn cell disease may occur as a rare comcurrence some years after the original illness of
plication of lymphoma. Both men and women are afincreasfected, and the symptoms typically have their onset
ing weakness in previously involved or seemingly
West
afunin- Nile Virus Infection
ter the diagnosis of lymphoma has been established.
volved
muscles.
Muscle pain
and ease
of fatigue
West
Nile
virus infection
is acquired
from
infectedare
The principal manifestation is weakness, which
common. Slow
progression
occurs
and may is
lead
to inmosquitos.
Its most
common
manifestation
meninprimacreasing restriction
ofdisorder
daily activities.
It probably
goencephalitis,
but a
resembling
Guillainrily affects the
legs, may be
patchy
in its distribution,
INFECTIVE
DISORDERS
OF
ANTERIOR
relatessyndrome also occurs. Acute paralytic polioBarr
and
spares
bulbar
and
respiratory
muscles.
The myelitis
HORN CELLS
to loss ofisanterior
cells with aging
a pool
anotherhorn
manifestation
and is from
characterized
reexes
thatacute,
was depleted
by the original
infection. weakness
There is
Polio Virus Infection
by
focal or generalized,
asymmetric
are depressed, and sensory abnormalities are minor
no
or
or
specic
treatment.
a rapidly
ascending quadriplegia that may be misPoliomyelitis due to infection with polio virusstill by
absent. Neurologic decits usually progress over taken for the Guillain-Barr syndrome. Electrodiagcommon in certain parts of the worldbecame rare in
months, followed by spontaneous improvement and,
nostic studies may be helpful in showing the nature
developed countries with the introduction of immuin
nization programs. It is caused by an RNA virus of and
the extent of involvement, distinguishing the
some cases, resolution.
disorder
from a neuropathy, and guiding prognosis. Treatment

MOTOR DEFICITS / 177

is supportive, as when poliomyelitis follows polio virus
the affected side (see Table 512); with more
infection.
centrally
directed herniations, the spinal cord may also be involved (Figure 54B), leading to a spastic paraparesis
and sensory disturbance in the legs, sometimes
NERVE ROOT AND PLEXUS
accompanied by impaired sphincter function. The diagnosis
LESIONS
is
conrmed
CT scanning, MRI, or myelography. SurCERVICALby
SPONDYLOSIS
ACUTE INTERVERTEBRAL DISK
gical treatment may be needed.
This disorder has been described on page
PROLAPSE
171.
Lumbar Disk Prolapse

Acute prolapse of a lumbar disk (Figure 54C and TRAUMATIC AVULSION OF NERVE ROOTS
Paralysis
Table 512) generally leads to pain in the back andErb-Duchenne
in
a
avulsion of the C5 and C6 roots can occur
radicular distribution (L5 or S1) in the leg, where itTraumatic
is
atAbirth as a result of traction on the head during
often accompanied by numbness and paresthesias.
delivmotor decit also may be found; this depends on the
ery of the shoulder. It can also be the result of injuries
root affected. An L5 radiculopathy causes weakness
causing excessive separation of the head and
of
shoulder.
dorsiexion of the foot and toes, whereas S1 root involvement produces weakness of plantar exion ofIt leads to loss of shoulder abduction and elbow exion. In consequence, the affected arm is held
the
foot and a depressed ankle jerk. Movement of the internally
rotated at the shoulder, with a pronated forearm and
spine
extended elbow. The biceps and brachioradialis jerks
is restricted, and there is local back tenderness and
are lost, but sensory impairment is usually
palinconspicupable spasm of the paraspinous muscles. Straight-leg
Klumpke Paralysis
raising in the supine position is restricted, often toous, since it is conned to a small area overlying the
Involvement
of the C8 and T1 roots causes paralysis
deltoid muscle.
about 20 or 30 degrees of hip exion, from a normal
value of about 80 or 90 degrees, because of reexand wasting of the small muscles of the hand and of
the
spasm
long nger exors and extensors. Horner syndrome is
of the hamstring muscles (Lasgue sign). A centrally
prolapsed disk can lead to bilateral symptoms andsometimes an associated nding. This kind of lower
plexus paralysis often follows a fall that has been arsigns
rested
by grasping
a xed
object
onepain
handabout
or
and to sphincter involvement.
This disorder
typically
begins
withwith
severe
may
The symptoms and signs of a prolapsed lumbar the
in- shoulder followed within a few days by weakness,
from traction
the abducted
arm. in the arm,
NEURALGIC
AMYOTROPHY
(IDIOPATHIC
tervertebral disk can be either sudden or insidiousresult
reex
in
changes,
and on
sensory
disturbances
onset and may follow trauma. Pelvic and rectal
ofBRACHIAL PLEXOPATHY)
examiten involving the C5 and C6 segments especially.
nation and plain x-rays of the spine help to exclude
Symptoms and signs are usually unilateral but may
lebe
sions such as tumors.
bilateral, and wasting of the affected muscles is often
Bed rest on a rm mattress for 2 or 3 days followed
profound. The motor decit sometimes corresponds
by gradual mobilization often permits symptoms toto
setthe territory of an individual nerve, especially the
tle, but persisting pain, an increasing neurologic axildecit,
lary, suprascapular, or radial nerve, but in other inor any evidence
of sphincter dysfunction should lead
stances appears to arise in the brachial plexus. Its
Cervical
Disk Prolapse
to
preAcute
protrusion
of a cervical
disk
can occur
at any
CT, MRI,
or myelography
(Figure
115)
followed
bycise cause is unknown. It sometimes occurs shortly
age,
surgical treatment. Drug treatment for pain includes
after
often
in
as- with no preceding trauma, and leads to pain minor
injury, injections, inoculations, or minor systhe
neck
and
radicular
pain
in
the
arm.
The
pain
is
pirin or acetaminophen with 30 mg of codeine, twotemic infections, but whether these are of etiologic
exdoses three or four times daily, or other nonsteroidal
releacerbated
head
movement.
lateralMuscle
herniation
analgesics by
such
as ibuprofen
orWith
naproxen.
vance is unclear. Familial cases occur occasionally, as
of
the disk, a motor, sensory, or reex decit may an
be
spasm
found
in
a
radicular
(usually
C6
or
C7)
distribution
on
may respond to cyclobenzaprine, 10 mg orally three
autosomal dominant disorder characterized by recurtimes daily or as needed and tolerated, or diazepam,
rent symptoms. The disorder has been mapped to a
510 mg orally three times daily or as tolerated. ge-

178 / CHAPTER 5
A

Spinal
cord
segment

Vertebral
body

Intervertebral disk
Anterior

C1

Posterior

C2
C3
C4

Cervical roots

C5
C6
C7

Compressed
nerve root

C7

C8
T1 T1

T2
T3
T4

Intervertebral disk

Nerve roots
Subarachnoid space

T5
T6
T7
T8
T9

Dura mater
L5

Thoracic roots

L4
T10
T11

L5

T12

S1
Anterior

L1
D

L2

Intervertebral
disk

Posterior
Nerve roots
Subarachnoid space

L3

Lumbar roots

L4
Dura mater

L4
L5

Posterior

L5
S1
S2
S3 Sacral roots
S4
S5
Coccygeal nerve
Anterior

L4
L5
S1
Anterior

Posterior

Figure 54. A: Lateral view of the vertebral column, showing the levels at which the various nerve roots
exit;
nerves exit above their numbered vertebral body in the cervical spine but below in the lumbar spine. B: Lateral
disk
prolapse in cervical spine, causing compression of exiting nerve root and compressing cervical cord. C: Lateral
disk
prolapse in lumbar spine, causing compression of the root exiting at the next lower vertebral level (eg, L4 disk
compresses the L5 nerve root). D: Central disk prolapse in lumbar spine, causing bilateral root compression.

MOTOR DEFICITS / 179

Table 512. The most common patterns of weakness, sensory symptoms, and reex changes in
nerve
root lesions.1
C5

C6

C7

C8

L4

L5

Deltoids
biceps

Biceps

Triceps,ngerFinger
Quadriceps Great toe
extensors
extensors
extension
plus
abductors of
index and
fth ngers

Pattern of
Lateral
sensory changes upper arm

Thumb

Middle
nger(s)

Depressed reex

Biceps

Triceps

Weak muscle(s)

S1
Plantar
exion
(tested
standing
get up on
toes)

Little nger Medial shin Medial foot, Lateral foot,

great toe
small toe
Knee

Ankle

Overlap and individual variation occur. In some cases this summary table does not distinguish root from single nerve lesions. If a peripheral nerve lesion is suspected see Appendix C or Tables 55 and 56.

netic locus on chromosome 17q25 in some but notOTHER CAUSES OF BRACHIAL

other cases.
PLEXOPATHY
Treatment is symptomatic. Recovery over the ensuBrachial plexopathy may occur in patients with
ing weeks and months is the rulebut it is
neoplassometimes
The
C8 and T1 roots or the lower trunk of the brachial
tic inltration or as a consequence of radiation
incomplete.
plexus may be compressed by a cervical rib or band
therapy,
arising fromRIB
the SYNDROME
seventh cervical vertebra. This leads
following median sternotomy, and after trauma. ElecCERVICAL
to
trophysiologic studies are important in dening the
weakness and wasting of intrinsic hand muscles, exespetent and severity of involvement and localizing the lecially those in the thenar eminence, accompanied sion.
by The absence of electrodiagnostic abnormalities
pain and numbness in the appropriate dermatomaldespite an adequate examination suggests an
disincorrect
tribution (often like that of an ulnar nerve lesion but
diagnosis and raises
the possibility of conversion
LUMBOSACRAL
PLEXOPATHY
extending up the medial border of the forearm). The
reacsubclavian artery may also be compressed; this forms
A
disorder
similar tooridiopathic
plexopathy
tions,
malingering,
so-called brachial
nonneurogenic
the basis of Adson test for diagnosing the disorder.octhoracic
The
casionally
affects(a
the
lumbosacraland
plexus.
Treatment
outlet syndrome
controversial
disputed
entity).
radial pulse decreases in amplitude when the seated
is
pasymptomatic. Intrapartum maternal lumbosacral
tient turns the head to the affected side and inhales
plexdeeply. A positive Adson test, however, also can beopathy is an uncommon but important cause of acute
seen
foot drop developing during labor. It occurs mostly in
in normal subjects; a supraclavicular bruit during the
short women and relates to compression of the lummaneuver supports the diagnosis of subclavian artery
bosacral trunk by the fetal head at the pelvic brim.
compromise.
Most patients recover completely within 6 months.
DISORDERS OF PERIPHERAL
X-rays may show the cervical rib or a long
transverse
NERVES
process of the seventh cervical vertebra, but normal
ndings do not exclude the possibility of a cervical
The term peripheral neuropathy designates a disturband. Electromyography shows evidence of chronic
bance in function of one or more peripheral nerves.
partial denervation in the handin a territory beyond
Several types of peripheral neuropathy are
that of any individual peripheral nerve. Nerve conduction studies show no evidence of peripheral nerve distinguishdisease, but there is a small or absent ulnar sensory able by the extent of involvement.
nerve
action potential on stimulation of the little nger.
Treatment is by surgical excision of the rib or band.

180 / CHAPTER 5
Depending upon the underlying cause, there may
Diphtheritic Polyneuritis
be selective involvement of motor, sensory, or autoInfection with Corynebacterium diphtheriae can occur
nomic bers or more diffuse involvement of all bers
either in the upper respiratory tract or by infection of
in
a
the peripheral nerve.
skin wound, and neuropathy results from a neurotoxin
The clinical decit is usually a mixed one, and sensory symptoms and signs are often the initialandthat is released by the organism. Palatal weakness
may
most conspicuousfeature of peripheral nerve
develop 23 weeks after infection of the throat, and
involvecument. Further discussion of these disorders and their
taneous diphtheria may be followed by focal
treatment is therefore deferred to Chapter 6, except
weakness
in
of neighboring muscles after a similar interval. Imthose instances in which presentation is typically with
paired pupillary responses to accommodation may
acute motor decits. For convenience, however, the
root and peripheral nerve supply of the major limboccur about 45 weeks after infection and a generalized
muscles is set forth in Tables 55 and 56. Reference
sensorimotor polyneuropathy after 13 months. The
to
weakness may be asymmetric and is often more
the tables should facilitate evaluation of patients prePOLYNEUROPATHY
senting with focal weakness of lower motor neuronmarked
proximally than distally. Respiratory paralysis occurs
type.
In polyneuropathy, because there is symmetric and
in
sisevere cases. Recovery usually occurs over the
multaneous involvement of various nerves, the
following
decits
23 months but may take longer in severe cases.
resulting from individual nerves cannot be recognized
In patients with polyneuropathy, CSF protein conclinically. Polyneuropathies are discussed in Chapter
tent is usually increased, and there may be a mild
6,
pleobut brief
mention is made here of those neuropathies
cytosis. Electrophysiologic studies show a slowing of
Acute
Inammatory
in
nerve conduction velocity, but this is often not maniPolyradiculoneuropathy
which
patients
present
with
acute
weakness.
fest until the patient has begun to improve clinically.
(Guillain-Barr Syndrome)
Treatment consists of early administration of equine
Paralytic
This disorder commonly presents with weakness that
diphtheriaShellsh
antitoxin Poisoning
without awaiting the results of
is
bacterial
culture,
provided
the
patient
is not
Mussels and clams found on
the
East and
West
often symmetric and most commonly begins in thehypersenCoasts
legs. The speed and extent of progression vary, but
in to horse serum. A 2-week course of penicillin or
sitive
of
the United States may be dangerous to eat,
severe cases there is marked weakness of all limbserythromycin
in
will usually eradicate the infection but
especially
addoes
alter the
incidence
serious
complications.
in
thenot
summer
months.
Theyof
feed
on poisonous
varidition to bilateral facial weakness. There may also In
be
eties of plankton and come to contain saxitoxin,
subjective sensory complaints, although objective patients with marked weakness, supportive
which
senmeasures,
blocks
sodium channelsand therefore action potensory disturbances are usually far less conspicuous including ventilatory support, are necessary.
tialsin motor and sensory nerves and in muscle. A
than
rapidly progressive acute peripheral neuropathy, with
motor decits. Autonomic involvement is common
sensory symptoms and a rapidly ascending paralysis,
and
Critical Illness Polyneuropathy
begins within 30 minutes after eating affected
may lead to a fatal outcome, as may aspiration pneushellsh
Patients
with
sepsis
and
multiorgan
failure
may
demonia or impaired respiration from weakness. Further
and may lead to respiratory paralysis and death.
velop
a
polyneuropathy
that
often
rst
comes
to
details about this disorder are given in Chapter 6.
There
attention when unexpected difculty is encountered in is no available antitoxin, but with proper supportive
Porphyria
weaning the patients from a mechanical ventilator.care
In (including mechanical ventilation if necessary)
the
Acute polyneuropathy may occur with the hereditary
more advanced cases, wasting and weakness of the
patient
completely.
A cathartic
or enema
hepatic recovers
porphyrias.
Attacks can
be precipitated
by
exmay
drugs (eg, barbiturates, estrogens, sulfonamides,
tremities are present and the tendon reexes are lost.
grise-remove unabsorbed toxin.
Sensory abnormalities are overshadowed by the help
ofulvin, phenytoin, succinimides) that can induce the
motor
decit. Electrophysiologic studies reveal an axonalenzyme
acid synthetase, or by
neuropathy. The underlying pathogenesis is obscure.
infecTreatment is supportive, with the long-term outlook
tion, a period of fasting, or, occasionally, menses or
being good in patients who recover from the underlypregnancy. Colicky abdominal pain frequently preing critical illness.

MOTOR DEFICITS / 181

cedes neurologic involvement, and there may alsocontains
be
arsenic in the acute phase. The diagnosis
acute confusion or delirium and convulsions. Weakof thallium poisoning is made by nding thallium in
ness is the major neurologic manifestation and is due
body tissues or uids, especially in urine. The degree
to a predominantly motor polyneuropathy that causes
of
a symmetric disturbance that is sometimes more neurologic recovery depends upon the severity of the
marked proximally than distally. It may begin in the
intoxication.
upper limbs and progress to involve the lower limbs Chelating agents are of uncertain value.
or
trunk. Progression occurs at a variable rate and can
Organophosphate Polyneuropathy
lead to complete accid quadriparesis with
Organophosphate compounds are widely used as inrespiratory
paralysis over a few days. Sensory loss occurs alsosecticides and are also the active principles in the
nerve gas of chemical warfare. They have a variety of
but
acute toxic effects, particularly manifestations of
is less conspicuous and extensive. The tendon
cholinergic crisis caused by inhibition of acetylreexes
Some organophosphates, however,
may be depressed or absent. The disorder may becholinesterase.
acalso
induce
a
delayed
polyneuropathy that generally
companied by fever, persistent tachycardia,
begins
about
13
weeks
after acute exposure. Cramphypertening
muscle
pain
in
the
legs
is usually the initial sympsion, hyponatremia, and peripheral leukocytosis. The
tom
of
neuropathy,
sometimes
followed by distal
CSF may show a slight increase in protein concentranumbness
and
paresthesias.
Progressive
leg
tion and a slight pleocytosis. The diagnosis is conweakness
rmed by demonstrating increased levels of porphobilinogen and
acid in the urine orthen occurs, along with depression of the tendon reexes. Similar decits may develop in the upper
deciency of uroporphyrinogen I synthetase in red
limbs after several days. Sensory disturbances also
blood cells (acute intermittent porphyria) or of coprodeporphyrinogen oxidase in lymphocytes (hereditary covelop in some instances, initially in the legs and then
proporphyria).
in the arms, but these disturbances are often mild or
Treatment is with intravenous dextrose to suppress
inconspicuous. Examination shows a distal symmetthe heme biosynthetic pathway and propranolol
ric, predominantly motor polyneuropathy, with wastto control tachycardia and hypertension. Hematin,
ing and accid weakness of distal leg muscles. In
4 mg/kg by intravenous infusion over 15 minutes
some patients, involvement may be severe enough to
once
is also
effective
in improving
the clinical
Acutedaily,
arsenic
or thallium
poisoning
can produce
a cause quadriplegia, whereas in others the weakness
state.
rap- The best index of progress is the heart rate.is
The
idly evolving sensorimotor polyneuropathy, often with
much milder. Mild pyramidal signs also may be presabdominal
and mental
symptoms
(but not the disturan accompanying
or preceding
gastrointestinal
ent. Objective evidence of sensory loss is usually
neuropathy)
may
helped
by a
chlorpromazine
bance.
Arsenic
may
also
cause
skin rash, withor
in-slight. The acute effects of organophosphate poisonAcute Arsenic
orbe
Thallium
Poisoning
another
Respiratory
failure
may ne- tocreased phenothiazine.
skin pigmentation
and marked
exfoliation,
ing may be prevented by the use of protective masks
cessitate
tracheostomy
and
mechanical
ventilation.
gether with the presence of Mees lines (transverseand clothing. Treatment after exposure includes dePreventing
acute attacks by avoiding known precipiwhite
contamination of the skin with bleach or soap and
tants is
lines)
onimportant.
the nails in long-standing cases. Thalliumwater and administration of atropine, 26 mg every 5
can
minutes, and pralidoxime, 1 g every hour for up to 3
produce a scaly rash and hair loss. Sensory
hours, both given intramuscularly or intravenously.
symptoms
There is no treatment for the neuropathy other than
are often the earliest manifestation of
supportive care. Recovery of peripheral nerve funcpolyneuropathy;
tion may occur with time, but central decits are
this is followed by symmetric motor impairment, usually permanent and may govern the extent of ultiwhich is usually more marked distally than proximally
mate functional recovery.
and occurs in the legs rather than the arms. The CSF
MONONEUROPATHY MULTIPLEX
protein may be increased, with little or no change in
cell content, and the electrophysiologic ndings This term signies that there is involvement of
various
sometimes resemble those of Guillain-Barr syndrome, nerves but in an asymmetric manner and at different
times, so that the individual nerves involved can
espeusually
cially in the acute phase of the disorder. The
be identied until the disorder reaches an advanced
diagnosis
of arsenic toxicity is best established by measuringstage. Comment here will be restricted to two
disorders
the
characterized by motor involvement in the absence
arsenic content of hair protected from external
of
contamination (eg, hair from the pubic region). Urine also sensory symptoms and signs.

Facial weakness of the lower motor neuron type

caused
by idiopathic facial nerve involvement outside the
immunoglobulin,
2 g/kg intravenously, given over
Lead Toxicity
cen35
days.
Improvement
is sometimes
tral nervous system, without
evidenceassociated
of aural or with
Lead toxicity is common among persons involved in
a
the manufacture or repair of storage batteries or more
decrease
in neurologic
anti-GM1 antibody
widespread
disease,levels.
has been designated
other
Bell
lead-containing products, the smelting of lead or MONONEUROPATHY SIMPLEX
palsy. The cause is unclear, but the disorder occurs
leadmore
commonly in pregnant
women
and diabetics.
In mononeuropathy
simplex there
is involvement
ofIna
containing ores, and the shipbreaking industry. It may
creasing
evidence
suggests
that
reactivation
of
single
peripheral
nerve.
Most
of
the
common
also occur in persons using lead-containing paints or
mononeuropathies entail both motor and sensory inthose who ingest contaminated alcohol. Inorganic herpes
simplex
virus
1 infection
in the 6).
geniculate
ganvolvement
(astype
discussed
in Chapter
Accordingly,
lead
glion
may
injure
the
facial
nerve
and
is
responsible
only Bell palsy, which leads primarily to a motor
can produce dysfunction of both the central and pefor
decit, is discussed here.
ripheral nervous systems. In children, who can
Bell palsy in at least some patients.
develop
Facial
weakness is often preceded or accompanied
toxicity by ingesting lead-containing paints that ake
Bell
Palsy
byispain about the ear. Weakness generally comes on
off old buildings or furniture, acute encephalopathy
abruptly but may progress over several hours or even
the major neurologic feature. The peripheral neuropaa
thy is predominantly motor, and in adults it is more
day or so. Depending upon the site of the lesion,
sethere
vere in the arms than in the legs. It typically affects
may be associated impairment of taste, lacrimation,
the
or
radial nerves, although other nerves may also be afhyperacusis. There may be paralysis of all muscles
fected, leading to an asymmetric progressive motor
supdisturbance. Sensory loss is usually inconspicuous or plied
ab- by the affected nerve (complete palsy) or
variable
sent. There may be loss or depression of tendon
weakness in different muscles (incomplete palsy).
reexes. Systemic manifestations of lead toxicity inClinclude anemia, constipation, colicky abdominal pain,
gum discoloration, and nephropathy. The extent toical examination reveals no abnormalities beyond the
territory of the facial nerve. Most patients recover
which exposed workers develop minor degrees of pecomripheral nerve damage as a result of lead toxicity is
pletely without treatment, but this may take several
not
This
is characterized
by progressive
clear.disorder
Multifocal
Similarly,
Motor
there
Neuropathy
is no agreement
about the days in some instances and several months in others.
asymmetA
lowest
ric
wasting
and
weakness,
electrophysiologic
concentration of blood lead that is associated withpoor prognosis for complete recovery is suggested by
evidence
severe pain at onset and complete palsy when the
damage to the peripheral nerves.
of The
multifocal
motor
demyelination
with
partial
motor
paoptimal approach to treatment is not known,
conduction
block
but
normal
sensory
responses,
and
but intravenous or intramuscular edetate calcium tient
di- is rst seen. Even if recovery is incomplete, perthe
presence
of
antiglycolipid
(usually
anti-GM1
IgM)
manent
disgurement or some other complication afsodium (EDTA) and oral penicillamine have been
antibodies
in
the
serum
of
many
patients.
Cramps
fects
only
about 10% of patients. It is not clear
used, as has dimercaprol (BAL).
and
whether
fasciculations sometimes occur and may lead to an
treatment with acyclovir or other antiviral agents conerfers any benet, as the results of methodologically
roneous diagnosis of motor neuron disease unless diselecsimilar studies have been conicting. Treatment with
trophysiologic studies are performed. There is no sencorticosteroids (prednisone, 60 mg/d orally for 3
sory loss or evidence of upper motor neuron
days,
involvement. The disorder typically has an insidious
tapering over the next 7 days), beginning within 5
onset and chronic course, but variants with a moredays
acute onset have been described. For a diagnosis to
after the onset of palsy, is said to increase the proporbe
tion of patients who recover completely. It should
made with condence, the motor decit should betherefore
in
be prescribed in patients who have a poor
the distribution of two or more named nerves and prognosis.
reHowever, the evidence that corticosteroids
lated to conduction block outside of common entrapare indeed benecial is incomplete, and they may
ment sites. The conduction block is a major conse-have
quence of demyelination, but axonal excitability unpleasant side effects. Other conditions that can
changes also contribute to conduction failure. Treatproment with prednisone and plasmapheresis has been
duce facial palsy include tumors, herpes zoster
disappointing, but patients may improve after treatinfection
ment with cyclophosphamide, 1 g/m2 intravenously
of the geniculate ganglion (Ramsay Hunt syndrome),
once a month for 6 months, or in response to human
Lyme disease, AIDS, and sarcoidosis.
182 / CHAPTER 5

MOTOR DEFICITS / 183

an immune-mediated decrease in the number of
DISORDERS OF NEUROMUSCULAR functioning acetylcholine receptors (Figure 55). In
TRANSMISSION
approximately 80% of cases, antibodies to the muscle
nicotinic
MYASTHENIA GRAVIS
acetylcholine receptor are present and lead to loss of
reMyasthenia gravis can occur at any age and is
ceptor function. In patients seronegative for these
sometimes
antiassociated with thymic tumor, thyrotoxicosis,
bodies, the disease is probably also immune
rheumamediated;
toid arthritis, or disseminated lupus erythematosus.
many of these patients have antibodies against the
More common in females than males, it is
muscharacterized
by uctuating weakness and easy fatigability of cle-specic receptor tyrosine kinase (MuSK) that is involved in the clustering of acetylcholine receptors
volunClinical
Findings
durtary muscles; muscle activity cannot be maintained,
ing
development
and
also
expressed
in mature
and
Although
the onset
of is
the
disease
is usually
insidious,
neuromuscular
junctions.
initially powerful movements weaken readily. There
is
the disorder is sometimes unmasked by a concurrent
A similar disorder in patients receiving penicila
lamine
for rheumatoid arthritis frequently remits
predilection for the external ocular muscles and
when
certain
Presynaptic nerve terminal
other cranial muscles, including the masticatory, the drug is discontinued.
facial,
pharyngeal, and laryngeal muscles. Respiratory and
limb muscles may also be affected. Weakness is due
Lambert-Eaton
to a
syndrome (antibody)
variable block of neuromuscular transmission related
to
Ca2+
Aminoglycoside
channel

Ca2+

Synaptic
vesicle

antibiotics
Active
zone

Synaptic
cleft

ACh

Botulism
(toxin)
Myasthenia
gravis (antibody)

ACh
receptors

Postsynaptic muscle membrane

Figure 55. Sites of involvement in disorders of neuromuscular transmission. At left, normal transmission
involves
depolarization-induced inux of calcium (Ca) through voltage-gated channels.This stimulates release of acetylcholine (ACh) from synaptic vesicles at the active zone and into the synaptic cleft. ACh binds to ACh receptors and
depolarizes the postsynaptic muscle membrane. At right, disorders of neuromuscular transmission result from
blockage of Ca channels (Lambert-Eaton syndrome or aminoglycoside antibiotics), impairment of Ca-mediated ACh
release (botulinum toxin), or antibody-induced internalization and degradation of ACh receptors (myasthenia
gravis).

184 / CHAPTER 5
infection, which leads to an exacerbation of
The most commonly used pharmacologic test is
symptoms.
the edrophonium (Tensilon) test. Edrophonium is
Exacerbations may also occur in pregnancy or before
given intravenously in a dose of 10 mg (1 mL), of
menses. Symptoms may be worsened by quinine, which 2 mg is given initially and the remaining 8 mg
quinidine, procainamide, propranolol, phenytoin, about 30 seconds later if the test dose is well
lithium, tetracycline, and aminoglycoside antibiotics,
tolerated.
which therefore should be avoided in such patients.
In myasthenic patients, there is an obvious improveMyasthenia follows a slowly progressive course. ment in the strength of weak muscles that lasts for
Patients
about 5 minutes.
present with ptosis, diplopia, difculty in chewing or Alternatively, 1.5 mg of neostigmine can be given
swallowing, nasal speech, respiratory difculties, or
intramuscularly, with a response that lasts for about
weakness of the limbs (Table 513). These symptoms
2 hours; atropine sulfate (0.6 mg) should be available
often uctuate in intensity during the day, and thistodiurnal variation is superimposed on longer-term
counteract the muscarinic cholinergic side effects of
spontainneous relapses and remissions that may last for creased salivation, diarrhea, and nausea. Atropine
weeks.
does
Clinical examination conrms the weakness andInvestigative
not affect nicotinic
cholinergic function at the neuroStudies
fatigability of affected muscles. The weakness does
muscular junction. The longer-acting neostigmine reX-rays
andincidence
CT scans of
of false-negative
the chest may evaluations.
reveal a
not
duces the
coexistconform to the distribution of any single nerve, root,
ing thymoma. Impaired neuromuscular transmission
or
level of the central nervous system. In more than can be detected electrophysiologically by a
decremental
90%
response of muscle to repetitive supramaximal
of cases the extraocular muscles are involved,
stimulaleading to
tion (at 2 or 3 Hz) of its motor nerve, but normal ndoften asymmetric ocular palsies and ptosis. Pupillary
ings do not exclude the diagnosis. Single-ber elecretromyography shows increased variability in the
sponses
are not affected. The characteristic feature
Diagnosis
interval between two muscle ber action potentials
of
The
diagnosis
of
myasthenia
gravis
can
generally
be
the disorder is that sustained activity of affected from the same motor unit in clinically weak muscles.
Measuring serum acetylcholine receptor antibody
conmuslevels
rmed
by
the
benet
that
follows
administration
of
Treatment
cles leads to temporarily increased weakness. Thus,
is often helpful, since increased values are found in
antisusMedications
(referred
to earlier)
that myasthenia
impair
of patients
with
generalized
cholinesterase
drugs;
the
power
of
affected
muscles
tained upgaze for 2 minutes can lead to increased8090%
neuromusgravis.
is
inuptocular transmission should be avoided. The following
enced
at
a
dose
that
has
no
effect
on
normal
muscles
sis, with power in the affected muscles improving approaches to treatment are recommended.
and
after 513. Presenting symptoms in myasthenia A. ANTICHOLINESTERASE DRUGS
Table
slight,
any,Ineffect
on muscles
Treatment with these drugs provides symptomatic
a brief 1ifrest.
advanced
cases, weakened
there may by
be other
some
gravis.
causes.
benmild
et without inuencing the course of the underlying
atrophy
of
affected
muscles.
Sensation
is
normal,
and
Symptom
Percentage of Patients
disease. The mainstay of treatment is pyridostigmine,
there are usually no reex changes.
at
Diplopia
41
doses individually determined but usually between
Ptosis
25
30 and 180 mg (average, 60 mg) four times daily. The
older drug neostigmine may still be used, in rare inDysarthria
16
stances, by parenteral administration. Small doses of
Lower extremity weakness
13
atropine may attenuate side effects such as bowel
Generalized weakness
11
hyperDysphagia
10
motility or hypersalivation. Overmedication can lead
to
Upper extremity weakness
7
increased weakness, which, unlike myasthenic weakMasticatory weakness
7
B.
THYMECTOMY
ness,
is unaffected or enhanced by intravenous edroThymectomy
should
be performed
in patients
under
phonium.
Such
a cholinergic
crisis may
be accompa1
Adaptedfrom
HerrmannC
Jr:Myasthenia
60
years
of
age,
and
considered
in
those
older,
with
nied
by
pallor,
sweating,
nausea,
vomiting,
salivation,
gravisCurrent
concepts.
WestJMed
colicky abdominal pain, and miosis.

MOTOR DEFICITS / 185

weakness that is not restricted to the extraocular MYASTHENIC SYNDROME
mus(LAMBERT-EATON SYNDROME)
cles. Although thymectomy usually leads to symptoThis disorder has a well-recognized association with
matic benet or remission, the mechanism by which
an
it
confers benet is unclear, and its benecial effect underlying neoplasm and occasionally may be associC.
CORTICOSTEROIDS
ated with such autoimmune diseases as pernicious
may
Corticosteroids
are indicated for patients who haveanenot be evident immediately.
remia; occasionally no cause is found. In the
sponded poorly to anticholinesterase drugs and have
paraneoplasaltic disorder, antibodies directed against tumor
ready undergone thymectomy. Treatment is initiated
antigens
with the patient in the hospital, as weakness may cross-react
iniwith voltage-gated calcium channels intially be exacerbated. An initial high dose of
volved in acetylcholine release, leading to a
prednisone
disturbance
(60100 mg/d orally) can be tapered gradually to aof neuromuscular transmission (see Figure 55).
relClinically there is weakness, especially of the proxiatively low maintenance level (515 mg/d) as
mal muscles of the limbs. Unlike myasthenia gravis,
improvehowever, the extraocular muscles are
D.
AZATHIOPRINE
ment
occurs. Alternate-day treatment is helpful in characteristically
reThis
drug
be usedofinside
patients
with
severe
ducing
thecan
incidence
effects,
which
areor prospared, and power steadily increases if a contraction
gressive
despite
thymectomy
and treatment
describeddisease
(as clinical
ndings)
in the section
on is
with
hyperamaintained. Autonomic disturbances, such as dry
anticholinesterases
be
drenalism in Chapterand
1. corticosteroids. It can alsomouth,
constipation, and impotence, may also occur.
given in place of high doses of corticosteroids to pa- The diagnosis is conrmed electrophysiologically
tients who show no sustained benet with low doses.
by
The usual dose is 23 mg/kg/d, increased from a the response to repetitive nerve stimulation. There is
lower
a
E.
PLASMAPHERESIS
initial
dose.
remarkable increase in the size of the muscle
Plasmapheresis may be used to achieve temporary
response
imto stimulation of its motor nerve at high rateseven
provement in patients deteriorating rapidly or in
in
myasmuscles that are not clinically weak. The presence of
thenic crisis, and in certain special circumstances,
autoantibodies to the P/Q subtype of voltage-gated
such
calF.
IMMUNOGLOBULINS
asINTRAVENOUS
prior to surgery
that is likely to produce postoperacium channels, found on the presynaptic membrane
Intravenous
immunoglobulins
tive respiratory
compromise. also have been used to
provide temporary benet in circumstances similarofto
the neuromuscular junction, is highly sensitive and
those in which plasmapheresis is used.
specic to the Lambert-Eaton syndrome of any etiology.
G. MYCOPHENOLATE MOFETIL
This agent selectively inhibits proliferation of T and BImmunosuppressive drug therapy (corticosteroids
and azathioprine as described earlier for myasthenia
lymphocytes and has been used as an
gravis) and plasmapheresis or intravenous imimmunosuppresmunoglobulin therapy may lead to improvement.
sant with only modest side effects, including diarrhea,
nausea, abdominal pain, fever, leukopenia, and Guanidine hydrochloride, 2550 mg/kg/d in three or
BOTULISM
four divided doses, is sometimes helpful in seriously
edema.
but adverse
effects
the drug
inSeveral studies indicate that many patients with disabled
The toxinpatients,
of Clostridium
botulinum
canofcause
neuroclude
bone
marrow
suppression
and
renal
failure.
The
myasmuscular paralysis. It acts by preventing the release
response
to treatment with anticholinesterase drugs
thenia gravis improve or are able to lower their
of
such
as
pyridostigmine
or neostigmine,
alone
in
steroid
acetylcholine at neuromuscular
junctions
and or
autocombination
with
guanidine,
is
variable.
3,4-Diintake in response to this medication (1 g twice daily
nomic synapses (see Figure 55). Botulism occurs
Prognosis
aminopyridine
(investigational in the United States),
by mouth), but usually after a delay of several
most
at
doses
up
to
25
mgingestion
orally four
daily, may
immonths.
commonly following
of times
home-canned
food
Most
patients can be managed successfully with drug
prove
and autonomic
dysfunction;
contaminated
with the toxin;
it occurs rarely
treatment. The disease may have a fatal outcome that
be- isweakness
paresthefrom
infected wounds. The shorter the latent period
cause of respiratory complications such as aspiration
sia is a common
side
and
seizures
mayofoccur.
between
ingestion
of effect,
the toxin
and
the onset
pneumonia.
The disease improves with treatment of the
sympunderlying
toms, the greater the dose of toxin and the risk for
condition.
further involvement of the nervous system.

186 / CHAPTER 5

Clinical Findings
Fulminating weakness begins 1272 hours after MYOPATHIC DISORDERS
ingestion of the toxin and characteristically is manifested
MUSCULAR DYSTROPHIES
by
diplopia, ptosis, facial weakness, dysphagia, nasalThe muscular dystrophies are a group of inherited
speech, and then difculty with respiration; weakness
myusually appears last in the limbs. In addition to theopathic disorders characterized by progressive
momuscle
tor decit, blurring of vision is characteristic, and weakness and wasting. They are subdivided by their
there
mode of inheritance, age at onset, distribution of inmay be dryness of the mouth, paralytic ileus, and volved muscles, rate of progression, and long-term
posouttural hypotension. There is no sensory decit, and look
the (Table 514). A more satisfactory means of
tendon reexes are usually unchanged unless the classiinvolved muscles are quite weak. Symptoms can
cation may be on genetic grounds. A number of
progress
genes
for several days
after their onset.
Investigative
Studies
have now been associated with the different
In infants, enteric infection with local productionmuscular
of
Once
the leads
diagnosis
suspected,
thepicture
local health
the toxin
to a is
different
clinical
with audystrophies (Table 515). These skeletal muscle
thority
A.
DUCHENNE DYSTROPHY
hypo- should be notied and samples of the
genes
patients
The
most
common form
muscular dystrophy,
it is
tonia, constipation, progressive weakness, and a poor
encode
sarcolemmal
(eg,ofsarcoglycans),
cytoskeletal
serum
and
the
contaminated
food
(if
available)
sent
an
suck.
(eg,
to
X-linked
disorder
that predominantly
affectsand
males.
dystrophin),
cytosolic,
extracellular matrix,
be assayed for toxin. The most common types of Symptoms begin by age 5 years, and patients are
nuclear
toxin
typimembrane proteins. Abnormalities of these proteins
encountered clinically are A, B, and E. Electrophysiocally
severely
by adolescence,
with death
may lead
to a disabled
greater susceptibility
to necrosis
of
logic studies may help conrm the diagnosis, sinceocmusthe
curring
in the
decade. Toe
walking, waddling
cle bers,
but third
the molecular
mechanisms
involved
evoked
muscle response tends to increase in size progait,
Treatment
are
gressively with repetitive stimulation of motor nerves
and
an inability
to runheterogeneity
are early symptoms.
not yet
clear. Genetic
for the Weakness
same
Patients
should be hospitalized, because respiratory
at
is
pheinfast rates.
most pronounced
in the proximal
lower
extremities
has led to subdivision
of the
main
clinical
sufciency can develop rapidly and necessitates notype
but
disorventilaalso affects
proximal
extremities.
but thethe
basis
for theupper
different
clinical In
tory assistance. Treatment with trivalent antitoxin ders,
attempt(ABE) is commenced once it is established that thephenotypes
ing
to rise to stand from a supine position, patients
is unknown.
pacharacteristically
musttreatment
use their arms
tomuscular
climb up
There is no specic
for the
tient is not allergic to horse serum, but the effect on
their
dysthe
bodies
(Gowers
sign). Pseudohypertrophy
of the
trophies.
It is important
to encourage patients
to lead
course of the disease is unclear.
calves
normal a life as possible. Deformities and contracGuanidine hydrochloride (2550 mg/kg/d in di- as
caused
by fatty
inltration
of muscle
is common.
tures often
can be
prevented
or ameliorated
by The
vided doses), a drug that facilitates release of acetylheart
is
involved
late
in
the
course,
and
mental
physical
choline from nerve endings, is sometimes helpful in
retardatherapy and orthopedic procedures. Prolonged bed
improving
muscle
strength;
anticholinesterase
drugs
AMINOGLYCOSIDE ANTIBIOTICS
tion
rest is a frequent accompaniment. Serum CK levels
are
are be avoided, as inactivity often leads to
Large
doses
of antibiotics
suchand
as kanamycin
generally
of no
value. Nursing
supportive and
caremust
exceptionally
high.
worsening
genare
No
denitive
treatment is available, but
tamicin
can produce a clinical syndrome rather likeof disability.
important.
prednisone,
botulism, because the release of acetylcholine from
0.75 mg/kg/d orally, may improve muscle strength for
nerve endings is prevented. This effect may be
up to 3 years. Side effects include weight gain,
related
cushingto calcium channel blockade (see Figure 55). Sympoid appearance, and hirsutism; the long-term effects
toms resolve rapidly as the responsible drug is elimiof prednisone in this disorder are uncertain.
nated from the body. Note that these antibiotics are
Deazacort
particularly dangerous in patients with preexisting
(0.9 mg/kg/d), an analogue of prednisone, is probably
disas
turbances of neuromuscular transmission and are
effective as prednisone but with fewer side effects.
thereCreafore best avoided in patients with myasthenia gravis.
tine monohydrate (510 g/d) may also be benecial.

Table 514. The muscular dystrophies.

Disorder

Inheritance

Onset (Years)

Distribution

Prognosis

Serum CK

Notes

Duchenne

X-linked recessive

15

Pelvic, then shoulder Rapid progression; die within

Marked increaseMay be pseudohypertrophy of
girdle; later, limb and about 15 years after onset
muscles at some stage; cardiac
respiratory muscles
involvement, skeletal deformities, and
muscle contractures occur; intellectual retardation is common

Becker

X-linked recessive

525

Pelvic, then shoulder Slow progression; may have

Increase
girdle
normal life span

Usually no cardiac involvement,

skeletal deformities, or contractures

Limb-girdle
(Erb)

Autosomal recessive1030
or dominant, or
sporadic

Pelvic or shoulder
Variable severity and rate of
Mild increase
girdle initially, with
progression; may be severe
later spread to other disability in middle life
muscles

Variable clinical expression; may be

hypertrophy of calves; normal
intellectual function; cardiac
involvement is rare; many subtypes
have been described

Facioscapulo- Autosomal dominantAny age

humeral

Face and shoulder

Slow progression; minor Often normal
girdle initially; later, disability; usually normal life
pelvic girdle and legs span

Aborted or mild cases are common;

muscle hypertrophy, contractures,
and deformities are rare

EmeryDreifuss

X-linked recessive or510

autosomal dominant

Humeroperoneal or
scapuloperoneal

Variable expression; contractures,

skeletal deformities, cardiomyopathy,
cardiac conduction defects are common; no pseudohypertrophy

Distal

Autosomal dominant4060
or recessive

Onset distally in
Slow progression
extremities; proximal
involvement later

Ocular

Autosomal dominantAny age

External ocular muscles.
Not known
(may be recessive) (usually 530) Mild weakness of face,
neck, and arms may
occur

Often normal

Oculopharyngeal

Autosomal dominantAny age

As in the ocular form, Not known

but with dysphagia

Often normal

Paraspinal
dystrophy

Unknown

Paraspinal muscles

Mild increase

Myotonic
dystrophy

Autosomal dominantAny age

(usually
2040)

40 and over

Variable

Variable progression

Facial and
Variable severity and
sternomastoid muscles
progression
and distal muscles in
the extremities

Increase

Often normal

Leads to back pain and marked

kyphosis

Normal or mild Associated features include

increase
myotonia, cataracts, gonadal atrophy,
endocrinopathies, cardiac
abnormalities, intellectual changes;
asymptomatic carriers of the gene
may sometimes be detected by clinical examination, slit lamp examination for lenticular abnormalities, or
electromyography

188 / CHAPTER 5
Clinical onset in childhood is followed by slow
progression, with development of contractures, weakness
and
X-linked
wasting (particularly of triceps and biceps in the
Duchenne/Becker XR
Xp21
arms,
Emery-Dreifuss XR
Xq28
and of peronei and tibialis anterior in the legs, with
later spread to the girdle muscles), cardiac
Emery-Dreifuss
AD 1q21.2
conduction
AR
1q21.2
abnormalities, and cardiomyopathy. The serum CK is
LIMB-G
IRDLE D
YSTROPHY Cardiac function should be
Limb girdle
AD 5q22q34; 1q1121; 3p25; D.
usually
mildly
increased.
Previously
catchall
designation
that ifprobably
sub6q23; 7q; 7q32
monitored a
and
a pacemaker
inserted
necessary.
15q15; 2p13; 13q12; 17q21; sumed
AR
Physi- a variety of disorders, including undiagnosed
4q12; 5q3334; 17q1112; cases
of other
dystrophies,
it is (in classic
form) inhercal therapy
is important
to maintain
mobility.
9q33.2; 19q13.3; 2q24.3
ited in autosomal recessive fashion (see Table 515).
Patients with different genetic mutations may be cliniFacioscapulohumeralAD 4q35
cally indistinguishable, and patients with the same
Oculopharyngeal
AD 14q11.2q13
mutation may show marked phenotypic variation, even
Distal
within the same family. The disorder begins clinically
Miyoshi
AR
2p13
between late childhood and early adulthood. In conTibial
AD 2q13
trast to Duchenne and Becker dystrophies, the
shoulder
Congenital
AR
6q22; 9q31q33; 12q13;
and pelvic girdle muscles are affected to a more
1p35p36; 1p32p34
nearly
Myotonic dystrophy AD 19q13.2q13.3; 3q21.3
equal
extent. Pseudohypertrophy
E.
FACIOSCAPULOHUMERAL
DYSTROPHY is not seen, and
serum
CK levels
are less disorder
elevated.that usually has its
An
autosomal
dominant
onset in adolescence, this is compatible with a
normal
life span. The genetic defect is a rearrangement of a
A genetic defect responsible for Duchenne dystrohomeobox gene localized to chromosome 4q35. The
phy has been identied and forms the basis of a diagclinical severity of this condition is highly variable.
nostic test. The gene in question is located on the
Weakness is typically conned to the face, neck, and
short
shoulder girdle, but foot drop can occur. Winged
arm of the X chromosome and codes for the protein
scapulae are common. The heart is not involved, and
dystrophin, which is absent or profoundly reduced in
serum CK levels are normal or only slightly elevated.
muscle from patients with the disorder. The absence
F. DISTAL MYOPATHY
of
The autosomal dominant variety typically presents
dystrophin from synaptic regions of cerebral cortical
after
neurons may contribute to mental retardation in paage 40, although onset may be earlier and symptoms
tients with Duchenne dystrophy. Gene therapy has
more severe in homozygotes. Small muscles of the
not
hands and feet, wrist extensors, and the dorsiexors
B.
B
ECKER DYSTROPHY
proven effective at this time for treating this
of
This
is
also
X-linked
and
associated
with
a
pattern
of
muscular
the foot are affected. The precise pattern of involveweakness
similar
to
that
observed
in
Duchenne
dystrophy.
ment varies in the different subtypes of the disorder.
dystrophy. Its average onset (11 years) and age at deathThe course is slowly progressive. Distal myopathies
with autosomal recessive inheritance or occurring
(42
years) are later, however. Cardiac and cognitive sporadically are also described and present with
impairprogressive
ment do not occur, and serum CK levels are less striklegOweakness
in adolescents or young adults. LateG.
CULAR DYSTROPHY
ingly elevated than in Duchenne dystrophy. In
onset
This
is
typically
an autosomal dominant disorder, alcontrast
variants
are
also
described;
in one,
there
selective
though
recessive
and sporadic
cases
also is
occur.
to Duchenne dystrophy, dystrophin levels in muscle
inC.
E
MERY
-D
REIFUSS
M
USCULAR
D
YSTROPHY
Some
are
volvement
of the posterior
calves. in mitochondrial
cases
are associated
with deletions
This
disorder
occurs
in an X-linked
recessive
(Xq28)
normal
in Becker
dystrophy,
but the
protein is
qualitaand
rarer
autosomal
and recessive
forms.
DNA. Onset is usually before age 30 years. Ptosis is
tively
altered.
It is notdominant
clear whether
steroids have
the
any
earliest manifestation, but progressive external
role in treatment of this dystrophinopathy.
ophthalTable 515. Genetic basis of muscular
dystrophies.

MOTOR DEFICITS / 189

moplegia subsequently develops; facial weakness have
is
been described, including point mutations and
also
large-scale deletions. Patients may present with
common, and subclinical involvement of limb muscles
Kearnsmay occur. The course is slowly progressive. The Sayre-Daroff syndrome, as discussed in Chapter 4, or
extent
with limb weakness that is exacerbated or induced by
to which ocular dystrophy is distinct from oculophaactivity. In other patients, the symptoms and signs
H.
OCULOPHARYNGEAL
DYSTROPHY
ryngeal
dystrophy (see
below) is unclear in many are
An
autosomal dominant disorder, this is found withofincases.
central neurologic dysfunction and may include
creased frequency in certain geographic areas,
myincluding
oclonic epilepsy [myoclonic epilepsy, ragged red ber
Quebec and the southwestern United States. It most
syndrome, (MERRF)], or the combination of mitooften begins in the third to fth decade. Findings inchondrial myopathy, encephalopathy, lactic acidosis,
clude ptosis, total external ophthalmoplegia,
and strokelike episodes (MELAS). These various syndysphagia,
dromes are caused by separate abnormalities of
facial weakness, and often proximal limb weakness.
mitoSerum CK is mildly elevated. Dysphagia is particularly
chondrial DNA. Investigations may include muscle
incapacitating and may require nasogastric feeding
or
biopsy,
measurement of serum and CSF lactate, and
I.
P
ARASPINAL
D
YSTROPHY
gastrostomy.
imaging studies. Treatment is generally supportive.
Progressive paraspinal weakness may develop after
Mitochondrial DNA depends for its proper functhe
tion on various factors encoded by nuclear DNA. Muage of 40 in patients of either gender, some of whom
tations in nuclear genes may thus affect
may have a family history of the disorder. Back pain
mitochondrial
and a marked kyphosis (bent spine syndrome) are
function. This is exemplied by mutations in the gene
characteristic. The serum CK is mildly elevated. CT
for thymidine phosphorylate, which lead to an
scans show fatty replacement of paraspinal muscles.
autosoMYOTONIC
CONGENITAL MYOPATHIES
mal recessiveDISORDERS
disorder called mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), manifest
The congenital myopathies are a heterogeneous In myotonia, an abnormality of the muscle ber memby gastrointestinal dysmotility and skeletal muscle
brane (sarcolemma) leads to marked delay before the
group
abnormalities.
affected muscles can relax after a contraction; this
of rare and relatively nonprogressive disorders that
leads
usuto apparent muscle stiffness. In at least some cases,
ally begin in infancy or childhood but may not
the
become
disorder appears to be related to a decrease in
clinically apparent until adulthood. Most are
chloride
characterized by predominantly proximal muscle weakness,ion
hy-conductance across the sarcolemma. On
examinapotonia, hyporeexia, and normal serum CK; many
tion, it is frequently possible to demonstrate
are
myotonia
inherited. They are classied according to ultrastrucby difculty in relaxing the hand after sustained grip
tural histopathologic features and are diagnosed by
muscle biopsy. They include nemaline myopathy, or
by persistent contraction after percussion of the belly
characterized by rod-shaped bodies in muscle bers, of
Myotonic Dystrophies
a muscle. Electromyography of affected muscles may
which
Myotonic
dystrophy type
1 (DM1) is adischarges
dominantly
reveal characteristic
high-frequency
ofinpoare also seen in some patients with AIDS-related myherited
disorder
that
usually
is
manifest
in
the
third
tentials that wax and wane in amplitude and
opathy (see below); central core disease, which may
or
frequency,
be
Mitochondrial
Myopathies
fourth
decade,
may appear
earlylike
childproducing
over although
the EMG it
loudspeaker
a in
sound
that
associated with malignant hyperthermia as a
The
mitochondrial
myopathies
are
a
clinically
heterohood.
The
gene
defect
is
an
expanded
trinucleotide
of a dive bomber or chain-saw.
complica(CTG) repeat in a gene localized to chromosome
geneous
group anesthesia;
of disorders myotubular
caused by defective
tion of general
or centronuoxida19q13.219q13.3, and this expanded trinucleotide reclear myopathy; and mitochondrial myopathies, such
peat forms the basis of a diagnostic test. The protein
tive
phosphorylation
and
accompanied
by
structural
as Kearns-Sayre-Daroff syndrome, a cause of progresmitochondrial
abnormalities
on
skeletal
muscle
sive external ophthalmoplegia (see Chapter 4). Noencoded by this gene has been designated myotoninbiopsy.
treatment is available for any of these disorders. protein kinase. Occasional patients, however, have
Their morphologic signature is the ragged red ber
clinical features resembling myotonic dystrophy but no
seen with the modied Gomori stain, containing accumulations of abnormal mitochondria. Since the rst
repeat expansion of the myotonin-protein kinase gene.
reported pathogenic mutation of human mitochondrial
Myotonia accompanies weakness and wasting of the
faDNA in the 1980s, a large number of other mutations
cial, sternomastoid, and distal limb muscles (Figure

190 / CHAPTER 5
56). There may also be cataracts, frontal baldness,
Myotonia Congenita
tesMyotonia congenita (Thomsen disease) is usually inticular atrophy, diabetes mellitus, cardiac
herited as a dominant trait that relates to a mutation
abnormalities,
on
and intellectual changes.
chromosome 7q35. Generalized myotonia without
A group of related myotonic disorders shows
weakness is usually present from birth, but symptoms
linkage
may not develop until early childhood. Muscle
not to the myotonin-protein kinase gene but to chrostiffness
mosome 3q21.3. Patients with proximal myotonic myis enhanced by cold and inactivity and relieved by
opathy have myotonia, cataracts, primarily proximal
weakness, and a less severe course than DM1. Theexercise. Muscle hypertrophy, sometimes pronounced, is
disorder is usually dominantly inherited, but sporadicalso a feature. A recessive form (Becker disease) with
later onset is associated with slight weakness and
cases also occur. A variant with more severe muscle
Polymyositis and dermatomyositis are characterized
atroinby of distal muscles and also maps to chromosome
volvement and hearing loss has been described. Inphy
destruction of muscle bers and inammatory inltra7q35.
mytion
of muscles.
Polymyositis
can occur
at any age; it
Treatment
with
quinine sulfate,
procainamide,
otonic dystrophy type 2 (DM2) the clinical characterINFLAMMATORY
MYOPATHIES
progresses
at
a
variable
rate
and
leads
to
weakness
tocainide, mexilitene, or phenytoin may help
the
istics are similar to DM1, with signicant distal
and
myotonia.
Trichinosis,
Toxoplasmosis,
&
Sarcoidosis
weakness despite the genetic difference.
wasting, especially of the proximal limb and girdle
Myotonia can be treated with quinine sulfate, musThese disorders may lead to an inammatory
300400 mg three times daily; procainamide, 0.51
g (Table 516). It is often associated with muscle
disorder
cles
four times daily; or phenytoin, 100 mg three timespain,
of muscle,
but thisdysphagia,
is uncommon.
tenderness,
and respiratory
daily. In myotonic dystrophy, phenytoin is perhapsdifculties.
Polymyositis & Dermatomyositis
the
Raynaud phenomenon, arthralgia, malaise, weight
drug of choice, since the other drugs may have loss,
undesirand a low-grade fever round out the clinical picture.
able effects on cardiac conduction. There is no treatDermatomyositis is distinguished clinically by the
ment for the weakness that occurs, and
prespharmacologic
ence of an erythematous rash over the eyelids, about
maneuvers do not inuence the natural history. the
eyes (heliotrope rash), or on the extensor surfaces of
the
joints. There are also immunologic and
histopathologic
differences between the two disorders.
Dermatomyositis
is a microangiopathy affecting skin and muscle: lysis
of
endomysial capillaries is caused by activation and
deposition of complement, leading to muscle ischemia. In
polymyositis, muscle bers expressing MHC class I
antigens are invaded by clonally expanded CD8positive
cytotoxic T-cells, leading to necrosis.
Polymyositis/dermatomyositis has been reported in
association with various autoimmune disorders,
including scleroderma, lupus erythematosus, rheumatoid
arthritis, and Sjgren syndrome. In addition, there is a
denite correlation between adult-onset
Figure 56. Photograph of a 37-year-old man with
dermatomyosimyotonic dystrophy, showing frontal baldness, bilateraltis and cancer. The serum CK is generally elevated in
ptosis, and wasting of the temporalis, facial, and sternpatients with polymyositis or dermatomyositis, someocleidomastoid muscles. (CourtesyofRGriggs.)
times to very high levels, but normal values do not
exclude the diagnosis. At electromyography, an abundance of short, low-amplitude, polyphasic motor unit
potentials is found, as in any myopathic process; but

MOTOR DEFICITS / 191

Table 516. Symptoms and signs of polymyositis. Inclusion Body Myositis
This disorder is more common in men than women
and has an insidious onset, usually after 50 years of
age,
with painless proximal weakness of the lower and
Initial symptom
then
Lower extremity weakness
42
the upper extremities. The disease is progressive and
Skin rash
25
Myalgia or arthralgia
is
15
Upper extremity weakness
8
associated with early depression of the knee reexes.
Dysphagia
2
There may be distal weakness, but this is usually less
Other
2
seNeurologic signs
vere than proximal weakness. The etiology of the
Proximal upper extremity weakness
99
myositis is unknown, but accumulating evidence sugProximal lower extremity weakness
80
gests a T-cell-mediated myocytotoxicity and probably
Neck exor weakness
65
a
Dysphagia
62
multifactorial genetic susceptibility to the disease.
Muscle pain or tenderness
48
Distal limb weakness
Asso35
Muscle atrophy
ciated disorders include various autoimmune distur35
Contractures
bances, diabetes mellitus, and diffuse peripheral neu35
Facial weakness
ropathy. Serum CK levels may be normal or
5
Extraocular muscle weakness
increased.
2
AIDS
Nonneurologic signs
The diagnosis is conrmed by histologic examination.
Heliotrope rash
Several
formsisofunresponsive
myopathy can
in patients with
The disorder
to occur
immunosuppressive
Arthropathy
40
otherwise
asymptomatic
HIV-1
infection
or with AIDS
or
Raynaud phenomenon
35
(Table
517). These disorders
be distinguished
by
immunomodulatory
therapies.can
Conicting
reports on
Other rash
30
muscle
biopsy.
The most common
is polymyositis,
the utility
of intravenous
globulin therapy
make its
20
which
role may be caused by autoimmune mechanisms
AdaptedfromBarwickDD,WaltonJN:Polymyosi
trigunclear.
tis.AmJMed1963;35:646.
gered by HIV-1 infection. It resembles polymyositis in
abnormal spontaneous activity is often conspicuous
patients without HIV-1 infection (see earlier) and may
as
respond to treatment with corticosteroids. Patients
well. Muscle biopsy usually shows muscle ber
with
necrosis
AIDS may also develop a myopathy associated with
and inltration with inammatory cells, and is importype II muscle ber atrophy. Malnutrition, cachexia,
tant for accurate diagnosis.
immobility, or remote effects of AIDS-related tumors
Treatment is with antiinammatory drugs. Pred-may have a pathogenetic role. Proximal muscle weaknisone is commonly used in an initial dose of 60 orness
80 is the major nding, and serum CK is normal.
mg/d, along with potassium supplements and
Rod-body myopathy is a noninammatory disorder
frequent
characterized by rod-shaped bodies and selective loss
antacids if necessary. As improvement occurs and of
serum CK values decline, the dose is gradually
thick laments. Clinical features include proximal
tapered
musto maintenance levels that usually range between cle
10 weakness and moderate elevation of serum CK.
and 20 mg/d. Patients may need to continue this regiTreatment with corticosteroids or plasmapheresis
men for 23 years, however; too rapid a reduction may
in
dose may lead to relapse.
be helpful. A mitochondrial myopathy (in which musIntravenous immunoglobulin is also efcacious in
cle biopsy specimens show the ragged red bers
dermatomyositis and can be used with or in place indicaof
steroids. Methotrexate or azathioprine have also been
tive
damaged
mitochondria)
can occur in patients
Tableof517.
AIDS-related
myopathies.
used, either alone or in combination with cortico- receiving zidovudine for treatment of AIDS and may
steroids; they are particularly useful in corticosteroidcoexist
with polymyositis. The disorder is
Polymyositis
resistant patients. Newer immunosuppressants with
characterized
Type II muscle ber atrophy
less
clinically
bymyopathy
proximal muscle weakness, myalgia, and
Rod-body
troublesome side effects, such as mycophenolate Zidovudine-induced mitochondrial myopathy
mofetil, also may be helpful but are still under study.Acute rhabdomyolysis
Physical therapy may help to prevent contractures,
and,
as the patient responds to antiinammatory drugs,
active exercise may hasten recovery.
Percentage of
Patients

192 / CHAPTER 5
moderate to marked elevation of serum CK; it is 1q32. The clinical disorder is genetically
thought to result from a toxic effect of zidovudine heterogeneous
on
muscle. Mild symptoms may be controlled with nonand also has been associated with mutations at
steroidal antiinammatory drugs or corticosteroids,
11q13q14 and at 17q23.1q25.3.
and more severe involvement may respond to disconAcetazolamide or oral potassium supplements often
tinuing zidovudine. If there is no response, a muscle
prevent attacks, and ongoing attacks may be aborted
biopsy should be performed to look for other causes
by potassium chloride given orally or even intraof
venously. If hyperthyroidism is associated, its treatmyopathy. Acute rhabdomyolysis sometimes occurs
ment may prevent recurrences. Attacks associated
in
with
patients with HIV-1 infection and causes myalgia, hyperkalemia also tend to come on after exercise but
muscle weakness, and an elevated serum CK; it may
are usually much briefer, lasting less than 1 hour.
also
relate
to
medication
or
opportunistic
infection.
Severe attacks may be terminated by intravenous
Polymyalgia Rheumatica
calPolymyalgia rheumatica, which is more common incium gluconate, intravenous diuretics (furosemide,
women than in men, generally occurs in patients over
2040 mg), or glucose, while daily acetazolamide or
the age of 50 years and is best regarded as a variant
chlorothiazide may help prevent further episodes.
of
Many families with this disorder have a defect in the
giant cell arteritis. It is characterized by muscle pain
sodium channel gene (SCN4A) for the on
and stiffness, particularly about the neck and girdle
chromosome 17q23.1q25.3; several allelic mutations
muscles. Headache, anorexia, weight loss, and lowhave been recognized and account for some phenograde fever may be conjoined, and the erythrocyte
typic variation, such as the presence of myotonia or
sediparamyotonia. Paramyotonia congenita is a domimentation rate is increased. Serum enzymes, elecnantly inherited disorder, related to mutation of the
tromyography, and muscle biopsy are normal.
SCN4A gene, in which weakness and myotonia are
There is usually a dramatic response to treatment
provoked by cold and worsened by exercise; attacks
with corticosteroids in low dosage (eg, prednisone,
of
1015 mg/d orally). Treatment is monitored by clinical
hyperkalemic periodic paralysis may also occur.
parameters and sedimentation rate and may need to
Normokalemic periodic paralysis is sometimes unrebe
sponsive to treatment; in severe attacks, it may be
continued for 1 year or more if serious complications
imare to be avoided, as indicated
in Chapter 2 in the
Eosinophilia-Myalgia
Syndrome
possible to move the limbs, but respiration and swaldislowing are rarely affected.
Eosinophilia-myalgia
syndrome produces muscle pain
cussion on giant cell arteritis.
and weakness associated with inammation of skin Proximal muscle weakness may also occur in osteomalacia, often MYOPATHIES
with associated bone pain and tenderENDOCRINE
and
ness,
mild
hypocalcemia,
and elevated serum
other soft tissues but little direct involvement of musMyopathy
may occur in association with hyper- or hyalkaline
cle. Because the prominent symptoms are sensory,
pothyroidism,
hyper- orimproves
hypoparathyroidism,
hyperphosphatase. Strength
following treatment
this
or
with vitamin D.
Proximal
myopathic
weakness
may
disorder
is
discussed
in Chapter
6. result from
METABOLIC
MYOPATHIES
hypoadrenalism, hypopituitarism, and acromegaly.
chronic
Treatment is that of the underlying endocrine
hypokalemia, and once the metabolic disturbance disorder.
ALCOHOLIC MYOPATHIES
has
been corrected, power usually returns to normal Acute Necrotizing Myopathy
within
Heavy binge drinking may result in an acute necrotiza few weeks. Acute hypo- or hyperkalemia may also
ing myopathy that develops over 1 or 2 days.
lead to muscle weakness that is rapidly reversed by
Presentcoring symptoms include muscle pain, weakness, and
recting the metabolic disturbance.
The periodic paralysis syndromes, which may besometimes dysphagia. On examination, the affected
are swollen, tender, and weak. Weakness is
familial (dominant inheritance), are characterized muscles
by
proximal
in distribution and may be asymmetric or
episodes of accid weakness or paralysis that may be
focal.
Serum
CK is moderately to severely elevated,
asand myoglobinuria may occur. As hypokalemia and
sociated with abnormalities of the plasma potassium
hypophosphatemia can produce a similar syndrome
level. Strength is normal between attacks. In the hyin
pokalemic form, sometimes associated with thyrotoxialcoholic patients, serum potassium and phosphorus
cosis, attacks tend to occur on awakening, after exerconcentrations should be determined. With absticise, or after a heavy mealand may last for several
days. The disorder is due to a mutation in the genenence from alcohol and a nutritionally adequate diet,
encoding the dihydropyridine receptor on chromosome

MOTOR DEFICITS / 193

recovery can be expected over a period of weeks to
serum potassium level must be monitored, as it may
months.
rise rapidly.

Chronic Myopathy
Chronic myopathy characterized by proximal
MOTOR-UNIT HYPERACTIVITY
weakness
of the lower limbs may develop insidiously over STATES
weeks
to months in alcoholic patients. Muscle pain is not a
Disorders affecting the central or peripheral nervous
prominent feature. Cessation of drinking and an imsystem at a variety of sites can produce abnormal, inproved diet are associated with clinical improvement
creased activity in the motor unit (Table 518).
over several months in most cases.

DRUG-INDUCED MYOPATHIES

CENTRAL DISORDERS
Myopathy can occur in association with administraStiff-Person Syndrome
tion of corticosteroids, chloroquine, clobrate, emetine, aminocaproic acid, certain
bretylium tosylate, colchicine, HMG-CoA reductaseThis is a rare, usually sporadic, and slowly
progressive
inhibitors, zidovudine, or drugs that cause potassium
disorder manifested by tightness, stiffness, and
depletion. Symptoms vary from an asymptomatic inrigidity
crease in serum CK levels to acute rhabdomyolysis,
depending on the causal agent and the individual of
pa-axial and proximal limb muscles with
superimposed
tient. Necrotizing myopathies are due mainly to
painful spasms that may be accompanied by hyperlipid-lowering drugs, and mitochondrial myopathies
hidrosis and an increase in blood pressure.
to antiretroviral nucleoside analogues. Corticosteroid
myopathy is particularly common. Drug-induced Examination
may show tight muscles, a slow or cautious gait, and
myopathies are usually reversible if the causal agent
hyperreexia. The disorder sometimes has an autoimis
mune basis and it may be associated with other
discontinued.
autoimMYOGLOBINURIA
mune disorders. Many patients have diabetes. StiffperThis can result from muscle injury or ischemia (irreson syndrome can be distinguished from tetanus by
spective of its cause) and leads to a urine that is dark
its
red. The following causes are important:
more gradual onset and by the absence of trismus
Excessive unaccustomed exercise, leading to
(lockjaw). In some cases, the blood contains autoantimuscle
bodies against glutamic acid decarboxylase, which is
necrosis (rhabdomyolysis) and thus to myoglobin-inuria, sometimes on a familial basis.
volved in synthesis of the neurotransmitter
Crush injuries.

Muscle infarction.
tyric acid (GABA), and is concentrated in pancreatic
Prolonged tonic-clonic convulsions.
and in GABAergic neurons of the central
Polymyositis.
nerv Chronic potassium depletion.
Tetanus
ous system. A defect in central GABAergic
An acute alcoholic binge.
transmission
Certain viral infections associated with muscle Tetanus, a disorder of central inhibitory
has been proposed as the cause of the disorder, and
neurotransmisweaktreatment is with drugs that enhance GABAergic
sion caused by a toxin produced by Clostridium
ness and pain.
transtetani,
Hyperthermia.
mission, such as diazepam, 575 mg orally four times
Serum CK levels are elevated, often greatly. Myoglois
discussed earlier in this
chapter.
Metabolic myopathies (eg, McArdle disease).
PERIPHERAL
DISORDERS
daily. Baclofen,NERVE
vigabatrin,
sodium valproate, and
bin can be detected in the urine by the dipstick test
Cramps
gabapentin also may be helpful for relieving
for heme pigment; a positive test indicates the pressymptoms
ence of myoglobin in the urine unless red blood cells
These
involuntary
and typically
contractions
in some
patients. Treatment
withpainful
intravenous
imare present. In severe cases, myoglobinuria may lead
of
munoglobulins is sometimes effective in refractory
to renal failure, and peritoneal dialysis or
a
muscle or portion of a muscle are thought to arise
cases.
hemodialysis
dismay then be necessary. Otherwise, treatment
tally in the motor neuron. Palpable knotlike hardening
consists
of increasing the urine volume by hydration. The of the muscle may occur. Cramps are
characteristically

194 / CHAPTER 5
Table 518. Motor-unit hyperactivity states.
Site of Pathology

Syndrome

Clinical Features

Central nervous system

Stiff-person syndrome Rigidity, spasms

Peripheral nerve

Muscle

Treatment
Diazepam
Baclofen
Sodium valproate
Vigabatrin
Gabapentin
Immunosuppression

Tetanus

Rigidity, spasms

Cramps

Painful contraction of single muscle relieved

Quinine
by
passive stretch
Phenytoin
Carbamazepine

Neuromyotonia

Stiffness, myokymia, delayed relaxation Phenytoin

Carbamazepine

Tetany

Chvostek sign
Trousseau sign
Carpopedal spasm

Calcium
Magnesium
Correction of alkalosis

Hemifacial spasm

Involuntary hemifacial contraction

Carbamazepine
Botulinum toxin
Decompressive surgery

Myotonia

Delayed relaxation, percussion myotonia Phenytoin

Carbamazepine
Procainamide
Quinine
Tocainide
Mexilitene

Malignant hyperthermiaRigidity, fever

Diazepam

Dantrolene

follow irradiation of the nervous system. In acquired

relieved by passive stretching of the affected muscle.
They usually represent a benign condition and areneuromyotonia, antibodies against voltage-gated
potascommon at night or during or after exercise. However, sium channels are often found in the serum and CSF.
cramps may also be a manifestation of motor neuronSymptoms may be controlled with phenytoin,
disease or polyneuropathy, metabolic disturbances300400 mg/d orally, or carbamazepine, 200400 mg
orally three times a day.
(pregnancy, uremia, hypothyroidism, adrenal insufTetany
ciency), or uid or electrolyte disorders (dehydration,
hemodialysis). If a reversible underlying cause cannot
Tetanynot to be confused with tetanus (see above)
be

found, daytime cramps may respond to treatment is a hyperexcitable state of peripheral nerves usually
with
asphenytoin, 300400 mg/d orally, or carbamazepine,
sociated with hypocalcemia, hypomagnesemia, or
200400
mg
orally
three
times
a
day.
Nocturnal
alkaNeuromyotonia (Isaacs syndrome) is a rare, sporadic
cramps
losis. Signs of tetany (Chvostek sign, Trousseau sign,
disNeuromyotonia
may
respond
to
a
single
oral
bedtime
dose
of
quinine
spasm) are described in the section on
order that produces continuous muscle stiffness, carpopedal
Hemifacial
Spasm
sulfate
(325
mg),
phenytoin
(100300
mg),
carbahypocalcemia
in Chapter 1. Treatment is by correction
rippling
mazepine
(200400
mg),
or
diazepam
(510
mg).
of
the
underlying
disorder.
Hemifacial spasmelectrolyte
is characterized
by repetitive,
muscle movements (myokymia), and delayed
involrelaxation
following muscle contraction. Some cases have anuntary contractions of some or all of the muscles supplied by one facial nerve. Symptoms often commence
autoin the orbicularis oculi and then spread to the cheek
somal dominant mode of inheritance; in others, the
and levator anguli oris muscles. The contractions inineuromyotonia occurs as a paraneoplastic disorder, ortially
in are brief but become more sustained as the
disorassociation with other autoimmune diseases or with der progresses; they may be provoked by blinking or
hereditary motor and sensory neuropathies. It may
also

MOTOR DEFICITS / 195

voluntary activity. Slight facial weakness may alsoArgov
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