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Pediatric neuroradiology, part 1:

Embryologic basis for brain


malformation
Dianna M. E. Bardo, MD

K
nowledge of basic brain cephalus and can develop at almost telencephalon anteriorly and the dien-
embryology provides the foun- any time of brain development. Recog- cephalon posteriorly; the rhomben-
dation for making diagnoses of nition of the imaging milestones in cephalon divides into the anterior
brain malformations, heritable dis- postnatal brain maturation, primarily metencephalon and the posterior mye-
eases, congenital neoplasms and even the process of myelination, is impor- lencephalon. The mesencephalon re-
disorders of postnatal development. tant in differentiating dysmyelination mains a single vesicle and retains the
Malformation is defined as defective from degenerative processes. name mesencephalon (Figure 3).
or abnormal formation, especially At the same time, cavities that will
when acquired during development. Brain embryology become the ventricular system form
An anomaly is a marked deviation The earliest steps in the development within each vesicle. The lateral ventri-
from normal, especially as a result of of the brain occur at about 17 days of cles develop in the forebrain (prosen-
congenital or hereditary defects. The gestation when the neural plate, a thick- cephalon). The third ventricle develops
term syndrome is defined as a set of ening of the ectoderm, forms in the dor- from the cavity in the midbrain (mesen-
symptoms occurring together. A syn- sal midline of the embryo and begins to cephalon) and the fourth ventricle from
drome may be due to malformation or differentiate into neurons. By the 20th the cavity in the hindbrain (rhomben-
hereditary defects.1 day of gestation, the neural tube is cephalon). The foramina of Monro con-
Timing of brain malformations and formed and begins to close in the early nect the lateral and third ventricles; the
anomalies can be estimated through stages of neurulation (Figure 2). Neuru- third ventricle drains to the fourth ven-
critical assessment of absent or mal- lation continues through stages of vesi- tricle via the aqueduct of Sylvius. As
formed structures.2 (Figure 1) Herita- cle formation and the dorsal and ventral this process occurs, the choroid plexus
ble neurological diseases are caused by stages of induction. develops from blood vessels that
genetic errors that cause defects in the The brain forms at the rostral end of invade the ventricles from the dien-
normal processes of brain formation the neural tube. By the middle of the cephalon and the myelencephalon.5
and typically have imaging stigmata fourth week of gestation, 3 distinct pri- Differentiation of the secondary
that, when learned, are easily recogniz- mary vesicles have developed. As the vesicles occurs rapidly. The telen-
able. Congenital brain neoplasms, mal- primary vesicles mature and are cephalon expands to commence forma-
formations and other neurological folded, they differentiate into sec- tion of the cerebral hemispheres by
diseases may be associated with hydro- ondary vesicles during the fifth week week 11 of gestation. Importantly, each
of gestation.3,4 cerebral hemisphere is formed individ-
Dr. Bardo is an A ssociate Professor of The 3 primary vesicles are the fore- ually through the process of neuronal
Radiology and Cardiovascular Medi- brain (prosencephalon), midbrain (mes- proliferation. During this time the cere-
cine, and Director of Cardiac Radiology encephalon) and hindbrain (rhomb- bral cortex, basal ganglia and anterior
and Pediatric Neuroradiology, at Oregon encephalon). The secondary vesicles commissure are formed. Cortical cells
Health and Science University, Portland, arise from the primary vesicles: continue to migrate throughout ges-
OR.
the prosencephalon divides into the tation until about the 35th week.

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FIGURE 1. Brain embryology timeline. Weeks and months of prenatal development and early postnatal development are cross-referenced with
processes of neurulation, cerebral and cerebellar hemisphere definition, brainstem formation and myelination (Adapted from reference 2).

FIGURE 2. Neurulation. The neural plate


forms early in gestation from a layer of ecto-
derm. The notochord lies deep to the neural FIGURE 3. Primary and secondary vesicles. The primary vesicles are the prosencephalon,
plate, within the mesoderm. As the neural mesencephalon and rhombencephalon. Secondary vesicles are formed when the prosen-
folds form along the midline and fuse cephalon divides into the anterior telencephalon and the posterior diencephalon and the
together, the ectoderm in the midline is rhombencephalon divides into the anterior metencephalon and the posterior myelencephalon.
transformed, isolating the neural tube. The mesencephalon remains a single vesicle, retaining its name.

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A B

FIGURE 4. Occiptal cephalocele. A rounded


cerebral spinal fluid (CSF) signal mass pro-
trudes from the occiput of this 32-week-old
fetus (black arrows). The posterior fossa
contains a small cerebellum and CSF. The
atrium of the lateral ventricle is enlarged.

The insular cortex and early formation


of the Sylvian fissure occur during
FIGURE 5. Frontoethmoidal encephalocele. (A) T2-weighted coronal MR image shows herni-
weeks 11 to 28 of gestation through a ation of cerebral tissue into the midline, through the nasofrontal suture (white arrow). (B) 3-
process termed operculization. Defini- dimensional CT reconstruction of the facial bones shows the midline osseous defect due to
tion of the sulci and gyri, which define this frontoethmoidal encephalocele (asterisk). The metopic sutures are widened (black
the lobes of the cerebral hemispheres, is arrows) due to hydrocephalus, which causes elevated intracranial pressure.
not complete until the 35th week. The
diencephalon develops into the epithal-
amus, thalamus, hypothalamus, globi
pallidi, the pineal gland and the neuro-
hypophysis of the pituitary gland.5–9
The cerebral commissures of the
telencephalon begin to form during the
seventh week of gestation when a
thickening of the lamina terminalis
arises at the rostral end of the neural
tube, becoming the lamina reuniens
and the massa commissuralis.9 These
cells are the site of origin of the ante-
rior commissure and the corpus callo-
sum, respectively. The corpus cal-
losum is the largest of the decussating
white matter tracts. Its progression of
development is reported to be in
sequence, beginning with the posterior
aspect of the genu, followed by the
body, splenium, anterior genu and the
rostrum during weeks 10 to 12 of ges-
tation.10 This sequence of events has
been challenged, raising controversy.6,7
Structures arising from the mesen-
cephalon are the superior and inferior
colliculi of the tectum, cerebral pedun- FIGURE 6. Chiari I malformation. On a midline sagittal T1 sequence the cerebellar tonsils are
cles, optic lobes, optic tectum, tegmen- pointed and herniated below the foramen magnum to the level of the C2 posterior arch (white
tum and somatic motor neurons of arrow).

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of the rhombencephalon develops into


nerve fibers that form the medulla
oblongata. Somatic motor nerves of
cranial nerves VI and XII and the vis-
ceral motor neurons of cranial nerves V,
VII, IX, X and XI are developed from
the myelencephalon. The rostral neural
tube is contiguous with the myelen-
cephalon and forms the spinal cord.5
As each malformation is described,
timing and the basis of the abnormal
embryological process will be refer-
enced. I will not discuss spinal pathol-
ogy in this article.
FIGURE 7. Chiari I skull base. On a sagittal midline T1 sequence the clivus lies horizontal and
the posterior rim of the occiput is cupped (double arrows). These skull base changes may
Brain malformations
result in a small posterior fossa. The cerebellar tonsils are pointed and extend below the fora- Neurulation
men magnum to the level of the C1 posterior ring (black arrow). Dorsal induction and ventral induc-
tion are 2 processes of neurulation in
brain embryology that occur subsequent
to the early formation of the primaryand
secondary vesicles.

Neurulation (3 to 4 weeks)
Dorsal induction occurs at 3 to 4
weeks gestation and is the process by
which the neural tube closes, forming
the spinal cord. There are 3 phases of
dorsal induction; neurulation, canaliza-
tion and retrogressive differentiation.
Failed closure of the rostral end of the
neural tube can result in anencephaly, a
defect in which brain tissue is com-
pletely absent, a malformation that is
incompatible with postnatal life. Other
major malformations of abnormal dor-
sal induction are cephalocele and the
Chiari II malformation.11

Cephalocele
Cephalocele is an extension of
intracranial contents (e.g. meninges,
CSF and/or brain) through a dural and
calvarial defect. The type of malforma-
tion is named for its anatomic location
and the contents included in the herni-
FIGURE 8. Normal midline sagittal. On a sagittal midline T2 sequence the cerebellar tonsils lie ated tissue. The defect is usually mid-
at the level of the foramen magnum. The foramen magnum is defined by the basion (midline of line and is typically occipital in those
the ventral rim of the occipital bone) and the opisthion (midline of the posterior rim of the occip-
of European descent (Figure 4) and
ital bone, dotted white line).
frontoethmoidal in those with Asian
cranial nerves III and IV. The cerebel- spheres, the cerebellar hemispheres are heritage (Figure 5). Chiari III malfor-
lum and pons arise from the meten- formed by paired dorsal swellings that mation is an occipital, C1-to-C2
cephalon portion of the rhomb- grow individually and are aligned at the encephalocele that may contain cere-
encephalon. Like the cerebral hemi- midline. The myelencepahlon portion bellar tissue and CSF. 12

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FIGURE 9. Chiari II malformation. The posterior fossa is small, result- FIGURE 10. Severe hydrocephalus vs. hydranencephaly. Nearly all
ing in crowding of the normal cerebellum, through the foramen mag- cerebral tissue is replaced by CSF in this patient with severe hydro-
num (dotted white line). The fourth ventricle is elongated in a vertical cephalus. There is minimal cerebral tissue adjacent to the falx cerebri
dimension (asterisk) and the tectum is beaked (black arrow). The clivus and the inner table of the calvaria (white arrows). In hydranen-
is vertical (white arrow). cephaly, this cerebral tissue is absent.

Chiari malformations are controver-


sial, such as Chiari IV: hypoplasia of
the cerebellum alone or in association
with Chiari II.13 Chiari zero is also a
controversial designation: indicating
normal position of the cerebellar ton-
sils on imaging studies, but clinical
presentation of headache, which is
reminiscent of the experiences of
patients with Chiari I (personal com-
munication, David M. Frim, MD,
Chairman of Neurosurgery, The Uni-
versity of Chicago, Chicago, IL).
Chiari I malformation is character-
ized by low-lying cerebellar tonsils
(Figure 6). The posterior fossa may be
small because of shortening of the
clivus. The foramen magnum is
defined on sagittal magnetic resonance
FIGURE 11. Aqueductal stenosis. The supratentorial ventricles are enlarged due to stenosis (MR) images by the ventral and dorsal
at the distal aqueduct of Sylvius (black arrow) with a patent proximal aqueduct. The volume of margins of the occipital bone, i.e. the
the fourth ventricle is normal (asterisk). clivus (basion) and occiput (opisthion).
Chiari malformations single brain malformation. They are Horizontal orientation of the clivus and
The Chiari malformations I through numerous malformations that can cupping of the occiput is seen in many
IV are not a continuum. The number occur during neurulation of the hind- patients, contributing to smallness of
designations I, II, III or IV do not brain and commonly are associated the posterior fossa (Figure 7). Normal
imply a progression of severity of a with hydrocephalus. Some of the cerebellar tonsils are oval in shape and

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FIGURE 12. Alobar holoprosencephaly. Axial CT shows the FIGURE 13. Septo-optic dysplasia. Coronal T2 image shows the septum pellu-
cerebral hemispheres are contiguous across the midline (white cidum is absent and the roof of the lateral ventricles is squared in relation to the
arrows). The ventricular system is abnormally formed, opening lateral walls (black arrows).
into a “monoventricle,” which fills the majority of the cranium.

the tentorium is low lying, resulting in


crowding of the cerebellum and brain-
stem into the cervical medullary junc-
tion and upper cervical spinal canal.
This crowding results in kinking of the
medullary cervical junction and elon-
gation of the fourth ventricle (Fig-
ure 9). Although many patients are
developmentally normal, agenesis of
the corpus callosum and cortical migra-
tion anomalies may accompany Chiari
II malformation.15

Neurulation (5 to 10 weeks)
Ventral induction takes place during
weeks 5 to 10 of neurulation. The brain
segments, neuronal proliferation occurs
and the face is formed. The primary and
secondary vesicles (prosencephalon,
mesencephalon and rhombencephalon)
form the cerebrum, midbrain, cerebel-
lum and lower brainstem. The cere-
brum and cerebellum each form 2
distinct hemispheres.
Failure of these neural proliferation
FIGURE 14. Ectopic neurohypophysis. Midline sagittal T1 image shows a small sella turcica processes results in midline supratentor-
(arrowhead). The neurohypophysis has a normal high signal on T1, but it is located superior to ial anomalies such as holoprosen-
the sella, near the hypothalamus (black arrow).
cephaly, agenesis of the corpus cal-
should lie <5 mm below a line drawn Chiari II malformation and menin- losum, pituitary maldevelopment and
between the ventral and dorsal borders gomyelocele are nearly always associ- posterior fossa malformations such as
of the foramen magnum (Figure 8).14 ated. The posterior fossa is small and Dandy-Walker malformation, cerebellar

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of cerebral encephalomalacia, proba-


A B bly the result of occlusion of both
internal carotid arteries and infarction
of all cerebral tissue (Figure 10).9,16

Aqueductal stenosis
Congenital stenosis of the aqueduct
of Sylvius can be due to intrinsic or
extrinsic narrowing or malformation of
the aqueduct. Abnormal histiogenesis
and proliferation of periaqueductal
grey matter in the midbrain can result
in primary stenosis or formation of
numerous minute channels through the
C D aqueduct. Mass effect on the quad-
rigeminal plate from supratentorial
hydrocephalus, or a mass, can cause
secondary narrowing of the aqueduct.
Pre- and postnatal infection, inflamma-
tory disease or intraventricular hemor-
rhage can lead to acquired aqueductal
stenosis due to fibrosis or gliosis, lead-
ing to stenosis. X-linked forms of
aqueductal stenosis are also described.
Stenosis results in lateral and third
ventricle hydrocephalus; the fourth
ventricle remains normal in volume
(Figure 11).17
FIGURE 15. Dysgenesis of the corpus callosum. (A) Midline sagittal T1 image shows the cor-
pus callosum is small and the splenium is not formed (white arrow). The cingulate sulcus is Holoprosencephaly
also unformed allowing the interhemispheric gyri to radiate toward the corpus callosum and Holoprosencephaly occurs due to
roof of the third ventricle (double arrow). (B and C) Colpocephaly and Probst bundles. The lat- failure of proliferation of cerebral tis-
eral ventricles lie parallel and the atria and occipital horns of the lateral ventricles are dilated sue to form 2 separate cerebral hemi-
(colpocephaly, asterisks). The myelinated white matter tracts that would normally form the
spheres. Normally, the right and left
corpus callosum are aligned along the medial margins of the lateral ventricles (Probst bun-
dles, white arrows) and cause indentations of the roof of the lateral ventricles, resulting in a cerebral hemispheres form indepen-
bullʼs horn configuration. The lateral ventricles lie parallel to these bundles of white matter. dently in a unified process of neuronal
The atria and occipital horns of the lateral ventricles are not divergent (widely spaced) as in a proliferation. Although prosenceph-
normal brain. (D) Axial CT shows the lateral ventricles are parallel and are separated by a alon formation abnormalities are pro-
CSF attenuation cyst (C) that lies in the interhemispheric fissure.
grammed for failure earlier in ges-
hypoplasia and rhombencephalosynap- to 12 of gestation. Obstruction at any tation, even before the neural tube
sis. Hydrocephalus due to aqueductal point of the ventricular system due to closes, it is during the proliferative
stenosis can also occur during this time.11 failure in the formation of these cavities phase of ventral induction that holo-
can occur at any time. Other sources of prosencephaly manifests. When the
Hydropcephalus ventricular obstruction are canalization hemispheres fail to develop into 2 sep-
Hydrocephalus is an enlargement of of the foramina and aqueducts, over- arate hemispheres but rather form a
the ventricular system in the brain and production of CSF by the choroid single, midline mass of cerebral tissue,
implies there is elevated intracranial pres- plexus, or diminished reabsorption the result is holoprosencephaly.
sure. Almost all of the malformations, through the arachnoid villi. Obstruction The most severe form of holoprosen-
diseases and syndromes mentioned in can occur prenatally, from the time of cephaly is termed alobar, because the
this article can be associated with formation, to birth, or postnatally and cerebral tissue bears no resemblance to
hydrocephalus. result in hydrocephalus. normally defined cerebral lobes (Fig-
The cavities that become the ventri- When severe, hydrocephalus may be ure 12). The lateral ventricles are also
cles, and the foramina and aqueducts difficult to differentiate from hydra- abnormal, forming a midline monoven-
connecting them, form during weeks 4 nencephaly, which is an extreme form tricle. Septo-optic dysplasia is the

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A B

FIGURE 16. Dandy-Walker complex. Axial CT shows the fourth ventricle (aster-
isk) is in direct communication with a fluid collection in the posterior fossa. The
lateral ventricles are enlarged (white arrows). Midline sagittal T1 image shows
the posterior fossa is enlarged and filled with CSF signal fluid. The torcular
Herophili is elevated (white arrow) and its position is at the peripheral margin of
the tentorium, which is located in the plane of the straight sinus (double arrows).

is usually seen in patients with holo-


prosencephaly. Facial malformations
are due to abnormal development of the
premaxillary segments of the face and
result in arrhinia and midline facial
clefts.19

Agenesis of the corpus callosum


Agenesis of the corpus callosum is
one of the most common malformations
of the brain.20 The corpus callosum
begins to form in the seventh week of
gestation and is complete by 18 to 20
weeks. There has been controversy
regarding the definitive order in which
segments of the corpus callosum are
formed, but its absence is known to be
FIGURE 18. Rhombencephalosynapsis. associated with a range of findings
FIGURE 17. Cerebellar hemisphere agene- Axial T2-weighted image reveals that cere- including normal development, Dandy-
sis. Axial CT image shows the left cerebellar bellar hemispheres are continuous across
hemisphere is absent but the vermis is intact
Walker complex, Chiari II malforma-
the midline (black arrows).
(black arrow). The left side of the posterior tion, numerous syndromes, and the
fossa is small and the occipital bone is thick- which the frontal, temporal, parietal and absence may be accompanied by seizure
ened due to unopposed growth (white occipital lobes are defined. The degree of disorders and mental retardation.6, 7
arrow). cerebral malformation is less severe than Radiographic findings of dysgenesis or
mildest form of the holoprosencephaly in the alobar form. Other midline struc- agenesis of the corpus callosum include
spectrum: the septum pellucidum and the tures, the falx and septum pellucidum are absence of, or a malformed corpus callo-
optic nerves are atrophic (Figure 13). dysplastic. Schizencephaly is associated sum (Figure 15), and parallel orientation
Pituitary gland malfunction is part of the in 50% of cases.9,17,18 of the lateral ventricles; normally the
syndrome of septo-optic dysplasia (Fig- Because there is a temporal relation- frontal horns lie closer together than the
ure 14). Semilobar and lobar forms of ship between facial formation and neu- occipital horns of the lateral ventricles.
holoprosencephaly describe the degree to ronal proliferation, facial malformation The occipital horns and atria of the lateral

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FIGURE19. Microcephaly. A midline sagittal T1-weighted image shows the size of FIGURE 20. Focal cortical dysplasia. Coronal FLAIR:
the brain and calvaria are small in this infant with a head circumference >3 stan- Abnormal high signal in the cortex and subcortical white
dard deviations below normal. matter of the left superior temporal gyrus (white arrow)
represents focal cortical dysplasia.

A B C

FIGURE 21. Heterotopia. (A and B) T1-weighted axial and reconstructed sagittal images show foci of cortical grey matter in an ectopic location
adjacent to the lateral ventricles (black arrows). The grey matter of the caudate nucleus is adjacent to the inferolateral surface of the lateral ven-
tricle (white arrows). (C) A coronal T1-weighted image demonstrates a band of cortical cells that has failed to migrate completely to the surface
of the cerebral hemispheres (paired arrows).

ventricles may be dilated, a finding indenting the ventricle which causes a outlet foramina. As a result, the roof of
termed colpocephaly (Figure 15). When bull’s horn configuration.20 the fourth ventricle does not develop
the corpus callosum is completely or par- The roof of the third ventricle can be normally and there is hypogenesis or
tially absent the cingulate gyrus does not displaced upward because the corpus agenesis of the cerebellar vermis. The
form normally, allowing interhemi- callosum is not limiting its superior fourth ventricle therefore communi-
spheric gyri to radiate toward the roof of expansion; an interhemispheric cyst or cates freely with extra-axial fluid in the
the lateral ventricles. The neurons that lipoma may be associated (Figure 15).20 posterior fossa (Figure 16) . The tento-
normally cross the midline to form the rium and position of the torcular
corpus callosum course along the inter- The Dandy-Walker complex Herophili are elevated; i.e. the posterior
hemispheric fissure, in groups of white The Dandy-Walker complex is the fossa is enlarged (Figure 16). The
matter called Probst bundles (Figure 15). result of malformation of the meten- Dandy-Walker complex encompasses a
These bundles lie along the superior cephalon portion of the rhombenceph- range of hypoplasia or dysplasia of the
medial surface of the lateral ventricles, alon leading to atresia of the cerebellar cerebellar hemispheres and/or vermis

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FIGURE 22. Polymicrogyria. The left cere- FIGURE 23. Lissencephaly. Axial CT: FIGURE 24. Hemimegalencephaly. On axial
bral hemisphere is severely dysmorphic. The The gryi and sulci did not develop normally CT the entire right side of the brain is larger
gyri are small and the numerous sulci do not in this full-term infant resulting in a smooth than the left (dotted white line). The cortex of
define the normal surface anatomy of the cortical surface and thick layer of cortex the right cerebral hemisphere is thicker
cerebrum. The cortex is lobular (black circle) (white arrows). The definition of the Sylvian (white arrows) and there is more white mat-
and its thickness is irregular. CSF signal, fissures is also underdeveloped (paired ter on the right and the volume of the right
midline, extra-axial fluid collections represent arrows). lateral ventricle is larger (R).
an interhemispheric cyst (C), which is associ-
ated with agenesis of the corpus callosum.
A B
which can be found in patients with
numerous diagnoses of chromosomal
anomalies and syndromes.11,21

Cerebellar hypoplasia
Cerebellar hypoplasia may be dif-
fuse or can be limited to a single hemi-
sphere and may involve the vermis.
Differentiating hypoplasia from other
cerebellar malformations, dysplasia
and atrophy requires determining that
the posterior fossa is normal volume
and determining the absence of an
associated cyst in communication with
the fourth ventrice (Figure 17).21
FIGURE 25. Schizencephaly. (A) An axial T2-weighted image shows cortical grey matter
extending from the ependymal surface of the left lateral ventricle (single arrow) through the
Rhombencephalosynapsis cerebral mantle (double arrows) to the cortical surface. The margins of each side of the schism
Although rhombencephalosynapsis abut one another. The lateral ventricle communicates with the subarachnoid space (*). (B) On
is usually described as a “fusion” axial CT the cortical grey matter extends along the margin of each side of the schism (double
anomaly, or dysplasia of the cerebellar arrow). The margins of the schism do not lie close to each other (arrows). The lateral ventricle
communicates directly with the subarachnoid space via a wide cleft.
hemispheres and vermis, and has been
described in a patient with holoprosen- The cerebellar hemispheres are continu- goal of producing organized cortical lay-
cephaly,9,21 I believe this malformation ous across the midline (Figure 18).9 ering. Failure of this process results in
is probably the result of failed neuronal microcephaly, megalencephaly, hetero-
proliferation of the cerebellar hemi- Neuronal proliferation, migration and topia, focal cortical dysplasia, polymicr-
spheres, much like holoprosencephaly histiogenesis (8 to 21 weeks) ogyria, lissencephaly, hemimegalen-
of the cerebral hemispheres. During this phase of development cephaly, schizencephaly, anomalies of
Imaging studies reveal an absence of neuronal cells undergo proliferation, dif- operculization, and phakomatoses.
the normal formation of midline struc- ferentiation and histiogenesis. Neuronal Phakomatoses and other inheritable neu-
tures of the posterior fossa including the stem cells migrate from the germinal rologic diseases will be discussed in part
vermis and mesencephalic structures. matrix to the cerebral cortex with the 2 of this article. Regulators of cortical

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A B C

FIGURE 26. Operculization. (A) Axial CT image shows the Sylvian fissures (S) are abnormally formed, and symmetric, resulting in a “figure 8”
formation of the cerebral hemispheres on this axial image. The cortex in the right Sylvian fissure is thickened (white arrows). (B) Axial T2-
weighted image shows the left Sylvian fissure is abnormally formed (arrows) and the overlying subarachnoid space is capacious (S). (C) Coro-
nal T2-weighted image shows that the right Sylvian fissure is abnormally formed and there are prominent vascular flow voids in the slightly
prominent subarachnoid space (black arrow).

malformation have been identified and plasia contain balloon cells, and may with abnormal sulcal formation. MR
associated with specific malformations show abnormal signal and architecture may also show a nodular appearance
of the cerebral cortex through molecular extending from the germinal matrix of the cortex and normal-to-increased
genetic studies.22 Vascular malforma- through the deep and subcortical white signal in the cortical tissue. There are
tions are thought to be formed during matter. Imaging findings are variable, numerous syndromes and patterns of
this time; indeed, many malformations depending on the involvement of white polymicrogyria, and many have been
of the cerebral cortices are accompanied matter and may show focal blurring of shown to correspond with chromoso-
by abnormal vasculature.11 Vascular the grey-white junction, or thinning or mal abnormalities (Figure 22).9,22
anomalies will not be discussed further thickening of the affected cerebral cor-
in this article. tex, which usually has high T2 signal Lissencephaly
on MR (Figure 20).9 Lissencephaly (smooth brain)
Microcephaly and megalencephaly describes the malformation with lack
Microcephaly and megalencephaly Heterotopia of gyral and sulcal development such
are due to disorders of neuronal and Heterotopia (singular: heterotopion) that the surface of the cerebral hemi-
glial proliferation or excess or reduced are abnormal anatomic locations of spheres is smooth, due to arrested neu-
apoptosis. Microcephaly is a malfor- cortical grey matter which are due to ronal migration. Agyria (complete
mation secondary to abnormal stem- premature arrest of neuronal migra- lissencephaly) or pachygyria (incom-
cell proliferation or apoptosis after tion. Typical locations of heterotopia plete lissencephaly) as well as a thick-
normal proliferation of stem cells. By are subependymal, where they are usu- ened cerebral cortex are seen on
definition, the head circumference in ally asymmetric, at the trigones of the imaging studies, differentiating lissen-
these children is ≥3 standard deviations lateral ventricles and subcortical, cephaly from malformations of neu-
below the norm. There are fewer gyri, where they may be focal (Figure 21) or ronal proliferation (Figure 23).9,22
the depth of the sulci is shallow and the generalized, forming a band or double
volume of white matter is diminished cortex underlying the normal-appearing Hemimegalencephaly
(Figure 19). cerebral cortices.9 Hemimegalencephaly is unilateral
Megalencephaly is the result of a gen- megalencephaly that is isolated, part of a
eralized increase in neuronal and glial Polymicrogyria hemihypertrophy syndrome or the result
proliferation or diminished apoptosis.9 In the later stages of neuronal migra- of hamartomatous overgrowth of one
tion, the 6 layers of the cerebral cortex cerebral hemisphere. The malformation
Focal cortical dysplasia are organized. When the deep layers of occurs because of defective neuronal
Focal cortical dysplasia is the result the cerebral cortex form numerous proliferation, migration and cortical
of abnormal migration of neurons to small gyri instead of organized cortical organization. The unilateral enlargement
the cerebral cortical cell layers. Histo- layers, the imaging result appears to be of the cerebral hemisphere includes pro-
logically, the cortical cells are also thickening or thinning of the cerebral portionate ventriculomegaly and unilat-
abnormal. Some forms of cortical dys- cortex, which is usually associated eral enlargement of CN I and CN II

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PEDIATRIC NEURORADIOLOGY
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