featured applied radiology article: pediatric neuroradiology part 1- embryo logic basis for brain...

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Knowledge of basic brainembryology provides the foun-dation for making diagnoses of

brain malformations, heritable dis-eases, congenital neoplasms and evendisorders of postnatal development.

Malformation is defined as defectiveor abnormal formation, especiallywhen acquired during development.An anomaly is a marked deviationfrom normal, especially as a result ofcongenital or hereditary defects. Theterm syndrome is defined as a set ofsymptoms occurring together. A syn-drome may be due to malformation orhereditary defects.1

Timing of brain malformations andanomalies can be estimated throughcritical assessment of absent or mal-formed structures.2 (Figure 1) Herita-ble neurological diseases are caused bygenetic errors that cause defects in thenormal processes of brain formationand typically have imaging stigmatathat, when learned, are easily recogniz-able. Congenital brain neoplasms, mal-formations and other neurologicaldiseases may be associated with hydro-

cephalus and can develop at almostany time of brain development. Recog-nition of the imaging milestones inpostnatal brain maturation, primarilythe process of myelination, is impor-tant in differentiating dysmyelinationfrom degenerative processes.

Brain embryologyThe earliest steps in the development

of the brain occur at about 17 days ofgestation when the neural plate, a thick-ening of the ectoderm, forms in the dor-sal midline of the embryo and begins todifferentiate into neurons. By the 20thday of gestation, the neural tube isformed and begins to close in the earlystages of neurulation (Figure 2). Neuru-lation continues through stages of vesi-cle formation and the dorsal and ventralstages of induction.

The brain forms at the rostral end ofthe neural tube. By the middle of thefourth week of gestation, 3 distinct pri-mary vesicles have developed. As theprimary vesicles mature and arefolded, they differentiate into sec-ondary vesicles during the fifth weekof gestation.3,4

The 3 primary vesicles are the fore-brain (prosencephalon), midbrain (mes-encephalon) and hindbrain (rhomb-encephalon). The secondary vesiclesarise from the primary vesicles: the prosencephalon divides into the

telencephalon anteriorly and the dien-cephalon posteriorly; the rhomben-cephalon divides into the anteriormetencephalon and the posterior mye-lencephalon. The mesencephalon re-mains a single vesicle and retains thename mesencephalon (Figure 3).

At the same time, cavities that willbecome the ventricular system formwithin each vesicle. The lateral ventri-cles develop in the forebrain (prosen-cephalon). The third ventricle developsfrom the cavity in the midbrain (mesen-cephalon) and the fourth ventricle fromthe cavity in the hindbrain (rhomben-cephalon). The foramina of Monro con-nect the lateral and third ventricles; thethird ventricle drains to the fourth ven-tricle via the aqueduct of Sylvius. Asthis process occurs, the choroid plexusdevelops from blood vessels thatinvade the ventricles from the dien-cephalon and the myelencephalon.5

Differentiation of the secondaryvesicles occurs rapidly. The telen-cephalon expands to commence forma-tion of the cerebral hemispheres byweek 11 of gestation. Importantly, eachcerebral hemisphere is formed individ-ually through the process of neuronalproliferation. During this time the cere-bral cortex, basal ganglia and anteriorcommissure are formed. Cortical cellscontinue to migrate throughout ges-tation until about the 35th week.

Pediatric neuroradiology, part 1:Embryologic basis for brainmalformation

Dianna M. E. Bardo, MD

Dr. Bardo is an A ssociate Professor ofRadiology and Cardiovascular Medi-cine, and Director of Cardiac Radiologyand Pediatric Neuroradiology, at OregonHealth and Science University, Portland,OR.

30 ! APPLIED RADIOLOGY© www.appliedradiology.com July–August 2009

PEDIATRIC NEURORADIOLOGY

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

FIGURE 2. Neurulation. The neural plateforms early in gestation from a layer of ecto-derm. The notochord lies deep to the neuralplate, within the mesoderm. As the neuralfolds form along the midline and fusetogether, the ectoderm in the midline istransformed, isolating the neural tube.

FIGURE 3. Primary and secondary vesicles. The primary vesicles are the prosencephalon,mesencephalon and rhombencephalon. Secondary vesicles are formed when the prosen-cephalon divides into the anterior telencephalon and the posterior diencephalon and therhombencephalon divides into the anterior metencephalon and the posterior myelencephalon.The mesencephalon remains a single vesicle, retaining its name.


The insular cortex and early formationof the Sylvian fissure occur duringweeks 11 to 28 of gestation through aprocess termed operculization. Defini-tion of the sulci and gyri, which definethe lobes of the cerebral hemispheres, isnot complete until the 35th week. Thediencephalon develops into the epithal-amus, thalamus, hypothalamus, globipallidi, the pineal gland and the neuro-hypophysis of the pituitary gland.5–9

The cerebral commissures of thetelencephalon begin to form during theseventh week of gestation when athickening of the lamina terminalisarises at the rostral end of the neuraltube, becoming the lamina reuniensand the massa commissuralis.9 Thesecells 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 decussatingwhite matter tracts. Its progression ofdevelopment is reported to be insequence, beginning with the posterioraspect of the genu, followed by thebody, splenium, anterior genu and therostrum during weeks 10 to 12 of ges-tation.10 This sequence of events hasbeen challenged, raising controversy.6,7

Structures arising from the mesen-cephalon are the superior and inferiorcolliculi of the tectum, cerebral pedun-cles, optic lobes, optic tectum, tegmen-tum and somatic motor neurons of


FIGURE 4. Occiptal cephalocele. A roundedcerebral spinal fluid (CSF) signal mass pro-trudes from the occiput of this 32-week-oldfetus (black arrows). The posterior fossacontains a small cerebellum and CSF. Theatrium of the lateral ventricle is enlarged.

FIGURE 5. Frontoethmoidal encephalocele. (A) T2-weighted coronal MR image shows herni-ation of cerebral tissue into the midline, through the nasofrontal suture (white arrow). (B) 3-dimensional CT reconstruction of the facial bones shows the midline osseous defect due tothis frontoethmoidal encephalocele (asterisk). The metopic sutures are widened (blackarrows) due to hydrocephalus, which causes elevated intracranial pressure.

A B

FIGURE 6. Chiari I malformation. On a midline sagittal T1 sequence the cerebellar tonsils arepointed and herniated below the foramen magnum to the level of the C2 posterior arch (whitearrow).


cranial nerves III and IV. The cerebel-lum and pons arise from the meten-cephalon portion of the rhomb-encephalon. Like the cerebral hemi-

spheres, the cerebellar hemispheres areformed by paired dorsal swellings thatgrow individually and are aligned at themidline. The myelencepahlon portion

of the rhombencephalon develops intonerve fibers that form the medullaoblongata. Somatic motor nerves ofcranial nerves VI and XII and the vis-ceral motor neurons of cranial nerves V,VII, IX, X and XI are developed fromthe myelencephalon. The rostral neuraltube is contiguous with the myelen-cephalon and forms the spinal cord.5

As each malformation is described,timing and the basis of the abnormalembryological process will be refer-enced. I will not discuss spinal pathol-ogy in this article.

Brain malformationsNeurulation

Dorsal induction and ventral induc-tion are 2 processes of neurulation inbrain embryology that occur subsequentto the early formation of the primaryandsecondary vesicles.

Neurulation (3 to 4 weeks)Dorsal induction occurs at 3 to 4

weeks gestation and is the process bywhich the neural tube closes, formingthe spinal cord. There are 3 phases ofdorsal induction; neurulation, canaliza-tion and retrogressive differentiation.Failed closure of the rostral end of theneural tube can result in anencephaly, adefect in which brain tissue is com-pletely absent, a malformation that isincompatible with postnatal life. Othermajor malformations of abnormal dor-sal induction are cephalocele and theChiari II malformation.11

CephaloceleCephalocele is an extension of

intracranial contents (e.g. meninges,CSF and/or brain) through a dural andcalvarial defect. The type of malforma-tion is named for its anatomic locationand the contents included in the herni-ated tissue. The defect is usually mid-line and is typically occipital in thoseof European descent (Figure 4) andfrontoethmoidal in those with Asianheritage (Figure 5). Chiari III malfor-mation is an occipital, C1-to-C2encephalocele that may contain cere-bellar tissue and CSF. 12


FIGURE 7. Chiari I skull base. On a sagittal midline T1 sequence the clivus lies horizontal andthe posterior rim of the occiput is cupped (double arrows). These skull base changes mayresult in a small posterior fossa. The cerebellar tonsils are pointed and extend below the fora-men magnum to the level of the C1 posterior ring (black arrow).

FIGURE 8. Normal midline sagittal. On a sagittal midline T2 sequence the cerebellar tonsils lieat the level of the foramen magnum. The foramen magnum is defined by the basion (midline ofthe ventral rim of the occipital bone) and the opisthion (midline of the posterior rim of the occip-ital bone, dotted white line).


Chiari malformationsThe Chiari malformations I through

IV are not a continuum. The numberdesignations I, II, III or IV do notimply a progression of severity of a

single brain malformation. They arenumerous malformations that canoccur during neurulation of the hind-brain and commonly are associatedwith hydrocephalus. Some of the

Chiari malformations are controver-sial, such as Chiari IV: hypoplasia ofthe cerebellum alone or in associationwith Chiari II.13 Chiari zero is also acontroversial designation: indicatingnormal position of the cerebellar ton-sils on imaging studies, but clinicalpresentation of headache, which isreminiscent of the experiences ofpatients 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 besmall because of shortening of theclivus. The foramen magnum isdefined on sagittal magnetic resonance(MR) images by the ventral and dorsalmargins of the occipital bone, i.e. theclivus (basion) and occiput (opisthion).Horizontal orientation of the clivus andcupping of the occiput is seen in manypatients, contributing to smallness ofthe posterior fossa (Figure 7). Normalcerebellar tonsils are oval in shape and


FIGURE 9. Chiari II malformation. The posterior fossa is small, result-ing in crowding of the normal cerebellum, through the foramen mag-num (dotted white line). The fourth ventricle is elongated in a verticaldimension (asterisk) and the tectum is beaked (black arrow). The clivusis vertical (white arrow).

FIGURE 10. Severe hydrocephalus vs. hydranencephaly. Nearly allcerebral tissue is replaced by CSF in this patient with severe hydro-cephalus. There is minimal cerebral tissue adjacent to the falx cerebriand the inner table of the calvaria (white arrows). In hydranen-cephaly, this cerebral tissue is absent.

FIGURE 11. Aqueductal stenosis. The supratentorial ventricles are enlarged due to stenosisat the distal aqueduct of Sylvius (black arrow) with a patent proximal aqueduct. The volume ofthe fourth ventricle is normal (asterisk).


should lie <5 mm below a line drawnbetween the ventral and dorsal bordersof the foramen magnum (Figure 8).14

Chiari II malformation and menin-gomyelocele are nearly always associ-ated. The posterior fossa is small and

the tentorium is low lying, resulting incrowding of the cerebellum and brain-stem into the cervical medullary junc-tion and upper cervical spinal canal.This crowding results in kinking of themedullary cervical junction and elon-gation of the fourth ventricle (Fig-ure 9). Although many patients aredevelopmentally normal, agenesis ofthe corpus callosum and cortical migra-tion anomalies may accompany ChiariII malformation.15

Neurulation (5 to 10 weeks)Ventral induction takes place during

weeks 5 to 10 of neurulation. The brainsegments, neuronal proliferation occursand the face is formed. The primary andsecondary vesicles (prosencephalon,mesencephalon and rhombencephalon)form the cerebrum, midbrain, cerebel-lum and lower brainstem. The cere-brum and cerebellum each form 2distinct hemispheres.

Failure of these neural proliferationprocesses results in midline supratentor-ial anomalies such as holoprosen-cephaly, agenesis of the corpus cal-losum, pituitary maldevelopment andposterior fossa malformations such asDandy-Walker malformation, cerebellar


FIGURE 12. Alobar holoprosencephaly. Axial CT shows thecerebral hemispheres are contiguous across the midline (whitearrows). The ventricular system is abnormally formed, openinginto a “monoventricle,” which fills the majority of the cranium.

FIGURE 13. Septo-optic dysplasia. Coronal T2 image shows the septum pellu-cidum is absent and the roof of the lateral ventricles is squared in relation to thelateral walls (black arrows).

FIGURE 14. Ectopic neurohypophysis. Midline sagittal T1 image shows a small sella turcica(arrowhead). The neurohypophysis has a normal high signal on T1, but it is located superior tothe sella, near the hypothalamus (black arrow).


hypoplasia and rhombencephalosynap-sis. Hydrocephalus due to aqueductalstenosis can also occur during this time.11

HydropcephalusHydrocephalus is an enlargement of

the ventricular system in the brain andimplies there is elevated intracranial pres-sure. Almost all of the malformations,diseases and syndromes mentioned inthis article can be associated withhydrocephalus.

The cavities that become the ventri-cles, and the foramina and aqueductsconnecting them, form during weeks 4

to 12 of gestation. Obstruction at anypoint of the ventricular system due tofailure in the formation of these cavitiescan occur at any time. Other sources ofventricular obstruction are canalizationof the foramina and aqueducts, over-production of CSF by the choroidplexus, or diminished reabsorptionthrough the arachnoid villi. Obstructioncan occur prenatally, from the time offormation, to birth, or postnatally andresult in hydrocephalus.

When severe, hydrocephalus may bedifficult to differentiate from hydra-nencephaly, which is an extreme form

of cerebral encephalomalacia, proba-bly the result of occlusion of bothinternal carotid arteries and infarctionof all cerebral tissue (Figure 10).9,16

Aqueductal stenosisCongenital stenosis of the aqueduct

of Sylvius can be due to intrinsic orextrinsic narrowing or malformation ofthe aqueduct. Abnormal histiogenesisand proliferation of periaqueductalgrey matter in the midbrain can resultin primary stenosis or formation ofnumerous minute channels through theaqueduct. Mass effect on the quad-rigeminal plate from supratentorialhydrocephalus, or a mass, can causesecondary narrowing of the aqueduct.Pre- and postnatal infection, inflamma-tory disease or intraventricular hemor-rhage can lead to acquired aqueductalstenosis due to fibrosis or gliosis, lead-ing to stenosis. X-linked forms ofaqueductal stenosis are also described.Stenosis results in lateral and thirdventricle hydrocephalus; the fourthventricle remains normal in volume(Figure 11).17

HoloprosencephalyHoloprosencephaly occurs due to

failure of proliferation of cerebral tis-sue to form 2 separate cerebral hemi-spheres. Normally, the right and leftcerebral hemispheres form indepen-dently in a unified process of neuronalproliferation. Although prosenceph-alon formation abnormalities are pro-grammed for failure earlier in ges-tation, even before the neural tubecloses, it is during the proliferativephase of ventral induction that holo-prosencephaly manifests. When thehemispheres fail to develop into 2 sep-arate hemispheres but rather form asingle, midline mass of cerebral tissue,the result is holoprosencephaly.

The most severe form of holoprosen-cephaly is termed alobar, because thecerebral tissue bears no resemblance tonormally defined cerebral lobes (Fig-ure 12). The lateral ventricles are alsoabnormal, forming a midline monoven-tricle. Septo-optic dysplasia is the


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 isalso unformed allowing the interhemispheric gyri to radiate toward the corpus callosum androof of the third ventricle (double arrow). (B and C) Colpocephaly and Probst bundles. The lat-eral ventricles lie parallel and the atria and occipital horns of the lateral ventricles are dilated(colpocephaly, asterisks). The myelinated white matter tracts that would normally form thecorpus 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 abull!s horn configuration. The lateral ventricles lie parallel to these bundles of white matter.The atria and occipital horns of the lateral ventricles are not divergent (widely spaced) as in anormal brain. (D) Axial CT shows the lateral ventricles are parallel and are separated by aCSF attenuation cyst (C) that lies in the interhemispheric fissure.

A B

C D


mildest form of the holoprosencephalyspectrum: the septum pellucidum and theoptic nerves are atrophic (Figure 13).Pituitary gland malfunction is part of thesyndrome of septo-optic dysplasia (Fig-ure 14). Semilobar and lobar forms ofholoprosencephaly describe the degree to

which the frontal, temporal, parietal andoccipital lobes are defined. The degree ofcerebral malformation is less severe thanin the alobar form. Other midline struc-tures, the falx and septum pellucidum aredysplastic. Schizencephaly is associatedin 50% of cases.9,17,18

Because there is a temporal relation-ship between facial formation and neu-ronal proliferation, facial malformation

is usually seen in patients with holo-prosencephaly. Facial malformationsare due to abnormal development of thepremaxillary segments of the face andresult in arrhinia and midline facialclefts.19

Agenesis of the corpus callosumAgenesis of the corpus callosum is

one of the most common malformationsof the brain.20 The corpus callosumbegins to form in the seventh week ofgestation and is complete by 18 to 20weeks. There has been controversyregarding the definitive order in whichsegments of the corpus callosum areformed, but its absence is known to beassociated with a range of findingsincluding normal development, Dandy-Walker complex, Chiari II malforma-tion, numerous syndromes, and theabsence may be accompanied by seizuredisorders and mental retardation.6, 7

Radiographic findings of dysgenesis oragenesis of the corpus callosum includeabsence of, or a malformed corpus callo-sum (Figure 15), and parallel orientationof the lateral ventricles; normally thefrontal horns lie closer together than theoccipital horns of the lateral ventricles.The occipital horns and atria of the lateral


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. Thelateral ventricles are enlarged (white arrows). Midline sagittal T1 image showsthe posterior fossa is enlarged and filled with CSF signal fluid. The torcularHerophili is elevated (white arrow) and its position is at the peripheral margin ofthe tentorium, which is located in the plane of the straight sinus (double arrows).

A B

FIGURE 17. Cerebellar hemisphere agene-sis. Axial CT image shows the left cerebellarhemisphere is absent but the vermis is intact(black arrow). The left side of the posteriorfossa is small and the occipital bone is thick-ened due to unopposed growth (whitearrow).

FIGURE 18. Rhombencephalosynapsis.Axial T2-weighted image reveals that cere-bellar hemispheres are continuous acrossthe midline (black arrows).


ventricles may be dilated, a findingtermed colpocephaly (Figure 15). Whenthe corpus callosum is completely or par-tially absent the cingulate gyrus does notform normally, allowing interhemi-spheric gyri to radiate toward the roof ofthe lateral ventricles. The neurons thatnormally cross the midline to form thecorpus callosum course along the inter-hemispheric fissure, in groups of whitematter called Probst bundles (Figure 15).These bundles lie along the superiormedial surface of the lateral ventricles,

indenting the ventricle which causes abull’s horn configuration.20

The roof of the third ventricle can bedisplaced upward because the corpuscallosum is not limiting its superiorexpansion; an interhemispheric cyst orlipoma may be associated (Figure 15).20

The Dandy-Walker complexThe Dandy-Walker complex is the

result of malformation of the meten-cephalon portion of the rhombenceph-alon leading to atresia of the cerebellar

outlet foramina. As a result, the roof ofthe fourth ventricle does not developnormally and there is hypogenesis oragenesis of the cerebellar vermis. Thefourth ventricle therefore communi-cates freely with extra-axial fluid in theposterior fossa (Figure 16) . The tento-rium and position of the torcularHerophili are elevated; i.e. the posteriorfossa is enlarged (Figure 16). TheDandy-Walker complex encompasses arange of hypoplasia or dysplasia of thecerebellar hemispheres and/or vermis


FIGURE19. Microcephaly. A midline sagittal T1-weighted image shows the size ofthe brain and calvaria are small in this infant with a head circumference >3 stan-dard deviations below normal.

FIGURE 20. Focal cortical dysplasia. Coronal FLAIR:Abnormal high signal in the cortex and subcortical whitematter 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 locationadjacent 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 surfaceof the cerebral hemispheres (paired arrows).


which can be found in patients withnumerous diagnoses of chromosomalanomalies and syndromes.11,21

Cerebellar hypoplasiaCerebellar hypoplasia may be dif-

fuse or can be limited to a single hemi-sphere and may involve the vermis.Differentiating hypoplasia from othercerebellar malformations, dysplasiaand atrophy requires determining thatthe posterior fossa is normal volumeand determining the absence of anassociated cyst in communication withthe fourth ventrice (Figure 17).21

RhombencephalosynapsisAlthough rhombencephalosynapsis

is usually described as a “fusion”anomaly, or dysplasia of the cerebellarhemispheres and vermis, and has beendescribed in a patient with holoprosen-cephaly,9,21 I believe this malformationis probably the result of failed neuronalproliferation of the cerebellar hemi-spheres, much like holoprosencephalyof the cerebral hemispheres.

Imaging studies reveal an absence ofthe normal formation of midline struc-tures of the posterior fossa including thevermis and mesencephalic structures.

The cerebellar hemispheres are continu-ous across the midline (Figure 18).9

Neuronal proliferation, migration andhistiogenesis (8 to 21 weeks)

During this phase of developmentneuronal cells undergo proliferation, dif-ferentiation and histiogenesis. Neuronalstem cells migrate from the germinalmatrix to the cerebral cortex with the

goal of producing organized cortical lay-ering. Failure of this process results inmicrocephaly, megalencephaly, hetero-topia, focal cortical dysplasia, polymicr-ogyria, lissencephaly, hemimegalen-cephaly, schizencephaly, anomalies ofoperculization, and phakomatoses.Phakomatoses and other inheritable neu-rologic diseases will be discussed in part2 of this article. Regulators of cortical


FIGURE 22. Polymicrogyria. The left cere-bral hemisphere is severely dysmorphic. Thegyri are small and the numerous sulci do notdefine the normal surface anatomy of thecerebrum. The cortex is lobular (black circle)and its thickness is irregular. CSF signal,midline, extra-axial fluid collections representan interhemispheric cyst (C), which is associ-ated with agenesis of the corpus callosum.

FIGURE 23. Lissencephaly. Axial CT: The gryi and sulci did not develop normallyin this full-term infant resulting in a smoothcortical surface and thick layer of cortex(white arrows). The definition of the Sylvianfissures is also underdeveloped (pairedarrows).

FIGURE 24. Hemimegalencephaly. On axialCT the entire right side of the brain is largerthan the left (dotted white line). The cortex ofthe right cerebral hemisphere is thicker(white arrows) and there is more white mat-ter on the right and the volume of the rightlateral ventricle is larger (R).

FIGURE 25. Schizencephaly. (A) An axial T2-weighted image shows cortical grey matterextending from the ependymal surface of the left lateral ventricle (single arrow) through thecerebral mantle (double arrows) to the cortical surface. The margins of each side of the schismabut one another. The lateral ventricle communicates with the subarachnoid space (*). (B) Onaxial CT the cortical grey matter extends along the margin of each side of the schism (doublearrow). The margins of the schism do not lie close to each other (arrows). The lateral ventriclecommunicates directly with the subarachnoid space via a wide cleft.

A B


malformation have been identified andassociated with specific malformationsof the cerebral cortex through moleculargenetic studies.22 Vascular malforma-tions are thought to be formed duringthis time; indeed, many malformationsof the cerebral cortices are accompaniedby abnormal vasculature.11 Vascularanomalies will not be discussed furtherin this article.

Microcephaly and megalencephalyMicrocephaly and megalencephaly

are due to disorders of neuronal andglial proliferation or excess or reducedapoptosis. Microcephaly is a malfor-mation secondary to abnormal stem-cell proliferation or apoptosis afternormal proliferation of stem cells. Bydefinition, the head circumference inthese children is !3 standard deviationsbelow the norm. There are fewer gyri,the depth of the sulci is shallow and thevolume of white matter is diminished(Figure 19).

Megalencephaly is the result of a gen-eralized increase in neuronal and glialproliferation or diminished apoptosis.9

Focal cortical dysplasiaFocal cortical dysplasia is the result

of abnormal migration of neurons tothe cerebral cortical cell layers. Histo-logically, the cortical cells are alsoabnormal. Some forms of cortical dys-

plasia contain balloon cells, and mayshow abnormal signal and architectureextending from the germinal matrixthrough the deep and subcortical whitematter. Imaging findings are variable,depending on the involvement of whitematter and may show focal blurring ofthe grey-white junction, or thinning orthickening of the affected cerebral cor-tex, which usually has high T2 signalon MR (Figure 20).9

HeterotopiaHeterotopia (singular: heterotopion)

are abnormal anatomic locations ofcortical grey matter which are due topremature arrest of neuronal migra-tion. Typical locations of heterotopiaare subependymal, where they are usu-ally asymmetric, at the trigones of thelateral ventricles and subcortical,where they may be focal (Figure 21) orgeneralized, forming a band or doublecortex underlying the normal-appearingcerebral cortices.9

PolymicrogyriaIn the later stages of neuronal migra-

tion, the 6 layers of the cerebral cortexare organized. When the deep layers ofthe cerebral cortex form numeroussmall gyri instead of organized corticallayers, the imaging result appears to bethickening or thinning of the cerebralcortex, which is usually associated

with abnormal sulcal formation. MRmay also show a nodular appearance of the cortex and normal-to-increasedsignal in the cortical tissue. There arenumerous syndromes and patterns ofpolymicrogyria, and many have beenshown to correspond with chromoso-mal abnormalities (Figure 22).9,22

LissencephalyLissencephaly (smooth brain)

describes the malformation with lackof gyral and sulcal development suchthat the surface of the cerebral hemi-spheres is smooth, due to arrested neu-ronal migration. Agyria (completelissencephaly) or pachygyria (incom-plete lissencephaly) as well as a thick-ened cerebral cortex are seen onimaging studies, differentiating lissen-cephaly from malformations of neu-ronal proliferation (Figure 23).9,22

HemimegalencephalyHemimegalencephaly is unilateral

megalencephaly that is isolated, part of ahemihypertrophy syndrome or the resultof hamartomatous overgrowth of onecerebral hemisphere. The malformationoccurs because of defective neuronalproliferation, migration and corticalorganization. The unilateral enlargementof the cerebral hemisphere includes pro-portionate ventriculomegaly and unilat-eral enlargement of CN I and CN II


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 slightlyprominent subarachnoid space (black arrow).


which of course are really glial tractsrather than true cranial nerves (Fig-ure 24).9,22

SchizencephalySchizencephaly may be the result of

abnormal cellular proliferation, migra-tion and/or cortical organization. Themalformation could be the result of afocal injury at the germinal matrix asneurons begin to migrate — a trans-mantle injury later in gestation may befamilial or caused by chromosomalmutation. The germinal matrix, locatedat the caudal thalamic groove is at themargin of the lateral ventricles. A cleftis formed in the cerebral mantle whenneurons fail to migrate from a focalarea of the germinal matrix.

Characteristic imaging findings maybe unilateral or bilateral; when bilat-eral, the clefts are typically symmetric.The cleft, lined by dysplastic grey mat-ter, extends from the margin of the lat-eral ventricle to the cerebral cortex andis in communication with the ventricleand the subarachnoid space overlyingthe cerebral hemisphere. The marginsof the cleft may be splayed (open lip)or lie in close apposition (closed lip,Figure 25).9,22

Anomalies of operculizationFormation of the Sylvian fissure and

insula begins during the 14th week ofgestation, between the orbitofrontal andtemporal lobes. The insula is defined byinfolding of the structures by the 19thweek of gestation.12 The process of for-mation of the Sylvian fissures is calledoperculization. Disorders of neuronalproliferation and neuronal migrationwhich are limited to the operculumresult in abnormal gyration and/or corti-cal dysplasia which is manifested asabnormalities in the processes managed

by these areas, namely speech, languageand pseudobulbar palsy.22,23

The imaging appearance can varyfrom wide Sylvian fissures, thickeningof the cortex, localized polymicrogyriaof the insula, and thickened or shallowgyri and they may be accompanied byanomalous vessels. When symmetricmalformation is found, the brain has a“figure 8” shape on axial images (Fig-ure 26).9,23

ConclusionDiagnoses in pediatric neuroradiol-

ogy encompass a broad range of brainmalformations, anomalies, and inher-ited and metabolic disease processes.An understanding of basic brainembryology provides the basis for amore thorough understanding of thesepathologic processes.

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Part 2 of this article will appear ina future issue of Applied Radiology.

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