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AJNR Am J Neuroradiol 21:1511–1519, September 2000

Cerebellar Cortical Dysplasia: MR Findings in aComplex Entity

Gustavo Soto-Ares, Christine Delmaire, Berengere Deries, Louis Vallee, and Jean Pierre Pruvo

BACKGROUND AND PURPOSE: MR imaging findings of cerebellar cortical dysplasia havebeen described as a new cerebellar malformation. The purpose of this study was to assess theassociation of cerebellar cortical dysplasia with other cerebral malformations.

METHODS: We retrospectively reviewed 46 MR examinations of patients presenting withdevelopmental delay, hypotonia, and facial deformities to identify abnormal folia or fissures orboth within cerebellar hemispheres or vermis suggesting cortical dysplasia.

RESULTS: Cerebellar cortical dysplasia was diagnosed in 17 patients. In two patients, it wasisolated. In the remaining 15 patients, the malformation was associated with vermian malfor-mation (n511), cerebral cortical dysplasias (n58), dysplasia of corpus callosum (n56), andheterotopia (n55). A widespread malformation of the posterior fossa was observed in eightpatients (Dandy-Walker, Chiari II and III, and hypoplasia of brain stem). One patient withhypertrophied cerebellar hemisphere had minor enlargement of the right cerebral hemisphereand lateral ventricle. He also had nodular heterotopia, suggesting unilateral megalencephaly.

CONCLUSION: Our study suggests that cerebellar cortical dysplasias are common in caseswith more widespread cerebral malformations. Technical progress providing high-quality tri-dimensional MR imaging of the cerebellum may explain its recent descriptions.

Focal cerebellar cortical disorganization or dyspla-sias are often observed in healthy newborns. Thesefindings may be found histiologically in 85% of147 newborns without other structural abnormali-ties and may persist during adult life (1). Themechanisms of such dysplasias (their formation andtheir regression), as well as their influence on ap-propriate positioning of components of cerebellarcortex, have been previously investigated, but arenot clearly understood (2). Moreover, there hasbeen speculation about the contributory role of thecerebellar cortical disorganization to the origin ofglial and cerebellar primitive neuroectodermal tu-mors (2, 3).

Different types of cerebellar dysplasias havebeen described. Rorke et al (1) described the fol-lowing histologic findings associated with cerebel-lar dysplasias: compact groups of mature neurons,focal or perivascular immature granular cell collec-tions, mixed cell rests containing both mature neu-rons and immature granule cells, and heterotopias.

Received October 15, 1999; accepted after revision March 1,2000.

From the Departments of Neuroradiology (G.S-A., C.D.,B.D., J.P.P.) and Pediatric Neurology (L.V.), Hopital RogerSalengro, Chru Lille France.

Address reprint requests to Gustavo Soto-Ares, Departementof Neuroradiology, Hopital Roger Salengro, Chru Lille 59037Lille—France.

q American Society of Neuroradiology

All of these findings were located in the deep whitematter at the cerebellar midline or in the nodulusof the vermis. Friede (4) described heterotopia anddisturbances of cortical layering or folia formation.The reason for their formation may be attributed toa genetic disorder, because they are particularlyprominent in infants with trisomies 13–15 and 18trisomies syndrome (1). Genetic abnormalitiescould lead to formation of dysplasias because ofalteration in the induction of progenitor cell deathor the anomalous migration of primitive neural andglial cells. Cortical dysplasias can be isolated oradjacent to a local defect. They also may be foundin cases of more widespread neurologic disease,such as congenital muscular dystrophies and ocu-locerebral syndromes, as well as in various geneticdisorders and granulomatosis meningoencephalitis.Hypomyelination and polymicrogyria are associat-ed with variable degree of hypoplasia of the ponsand cerebellar polymicrogyria or atrophy in con-genital muscular dystrophies (5). In many geneticdisorders, the most common findings include ponsor cerebellar hypoplasia or both, structural changesof the vermis, and cerebellar progressive atrophy(6). Finally, meningeal infectious damage in the fe-tus can lead to cortical developmental abnormali-ties, cystic cerebellar lesions, and polymicrogyria(4, 7). The inclusion of diffuse hypertrophy of cer-ebellar cortex (Lhermitte-Duclos) within cerebellardysplasia is debatable because of its histologic fea-

AJNR: 21, September 20001512 SOTO-ARES

tures (4). Only one case of isolated cerebellar cor-tical dysplasia has been described previously (8).

In the present report, we describe MR imagingfindings of cerebellar cortical dysplasia in 17 caseswith neither muscular dystrophy nor metabolic dis-ease. The purpose of this study was to determinethe association of cerebellar cortical dysplasia withother cerebral malformations.

MethodsWe retrospectively reviewed all MR images of the brain ob-

tained from pediatric patients in our hospital during the last 3years. Forty-six patients in whom posterior fossa malformationhad been identified were selected (age range, 10 days–14 years).The clinical indications for the MR study of these patients hadbeen developmental delay, cerebellar syndrome, facial or skel-etal deformities, and cerebral malformations diagnosed on thebasis of CT findings.

Further clinical, metabolic, and genetic investigations wereconducted with all selected patients. Metabolic and genetic dis-eases were investigated in cases of unclear diagnosis. Investi-gations included amino acid and organic aciduria chromatogra-phy and carnitine, esterified carnitine, and creatine kinasedosages. Genetic testing included 400- to 600-band karyotyping.

MR images were acquired with a 1.5-T unit (Siemens, Er-langen, Germany). For each subject, the following series ofimages were acquired. First, axial, sagittal, and coronal sliceswere acquired using a spin-echo T2-weighted sequence (sec-tions thickness, 5, 3, 4 mm, respectively). The acquisition pa-rameters were 5000/120/2 (TR/TE/excitations), a 20- to 25-cmfield of view and a 300 3 512 matrix. After that, an inversion-recovery sequence was acquired in one or two orthogonalplans, depending on the location of the abnormalities diag-nosed in previous sequences. In this sequence, the parameterswere 11520/400/60/2 (TR/TI/TE/excitations), a 20- to 25-cmfield of view and a 198 3 512 matrix. The same sequenceparameters were used for all the patients and the total scanningtime was about 20 minutes per patient.

MR imaging findings of these patients were analyzed to de-termine the frequency of cortical cerebellar dysplasia. Imageswere evaluated by two neuroradiologists who were blinded tothe clinical presentation to ascertain abnormal morphologiccharacteristics or orientation of fissures and folia within cere-bellar hemispheres or vermis, irregularity of the gray/whitematter junction, cystlike inclusions and hypertrophied, or hy-poplasic cerebellar hemispheres. These malformations werefound in 17 patients, and their clinical aspects and MR imagingfindings are summarized in Tables 1 and 2.

We determined specific characteristics of cortical dysplasias,which can differentiate them from more extensive syndromessuch as Dandy-Walker malformation, Joubert syndrome, tec-tocerebellar dysraphia, or rhombencephalosynapsis. Associa-tion with other hemispheric malformations such as heterotopia,corpus callosum dysplasia, abnormal cortical gyration, andwhite matter abnormalities were also investigated.

Results

Clinical Information (Table 1)In 17 patients, we found a high incidence of de-

velopmental delay, hypotonia, facial deformities,and abnormalities in eyes or in ocular motricity. Inmost cases of developmental delay, patients wereseverely affected with both cognitive and motor de-lay. Facial deformities included pro- and retroprog-nathism, enophtalmos, low-set ears, thin lips, and

nose deformations. No midline facial clefts werefound. Other frequent clinical presentations werestrabismus, nystagmus or abnormal eye movements,and skeletal deformities, most frequently found infingers with brachydactyly and clinodactyly.

According to the results of metabolic and ge-netic tests, no congenital muscular dystrophy waspresent in our patients. Chromosomal anomalies(45X/46XiXq and SD haploX) were diagnosed inonly one patient (case 5). One patient presentedcongenital toxoplasmosis (case 13). On the otherhand, a posterior fossa tumor was found in onepatient (ganglioneuroma) (case 11).

MR Features (Table 2)

Dysplastic abnormalities of cerebellar cortexwere observed in 17 patients. In eight patients, weidentified vertically orientated folia in cerebellarhemispheres (Fig 1). No foliation or defective fo-liation of cerebellar cortex or disorganized corticalarchitecture without a well-delimited gray/whitematter junction (Fig 2) was observed in 10 patients,and cystlike inclusions (Fig 3) were found in three.These findings were associated with diffuse en-largement of the cerebellar hemisphere (Fig 4) inone case, and with thickening of the cerebellar cor-tex (Fig 5) in another case. Irregular gray/whitematter junction (Fig 6) was seen in two cases andabnormal vertical fissures of the vermis (Fig 7)were seen in eight patients, leading to abnormalfoliation in one (case 17) (Fig 7b). Dysplasia wasisolated in two patients (cases 13 and 17). The re-maining 15 patients had other cerebral mal-formations.

The most frequent associated malformation wasa vermian malformation (agenesia, hypoplasia, dys-plasia, and atrophy) observed in 13 patients (cases1, 9, 12, 14, 15, 17). Cerebral cortical dysplasiawith irregular gray/white matter junction or polym-icrogyria was seen in eight patients (cases 1, 2, 4,5, 7, 10, 12, 14). Other associated malformationsincluded: dysplasia of the corpus callosum in sixpatients (corpus callosum was absent in one patient[case 7], hypoplasic in one [case 8], thinned andshortened in three patients [cases 2, 9, 12], andthinned in two [cases 14, 15]); heterotopia in sixpatients (subependymal in four patients [cases 2, 4,14, 16] and nodular within centrum ovale in two[cases 6, 9]); and posterior fossa malformation ineight patients (Dandy-Walker syndrome with se-vere vermian hypoplasia and hydrocephaly [case 3]and with moderate inferior vermian hypoplasia andventriculomegaly [case 15], Chiari II [case 2] andChiari III [case 12] malformation, and hypoplasiaof brain stem [cases 1, 7, 10, 12]. Patient 4 hadminor enlargement of the right parietal and occip-ital lobes and lateral ventricle associated with sub-ependymal heterotopia and patchy hyperintensitywithin white matter. These features may suggestunilateral megalenchephaly (Fig 4).

AJNR: 21, September 2000 CEREBELLAR CORTICAL DYSPLASIA 1513

TABLE 1: Clinical findings in cerebellar cortical dysplasias

Patient(No.) Sex/Age

PrenatalCourse

Clinical Background

Familial Personal Clinical Presentation Karyotype

1 F/3 yrs 5 months (gestation-al age), ventricu-lomegaly

None None Hypotonia, delayed motor, ab-normal eye movements

Normal

2 M/2 yrs Normal Mother: seizures None Microcephaly, retrognathism,strabismus, myelomeningo-cele

Normal

3 F/10 mos Dandy Walker? None Orbit capillaryhemangioma

Hypotonia, global develop-mental delay, strabismus

Normal

4 M/8 yrs Normal Mother: lipothymia at3rd month of pregnan-cy

Seizures at fivemonths

Apraxia, ataxia, speech andcognitive developmentaldelay

Not investigated

5 M/10 mos Diminished motoractivity 48 hrsbefore birth

Mother: influenza at 2and 6 months

None Axial hypotonia, spastic tetra-paresia, motor developmen-tal delay

45X/46XiXq andSD haploX

6 F/1.5 yrs Normal None Palpebral angio-ma

Difficulty in swallowing, hy-potonia, global develop-mental delay, oral regiondeformities, strabismus, cli-nodactilyly

Normal

7 M/10 days Ventricular enlarge-ment, hydramnios

Mother: syncope in earlypregnancy

None Severe hypotonia, microceph-aly, hand skeletal malfor-mations, facial deformities

Normal

8 M/6 yrs Occipital cysticmalformation at24 weeks

None None Prognathism, blindness, nys-tagmus, hypotonia, globaldevelopmental delay

Not investigated

9 F/17 yrs Normal Uncle: developmentaldelay and seizure

None Hand skeletal malformations,microcephalia, global de-velopmental delay, extra-pyramidal signs, ataxia

Normal

10 F/1 yr Ventriculomegaly None None Scoliosis, kidney dysplasia,hypotonia, motor delay,West syndrome

Normal

11 F/2 yrs Normal None Difficulty inswallowing

Hypotonia, global develop-mental delay strabismus,left hemiparesis

Normal

12 M/14 yrs Normal None Occipital cephalo-cele, hydro-cephalus

Tetraparesis, tremor, seizures,optic atrophy

Not investigated

13 F/7 yrs Normal Toxoplasmosis at 3rd tri-mester

Congenital toxo-plasmosis, sei-zures

Seizure, pyramidal syndrome Not investigated

14 F/8 mos Normal Allergic asthma Visual com-plaints, irrita-bility

Microcephalia, developmentaldelay, tetrapyramidal syn-drome, hypotonia, abnor-mal movements

Not investigated

15 F/6 yrs Oligoamnios Grandfather: epileptic Neonatal epilepsy,immune defi-ciency

Tetrapyramidal syndrome,global developmental delay,facial deformities, strabis-mus, nystagmus, kidneymalformation

Normal

16 M/4.9 yrs Oligoamnios None Prematurity(840 g)

Nose deformation, low-setears and syndactylia, mi-crocephalia, global devel-opmental delay

Normal

17 M/1.2 yrs First-trimester hem-orrhage

None None Large forehead, enophtalmosand thin lips, skeletal de-formities, hypotonia, anddevelopmental delay

Normal

AJNR: 21, September 20001514 SOTO-ARES

TABLE 2: MR features in cerebellar cortical dysplasia and associated malformations

Patient(No.) Sex/Age

Cerebellar Cortex& Hemispheres Vermis

Posterior FossaMalformation Cerebral Cortex

White Matter(T2)

AssociatedMalformation

1 F/3 yrs Bilateral cystlikeinclusions, dis-ordered corticalarchitecture

Abnormal medialfissure

Pons hypoplasia Occipital and fron-tal polymicrogy-ria

Occipital hypersig-nal

Ventricular enlarge-ment

2 M/2 yrs Unilateral disor-dered architec-ture of the cor-tex, left hemi-spheric agenesia

Inferior hypopla-sia

Chiari II Parietal and occip-ital ‘‘stenogy-ria’’

Normal Subependymal het-erotopia

3 F/10 mos Bilateral verticalfolia, left hemi-spheric hyper-trophy, righthemispheric hy-poplasia

Inferior hypopla-sia, superiordisordered ar-chitecture

Dandy Walker Normal Normal Ventricular enlarge-ment

4 M/8 yrs Right hypertrophyand vertical ori-ented folia

Hypoplasia anddisorganized fo-lia

None Parietal and occip-ital hypertrophy

Parietal patchy hy-persignal

Nodular heterotopia,unilateral mega-lencephaly

5 F/10 mos Right and superiorcortical disor-ganization, lackof normal fis-sures and bilat-eral thickenedcortex

Inferior hypopla-sia

None Parietal and frontalpolymicrogyria

Hypersignal Ventricular enlarge-ment

6 F/1.5 yrs Normal Inferior hypopla-sia, superiordysplasia, ab-normal fissures

Horizontal superi-or cerebellar pe-duncles

Normal Periventricular cal-cifications (CT)

Centrum ovale,nodular heteroto-pia

7 M/10 days Bilateral hypopla-sia, lack of nor-mal fissures andunilateral cyst-like inclusions

Total agenesis Small and ponshypoplasia

Diffuse corticaldysplasia

Normal Callosal agenesis

8 M/6 yrs Bilateral verticalfolia and lack ofnormal arboriza-tion of the whitematter, linearheterotopia

Superior abnormalfissures, inferiorhypoplasia

Mega cisternamagna, Joubertsyndrome?

None Normal Callosal hypoplasia

9 F/17 yrs Bilateral verticalorientated folia

Hypoplasia, supe-rior abnormalfissures

None None Normal Thinned and short-ened corpus cal-losum, nodularheterotopia

10 F/1 yr Bilateral cystlikeinclusions

Normal? Pons hypoplasia Frontal/parietaldysplasia

Hypomyelination Hydrocephalus

11 F/2 yrs Extensive left cor-tical disorgani-zation contigu-ous to gangli-neuroma

Normal Pons and peduncleinfiltration

Normal Normal Hydrocephalus

12 M/14 yrs Left agenesis, righthypoplasia withabnormal fis-sures and verti-cal folia

Total agenesis Chiari II brainanomalies

Brain anomalies ofChiari II

Normal Brain anomalies ofChiari II

13 F/7 yrs Left disorganizedfolia with defec-tive fissures

Normal Left cerebellar pe-duncle hyperin-tensity

None Normal None

14 F/8 mos Bilateral defectivefoliation and hy-poplasia

Hypoplasia, de-fective foliation

None Frontal dysplasia Hypomyelination,calcifications

Subependymal het-erotopia, callosalthinning

AJNR: 21, September 2000 CEREBELLAR CORTICAL DYSPLASIA 1515

TABLE 2: Continued

Patient(No.) Sex/Age

Cerebellar Cortex& Hemispheres Vermis

Posterior FossaMalformation Cerebral Cortex

White Matter(T2)

AssociatedMalformation

15 F/6 yrs Bilateral disorgan-ized and verticalorientated folia

Hypoplasia, atro-phy

Dandy-Walkercomplex

None Normal Cavum verga, cal-losal thinning

16 M/4.9 yrs Bilateral abnormaland defectivefissures withpartial verticalfolia, irregulari-ty of the gray/white matterjunction

Normal None None Normal Bilateral subepen-dyma heteroto-pias, parahippo-campal dysplasia

17 M/1.2 yrs Bilateral inferiorvertical folia

Defective and ab-normal folia-tion, inferiorhypoplasia

None None Normal None

FIG 1. Patient 15, Dandy-Walker complex. Axial inversion-recovery (IR) T1-weighted image (11520/60/400/2 [TR/TE/TI/excitations])shows bilateral, vertical, orientated folia of the cerebellar cortex associated with an enlarged fourth ventricle.

FIG 2. Patient 8, possible Joubert malformation.A, Coronal IR T1-weighted image (11520/60/400/2) shows rostral vermian dysgenesis (black arrowhead), bilateral abnormal arbori-

zation of the white matter (double black arrowhead), and linear heterotopia (white arrow).B, Axial T2-weighted image (5000/120/2 [TR/TE/excitations]) shows vermian dysgenesis (short arrow) associated with mega cisterna

magna and prominent appearance of the superior cerebellar peduncles (long arrow).

DiscussionIn newborns, minor cerebellar dysplasias are

found histologically in the white matter and nod-ulus of the vermis. These midline cerebellar dys-plasias are common features of human cerebellardevelopment (2). Major cortical cerebellar dyspla-sias, however, represent a pathologic finding. Theyhave been reported in congenital muscular dystro-phies and related syndromes or in intrauterine in-fection (8–14). Only one case of isolated cerebellarcortical dysplasias has been described (8).

Based on neuroimaging findings of cerebral ab-normalities, our study showed that cerebellar cor-tical dysplasia may be associated with widespreadcerebral malformations and cases with isolated cer-

ebellar abnormalities are rare. They are associatedwith a poor prognosis and severe neurocognitivedefects, with global or motor developmental delay,hypotonia, oculomotor disease, and facial and skel-etal deformities.

The most relevant MR appearance of cerebellarcortex in these patients included: defective, large,or vertical fissures; irregular gray/white matterjunction; lack of normal arborization of the whitematter; and heterotopia within cerebellar hemi-spheres, all findings leading to disorganized folia-tion. Vertical abnormal fissures in vermis are alsopresent and in sagittal images its presence is shownas an abnormal foliation of vermian lobules. Otherradiologic findings were cortical thickening, hemi-

AJNR: 21, September 20001516 SOTO-ARES

FIG 3. Patient 1. Axial T2-weighted im-ages (5000/120/2) show cystlike inclusions(arrows), cortical dysplasia (arrowhead),and pons hypoplasia (black arrowhead)(A) associated with medial vermian fissure(long arrow), occipital polymicrogyria,white matter hyperintensity, and ventricularenlargement (B).

FIG 4. Patient 4. A, Axial IR T1-weighted image (11520/60/400/2) shows right cerebellar hypertrophy with vertical folia in an 8-year-old boy with ataxia and psychomotor retardation.

B, Coronal T2-weighted image (5000/120/2) shows associated malformations: minor parietal lobe (double arrow) and ventricle en-largement, nodular heterotopia (long arrow) and white matter hyperintensity (short arrows).

FIG 5. Patient 5. Ten-month-old boy with spastic tetraparesia, developmental delay, and difficulty in swallowing. Coronal T2-weightedimage (5000/120/2) shows right cerebellar cortical disorganization without normal fissures associated with hyperplasia of the rightcerebellar lobe and cortical thickening. Note white matter hyperintensities (black arrowheads) and cortical dysplasia (white arrows) insupratentorial images.

spheric hypertrophy, and cystlike corticalinclusions.

No patient in our study had metabolic or con-genital muscular dystrophy (CMD) disease. Nev-ertheless, the radiologic aspect of CMD describedby Barkovich (5) was present in four patients (cases1, 4, 5, 10), including white matter abnormalitiesassociated with cortical supratentorial dysplasiaand cystlike cortical abnormalities of cerebellarwhite matter (patient 1 and 10). Cystlike corticalabnormalities have been also reported in Fukuyamadisease. These abnormalities may represent sub-arachnoid spaces engulfed by the fusion of disor-

ganized folia (12). In cases of isolated cortical cer-ebellar dysplasia, Demaerel et al (8) suggested thatcystic inclusions represent sequelae of the migra-tion of neurons, which form the external granularlayer of cerebellar cortex at 11 to 13 weeks of ges-tation, or remnants of daughter cells, which migrateto form part of the outer molecular layer and innergranular layer at 16 weeks.

The understanding of cerebellar cortical dyspla-sia is facilitated by knowledge of cerebellar corticaldevelopment. Cerebellar cortical neurons have adual origin. Up to about 10 weeks of gestation, theneural cells that will form the deep nuclei and the

AJNR: 21, September 2000 CEREBELLAR CORTICAL DYSPLASIA 1517

FIG 6. Patient 16. MR imaging findings ina 4-year-old boy with microcephalia, motordelay, and facial deformities.

A, Coronal IR T1-weighted image(11520/60/400/2) shows bilateral cerebel-lar defective foliation and irregularity of thegray/white matter junction (black arrow-heads). Note subependymal heterotopiaalong the floor of the left temporal horn(white arrow).

B, Coronal IR T1-weighted images(11520/60/400/2) shows heterotopia (whitearrow) and associated cortical dysplasia ofparahippocampal gyrus (asterisk).

FIG 7. Patient 17. MR imaging findings ina 1 year-old boy with facial deformities, hy-potonia, and developmental delay.

A, Coronal IR T1-weighted image(11520/60/400/2) shows medial vermianfissure (arrow).

B, Sagittal IR T1-weighted image (sameparameters) shows lack of normal fissuresof the vermis associated with inferior ver-mis hypoplasia.

Purkinje layer of cerebellar cortex migrate radiallyoutward from the germinal matrix. In contrast, atapproximately 10 to 11 weeks, the neurons that willform the granular layer migrate tangentially overthe cerebellar surface (15). The early signs of fo-liation, which manifest prior to the formation of afissure, are a local increase in premigratory gran-ular cells and an indentation of the Purkinje celllayer.

Up to the 40th week, the cerebellar lamellae aremade up of four layers: the external granular layer,the molecular layer, the Purkinje cell layer, and theinternal granular layer. During the first 6 to 8months of extrauterine life, the external granularlayer subsides progressively as its cells migrate in-ward and the cerebellar lamellae assume their adultappearance with only three layers (16). The exter-nal granular layer, Purkinje cell layer, and the over-laying meningeal cells may be involved in themechanism of foliation (17).

Immunohistochemical observations described inthe developed mutant rat with cerebellar malfor-mations have shown that the cerebellar lamination

is disturbed by abnormal perivascular aggregationsof the external granule cells (EGCs). The abnormalaggregation of EGCs is preceded by an aberrantmigration and misorientation of Purkinje cells inthe hemispheres and a disturbed arrangement ofglial fibers, suggesting that Purkinje cell settlementmay be a key in cerebellar development. Moreover,a close relationship between defective developmentof the cerebellar vermis and cerebellar dysplasia ispresent. These findings have also been described inhuman cerebellar cortical dysplasia (2, 18). Thestage during which the perivascular aggregations ofEGCs are found in the rat corresponds to humangestation at 24 to 27 weeks (19). According tothese reports, mutation of a gene expressed in cer-ebellar development (17) or congenital infection,toxins, or radiation (15) are different causes af-fecting migration and proliferation in cerebellum,leading to vermian and cerebellar dysplasia and hy-poplasia. These findings were present in 11 of ourpatients. Nevertheless, only one had chromosomalabnormalities and another patient had congenitalinfection.

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In one patient, cerebellar dysplasia was contin-uous as well as contiguous to a posterior fossa tu-mor. Jay (3) has previously described this associa-tion. There was disorganization of the cortex, withfusion of folia, disorganization and misorientationof Purkinje cells, and irregularly oriented and tan-gled radial glialike processes, suggesting a role forabnormality of radial glia in the pathogenesis of thelesion. The authors proposed a possible pathoge-netic association between cortical dysplasia and de-velopment of the tumor. Cortical dysplasia wasconsidered to be an aberrant neuronal migration ormaturation, and its presence contiguous to the tu-mor suggested that the tumor arose as an abnormalgenetic control in the migration and differentiationof neuronal precursors.

Our MR imaging findings showed that dysplasiawas frequently associated with other malforma-tions. Few cases of isolated unilateral cerebellarcortical dysplasias have been described. Demaerelet al (8) reported one case with bilateral cerebellardysplasia. MR imaging characteristics were defec-tive or vertically oriented foliation, frequently as-sociated with vermian dysplasia. In our study, onlytwo patients had isolated bilateral cerebellar corti-cal dysplasia. Cerebellar cortex presented verticallyoriented or defective folia. In these patients, cere-bellar dysplasia was isolated; however, in one pa-tient, a congenital toxoplasmosis was diagnosed.Seven patients had unilateral disorganized corticalcomponents of cerebellar hemisphere. In these cas-es, cortical unilateral dysplasia was always associ-ated with other cerebral malformations.

Among patients with adjacent focal or wide-spread cerebral lesions, our findings concurred withprevious reports. In two patients, however, MR im-aging findings were unusual and consisted of anenlargement of the cerebellar cortex in one patient(case 5) and a hypertrophied cerebellar hemispherein another (case 4). Unusual malformations ofcerebellum have been previously described (eg,hamartoma associated with cerebral atrophy [20],macrocerebellum associated with delayed myelin-isation [21], hemimegalenchephaly with cerebellarinvolvement [22], and cerebellar monstrous hyper-trophy [23]). The features of these cases do notresemble those of our patients. In our study, hy-pertrophied cerebellar hemisphere was dysplasticwithout cerebral atrophy or delayed myelination.Two patients had cerebellar white matter abnor-malities, but one of them had also congenital toxo-plasmosis. Finally, another new cerebellar malfor-mation was recently reported with a partial midlinefusion of the cerebellar hemispheres (17), and De-marel et al (24) described vermian changes withassociated cerebellar abnormalities. In these cases,vertical folia and abnormal fissures were associatedwith defective foliation. Our findings are distinctfrom these descriptions. Fusion of the cerebellarhemisphere was not associated with cortical dys-plasia, vermian dysplasia was always associatedwith cerebellar abnormalities, and dysplasia was

associated with cerebral malformations in 15 of 17cases.

As previously described, when cortical dysplasiawas associated with polymicrogyria and other as-sociated malformations, cerebellar abnormalitiesmay have represented not only a single entity, buta spectrum of more extensive morphologic changes(8).

Further research is in progress by our group toexplain what symptoms were attributable to thecerebellar malformation in our patients. Investiga-tions are also indicated to understand the associa-tion among cerebellar cortical dysplasias, minor fa-cial anomalies, and hand-skeletal deformities withsupratentorial malformations. Indeed, abnormalitiesof the expression of the homeobox genes could leadto the development of malformations of the cere-bellum, basal forebrain and visual system, mandib-ular and maxillary arch patterning, and finger skel-etal anomalies (25).

In conclusion, cerebellar cortical dysplasias mayresult from different causes, both genetic and ac-quired. They have been reported in congenital mus-cular dystrophies and related syndromes or in in-trauterine infection. The most common featuresseem to be the vertically orientated folia instead ofthe normal horizontal folia pattern, disorganized fo-liation, and defective or abnormal fissures. In mostcases, cerebellar cortical dysplasia is associatedwith other cerebral malformations and immunohis-tological findings suggest that abnormal cell migra-tion caused by a disorder in early gestation resultin cerebellar dysplasia. A genetic effect responsiblefor the human vermis defect and cerebellar dyspla-sia has not been identified yet. Our study suggeststhat cerebellar cortical dysplasia is a common fea-ture in cases with widespread cerebral malforma-tions and this can be related to the technical ad-vances providing high-quality tridimensional MRimaging of the cerebellum in a period of renewedand widespread interest in the cerebellar involve-ment in cognitive processing.

AcknowledgmentsWe are grateful to Xavier Leclerc and Olivier Godefroy for

their review of the manuscript and their valuable commentsand to Antoine Drizenco and Frederic Lemarchand for assis-tance in obtaining the MR images.

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