Disorders of cortical formation

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DISORDERS OF CORTICAL FORMATION Radiologic-Pathologic

Correlation

Susan I. Blaser, MD, FRCPC, and Venita Jay, MD, FRCPC

Abnormalities have long been recognized in the brains of children with developmental delay and seizures. The advent of newer imaging techniques, such as high-resolution (thin slice three-dimensional gradient recalled echo [GREI) magnetic resonance (MR) imaging and surface reconstructions of three-dimensional data sets, has led to a greater in vivo understanding of these malformations. There has been reclassification of the disorders of cortical malformations according to embryologic stages of brain cortex development at which these malformations are proposed to have occurred. These stages are cellular proliferation, cellular migration to the developing cortex, and cortical organization.5 MALFORMATIONS OF ABNORMAL CELL PROLIFERATION Non-neoplastic The earliest lesions resulting in cortical malformations are those with onset during the This article originally appeared in Neuroimaging Clinics of North America, Volume 9, Number 1, February 1999.

From the Divisions of Neuroradiology Toronto, Toronto, Ontario, Canada

(SIB) and Neuropathology

period of cellular proliferation in the germinal zones. During the seventh fetal week, germinal layers begin to form in the vesicle walls of telencephalic outpouchings (vesicles) at the foramina of Monro. Cortical malformations occurring during this stage of neuronal and glial proliferation may be generalized, multifocal, or focal. Generalized malformations of abnormal cell proliferation include microcephaly with diminished cortical thickness or with diminished sulcation (Fig. 1). Commonly imaged focal or multifocal lesions include non-neoplastic disorders, such as hemimegalencephaly, focal cortical dysplasia (with balloon cells), and forme fruste tuberous sclerosis. Hemimegalencephaly may be associated with neurocutaneous or hemiovergrowth syndromes, such as hypomelanosis of Ito, epidermal nevus syndrome, or neurofibromatosis type 1. Proposed causes for hemispheric overgrowth in hemimegalencephaly include abnormal cellular proliferation and heteroploidy, defective cellular metabolism, or possibly an insult to the developing brain in the mid to late second trimester. In the event of a later insult to the developing brain, brain plasticity allows for the development of new synapses in the damaged brain, permitting the (VJ), The Hospital for Sick Children, and University of

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Figure 1. Tl-weighted (TR (TR 3000/ TE 120) axial image

600/TE 15) sagittal (A) and axial (f3) images, and T2-weighted (C) in a child with severe microcephaly showing a thin cortical ribbon. //lustration continued on opposite page

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Figure 1 (Continued). A Tl -weighted axial image second child with a similar degree of microcephaly fewer gyri and less well-developed sulcation.

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persistence of supernumerary axons and the potential for white matter overgrowth. Neuropathologic and neuroimaging features in hemimegalencephaly are abnormal neurons, lack of gray-white matter demarcation, disarrayed cortical lamination, gray matter heterotopias, broad gyri, and signal changes reflecting hypomyelination and gliosis. It is postulated that foci of agyria, with macroscopic heterotopias, extensive white matter gliosis, and less hemispheric white matter overgrowth, likely result from an earlier, more severe insult with destruction of the radial glial fibers. The variable patterns of cortical and white matter involvement demonstrated with neuroimaging likely reflect the variability in severity and timing of the precipitating insult (Fig. 2).‘, 5,I9823 Focal cortical clysplasia is characterized by neocortical abnormalities. The pathologic spectrum of focal cortical dysplasia includes significant abnormalities of neuronal size, shape, orientation, and lamination; indistinctness of the gray-white junction; and vari-

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ability in cortical thickness. Large bizarre neurons with abnormal Nissl patterns, giant neurons, binucleate neurons, a variable degree of cortical gliosis, and balloon cells with abundant pale eosinophilic cytoplasm are found. These balloon cells are similar to those seen in the cortical tubers and white matter lesions of tuberous sclerosis, and there is much overlap in the pathology of focal cortical dysplasia and tuberous sclerosis. Failure of myelin arborization, blurring of gray-white margins, variable sulcal depth and cortical thickness, and occasional hazy or dystrophic calcification may be appreciated on neuroimaging. Evidence of dual pathology, or focal cortical dysplasia in association with hippocampal sclerosis, should be sought (Fig. 3).‘, “, “, “, 26,28,3’ Imaging features in limited or form fv~sfe t&erotls sclerosis include demonstration of a solitary smooth pyramidal-shaped gyri with a central depression and abnormal signal of the subcortical white matter. The cortical and subcortical lesions are uncommonly calcified, tend not to enhance, and are best demonstrated on MR. These children lack the calcified subependymal nodules of tuberous sclerosis as well as other organ system lesions. The cortical tubers are characterized by aberrant neurons, scattered balloon cells, and gliosis. The white matter lesions of tuberous sclerosis are characterized by decreased myelin and accumulations of balloon cells. Although there are similarities in the pathology of focal cortical dysplasia and the fome fruste of tuberous sclerosis,the latter has, in general, more abundant balloon cells (Fig. 4).15,“8 ‘8,22,24

Neoplastic Lesions of proliferation after an abnormal induction event during brain development may be malformative, hamartomatous, neoplastic, or a combination. Malformative disorders consisting of neoplasiason a background of cfisorderedcortex or in association with focal cortical dysplasia include dysembryoplastic neuroepithelial tumor and ganglioglioma.5,7 Dysembryoplastic neuroepitlzelial tumors are supratentorial, predominantly temporal lobe Text covtinued on page48

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Figure 2. Tl-weighted (TR 600/TE 15) and T2-weighted (TR 2800/TE 90) axial images (A and B) demonstrate overgrowth of the right cerebral hemisphere in a patient with developmental delay, seizures, and hemimegalencephaly. Note the abnormal white matter signal and the unilateral ventriculomegaly. Surface reconstruction (C) from a three-dimensional data set (TR 15/TE 8) shows overgrowth of the hemisphere and gyri. Pathologic specimen (D) confirms shallow sulci, fused gyri, thickened cortex, blurred gray-white matter junction, and dysplastic white matter.

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Figure 3. Blurring of gray-white matter junction (arrow) (TR 600/TE 15) (A) and T2-weighted (B) (TR 2800/TE senting with myoclonic seizures. Surface reconstruction of focal dysplasia (arrow).

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is noted in the left frontal lobe on Tl-weighted 90) axial images in a 5-year-old patient pre(C) demonstrates shallow sulci in the region Illustration

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Figure 3 (Cori rtinued). tical dysplasia reveals orientation of Iieurons.

Pathologic specimen (0) (original magnification marked variability in neuronal size and shape,

x 112) in a child with focal corNissl pattern, and a hapha zard

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Figure 4. Forme fruste of tuberous sclerosis. Tl-weighted (TR 600/TE 15) axial image in a 2-yearold patient with partial seizures shows a single focally deformed gyrus with very low signal of the subcortical white matter (A). The T2-weighted (TR 3000/TE 120) axial image (I?) demonstrates high signal intensity. Calcification (shown on CT) is poorly appreciated. Pathologic specimen in another child shows a typical pyramidal shaped gyrus, deformed by a corticalkubcortical tuber (C), and dysmyelination (D). Illustration continued on following page

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tumors that are typically multinodular with a heterogeneous cell composition, including oligodendrocytes, neurons, astrocytes, and other cells. These lesions are typically fairly well-demarcated, wedge-shaped lesions extending from the cortex to the ventricle. Calcification, enhancement, and peritumoral edema are lacking on neuroimaging studies. These low-attenuation lesions may suggest an infarct on computed tomography (CT), although there is no volume loss over time, and scalloping of the inner table or calvarial bulging suggests slow growth. Lesions are low in signal on Tl-weighted images and high in signal on T2-weighted images and often have a multinodular or pseudocystic appearance. There is a spectrum of pathology in dysembryoplastic neuroepithelial tumors. On one end of the spectrum are multinodular lesions with intervening malformed cortex, in which there is some hesitation to use the designation tumor. On the other end are lesions, which are clearly neoplastic and have clinically demonstrated some growth potential. Because the term dysembryoplastic neuroepithelial tumor has only recently been introduced, such malformative and neoplastic lesions were previously labeled as hamartomas, gangliogliomas, or mixed gliomas (Fig. 5).g* i7**O

Gangliogliomas are typically demonstrated within the temporal lobe. In one large series of 51 gangliogliomas, 84% were found in the temporal lobe, 10% were found in the frontal lobe, 2% were found in the occipital lobe, and 4% were found in the posterior fossa. These lesions are typically hypodense (60% to 70%) on CT, with focal calcifications seen in 35% to 40%, contrast enhancement in 45% to 50%, and cysts in nearly 60%. The reported incidence of calcifications demonstrated on imaging in pediatric gangliogliomas is higher, seen in 61% of one series of 42 children. Features on MR imaging are less specific, with solid components isointense on Tl-weighted images, bright on proton density images, and slightly less bright on T2-weighted images. Although imaging features are not specific, an enhancing, cystic temporal lobe lesion with focal calcification should suggest the diagnosis of ganglioglioma. The pathologic features that suggest the diagnosis of ganglioglioma include a neoplastic glial and neuronal component and calcification. Because calcifications are often poorly demonstrated on MR imaging and because they increase specificity of imaging findings, documentation of calcium should be sought on CT after MR imaging demonstration of a temporal lobe tumor (Fig. 6).“, 27,33

Figure 5. Dysembryoplastic neuroepithelial tumor. Wedge-shaped, nonenhancing, very low signal intensity lesion on Tl-weighted (TR 600/TE 15) axial image (A) demonstrating very high signal intensity lesion on the T2-weighted (TR 2800/TE 90) axial image (5). Note the scalloping of the inner table, the multiple septations, and the lack of vasogenic edema or mass effect on the adjacent brain and ventricle. Pathologic specimen (C) demonstrates nodules on an abnormal background of cortical dysplasia, and a specimen of one of the nodules seen on high power (D) demonstrates oligodendroglial-like cells, some of which are actually immature neurons.

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Figure 6. A large, calcified, enhancing ganglioglioma with heterogeneous within the occipital lobe of a macrocephalic child on CT (A), and Tl -weighted ages before (13) and after (C) contrast administration. Location of ganglioglioma

signal is demonstrated (TR 600/TE 15) axial imin this child is atypical.

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DISORDERS MIGRATION

OF CELLULAR TO THE CORTEX

The onset of neuronal migration to the cortex occurs during the eighth fetal week. Initially, cells in the germinal zone elongate with the nucleus remaining in the portion of cell that is furthest from the ventricular surface. After mitosis, the newly formed cells are distant from the ventricular surface. Later in neuronal migration, as distance to travel increases, migration occurs along the radial glial fibers (RGF), which span the distance from the ventricular surface to pia. Disorders of neuronal migration occur when migration is halted. Abnormalities of neuronal migration may occur with damage to the RGF by placental ischemia, infection (cytomegalovirus), or maternal trauma or with altered chemotaxis of neurons along the fibers from toxin exposure or inborn errors of metabolism. Diffuse disorders of disruption of neuronal migration include band heterotopia, classic (type 1) lissencephaly, and cobblestone (type 2) lissencephaly. Marginal glioneuronal heterotopia and nodular cortical dysplasias, nests of ectopic glial elements and gray matter within the leptomeninges and at the crown of the gyri, are believed to be the result of overmigration, possibly through areas of superficial necrosis or disruption of the external glial limitans. These findings, recognizable only on pathologic specimens, are believed to give rise to the lacy or cobblestoned cortex in type 2 lissencephaly. More focal disorders of disrupted neuronal migration include subependymal or subcortical neuronal ec‘topia and heterotopias. Disorders of neuronal migration are characterized on imaging studies by gray matter localized along the pathways of migration to the cortex. These gray matter rests, nodules, or masses share the attenuation (CT) and signal characteristics (MR imaging) of normal gray matter on all imaging sequences. Small deposits of heterotopia may be identified with high-resolution gradient volume acquisitions, which augment tissue contrast between gray and white matter (Fig. 7).3, 5 Band heterotopia results from an early arrest of neuronal migration and gives the appear-

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ance of a continuous double cortex. The appearance has also been likened to a three-layer cake with the cortex and bilaterally symmetric, circumferential, subcortical layers of band heterotopia separated from each other by a thin white matter band. The cortex may be relatively normal or pachygyric. Shallow sulci are common. Band heterotopia has been reported to be an X-linked disorder with heterozygous females demonstrating band heterotopia and hemizygous males having classic lissencephaly. Seizures are common in band heterotopia, and mental retardation may be mild or moderate. Severity of symptoms correlates with the degree of disorganization of the overlying cortex, thickness of the continuous band of heterotopic gray matter, amount of T2 prolongation, and degree of ventriculomegaly. The brain in lissencephaly type 1 may have a smooth surface (complete lissencephaly) or may have a nearly smooth surface with some gyral formation along the inferior frontal and temporal lobes. The thick cortex has a fourlayered cortex composed of a molecular outer layer, an outer cellular layer, a cell sparse layer, and an inner cellular layer composed of arrested neurons. The arrest relates to a disruption of neuronal travel along the RGF, either from laminar necrosis or from disrupted chemotaxis. Imaging demonstrates broad, flat gyri with a thickened cortex and scanty white matter. Sylvian fissures are primitive, leading to an hourglass configuration of the brain. Type 2 or cobblestone lissencephaly is recognizable by its irregular surface, abnormal myelin, and the accompanying orbital and cerebellar anomalies (Figs. 8 and 9).2*10,29 Periventricular nodular heterotopia may be solitary, isolated lesions or may diffusely line the walls of both lateral ventricles. These lesions mimic the appearance of the subependyma1 tubers in tuberous sclerosis, although they do not calcify. When diffuse and bilateral, periventricular nodular heterotopia may be associated with mild cerebellar hypoplasia. Patients with periventricular or subependyma1 heterotopias may present with late-onset seizures, acquire normal early milestones, have normal motor development, and be of average or above-average intelligence. This

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Figure 7. Coronal cutaway view from a three-dimensional gradient-recalled echo (GRE) (TR 15/lE 8) surface reconstruction (A) and T2-weighted (TR 2800/TE 90) (B) axial image demonstrate shallow surface sulci and band heterotopia in a lo-year-old girl with drop attacks, developmental delay, and lack of speech.

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Figure 8. Lissencephaly type 1. Tl -weighted (TR 6001 TE 15) (A) and T2-weighted (TR 3000/TE 120) (B) coronal images in a severely delayed patient with Miller-Dieker syndrome show a smooth cortical surface. Thickened cortex with rare gyri along the inferior temporal lobes is seen on Tl -weighted (C) and TPweighted (D) coronal images in a patient with agyria-pachygyria complex and seizures. Similar features are demonstrated in an autopsy specimen (E) in another patient. Illustration continued on following page

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disorder has been linked to markers in distal Xq28 (Fig. 10). Subcortical gray matter Izeterotopias also may be focal or diffuse. The greater the heterotopic mass, the more dysplastic the overlying cortex. Those patients with thick

heterotopias and overlying gyral anomalies are more likely to have associated psychomotor delay (Fig. 11). Deep infolding of thickened cortex, or deep clefts lined by heterotopia, often frontal, may also occur and are frequently

Figure 9. Lissencephaly type 2. A small distorted pons, rotation of the superior vermian remnant and agenesis of the inferior vermis are shown on this Tl-weighted (TR 600/TE 15) sagittal image in a patient with Walker-Warburg syndrome (A). Primitive Sylvian fissures lead to an hourglass configuration of the brain, and the cortex is lacy or cobblestoned on a T2-weighted (TR 3000/TE 120) axial image (13).

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Figure 10. Subependymal heterotopia. A and 8, Cutaway views of surface reconstruction from a three-dimensional GRE data set (TR 15/TE 8) reveal bilateral symmetrical subependymal nodules of heterotopic gray matter (arrows) in an otherwise normal child. The nodules were an incidental finding that simulated lesions of tuberous sclerosis on a head ultrasound performed during the neonatal period. The nodular densities are uncalcified and match gray matter on this and all other imaging sequences. Similar features are shown on an autopsy specimen of another patient (C).

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Figure 11. Subcortical heterotopia. A larger mass of right occipital heterotopic gray matter (arrows) is shown on axial Tl-weighted (TR 600/TE 15) (A), axial (B), and coronal T2-weighted (TR 2600/TE 90) (C) images in a child with complex partial seizures. There is a diffusely abnormal overlying cortex (C).

associated on imaging with primitive vertical venous structures (Fig. 12).3, Js‘Or“. 13,I6 DISORDERS OF CORTICAL ORGANIZATION The primitive sylvian fissure is the first sulcus to form, at approximately 14 to 20 weeks,

whereas the rolandic fissure, the parietooccipital, and the superior temporal gyri form later. By 32 to 33 weeks, large numbers of cortical sulci are visible, and by 38 to 40 weeks, there is a nearly normal adult sulcal pattern. After full-term birth, the sulci continue to deepen over the next weeks. The final group of disorders are those that are associated with

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Figure 12. Cortical infolding (deep clefting) shown on a three-dimensional surface reconstruction from a GRE (TR 15/TE 8) data set (A) with cutaway view (6) in a patient with development delay and seizures shows deep cortical clefts lined by heterotopia.

disruption of the process of gyral formation and subsequent cellular organization of the cortex. These disorders include generalized polymicrogyria (PMG) or focal and multifocal disorders such asfocal PMG, bilnteral symmetric PMG, and schizencephaly zoith or without PMG. The imaging appearance of dysplasias of cortical organization includes abnormalities of the cortical gyral pattern without radiographically evident subjacent heterotopias. The imaging appearance of generalized or focal polymicrogyria can be quite variable. Typically, there is a thick cortex with many small gyri separated by shallow sulci. The gyri may, however, be so small that they are difficult to discern on imaging. The appearance then is of a flat thickened cortex, simulating pachygyria or agyria. Small areas of cortical thickening may be better defined with adjunctive threedimensional MR reformatted images (Fig. 13). Bilateral opercular or perisylvian syndrome is a bilateral symmetric PMG disorder consisting of primitive sylvian fissures, primitive draining veins, and symmetric involvement of the

Figure 13. Focal gyral thickening. Small focal area of cortical thickening (poorly resolved on routine images) is well defined (arrows) on surface reconstruction from a threedimensional data set (TR 15/ TE 8).

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operculum with polymicrogyria or pachygyria. Patients may present with seizures, motor and speech disorders, mental retardation, and a congenital pseudobulbar syndrome (Fig. 14). Schizencephaly, or gray matjer lined clefts of the brain, occurs after disruption of the RGF units from the ventricle to the pial surface. Smaller clefts may have coapted walls

or closed lips. Larger clefts, or those with open lips, may allow free communication of the ventricles with the pericerebral spaces (Fig. 15).“~~ Also included in disorders of cortical organization are cortical dysylasia without ballootz cells, with imaging features similar to the previously described focal cortical dysplasia with

Figure 14. Bilateral opercular dysplasia is present in a 16year-old patient with a history of spastic diplegia and recent onset of seizures. Primitive sylvian fissures lined by thickened cortex are seen on Tl -weighted (TR 600/TE 15) (A) and T2-weighted (TR 2800/TE 90) (6) axial images. C, Pathologic specimen of a patient with opercular dysplasia demonstrates the vertical Sylvian fissure.

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Figure 15. Closed-lip schizencephaly is seen on the right, and a deep (TR 600/TE 15) (Al and T2-weiahted (TR 2600/TE 90) (B) axial with psychomotcr ‘delay and micrkephaly. Open-lip schi;encephaly (C) and T2-weighted (D) coronal views in a 2-year-old patient presenting lllustra

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cleft on the lett on Tl -weighted imaaes in a 2-vear-old catient is dkumented bn Ti -weighted with spastic quadriparesis. tion continued on following page

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Figure 15 (Continued). the latter child defines an additional child.

Surface reconstruction (E) from a three-dimensional the cortical defects. Pathologic specimen (F) shows

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balloon cells, and microdysgenesis. Small foci of cortical dysplasia may require serial imaging over time, becoming apparent only when myelin maturation is complete. Other foci may be apparent only with high-resolution, highcontrast imaging, such as is possible with GRE sequences. Microdysgenesis is radiographi-

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tally undetectable with pathologic features consisting of subtle neocortical abnormalities: neuronal ectopias within the white matter, abnormal neurons within the molecular layer, neuronal clustering; bare areas within cortical layers 2 to 6, and Chaslin’s subpial gliosis (Fig. 16).6,‘7,3’

Figure 16. Focal cortical dysplasia. A, Axial TP-weighted (TR 3000ITE 120) image demonstrating normally incomplete myelin maturation of the temporal lobes at 1 year of age. B, By 3 years of age, myelin maturation and arborization has occurred on the left, and now residual blurring of the gray-white matter junction is seen on the right in association with focal cortical dysplasia C, Routine coronal Tl-weighted (TR 600/TE 20) image in another child with complex partial seizures show some slight asymmetry of the peri-insular cortex. D, One-millimeter coronal reconstructions from a three-dimensional GRE (TR 15/TE 8) data set of the same region better define the thin cortical ribbon and blurred gray-white matter junction, again in association with focal cortical dysplasia.

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ACKNOWLEDGMENT Special performing

thanks to Stephanie Holowka, the surface reconstructions.

MRT

(R)

for

References 1. Barkovich AJ, Chuang SH: Unilateral megalencephaly: Correlation of MR imaging and pathologic characteristics. AJNR Am J Neuroradiol11:525-531,199O AJ, Guerrini R, Battaglia G, et al: Band het2. Barkovich erotopia: Correlation of outcome with magnetic resonance imaging parameters. Ann Neurol36:609-617, 1994 3. Barkovich AJ, Knos BO: Gray matter heterotopias: MR character%& and correlation with developmental and neurologic manifestations. Radiology 182:493-499,1992 4. Barkovich AJ, Kjos BO: Nonlissencephalic cortical dysplasias: Correlation of imaging findings with clinical deficits. AJNR Am J Neuroradiol13:95-103,1992 5. Barkovich AJ, Kuzniecky RI, Dobyns WB, et al: A classification scheme for malformations of cortical development. Neuropediatrics 27:59-63,1996 6. Bastos AC, Korah IP, Cendes F, et al: Curvilinear reconstruction of 3D magnetic resonance imaging in patients with partial epilepsy: A pilot study. Magn Reson Imaging 13:1107-1112,1995 7. Becker LE: Central neuronal tumors in childhood: Relationship to dysplasia. J Neurooncol24:13-19,1995 8. Cochrane DD. Poskitt Kl. Norman MG: Sureical implications of cerebral d&genesis. Can J N&r01 Sci 18:181-195,1991 9. Daumas-Duport C, Scheithauer SW, Chodkiewicz JP: Dysembryoplastic neuroepithelial tumor: A surgically curable tumor of young patients with intractable partial seizures. Neurosurgery 23:545-556,1988 10. Dobyns WB, Truwit CL: Lissencephaly and other malformations of cortical development: 1995 update. Neuropediatxics 26:132-147,1995 11. Dome I-IL, O’Gorman AM, Melanson D: Computed tomography of intracranial gangliogliomas. AJNR Am J Neuroradiol7:281-285,1986 12 Dubeau F, Tampieri D, Lee N, et al: Periventricular and subcortical-nodular heterotopia: A study of 33 uatients. Brain 118:127~1287,1995 13 Eksioglu YZ, Scheffer IE, Cardenas I’, et al: Periventricular heterotopia: An X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron l&77-87,1996 14. Farrell MA, DeRosa MJ, Cm-ran JG, et al: Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy. Acta Neuropathol 83:24&259,1992 15. Freide RL: Dysplasias of cerebral cortex. In Developmental Neuropathology, ed 2. Berlin, Springer-Verlag, 1989

MA, Super M: Familial bilateral 16. Jardine PE, Clarke periventricular nodular heterotopia mimics tuberous sclerosis. Arch Dis Child 74:244-246,1996 17. Jay V, Becker LE, Otsubo H, et al: Pathology of temporal lobectomy for refractory seizures in children: Review of 20 cases including some unique malformative lesions. J Neurosurg 79:53-61,1993 V, Rutka JT Crystalline inclusions in 18. Jay V, Edwards a subependymal giant cell tumor in a patient with tuberous sclerosis. Ultrashuct Path01 17:503-513,1993 19. Kimura M, Yoshino K, Maeoka Y, et al: Hypomelanosis of Ito: MR findings. Pediatr Radio1 24:68-69,1994 T, Bergey GK, Rothman MI, et al: Radio20. Kuroiwa logic appearance of the dysembroplastic neuroepithelial tumor. Radiology 197:233-238,1995 21. Kuzniecky R, Garcia JH, Gaught E, et al: Cortical dysplasia in temporal lobe epilepsy: Magnetic resonance imaging correlations. Ann Neurol29:293-298,1991 22. Martin N, Debussche C, De Broucker T, et al: Gadolinium-DTPA enhanced MR imaging in tuberous sclerosis. Neuroradiology 31:492-497,1990 23. Manz HJ, Phillips TM, Rowden G, et al: Unilateral megalencephaly, cerebral cortical dysplasia, neuronal hypertrophy, and heteropia. Acta Neuropathol45:97103,1979 24. Menor F, Marti-Bonmati L, Mulas F, et al: Neuroimaging in tuberous sclerosis: A clinico-radiological evaluation in pediatric patients. Pediatr Radio1 22485-489, 1992 25. Miller DC, Lang FE, Epstein FJ: Central nervous system gangliogliomas: Part 1. Pathology. J Neurosurg 79:859-866,1993 26. Moreland DB, Glasauer FE, Egnatchik JG, et al: Focal cortical dysplasia. J Neurosurg 68:487-490,1988 27. Otsubo H, Hoffman HJ, Humphreys RF’, et al: Detection and management of gangliogliomas in children. Surg Neurol38:371-378,1992 28. Otsubo H, Hwang I’, Jay V, et al: Focal cortical dysplasia in children with localization related epilepsy: EEG, MRI and SPECT findings. Pediatr Neurol9:101107,1993 29. Palmini A, Andermann F, Aicardi J, et al: Diffuse cortical dysplasia, or the ‘double cortex’ syndrome: The clinical and epileptic spectrum in 10 patients. Neurology 41:165tX662,1991 30. Raymond AA, Fish DR, Stevens JM, et al: Subependyma1 heterotopia: A distinct neuronal migration disorder associated with epilepsy. J Neurol Neurosurg Psychiatry 57:119%1202,1994 31. Rolland Y, Adamsbaum C, Sellier N, et al: Opercular malformations: Clinical and MRI features in 11 children. Pediatr Radio1 25fsuppl l):S2-SB, 1995 32. Taylor DC, Falconer MA, Bruton CJ, et al: Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry 34:369-387,197l 33. Zentner J, Wolf HK, Osterhm B, et al: Gangliogliomas: Clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 57:1497-1502,1994 Address

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Susan I. Blaser, MD, FRCPC Department of Diagnostic Imaging Division of Neuroradiology The Hospital for Sick Children 555 University Avenue Toronto, Ontario Canada M5G 1X8