Cortical dysplasiaCortical dysplasia

소아과 소아과 R3 R3 황대환황대환

Cortical dysplasiaCortical dysplasia

Disturbed development of cells that normalDisturbed development of cells that normally participate in formation of the cerebral cly participate in formation of the cerebral cortex ortex Disorders of cortical development Disorders of cortical development

known causes : intrauterine infection & iscknown causes : intrauterine infection & ischemia, and chromosomal mutations hemia, and chromosomal mutations

Manifestation : epilepsy, development delaManifestation : epilepsy, development delay, focal neurologic signsy, focal neurologic signs

Normal cortical developmentNormal cortical development

1) 1) ProliferationProliferation proliferation of neurons in the ventricular zone and glia in the subvenproliferation of neurons in the ventricular zone and glia in the subven

tricular zonetricular zone

2) 2) MigrationMigration Migration of postmitotic neurons to the cortical plateMigration of postmitotic neurons to the cortical plate Heading for the deepest layers and then for the superfricial layerHeading for the deepest layers and then for the superfricial layer Between the 8th and 24th weeks of gestationBetween the 8th and 24th weeks of gestation

3) 3) Cortical organizationCortical organization : : vertical and horizontal organization of neurons within the cortex and vertical and horizontal organization of neurons within the cortex and

elaboration of axonal and dendritic branch elaboration of axonal and dendritic branch terminal differentiations, apoptosis, synapse elimination, cortical reterminal differentiations, apoptosis, synapse elimination, cortical re

modelingmodeling

Classification of MCD (1)Classification of MCD (1)

Classification of MCD (2)Classification of MCD (2)

Focal cortical dysplasiaFocal cortical dysplasia Caused by abnormal neuronal and glial proliferation. Caused by abnormal neuronal and glial proliferation. Non-familial, non-syndromic, localization-related epilepsyNon-familial, non-syndromic, localization-related epilepsy Clinical manifestations : Clinical manifestations : Seizures usually begin 2~3 years old, even at birthSeizures usually begin 2~3 years old, even at birth Simple partial, complex partial, or secondary generalizationSimple partial, complex partial, or secondary generalization If extensive regions, neurologic impairment such as mental subnormIf extensive regions, neurologic impairment such as mental subnorm

ality and hemiparesisality and hemiparesis Focal cortical dysplasia account for 25% of intractable partial epilepsFocal cortical dysplasia account for 25% of intractable partial epileps

y in childreny in children

Extra-temporal lobe : frontal, pre- and post- central gyrus Extra-temporal lobe : frontal, pre- and post- central gyrus Temporal lobeTemporal lobe

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Focal cortical dysplasiaFocal cortical dysplasiaMRI :

Focal abnormal gyral(cotical) thickening

Blurring of the cortical-white matter junction

Focal cortical dysplasiaFocal cortical dysplasia

(A1) T1WI : cortical thickening

(A2) Proton-density-WI : blurring of interface between GM and WM

(A3) T2WI : increased signal change

(A4) FLAIR image : increased signal change

Focal cortical dysplasiaFocal cortical dysplasia

Histologic features : -Disruption of cortical lamination -Giant neurons, dysplastic "balloon cells" in WM -Excess of neurons on the WM, causing blurring of the interface between GM and WM

HeterotopiaHeterotopia

Collections of normal neurons in abnormal locationsCollections of normal neurons in abnormal locations Failure of neurons to migrate to the cortical plateFailure of neurons to migrate to the cortical plate

Arrest of radial migration and occurs from the subependyArrest of radial migration and occurs from the subependymal zone to the cortexmal zone to the cortex

They may occur as single lesions adjacent to the ventricle They may occur as single lesions adjacent to the ventricle or in the more superficial white matteror in the more superficial white matter

Periventricular nodular heterotopiaPeriventricular nodular heterotopia Subcortical band heterotopiaSubcortical band heterotopia

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Periventricular nodular heterotopia (SubependyPeriventricular nodular heterotopia (Subependymal nodular heterotopia) mal nodular heterotopia)

Neurons generated in a periventricular location have altogether Neurons generated in a periventricular location have altogether failed to migrate, leading to nests or nodules of neurons abuttinfailed to migrate, leading to nests or nodules of neurons abutting the ventricular ependymal liningg the ventricular ependymal lining

Multiple bilateral gray matter nodules in the walls of the lateral Multiple bilateral gray matter nodules in the walls of the lateral ventriclesventricles

X-linked (Xq28)X-linked (Xq28) Males much more severely affected Males much more severely affected

Bilateral lesions (75%)Bilateral lesions (75%)

Seizures starting at any age (often begin in the second decade ) Seizures starting at any age (often begin in the second decade ) variable degrees of mental impairment (mild in females and sevvariable degrees of mental impairment (mild in females and severe in males)ere in males)

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Periventricular nodular heterotopia Periventricular nodular heterotopia

Multiple smooth nodules of cortical gray matter nodules lining the lateral ventricle

Periventricular nodular heterotopiaPeriventricular nodular heterotopia

Isointensity of periventricular tissue with normal GM

Nodules of heterotopia abutting the lateral ventricles bilaterally

Nodules of GM within WM (★)

Subcortical band heterotopiaSubcortical band heterotopia

““Diffuse cortical dysplasia” or “ double cortex syndrome”Diffuse cortical dysplasia” or “ double cortex syndrome” These bands are commonly just separated from the overlying cThese bands are commonly just separated from the overlying c

ortex by a thin shell of WMortex by a thin shell of WM These bands are made of neurons that did not complete migraThese bands are made of neurons that did not complete migra

tiontion The cortex overlying the heterotopias is mildy thickened or norThe cortex overlying the heterotopias is mildy thickened or nor

mal and the temporal lobes are normal (vs. lissencephaly)mal and the temporal lobes are normal (vs. lissencephaly)

DCX on the X chromosome, LIS 1 gene on chromosom17DCX on the X chromosome, LIS 1 gene on chromosom17

Infantile spasms, Lennox-Gastaut syndrome, or other forms of Infantile spasms, Lennox-Gastaut syndrome, or other forms of generalized seizures.generalized seizures.

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Subcortical band heterotopias Subcortical band heterotopias -MRI-MRI

-Thick subcortical GM band are found in subcortical WM

LISSENCEPHALY(smooth brain)LISSENCEPHALY(smooth brain) Smooth cortex with minimal sulcationSmooth cortex with minimal sulcation Migration of all cortical neurons has been severely affected and the Migration of all cortical neurons has been severely affected and the

brain is smoothbrain is smooth Gyri may be flat and few(Gyri may be flat and few(pachygyriapachygyria) or absent() or absent(agyriaagyria) ) The GM-WM interface is smoothThe GM-WM interface is smooth Cortical organization is disrupted, and WM is attenuatedCortical organization is disrupted, and WM is attenuated Severe developmental delay, microcephaly, intractable seizures, and Severe developmental delay, microcephaly, intractable seizures, and

premature death. premature death.

DCX on the X chromosome, LIS 1 gene on chromosom17DCX on the X chromosome, LIS 1 gene on chromosom17 17p13.3(which contains LIS 1)17p13.3(which contains LIS 1) Miller-Dieker syndrome Miller-Dieker syndrome Xq22Xq22

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Type I Lissencephaly(classic form)Type I Lissencephaly(classic form)

HistologyHistology a four-layered cortex instead of the normal 6-layered ribbona four-layered cortex instead of the normal 6-layered ribbon ( layer 4 is composed of a broad band of disorganized neurons)( layer 4 is composed of a broad band of disorganized neurons) a four-layered, abnormally thick cortex, and hypoplasia of the corpus a four-layered, abnormally thick cortex, and hypoplasia of the corpus

callosum and widespread neuronal heterotopiascallosum and widespread neuronal heterotopias

Hypotonia in early life and onset of seizures by age 6 monthsHypotonia in early life and onset of seizures by age 6 months Infantile spasms and myoclonic and tonic seizures Infantile spasms and myoclonic and tonic seizures Mental retardation and spastic quadriplegia Mental retardation and spastic quadriplegia

Miller-Dieker Syndrome (MDS) & isolated lissencephaly sequence (ILMiller-Dieker Syndrome (MDS) & isolated lissencephaly sequence (ILS)S)

deletions or mutations of the LIS1 gene on chromosome 17p13.3deletions or mutations of the LIS1 gene on chromosome 17p13.3

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Type I Lissencephaly- MRIType I Lissencephaly- MRI•MRI : Thickened cortex, Diminished white matter, Vertical sylvian fissures, giving a typical figure 8 appearance to the brainSmooth cerebral surface,

Type II lissencephaly ( Cobblestone Type II lissencephaly ( Cobblestone lissencephaly )lissencephaly )

Over-migration of neurons and glia through gaps in the glial limiting Over-migration of neurons and glia through gaps in the glial limiting membrane deep into the leptomeninges, forming neurons admixed wmembrane deep into the leptomeninges, forming neurons admixed with the leptomeninges over the surface of the brainith the leptomeninges over the surface of the brain

Cobble stone cortex, abnormal WM, enlarged ventricles, small brain Cobble stone cortex, abnormal WM, enlarged ventricles, small brain stem, small cerebellumstem, small cerebellum

Associated with congenital muscular dystrophy and eye abnormalitieAssociated with congenital muscular dystrophy and eye abnormalitiess

The Walker-Warburg syndrome, muscle-eye-brain disease, and FukuyThe Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuy

ama congenital muscular dystrophy ama congenital muscular dystrophy

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PolymicrogyriaPolymicrogyria Presence of an excess number of abnormaPresence of an excess number of abnorma

lly small gyri that produce an irregular cortilly small gyri that produce an irregular cortical surfacecal surface

The outermost cortical layer(molecular layeThe outermost cortical layer(molecular layer) commonly fuses, which lead to an appear) commonly fuses, which lead to an appearance of an overly smooth cortical surfacerance of an overly smooth cortical surface

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Bilateral perisylvian polymicrogyriaBilateral perisylvian polymicrogyria

Pseudobulbar palsy, spastic quadriparesis, learniPseudobulbar palsy, spastic quadriparesis, learning disability, epilepsy, and mental retardationng disability, epilepsy, and mental retardation

Dysarthria, and an inability to protrude or move tDysarthria, and an inability to protrude or move their tongue laterallyheir tongue laterally

90% of patients have seizures90% of patients have seizures (complex partial seizures and drop attacks being (complex partial seizures and drop attacks being

most common )most common ) Mutation in MECP2 gene Mutation in MECP2 gene

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Bilateral sylvian dysplasia-Bilateral sylvian dysplasia-MRIMRI

Thickened cortex bilaterally in the sylvian and perisylvian regions

The GM to WM interface is clear, and in some regions is excessively folded

The Sylvian fissures are widened and abnormally figured

Excess digitations in perisylvian grey matter

The overlying cortex appears smooth

SchizencephalySchizencephaly

Presence of unilateral or Presence of unilateral or bilateral GM-lined clefts wbilateral GM-lined clefts within the cerebral hemisphithin the cerebral hemispheres, extending from the eres, extending from the pial surface to the ependypial surface to the ependymal liningmal lining

Frequently, the borders of Frequently, the borders of the clefts are surrounded the clefts are surrounded by abnormal brain, particuby abnormal brain, particularly microgyrialarly microgyria

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TreatmentTreatment

Drugs : usually intractable ( >60~70%) Drugs : usually intractable ( >60~70%) Surgery : Surgery : complete resection of the epileptogenic zone is rcomplete resection of the epileptogenic zone is r

equiredequired Impossible in diffuse of bilateral dysplasia(Impossible in diffuse of bilateral dysplasia( for for

patients with drop attack, corpus callosotomy is patients with drop attack, corpus callosotomy is alternative)alternative)

CONCLUSION CONCLUSION Malformation of cortical development are increasingly recMalformation of cortical development are increasingly rec

ognized as causes of development delay, cognitive deficitognized as causes of development delay, cognitive deficits and epilepsys and epilepsy

The current classification of these disorders allows for thThe current classification of these disorders allows for the proper recognition of distinct clinico-imaging entities e proper recognition of distinct clinico-imaging entities

Treatment of the epilepsy associated with cortical dysplaTreatment of the epilepsy associated with cortical dysplasia is often frustrating, but surgical approaches based on sia is often frustrating, but surgical approaches based on accurately defining epileptogenic regions are proving incraccurately defining epileptogenic regions are proving increasingly successfuleasingly successful

Genetic diagnosis is important for accurate counseling of Genetic diagnosis is important for accurate counseling of familiesfamilies