Cortical dysplasia 소아과 R3 황대환

Cortical dysplasia Disturbed development of cells that normally participate in formation of the cerebral cortex  Disorders of cortical development known causes : intrauterine infection & ischemia, and chromosomal mutations Manifestation : epilepsy, development delay, focal neurologic signs

Normal cortical development 1) Proliferation proliferation of neurons in the ventricular zone and glia in the subventricular zone 2) Migration Migration of postmitotic neurons to the cortical plate Heading for the deepest layers and then for the superfricial layer Between the 8th and 24th weeks of gestation 3) Cortical organization : vertical and horizontal organization of neurons within the cortex and elaboration of axonal and dendritic branch terminal differentiations, apoptosis, synapse elimination, cortical remodeling

Classification of MCD (1)

Classification of MCD (2)

Focal cortical dysplasia 1 Caused by abnormal neuronal and glial proliferation. Non-familial, non-syndromic, localization-related epilepsy Clinical manifestations : Seizures usually begin 2~3 years old, even at birth Simple partial, complex partial, or secondary generalization If extensive regions, neurologic impairment such as mental subnormality and hemiparesis Focal cortical dysplasia account for 25% of intractable partial epilepsy in children Extra-temporal lobe : frontal, pre- and post- central gyrus Temporal lobe

Focal cortical dysplasia MRI : Focal abnormal gyral(cotical) thickening Blurring of the cortical-white matter junction

Focal 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 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

Heterotopia Collections of normal neurons in abnormal locations 2 Collections of normal neurons in abnormal locations Failure of neurons to migrate to the cortical plate Arrest of radial migration and occurs from the subependymal zone to the cortex They may occur as single lesions adjacent to the ventricle or in the more superficial white matter Periventricular nodular heterotopia Subcortical band heterotopia

Periventricular nodular heterotopia (Subependymal nodular heterotopia) 2-1 Neurons generated in a periventricular location have altogether failed to migrate, leading to nests or nodules of neurons abutting the ventricular ependymal lining Multiple bilateral gray matter nodules in the walls of the lateral ventricles X-linked (Xq28) Males much more severely affected Bilateral lesions (75%) Seizures starting at any age (often begin in the second decade ) variable degrees of mental impairment (mild in females and severe in males)

Periventricular nodular heterotopia Multiple smooth nodules of cortical gray matter nodules lining the lateral ventricle

Periventricular nodular heterotopia Isointensity of periventricular tissue with normal GM Nodules of heterotopia abutting the lateral ventricles bilaterally Nodules of GM within WM (★)

Subcortical band heterotopia 2-2 Subcortical band heterotopia “Diffuse cortical dysplasia” or “ double cortex syndrome” These bands are commonly just separated from the overlying cortex by a thin shell of WM These bands are made of neurons that did not complete migration The cortex overlying the heterotopias is mildy thickened or normal and the temporal lobes are normal (vs. lissencephaly) DCX on the X chromosome, LIS 1 gene on chromosom17 Infantile spasms, Lennox-Gastaut syndrome, or other forms of generalized seizures.

Subcortical band heterotopias -MRI -Thick subcortical GM band are found in subcortical WM

LISSENCEPHALY(smooth brain) 3 LISSENCEPHALY(smooth brain) Smooth cortex with minimal sulcation Migration of all cortical neurons has been severely affected and the brain is smooth Gyri may be flat and few(pachygyria) or absent(agyria) The GM-WM interface is smooth Cortical organization is disrupted, and WM is attenuated Severe developmental delay, microcephaly, intractable seizures, and premature death. DCX on the X chromosome, LIS 1 gene on chromosom17 17p13.3(which contains LIS 1) Miller-Dieker syndrome Xq22

Type I Lissencephaly(classic form) 3-1 Histology a four-layered cortex instead of the normal 6-layered ribbon ( layer 4 is composed of a broad band of disorganized neurons) a four-layered, abnormally thick cortex, and hypoplasia of the corpus callosum and widespread neuronal heterotopias Hypotonia in early life and onset of seizures by age 6 months Infantile spasms and myoclonic and tonic seizures Mental retardation and spastic quadriplegia Miller-Dieker Syndrome (MDS) & isolated lissencephaly sequence (ILS) deletions or mutations of the LIS1 gene on chromosome 17p13.3

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

Type II lissencephaly ( Cobblestone lissencephaly ) 3-2 Over-migration of neurons and glia through gaps in the glial limiting membrane deep into the leptomeninges, forming neurons admixed with the leptomeninges over the surface of the brain Cobble stone cortex, abnormal WM, enlarged ventricles, small brain stem, small cerebellum Associated with congenital muscular dystrophy and eye abnormalities The Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy

Polymicrogyria 4 Presence of an excess number of abnormally small gyri that produce an irregular cortical surface The outermost cortical layer(molecular layer) commonly fuses, which lead to an appearance of an overly smooth cortical surface

Bilateral perisylvian polymicrogyria 4-1 Pseudobulbar palsy, spastic quadriparesis, learning disability, epilepsy, and mental retardation Dysarthria, and an inability to protrude or move their tongue laterally 90% of patients have seizures (complex partial seizures and drop attacks being most common ) Mutation in MECP2 gene

Bilateral sylvian dysplasia-MRI 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

Schizencephaly 5 Presence of unilateral or bilateral GM-lined clefts within the cerebral hemispheres, extending from the pial surface to the ependymal lining Frequently, the borders of the clefts are surrounded by abnormal brain, particularly microgyria

Treatment Drugs : usually intractable ( >60~70%) Surgery : complete resection of the epileptogenic zone is required Impossible in diffuse of bilateral dysplasia( for patients with drop attack, corpus callosotomy is alternative)

CONCLUSION Malformation of cortical development are increasingly recognized as causes of development delay, cognitive deficits and epilepsy The current classification of these disorders allows for the proper recognition of distinct clinico-imaging entities Treatment of the epilepsy associated with cortical dysplasia is often frustrating, but surgical approaches based on accurately defining epileptogenic regions are proving increasingly successful Genetic diagnosis is important for accurate counseling of families