Cortical dysplasia

 소아과 R3 황대환
 Cortical dysplasia

 Disturbed development of cells that nor

mally participate in formation of the cer
ebral cortex  Disorders of cortical de
velopment
 known causes : intrauterine infection & i
schemia, and chromosomal mutations
 Manifestation : epilepsy, development d
elay, focal neurologic signs
 Normal cortical development
 1) Proliferation
 proliferation of neurons in the ventricular zone and glia in the su
bventricular zone

 2) Migration
 Migration of postmitotic neurons to the cortical plate
 Heading for the deepest layers and then for the superfricial laye
r
 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)
 1
Focal cortical dysplasia
 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 subn
ormality and hemiparesis
 Focal cortical dysplasia account for 25% of intractable partial e
pilepsy 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
 2
Heterotopia

 Collections of normal neurons in abnormal locations

 Failure of neurons to migrate to the cortical plate

 Arrest of radial migration and occurs from the subepe

ndymal zone to the cortex
 They may occur as single lesions adjacent to the vent
ricle or in the more superficial white matter

 Periventricular nodular heterotopia

 Subcortical band heterotopia
 2-1
Periventricular nodular heterotopia (Subepen
dymal nodular heterotopia)
 Neurons generated in a periventricular location have altoget
her failed to migrate, leading to nests or nodules of neuron
s abutting the ventricular ependymal lining

 Multiple bilateral gray matter nodules in the walls of the late

ral ventricles

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

 Bilateral lesions (75%)

 Seizures starting at any age (often begin in the second dec

ade ) variable degrees of mental impairment (mild in female
s 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 (★)
 2-2

Subcortical band heterotopia

 “Diffuse cortical dysplasia” or “ double cortex syndrome”
 These bands are commonly just separated from the overlyi
ng 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. lissencepha
ly)

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

 Infantile spasms, Lennox-Gastaut syndrome, or other form

s of generalized seizures.
 Subcortical band heterotopias -MRI

-Thick subcortical GM band

are found in subcortical WM
 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
 3-1

Type I Lissencephaly(classic form)

 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 sequenc

e (ILS)
deletions or mutations of the LIS1 gene on chromosome 17p1
3.3
 Type I Lissencephaly- MRI
•MRI :
Thickened cortex,
Diminished white matter,
Vertical sylvian fissures, giving a typi
cal figure 8 appearance to the brain
Smooth cerebral surface,
Type II lissencephaly ( Cobblesto 3-2

ne lissencephaly )
 Over-migration of neurons and glia through gaps in the glial limi
ting membrane deep into the leptomeninges, forming neurons a
dmixed with the leptomeninges over the surface of the brain

 Cobble stone cortex, abnormal WM, enlarged ventricles, small b

rain stem, small cerebellum
 Associated with congenital muscular dystrophy and eye abnorm
alities

 The Walker-Warburg syndrome, muscle-eye-brain disease, and

Fukuyama congenital muscular dystrophy
 4

Polymicrogyria
 Presence of an excess number of abnor
mally small gyri that produce an irregula
r cortical surface
 The outermost cortical layer(molecular l
ayer) commonly fuses, which lead to an
appearance of an overly smooth cortical
surface
 4-1
Bilateral perisylvian polymicrogyria

 Pseudobulbar palsy, spastic quadriparesis, le

arning disability, epilepsy, and mental retardat
ion
 Dysarthria, and an inability to protrude or mov
e their tongue laterally
 90% of patients have seizures
(complex partial seizures and drop attacks bei
ng most common )
 Mutation in MECP2 gene
 Bilateral sylvian dysplasia-MRI
Thickened cortex bilaterally in the sylvia
n and perisylvian regions

The GM to WM interface is clear, and in

some regions is excessively folded

The Sylvian fissures are widened and a

bnormally figured

Excess digitations in perisylvian grey m

atter

The overlying cortex appears smooth

 5
Schizencephaly
 Presence of unilateral or
bilateral GM-lined clefts
within the cerebral hemi
spheres, extending from
the pial surface to the e
pendymal lining
 Frequently, the borders
of the clefts are surroun
ded 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( f
or patients with drop attack, corpus callosoto
my is alternative)
 CONCLUSION
 Malformation of cortical development are increasingly
recognized as causes of development delay, cognitiv
e deficits and epilepsy
 The current classification of these disorders allows fo
r the proper recognition of distinct clinico-imaging en
tities
 Treatment of the epilepsy associated with cortical dys
plasia is often frustrating, but surgical approaches ba
sed on accurately defining epileptogenic regions are
proving increasingly successful
 Genetic diagnosis is important for accurate counselin
g of families