Transcript Cortical dysplasia

Cortical dysplasia
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소아과 R3 황대환
Cortical dysplasia
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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
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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
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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
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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)
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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
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X-linked (Xq28)
Males much more severely affected
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Bilateral lesions (75%)
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2-1
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 (★)
2-2
Subcortical band heterotopia
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“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
-Thick subcortical GM band
are found in subcortical WM
-MRI
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LISSENCEPHALY(smooth brain)
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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)
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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
•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
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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
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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
4-1
Bilateral perisylvian polymicrogyria
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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
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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
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Treatment
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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
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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