FOCAL CORTIKAL DYSPLASIA

Saumy Dewi Ratih

Departemen Ilmu Kesehatan Anak.

Fakultas Kedokteran dan Kesehatan Masyarakat dan keperawatan
Universitas Gadjah Mada
RSUP DR Sardjito
 Development of the Cerebral Cortex
This intricate, complex process can be divided into 3 general phases
(below) that overlap in time

PROLIFERATION/ ORGANIZATION/
MIGRATION
APOPTOSIS MATURATION

• Begins in germinal zones • Greatest between 8 – 24 • 28-40 weeks

during 4-5th week of weeks of gestation, ends
gestation by 27 weeks
• Germinal zone: along • Neurons migrate along
lateral ventricle margin fascicles formed by radial
glial cell processes, from
• Both neurogenesis and germinal zones
gliogenesis peripherally to cortex
• ”Inside-out” pattern
(early migrating cells are
located deeper in cortex)
• Cortex is organized into
6 functional layers
• Establish connectivity
with other neurons
• Neuron location
determined by genetics
and interactions with
other CNS components
Cerebral Cortex
•

• *
Cerebral Cortex
• Normal neocortex
– 6-layered neocortex
present in over 90% brain
• Olfactory paleocortex &
hippocampal archicortex
*
composed of 3 layers
• Normal neocortex is 1-3 *
mm in thickness
Magnified T1-weighted image
– Thinner at depth of demonstrating normal gyri.
sulcus (*) indicates depth of sulcus,
(*)
green arrow indicates crown of
– Thicker at crown of gyrus
gyrus.
(green arrow)
 Malformations of Cortical Development
(MCD)
 MCDs are microro-or macroscopic abnormalities of the
cerebral cortex that result from interruption of
normal cortical formation
• This presentation will review the • Most patients with MCDs have
imaging findings of the following MCDs: epilepsy
– Microcephaly with Simplified Gyral – MCDs cause 25-40% of intractable,
medically refractory epilepsy
Pattern (MSG)
– Exceptions: MSG
– Classic
Lissencephaly
(agyria-
pachygyria)
– Band Heterotopia
– Gray Matter (GM)
Heterotopia
– Polymicrogyria
(PMG)
 Malformations of Cortical
Development (MCDs)
• MCDs have been increasingly recognized
in recent
decades due to improved MRI resolution
• At least 75% of patients with MCDs have epilepsy

• The presence of an MCD in and of itself is associated

with medically refractory epilepsy
– Surgery is becoming more commonplace in the setting
of refractory pediatric epilepsy
Phases of Cortical Development in Which Specific
MCDs Occur (Some Involve More Than One)

PROLIFERATION/ ORGANIZATION/
MIGRATION
APOPTOSIS MATURATION

Microcephaly with Simplified

Lissencephaly
Gyral Pattern

Band Heterotopia
Type IIb Focal Cortical
Dysplasia
Gray Matter (Nodular)
Heterotopia
Hemimegalencephaly

Schizencephaly

Polymicrogyria

Focal Cortical Dysplasia Types I and

IIa
 Focal Cortical Dysplasia

• Focal Cortical Dysplasia (FCD) is defined as cortical disorganization with

abnormal laminar architecture
– can be associated with heterotopia & polymicrogyria

• FCDs are categorized according to 2011 ILAE classification (see following

slide)

• FCDs are the most important etiology of focal, medically refractory epilepsy
– found in almost ½ of pathologic specimens from surgery done for
refractory epilepsy
• Type IIb FCD is considered a disorder of proliferation

• The remainder of FCDs are considered disorders of late migration and

organization and will be presented accordingly
 Abbreviated ILAE Classification

• FCD Type I – Architectural cortical abnormalities

(such as abnormal lamination)

• FCD Type II – Architectural abnormality and cell

abnormality consisting of dysmorphic neurons or
balloon cells
– Balloon cells also seen in tubers of tuberous
sclerosis upon pathologic examination
 Disorders of Proliferation
Focal Cortical Dysplasia, Type IIb

• Imaging findings of FCDs include:

– Thickened cortex
– Blurring of gray-white (GW) matter jxn
• ↑ cortical and/or WM signal
– Transmantle signal abnormality that
extends to and tapers towards ventricular
– margin; usually in Type IIb
“Bottom of sulcus” configuration – GW
*
blurring at the depth of a sulcus that
extends in a transmantle fashion (also
– associated with Type IIb)
– Abnormal gyral pattern
↓ focal or lobar volume

9-year-old with drug-resistant epilepsy. Axial T2-
weighted image shows a large wedge-shaped
area of T2-hyperintensity involving both GM &
WM in the right parietal lobe. Margins of the
abnormality are indicated by (→).
Note additional findings of scattered cortical
thickening, GW junction blurring (→), as well
as ill-defined extension and tapering into the
WM along the anterior margin of the lesion (*)
on this image.
 Disorders of Proliferation
Focal Cortical Dysplasia, Type IIb

• Note transmantle extent of

the wedge-shaped T2/FLAIR
hyperintense lesion on high
resolution FLAIR images in
the same patient

• Surgical resection: Type IIb

FCD
• Patient has been seizure
free since surgery (> 1 year)
Sagittal high resolution FLAIR image
in the same patient shows the wedge shaped
area of right parietal hyperintensity extending
from the cortex (delineated by [→])
to the ventricular margin (→).
Imaging in MCDs

Axial PET image shows focal hypometabolism in the right anterior frontal lobe (→).
This triggered reevaluation of the patient’s prior MRI (12-year-old with intractable
epilepsy). Upon additional review, a funnel shaped area of high FLAIR signal was found
in the same region (→), compatible with a subtle cortical dysplasia (“bottom of the
sulcus sign”). The transmantle extent is best seen on sagittal FLAIR images (→).
 Symptom
• Focal cortical dysplasia may involve any part of the brain, may vary in size and
location and may be multifocal

• Epilepsy, sometimes associated with mental retardation, particularly with early seizure onset.
• There are no significant neurological deficits despite large areas of brain tissue occupied by a lesion.
• Symptoms appear at any age, mostly in childhood, but also occur in adults. Epilepsy is usually drug-
resistant.
• Patients with FCD type II manifest earlier onset comparing to type I
• Focal cortical dysplasia type I is related to temporal lobe seizures .
• In patients with FCD type II, multilobar lesions are found, involving hemisphere, often with
extratemporal location and mainly in the frontal lobe. Therefore seizures with early onset in neonatal
period or childhood are more likely FCD type II with multilobar or hemispheric lesion, while FCD
type I with a small focus, usually in the temporal lobe, predominates in adults
Global developmental delay (GDD) atau keterlambatan
perkembangan global (KPG) 
• Definisi : Merupakan keterlambatan bermakna pada lebih dari dua domain
perkembangan.

• Domain Perkembangan : Motorik halus, motorik kasar, bahasa/berbicara,

personal sosial/interaksi sosial, kognitif, dan aktivitas sehari-hari. 

• Angka kejadian sekitar 1%-3% anak-anak < 5 tahun di seluruh dunia.

• Etiologi sangat bervariasi dapat dibedakan menjadi kejadian prenatal,

perinatal, pasca natal, dan idiopatik. Etiologi paling banyak adalah disgenesis
serebral. 

Tanuwijaya S. Kebutuhan dasar tumbuh kembang anak. Dalam: Narendra M, Sularyo S, Soetjiningsih, Suyitno H, Ranuh IGN, penyunting. Buku ajar tumbuh kembang
anak dan remaja, edisi ke-1. Jakarta: Sagung Seto; 2002.h.13-21.
https://www.cps.ca/en/documents/position/evaluation-of-the-child-with-global-developmental-delay-and-
Table 1. Causes of global developmental delay/intellectual disability
intellectual-disability
Broad category  Possible causes  Proportion of diagnostic yield* 

Prenatal intrinsic  Genetic Up to 47%

Central nervous system malformations Up to 28%
Metabolic

Prenatal extrinsic  Teratogens/toxins (drugs of abuse, Up to 21%

medications, etc.)
Infections

Perinatal  Asphyxia Up to 55%

Prematurity
Neonatal complications

Postnatal  Neglect/psychosocial environment Up to 11%

Infections
Trauma
Toxins
.cps.ca/en/documents/position/evaluation-of-the-child-with-global-developmental-delay-and-
Table 2. History and physical and neurodevelopmental exams
History  Physical and neurodevelopmental exams 
intellectual-disabilityFamily history  Physical exam
Three-generations review, looking for:  Growth parameters
 Recurrent miscarriages  Head shape
 Birth defects  Fontanelle
 Infant deaths  Cutaneous stigmata
 GDD/ID   Spine
 Neurologic conditions  Heart abnormalities
 Genetic conditions   Abdomen check for organomegaly
  Ethnic background   Limb abnormalities
 Consanguinity   Genital abnormalities

Psychosocial history  Neurodevelopmental exam 

 Parent language, education,  Neurological exam
employment   Congenital abnormalities 
 Parental drug/alcohol abuse  Dysmorphic features 
 Child care arrangements   Current developmental level 
 History of abuse or neglect and
involvement of child protective
services

Prenatal history   
 Prenatal ultrasound 
 Screening for fetal aneuploidy
 Maternal diabetes or hypertension 
 Infections
 Exposure to medications or toxins

Birth history   
 Weight and height 
 Head circumference
 Apgar score 
 Length of hospitalization

Red flags suggestive of inborn errors of  

metabolism 
Developmental milestones   
 Regression or lack of milestones
 Timing of parents’ first concern 
GDD Global developmental delay; ID Intellectual disability
Figure 1. Algorithm for investigating global developmental delay or intellectual disability.
.cps.ca/en/documents/position/evaluation-of-the-child-with-global-developmental-delay-and-
intellectual-disability
Continue

• If the diagnosis is not established, consider consultation with genetics/metabolic

specialist.
• Chromosomal microarray and Fragile X DNA testing are first-line investigations for
children with unexplained GDD/ID.
• Brain imaging is recommended as a first-line investigation for patients with
microcephaly, macrocephaly, seizures or abnormal neurological findings.
• For others, imaging may be postponed until first-line genetic and metabolic
investigations have been performed. Magnetic resonance imaging (MRI) is the
modality of choice.
• Order lead level and iron studies for children at risk.
Summary
• MCDs are a heterogeneous group of disorders
involving abnormal formation of the cerebral cortex
• An interdisciplinary approach is critical to the work-
up and management of MCDs in children

•
References & Suggested Readings
• Raybaud C, Widjaja E. Development & Dysgenesis of the Cerebral
Cortex: Malformations of Cortical Development. Neuroimaging Clin
N Am. 2011: 483-543
• Leach JL, Greiner HM, Lilles L, Mangano FT. Imaging Spectrum of
Cortical Dysplasias in Children. Semin Roentgenol. 2014: 99-111

• Leventer RJ, Guerrini R, Dobyns WB. Malformations of Cortical

Development and Epilepsy. Dialogues in Clin Neurosci. 2008: 47-62

• Kline-Fath B, Chapters 6.2 & 12.1. In: Fundamental and Advanced

Fetal Imaging Ultrasound and MRI. Philadelphia. Wolters-Kluwer.
2015. pp 184-219, 345-423