ArticlePDF Available

Malformations of Cerebral Cortical Development: Clinical and Imaging Features

Authors:

Abstract and Figures

Malformations of cortical development (MCDs) comprise a variable spectrum of clinical, neuroradiologic, and histopathologic findings. MCDs are increasingly recognized as significant causes of epilepsy, developmental delays, and congenital neurologic deficits. The aim of this study was to determine the types, relative frequencies, and clinical and imaging features of MCDs. Data were collected in 2 hospitals and a medical imaging center during a 9-year period. Twenty-six patients (17 men and 9 women; age range, 5 mo to 29 y; mean age, 10.8 y) with an MCD were evaluated. The results of magnetic resonance imaging studies were retrospectively reviewed for type, extension, and classification of the malformations and for associated findings. Clinical findings were obtained by a review of the patients' medical records. Of the patients studied, epilepsy was present in 65%, mental and/or motor retardation was identified in 34.6%, and skin lesions were noted in 15%. The following types of MCD were identified: malformations of the heterotopic gray matter in 35% of the subjects, focal cortical dysplasia (23%), subependymal and cortical tubers (19%), pachygyria (15%), polymicrogyria (15%), schizencephaly (15%), and type 1 lissencephaly (8%). Approximately, 27% of the subjects had the following other types of cerebral malformation: callosal agenesis (8%), ventriculomegaly (8%), or agenesis of the septum pellucidum (4%). Our study indicated that the most common forms of MCD are heterotopia and focal cortical dysplasia. Patients with an MCD tended to have a higher prevalence of epilepsy, developmental delays, and neurologic deficits. Most patients with heterotopia had other malformations of cortical dysplasia. Some patients with an MCD also exhibited other malformations of the brain.
Content may be subject to copyright.
Malformations of Cerebral Cortical Development
Clinical and Imaging Features
Zafer Koc, MD,* Filiz Koc, MD,
w
and Haydar Kaderoglu, MD
z
Abstract: Malformations of cortical development (MCDs)
comprise a variable spectrum of clinical, neuroradiologic, and
histopathologic findings. MCDs are increasingly recognized as
significant causes of epilepsy, developmental delays, and
congenital neurologic deficits. The aim of this study was to
determine the types, relative frequencies, and clinical and
imaging features of MCDs. Data were collected in 2 hospitals
and a medical imaging center during a 9-year period. Twenty-six
patients (17 men and 9 women; age range, 5 mo to 29 y; mean
age, 10.8 y) with an MCD were evaluated. The results of
magnetic resonance imaging studies were retrospectively re-
viewed for type, extension, and classification of the malforma-
tions and for associated findings. Clinical findings were obtained
by a review of the patients’ medical records. Of the patients
studied, epilepsy was present in 65%, mental and/or motor
retardation was identified in 34.6%, and skin lesions were noted
in 15%. The following types of MCD were identified:
malformations of the heterotopic gray matter in 35% of the
subjects, focal cortical dysplasia (23%), subependymal and
cortical tubers (19%), pachygyria (15%), polymicrogyria (15%),
schizencephaly (15%), and type 1 lissencephaly (8%). Approxi-
mately, 27% of the subjects had the following other types of
cerebral malformation: callosal agenesis (8%), ventriculomegaly
(8%), or agenesis of the septum pellucidum (4%). Our study
indicated that the most common forms of MCD are heterotopia
and focal cortical dysplasia. Patients with an MCD tended to
have a higher prevalence of epilepsy, developmental delays, and
neurologic deficits. Most patients with heterotopia had other
malformations of cortical dysplasia. Some patients with an
MCD also exhibited other malformations of the brain.
Key Words: cortical malformation, cortical dysplasia, lissence-
phaly, clinical findings, magnetic resonance imaging
(Neurosurg Q 2007;17:23–28)
Malformations of cortical development (MCDs) are
rare disorders that represent patterns of aberrant
architectural organization of the cerebral cortex and
adjacent white matter. It is rare to diagnose those
malformations in utero until late in the pregnancy,
although the presence of microcephaly or abnormalities
of the corpus callosum, lateral ventricles, or cerebellum
may be the first detectable sign of a more extensive brain
malformation involving the cerebral cortex. Patients with
an MCD usually present during early childhood with
drug-resistant epilepsy, mental and/or psychomotor
developmental delay, or hemiparesis.
1–5
Magnetic resonance imaging (MRI) provides the
anatomic detail necessary for the diagnosis of MCDs,
which may appear as a focal lesion or multilobar lesions
manifested as increased thickness of gray matter, blurred
boundaries toward the near white matter, or an abnormal
gyral pattern.
6–8
The early identification and selection of patients
who may be candidates for the surgical treatment of
epilepsy are important in the diagnostic evaluation of
patients with an MCD. Surgical intervention at an
appropriate time in select patients offers a chance for
freedom from seizures and improved cognitive outcome.
2
MCDs are more often diagnosed now than before
the advent of MRI.
9,10
The aim of this study was to
determine the types, relative frequency, clinical findings,
and imaging features of MCDs.
MATERIALS AND METHODS
Data from 26 patients (17 men and 9 women; age
range, 5 mo to 29 y; mean age ± SD, 10.8 ± 8.3 y) with a
diagnosed MCD were retrospectively analyzed. Patients’
data were collected from 2 hospitals and a medical
imaging center during a 9-year period. The results of MRI
studies of the cerebral malformations in all patients were
obtained by means of 3 different MRI units. An
experienced radiologist analyzed each subject’s MRI scan
of the brain. The classification, morphologic type and
shape, and site of the MCD were recorded, as were the
presence and degree of associated malformations and
anomalies. An experienced neurologist reviewed and
recorded each patient’s presenting complaints, clinical
findings, results of neurologic evaluations, electroence-
phalographic reports, and results of follow-up.
RESULTS
The clinical features and MRI findings of the 26
patients are summarized in the Table 1. The patients’
presenting complaints were primarily as follows: seizure
Copyright r2007 by Lippincott Williams & Wilkins
From the *Department of Radiology, Baskent University School of
Medicine; wThe Department of Neurology, Cukurova University
School of Medicine; and zThe Neurotip Medical Imaging Center,
Adana, Turkey.
Reprints: Zafer Koc, MD, Department of Radiology, Baskent
University School of Medicine, Adana, Turkey (e-mail: zaferkoc@
superonline.com).
ORIGINAL ARTICLE
Neurosurg Q Volume 17, Number 1, March 2007 23
TABLE 1. Imaging and Clinical Findings in 26 Patients With Malformation of Cerebral Cortical Development
Imaging Findings (Brain MRI) Clinical Findings
Patient
No.
Age
(y)/Sex
Malformation of Cortical Development,
Location Additional Findings Presenting Complaints Associated Clinical Findings
1 6/F Classic type 1 lissencephaly and a diffuse, flail,
thickened cortex
Ventriculomegaly Seizures Myoclonic epilepsy, spastic
quadriparesis, MR
2 5 Mo/M Bilateral parietal open lip schizencephaly and
heterotopia
Afebrile convulsions Infantile spasm and motor
retardation
3 16/M Right parietal polymicrogyria, cortical
dysplasia, heterotopia
Seizures SPE
4 29/F Bilateral diffuse subependymal nodular
heterotopia
Seizures CPE
5 11/M Right parietal focal cortical dysplasia and
subependymal heterotopia
Aqueductal stenosis and cerebellar
hypoplasia, Dandy-Walker variant
Seizures SPE
6 28/F Cortical hamartomas and TS Subependymal calcified nodules Skin lesions and
abdominal distension
Renal AML
7 3/M Bifrontal pachygyria (incomplete
lissencephaly
Focal conical thickening and relative loss
of gray-white matter interface
Developmental delay MMR, pyramidal signs, facial
dysmorphia
8 1/M Conical hamartoma and TS Adenoma sebaceum None
9 24/F Left frontal focal conical dysplasia Focal conical thickening Seizures CPE
10 10/M Left parietal open-lip schizencephaly and
heterotopia
Callosal agenesis and left frontoparietal
hemispheric dysplasia
Seizures SGE, MR, dysmorphic changes
11 18/M Bilateral (right frontal and left parietal) open-
lip schizencephaly and heterotopia
Right temporal arachnoid cyst Development delay and
seizures
CPE, spastic quadriplegia, MMR,
abnormal conjugate gaze
12 I7/F Right parietal local conical dysplasia Agenesis of septum pellucidum Seizures SGE
13 5/M Bilateral (right parietal and left frontal) open-
lip schizencephaly, heterotopia, left frontal
polymicrogyria
Seizures Myoclonic partial epilepsy
14 1/F Classical type I lissencephaly Ventriculomegaly Developmental delay MMR
15 1/F Conical hamartomas and TS Cortical and subependymal nodules Development delay None
16 15/M Conical hamartomas and TS Giant cell astrocytoma and cortical and
subependymal nodules
Skin lesions None
17 11/M Left frontal polymicrogyria and subcortical
heterotopia
Seizures CPE
18 6 Mo/M Bitemporal pachygyria (incomplete
lissencephaly)
Afebrile convulsions and
development delay
Myoclonic and generalized tonic
seizures, hypotonia
19 7/M Left temporal focal conical dysplasia Dysmorphic changes in the left temporal
area
Behavioral disorder and
seizures
Dysmorphic face. MR, CPE
20 5/M Left parietal focal conical dysplasia Left parietal corneal-subcortical lesion
high signal on T2-weighted images
Seizures SGE
21 15/F Bilateral subependymal nodular heterotopia Seizures CPE
22 16/M Bilateral temporoparietal pachygyria and
occipital polymicrogyria (incomplete
lissencephaly)
Developmental delay Pyramidal signs and MMR
23 11/M Conical hamartomas and TS Subependymal calcified nodules and a
mass adjacent to the foramen of Monro
Skin lesions Multiple retinal nodular hamartomas
24 12/M Right frontal focal conical dysplasia Dysplastic area of the right frontal and
anterior interhemispheric
Headache No
25 16/F Left subependymal focal nodular heterotopia Seizures CPE
26 2/M Bilateral frontal pachygyri (incomplete
lissencephaly)
Callosal agenesis Status epilepticus Myoclonic and generalized tonic
seizures, MMR
AML indicates angiomyolipoma; CPE complex partial epilepsy; F, female; M, male; MMR, mental-motor retardation; MR, mental retardation; SPE, simple partial epilepsy; SGE, secondary generalized epilepsy;
TS, tuberous sclerosis.
Koc et al Neurosurg Q Volume 17, Number 1, March 2007
24 r2007 Lippincott Williams & Wilkins
in 14 patients, developmental delay,
6
afebrile convulsion,
2
skin lesions,
4
status epilepticus,
1
headache,
1
and beha-
vioral disorder.
1
A family history of epilepsy was negative
in all patients, although epilepsy was a major clinical
finding in 17 (65.4%) of the patients studied. Eleven of
those patients experienced partial seizures, and 3 ex-
hibited generalized epileptic seizures. Temporal lobe
seizures were thought to afflict 5 of those patients, and
the remaining 6 were thought to experience seizures from
extratemporal (frontal and parietal) foci.
Heterotopic gray matter, the most frequent type of
the MCD noted in the study, was identified in 9 (34.6%)
of the subjects. Subependymal (periventricular) hetero-
topic gray matter was identified in 4 (15.4%) of the
patients (Fig. 1). Heterotopia as an associated finding was
identified in 5 (19.2%) of the patients, most of whom had
schizencephaly. Schizencephaly with heterotopic gray
matter was identified in 4 (15.4%) of the patients
(Fig. 2), and agenesis of the septum pellucidum was
noted as an associated finding in 1 patient. Focal cortical
dysplasia (FCD) was identified in 6 (23%) of the patients,
4 (67%) of whom experienced seizures. Polymicrogyria
was identified in 4 (15.4%) of the patients (Fig. 3).
Subependymal and cortical tubers (tuberous sclerosis)
were identified in 5 (19.2%) of the patients. Classic type 1
lissencephaly (agyria-pachygyria complex) (Fig. 4A) was
identified in 2 (7.7%) patients, and pachygyria was
identified in 4 (15.4%) (Figs. 4B–D). Associated other
malformations of the brain were identified in 7 (26.9%)
of the patients studied. Callosal agenesis was identified in
2 patients, and ventriculomegaly was identified in
2 patients. Aqueductal stenosis and cerebellar hypoplasia
(the Dandy-Walker variant), a temporal arachnoid cyst,
and agenesis of the septum pellucidum were observed in
1 patient each.
DISCUSSION
MCDs represent patterns of aberrant architectural
organization of the cerebral cortex and adjacent white
matter.
11
Many of these malformations develop during
the neonatal period or infancy.
12–16
Embryologic devel-
opment of the cerebral cortex is a complex process that
can be summarized in 3 main steps: cell proliferation,
neuronal migration, and cortical organization.
11
Microcephaly is thought to result from decreased
FIGURE 2. A and B, Patient 2. A, Axial
T1-weighted spin echo and B, T2-
weighted turbo spin echo brain MRIs
show bilateral parietal open-lip schizen-
cephaly (black arrows, B) and hetero-
topic gray matter on both sides of the
fissures (open arrows, B).
FIGURE 1. A to C, Patient 4. A, Axial T1-weighted spin echo; B, axial T2-weighted turbo spin echo; and C, coronal T2-weighted
turbo spin echo brain MRIs show diffuse, subependymal, well-defined small nodules of heterotopic gray matter along the lateral
borders of the lateral ventricles (arrows, A–C) that appear isointense with normal gray matter.
Neurosurg Q Volume 17, Number 1, March 2007 Cerebral Cortical Malfunctions
r2007 Lippincott Williams & Wilkins 25
cell proliferation and increased apoptosis, and macro-
cephaly is attributed to increased cell proliferation and
decreased apoptosis. Cortical hamartomas of tuberous
sclerosis, cortical dysplasia with balloon cells, and
hemirnegalencephaly are thought to result from the
abnormal proliferation of neuronal cells.
11
Heterotopia
of the gray matter, lissencephaly and subcortical band
heterotopia, or cobblestone complex and congenital
muscular dystrophy are thought to result from abnormal
neuronal migration.
11
When there is a primary, limited,
pure deficit in neuronal migration onset, the remaining
neuroblasts may migrate normally to form the regular
cortex, and subependymal (periventricular) heterotopia
develops. When the later stage of neuronal migration and
cortical organization is impaired, polymicrogyria, schi-
zencephaly, cortical dysplasia without balloon cells, or
microdysgenesia may develop.
12
The causes of MCDs are heterogeneous and may be
genetic or acquired.
10
These malformations may be isolated
findings or associated with other cortical and brain
malformations such as callosal agenesis or dysgenesis,
hydrocephalus, cerebellar hypoplasia, or mega cisterna
magna.
12–15
In our study, associated other types of brain
malformations were observed in 27% of the patients.
MCDs are a frequent cause of symptomatic focal
epilepsy in childhood and adulthood.
1,5,9,10,16
Although
the exact prevalence of MCD is unknown, its incidence in
patients who undergo surgical treatment for epilepsy has
been shown to vary from 12% to 40% and is more
frequent in children.
17
In particular, FCDs are increas-
ingly diagnosed in epileptic patients as a result of
improved MRI techniques. About 76% of the patients
with FCDs are thought to suffer from drug-resistant
epilepsy.
18–21
Surgical treatment offers a promising
therapeutic option for those individuals.
22
Our study
revealed that most of the patients with an MCD present
with that disorder in the neonatal period or during
childhood and that most of those patients (65%) also had
had epilepsy. This finding is consistent with data in the
literature.
2,12,23
In their study, Leventer and colleagues
23
reported
no sex-related prevalence of MCDs in pediatric patients
but noted that among adult patients, more women than
men had an MCD. In our series, we noted MCDs in more
boys than girls, but we found a female predominance of
those disorders in adults.
In many individuals with FCD, epilepsy manifests
early. However, in a few such patients, epilepsy does
FIGURE 3. A to C, Patient 3. A, Axial T1-weighted spin echo; B, axial T2-weighted turbo spin echo; and C, coronal T2-weighted
turbo spin echo brain MRIs show right parietal polymicrogyria (open arrows, A–C). Cortical dysplasia extends to the posterior
frontal region. Right parietal gyral asymmetry can be seen clearly, especially when compared with the left side. Note the right
parietal subcortical linear hyperintensities representing indistinct cortex-subcortical white-matter boundaries (arrows, B).
FIGURE 4. A to D, Patient 14. A, Axial proton density intermediate MRI of a patient with type 1 lissencephaly shows a thin,
smooth outer layer (arrow) and a thick inner band of gray matter with distinct gray-white matter boundaries (open arrow).
Primitive shallow sylvian fissures give the brain a typical ‘‘hour-glass’’ configuration. Patient 22. B, Axial T1-weighted spin echo; C,
proton density intermediate; and D, T2-weighted turbo spin echo brain MRIs reveal temporoparietal pachygyria with shallow sulci
and flat gyri (open arrow, B–D) and polymicrogyria of the bilateral occipital cortex (white arrows, B).
Koc et al Neurosurg Q Volume 17, Number 1, March 2007
26 r2007 Lippincott Williams & Wilkins
appear until the second to sixth decade of life. In some
patients, epilepsy can be controlled over a certain period
of time by antiepileptic drugs. Factors contributing to the
epileptogenicity of FCDs or influence the pharmacologic
treatment of epilepsy are unknown. Although dysgenesis of
the cortex and misconnection resulting from neuronal
malpositioning are usually thought to cause epilepsy, a
modified hypothesis suggests that the primary cause of
epilepsy might be abnormal interneuronal connectivity
rather than simply neuronal malpositioning.
4,17
In our
study, most epileptic patients with FCD began to experience
the symptoms of epilepsy during their first decade of life.
It has been suggested that MCDs most frequently
develop in the frontal lobes of the brain, which account
for the largest volume of brain tissue.
23
However, another
investigator reported that MCDs most frequently affected
the extratemporal areas.
24
We found the frontal and
parietal lobe to be the areas most frequently affected by
an MCD.
Although enhanced computed tomography or MRI
is recommended for the routine imaging of epileptic
patients with a possible MCD, MRI is sufficient as sole
imaging modality in most patients.
25
MRI is the most
effective noninvasive imaging method for the in vivo
diagnosis of MCD; its reported sensitivity ranges between
50% and 70%.
12,26
MRI findings of MCDs reveal a
spectrum of cytoarchitectural abnormalities that affect
the cortical and subcortical structure.
3
Cortical thicken-
ing with or without signal change, abnormal gyral
formation, and focal subcortical signal changes have
been reported as common MRI findings in patients with a
focal MCD.
27
Periventricular nodular heterotopia is a malforma-
tion of cortical development characterized by single or
multiple nodules of gray matter along the external walls
of the lateral ventricles.
12
Those nodules usually bulge
into the ventricle and may be multiple, bilateral, or
unilateral. MRI findings of FCD include focal cortical
thickening, alterations in the sulci and gyri patterns,
blurred boundaries between gray-matter and white-
matter transition, and T2-signal elongation of the
subcortical white matter that tapers toward the ventri-
cle.
3,5
MRI findings of the pachygyria-polymicrogyria
(incomplete lissencephaly) include figure-of-8 brain mor-
phology, vertical shallow sylvian fissures, and a smooth
brain with a thick cortex.
28
Polymicrogyria can be seen as
an irregular cortical surface: a small, fine, undulating
cortex with normal thickness in patients younger than
12 months; a thick bumpy cortex in patients older than
12 months; and an indistinct cortical-white-matter junc-
tion.
28
Lissencephaly type 1 appears as a distinct gray-
white matter boundary or an ‘‘hour-glass’’ configuration
of the brain on the results of Tl-weighted and T2-
weighted MRI. Periventricular and subcortical white
matter calcification can be seen in patients with cyto-
megalovirus-related lissencephaly on T2-weighted gradi-
ent echo MRI.
28
Schizencephaly is seen as an infolding of
the gray matter, which may be nodular, pachygyric or
polygyric, along the transmantle clefts. Heterotopia or an
absence or partially deficient septum pellucidum may be
associated findings.
28
Because problems of connectivity may be important
in the clinical outcome of patients with epilepsy, diffusion
tensor imaging and white matter tractography are helpful
new tools for the assessment of brain connectivity via
high-field MRI.
29
It has been suggested that using voxel-
based morphometry to perform automated analysis of
MRI scans can reveal cortical abnormalities overlooked
during visual inspection.
5
Patients with MCD represent a heterogeneous
group, most of these patients present with epilepsy at
different age of onset. Greater knowledge about the
genetic basis of MCDs and the mechanisms of brain
development has resulted in a continual improvement of
the treatment of MCDs. MRI studies of the brain reveal a
wide spectrum of findings that represent different imaging
features of MCDs. With the progressive improvement of
MRI techniques, MCDs are being seen in vivo with
increasing frequency in patients with epilepsy, and
certain types of epilepsy previously considered crypto-
genetic are now recognized as being associated
with MCDs. More comprehensive and detailed MRI
characterization and determining the exact location of
these lesions can help in presurgical evaluations and in
modifying the surgical interventions that will improve the
patient’s prognosis.
CONCLUSIONS
The most common forms of MCD are heterotopia
and FCD. Patients with an MCD tend to have a higher
incidence of epilepsy, developmental delays, and neuro-
logic deficits. Some patients with an MCD also exhibit
other malformations of the brain, such as callosal
agenesia, cerebellar hypoplasia, or mega cisterna magna,
and most patients with heterotopia have other malforma-
tions of cortical dysplasia.
REFERENCES
1. Koc F, Bozdemir H, Koc Z, et al. A case of schizencephaly
associated with skeletal deformities and abnormal eye movements.
Neurosurgery Q. 2005;15:72–74.
2. Gupta A, Carreno M, Wyllie E, et al. Hemispheric malformations of
cortical development. Neurology. 2004;62(6 suppl 3):S20–S26.
3. Hildebrandt M, Pieper T, Winkler P, et al. Neuropathological
spectrum of cortical dysplasia in children with severe focal
epilepsies. Acta Neuropathol (Bed). 2005;110:1–11. [Epub 2005
June 17].
4. Sarnat HB, Menkes JH. Microcephaly. In: Menkes JH, Sarnat HB,
eds. Child Neurology. 6th ed. Philadelphia, PA: Lippincott Williams
& Wilkins; 2000:348–354.
5. Bonilha L, Montenegro MA, Rorden C, et al. Voxel-based
morphometry reveals excess gray matter concentration in patients
with focal cortical dysplasia. Epilepsia. 2006;47:908–915.
6. Colliot O, Bernasconi N, Khalili N, et al. Individual voxel-based
analysis of gray matter in focal cortical dysplasia. Neuroimage.
2006;29:162–171.
7. Colliot O, Antel SB, Naessens VB, et al. In vivo profiling of focal
cortical dysplasia on high-resolution MRI with computational
models. Epilepsia. 2006;47:134–142.
8. Urbach H, Scheffler B, Heinrichsmeier T, et al. Focal cortical
dysplasia of Taylor’s balloon cell type: a clinicopathological entity
Neurosurg Q Volume 17, Number 1, March 2007 Cerebral Cortical Malfunctions
r2007 Lippincott Williams & Wilkins 27
with characteristic neuroimaging and histopathological features,
and favorable postsurgical outcome. Epilepsia. 2002;43:33–40.
9. Barkovich AJ, Kuzniecky RI, Jackson GD, et al. Classification
system for malformations of cortical development: update 2001.
Neurology. 2001;57:2168–2178.
10. Barkovich AJ, Kuzniecky RI, Jackson GD, et al. A developmental
and genetic classification for malformations of cortical development.
Neurology. 2005;65:1873–1887.
11. Barkovich AJ, Kuzniecky RI, Dobyns WB, et al. A classification
scheme for malformations of cortical development. Neuropediatrics.
1996;27:59–63.
12. d’Orsi G, Tinuper P, Bisulli F, et al. Clinical features and long term
outcome of epilepsy in periventricular nodular heterotopia. Simple
compared with plus forms. J Neurol Neurosurg Psychiatry. 2004;
75:873–878.
13. Bargallo N, Puerto B, De Juan C, et al. Hereditary subependyma1
heterotopia associated with mega cisterna magna: antenatal
diagnosis with magnetic resonance imaging. Ultrasound Obstet
Gynecol. 2002;20:869.
14. Koc Z, Koc F. Epilepsia with severe callosal hypogenesia, lipomas
and single anterior cerebral artery. Neurosurg Q. 2005;15:164–166.
15. Koc Z, Koc F, Kizilkilic O, et al. Imaging and clinical findings of
intracranial lipomas. Neurosurg Q. 2005;15:164–166.
16. Fauser S, Huppertz HJ, Bast T, et al. Clinical characteristics in focal
cortical dysplasia: a retrospective evaluation in a series of 120
patients. Brain. 2006;129(Pt 7):1907–1916.
17. Keene DL, Jimenez CC, Ventureyra E. Cortical microdysplasia and
surgical outcome in refractory epilepsy of childhood. Pediatr
Neurosurg. 1998;29:69–72.
18. Semah F, Picot MC, Adam C, et al. Is the underlying cause of
epilepsy a major prognostic factor for recurrence? Neurology.
1998;51:1256–1262.
19. Kassubek J, Huppertz HJ, Spreer J, et al. Detection and localization
of focal cortical dysplasia by voxel-based 3-D MRI analysis.
Epilepsia. 2002;43:596–602.
20. Wilke M, Holland SK, Myseros JS, et al. Functional magnetic
resonance imaging in pediatrics. Neuropediatrics. 2003;34:225–233.
21. Huppertz HJ, Grimm C, Fauser S, et al. Enhanced visualiza-
tion of blurred gray-white matter junctions in focal cortical
dysplasia by voxel-based 3D MRI analysis. Epilepsy Res. 2005;
67:35–50.
22. Fauser S, Schulze-Bonhage A, Honegger J, et al. Focal cortical
dysplasias: surgical outcome in 67 patients in relation to histo-
logical subtypes and dual pathology. Brain. 2004;127(Pt 11):
2406–2418.
23. Leventer RJ, Phelan EM, Coleman LT, et al. Clinical and imaging
features of cortical malformations in childhood. Neurology.
1999;53:715–722.
24. Hirabayashi S, Binnie CD, Janota I, et al. Surgical treatment of
epilepsy due to cortical dysplasia: clinical and EEG findings.
J Neurol Neurosurg Psychiatry. 1993;56:765–770.
25. Whiting S, Duchowny M. Clinical spectrum of cortical dysplasia in
childhood: diagnosis and treatment issues. J Child Neural. 1999;
14:759–771.
26. Andreoli TE, Bennett JC, Carpenter CJ, et al. eds. Cecil
Essentials of Medicine. Philadelphia: WB Saunders Company; 1993:
841–850.
27. Lee SK, Choe G, Hong KS, et al. Neuroimaging findings of cortical
dyslamination with cytomegaly. Epilepsia. 2001;42:850–856.
28. Osborn AG. Congenital malformations. In: Osborn AG, ed.
Diagnostic Imaging Brain. lst ed. Altona: Amirsys; 2004:50–74.
29. Lim CC, Yin H, Loh NK, et al. Malformations of cortical
development: high-resolution MR and diffusion tensor imaging of
fiber tracts at 3T. AJNR Am J Neuroradiol. 2005;26:61–64.
Koc et al Neurosurg Q Volume 17, Number 1, March 2007
28 r2007 Lippincott Williams & Wilkins
... Migrational malformation rate in our study is lower than in the literature. 5,[23][24][25][26][27][28][29][30][31][32] Fifty-six percent of the patients were male, which is consistent with pediatric literature from our country. 5,29,33,34 In studies including pediatric populations, gender difference has not been noted. ...
... This rate is given as 40% to 61.4% in the literature. 5,[28][29][30]35 In our study, mean age of seizure onset was 21.4±35.9 months (median 5.5 months), and in 70% of the patients with epilepsy, seizures started within the first year of life. ...
... months in pediatric studies. 5,30,32,41 Differing from the literature, we included the microcephaly group in our study. Similar to our study, Yvette de Wit et al. 41 included the same group. ...
Article
Full-text available
Aim: The purpose of this study is to classify the malformations of cortical development in children according to the embryological formation, localization, and neurodevelopmental findings. Seizure/epilepsy and electrophysiological findings have also been compared. Material and methods: Seventy-five children (age: 1 month-16.5 years; 56% male) followed with the diagnosis of malformation of cortical development, in Marmara University Pendik Research and Educational Hospital Department of Pediatric Neurology, were included in the study. Their epilepsy characteristics, electroencephalogram (EEG) findings, and prognosis were reported. Neurodevelopmental characteristics were evaluated by the Bayley Scales of Infant and Toddler Development (Bayley-III) for the ages of 0-42 months (n = 30); the Denver Developmental Screening Test-II (DDST-II) for ages 42 months-6 years (n = 11); and the Wechsler Intelligence Scales for Children (WISC-R), used for children 6 years and older (n = 34). Results: The patients were classified as 44% premigrational (14.6% microcephaly, 24% tuberous sclerosis, 2.7% focal cortical dysplasia, 1.3% hemimegalencephaly, and 1.3% diffuse cortical dysgenesis); 17.3% migrational (14.6% lissencephaly, 2.7% heterotopia); and 38.6% postmigrational (14.6% schizencephaly, 24% polymicrogyria) developmentally. According to involved area, the classification was 34.7% hemispheric/multilobar, 33.3% diffuse, and 32% focal. Seventy-five percent of the patients had a history of epilepsy, and 92% were resistant to treatment. The seizures started before the age of 12 months in diffuse malformations, and epileptic encephalopathy was more common in microcephaly with a rate of 80% and lissencephaly with a rate of 54.5% in the first EEGs. Ninety-five percent of patients had at least one level of neurodevelopmental delay detected by DDST/Bayley-III; this was more common in patients with accompanying epilepsy (P < .05). As seen more commonly in patients with diffuse pathologies and intractable frequent seizures, mental retardation was detected by WISC-R in 64.5% of patients (P < .05). Conclusion: In cases with cortical developmental malformation, epilepsy/EEG features and neurodevelopmental prognosis can be predicted depending on the developmental process and type and extent of involvement. Patients should be followed up closely with EEG.
Article
Hemimegalencephaly is a disorder of neuronal proliferation that causes an overgrowth of all or part of a cerebral hemisphere. Its pathogenesis is still unknown. We present the case of an adult patient with a history of childhood-onset epilepsy, which was refractory to medical treatment and associated with moderate mental retardation. He was admitted to the hospital for seizure control. Magnetic resonance imaging showed hemispheric asymmetry with enlarged right cerebral hemisphere and poor gray-white matter differentiation. The objective of this paper is to present a rare cause of epilepsy that is usually diagnosed during childhood. Hemimegalencephaly should be suspected in cases of early onset of difficult-to-control epilepsy, especially when associated with macrocephaly and delayed psychomotor development. Timely indication for neuroimaging allows establishing the diagnosis and providing other treatment options.
Article
Full-text available
Intracranial lipomas (ICLs) are rare congenital malformations associated with some central nervous system anomalies and clinical findings. The aims of this study were to assess the locations, associated malformations, and imaging and clinical findings of patients with ICLs. Based on published reports, the neuroradiologic features, clinical symptoms and signs, differential diagnosis, and surgical indications are discussed. Seventeen cases of ICL were reviewed, on which the results of neurologic and radiologic examinations were based, including computed tomography (CT) and magnetic resonance imaging (MRI) findings. A total of 20 lipomas were observed in 17 patients. The locations of the lipomas were interhemispheric fissure and/or callosal (45%), choroid plexus and/or intraventricular (15%), pericallosal (10%), the quadrigeminal plate and/or superior cerebellar cistern (10%), the prepontine cistern (10%), hypothalamic and/or suprasellar (5%), and the Sylvian fissure (5%), respectively. Associated midline anomalies were observed in 3 patients with callosal and/or pericallosal lipoma and in 1 patient with a Sylvian fissure lipoma. Two patients had epilepsia. One patient had a lipoma of the quadrigeminal plate cistern causing obstructive hydrocephalus by compression and partial obstruction of the aqueduct. Presenting complaints and results of the neurologic examinations were not associated with lipomas in the other 14 patients. CT and MRI easily showed the fatty content of the ICLs and associated anomalies in all patients. ICLs are mostly located midline and discovered incidentally. Sometimes, there are associated midline anomalies and vascular variants; the most common associated neurologic symptom is epilepsy. They rarely require surgical intervention.
Article
Full-text available
Schizencephaly is an extremely rare developmental disorder characterized by abnormal clefts in the brain's cerebral hemispheres. The major clinical features are mental-motor retardation, seizures, microcephaly, and hemiparesis or quadriparesis. A male patient with schizencephaly who has spastic quadriparesis, optic atrophy, abnormal eye movements, nystagmus, and skeletal deformities is presented.
Article
Full-text available
An interhemispheric lipoma is rare and is often associated with agenesis or hypogenesis of the corpus callosum. A 14-year-old girl who lost consciousness was brought to emergency room. It was stated that she had had a convulsion. During the neurologic examination, generalized tonic-clonic seizures were observed. Hypogenesis of the corpus callosum, interhemispheric and intraventricular lipomas, a single anterior cerebral artery, and mild hypoplasia in the cingulate gyri were observed on cerebral computed tomography and magnetic resonance imaging.
Article
Full-text available
Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.
Article
Management of Venous strokes with the KEM Protocol. Our experience in management of acute and sub-acute cases of venous strokes with heparin or local thrombolysis with urokinase according to KEM Hospital, INR protocol will be presented. All patients included had angiographically proven cerebral venous sinus thrombosis. Patients were classified according to clinical status scale into mild1-3 and severe clinical grade4-6. The study was divided into three phases. Phase I included 27 patients all treated with systemic heparin. Phase Il included 72 patients, 30 were in severe clinical grade and 52 in mild. 26 were thrombolysed with 14 in severe and 12 in mild clinical grade. A prospective study was carried out in 180 patients according to a defined protocol in Phase 111. 133 of these were in mild clinical grade and 47 in the severe. 67 patients were thrombolysed. In the thrombolysed group 27 patients were in mild & 40 in severe clinical grade. 113 patients were treated with systemic heparin. Adjunctive medical therapy was given as required. Following acute management all were anticoagulated for 6 months. Phase I showed 100% mortality in severe clinical group and 23.53% in mild clinical grade. In Phase II mortality in severe clinical group was 75% in non-thrombolysed group and 57.14% in thrombolysed group. There were no deaths in mild clinical grade patients who were thrombolysed. In Phase 111 in Severe clinical grade, mortality in thrombolysed group was 35% and non-thrombolysed group was 100%. In mild clinical group there was 100% recovery in thrombolysed group and 94.4% in non-thrombolysed group. There was complete clinical recovery in 84.4% of patients in Phase 111. 2 patients had intracranial haemorrhage on Urokinase therapy. The line of treatment of venous strokes with heparin or local thrombolysis can be decided according to the KEM protocol. Patients with Cerebral venous sinus thrombosis had better outcome when managed according to our protocol.
Article
Disorders of cortical development form a spectrum of lesions produced by insults to the developing neocortex. These conditions typically first manifest in childhood with epilepsy, developmental delay, and focal neurologic signs. Although the clinical and electrophysiologic findings are often nonspecific, high-resolution magnetic resonance imaging facilitates diagnosis during life, and assists in delineating specific clinical syndromes. While many patients are dysmorphic and severely affected by mental retardation and epilepsy, some have normal or near-normal cognitive function and no seizures. Molecular studies of dysplastic cortex are providing new insights into the basic mechanisms of brain function and development, while pathologic analysis of tissue removed at surgery is helping to define epileptic circuitry. 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. (J Child Neurol 1999;14:759-771).
Article
Disorders of cortical development form a spectrum of lesions produced by insults to the developing neocortex. These conditions typically first manifest in childhood with epilepsy, developmental delay, and focal neurologic signs. Although the clinical and electrophysiologic findings are often nonspecific, high-resolution magnetic resonance imaging facilitates diagnosis during life, and assists in delineating specific clinical syndromes. While many patients are dysmorphic and severely affected by mental retardation and epilepsy, some have normal or near-normal cognitive function and no seizures. Molecular studies of dysplastic cortex are providing new insights into the basic mechanisms of brain function and development, while pathologic analysis of tissue removed at surgery is helping to define epileptic circuitry. 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.
Article
Malformations of the cerebral cortex are being recognized more frequently as a cause of epilepsy, developmental delay, neurological deficits, and mental retardation. Nonetheless, a standard nomenclature and classification system of these malformations, based upon state-of-the art knowledge derived from genetics, embryology, imaging, and pathology, has not been devised. In this manuscript, we propose such a classification system. Moreover, we have constructed the system such that both the framework and the classifications themselves are flexible and can be adapted as our knowledge of the embryology, genetics, imaging, and pathology of these disorders advances. We believe that the use of this classification system will help both clinicians and researchers to understand and think about these disorders and their causes better. In turn, we hope that this improved understanding will lead to further refinements in classification, to advances in our knowledge and, ultimately, to improvements in therapy.
Article
This paper examines the relationship between the degree and type of cortical microdysplasia as reported on pathological examination and the degree of seizure control after cortical resection in 70 children with medically refractory epilepsy. Cases selected for this review had to have had medically refractory epilepsy; had their first cortical resection before the age of 18 years, and have sufficient pathological material available for review. The pathological review was done blinded as to results of seizure control outcome postsurgery. Pathological material was classified to type and degree of microdysplasia, according to the classification scheme of Brannstrom. 11% of patients had no evidence of dysplasia; 77% had microdysplasia type 2, and 12% had focal dysplasia (type 3). No significant correlation between degree of seizure control postoperatively and type of microdysplasia was seen in this series.
Article
We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region. A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy. Seizure control (>1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS. In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.