Articles

Terminology and classification of the

cortical dysplasias
A. Palmini, MD, PhD; I. Najm, MD; G. Avanzini, MD; T. Babb, PhD; R. Guerrini, MD;
N. Foldvary-Schaefer, DO; G. Jackson, MD; H.O. Lüders, MD, PhD; R. Prayson, MD, PhD;
R. Spreafico, MD, PhD; and H.V. Vinters, MD

Abstract—Background: There have been difficulties in achieving a uniform terminology in the literature regarding issues
of classification with respect to focal cortical dysplasias (FCDs) associated with epilepsy. Objectives: To review and refine
the current terminology and classification issues of potential clinical relevance to epileptologists, neuroradiologists, and
neuropathologists dealing with FCD. Methods: A panel discussion of epileptologists, neuropathologists, and neuroradiolo-
gists with special expertise in FCD was held. Results: The panel proposed 1) a specific terminology for the different types
of abnormal cells encountered in the cerebral cortex of patients with FCD; 2) a reappraisal of the different histopathologic
abnormalities usually subsumed under the term “microdysgenesis,” and suggested that this terminology be abandoned;
and 3) a more detailed yet straightforward classification of the various histopathologic features that usually are included
under the heterogeneous term of “focal cortical dysplasia.” Conclusion: The panel hopes that these proposals will stimulate
the debate toward more specific clinical, imaging, histopathologic, and prognostic correlations in patients with FCD
associated with epilepsy.
NEUROLOGY 2004;62(Suppl 3):S2–S8

Malformations caused by abnormalities of cortical
development (MCD),1 also known as disorders of cor-
tical development,2 cortical dysplasias,3-5 cortical dys-
genesis,6,7 or neuronal migration disorders (NMDs),8,9
have been recognized increasingly in patients with
drug-resistant epilepsy. Advances in basic and clini-
cal neurosciences have opened exciting avenues for
research on the mechanisms of epileptogenicity and
cerebral dysfunction in patients with MCD.
The advent of various MRI techniques has facili-
tated the in vivo identification of a large group of corti-
cal malformations in patients with epilepsy.5,10-12 There
has been progress in the understanding of various
pathogenetic mechanisms,13-18 engineering and testing
of various animal models of MCD;19-21 description of
direct clinical-electrographic correlations,22-25 and the
delineation of surgical strategies26-29 for management of
the various types of MCD associated with epilepsy. De-
spite these advances, it has become obvious that there
was a lack of uniform, well-defined clinically sound
histopathologic nomenclature for and classification of
these disorders. Such classification may allow for fur-
ther progress in understanding these entities through
improved communication at the clinical/electrographic,
histopathologic, and basic scientific levels of research.
Previous studies indicated that the pathogenesis
of the various histopathologic patterns is multifacto-
rial: genetic mutations,13,14,30,31 in utero injuries at
different stages of brain development,6,32-35 and even
perinatal or postnatal insults may contribute to their
etiology.36,37 The type, timing, and severity of envi-
ronmental insults or the nature of genetic mutation
and the impact of an abnormal gene product at dif-
ferent stages of brain development will likely influ-
ence the expression of the histopathologic and
anatomic types of MCD.
Previous attempts to classifying MCDs provided
either simplistic or complex classification schemes
that addressed specific aspects of these disor-
ders.5,26,38 Thus far, the most comprehensive classifi-
cation is that proposed by Barkovich et al.,1 who
have included embryologic, histopathologic, imaging,
and genetic aspects within their scheme. The major
merit of this classification is its organization of the
various types of MCD within an embryologic-
pathophysiologic framework, recognizing that MCD
could be caused by abnormalities during specific
stages of cortical development (neuroglial prolifera-
tion and differentiation, neuronal migration, and
postmigratory cortical organization). This classifica-

From the Pontificia Universidade Católica do Rio Grande do Sul (PUCRS) (Dr. Palmini), Porto Alegre, Brazil; The Cleveland Clinic Foundation (Drs. Najm,
Foldvary-Schaefer, Lüders, and Prayson), Cleveland, OH; Istituto Nazionale Neurologico “C. Besta” (Drs. Avanzini and Spreafico), Milan, Italy; Wayne State
University (Dr. Babb), Detroit, MI; Istituto de Neuropsichiatria Infantile (R. Guerrini), University of Pisa, Italy; Austin Hospital (Dr. Jackson), Melbourne,
Australia; and University of California Los Angeles Medical Center (Dr. Vinters), Los Angeles, CA.
I.N. was supported by grants K08-NS02046 and R21-NS42354 from the NIH.
Address correspondence and reprint requests to André Palmini, Serviço de Neurologia, Hospital São Lucas da PUCRS, Avenida Ipiranga 6690, Porto Alegre,
RS, Brazil, CEP 90610-000; e-mail: apalmini@uol.com.br

S2 Copyright © 2004 by AAN Enterprises, Inc.

tion1 did not emphasize a key issue in current epilep-
tology, the existence of focal cortical dysplasias
(FCDs), which are localized malformations increas-
ingly associated with refractory seizures and cur-
rently operated on at most epilepsy centers.39-42 A
good clinical correlation to the different aspects of
the histopathologic findings within FCDs has not
been described.
Thus, we suggest that it may be time for a reap-
praisal of nomenclature and classification issues in
patients with MCD, particularly for those harboring
FCD and other subtle microscopic abnormalities,
usually encompassed under the term microdysgen-
esis. This panel of epileptologists working in the area
of epilepsy surgery, neuropathologists, neuroradiolo-
gists, and basic scientists attempted to organize a
scheme that could be of practical and broad applica-
tion. We hope that the use of the proposed classifica-
tion scheme in everyday practice and for research
purposes will refine and validate its usefulness.
Our proposal is divided into three parts: 1) defini-
tion of terminology for the histopathologic descrip-
tion of FCDs; 2) description of selected aspects of
FCDs; and 3) a classification proper, in which differ-
ent histopathologic subtypes are described and corre-
lated with their current status of identification by
MRI, as well as with some clinical features and prog-
nostic aspects.
Definition of terms: toward a uniform nomen-
clature. The first issue debated was the preferred
denomination for this entire group of entities. There
are “developmental” factors that may be independent
of the mechanism of injury (genetic, intrauterine, or
even perinatal) and that substantially affect cortical
mantle formation.36,37 Because one or more of the
mechanisms important in corticogenesis can be af-
fected and because even the malpositioning of nodu-
lar or laminar aggregates of neuroblasts and glial
cells in heterotopic positions actually represent in-
terferences with cortical formation (these cells were
destined originally for the cerebral cortex), the panel
agreed with the denomination “malformations due to
abnormal cortical development.” Accordingly, the
panel suggested that the denomination “cortical dys-
plasias” should be applied only to the subtype of
MCD in which the developmental abnormality is
strictly or mostly intracortical. Thus, FCD would be
a good term within this framework only. Additional
subdivision of FCD based on histologic/cellular char-
acteristics will be presented. Likewise, the term
“neuronal migration disorder,” historically applied to
all forms of MCD in the early 1990s,8,9 would suggest
that all MCDs were caused by predominant interfer-
ences with migratory mechanisms affecting cortical
neuronal precursors. It is clear that other pathoge-
netic mechanisms apply as well; therefore, NMDs
are more correctly considered a subtype of MCD.
Moreover, MCD would be descriptive of the micro-
dysgeneses that were proposed originally by
Meencke et al.43 to describe minimal, subtle abnor-
Figure 1. Cresylecht violet staining shows the dysmorphic
neurons. Note the high Nissl stain density and the various
directions of the neurons; scale bar, 50 ␮m.
malities of intracortical architecture in patients with
generalized epilepsies undergoing autopsy studies.
Furthermore, the panel thought that the following
terms should be either more clearly defined or
replaced.
Microdysgenesis. This term has been the focus of
significant confusion since it was proposed original-
ly.43 Some authors have used the term to describe
subtle derangements of focal cortical architecture
such as 1) cortical laminar disorganization; 2) single
(or small aggregates of) heterotopic white matter
neurons and neurons in the molecular layer; 3) per-
sistent subpial granular layer; and 4) marginal glio-
neuronal heterotopia.41 In contrast, others have used
the term microdysgenesis to describe any type of
MRI-negative MCD.44 Because many instances of
MRI-negative MCDs can be associated with severe
histopathologic abnormalities, including dysplastic
neurons and balloon cells, there is a clear histologic
lack of congruence between the two uses of the term
microdysgenesis.22,26,45-47 The panel recommended
that the use of the term microdysgenesis should be
abandoned. Because most of the mild abnormalities
reviewed by Mischel et al.41 involve cortical layer I, a
proposal was made to subdivide the mildest forms of
MCD into those characterized by ectopically placed
neurons in or adjacent to layer I, and those in which
abnormalities are outside layer I (see below).
Cellular abnormalities. Dysmorphic neurons.
These are misshapen cells with abnormal orienta-
tion, size, cytoskeletal structure, and atypical den-
dritic processes. Nissl substance can be seen in
clumps, and the cells are rich in cytoplasmic neuro-
filaments (SMI 31; figure 1).48,49
Balloon cells. These are abnormal cellular ele-
ments with a thin membrane; pale, glassy, and eo-
March 2004 NEUROLOGY 62(Suppl 3) S3

Figure 2. H-E staining shows a large balloon cell in the
subcortical white matter. Note the large opalescent cyto-
plasm and the eccentric nucleus; scale bar, 100 ␮m.
sinophilic cytoplasm; and eccentric nucleus (or
nuclei, because some are multinucleated). Balloon
cells usually are of increased size compared with
gemistocytic astrocytes. Previous immunocytochemi-
cal studies have shown that these cells have neuro-
nal or glial characteristics.49,50 Most balloon cells are
vimentin positive, but others are glial (e.g., glial
fibrillary acidic protein) or neuron-specific enolase/
MAP/NeuN-immunoreactive (Najm et al., personal
communication).49 These data suggest some degree of
heterogeneity among the cells with partial commit-
ment toward glial or neuronal differentiation (figure 2).
Giant neurons. These are neurons of increased
size (compared with layer V pyramidal neurons) with
central nuclei. However, they preserve a pyramidal
morphology (i.e., are not dysmorphic) and do not
overexpress cytoplasmic neurofilaments (figure 3).
Immature neurons. These are round (or oval)
cells, all homogeneous, with a large (immature) nu-
cleus and a thin rim of cytoplasm. They are not dys-
Figure 3. H-E staining shows a giant neuron with central
nucleus. Note the presence of smaller dysmorphic neurons;
scale bar, 100 ␮m.
S4 NEUROLOGY 62(Suppl 3) March 2004
morphic or giant but sometimes are seen in association
with giant or dysmorphic neurons. They are occasion-
ally the most common cell types in macroscopically vis-
ible heterotopic nodules.7,49
(Microscopic) neuronal heterotopias. These
microscopic abnormalities are mainly caused by ar-
chitectural disorganization. They are clusters of mis-
placed neurons. Conversely, the macroscopic
heterotopia (periventricular, subcortical nodular,
and band heterotopia) are grossly apparent well-
defined abnormalities of neuroblast migration (see
below).
Histopathology of FCDs. As discussed previ-
ously, there are several cellular elements, which may
occur in variable combinations, leading to specific
histopathologic features in cortical dysplastic lesions.
There is increasing information on correlations be-
tween the histopathologic and electroclinical and
MRI abnormalities of FCD.2,46,51-55 Thus, the panel
decided to re-evaluate the several histopathologic
scenarios that have been subsumed under the gen-
eral term “focal cortical dysplasias,” with a view to a
more clinically meaningful classification.
Over the years, there has been some degree of het-
erogeneity in the clinical, surgical, and histopathologic
literature, and terms like “focal cortical dysplasia,”
“mild cortical dysplasia,” “Taylor-type focal cortical
dysplasia,” “balloon cell dysplasia,” “non– balloon cell
dysplasia,” and “microdysgenesis” all have been ap-
plied to describe architectural and cellular abnormali-
ties of the cortical mantle.5,16,44,46,48,55,56 For example,
some authors use the descriptor Taylor-type FCD only
when balloon cells are present,16,57 whereas others, in-
cluding Taylor et al.3 in their original report, include
some patients whose lesions had dysmorphic neurons
but lacked balloon cells. Although the panel accepted
that a definitive understanding of the relevance of each
cell type or architectural abnormality among the vari-
ous possible combinations relies on further develop-
ments on the mechanisms of corticogenesis and their
relation to clinical and imaging findings, a tentative
practical approach was attempted.
As a first step, it was consensually accepted that
one or more of the following might be present in
these lesions: dyslamination and other mild abnor-
malities (architectural abnormalities), “immature”
neurons, giant neurons, dysmorphic neurons, and
balloon cells. The most frequent histopathologic pic-
tures combining these elements then were agreed on
and considered to be the following.
Isolated architectural abnormalities (dyslamina-
tion). These are intracortical lesions that are charac-
terized by dyslamination and columnar disorganiza-
tion. These lesions represent the mildest end of the
histopathologic spectrum of FCD and may most closely
approximate the original description of microdysgen-
esis. In the medial temporal lobe, particularly in the
hippocampus, abnormalities of the infolding of the den-
tate gyrus and focal dyslamination may occur.58
 Architectural abnormalities associated with giant
neurons. In these lesions, the defining abnormality
is the presence of giant neurons. These lesions do not
contain dysmorphic or balloon cells. Whether the
presence of these cells has any clinical meaning and
thus differentiates the lesions from those harboring
only dyslamination is unclear.
Architectural abnormalities associated with dys-
morphic neurons. Irrespective of the occasional co-
occurrence of giant or immature neurons, the
hallmark of these lesions is the presence of clearly
dysmorphic neurons as defined previously.48,49 Accu-
mulation of neurofilaments within neuronal cyto-
plasm of these cells leads to distorted morphology of
the perikarya, proximal axons, and dendrites. It is
theoretically conceivable that these reflect more se-
vere abnormalities from a histopathologic stand-
point.41 In the original publication of Taylor et al.,3 4
of 10 patients had this histopathologic picture.
Architectural abnormalities associated with dys-
morphic neurons and balloon cells. These lesions
are characterized mainly by the presence of balloon
cells that are intermixed typically with dysmorphic
neurons in patients with severe architectural disor-
ganization. Six of the 10 original patients reported
by Taylor et al.3 had a similar histopathologic pat-
tern. These lesions are considered to represent the
most severe end of the spectrum of histopathologic
abnormalities of FCD.41
There is preliminary evidence that the presence of
dysmorphic neurons, with or without balloon cells, is
associated with higher degrees of epileptogenicity.2
Moreover, recent studies suggest that the main his-
topathologic subtypes that show MRI abnormalities
are those that contain dysmorphic neurons with or
without balloon cells.4,46,47,54 These results suggest
the separation of the histologic subtypes as delin-
eated will allow much better electroclinical, imaging,
and histopathologic correlations.
A classification scheme: imaging, histopathol-
ogy, and potential clinical relevance. Consider-
ing the definition of terms and the re-evaluation of
the histopathologic scenarios mentioned here, the
following classification is proposed.
Mild MCD
Type I: with ectopically placed neurons in or adja-
cent to layer I
Type II: with microscopic neuronal heterotopia
outside layer I
Structural imaging: both types probably are not
detectable by current MRI techniques
Histopathology: as described previously
Potential clinical relevance. It has been shown
that these mild MCDs may be related to epilepsy and
other behavioral and cognitive abnormalities.44,59-61
Because diagnosis usually is retrospective, clear clin-
ical and epileptic profiles of patients with these mild
malformations are not available. Thus, there is some
Figure 4. Cresylecht violet staining of sections represent-
ing normal neocortex and type I, type IIA, and type IIB
malformations of cortical development; scale bar, 100 ␮m.
debate on the role of these mild changes in the cau-
sation of epilepsy in general but especially when the
histologic abnormalities are found in mesial tempo-
ral structures, leading to microscopic heterotopia in
the dentate or parahippocampal gyri.60,61 Likewise,
the association of mesial limbic malformations with
schizophrenia and autism has attracted the atten-
tion of nonepileptologists to the putative clinical con-
sequences of mild MCD.62-64
FCDs (figure 4)
Type I: no dysmorphic neurons or balloon cells
Type IA: isolated architectural abnormalities
(dyslamination, accompanied or not by other
abnormalities of mild MCD)
Type IB: architectural abnormalities, plus giant
or immature, but not dysmorphic neurons
Structural imaging: it is unclear at the time of this
report whether type I FCD as defined here can
be identified in vivo by current MRI techniques.
Should a common nomenclature be used by vari-
ous centers, it is likely that imaging-histo-
pathologic correlations soon will clarify this issue.
Histopathology: as described previously
Potential clinical relevance. It is likely that some
of these patients will have epilepsy, whereas others
will not; those without epilepsy may be either
asymptomatic or instead seek treatment for learning
disorders or other types of cognitive impairment.
There are no specific data delineating a clinical or
neurophysiologic profile of patients with epilepsy
and type IA/B FCDs. Because hitherto most of these
mild abnormalities defy in vivo imaging recognition,
the only available evidence is from patients undergo-
ing epilepsy surgery in whom such mild abnormali-
ties were the only histopathologic finding.5,55 This
suggests that at least some patients with type IA/B
FCD can have medically refractory epilepsy. How-
ever, whether this is a common occurrence or repre-
sents only the most severe end of a spectrum is
unclear. Interestingly, surgical patients in whom
these mild MCDs were found retrospectively tend to
have much better results compared with the surgical
results obtained from patients with other types of
FCDs.
March 2004 NEUROLOGY 62(Suppl 3) S5
 Type II: Taylor-type FCD (dysmorphic neurons
without or with balloon cells)
Type IIA: architectural abnormalities with dys-
morphic neurons but without balloon cells
Type IIB: architectural abnormalities with dys-
morphic neurons and balloon cells
Structural imaging: these are the focal lesions
most commonly identified on MRI. However, one
should be aware that several different imaging
possibilities might be observed in patients with
Taylor-type FCD. MRI can be either normal,45,47
despite the use of high-resolution techniques, or
may demonstrate one or more of the following
characteristics: 1) focal areas of increased corti-
cal thickness;46,47 2) blurring of the cortex (gray)/
white matter junction;51,54 3) increased signal on
T2-weighted, proton density, or fluid-attenuated
inversion recovery sequences (more likely to oc-
cur in balloon cell-containing lesions);51,54 and 4)
extension of cortical tissue with increased signal
from the surface to the ventricle (transmantle
dysplasia).65-67
Histopathology: as detailed previously
Potential clinical relevance. Type IIA/B FCDs
are characterized by truly abnormal, grossly dysmor-
phic cellular elements, which are accompanied by un-
questionable abnormalities in inhibitory and excitatory
neurotransmission. Data collected through immunocy-
tochemical studies support an increase in excitatory
amino acid neurotransmission and an overall decrease
in intralesional and perilesional inhibition.16,48,49 The
net result is a high degree of intrinsic epileptogenicity,
which has been demonstrated by experimental and
clinical studies.22,23,26,42,68,69 Most patients diagnosed by
imaging studies (see above) as having lesions identi-
fied as type IIA/B FCD have medically intractable
partial epilepsy, with frequently disabling motor and
secondary generalized seizures. Many patients have
a history of status epilepticus, including epilepsia
partialis continua, and scalp EEG and acute electro-
corticography often show continuous spiking or other
highly epileptogenic patterns, attesting to some type
of re-entrant excitatory circuitry unopposed by faulty
inhibition.26,52,55 These patients often are correctly di-
agnosed before surgery, but surgical results still are
not fully satisfactory in many of them. Issues related
to a preferential localization around the perirolandic
cortex and to a microscopic extension of abnormal
tissue beyond the MRI lesional margins often are
mentioned to explain unsatisfactory results.
Dysplastic tumors. There are at least two types
of tumor that may represent a more extreme end of
the histopathologic spectrum of FCDs. Dysembryo-
plastic neuroepithelial tumors (DNETs) and ganglio-
gliomas may be associated with surrounding cortical
regions displaying abnormal cytoarchitecture (dys-
lamination) and large, at times dysmorphic, neurons
and glial cells.70,71 Subcortical heterotopic neurons
also can be seen.40,72
S6 NEUROLOGY 62(Suppl 3) March 2004
Structural imaging and histopathology. Both le-
sions usually are restricted to the cortex and may
present a combination of cystic and calcified areas.
Perhaps the most striking imaging aspect is that the
MRI signal often is irregular and poorly delineated,
attesting to the presence of different histopathologic
elements and the association of perilesional dysplas-
tic and immediately subcortical heterotopic cells.
There is no perilesional edema or mass effect.40,72
Clinical relevance. DNETs and gangliogliomas
are (with rare exception) benign lesions from an on-
cologic point of view. However, they often are associ-
ated with medically refractory partial seizures,
which usually manifest clinically before 20 years of
age. Patients with DNETs and epilepsy may be
cured with surgery, providing complete resection is
feasible. Remaining tumoral or dysplastic tissue may
be associated with persistent seizures, despite major
lesion resection.40,72
Challenges for the future. This report repre-
sents an attempt toward a simple yet practical classi-
fication for FCDs that may be beneficial for clinicians
and researchers who are interested in the management
of FCDs and an understanding of mechanisms by
which they cause epilepsy. Some imaging and his-
topathologic correlations were suggested, but there has
been no attempt to include an embryologic perspective
in the classification. It is likely that advances in the
molecular neurobiology of these disorders will signifi-
cantly change our views in terms of pathogenesis. To
further understand these disorders and to validate the
usefulness of this proposed classification, there is need
for the following: 1) clinical-electrical-pathologic corre-
lations in patients with epilepsy who are undergoing
electrocorticographic and depth electrode recording
evaluations;73 2) imaging-pathologic-functional correla-
tions based on careful studies of surgically resected
cortical samples; and 3) cellular-molecular studies of
the mechanisms of epileptogenicity through direct cor-
relation with electrocorticographic data obtained
through invasive recordings.18
Note added in proof. Recent utilization of this classification
framework has generated initial data suggesting that the different
types of FCD indeed tend to be associated with some specific
anatomical, clinical, electrographic, and imaging characteris-
tics.74,75 Thus, Type I focal cortical dysplastic lesions have been
shown to be most often localized to the temporal lobes, to lack
highly specific electrographic patterns, and to present on MRI as
hypoplasia of the temporal pole and/or increased signal in the
white matter core, with poorly defined limits. On the other hand,
Type II (Taylor type) FCD has been increasingly shown to repre-
sent an extratemporal entity, with lesions localized to one of four
major anatomical subcompartments: frontal lobe only, fronto-
central, peri-rolandic, or in the posterior quadrant. In addition, it
has been confirmed that these lesions are frequently associated
with ictal-like patterns or direct cortical recordings.22,76,77 Finally, a
recent report advances one step further, suggesting that the sub-
divisions of Type II FCD may be differently related to ictal gener-
ation and preservation of function.78 In patients with peri-rolandic
FCD, those portions of the lesions classified as Type IIA were
shown to harbor the ictal onset zone and to retain motor function,
in contrast to those portions of the lesions containing balloon cells
(Type IIB), which were functionally silent and not associated with
seizure onset. If confirmed, these findings may have a significant
impact in surgical planning, and will emphasize even more the
need for in vivo MRI identification of subtypes of FCD.
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