Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008;10(1):47-62.
doi: 10.31887/DCNS.2008.10.1/rjleventer.

Malformations of cortical development and epilepsy

Richard J Leventer  1 , Renzo Guerrini, William B Dobyns
Affiliations
Review

Malformations of cortical development and epilepsy

Richard J Leventer et al. Dialogues Clin Neurosci. 2008.

Abstract
in English, Spanish, French

Malformations of cortical development (MCDs) are macroscopic or microscopic abnormalities of the cerebral cortex that arise as a consequence of an interruption to the normal steps of formation of the cortical plate. The human cortex develops its basic structure during the first two trimesters of pregnancy as a series of overlapping steps, beginning with proliferation and differentiation of neurons, which then migrate before finally organizing themselves in the developing cortex. Abnormalities at any of these stages, be they environmental or genetic in origin, may cause disruption of neuronal circuitry and predispose to a variety of clinical consequences, the most common of which is epileptic seizures. A large number of MCDs have now been described, each with characteristic pathological, clinical, and imaging features. The causes of many of these MCDs have been determined through the study of affected individuals, with many MCDs now established as being secondary to mutations in cortical development genes. This review will highlight the best-known of the human cortical malformations associated with epilepsy. The pathological, clinical, imaging, and etiologic features of each MCD will be summarized, with representative magnetic resonance imaging (MRI) images shown for each MCD. The malformations tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly, classical lissencephaly, subcortical band heterotopia, periventricular nodular heterotopia, polymicrogyria, and schizencephaly will be presented.

Las malformaciones del desarrollo cortical (MDC) son anormalidades macro o microscópicas de la corteza cerebral que surgen como consecuencia de una interrupción de las etapas normales en la formación de la placa cortical, La corteza cerebral desarrolla su estructura básica durante los dos primeros trimestres del embarazo como una serie de etapas sobrepuesitas, que se inician con la proliferación y diferenciación de neuronas las cuales luego migran antes de organizarse finalmente en la corteza desarrollada. Las anormalidades en cualquiera de estas etapas, sean ellas de origen ambiental o genético, pueden causar interrupción de los circuitos neuronales y predisponer a una variedad de consecuencias clínicas, siendo las más comunes las convulsiones epilépticas, Actualmente se ha descrito un gran número de MDC, cada una con sus características patológicas, clínicas y de imágenes. Las causas de gran parte de estas MDC se han determinado mediante el estudio de sujetos afectados, y actualmente se ha establecido que muchas de ellas son secundarias a mutaciones en genes del desarrollo cortical. Esta revisión destaca lo mejor conocido de las malformaciones corticales humanas asociadas con la epilepsia. Se resumen las características patológicas, clínicas, de imágenes y etiológicas de cada MDC, con imágenes representativas de resonancia nuclear magnética para cada una de ellas. Se presentan las malformaciones de la esclerosis tuberosa, displasia cortical focal, hemimegalencefalia, lisencefalia clásica, heterotopia subcortical en banda, heterotopia nodular periventricular, polimicrogiria y esquizencefalia.

Les malformations du développement cortical (MDC) sont des anomalies macroscopiques ou microscopiques du cortex cérébral qui surviennent comme conséquence d'une interruption des étapes normales de formation de la lame corticale. Le cortex humain développe ses structures de base pendant les deux premiers trimestres de la grossesse, par le biais d'une série d'étapes chevauchantes, commençant par la prolifération et la différenciation des neurones qui migrent ensuite avant de s'organiser finalement dans le cortex en développement. Les anomalies survenant à chacune de ces étapes, qu'elles soient d'origine environnementale ou génétique, peuvent interrompre le circuit neuronal et prédisposer à des conséquences cliniques variées, la plus fréquente étant les crises épileptiques. Un grand nombre de MDC ont été décrites à ce jour, chacune avec ses caractéristiques pathologiques, cliniques et d'imagerie propres. Les causes de la plupart de ces MDC ont été déterminées en étudiant les sujets atteints, et de nombreuses MDC seraient secondaires des mutations affectant des gènes du développement cortical. Cet article mettra en évidence les malformations corticales humaines les plus connues associées à l'épilepsie. Les caractéristiques pathologiques, cliniques, d'imagerie et étiologiques de chaque MDC seront résumées, des images d'IRM (imagerie par résonance magnétique) illustrant chacune d'entre elles. Les malformations telles la sclérose tubéreuse de Bourneville, la dysplasie corticale focale, l'hémiencéphalomégalie, la lissencéphalie classique, l'hétérotopie en bandes sous-corticale, l'hétérotopie nodulaire périventriculaire, la polymicrogyrie et la schizencéphalie seront présentées.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Imaging features of tuberous sclerosis. Axial T2 -weighted MRI (left) and contrast-enhanced axial T1 -weighted MRI (right). The image on the left shows multiple focal areas of broadened gyri, blurring of the gray-white junction and increased signal in the subcortical white matter typical of cortical tubers. The image on the right shows multiple subependymal nodules (arrows) consistent with subependymal hamartoma and a large enhancing lesion at the right foramen of Monro consistent with a giant cell astrocytoma. MRI, magnetic resonance imaging
Figure 2.
Figure 2.. Imaging features of focal cortical dysplasia. Coronal T2weighted MRI (left) and axial T1 -weighted MRI (right) of two patients with focal cortical dysplasia. The image on the left shows area of gyral irregularity and increased subcortical signal (arrow) consistent with cortical dysplasia with signal change. The image on the right shows an area of unusual gyral formation and underlying thickening and blurring of the gray-white junction (arrow) consistent with cortical dysplasia without signal change. (No signal increase was seen on T2 weighted images.) MRI, magnetic resonance imaging
Figure 3.
Figure 3.. Imaging features of hemimegalencephaly. Axial T2-wieghted MRI (left) and coronal T2 -weighted MRI (right) of an infant with hemimegalencephaly showing an enlarged and dysmorphic left hemisphere containing an enlarged lateral ventricle, periventricular heterotopic gray, excessive white matter, abnormal white matter signal, and gyral irregularity suggestive of polymicrogyria, all characteristic of hemimegalencephaly. MRI, magnetic resonance imaging
Figure 4.
Figure 4.. Imaging features of classical lissencephaly contrasting the P>A gradient with the A>P gradient. Axial T1 -weighted MRI scans. The image on the left shows near-complete agyria posteriorly transitioning to pachygyria anteriorly. This is the P>A gradient consistent with a mutation of the LIS1 gene. The image on the right shows severe pachygyria anteriorly transitioning to mild pachygyria posteriorly. This is the A>P gradient consistent with a mutation of the DCX gene. MRI, magnetic resonance imaging
Figure 5.
Figure 5.. Imaging features of classical lissencephaly showing the four severity grades. All images are T1 - or T2 -weighted MRI scans. The top row shows axial scans and the bottom row coronal scans. Grade 1 is near complete agyria, grade 2 is posterior agyria and rudimentary shallow gyri anteriorly, grade 3 is posterior agyria and anterior pachygyria, and grade 4 is generalized pachygyria. MRI, magnetic resonance imaging
Figure 6.
Figure 6.. Imaging features of subcortical band heterotopia. Sagittal (left) and coronal (right) T1-weighted MRIs showing typical features of subcortical band heterotopia with bilateral, symmetric band of tissue with identical signal to cortical gray matter interspersed in the subcortical white matter between the normal cortex and the lateral ventricle. MRI, magnetic resonance imaging
Figure 7.
Figure 7.. Imaging features of periventricular nodular heterotopia. Axial T1 weighted MRI showing too patients with bilateral periventricular nodular heterotopia, manifest by nodules of tissue with identical signal to cortical gray matter located in the periventricular region (arrows). The image on the left shows scattered nodules separated by normal white matter, whereas the image on the right shows contiguous nodules completely lining the lateral ventricle. MRI, magnetic resonance imaging
Figure 8.
Figure 8.. MRI features of polymicrogyria. T1-weighted parasagittal image (left) of a patient with perisylvian polymicrogyria (PMG) showing an abnormally extended Sylvian fissure surrounded by overfolded gray matter with an irregular surface and stippling of the graywhite junction (arrows). The image on the right is a 3D surface reconstruction of another patient with perisylvian PMG highlighting the abnormal extension and orientation of the Sylvian fissure. MRI, magnetic resonance imaging
Figure 9.
Figure 9.. Imaging features of schizencephaly. Coronal T1 - (left) and axial T1 (right)-weighted MRI scans. Both images show full-thickness clefts lined by irregular gray matter (arrows). The image on the left shows bilateral closed-lip schizencephaly (SCZ) and the image on the right shows right open-lipped SCZ and agenesis of the septum pellucidum. MRI, magnetic resonance imaging
See this image and copyright information in PMC

References

    1. Kuzniecky RI., Jackson GD. Magnetic Resonance in Epilepsy. New York, NY: Raven Press; 1995:183–202.
    1. Guerrini R., Holthausen H., Parmeggiani L., et al. Epilepsy and malformations of the cerebral cortex. In: Roger J, Bureau M, Dravet C, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. 3rd ed. London, UK: John Libbey; 2002:457–479.
    1. Leventer RJ., Phelan EM., Coleman LT., et al. Clinical and imaging features of cortical malformations in childhood. Neurology. 1999;53:715–722. - PubMed
    1. Barkovich AJ., Kuzniecky RI., Jackson GD., et al. A developmental and genetic classification for malformations of cortical development. Neurology. 2005;65:1873–1887. - PubMed
    1. Gomez MR. Tuberous Sclerosis 2nd ed. New York, NY: Raven Press; 1988

MeSH terms