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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
REVIEW
Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations.
Brain Pathology 2002 April
This review will consider patterns of developmental neuropathologic abnormalities-malformations of cortical development (MCD)--encountered in infants (often with infantile spasms), children, and adults with intractable epilepsy. Treatment of epilepsy associated with some MCD, such as focal cortical dysplasia and tubers of tuberous sclerosis, may include cortical resection performed to remove the "dysplastic" region of cortex. In extreme situations (eg, hemimegalencephaly), hemispherectomy may be carried out on selected patients. Neuropathologic (including immunohistochemical) findings within these lesions will be considered. Other conditions that cause intractable epilepsy and often mental retardation, yet are not necessarily amenable to surgical treatment (eg, lissencephaly, periventricular nodular heterotopia, double cortex syndrome) will be discussed. Over the past 10 years there has been an explosion of information on the genetics of MCD. The genes responsible for many MCD (eg, TSC1, TSC2, LIS-1, DCX, FLN1) have been cloned and permit important mechanistic studies to be carried out with the purpose of understanding how mutations within these genes result in abnormal cortical cytoarchitecture and anomalous neuroglial differentiation. Finally, novel techniques allowing for analysis of patterns of gene expression within single cells, including neurons, is likely to provide answers to the most vexing and important question about these lesions: Why are they epileptogenic?
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