Seizure susceptibility in polymicrogyria: clinical and experimental approaches

Abstract

Polymicrogyria is a cerebral cortical malformation characterized by an excessively folded cortical ribbon of miniature and individually thin convolutions. Although polymicrogyria is a highly epileptogenic lesion, its epileptogenic mechanism is unclear. The anomalous cortex associated with polymicrogyria includes less excitable neural tissue such as a cell sparse zone, but involves a part of a larger epileptic network extending to adjacent cortical areas. This malformation can be modeled in rats with a transcortical prenatal or neonatal freeze lesion, which mimics the histological characteristics of a human four-layered polymicrogyria. Several hypotheses have so far been presented for seizure susceptibility in polymicrogyria, including alterations of glutamate receptor distribution, abnormalities in ion channels, new excitatory or inhibitory connections, and downregulation of GABA(A) receptor subunits. The cortical hyperexcitability in polymicrogyria may be reduced by the inhibitory neuronal network. Further detailed investigations of a population with aberrantly migrating inhibitory interneurons will provide novel and important insights into the pathogenetic mechanisms of epilepsy in polymicrogyria.