Basic mechanisms of epileptogenesis in pediatric cortical dysplasia

Cortical dysplasia (CD) is a neurodevelopmental disorder due to aberrant cell proliferation and differentiation. Advances in neuroimaging have proven effective in early identification of the more severe lesions and timely surgical removal to treat epilepsy. However, the exact mechanisms of epileptogenesis are not well understood. This review examines possible mechanisms based on anatomical and electrophysiological studies. CD can be classified as CD type I consisting of architectural abnormalities, CD type II with the presence of dysmorphic cytomegalic neurons and balloon cells, and CD type III which occurs in association with other pathologies. Use of freshly resected brain tissue has allowed a better understanding of basic mechanisms of epileptogenesis and has delineated the role of abnormal cells and synaptic activity. In CD type II, it was demonstrated that balloon cells do not initiate epileptic activity, whereas dysmorphic cytomegalic and immature neurons play an important role in generation and propagation of epileptic discharges. An unexpected finding in pediatric CD was that GABA synaptic activity is not reduced, and in fact, it may facilitate the occurrence of epileptic activity. This could be because neuronal circuits display morphological and functional signs of dysmaturity. In consequence, drugs that increase GABA function may prove ineffective in pediatric CD. In contrast, drugs that counteract depolarizing actions of GABA or drugs that inhibit the mammalian target of rapamycin (mTOR) pathway could be more effective.