Wiring, dysmorphogenesis and epilepsy: a hypothesis

Cerebral cortical dysgenesis has been found by magnetic resonance imaging to be the second most common pathology underlying medically refractory chronic partial epilepsy. Patients with the latter condition form the largest group in specialist epilepsy clinics. The pathogenesis of the epilepsy in cortical dysgenesis remains largely obscure. The most popular current hypothesis holds neuronal misconnection secondary to neuronal malpositioning culpable for seizure activity. However, a review of the published literature of cortical dysgenesis and an analysis of newer magnetic resonance and histopathological data, suggests that this view is no longer tenable. A modified hypothesis is proposed in which neuronal connectivity itself is postulated to be the primary motive force in both cerebral morphogenesis and epileptogenesis in cases of cortical dysgenesis. This hypothesis leads to the generation of a model for cortical development and directly testable predictions of intercellular connectivity, as well as a potential tool for the prediction of the possibility of freedom from seizure activity after surgical resection of dysgenetic lesions in individual cases.