Cortical malformations and epilepsy: New insights from animal models

In the last decade, the recognition of the high frequency of cortical malfo rmations among patients with epilepsy especially children, has led to a ren ewed interest in the study of the pathophysiology of cortical development. This field has also been spurred by the recent development of several exper imental genetic and non-genetic, primarily rodent, models of cortical malfo rmations. Epileptiform activity in these animals can appear as spontaneous seizure activity in vivo, in vitro hyperexcitability, or reduced seizure su sceptibility in vitro and in vivo. In the neonatal freeze lesion model, tha t mimics human microgyria, hyperexcitability is caused by a reorganization of the network in the borders of the malformation. In the prenatal methylaz oxymethanol model, that causes a diffuse cortical malformation, hyperexcita bility is associated with alteration of firing properties of discrete neuro nal subpopulations together with the formation of bridges between normally unconnected structures. In agreement with clinical evidence, these experime ntal data suggest that cortical malformations can both form epileptogenic f oci and alter brain development in a manner that causes a diffuse hyperexci tability of the cortical network.