Pathophysiological Mechanisms of Focal Cortical Dysplasia: A Critical Review of Human Tissue Studies and Animal Models

Cortical dysplasia (CD, also known as malformations of cortical development) are the pathological substrates in a large percentage of patients with pharmacoresistant epilepsy who may be amenable to surgical treatment. Therefore, research on the mechanisms of dysplastic lesion formation and epileptogenicity is of paramount importance for the prevention, detection, and treatment of CD-induced epilepsy. The purpose of this review is to discuss and critically evaluate the current state and results of human tissue experimentation (focusing on reported results of studies done on neocortical dysplastic tissue resected from patients with pharmacoresistant epilepsy), and to discuss some of the concerns related to research that uses surgically resected epileptic human tissue. The use of better animal models of CD as a tool toward the better understanding of the mechanisms of pathogenesis, epileptogenesis, and epileptogenicity of dysplastic lesions will be reviewed from the perspective of their usefulness in a model of translational research that should ultimately result in better diagnostic and therapeutic techniques of CD.