Focal cortical dysplasia: a neuropathological and developmental perspective

Focal cortical dysplasia (FCD) is a rare, sporadic disorder which is a reco gnised cause of chronic epilepsy. It is proposed to result from disordered neuronal migration and differentiation and has characteristic histological features which include disturbed cortical lamination, large abnormal neuron s and the presence of large balloon cells with glassy eosinophilic cytoplas m and pleomorphic eccentric nuclei. These latter express both glial and neu ronal markers indicative of abnormal neuroglial differentiation. In this pa per we review the current literature on the neuropathology of FCD and discu ss potential mechanisms. We focus on growth factors, signalling pathways an d candidate genes with known roles in Drosophila and vertebrate brain devel opment that could be responsible for the developmental brain changes seen i n FCD. At issue are the factors that influence cell fate and differentiatio n and which regulate neural migration. Some of the molecular pathways, such as those involving the Notch and the Wnt pathways have particularly import ant roles in neuroglial differentiation in vertebrates, and these are propo sed as potential candidates. (C) 1999 Elsevier Science B.V. All rights rese rved.