Are some focal cortical dysplasias post‐migratory cortical malformations?

Abstract

th week of gestation. Studies and debates on the developmental events that shape the neocortex date back to the first pioneers of neuroscience. However, during the last decade, an increasing bulk of literature has proved that the mechanisms underlying cortical development are much more complex than previously thought, and the rather simplistic schemes conceived in the past are now under permanent revision. Despite the very fast pace of identification of genes involved in cortical development, cell-specific gene expression analysis is not available nor is the knowledge about the intimate mechanisms that govern corticogenesis. Nevertheless, both genetic and environmental mechanisms have been identified in corticogenesis and three essential developmental steps are recognized : proliferation, migration and differentiation. This applies to all mammalian species including humans, whose brains reach maximal growth increase and complexity only during the last two months of gestation. Any disturbance, regardless of the cause, can lead to a wide range of morphological alterations, from severe brain malformations to local disruption of cortical structure. Improvement of our knowledge about basic mechanisms of corticogenesis require, therefore, a continuous debate and revision of concepts, nomenclature and classification schemes. In recognition that more complex mechanisms are involved in corticogenesis, these pathologies, originally defined as Neuronal Migration Disorders (NMDs), are now listed under the less ambiguous term of Malformations of Cortical Development (MCDs). MCDs represent a wide group of brain alterations encompassing many disorders with different pathogenesis, genetic abnormalities, structural neuropathological defects and clinical features. Notwithstanding, MCDs are frequently associated with neurological deficits and represent one of the most common causes of refractory epilepsies. Increasing advances in neuroimaging techniques, the refinement of neuropathological procedures and the recognition of several molecular pathways and genetic impact of MCD have led to the necessity for new classification schemes also useful in clinical practice. In consideration of the three main developmental processes, Barkovich