Are some idiopathic epilepsies disorders of ion channels?: A working hypothesis

Epilepsy is a common neurological disease and encompasses a variety of diso rders with paroxysms. Although there is a generic component in the pathogen esis of epilepsy, the molecular mechanisms of this syndrome remains poorly understood. Linkage analysis and positional cloning have not been sufficien t tools for determining the pathogenic mechanisms of common idiopathic epil epsies, and hence, novel approaches, based on the etiology of epilepsy, are necessary. Recently, many paroxysmal disorders, including, epilepsy, have been considered to be due to ion channel abnormalities or channelopathies. Results of recent studies employing gene analysis in animal models of epile psy and human familial epilepsies support the hypothesis that at least some of the so called idiopathic epilepsies, i.e. epilepsies currently, classif ied as idiopathic could be considered as a channelopathy. This hypothesis i s consistent with the putative prerequisites for genes responsible for the majority of idiopathic epilepsies that call adequately explain the followin g characteristics of epilepsy. Neuronal hyperexcitability, dominant inherit ance with various penetrance, pharmacological role of some conventional ant iepileptic drugs, age dependency in the onset of epilepsy, and the involvem ent of genetic factors in the pathogenesis of post-traumatic epilepsy. Sear ch for mutations in ion channels expressed in the central nervous system ma y help in finding defects underlying some of idiopathic epilepsies, thereby enhancing, our understanding of the molecular pathogenesis of epilepsy. A working hypothesis to view certain idiopathic epilepsies as disorders of io n channels should provide a new insight to our understanding of epilepsy an d allow the design of novel therapies. (C) 2000 Elsevier Science B.V. All r ights reserved.