Generalized Epileptic Disorders: An Update

Generalized epileptic disorders are characterized by seizures in which there are symptoms of bilateral cerebral involvement, and an electroencephalogram in which synchronous abnormal activity is recorded in both hemispheres at seizure onset (1). Generalized epilepsies result from alterations in the function of the whole brain or of major brain systems, and are often the expression of inborn errors in which the molecular etiology can be identified through genetic approaches. Thus, insights gained from genetic studies of the generalized epilepsies are beginning to answer the age-old question: “What is the cause of epilepsy?” Indeed, concepts of pathogenesis developed in generalized epilepsies may provide clues to the etiologies of the more common focal epileptic disorders. Having passed what is truly a milestone event in epilepsy research—the cloning of the first human idiopathic generalized epilepsy genes (see 2,3)—it seemed an opportune time to review the scope of research progress on the generalized epilepsies. We begin with a brief summary of the clinical features of the generalized epilepsies and then describe new developments in the genetics of these disorders. Current understanding of the cellular and network mechanisms leading to some forms of generalized seizures also are considered. Finally, drug treatment is discussed in the context of the pathophysiologic mechanisms. This review originated at Focus on Epilepsy V, an international symposium held in Quebec City in May 1999. A list of the faculty that participated in this conference is given later (4,5).