Generalized epilepsies: current conceptions and therapeutic approaches

Abstract

The concepts of generalized epilepsy have recently undergone considerable changes: the features of focality in generalized epilepsies and the typical features of idiopathic generalized epilepsies in focal epilepsies have been revealed. The closeness of these forms is also supported by genetic studies when one genetic abnormality shows diverse focal and generalized phenotypes in different members of one family. In this connection, the Commission on Classification and Terminology of the International League Against Epilepsy proposes to abandon the identification of the forms of epilepsy on the principle of focal and generalized seizures, by changing it for the notion Tneural network that involves different local and common brain mechanisms in each individual case. These neuropathophysiological concepts give an insight into why the pharmacotherapy based on a model of focal and generalized seizures is ineffective or occasionally even aggravates the disease. The current approach makes it preferential to choose a broad-spectrum drug that is effective in any types of seizures and forms of epilepsy, by taking into account its efficacy, dose titration rate, dosage form, side effects, and cost. Among broad-spectrum agents (valproate (VPA), levetiracetam, lamotrigine, topiramate), the original controlled release dosage forms of VPA (Depakine chrono and Depakine chromosphere) have a priority as first-line drugs for the initial treatment of generalized epilepsies. The paper considers the basic pharmacokinetic and pharmacodynamics properties of the drugs for the treatment of epilepsy and the algorithms of therapy for individual entities of generalized epilepsy.