Basic cellular and molecular mechanisms of refractory epilepsy: a review of current hypotheses

Abstract

Clarification of refractory epilepsy mechanisms is of great significance for its precise diagnosis and adequate therapeutic approach. This review presents current hypotheses of refractory epilepsy formation: 1. Hypothesis of genetic factors; 2. Hypothesis of multi-drug transporters; 3. Target hypothesis; 4. Hypothesis of mechanisms related to antiepileptic drugs – development of tolerance and ineffective mechanisms of action 5. Hypothesis of epilepsy related factors – seizure etiology, epilepsy progression, structural brain changes or neural net alterations. The latter hypothesis is closely related to the hypothesis of intrinsic severity as a determinant of antiepileptic drug resistance. A combination of mechanisms is also a possible explanation of refractoriness. Each of these hypotheses characterizes refractory epilepsy to a different extent without attaining an explicit and complex explanation of epileptogenesis.