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

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.