Refractory epilepsy: diagnosis and etiology

Epilepsy is a chronic condition, and in about one_thirth patients with epilepsy, drug resistant epilepsy will be happen eventually. Drug resistant epilepsy is a chronic and life treating condition which can lead to dangerous complications such as SUDEP. Drug resistant epilepsy (DRE) is defined as the failure of adequate trials of two tolerated, appropriately chosen anti-epileptic drugs (AED), whether as monotherapies or in combinations, to achieve sustained seizure freedom. According to ILAE, the duration definition for seizure freedom period could be either three times the period interseizure interval or one year, whichever is longer. The development of the proposed consensus definition was driven by the growing need among medical practitioners and clinical researchers to adopt a common language in recognizing drug resistant epilepsy in the face of rapidly expanding therapeutic options.It is clear that the mechanism(s) of DREs are most likely multifactorial, involving environmental, genetic, as well as disease and drug-related factors. During past years, several hypotheses have been proposed for DREs such as (1) pharmacokinetic hypothesis, (2) the neural network hypothesis, (3) the intrinsic severity hypothesis, (4) the gene variant hypothesis, (5) the target hypothesis, and finally the (6) transporter hypothesis. Each of these mechanisms has its own supporting findings, but none of them can fully explain the underlying mechanism for DREs. The aim of this review is defining DRE and discuss underlying mechanisms and etiologies.