Pharmacoresistant epilepsy: Definition and explanation

Epilepsy is one of the commonest neurological disorders, estimated to affect more than 60 million people worldwide. In the majority of these patients, seizures can be effectively suppressed with antiepileptic drugs (AEDs). Still, a significant percentage of patients (estimated to exceed 40% in some studies) exhibit pharmacoresistance during the course of their frequently lifelong condition.

We review our current understanding of some of the many missing pieces that constitute the puzzle of pharmacoresistant epilepsy (PRE), which can be practically defined as failure to achieve seizure freedom following adequate trials of two tolerated and appropriately chosen AEDs. The complexity of PRE reflects the dynamic nature of the underlying disease biology and the multiplicity of mechanisms of drug resistance.

We summarize some of the known clinical predictors, patterns and causes of treatment failure and examine potential underlying pathophysiological mechanisms and implications for the development of future therapies