Pharmacotherapeutic strategies for drug-resistant epilepsy in children.

Drug resistance is defined as the failure of adequate trials of two tolerated and appropriately chosen antiseizure medications to achieve sustained seizure freedom. In case of uncontrolled seizures, pseudo-drug-resistance (poor compliance, a worsening effect of an antiseizure medication, a diagnosis of psychogenic non-epileptic seizure) should be first ruled out in case of pediatric epilepsies. This paper discusses the process of choosing antiseizure medication and the concepts of rationale polytherapy and precision medicine. In drug-resistant epilepsy, when curative surgery is not feasible, the aim of the treatment is focused on the improvement of quality of life rather than on seizure count. In recent years, despite an increase in available antiseizure medications, the incidence of drug-resistant epilepsy has not changed. Precision medicine may offer in rare epilepsies a mechanism-driven treatment, but it is still unclear if this will end up in an improvement of efficacy in drug-resistant epilepsies. Gene therapy with antisense oligonucleotides or Adeno-associated Virus (AAV) is transitioning from the experimental side to the first human trial. It may modify the natural history of selected epileptic syndromes.