Place of neurosteroids in the treatment of status epilepticus

Abstract

The treatment of refractory or super-refractory status epilepticus (SE) currently relies on low-evidence strategies, including general anesthetics to induce pharmacologic coma, ketogenic diet, immunosuppression, and other physical measures. Besides the formal uncertainty regarding efficacy, concerns have been about tolerability. In this situation, identification of alternative, higher evidence treatments is urgently needed. Allopregnanolone is an endogenous neurosteroid exerting a positive allosteric modulation on γ-aminobutyric acid (GABA) A receptors. In animal experiments it has been demonstrated that this neurosteroid displays relevant antiseizure properties in a variety of SE models, and that the tolerance to benzodiazepines, relying on receptor internalization, does not affect its action. An experimental clinical use in patients with SE older than 2 years was initated more than 5 years ago. Being a naturally occurring compound, no relevant adverse events are expected, and until now its safety profile appears reassuring. Preliminary results of a phase I/II trial seemed promising, but a recent well-designed randomized, placebo-controlled trial could not find any difference in terms of efficacy; tolerability seemed nevertheless good. Patients with refractory and super-refractory SE still deserve further well-designed studies to improve current treatment options.