Place of neurosteroids in the treatment of status epilepticus

Epilepsia
Andrea O Rossetti

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 neverthele...Continue Reading

References

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Mar 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Howard P GoodkinJaideep Kapur
Mar 11, 2008·Epilepsia·Guenther Sperk
Oct 13, 2009·Epilepsia·Jan NovyAndrea O Rossetti
Sep 6, 2013·Epilepsia·Michael A RogawskiChristoph Lossin
Jun 14, 2014·Intensive Care Medicine·Andrea O Rossetti, Thomas P Bleck
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Feb 6, 2015·Critical Care Medicine·Nicola A MarchiAndrea O Rossetti
Apr 16, 2016·Acta Neurologica Scandinavica·L DelajA O Rossetti
Aug 6, 2017·Annals of Neurology·Eric S RosenthalStephen J Kanes

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Citations

Nov 8, 2018·Expert Opinion on Pharmacotherapy·Alessandra MoranoCarlo Di Bonaventura
Jan 10, 2021·Neuroscience Letters·Jaideep Kapur, Suchitra Joshi
Dec 17, 2020·International Journal of Molecular Sciences·Maxime LévesqueMassimo Avoli

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