{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:15:05Z","timestamp":1762542905294,"version":"3.41.0"},"reference-count":27,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The treatment of refractory or super\u2010refractory status epilepticus (<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>) currently relies on low\u2010evidence 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 \u03b3\u2010aminobutyric acid (<jats:styled-content style=\"fixed-case\">GABA)<jats:sub>A<\/jats:sub><\/jats:styled-content>receptors. In animal experiments it has been demonstrated that this neurosteroid displays relevant antiseizure properties in a variety of<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>models, and that the tolerance to benzodiazepines, relying on receptor internalization, does not affect its action. An experimental clinical use in patients with<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>older than 2\u00a0years was initated more than 5\u00a0years 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\/<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>trial seemed promising, but a recent well\u2010designed randomized, placebo\u2010controlled trial could not find any difference in terms of efficacy; tolerability seemed nevertheless good. Patients with refractory and super\u2010refractory<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>still deserve further well\u2010designed studies to improve current treatment options.<\/jats:p>","DOI":"10.1111\/epi.14481","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T11:26:13Z","timestamp":1535628373000},"page":"216-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Place of neurosteroids in the treatment of status epilepticus"],"prefix":"10.1111","volume":"59","author":[{"given":"Andrea O.","family":"Rossetti","sequence":"first","affiliation":[{"name":"Neurology service University Hospital (CHUV) and Faculty of Biology and Medicine Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr215"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-014-3363-z"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.041947"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02323.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12605"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003224"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182591ff1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000881"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1703"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12289"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-19-07532.1997"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4944-04.2005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00606-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01336.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00046-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3426-07.2008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(02)00172-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2435457100"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1210\/endo.133.3.8365352","article-title":"Neurosteroids: 3 alpha\u2010hydroxy\u20105 alpha\u2010pregnan\u201020\u2010one and its precursors in the brain, plasma, and steroidogenic glands of male and female rats","volume":"133","author":"Corpechot C","year":"1993","journal-title":"Endocrinology"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0148-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/S0022-3565(24)39026-3","article-title":"Chronic treatment with the neuroactive steroid ganaxolone in the rat induces anticonvulsant tolerance to diazepam but not to itself","volume":"295","author":"Reddy DS","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13625"},{"key":"e_1_2_8_25_1","first-page":"106","article-title":"Successful alopregnanolone treatment of new onset refractory status peilpeticus (NORSE) syndrome: first in man experience","volume":"54","author":"Vaitkevicius H","year":"2013","journal-title":"Epilepsia"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24295"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25008"},{"key":"e_1_2_8_28_1","unstructured":"http:\/\/investor.sagerx.com\/news-releases\/news-release-details\/sage-therapeutics-reports-top-line-results-phase-3-status-trial. 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