{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:56Z","timestamp":1788922196556,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010 NEU2\u20100006 (AUTONOMIC)"],"award-info":[{"award-number":["ANR\u201021\u2010 NEU2\u20100006 (AUTONOMIC)"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post\u2010ictal hypoxemia and immobility after focal to bilateral tonic\u2013clonic seizures (FBTCS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ENALEPSY is a double\u2010blind placebo (PCB)\u2010controlled trial conducted in patients with focal epilepsy undergoing long\u2010term video\u2010EEG monitoring (LTM). Patients with a FBTCS during LTM were randomized 1:1 to receive intravenous NLX or PCB within the 2\u2009min following the end of FBTCS. After database lock, a discrepancy between the allocated arm and the received treatment was detected, resulting in a 4:1 NLX:PCB ratio. To further explore the efficacy of NLX, we used historical control (HC) data collected in patients included in the REPO\n                      <jats:sub>2<\/jats:sub>\n                      MSE study whose characteristics matched those of patients randomized in ENALEPSY. The efficacy of NLX was then assessed versus PCB and versus HC. The primary endpoint was the delay between the end of the seizure and recovery of SpO\n                      <jats:sub>2<\/jats:sub>\n                      \u2009\u2265\u200990%. Secondary efficacy outcomes included desaturation nadir and duration of the post\u2010ictal immobility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      33 patients contributed to the NLX group, 7 to the PCB group, and 43 to the HC group. The proportion of FBTCS type 1 or 3 was 84% in NLX, 100% in PCB, and 84% in HC. NLX did not improve the delay of recovery of SpO\n                      <jats:sub>2<\/jats:sub>\n                      \u2009\u2265\u200990% or the desaturation nadir. By contrast, the duration of the post\u2010ictal immobility differed across groups. The time to mobility recovery within the first 5\u2009min post\u2010ictal was very similar in the PCB (200.3\u2009\u00b1\u2009215.8\u2009s) and HC (194.4\u2009\u00b1\u2009192.0\u2009s) groups, and significantly shorter in the NLX group (128.9\u2009\u00b1\u2009151.1\u2009s) when compared to HC (Hazard Ratio, 1.84; 95% CI, 1.11\u20133.05;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>NLX did not prevent post\u2010ictal respiratory dysfunction but might reduce the duration of post\u2010ictal immobility. Confirmation of this effect and its impact on SUDEP risk will require additional studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Release of endogenous opioids might participate in the severity of post\u2010ictal hypoxemia and immobility after focal to bilateral tonic\u2013clonic seizures (FBTCS). We conducted a multicenter double\u2010blind randomized placebo\u2010controlled trial evaluating the efficacy of an opioid antagonist, naloxone (NLX), administered within 2\u2009min following the end of FBTCS. The efficacy of NLX was further explored with a comparison with historical control. NLX did not improve the delay of recovery or the severity of post\u2010ictal hypoxemia. Post\u2010ictal immobility was significantly shorter in the NLX group when compared to historical control. The impact of these results on SUDEP prevention will require additional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70046","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:59:32Z","timestamp":1745819972000},"page":"880-893","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic\u2013clonic seizures"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-8515","authenticated-orcid":false,"given":"Sylvain","family":"Rheims","sequence":"first","affiliation":[{"name":"Department of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University  Lyon France"},{"name":"Lyon's Neuroscience Research Center INSERM U1028\/CNRS UMR 5292\/Lyon 1 University  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Chorfa","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Hospices Civils de Lyon and University of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Neurology H\u00f4pital Pellegrin  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0833-8850","authenticated-orcid":false,"given":"Edouard","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Maillard","sequence":"additional","affiliation":[{"name":"Neurology Department University Hospital of Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Valton","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Toulouse  Toulouse France"},{"name":"Brain and Cognition Research Centre (CerCo), CNRS, UMR5549  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1678-0297","authenticated-orcid":false,"given":"Fabrice","family":"Bartolomei","sequence":"additional","affiliation":[{"name":"APHM Timone Hospital, Epileptology and Cerebral Rhythmology  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Derambure","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Lille University Medical Center, EA 1046, University of Lille2  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-8114","authenticated-orcid":false,"given":"Vincent","family":"Navarro","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Epilepsy Unit, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne Universit\u00e9  Paris France"},{"name":"Paris Brain Institute (ICM; INSERM, CNRS) ERN EpiCare  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Biberon","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology University Hospital of Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle","family":"Crespel","sequence":"additional","affiliation":[{"name":"Epilepsy Unit  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Nica","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine Lemesle","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Dijon  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Saint\u2010Etienne  Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Petit","sequence":"additional","affiliation":[{"name":"La Teppe Epilepsy Center  Tain l'Hermitage France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Rossero","sequence":"additional","affiliation":[{"name":"Lyon's Neuroscience Research Center INSERM U1028\/CNRS UMR 5292\/Lyon 1 University  Lyon 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