{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:08:51Z","timestamp":1789542531765,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012739","name":"Zogenix","doi-asserted-by":"publisher","award":["Funding for professional medical writing\/editing"],"award-info":[{"award-number":["Funding for professional medical writing\/editing"]}],"id":[{"id":"10.13039\/100012739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>SCN8A<\/jats:italic>\u2010developmental and epileptic encephalopathy is caused by pathogenic variants in the <jats:italic>SCN8A<\/jats:italic> gene encoding the Na<jats:sub>v<\/jats:sub>1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox\u2013Gastaut syndrome. The effect of fenfluramine treatment was assessed in a retrospective series of three patients with intractable <jats:italic>SCN8A<\/jats:italic> epilepsy and severe neurodevelopmental comorbidity (n\u00a0=\u00a02 females; age 2.8\u201313\u2009years; 8\u201316 prior failed antiseizure medications [ASM]; treatment duration: 0.75\u20134.2\u2009years). In the 6\u00a0months prior to receiving fenfluramine, patients experienced multiple seizure types, including generalized tonic\u2013clonic, focal and myoclonic seizures, and status epilepticus. Overall seizure reduction was 60%\u201390% in the last 3, 6, and 12\u00a0months of fenfluramine treatment. Clinically meaningful improvement was noted in \u22651 non\u2010seizure comorbidity per patient after fenfluramine, as assessed by physician\u2010ratings of \u2265\u201cMuch Improved\u201d on the Clinical Global Impression of Improvement scale. Improvements included ambulation in a previously non\u2010ambulant patient and better attention, sleep, and language. One patient showed mild irritability which resolved; no other treatment\u2010related adverse events were reported. There were no reports of valvular heart disease or pulmonary arterial hypertension. Fenfluramine may be a promising ASM for randomized clinical trials in <jats:italic>SCN8A<\/jats:italic>\u2010related disorders.<\/jats:p>","DOI":"10.1002\/epi4.12623","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T14:23:43Z","timestamp":1657290223000},"page":"525-531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of fenfluramine on seizures and comorbidities in <scp><i>SCN8A<\/i>\u2010developmental<\/scp> and epileptic encephalopathy: A case series"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-3365","authenticated-orcid":false,"given":"\u00c1ngel","family":"Aledo\u2010Serrano","sequence":"first","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3120-3479","authenticated-orcid":false,"given":"Borja","family":"Cabal\u2010Paz","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"},{"name":"Neurology Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-6022","authenticated-orcid":false,"given":"Elena","family":"Gardella","sequence":"additional","affiliation":[{"name":"Department of Epilepsy Genetics and Personalized Treatment, Member of ERN\u2010Epicare Danish Epilepsy Center  Dianalund Denmark"},{"name":"University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1964-7739","authenticated-orcid":false,"given":"Pablo","family":"G\u00f3mez\u2010Porro","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"},{"name":"Neurology Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otilia","family":"Mart\u00ednez\u2010M\u00fagica","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Section, Pediatrics Department Donostia University Hospital  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2743-0978","authenticated-orcid":false,"given":"Alvaro","family":"Beltr\u00e1n\u2010Corbellini","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9387-1088","authenticated-orcid":false,"given":"Rafael","family":"Toledano","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"},{"name":"Epilepsy Unit, Neurology Department Ramon y Cajal University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Garc\u00eda\u2010Morales","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"},{"name":"Epilepsy Unit, Neurology Department Cl\u00ednico San Carlos University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-0793","authenticated-orcid":false,"given":"Antonio","family":"Gil\u2010Nagel","sequence":"additional","affiliation":[{"name":"Neurology Department, Epilepsy Program Ruber Internacional Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Hammer MF","year":"2016"},{"issue":"1","key":"e_1_2_8_3_1","article-title":"A novel SCN8A mutation in a case of early\u2010onset infantile epileptic encephalopathy: a case report","volume":"92","author":"Keshri S","year":"2022","journal-title":"Acta Biomed"},{"issue":"3","key":"e_1_2_8_4_1","first-page":"S77","article-title":"Phenotypic and genetic spectrum of SCN8A\u2010related disorders, treatment options, and outcomes","volume":"60","author":"Gardella 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