{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:17:05Z","timestamp":1784942225197,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The\n                      <jats:italic>SCN1A<\/jats:italic>\n                      gene is implicated in a broad spectrum of epilepsy phenotypes, ranging from self\u2010limited genetic epilepsy with febrile seizures plus (GEFS+) to severe developmental and epileptic encephalopathies such as Dravet syndrome (DS). While fenfluramine (FFA) has demonstrated strong efficacy in DS, its role in\n                      <jats:italic>SCN1A<\/jats:italic>\n                      \u2010related epilepsies beyond DS has not been thoroughly investigated. We conducted a multicenter observational study including 11 patients with\n                      <jats:italic>SCN1A<\/jats:italic>\n                      \u2010related GEFS+ who received FFA as adjunctive therapy. All patients had previously failed to achieve adequate seizure control with valproate and, in most cases, additional antiseizure medications. FFA was introduced following the DS titration protocol, with a mean dose of 0.39\u2009mg\/kg\/day. FFA addition led to a mean seizure frequency reduction of 91%, with more than half of the patients achieving complete seizure freedom. Reduced EEG abnormalities were documented in 5\/11 patients of the cohort, including complete normalization in 3\/11 patients. Furthermore, subjective caregiver reports indicated perceived improvements in patients' alertness and behavioral responses. FFA was well tolerated, with only mild and transient adverse events reported. These findings support the potential role of FFA as an effective and well\u2010tolerated treatment option in patients with\n                      <jats:italic>SCN1A<\/jats:italic>\n                      \u2010related GEFS+.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>GEFS+ is a genetic epilepsy frequently caused by changes in the SCN1A gene. In a multicenter real\u2010world study of 11 people with SCN1A\u2010related GEFS+, adding fenfluramine to usual care substantially reduced seizures, with several becoming seizure\u2010free. EEG recordings improved, and caregivers reported better alertness in some patients. Treatment was generally well tolerated, with only mild, temporary side effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70187","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:05:36Z","timestamp":1773025536000},"page":"619-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fenfluramine in\n                    <scp>SCN1A<\/scp>\n                    \u2010related\n                    <scp>GEFS<\/scp>\n                    +: A multicenter observational study on efficacy,\n                    <scp>EEG<\/scp>\n                    improvement, and tolerability"],"prefix":"10.1002","volume":"11","author":[{"given":"Giovanni B.","family":"Dell'Isola","sequence":"first","affiliation":[{"name":"Department of Developmental Disabilities IRCCS San Raffaele Roma  Rome Italy"},{"name":"Department of Medicine and Surgery Saint Camillus International University of Health Sciences  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3401-6994","authenticated-orcid":false,"given":"Alice","family":"Muda","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Psychiatry Unit, Spedali Civili Children's Hospital University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neuroscience and Medical Genetics Department, Meyer Children's Hospital IRCCS European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Florence Italy"},{"name":"NEUROFARBA Department University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Boncristiano","sequence":"additional","affiliation":[{"name":"Neuroscience and Medical Genetics Department, Meyer Children's Hospital IRCCS European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pietrafusa","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy, and Movement Disorders Unit, Bambino Ges\u00f9 Children's Hospital, IRCCS European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Polselli","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Systems Medicine Department Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1109-7296","authenticated-orcid":false,"given":"Francesca","family":"Bisulli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"},{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ragona","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica Immacolata","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Vigevano","sequence":"additional","affiliation":[{"name":"Department of Developmental Disabilities IRCCS San Raffaele Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16386"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2011.02994.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2011.02997.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17882"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.832929"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708283370901"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(88)90089\u20105"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168416"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32500\u20100"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.4113"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17274"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22782"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70187","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi4.70187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T12:29:40Z","timestamp":1778934580000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/epi4.70187"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70187","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"2025-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}