{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:58Z","timestamp":1791928978414,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["project MNESYS (PE0000006)"],"award-info":[{"award-number":["project MNESYS (PE0000006)"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Gain\u2010of\u2010function (GoF) variants in <jats:italic>KCNT1<\/jats:italic> encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild\u2010type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled three pediatric patients carring de novo KCNT1 genetic variants linked to EIMFS. Functional and pharmacological studies to assess fluoxetine's ability to counteract in vitro variant\u2010induced functional effects were performed with patch\u2010clamp electrophysiology on heterologous channel expression in mammalian Chinese hamster ovary cells. Neuropsychological assessment, electroencephalogram and seizure diary were evaluated at baseline and every 3\u2009months during the study. Electrocardiography and blood levels of medications were monitored for safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All 3 <jats:italic>KCNT1<\/jats:italic> variants displayed GoF effects in vitro. Exposure to fluoxetine (10\u03bcM) blocked both WT and mutant KCNT1 channels, therefore, counteracting variant\u2010induced functional effects. Treatment with fluoxetine caused a variable reduction of seizure frequency (25\u201375%). Improvement in visual attention, participation, and muscle tone was also reported. No adverse events were reported except for transient dyskinesia in 1 patient, which was probably related to an increase in fluoxetine plasma level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Fluoxetine may be a potential targeted medication in EIMFS caused by <jats:italic>KCNT1<\/jats:italic> GoF variants. Further research is needed to assess its long\u2010term efficacy and safety. 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Tiberio\u201d University of Molise  Campobasso Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Correale","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit Bambino Ges\u00f9 Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Falamesca","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit Bambino Ges\u00f9 Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Filosomi","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit Bambino Ges\u00f9 Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Goffredo","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Drug Biology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-9374","authenticated-orcid":false,"given":"Maria Virginia","family":"Soldovieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Science \u201cV. 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