{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:05:17Z","timestamp":1792591517338,"version":"4.5.0"},"reference-count":8,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010571","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft, Forschung und Technologie","doi-asserted-by":"publisher","award":["DZKJ, 01GL2401A"],"award-info":[{"award-number":["DZKJ, 01GL2401A"]}],"id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Dravet syndrome (DS), caused by loss-of-function variants in\n                    <jats:italic>SCN1A<\/jats:italic>\n                    , is classically aggravated by chronic sodium-channel blocker treatment, reflecting impaired interneuron excitability as a core disease mechanism. Cenobamate (CNB) challenges this: adult DS cases with substantial seizure reduction have been reported, while pediatric experience is mixed and includes a small cohort with no responders and frequent worsening. We report a 7-year-old girl with\n                    <jats:italic>SCN1A<\/jats:italic>\n                    -associated DS and severe developmental impairment who showed marked reduction of generalized tonic\u2013clonic seizures (GTCS) and total seizure burden with adjunctive CNB therapy. At maintenance CNB dose, which was added to valproate, clobazam and cannabidiol, a total seizure reduction of 80% was noted. An attempt to taper CNB failed because of marked seizure increase nearly back to the pre-CNB state. When CNB was returned to stable maintenance therapy levels, seizures markedly improved with no GTCS noted since October 2025. In addition, we describe a 17-year adolescent male with DS who had GTCS and daily eyelid myoclonia. He achieved suppression of seizures on low-dose CNB (50\u00a0mg\/day), with only one breakthrough GTCS secondary to a missed evening medication and no reported adverse effects. Taken together with prior pediatric reports, these cases highlight the need for controlled studies to balance potential efficacy against the risk of seizure worsening when considering cenobamate in pediatric DS.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1809113","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:14:31Z","timestamp":1781086471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cenobamate in pediatric Dravet syndrome: two responder cases highlighting the limits of simple \u201csodium-channel blocker\u201d labeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Konstantin L.","family":"Makridis","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"Center for Chronically Sick Children, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"Institute of Cell- and Neurobiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Section CNS Development and Neurologic Disease","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda C.","family":"Laux","sequence":"additional","affiliation":[{"name":"Division of Neurology, Ann and Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Kaindl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"Center for Chronically Sick Children, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"Institute of Cell- and Neurobiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Section CNS Development and Neurologic Disease","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1038\/s41598-017-01851-9","article-title":"Unexpected efficacy of a novel sodium channel modulator in Dravet syndrome","volume":"7","author":"Anderson","year":"2017","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e83","DOI":"10.1111\/epi.18426","article-title":"Lack of effectiveness and seizure worsening with cenobamate in pediatric patients with Dravet syndrome","volume":"66","author":"Cagigal","year":"2025","journal-title":"Epilepsia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.seizure.2023.09.006","article-title":"Real-world experience with cenobamate: a systematic review and meta-analysis","volume":"112","author":"Makridis","year":"2023","journal-title":"Seizure"},{"key":"B4","doi-asserted-by":"publisher","first-page":"950171","DOI":"10.3389\/fneur.2022.950171","article-title":"Real-world experience treating pediatric epilepsy patients with cenobamate","volume":"13","author":"Makridis","year":"","journal-title":"Front Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1111\/epi.17427","article-title":"Successful treatment of adult Dravet syndrome patients with cenobamate","volume":"63","author":"Makridis","year":"","journal-title":"Epilepsia"},{"key":"B6","first-page":"79","article-title":"Exploration of the mechanism of action of cenobamate seizure","volume":"134","author":"Sankar","year":"2025","journal-title":"arXiv"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1111\/epi.17274","article-title":"International consensus on diagnosis and management of Dravet syndrome epilepsia","volume":"63","author":"Wirrell","year":"2022","journal-title":"Epilepsia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nn1754","article-title":"Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy","volume":"9","author":"Yu","year":"2006","journal-title":"Nat. Neurosci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1809113\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:14:32Z","timestamp":1781086472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1809113\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":8,"alternative-id":["10.3389\/fphar.2026.1809113"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1809113","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"article-number":"1809113"}}