{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:35:13Z","timestamp":1783402513738,"version":"3.54.6"},"reference-count":14,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Thr226Met pathologic variant of the SCN1A gene has been associated with the clinical development of an early infantile developmental and epileptic encephalopathy (EIDEE) different from Dravet's syndrome. The electrophysiological mechanisms of the mutated channel lead to a paradoxical gain and loss of function. The use of sodium channel blockers (SCB) that counteract this gain of function has been described in previous studies and they can be safely administered to patients carrying mutations in other sodium channel subtypes without causing a worsening of seizures. We report the use of SCB in a child harboring the Thr226Met pathologic variant of SCN1A with early-onset pharmaco-resistant migrating seizures, as well as developmental delay. Lacosamide led to a dramatic reduction in seizure frequency; however, only a mild improvement in the epileptic activity depicted by electroencephalography (EEG) was achieved. The introduction of carbamazepine as an add-on therapy led to a notable reduction in epileptic activity via EEG and to an improvement in sensorimotor development. Despite the overall clinical improvement, the patient developed febrile seizures and a nonepileptic jerking of the right hand. In this case of EIDEE with the Thr226Met variant, we demonstrate a beneficial pharmacological intervention of SCB in contrast to findings described in current literature. Our report encourages the cautious use of SCB at early stages of the disease in patients carrying this pathologic variant.<\/jats:p>","DOI":"10.1055\/a-2133-5343","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T22:50:15Z","timestamp":1689807015000},"page":"417-421","source":"Crossref","is-referenced-by-count":5,"title":["Use of Sodium Channel Blockers in the Thr226Met Pathologic Variant of SCN1A: A Case Report"],"prefix":"10.1055","volume":"54","author":[{"given":"Brenda Carolina","family":"N\u00e1jera-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Epilepsy Center - Neuropediatrics, DRK Kliniken Berlin, Westend, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Seeber","sequence":"additional","affiliation":[{"name":"Epilepsy Center - Neuropediatrics, DRK Kliniken Berlin, Westend, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Goldhahn","sequence":"additional","affiliation":[{"name":"Epilepsy Center - Neuropediatrics, DRK Kliniken Berlin, Westend, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-5299","authenticated-orcid":false,"given":"Axel","family":"Panzer","sequence":"additional","affiliation":[{"name":"Epilepsy Center - Neuropediatrics, DRK Kliniken Berlin, Westend, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1093\/brain\/awac210","article-title":"The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications","volume":"145","author":"A Brunklaus","year":"2022","journal-title":"Brain"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/humu.22782","article-title":"The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype","volume":"36","author":"H Meng","year":"2015","journal-title":"Hum Mutat"},{"issue":"07","key":"ref3","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1212\/WNL.0b013e31820c309b","article-title":"Genotype-phenotype associations in SCN1A-related epilepsies","volume":"76","author":"S M Zuberi","year":"2011","journal-title":"Neurology"},{"issue":"22","key":"ref4","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1523\/JNEUROSCI.5270-06.2007","article-title":"Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation","volume":"27","author":"I 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Kellinghaus","year":"2009","journal-title":"Ther Clin Risk Manag"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2011.02.083","article-title":"The developmental changes of Na(v)1.1 and Na(v)1.2 expression in the human hippocampus and temporal lobe","volume":"1389","author":"W Wang","year":"2011","journal-title":"Brain Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.eplepsyres.2014.11.021","article-title":"Current understanding of the mechanism of action of the antiepileptic drug lacosamide","volume":"110","author":"M A Rogawski","year":"2015","journal-title":"Epilepsy Res"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"31879","DOI":"10.1038\/srep31879","article-title":"Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures","volume":"6","author":"C Peters","year":"2016","journal-title":"Sci 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