{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:57:33Z","timestamp":1791950253321,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>KCNT1<\/jats:italic>\u2010related epilepsies encompass three main phenotypes: (i) epilepsy of infancy with migrating focal seizures (EIMFS), (ii) autosomal dominant or sporadic sleep\u2010related hypermotor epilepsy [(AD)SHE], and (iii) different types of developmental and epileptic encephalopathies (DEE). Many patients present with drug\u2010resistant seizures and global developmental delays. In addition to conventional anti\u2010seizure medications (ASM), multiple alternative therapies have been tested including the ketogenic diet (KD), cannabidiol (CBD\u2014including Epidyolex \u00a9 and other CBD derivatives) and quinidine (QUIN). We aimed to clarify the current state of the art concerning the benefits of those therapies administered to the three groups of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a literature review on PubMed and EMBase with the keyword \u201cKCNT1\u201d and selected articles reporting qualitative and\/or quantitative information on responses to these treatments. A treatment was considered beneficial if it improved seizure frequency and\/or intensity and\/or quality of life. Patients were grouped by phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 43 studies including 197 patients were reviewed. For EIMFS patients (32 studies, 135 patients), KD resulted in benefit in 62.5% (25\/40), all types of CBD resulted in benefit in 50% (6\/12), and QUIN resulted in benefit in 44.6% (25\/56). For (AD)SHE patients (10 studies, 32 patients), we found only one report of treatment with KD, with no benefit noted. QUIN was trialed in 8 patients with no reported benefit. For DEE patients (10 studies, 30 patients), KD resulted in benefit for 4\/7, CBD for 1\/2, and QUIN for 6\/9. In all groups, conventional ASM are rarely reported as beneficial (in 5%\u201325% of patients).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Ketogenic diet, CBD, and QUIN treatments appear to be beneficial in a subset of patient with drug\u2010resistant epilepsy. The KD and CBD are reasonable to trial in patients with KCNT1\u2010related epilepsy. Further studies are needed to identify optimal treatment strategies and to establish predictive response factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>We performed an extensive review of scientific articles providing information about the therapeutic management of epilepsy in patients with epilepsy linked to a mutation in the KCNT1 gene. Conventional anti\u2010seizure treatments were rarely reported to be beneficial. The ketogenic diet (a medical diet with very high fat, adequate protein and very low carbohydrate intake) and cannabidiol appeared to be useful, but larger studies are needed to reach a conclusion.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12975","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T07:14:15Z","timestamp":1719040455000},"page":"1176-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Efficacy of anti\u2010seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in <i>KCNT1<\/i>\u2010related epilepsy: A systematic review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2376-8026","authenticated-orcid":false,"given":"Mathilde","family":"Gras","sequence":"first","affiliation":[{"name":"Reference Center for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, APHP, Member of EPICARE Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Institut Imagine, INSERM U1163, Universit\u00e9 Paris Cite  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bearden","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Neurology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"West","sequence":"additional","affiliation":[{"name":"KCNT1 Epilepsy Foundation (501C3). President. Co\u2010Founder. Director of Clinical Medicine  Newport Beach California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-4074","authenticated-orcid":false,"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, APHP, Member of EPICARE Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Institut Imagine, INSERM U1163, Universit\u00e9 Paris Cite  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858418763752"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17648"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00209"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab219"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz240"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15479"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000100"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2022.10.017"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004769"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2019.12.024"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14551"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2023.01.017"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102230"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2022-0241"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10808-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2020-0182"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008842"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16480"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.648519"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.05.002"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00739-y"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2019.02.002"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2017.11.017"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2019.1026"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.02.019"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073819854853"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50847"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.AIAN_229_18"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-231178"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000363"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-0657-9"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2017.09.008"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004762"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.708"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.08.057"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004674"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2016.08.002"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2015.12.012"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2016.01.004"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0000000000000178"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13072"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24520"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.06.024"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24229"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.08.096"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2441"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.03.016"},{"key":"e_1_2_11_50_1","first-page":"834","article-title":"Efficacy of anti\u2010seizure medications, quinidine, and ketogenic diet therapy for KCNT1\u2010related epilepsy and genotype\u2010efficacy correlation analysis","volume":"12","author":"Lin Z","year":"2021","journal-title":"Front Neurol"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24128"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2023.109315"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2011.0406"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146090"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101100"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:48:05Z","timestamp":1755863285000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,22]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/epi4.12975"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12975","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,22]]},"assertion":[{"value":"2024-01-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}