{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:00:31Z","timestamp":1789837231361,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled a cohort of 77 patients with a mean current age of 7.94\u2009\u00b1\u20093.83\u2009years. The mean age of seizure onset was 15.5\u2009months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox\u2013Gastaut syndrome showed the most significant improvement (14\/15) followed by patients with Dravet syndrome (6\/8), and West syndrome (3\/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient\u2019s age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1484752","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T05:03:57Z","timestamp":1726635837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes"],"prefix":"10.3389","volume":"15","author":[{"given":"Osama Y.","family":"Muthaffar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas S.","family":"Alyazidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daad","family":"Alsowat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz A.","family":"Alasiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raidah","family":"Albaradie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamyaa A.","family":"Jad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husam","family":"Kayyali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M. S.","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed K.","family":"Bamaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Alsubaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Daghistani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh S.","family":"Baeesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meshari A.","family":"Alaifan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhakim","family":"Makraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar N.","family":"Alsharief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Imran","family":"Naseer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/J.1528-1167.2008.01579.X","article-title":"The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country","volume":"49","author":"Picot","year":"2008","journal-title":"Epilepsia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.17712\/NSJ.2017.4.20170231","article-title":"Publications pattern of clinical epilepsy research in Saudi Arabia","volume":"22","author":"Baeesa","year":"2017","journal-title":"Neurosciences"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/J.1528-1167.2009.02397.X","article-title":"Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"ref4","first-page":"87","article-title":"Epilepsy: treatment options","volume":"96","author":"Liu","year":"2017","journal-title":"Am Fam Physician"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1136\/archdischild-2012-302822","article-title":"Diagnosis and management of the epilepsies in children: a summary of the partial update of the 2012 NICE epilepsy guideline","volume":"97","author":"Appleton","year":"2012","journal-title":"Arch Dis Child"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"434220","DOI":"10.3389\/FNINS.2019.00005\/BIBTEX","article-title":"Ketogenic diet and epilepsy: what we know so far","volume":"13","author":"D\u2019Andrea Meira","year":"2019","journal-title":"Front Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.3390\/NU11102510","article-title":"Ketogenic Diet and Epilepsy","volume":"11","author":"U\u0142amek-Kozio\u0142","year":"2019","journal-title":"Nutr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1001\/JAMA.1928.02690450007003","article-title":"The ketogenic diet","volume":"90","author":"Peterman","year":"1928","journal-title":"JAMA J Am Med Assoc"},{"key":"ref9","first-page":"307","article-title":"The effects of ketonemia on the course of epilepsy","volume":"2","author":"Rm","year":"1921","journal-title":"Mayo Clin Proc"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/J.YEBEH.2014.02.026","article-title":"Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy","volume":"33","author":"Yuen","year":"2014","journal-title":"Epilepsy Behav"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/J.1528-1167.2008.01821.X","article-title":"History of the ketogenic diet","volume":"49","author":"Wheless","year":"2008","journal-title":"Epilepsia"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1017\/S0025727300018640","article-title":"The falling sickness: a history of epilepsy from the Greeks to the beginnings of modern neurology","volume":"17","author":"Cule","year":"1973","journal-title":"Med Hist"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/J.JTUMED.2023.03.006","article-title":"Regulatory effects of ketogenic diet on the inflammatory response in obese Saudi women","volume":"18","author":"Alkhorayef","year":"2023","journal-title":"J Taibah Univ Med Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2329048X231215630","article-title":"GAMT deficiency among pediatric population: clinical and molecular characteristics and management","volume":"10","author":"Almaghrabi","year":"2023","journal-title":"Child Neurol Open"},{"key":"ref15","first-page":"235","article-title":"Ketogenic diet update and application","volume":"11","author":"Bahassan","year":"2006","journal-title":"Neurosciences"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3389\/FPHAR.2012.00059","article-title":"The ketogenic diet as a treatment paradigm for diverse neurological disorders","volume":"3","author":"Stafstrom","year":"2012","journal-title":"Front Pharmacol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1007\/S11940-008-0043-8","article-title":"The ketogenic diet: uses in epilepsy and other neurologic illnesses","volume":"10","author":"Bara\u00f1ano","year":"2008","journal-title":"Curr Treat Options Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/S13668-022-00405-4","article-title":"The efficacy and safety of ketogenic diets in drug-resistant epilepsy in children and adolescents: a systematic review of randomized controlled trials","volume":"11","author":"Desli","year":"2022","journal-title":"Curr Nutr Rep"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1001\/JAMA.1928.02700020007003","article-title":"Ketogenic diet treatment of epilepsy in adults","volume":"91","author":"Barborka","year":"1928","journal-title":"JAMA J Am Med Assoc"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/S1474-4422(08)70092-9","article-title":"The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial","volume":"7","author":"Neal","year":"2008","journal-title":"Lancet Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.yebeh.2015.10.021","article-title":"A prospective study of the modified Atkins diet for adults with idiopathic generalized epilepsy","volume":"53","author":"Kverneland","year":"2015","journal-title":"Epilepsy Behav"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/EPI4.12098","article-title":"Ketogenic diet for treatment of intractable epilepsy in adults: a meta-analysis of observational studies","volume":"3","author":"Liu","year":"2018","journal-title":"Epilepsia Open"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1001\/JAMAPEDIATRICS.2022.5648","article-title":"Efficacy and safety of dietary therapies for childhood drug-resistant epilepsy: a systematic review and network Meta-analysis","volume":"177","author":"Devi","year":"2023","journal-title":"JAMA Pediatr"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"530","DOI":"10.3389\/fneur.2018.00530","article-title":"The efficacy of ketogenic diet for specific genetic mutation in developmental and epileptic encephalopathy","volume":"9","author":"Ko","year":"2018","journal-title":"Front Neurol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e55","DOI":"10.1111\/J.1528-1167.2011.03394.X","article-title":"Efficacy of the ketogenic diet: which epilepsies respond?","volume":"53","author":"Thammongkol","year":"2012","journal-title":"Epilepsia"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/EPI.13670","article-title":"Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/J.JCLINEPI.2007.11.008","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"61","author":"von Elm","year":"2008","journal-title":"J Clin Epidemiol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/GIM.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/PST.185","article-title":"Sample size of 12 per group rule of thumb for a pilot study","volume":"4","author":"Julious","year":"2005","journal-title":"Pharm Stat"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.21037\/tp-23-211","article-title":"Effect of a ketogenic diet on decrease of seizures in refractory epilepsy among children (infancy to 14 years old) in Saudi Arabia: a cross-sectional study","volume":"12","author":"Baghdadi","year":"2023","journal-title":"Transl Pediatr"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/J.EBCR.2018.11.001","article-title":"Implementation of ketogenic diet in children with drug-resistant epilepsy in a medium resources setting: Egyptian experience","volume":"11","author":"Gerges","year":"2019","journal-title":"Epilepsy Behav Case Reports"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1177\/1535759719888896","article-title":"Earlier is not always better: outcomes when epilepsy occurs in early life versus adolescence","volume":"20","author":"Nickels","year":"2020","journal-title":"Epilepsy Curr"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"135753","DOI":"10.1016\/J.NEULET.2021.135753","article-title":"Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis","volume":"750","author":"Reddy","year":"2021","journal-title":"Neurosci Lett"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1002\/EPI4.12632","article-title":"Differences between men and women in response to antiseizure medication use and the likelihood of developing treatment resistant epilepsy","volume":"7","author":"Cepeda","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/J.SEIZURE.2020.07.011","article-title":"Efficacy of the ketogenic diet in patients with Dravet syndrome: a meta-analysis","volume":"81","author":"Wang","year":"2020","journal-title":"Seizure"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/EPI4.12899","article-title":"Long-term effectiveness and tolerability of ketogenic diet therapy in patients with genetic developmental and epileptic encephalopathy onset within the first 6 months of life","volume":"9","author":"Song","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"106993","DOI":"10.1016\/J.EPLEPSYRES.2022.106993","article-title":"Effects of the ketogenic diet therapy in patients with STXBP1-related encephalopathy","volume":"186","author":"Nam","year":"2022","journal-title":"Epilepsy Res"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/EPI.13701","article-title":"Modified Atkins diet is an effective treatment for children with Doose syndrome","volume":"58","author":"Wiemer-Kruel","year":"2017","journal-title":"Epilepsia"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/J.BRAINDEV.2015.12.012","article-title":"Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy","volume":"38","author":"Mori","year":"2016","journal-title":"Brain and Development"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/J.EJPN.2015.09.001","article-title":"Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy","volume":"20","author":"M\u00fcller","year":"2016","journal-title":"Eur J Paediatr Neurol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/J.EPLEPSYRES.2014.10.014","article-title":"Efficacy and tolerability of the ketogenic diet in Dravet syndrome - comparison with various standard antiepileptic drug regimen","volume":"109","author":"Dressler","year":"2015","journal-title":"Epilepsy Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1111\/J.1469-8749.2012.04233.X","article-title":"Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution\u2019s experience and summary of the literature","volume":"54","author":"Lemmon","year":"2012","journal-title":"Dev Med Child Neurol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/J.1528-1167.2011.03009.X","article-title":"Nonpharmacologic treatments of Dravet syndrome: focus on the ketogenic diet","volume":"52","author":"Caraballo","year":"2011","journal-title":"Epilepsia"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e54","DOI":"10.1111\/J.1528-1167.2011.03107.X","article-title":"Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study","volume":"52","author":"Nabbout","year":"2011","journal-title":"Epilepsia"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1177\/08830738030180011801","article-title":"Ketogenic diet in Rett syndrome","volume":"18","author":"Liebhaber","year":"2003","journal-title":"J Child Neurol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/DMCN.13687","article-title":"The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy","volume":"60","author":"Villaluz","year":"2018","journal-title":"Dev Med Child Neurol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/J.SEIZURE.2021.11.008","article-title":"Evaluation of the seizure control and the tolerability of ketogenic diet in Chinese children with structural drug-resistant epilepsy","volume":"94","author":"Dou","year":"2022","journal-title":"Seizure"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/NU12092616","article-title":"Therapeutic use of the ketogenic diet in refractory epilepsy: what we know and what still needs to be learned","volume":"12","author":"Zarnowska","year":"2020","journal-title":"Nutrients"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3390\/NU12020306","article-title":"Safety and effectiveness of the prolonged treatment of children with a ketogenic diet","volume":"12","author":"Herrero","year":"2020","journal-title":"Nutrients"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1038\/S41598-023-27373-1","article-title":"El Gendy YGA: ketogenic diet for epilepsy control and enhancement in adaptive behavior","volume":"13","author":"el-Rashidy","year":"2023","journal-title":"Sci Rep"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/J.PEDIATRNEUROL.2018.12.012","article-title":"The ketogenic and modified Atkins diet therapy for children with refractory epilepsy of genetic etiology","volume":"94","author":"Jagadish","year":"2019","journal-title":"Pediatr Neurol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/diseases9020039","article-title":"Incidence and characteristics of kidney stones in patients on ketogenic diet: a systematic review and Meta-analysis","volume":"9","author":"Acharya","year":"2021","journal-title":"Diseases"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1046\/J.1528-1157.2002.11302.X","article-title":"Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet","volume":"43","author":"Kossoff","year":"2002","journal-title":"Epilepsia"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/EPI4.12225","article-title":"Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the international ketogenic diet study group","volume":"3","author":"Kossoff","year":"2018","journal-title":"Epilepsia Open"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1484752\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T05:03:59Z","timestamp":1726635839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1484752\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":54,"alternative-id":["10.3389\/fneur.2024.1484752"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1484752","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]},"article-number":"1484752"}}