{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:27Z","timestamp":1791395427538,"version":"4.3.3"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","award":["CRAD001X2204T"],"award-info":[{"award-number":["CRAD001X2204T"]}],"id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102023\u201000266971"],"award-info":[{"award-number":["RS\u20102023\u201000266971"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective, crossover, placebo\u2010controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4\u201340\u2009years with pathologically confirmed FCD 2 and a history of \u22653 seizures per month for two out of the 3\u2009months prior to screening. The trial included a 4\u2010week baseline phase, two 12\u2010week core phases, and a 29\u2010week extension phase. Patients received everolimus or placebo in a blinded manner during core phase I, with crossover to the alternate treatment in core phase II. Everolimus dosage started at 4.5\u2009mg\/m<jats:sup>2<\/jats:sup>\/day, targeting a serum level of 5\u201315\u2009ng\/mL. The primary outcome was the proportion of patients achieving \u226550% seizure reduction from baseline in the last month of each core phase. Safety profiles were compared between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between May 11, 2017, and June 19, 2020, 21 patients completed the core phases. There was no significant difference in the primary outcome between everolimus and placebo groups (24% vs. 19%, p\u2009=\u20090.66). The patients showed varied responses. Three patients with a pathogenic variant in the <jats:italic>MTOR<\/jats:italic> gene or no genetic abnormalities achieved seizure freedom with everolimus in the last month of the core phase, while none of the patients with variants in other genes did. Adverse events, such as mucositis or skin ulceration, were more common with everolimus (19\/21 vs. 7\/21, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). All adverse events resolved without study drug withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Everolimus treatment for 12\u2009weeks did not show overall superiority in reducing seizures compared to placebo. However, it showed promise, mostly in patients with a pathogenic variant in the <jats:italic>MTOR<\/jats:italic> gene, highlighting the need for further research into patient\u2010specific factors influencing treatment response. The everolimus treatment was generally safe and manageable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>This study tested everolimus for reducing seizures in patients with focal cortical dysplasia type 2 (FCD 2). While the drug was not more effective than a placebo for most, few patients showed better results, with some becoming seizure\u2010free. Side effects were common but manageable. More research is needed to understand why certain patients respond better to treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.13104","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T16:38:34Z","timestamp":1732811914000},"page":"243-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-1942","authenticated-orcid":false,"given":"Se Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-8847","authenticated-orcid":false,"given":"Hoon\u2010Chul","family":"Kang","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Ho","family":"Roh","sequence":"additional","affiliation":[{"name":"Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongsung","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy Yonsei University  Incheon Republic of Korea"},{"name":"School of Pharmacy Jeonbuk National University  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Lok","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy Yonsei University  Incheon Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok\u2010Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-9406","authenticated-orcid":false,"given":"Donghwa","family":"Yang","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"},{"name":"Division of Pediatric Neurology, Department of Pediatrics National Health Insurance Service Ilsan Hospital  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Som","family":"Choi","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"},{"name":"Department of Pediatrics Ewha Womans University Seoul Hospital, Ewha Womans University School of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Department of Pediatrics Yonsei University College of Medicine, Severance Children's Hospital, Epilepsy Research Institute  Seoul Republic of Korea"},{"name":"Department of Pediatrics Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine  Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) SoVarGen, Inc.  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