{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:34:50Z","timestamp":1790742890205,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20lk0201069h0004"],"award-info":[{"award-number":["20lk0201069h0004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08236"],"award-info":[{"award-number":["20K08236"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JPMH20FC1039"],"award-info":[{"award-number":["JPMH20FC1039"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen patients (aged 6\u201357\u2009years) with FCD type II received sirolimus at an initial dose of 1 or 2\u2009mg\/day based on body weight (FCDS\u201001). In 15 patients, the dose was adjusted to achieve target trough ranges of 5\u201315\u2009ng\/mL, followed by a 12\u2010week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES\u2010FCD) in which 60 patients with FCD type II were included as an external control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1\u20134\u2010, 5\u20138\u2010, and 9\u201312\u2010week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus\u2010treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL\u20106 level was elevated over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51505","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T12:41:41Z","timestamp":1642509701000},"page":"181-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Sirolimus for epileptic seizures associated with focal cortical dysplasia type <scp>II<\/scp>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-8553","authenticated-orcid":false,"given":"Mitsuhiro","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Pediatrics Showa University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kada","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center  Nagoya 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