{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:06:26Z","timestamp":1789200386114,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102024\u201000405260"],"award-info":[{"award-number":["RS\u20102024\u201000405260"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102025\u201002263053"],"award-info":[{"award-number":["RS\u20102025\u201002263053"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102025\u201025458096"],"award-info":[{"award-number":["RS\u20102025\u201025458096"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201000555034"],"award-info":[{"award-number":["RS\u20102025\u201000555034"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004080","name":"Korea Drug Development Fund","doi-asserted-by":"publisher","award":["RS\u20102025\u201002213662"],"award-info":[{"award-number":["RS\u20102025\u201002213662"]}],"id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2026\u2010ER0602\u201000"],"award-info":[{"award-number":["2026\u2010ER0602\u201000"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To evaluate long\u2010term developmental outcomes and identify independent predictors of favorable developmental outcomes at 3\u2009years of age in children with infantile epileptic spasms syndrome (IESS) treated with a standardized stepwise vigabatrin and high\u2010dose prednisolone protocol.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This prospective single\u2010center cohort study enrolled 236 children with IESS managed according to a standardized protocol between March 2016 and April 2022 at Severance Children's Hospital. All patients received initial vigabatrin, with high\u2010dose oral prednisolone added for non\u2010vigabatrin responders. Developmental outcome at 3\u2009years was classified as favorable (mental quotient [MQ] \u2265\u200970 and psychomotor quotient [PMQ] \u2265\u200970) or unfavorable using the Bayley Scales of Infant and Toddler Development, Second Edition. Independent predictors were identified by multivariable logistic regression using Firth's penalized method to address complete separation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall treatment response was achieved in 175 patients (74.2%). At 3\u2009years, 49 patients (20.8%) achieved favorable developmental outcome. On multivariable analysis, etiology and treatment response were the only independent predictors. Compared to unknown etiology, structural etiology (aOR 0.085; 95% CI 0.026\u20130.281;\n p<\/jats:italic>\n \u2009<\u20090.001) and genetic etiology (aOR 0.023; 95% CI 0.002\u20130.357;\n p\u2009=<\/jats:italic>\n \u20090.007) were associated with significantly lower odds of favorable developmental outcome. Unresponsive patients had markedly lower odds compared to vigabatrin responders (aOR 0.030; 95% CI 0.002\u20130.523;\n p\u2009=<\/jats:italic>\n \u20090.02). Notably, none of the 49 patients with genetic etiology and none of the 61 unresponsive patients achieved favorable developmental outcome. Lead time showed a significant univariable association, but this association was attenuated after adjustment for other prognostic factors.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n Etiology and treatment response are the dominant independent predictors of favorable developmental outcome at 3\u2009years in children with IESS. These findings underscore the need for early etiological diagnosis and individualized treatment strategies, particularly in patients with genetic etiology or those unresponsive to first\u2010line therapy.<\/jats:p>\n <\/jats:sec>\n \n Plain Language Summary<\/jats:title>\n Infantile epileptic spasms syndrome (IESS) is a severe epilepsy of infancy that often leads to lasting developmental problems. In this study of 236 children with IESS treated with a stepwise vigabatrin and prednisolone protocol, developmental outcome at age 3 was mainly associated with the underlying cause of IESS and response to treatment. Children without an identified underlying cause and those who responded to treatment had better developmental outcomes than children with a structural or genetic cause or those who did not respond. These findings emphasize the importance of careful evaluation and individualized treatment in children with IESS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi4.70319","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:42:12Z","timestamp":1789198932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010term developmental outcome in infantile epileptic spasms syndrome after high\u2010dose prednisolone and vigabatrin treatment"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5685-2843","authenticated-orcid":false,"given":"Soyoung","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Department of Pediatrics Soonchunhyang University Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-2564","authenticated-orcid":false,"given":"Hui Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Epilepsy Research Institute, Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-1942","authenticated-orcid":false,"given":"Se Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Epilepsy Research Institute, Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-9343","authenticated-orcid":false,"given":"Joon Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Epilepsy Research Institute, Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-8432","authenticated-orcid":false,"given":"Ara","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Epilepsy Research Institute, Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Hanim Center for Precision Medicine, Epilepsy Research Institute, Severance Children's Hospital Yonsei University College of Medicine 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":"Department of Pediatric Neurology, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Epilepsy Research Institute, Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"Hanim Center for Precision Medicine, Epilepsy Research Institute, Severance Children's Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"issue":"10","key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1111\/j.1528-1167.2010.02657.x","article-title":"Infantile spasms: a U.S. consensus report","volume":"51","author":"Pellock JM","year":"2010","journal-title":"Epilepsia"},{"issue":"6","key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/epi.17239","article-title":"ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE task force on nosology and definitions","volume":"63","author":"Zuberi SM","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.eplepsyres.2014.11.012","article-title":"Neurodevelopmental outcome of infantile spasms: a systematic review and meta\u2010analysis","volume":"109","author":"Widjaja E","year":"2015","journal-title":"Epilepsy Res"},{"issue":"11","key":"e_1_2_14_5_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1474-4422(05)70199-X","article-title":"The United Kingdom infantile spasms study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial","volume":"4","author":"Lux AL","year":"2005","journal-title":"Lancet Neurol"},{"issue":"9447","key":"e_1_2_14_6_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(04)17400-X","article-title":"The United Kingdom infantile spasms study comparing vigabatrin with prednisolone or tetracosactide at 14\u2009days: a multicentre, randomised controlled trial","volume":"364","author":"Lux AL","year":"2004","journal-title":"Lancet"},{"issue":"1","key":"e_1_2_14_7_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1474-4422(16)30294-0","article-title":"Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open\u2010label trial","volume":"16","author":"O'Callaghan FJK","year":"2017","journal-title":"Lancet Neurol"},{"issue":"10","key":"e_1_2_14_8_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S2352-4642(18)30244-X","article-title":"Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18\u2010month outcomes of an open\u2010label, randomised controlled trial","volume":"2","author":"O'Callaghan FJK","year":"2018","journal-title":"Lancet Child Adolesc Health"},{"issue":"7","key":"e_1_2_14_9_1","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/j.1528-1167.2011.03127.x","article-title":"The effect of lead time to treatment and of age of onset on developmental outcome at 4\u2009years in infantile spasms: evidence from the United Kingdom infantile spasms study","volume":"52","author":"O'Callaghan FJK","year":"2011","journal-title":"Epilepsia"},{"key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.eplepsyres.2015.07.008","article-title":"Improving the inter\u2010rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms","volume":"116","author":"Mytinger JR","year":"2015","journal-title":"Epilepsy Res"},{"issue":"5","key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1136\/adc.2009.160606","article-title":"Developmental and epilepsy outcomes at age 4\u2009years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: a multi\u2010centre randomised trial","volume":"95","author":"Darke K","year":"2010","journal-title":"Arch Dis Child"},{"issue":"4","key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/epi4.12540","article-title":"Confirmation of infantile spasms resolution by prolonged outpatient EEGs","volume":"6","author":"Yuskaitis CJ","year":"2021","journal-title":"Epilepsia Open"}],"container-title":["Epilepsia 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