{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:19:40Z","timestamp":1789521580167,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Timely referral and efficient presurgical evaluation are important to optimize postoperative seizure and developmental outcomes in epilepsy surgery patients. We aimed to identify determinants of time intervals from epilepsy diagnosis to referral to specialized centers and epilepsy surgery in children with malformations of cortical development (MCDs) and low\u2010grade epilepsy\u2010associated tumors (LEATs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study in 3 European centers, including children with MCD or LEAT who underwent epilepsy surgery between 2010 and 2020. Primary endpoints were (1) time interval between epilepsy diagnosis and referral for presurgical evaluation, (2) duration of presurgical evaluation trajectory, and (3) time from diagnosis to surgery. The secondary endpoint was postoperative seizure outcome. In our primary analysis, we performed a multivariable Cox proportional hazards analysis and used histopathological diagnosis, age at first seizure, presence of developmental delay, 1st seizure classification, initial EEG and MRI findings, duration until drug resistance, and family history as covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 507 children included, 259 (51%) had an MCD and 248 (49%) had a LEAT. Earlier drug resistance and the presence of an MR\u2010visible epileptogenic lesion were associated with shorter times from diagnosis to referral and surgery, and later onset of seizures was associated with a shorter time to surgery. LEAT was associated with a shorter presurgical evaluation and shorter time to surgery. An older age at surgery, shorter time from diagnosis to surgery, and a histopathological diagnosis of FCDII and LEAT were all independently associated with better postoperative seizure outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Epilepsy surgery was performed earlier in children with MR\u2010visible lesions and early drug resistance, particularly those with LEAT, and a shorter duration to epilepsy surgery was associated with better seizure outcomes. Many patients were initially considered MRI\u2010negative in the referring center, highlighting the importance of early referral, epilepsy\u2010dedicated MRI protocols, and experienced neuroradiologists. Increasing awareness of timely referral and surgery benefits is crucial for improving outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Children with severe focal structural epilepsy who have not responded to medication often benefit from surgery, especially when they are referred early. This study of 507 children found that certain factors\u2014such as visible brain abnormalities on the first MRI, especially a specific type of brain tumor (LEAT), early signs of drug resistance, and seizures starting later in childhood\u2014were linked to shorter times from diagnosis to surgery and that shorter time to surgery was linked to better seizure outcomes. Many children whose initial MRIs appeared to be normal were later found to have an epileptogenic brain lesion when examined at specialized centers. Early referral, advanced imaging, and expert evaluation are key to improving postsurgical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70074","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T09:55:54Z","timestamp":1754474154000},"page":"1345-1352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["What determines the timing of epilepsy surgery in children with cortical malformations and low\u2010grade epilepsy\u2010associated tumors?"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-1098","authenticated-orcid":false,"given":"Maurits W. C. B.","family":"Sanders","sequence":"first","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4795-152X","authenticated-orcid":false,"given":"Matyas","family":"Ebel","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, Second Faculty of Medicine Charles University and Motol University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswin","family":"Chari","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel","family":"Fleumer","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca M.","family":"Vasilica","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-5804","authenticated-orcid":false,"given":"Maria H.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tisdall","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3462-7421","authenticated-orcid":false,"given":"Barbora","family":"Splitkova","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, Second Faculty of Medicine Charles University and Motol University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anezka","family":"Belohlavkova","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, Second Faculty of Medicine Charles University and Motol University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1511-6834","authenticated-orcid":false,"given":"Willem M.","family":"Otte","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor E.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-4829","authenticated-orcid":false,"given":"J. Helen","family":"Cross","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees P. J.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Krsek","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, Second Faculty of Medicine Charles University and Motol University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703784"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00569.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30220-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107093"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl316"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2018.1455503"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-019-04124-0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.10.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70325-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007753"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17301"},{"key":"e_1_2_9_14_1","first-page":"609","volume-title":"Surgical treatment of the epilepsies","author":"Engel J","year":"1993"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02397.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12176"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30127-2"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17350"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.03.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2022.100561"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.03.009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.03504.x"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T10:32:05Z","timestamp":1764671525000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/epi4.70074"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70074","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2024-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}