{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:08:25Z","timestamp":1788743305018,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Patients with focal, lesional epilepsy present with seizures at variable ages. Larger lesion size and overlap with sensorimotor or default mode network (DMN) have been associated with younger age at seizure onset in cohorts with mixed types of focal cortical dysplasia (FCD). Here, we studied determinants of age at seizure onset in patients with bottom\u2010of\u2010sulcus dysplasia (BOSD), a discrete type of FCD with highly localized epileptogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighty\u2010four patients (77% operated) with BOSD were studied. Demographic, histopathologic, and genetic findings were recorded. BOSD volume and anatomical, primary versus association, rostral versus caudal, and functional network locations were determined. Normative functional connectivity analyses were performed using each BOSD as a region of interest in resting\u2010state functional magnetic resonance imaging data of healthy children. Variables were correlated with age at seizure onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median age at seizure onset was 5.4 (interquartile range\u2009=\u20092\u20137.9) years. Of 50 tested patients, 22 had somatic and nine had germline pathogenic mammalian target of rapamycin (mTOR) pathway variants. Younger age at seizure onset was associated with greater BOSD volume (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.002), presence of a germline pathogenic variant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.04), DMN overlap (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.04), and increased functional connectivity with the DMN (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05, false discovery rate corrected). Location within sensorimotor cortex and networks was not associated with younger age at seizure onset in our relatively small but homogenous cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Greater lesion size, pathogenic mTOR pathway germline variants, and DMN connectivity are associated with younger age at seizure onset in small FCD. Our findings strengthen the suggested role of DMN connectivity in the onset of FCD\u2010related focal epilepsy and reveal novel contributions of genetic etiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17947","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:20:32Z","timestamp":1710555632000},"page":"1644-1657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Why did my seizures start now? Influences of lesion connectivity and genetic etiology on age at seizure onset in focal epilepsy"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9894-4610","authenticated-orcid":false,"given":"Emma","family":"Macdonald\u2010Laurs","sequence":"first","affiliation":[{"name":"Department of Neurology Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6534-2800","authenticated-orcid":false,"given":"Aaron E. L.","family":"Warren","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Medicine University of Melbourne  Melbourne Victoria Australia"},{"name":"Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-5607","authenticated-orcid":false,"given":"Richard J.","family":"Leventer","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6388-7444","authenticated-orcid":false,"given":"A. Simon","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26442"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2021.106598"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00022-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17130"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1996.tb01026.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001229107"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2106-10.2011"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/pmed.1998.0274"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17495"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad379"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac117"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010670"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.004"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405003111"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.1988"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012147"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0395"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.116946"},{"key":"e_1_2_12_21_1","first-page":"58","article-title":"Symmetric 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