{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:14:03Z","timestamp":1791994443597,"version":"4.4.0"},"reference-count":90,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R400\u20102022\u20101205"],"award-info":[{"award-number":["R400\u20102022\u20101205"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R402\u20102022\u20101506"],"award-info":[{"award-number":["R402\u20102022\u20101506"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF16OC0 019126"],"award-info":[{"award-number":["NNF16OC0 019126"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF22OC0075033"],"award-info":[{"award-number":["NNF22OC0075033"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010078","name":"Region Midtjylland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019563","name":"Epilepsiforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019563","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was undertaken to evaluate whether elevated serum levels of S100 calcium\u2010binding protein beta (S100B) provide a prognostic biomarker for the development of epilepsy after traumatic brain injury (TBI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a register\u2010based cohort study in adults (\u226518\u2009years of age) who presented to Danish emergency departments between 2013 and 2022 with a head injury and underwent serum S100B sampling. We classified injury severity hierarchically according to TBI diagnoses (No TBI, mild TBI without [mTBI\u2212] and with [mTBI+] detectable lesions) recorded the first week after injury admission. Epilepsy onset was set to the date of the first epilepsy diagnosis or first redeemed antiseizure medication prescription after TBI. Persons were followed until epilepsy onset, death, or December 31, 2022, whichever came first. We estimated hazard ratios (HRs) and absolute risk (AR) of epilepsy according to S100B levels with corresponding 95% confidence intervals (CIs), according to injury severity, age, sex, and multimorbidity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean serum S100B levels increased with TBI severity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). A 1\u2010unit S100B increase (in \u03bcg\/L) after TBI carried increased epilepsy risk (HR\u2009=\u20091.46, 95% CI\u2009=\u20091.20\u20131.77), but only in mTBI+ patients (HR\u2009=\u20092.12, 95% CI\u2009=\u20091.55\u20132.92). The overall 5\u2010year AR of epilepsy after any head injury was 3.8% (95% CI = 1.5%\u20137.8%), 2.0% (95% CI = 1.2%\u20133.1%), and 1.0% (95% CI = .8%\u20131.3%) in patients with S100B levels of 2.0, 1.0, and .1 \u03bcg\/L, respectively, and in the subgroup of mTBI+ patients the ARs were 21.3% (95% CI = 9.0%\u201338.2%), 5.7% (95% CI = 2.6%\u201310.6%), and .8% (95% CI = .2%\u20132.4%). Age and sex had minor influence on the association, but having a high multimorbidity score (HR = 2.03, 95% CI = 1.28\u20133.23) was a pivotal modifier, rendering the association insignificant in those without (HR = 1.21, 95% CI = 0.88\u20131.67).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Elevated serum S100B levels after TBI were associated with subsequent epilepsy, likely reflecting the extent of intracranial injury. Despite study limitations, these findings support the potential of S100B as a prognostic biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70049","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:48:39Z","timestamp":1766497719000},"page":"1332-1344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>S100<\/scp>\n                    calcium\u2010binding protein beta (S100B) in serum as a biomarker for epilepsy after traumatic brain injury: A register\u2010based cohort study in Danish adults"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-7969","authenticated-orcid":false,"given":"Kasper","family":"Lolk","sequence":"first","affiliation":[{"name":"Department of Public Health, National Center for Register\u2010Based Research Aarhus University  Aarhus Denmark"},{"name":"Center for Integrated Register\u2010Based Research Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9445-4545","authenticated-orcid":false,"given":"Johan","family":"Zelano","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Wallenberg Center of Molecular and Translational Medicine University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Neurology Sahlgrenska University Hospital, member of European Reference Network EpiCARE  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-2614","authenticated-orcid":false,"given":"Betina Bitsch","family":"Trabjerg","sequence":"additional","affiliation":[{"name":"Department of Public Health, National Center for Register\u2010Based Research Aarhus University  Aarhus Denmark"},{"name":"Center for Integrated Register\u2010Based Research Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-4170","authenticated-orcid":false,"given":"Julie Werenberg","family":"Dreier","sequence":"additional","affiliation":[{"name":"Department of Public Health, National Center for Register\u2010Based Research Aarhus University  Aarhus Denmark"},{"name":"Center for Integrated Register\u2010Based Research Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9385-6435","authenticated-orcid":false,"given":"Jakob","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60214-2"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801013380104"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1993.tb02586.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1552923"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00850.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10090"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2003.50022"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09926-w"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa448"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119605"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-023-00807-2"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.11.009"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0574-x"},{"issue":"9","key":"e_1_2_12_15_1","article-title":"Guidelines for the initial management of adult patients with minimal to moderate head injury","volume":"176","author":"Eskesen V","year":"2014","journal-title":"Ugeskr Laeger"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-019-01288-x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0533-y"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13049-021-00891-5"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2013-0621"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107080"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6375"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2012.2579"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2019.105380"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2020.03.012"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2016.1144410"},{"issue":"1","key":"e_1_2_12_26_1","first-page":"236","article-title":"S\u2010100 protein as marker of the blood\u2010brain barrier disruption in children with internal hydrocephalus and epilepsy\u2010\u2010a preliminary study","volume":"49","author":"Sendrowski K","year":"2004","journal-title":"Rocz Akad Med Bialymst"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(12)70940-4"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2012.10.012"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-12-15"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-9026-1"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.08.036"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(99)00026-1"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00456"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00492"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2021.08.012"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106520"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"issue":"3","key":"e_1_2_12_38_1","first-page":"250","article-title":"Recommendations on measurement units \u2010 why and how","volume":"30","author":"Hansen YBL","year":"2019","journal-title":"EJIFCC"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S245060"},{"issue":"4","key":"e_1_2_12_40_1","first-page":"441","article-title":"The Danish civil registration system. A cohort of eight million persons","volume":"53","author":"Pedersen CB","year":"2006","journal-title":"Dan Med Bull"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-014-9930-3"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810394717"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810395825"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494811405098"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810394715"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-007-1489-2"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/neur.2024.0101"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-016-3046-3"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.835597"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v042.i08"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2023.111187"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2000.17.113"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7522"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056805"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00327"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-7241-21-52"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0929-7820"},{"key":"e_1_2_12_59_1","volume-title":"10th special report to the US congress on alcohol and health: highlights from current research","author":"Abuse NIoA, Alcoholism","year":"2000"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/emp2.13245"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02412-2"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.4274\/ArchEpilepsy.2023.231289"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2003.00159.x"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1586729"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(00)00478-0"},{"issue":"02","key":"e_1_2_12_66_1","first-page":"115","article-title":"Brain function in children with untreated epilepsy: relationship to biomarkers of brain damage","volume":"2","author":"Hamed SA","year":"2013","journal-title":"J Pediatr Epilepsy"},{"key":"e_1_2_12_67_1","first-page":"90","article-title":"S100B protein levels in patients admitted to an emergency service due to seizures","volume":"26","author":"Do\u011fan FS","year":"2013","journal-title":"Marmara Med J"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/44.5.1056"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076602"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2024.111313"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab055"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1080\/02699050050203540"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.2366"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000209534.61058.35"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/HTR.0b013e3181e57e22"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12873-024-01124-5"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.800015"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02285.x"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.0689"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2007.05.009"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03581.x"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-199308000-00035"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17732"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2024-334547"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17497"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013733107520"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1044\/2020_AJSLP-20-00081"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-50"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12245-023-00530-z"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/jalm.2019.031187"},{"key":"e_1_2_12_91_1","article-title":"Kun hvert andet hospital bruger blodpr\u00f8ve fremfor CT\u2010scanning ved hjernerystelse","author":"Cuculiza M","year":"2019","journal-title":"SundhedspolitiskTidskriftdk"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70049","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:36:08Z","timestamp":1774280168000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,23]]},"references-count":90,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/epi.70049"],"URL":"https:\/\/doi.org\/10.1002\/epi.70049","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,23]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}