{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:23:59Z","timestamp":1774326239724,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"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":["NNF17OC0029860"],"award-info":[{"award-number":["NNF17OC0029860"]}],"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Traumatic brain injury (TBI) and stroke are well\u2010known causes of acquired epilepsy. TBI is also a risk factor for stroke, and injury\u2010induced stroke may indirectly convey a proportion of the epilepsy risk following TBI. We studied the extent to which the effect of TBI on epilepsy operated through intermediary stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed a nationwide, matched, register\u2010based cohort of adults  40\u2009years of age whose first TBI at Danish hospitals was recorded between 2004 and 2016. A matched reference population was sampled for comparison. During follow\u2010up, we recorded all acute strokes. Cox proportional hazard models and the difference method were used to estimate the total and controlled direct effect hazard ratios (HRs) of TBI on epilepsy and the indirect effect HRs of TBI on epilepsy operating through stroke, and to calculate the proportion eliminated. Analyses were stratified by severity of, age at, and time since TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We followed 57\u2009900 persons with TBI (48.6% males) from median age 61\u2009years (interquartile range\u00a0=\u00a051\u201375), and 561\u2009977 age\u2010 and sex\u2010matched references. The total effect of TBI on epilepsy was higher for persons aged 40\u201359\u2009years (HR\u00a0=\u00a05.15, 95% confidence interval [CI] =\u20094.65\u20135.72) than for persons aged  60\u2009years (HR\u00a0=\u00a04.55, 95% CI\u00a0=\u00a04.19\u20134.95). In contrast, the indirect effect of TBI mediated by stroke was lower for persons aged 40\u201359\u2009years (HR\u00a0=\u00a01.02, 95% CI\u00a0=\u00a01.02\u20131.03) than for persons aged  60\u2009years (HR\u00a0=\u00a01.05, 95% CI\u00a0=\u00a01.04\u20131.06). We estimated 2.3% and 5.6% of the risk of epilepsy after TBI to operate through stroke for these age groups, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Less than 6% of the risk of epilepsy following TBI operated through intermediary stroke. However, this mechanism seems to play an increasing role with age and for late onset epilepsies. This warrants further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17497","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T13:46:35Z","timestamp":1671543995000},"page":"718-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Traumatic brain injury, stroke, and epilepsy: A mediation study in a Danish nationwide cohort"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-7969","authenticated-orcid":false,"given":"Kasper","family":"Lolk","sequence":"first","affiliation":[{"name":"National Center for Register\u2010Based Research, School of Business and Social Sciences Aarhus University  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Center for Integrated Register\u2010Based Research Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theis","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Elwert","sequence":"additional","affiliation":[{"name":"Department of Sociology University of Wisconsin\u2013Madison  Madison Wisconsin USA"},{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin\u2013Madison  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie W.","family":"Dreier","sequence":"additional","affiliation":[{"name":"National Center for Register\u2010Based Research, School of Business and Social Sciences Aarhus University  Aarhus Denmark"},{"name":"Center for Integrated Register\u2010Based Research Aarhus University  Aarhus 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