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Focusing on biomarkers across biofluid\u2010based protein, genetic, neuroimaging, and neurophysiological categories, this review distinguishes between TBI patients who develop PTE and those who do not. The review adheres to established methodologies outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data presentation follows the Meta\u2010analyses of Observational Studies (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses (PRISMA) guidelines. Medline, Embase, and Web of Science were systematically searched and yielded 7538 records, of which 18 met inclusion criteria (moderate\u2013severe TBI in humans, follow\u2010up of at least 6\u2009months, and no prior history of epilepsy). The review aggregates data from 15 cohort and 3 case\u2013control studies (risk of bias was assessed using the Newcastle\u2010Ottawa Scale). Statistically significant biomarkers were identified, with neurophysiological biomarkers showing the strongest effect size in a two\u2010study meta\u2010analysis. PTE, a severe long\u2010term outcome of TBI affecting 2% to 53% of individuals with TBI, lacks validated biomarkers for forecasting development, crucial for designing preventive clinical trials. A multimodal approach, integrating biofluid\u2010based protein, genetic, neuroimaging, and neurophysiological data, offers a promising strategy to enhance the predictability of PTE development and, potentially, its treatment. The study's protocol is registered in the International Prospective Register of Systematic Reviews PROSPERO (Registration ID: CRD42023470245).<\/jats:p>","DOI":"10.1111\/epi.18131","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T14:34:41Z","timestamp":1731422081000},"page":"6-32","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exploring multimodal biomarker candidates of post\u2010traumatic epilepsy following moderate to severe traumatic brain injury: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-7598","authenticated-orcid":false,"given":"Alexander A.","family":"Bruckhaus","sequence":"first","affiliation":[{"name":"Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0240-1840","authenticated-orcid":false,"given":"Tuba","family":"Asifriyaz","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-9780","authenticated-orcid":false,"given":"Kseniia","family":"Kriukova","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7198-8621","authenticated-orcid":false,"given":"Terence J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The School of Translational Medicine, The Alfred Centre Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9145-0098","authenticated-orcid":false,"given":"Denes V.","family":"Agoston","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics, School of Medicine USU  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-5627","authenticated-orcid":false,"given":"Richard J.","family":"Staba","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-8439","authenticated-orcid":false,"given":"Nigel C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The School of Translational Medicine, The Alfred Centre Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9476","authenticated-orcid":false,"given":"Solomon L.","family":"Mosh\u00e9","sequence":"additional","affiliation":[{"name":"Saul R. 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