{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:58:46Z","timestamp":1791669526113,"version":"4.3.4"},"posted":{"date-parts":[[2026,6,2]]},"group-title":"Neurology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["1K23NS136767"],"award-info":[{"award-number":["1K23NS136767"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS127892"],"award-info":[{"award-number":["R01NS127892"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["U01NS1365885"],"award-info":[{"award-number":["U01NS1365885"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["U01NS086090"],"award-info":[{"award-number":["U01NS086090"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living","award":["H133A120085"],"award-info":[{"award-number":["H133A120085"]}]},{"name":"National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living","award":["90DP0039"],"award-info":[{"award-number":["90DP0039"]}]},{"name":"National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living","award":["90DPTB0011"],"award-info":[{"award-number":["90DPTB0011"]}]},{"name":"National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living","award":["90DPTB0027"],"award-info":[{"award-number":["90DPTB0027"]}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["W81XWH-14-2-0176"],"award-info":[{"award-number":["W81XWH-14-2-0176"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chen Institute MGH Research Scholar Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Predicting specific cognitive, psychiatric, and health-related sequelae in patients after acute traumatic brain injury (TBI) remains an important but challenging clinical problem. Acute phase computed tomography (CT) scans acquired show hemorrhagic contusions, a common type of traumatic pathology. However, whether CT-measured contusions predict long-term sequelae is uncertain.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We established a Screening Cohort of patients with acute TBI who received care at a single TBI Model Systems (TBIMS) inpatient rehabilitation facility. Regions of hemorrhagic contusion and edema were labeled on acute brain CT scans using the fully-automated Brain Lesion Analysis and Segmentation Tool (BLAST-CT). We screened 198 outcome variables at 1-year post-injury for association with acute hemorrhagic contusion volume using the Harrell\u2019s Concordance index (C-index), controlling for multiple comparisons using 5,000 outcome permutations. Finally, we tested whether the significant associations in the TBIMS database replicated in acute (Transforming Research and Clinical Knowledge in TBI [TRACK-TBI]) and chronic (Vietnam Head Injury Study [VHIS]) external validation cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The TBIMS Screening Cohort included 345 participants (mean \u00b1 SD age: 55.7 \u00b1 21.5 years) with median [IQR] contusion volume 2.3 cc [0.1, 14.6]. Among 198 candidate outcome variables, only delayed seizures were significantly associated with acute hemorrhagic contusion volume (C-index = 0.81; P\n                    <jats:sub>FWE<\/jats:sub>\n                    = 0.007). Contusion volume was not significantly associated with commonly-used measures of global functioning like the Glasgow Outcome Scale Extended, (C-index = 0.55; P\n                    <jats:sub>FWE<\/jats:sub>\n                    = 1). Within the screening cohort, 30 ccs was the optimal volume threshold for discriminating patients with versus without delayed seizures (OR 12.6, 95% CI: [4.6, 34.3]). Contusions larger than 30 cc remained significantly associated with delayed seizures in two external cohorts: (TRACK-TBI OR 4.1 [1.5, 11.2]; VHIS OR 3.2 [1.7, 6.2]).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Across three cohorts of patients with TBI, CT-derived contusion volume is robustly associated with the development of delayed seizures, in contrast to commonly-used outcomes measuring global functioning. A 30-cc volume threshold can be used to improve epilepsy prediction models and enrich populations for clinical trials.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.01.26354621","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:35:12Z","timestamp":1780457712000},"source":"Crossref","is-referenced-by-count":1,"title":["Contusion Volume is a Cross-cohort Predictor of Delayed Seizures after Traumatic Brain Injury"],"prefix":"10.64898","author":[{"given":"Ajitesh","family":"Nanda","sequence":"first","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, and Radiology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Sun","sequence":"additional","affiliation":[{"name":"Biostatistics Research Center, Herbert Wertheim School of Public Health, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic L.W.V.J.","family":"Schaper","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, and Radiology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3072-6198","authenticated-orcid":false,"given":"Jennifer A","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, and Radiology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Cohen-Zimerman","sequence":"additional","affiliation":[{"name":"Cognitive Neuroscience Laboratory, Brain Injury Research, Shirley Ryan Ability Lab, Chicago, IL"},{"name":"Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J","family":"Markowitz","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3900-356X","authenticated-orcid":false,"given":"Eric S","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA"},{"name":"Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Neurology, Mass General Brigham and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Fox","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, and Radiology, Brigham and Women\u2019s Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L","family":"Edlow","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA"},{"name":"Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Boston, MA"},{"name":"Department of Neurology, Mass General Brigham and Harvard Medical School, Boston, MA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Grafman","sequence":"additional","affiliation":[{"name":"Cognitive Neuroscience Laboratory, Brain Injury Research, Shirley Ryan Ability Lab, Chicago, IL"},{"name":"Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey T","family":"Manley","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA"},{"name":"Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T","family":"Giacino","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA"},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Jain","sequence":"additional","affiliation":[{"name":"Biostatistics Research Center, Herbert Wertheim School of Public Health, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena G","family":"Bodien","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Neurological Surgery, and Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Snider","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Departments of Neurology, Psychiatry, and Radiology, Brigham and Women\u2019s Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Department of Neurology, Mass General Brigham and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TRACK-TBI Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"11","key":"2026060503150735000_2026.06.01.26354621v1.1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic brain injury: progress and challenges in prevention, clinical care, and research","volume":"21","year":"2022","journal-title":"The Lancet Neurology"},{"issue":"1","key":"2026060503150735000_2026.06.01.26354621v1.2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1474-4422(18)30415-0","article-title":"Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"18","year":"2019","journal-title":"The Lancet Neurology"},{"key":"2026060503150735000_2026.06.01.26354621v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9993(03)00287-9"},{"key":"2026060503150735000_2026.06.01.26354621v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2013.11.004"},{"key":"2026060503150735000_2026.06.01.26354621v1.5","unstructured":"Schneider ALC , Huie JR , Boscardin WJ , et al. 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