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Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium

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dc.contributor.authorMcCrea, Michael A.en
dc.contributor.authorBroglio, Steven P.en
dc.contributor.authorMcAllister, Thomas W.en
dc.contributor.authorGill, Jessica M.en
dc.contributor.authorGiza, Christopher C.en
dc.contributor.authorHuber, Daniel L.en
dc.contributor.authorHarezlak, Jaroslawen
dc.contributor.authorCameron, Kenneth L.en
dc.contributor.authorHouston, Megan N.en
dc.contributor.authorMcGinty, Gerald T.en
dc.contributor.authorJackson, Jonathan C.en
dc.contributor.authorGuskiewicz, Kevin M.en
dc.contributor.authorMihalik, Jason P.en
dc.contributor.authorBrooks, M. Alisonen
dc.contributor.authorDuma, Stefan M.en
dc.contributor.authorRowson, Stevenen
dc.contributor.authorNelson, Lindsay D.en
dc.contributor.authorPasquina, Paulen
dc.contributor.authorMeier, Timothy B.en
dc.contributor.authorForoud, Tatianaen
dc.contributor.authorKatz, Barry P.en
dc.contributor.authorSaykin, Andrew J.en
dc.contributor.authorCampbell, Darren E.en
dc.contributor.authorSvoboda, Steven J.en
dc.contributor.authorGoldman, Joshua T.en
dc.contributor.authorDiFiori, John P.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2020-05-21T13:02:38Zen
dc.date.available2020-05-21T13:02:38Zen
dc.date.issued2020-01-24en
dc.description.abstractQuestion Is sport-related concussion associated with levels of traumatic brain injury biomarkers in collegiate athletes? Findings In this case-control study of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport athletes, the athletes with concussion had significant elevations in multiple traumatic brain injury biomarkers compared with preseason baseline and with 2 groups of control athletes without concussion during the acute postinjury period. Meaning These results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in sport-related concussion. This case-control study examines the association between sport-related concussion and levels of traumatic brain injury biomarkers in collegiate athletes. Importance There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group x visit) was found for GFAP (F-7,F-1507.36 = 16.18, P < .001), UCH-L1 (F-7,F-1153.09 = 5.71, P < .001), and tau (F-7,F-1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F-7,F-1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (beta = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (beta = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.en
dc.description.notesThis work received support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium funded in part by the NCAA and the DOD andwas supported by award W81XWH-14-2-0151 from the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program.en
dc.description.sponsorshipGrand Alliance Concussion Assessment, Research, and Education (CARE) Consortium - NCAA; DODUnited States Department of Defense; Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program [W81XWH-14-2-0151]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1001/jamanetworkopen.2019.19771en
dc.identifier.issn2574-3805en
dc.identifier.issue1en
dc.identifier.pmid31977061en
dc.identifier.urihttp://hdl.handle.net/10919/98508en
dc.identifier.volume3en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleAssociation of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortiumen
dc.title.serialJAMA Network Openen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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