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Updated: Oct 16, 2025
Objectively Assessing Sports Concussion Utilizing Visual Evoked Potentials
Published on: April 27, 2021
Proteomic Discovery of Noninvasive Biomarkers Associated With Sport-Related Concussions
Cassandra C Daisy1, Speros Varinos1, David R Howell1
1From the Vascular Biology Program (C.C.D., S.V., K.K., M.A.M.), Division of Sports Medicine (D.R.H., W.P.M.), Department of Orthopaedics, Brain Injury Center (D.R.H., R.M., W.P.M.), Sports Concussion Clinic (R.M.), Division of Sports Medicine, Division of Emergency Medicine (R.M.), Department of Urology (R.S.L., J.W.F.), Department of Anesthesia (D.Z.), and Department of Surgery (M.A.M.), Boston Children's Hospital; The Micheli Center for Sports Injury Prevention (D.R.H., R.M., W.P.M.), Waltham, MA; Sports Medicine Center (D.R.H.), Children's Hospital Colorado; Department of Orthopedics (D.R.H.), University of Colorado School of Medicine, Aurora; Departments of Pediatrics (W.P.M.), and Orthopaedic Surgery (W.P.M.), and Surgery (R.S.L., J.W.F., D.Z., M.A.M.), Harvard Medical School; and Harvard Sports Medicine (F.W., B.B.), Boston, MA.
Background And Objectives:
Sport-related concussions affect millions of individuals across the United States each year, and current techniques to diagnose and monitor them rely largely on subjective measures. Our goal was to discover and validate objective, quantifiable noninvasive biomarkers with the potential to be used in sport-related concussion diagnosis.
Methods:
Urine samples from a convenience series of healthy control collegiate athletes who had not sustained a concussion and athletes who sustained a concussion as diagnosed by a sports medicine physician within 7 days were collected prospectively and studied. Participants also completed an instrumented single-task gait analysis as a functional measure. Participants were recruited from a single collegiate athletic program and were ≥18 years of age and were excluded if they had a concomitant injury, active psychiatric conditions, or preexisting neurologic disorders. Using Tandem Mass Tags (TMT) mass spectroscopy and ELISA, we identified and validated urinary biomarkers of concussion.
Results:
Forty-eight control and 47 age- and sex-matched athletes with concussion were included in the study (51.6% female, 48.4% male, average age 19.6 years). Participants represented both contact and noncontact sports. All but 1 of the postconcussion participants reported experiencing symptoms at the time of data collection. Insulin-like growth factor 1 (IGF-1) and IGF binding protein 5 (IGFBP5) were downregulated in the urine of athletes with concussions compared to healthy controls. Multivariable risk algorithms developed to predict the probability of sport-related concussion showed that IGF-1 multiplexed with single-task gait velocity predicts concussion risk across a range of postinjury time points (area under the curve [AUC] 0.786, 95% confidence interval [CI] 0.690-0.884). When IGF-1 and IGFBP5 are multiplexed with single-task gait velocity, they accurately distinguish between healthy controls and individuals with concussion at acute time points (AUC 0.835, 95% CI 0.701-0.968, p < 0.001).
Discussion:
These noninvasive biomarkers, discovered in an objective and validated manner, may be useful in diagnosing and monitoring sport-related concussions in both acute phases of injury and several days after injury.
Trial Registration Information:
ClinicalTrials.gov Identifier: NCT02354469 (submitted February 2015, first patient enrolled August 2015).
Classification Of Evidence:
This study provides Class III evidence that urinary IGF-1 and IGFBP5 multiplexed with single-task gait velocity may be useful in diagnosing sport-related concussion.
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