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To critically review current knowledge on the positive and negative predictive value of blood biomarkers for concussion; to illustrate the clinical and biological contexts that help evaluate the use of these markers in sport-related traumatic brain injuries (TBIs).This systematic review was performed in accordance with PRISMA guidelines. We reviewed the measurement, clinical utility, endpoint, and biological significance of blood biomarkers in concussion.A total of 4352 publications were identified. Twenty-six articles relating to blood biomarkers were included in the review. Four common blood biomarkers, namely S100B, tau, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), were examined. Overall, the studies showed S100B measurement and use, either acutely or at several time points, can distinguish injured from noninjured patients with an uncertain degree of utility in predicting mortality. At present, S100B has largely become an acceptable biomarker of TBI; however, studies have begun to highlight the need to incorporate clinical symptoms instead of S100B concentration in isolation on the basis of inconsistent results and lack of specificity across published studies. Further research is needed to evaluate and validate the use of tau, NSE, and GFAP as a diagnostic aid in the management of concussion and TBI.At present, blood biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. Blood biomarkers, in combination with other clinical data, such as head computed tomography, would maximize the diagnostic accuracy. The methodological limitations evident in blood biomarker research results in the need for the clinical utility of blood biomarker use in concussion to be further explored.