A prospective study of acute blood‐based biomarkers for sport‐related concussion

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Objective

Prospectively characterize changes in serum proteins following sport‐related concussion and determine if candidate biomarkers discriminate concussed athletes from controls and are associated with duration of symptoms following concussion.

Methods

High school and collegiate athletes were enrolled between 2015 and 2018. Blood was collected at pre‐injury baseline and within 6 hours (early‐acute) and at 24‐48 hours (late‐acute) following concussion in football players (n = 106), matched uninjured football players (n = 84) and non‐contact sport athletes (n = 50). Glial fibrillary acidic protein, ubiquitin c‐terminal hydrolase‐L1, S100 calcium binding protein B, alpha‐II‐spectrin breakdown product 150, interleukin‐6, interleukin‐1 receptor antagonist and c‐reactive protein were measured in serum. Linear models assessed changes in protein concentrations over time. Receiver operating curves quantified the discrimination of concussed athletes from controls. A Cox proportional hazard model determined if proteins were associated with symptom recovery.

Results

All proteins except glial fibrillary acidic protein and c‐reactive protein were significantly elevated at the early‐acute phase post‐injury relative to baseline and both control groups and discriminated concussed athletes from controls with areas under the curve of 0.68‐0.84. The candidate biomarkers also significantly improved the discrimination of concussed athletes from non‐contact controls compared to symptom severity alone. Glial fibrillary acidic protein was elevated post‐injury relative to baseline in concussed athletes with a loss of consciousness or amnesia. Finally, early‐acute levels of interleukin‐1 receptor antagonist were associated with the number of days to symptom recovery.

Interpretation

Brain injury and inflammatory proteins show promise as objective diagnostic biomarkers for sport‐related concussion, while inflammatory markers may provide prognostic value.

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