Prospective Assessment of Acute Blood Markers of Brain Injury in Sport-Related Concussion

Abstract

There is a pressing need to identify objective biomarkers for the assessment of sport-related concussion (SRC) to reduce the reliance on clinical judgment for the management of these injuries. The goal of the current study was to prospectively establish the acute effects of SRC on serum levels of S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Collegiate and high school football players were enrolled and provided blood at pre-season. Injured athletes participated in follow-up visits at ∼6 and 24-48 h following documented SRC (n = 32). Uninjured football players participated in similar follow-up visits and served as controls (n = 29). The median time between injury and blood collection was 2 h (6 h visit) and 22.5 h (24-48 h visit) in concussed athletes. Concussed athletes had significantly elevated UCH-L1 levels at the 6 h visit relative to pre-season levels (Z = 2.22, p = 0.03) and levels in control athletes (Z = 3.02, p = 0.003). Concussed athletes also had elevated S100B at 6 h relative to pre-season (Z = 2.07, p = 0.04) and controls (Z = 2.75, p = 0.006). Both markers showed fair discrimination between concussed and control athletes (UCH-L1 area under receiver operating characteristic curve [AUC] [95% CI] = 0.74 [0.61-0.88], S100B AUC = 0.72 [0.58-0.87]). Percent-change of UCH-L1 and S100B at 6 h relative to pre-season also showed fair discrimination (AUC = 0.79 [0.66-0.92] and AUC = 0.77 [0.64-0.90]). GFAP levels did not differ between groups or in concussed athletes relative to pre-season. This study provides prospective evidence of significant increases in serum levels of UCH-L1 and S100B during the early acute period following SRC, and lays the foundation for future studies examining the clinical potential for blood-based biomarkers in the early detection of concussion.

Keywords: GFAP; S100B; UCH-L1; mild traumatic brain injury.

FIG. 1.

Biomarker levels at each visit. Shown in the left panel are individual biomarker levels at each visit for each group. The horizontal line represents the group median at that time point. Shown in the right panel are group medians for each group across visits. GFAP, glial fibrillary acidic protein; UCH-L1, ubiquitin C-terminal hydrolase-L1; S100B, S100 calcium-binding protein beta.

FIG. 2.

Discrimination of concussed from control athletes at the early acute period. Shown are receiver operating characteristic (ROC) curves for glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and S100 calcium-binding protein beta (S100B) at the 6 hour visit (A), and the ROC curve for the percent signal change at the 6 h visit relative to baseline (B). Solid line represents the ROC curve for the relevant biomarker; dotted line represents the reference line. The area under the curve (AUC) and the 95% CI are shown for each curve.

FIG. 3.

Percentage change in serum markers relative to pre-season baseline. Shown is the percent change in glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and S100 calcium-binding protein beta (S100B) for each athlete at the 6 h and 48 h visits relative to levels at the pre-season baseline.