A Prospective Study of Acute Blood‐Based Biomarkers for Sport‐Related Concussion

Abstract

Objective: Prospectively characterize changes in serum proteins following sport-related concussion and determine whether 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 preinjury baseline and within 6 hours (early acute) and at 24 to 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 whether 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 postinjury relative to baseline and both control groups and discriminated concussed athletes from controls with areas under the curve of 0.68 to 0.84. The candidate biomarkers also significantly improved the discrimination of concussed athletes from noncontact controls compared to symptom severity alone. Glial fibrillary acidic protein was elevated postinjury 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 sportrelated concussion, and inflammatory markers may provide prognostic value.

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

“…However, recent studies have shown that protein biomarker assays can detect even low levels of UCH-L1, S100B, and GFAP elevated after sport concussion not associated with CNS pathology detectable by computed tomography (CT) scans. 214,215 BBs have yet to be fully exploited for medical management of brain injury. However, as documented in Table 3, research laid the foundation for U.S. Food and Drug Administration (FDA) accelerated approval of measures of UCH-L1 and GFAP for acute diagnosis of TBI not associated with CT abnormalities versus moderate TBI associated with CT abnormalities.…”

“…However, recent studies have shown that protein biomarker assays can detect even low levels of UCH-L1, S100B, and GFAP elevated after sport concussion not associated with CNS pathology detectable by computed tomography (CT) scans. 214 , 215 …”

“…As reviewed in an earlier section, the potential utility of the BBs, GFAP and UCH-L1, to acutely diagnose even low levels of CNS injury, such as sport concussion, 214 , 215 and to triage moderate and severe TBI patients for imaging has been demonstrated. 217 , 271 , 315 , 316 In addition, BBs in combination with refined imaging classification systems can also assist in assessments of acute patient care needs (e.g., discharge vs. hospitalization), thereby assisting in maintaining a clinical care pathway that optimizes management of potentially scarce medical resources.…”

Head injury and concussion in cricket: Incidence, current guidance, and implications of sports concussion literature

“…Of note, there have been two recent large prospective studies. 48,49 Concussed athletes have been shown to have significant elevations in GFAP, UCH-L1 and tau acutely post-injury, with a panel combining multiple biomarkers showing adequate discrimination for detection of sports-related concussion. 48 Similarly, while on a panel of biomarkers consisting of: GFAP, UCH-L1, S100B, alpha-II-spectrin breakdown product 150, interleukin 6, interleukin 1 receptor antagonist (IL-1RA), and c-reactive protein, all proteins aside from GFAP and CRP demonstrated discrimination of concussed patients from non-concussed contact sport controls.…”

“…48 Similarly, while on a panel of biomarkers consisting of: GFAP, UCH-L1, S100B, alpha-II-spectrin breakdown product 150, interleukin 6, interleukin 1 receptor antagonist (IL-1RA), and c-reactive protein, all proteins aside from GFAP and CRP demonstrated discrimination of concussed patients from non-concussed contact sport controls. 49 Early prognostic prediction can help plan tailored management strategy, both for the player and for the team, giving advanced notice of players unlikely to make a fast recovery and allowing for resource allocation. There have been various studies assessing the use of blood biomarkers for this purpose in the realm of sports concussion.…”