February 18, 2020
Although blood biomarkers can aid in identifying the underlying mechanism of sport-related concussion (SRC), there is insufficient evidence to support the use of biomarkers for diagnosis and management, according to a study recently published in JAMA Network Open.
This prospective, multicenter, case-control study included data from a total of 1760 athletes and controls who completed clinical assessments and blood sample collection as baseline or control comparison data. During the study window, a total of 264 athletes who met study criteria (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] men) sustained a concussion and had clinical and blood testing at 5 points postinjury, including acute postinjury (24 to 48 hours), 7 days postinjury, and at follow ups for 6 months postconcussive event.
Control data were obtained from 138 matched contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] men) and 102 matched noncontact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] men) who completed the same testing on a similar schedule as the concussed athletes. Data on glial fibrillary acidic protein (GFAP), tau, neurofilament light chain, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) were collected. The Sport Concussion Assessment Tool-Third Edition (SCAT-3) evaluation tool for symptom severity and other metrics was used for assessment.
Among athletes with concussion, GFAP was higher than baseline for postinjury assessments (directly after injury, 0.430 pg/mL; P <.001; and at 7 days after return to play, 0.092 pg/mL; P =.002). At the acute postinjury and following points, GFAP was also higher than among contact sport controls (0.419 pg/mL; P <.001; and 0.191 pg/mL; P <.001, respectively) and noncontact sport controls (0.378 pg/mL; P <.001; and 0.177 pg/mL; P =.003, respectively).
A significant longitudinal interaction was found for tau (F7,1480.55 = 6.81; P <.001), GFAP (F7,1507.36 = 16.18; P <.001), and UCH-L1 (F7,1153.09 = 5.71, P <.001). For the combination of GFAP and UCH-L1 at the postinjury point, area under the curve ranged from 0.70 (P <.001 compared with noncontact sport controls) to 0.71 (P <.001 compared with contact sport controls); for combination of all, area under the curve was 0.72 (P <.001 for both contact and noncontact sport control comparisons). Including GFAP was associated with better classification of concussion than the SCAT-3 score alone at the postinjury point (contact sport controls, P =.001; noncontact sport controls, P =.005).
When concussion without posttraumatic amnesia (PTA) or loss of consciousness (LOC) was compared with concussion with these conditions, concussion without PTA or LOC had significantly higher GFAP levels at the postinjury point (0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P <.001).
Study findings may be limited by its focus on athletes involved in high-contact sports and the exclusion of athletes at different developmental stages or competitive levels. Moreover, group comparisons of biomarker results do not equate to diagnostic certainty at the individual case level, as such recommendations for clinical use of biomarkers in concussion assessment and management cannot be made from these findings.
The study researchers concluded that blood biomarkers help “inform the underlying pathophysiological mechanisms of concussion,” though “there is still not sufficient evidence to support broad implementation of biomarkers for clinical diagnosis, evaluation, and management of SRC.” Furthermore, “[the] goal of biomarkers should not be to replace signs and symptoms in clinical diagnosis of concussion but rather to augment clinical specificity and confidence with more objective indicators of brain injury.” The study researchers suggest further research to “optimize and validate a multiplex of biomarkers that would meet accepted standards for clinical adoption.”