Plasma biomarkers help determine sports-related concussion neuropathology

Key takeaways:

• Biomarker differences were observed among injured vs. uninjured participants.
• The researchers noted differences in age and sex and said these should be explored in future studies.

Plasma biomarkers shed light on concussion-related neuropathology in adolescents who played contact sports in Canada, supporting their use in pathophysiology, according to new research.

“Blood-based biomarkers of [sport-related concussion] have garnered significant interest for their relatively noninvasive and cost-effective potential in on-field and in-office and/or hospital assessment,” Jason B. Tabor, PhD, of Foothills Medical Center, in Canada, and colleagues wrote in JAMA Network Open.

The researchers examined associations between sport related concussion (SRC) and presence of plasma biomarkers in adolescents who participated in high-risk contact sports such as football, ice hockey and rugby throughout Canada.

From an initial pool of more than 8,000 adolescents enrolled in the Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study, which was conducted between September 2019 and November 2022, Tabor and colleagues conducted a prospective cohort study that included 849 individuals (67.2% boys), 695 of whom were uninjured, as well as 154 individuals with SRC. Enrollees contributed a total of 1,023 blood samples for biomarker analysis (uninjured, n = 695; those with SRC, n = 328).

Patients with SRC submitted blood collection as well as clinical testing at baseline and follow-up visits at 72 hours, 1 week and every other week until they were medically cleared for a return to play (RTP). Evaluations were aligned with the Sport Concussion Assessment Tool, Fifth Edition (SCAT5).

The researchers analyzed biomarkers with Quanterix assays, measuring plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL) and total tau (t-tau). Comparisons of biomarker levels among injured and uninjured groups were conducted at post-SRC intervals (postinjury days [PID] 0-3, 4-10, 11-28 and >28). Secondary analyses examined the associations between biomarker concentrations and clinical outcomes via SCAT5.

Among the uninjured group, 467 samples were from male participants and 222 from female participants; among the post-SRC group, 78 samples came from male participants and 75 from female participants.

Relative to those uninjured, the analysis revealed differences for GFAP (female participants: 17.8% increase; 95% CI, 0.064-0.263; male participants: 17.1% increase; 95% CI, 0.086-0.229), UCH-L1 (female participants: 43.4% increase; 95% CI, 0.125-0.596), NfL (male participants: 19% increase; 95% CI, 0.087-0.261), and t-tau (female participants: 22.9%; 95% CI, 0.391 to 0.13; male participants: 18.4%; 95% CI, 0.3 to 0.106) with respect to those with a shorter number of post-injury days (PID 0-3).

The researchers also noted differences across all biomarkers at PID 4 to 10, 11 to 28, and greater than 28 compared with uninjured participants.

Data further showed that higher GFAP after 28 days post-SRC was associated with earlier clearance to RTP (HR = 4.78; 95% CI, 1.59-14.31), with boys exhibiting lower GFAP (9.7%), but higher UCH-L1 (21.3%) compared with girls, while age was associated with lower GFAP (5.4% per year) and t-tau (5.3% per year).

“Overall, the biomarker differences mirror many trends observed in adults, suggesting consistent neurophysiological processes (eg, axonal injury, glial activation) occur following adolescent [sport-related concussion],” Tabor and colleagues noted.