Plasma Biomarkers of Traumatic Brain Injury in Adolescents With Sport-Related Concussion

Plasma biomarkers differ between adolescents with sport-related concussion and uninjured adolescents, supporting their continued use to assess concussion neuropathology, according to study results published in JAMA Network Open.

Researchers conducted the pan-Canadian Surveillance in High Schools and Community Sports to Reduce Concussions and their Consequences (SHRed Concussions) multicenter longitudinal cohort study between September 2019 and November 2022 to explore the relationship between sport-related concussion and plasma biomarkers in adolescents. Patients aged between 10 and 18 who participated in high-risk sports (ie, rugby, ice hockey, football) were eligible for inclusion. Blood collection occurred at baseline and follow-up assessments when possible. Primary outcomes included plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau). Multilevel multivariable linear regression models were used for all statistical analyses.

A total of 1023 blood samples were collected from 695 uninjured participants (boys, 67.2%) and 154 concussed participants (boys, 51.0%).

These findings highlight variations in biomarker levels in adolescents with SRC, suggesting their continued use in investigating concussion pathology in this understudied population

A history of at least 1 previous concussion was reported by 216 (31.1%; median days since most recent concussion, 478.5) members of the uninjured group and 80 members of the post-sport-related concussion group (52.2%; median days since most recent concussion, 530.5).

Acute (postinjury days 0-3) differences relative to uninjured measurements were found for the following plasma biomarkers:

• GFAP (girls: 17.8% increase; β, 0.164; 95% CI, 0.064-0.263; P =.001; boys: 17.1% increase; β, -0.157; 95% CI, 0.086-0.229; P <.001);
• UCH-L1 (girls: 43.4% increase; β, 0.361; 95% CI, 0.125-0.596; P =.003);
• NfL (boys: 19.0% increase; β, 0.174; 95% CI, 0.087-0.261; P <.001); and,
• t-tau (girls: -22.9%; β, -0.260; 95% CI, -0.391 to -0.130; P <.001; boys: -18.4%; β, -0.203; 95% CI, -0.300 to -0.106; P <.001).

For all plasma biomarkers at postinjury days 4 to 10, 11 to 28, and greater than 28, between-group differences were observed.

Compared with girls, boys exhibited lower GFAP (-9.7%), but higher UCH-L1 (21.3%). Age was linked to lower GFAP (-5.4% per year) and t-tau (-5.3% per year).

GFAP was positively associated with SCAT5 symptom total and severity score at postinjury days 0 to 3, while NfL was positively associated with symptom total at postinjury days 0 to 3, 4 to 10, and greater than 28, as well as severity score at postinjury days 0 to 3 and 4 to 10.

Although t-tau was negatively associated with symptom total at postinjury days 0 to 3 and 4 to 10, as well as severity score at postinjury days 0 to 3 and 4 to 10, it was positively associated at postinjury days beyond 28.

Higher GFAP after 28 days post-sport-related concussion was associated with faster recovery (hazard ratio [HR], 4.78; 95% CI, 1.59-14.31; P =.01).

Study limitations include pandemic-related disruptions and the limited age distribution of patients.

“These findings highlight variations in biomarker levels in adolescents with SRC [sport-related concussion], suggesting their continued use in investigating concussion pathology in this understudied population,” the study authors concluded.