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18-09-2024 | Traumatic Brain Injuries | Editor's Choice | News

Four brain injury biomarkers linked to concussion in teens

Author: Cher Thornhill

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medwireNews: Altered levels of four biomarkers may help indicate the severity of sports-related concussion (SRC) in children and adolescents, researchers from Canada report.

The team, from the University of Calgary in Alberta, measured levels of plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) in samples taken from 154 concussed children and adolescents, aged 10–18 years, who participated in high-risk sports, such as ice hockey and football.

Levels were taken at 0–3, 4–10, 11–28, and more than 28 days after SRC and compared with those for 695 uninjured participants. The median ages in the groups were 16.1 and 15.9 years, respectively, and over half were male (51.0 and 67.2%).

In the first 3 days after injury, boys and girls with SRC had GFAP levels that were a significant 17.1% and 17.8% higher, respectively, than those among boys and girls without SRC. Both boys and girls with than without SRC continued to have significantly higher levels of GFAP on days 4–10 and 11–28, while boys only also had significantly elevated GFAP beyond day 28. Boys with SRC had slightly lower GFAP levels than girls.

Researcher Jason Tabor and colleagues also report that age had an effect on GFAP levels among adolescents with SRC, decreasing by 5.41% with each increasing year in age.

UCH-L1 levels were also a significant 43.4% higher among girls on days 0–3 after SRC than in non-injured girls, and they remained significantly elevated beyond day 28, whereas there was no such increase in boys with SRC relative to those without. By contrast, NfL was only significantly elevated in boys with than without SRC on days 0–3 (19.0%) and 4–10 (11.6%).

And for t-tau, girls with versus without SRC had significantly lower levels on days 0–3 (22.9%) that remained significantly lower throughout the follow-up period, while boys with SRC had significantly lower t-tau levels on days 0–3 (18.4%) and 4–10 (8.0%) than those without, but higher levels on days 11–28 (9.1%). Boys had greater post-concussion differences in t-tau relative to their uninjured peers than did girls.

Levels of t-tau were also affected by age in adolescents with SRC, decreasing by 5.32% with each increasing year in age.

The investigators report in JAMA Network Open that there was a positive and significant relationship on days 0–3 between levels of GFAP and patient scores for total symptoms and severity on the Sport Concussion Assessment Tool, fifth edition.

A similar positive association was also found for symptom total score and severity score on days 0–3 and 4–10 for levels of NfL, while t-tau levels were negatively associated with symptom total score at these time points, but positively associated after day 28.

Of note, patients with high GFAP levels (median 70.36–133.41 pg/mL) more than 28 days after SRC were 4.78 times likely to have early recovery and return to play than those with lower levels (median 33.23–68.63 pg/mL).

“All biomarkers, except UCH-L1, were significantly associated with symptom burden,” Tabor et al write. However, they acknowledge: “The clinical significance of these associations is limited as effect sizes rarely exceeded a 1% change in biomarker concentration per unit increase in symptom score.”

The team continues that the “data suggest these biomarkers are sensitive to adolescent SRC, but they may not enhance typical recovery monitoring over established clinical protocols.”

Nevertheless, the authors add: “Future studies should consider biomarker associations with age and sex as they may have implications for potential clinical validation.”

JAMA Netw Open 2024; 7: e2431959

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