Plasma biomarkers may have a role in adolescent traumatic brain injuries

1. GFAP, UCH-L1, NfL, and t-tau are all promising plasma biomarkers that show sex specific changes in adolescents post sport-related concussion.

2. GFAP and NfL show positive associations with symptom totals and severity whereas t-tau shows negative associations initially post-injury (10 days) and then shows a positive association

Evidence Rating Level: 2 (Good)

Sport-related concussion (SRC) in adolescent population is an important area of research as rates of substantial impact of prolonged symptoms have increased in recent years. The developing brain is also more vulnerable to injury, further increasing the importance of injury identification. Diagnosis of SRC has no current gold standard, instead relying on subjective clinical examination where non-specific symptoms must be interpreted. An objective measure of SRC, such as blood-based biomarkers, could help solve this issue. Current research shows promising candidates for central nervous system (CNS) injury following SRC. These include glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and possibly total tau (t-tau). These findings have yet to be verified in an adolescent population. Therefore, this study aimed to identify blood-based biomarkers in adolescents with SRC. 1023 plasma samples from 695 uninjured and 154 concussed adolescents were collected and analyzed for presence of GFAP, UCH-L1, NfL, and t-tau. Samples were collected whenever possible and grouped into post-injury day (PID) 0-3, 4-10, 11-28, and >28. GFAP analysis showed sex-specific differences post-SRC. Post-SRC females had significantly higher GFAP in the acute and subacute phases of recovery (p=0.001 and p=0.02 respectively) but not past PID 28. Males however had higher GFAP at all time points. GFAP increases were also 5.4% less likely per year as age increased (p<0.001). UCH-L1 was increased in females post-SRC at all time points (p=0.003, p=0.03, p=0.002, and p<0.001 respectively). No significant changes were seen in males. NfL only showed significant changes in males comparing uninjured and PID 0-3 days. No changes in females were seen. Finally, t-tau showed lower t-tau in all post-SRC time points compared to uninjured levels. For males, lower t-tau levels were seen from PID 1-10 and higher t-tau levels from days 11-28. When comparing the biomarkers to symptoms, GFAP and NfL were positively associated with symptom total and severity whereas t-tau was negatively associated with symptom total and severity for the first 10 days then was positively associated. The key limitation of the study would be the lack of samples from uninjured individuals who later experienced SRC as well as later timepoints that could show biomarker changes throughout recovery.

Click to read the study in JAMA Network Open

Image: PD

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