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Blood-based biomarkers need further work to produce reliable assessments of sport-related concussions, according a large prospective analysis of college athletes.

Variability in serum biomarkers suggested inherent sensitivity and specificity limitations at baseline, reported Breton Asken, MS, of the University of Florida in Gainesville, and co-authors in Neurology.

"Our data show that cutoffs for normal or elevated biomarkers may differ based on factors like sex and race, but we don't yet know if there's a specific concentration that reliably signals a problem regardless of what's considered normal for a given subgroup," Asken told 番茄社区app.

"Concussion is a clinical diagnosis based on symptoms, while blood biomarkers capture a physiologic state," he added. "It is no surprise these do not always align."

No biomarker for concussion currently exists and diagnosis depends on clinical history, physical examination, and clinical acumen, noted Erin Bigler, PhD, of Brigham Young University, in Provo, Utah, and Ellen Deibert, MD, of Drexel University College of Medicine in York, Pennsylvania, in an .

"Limitations in diagnostic precision, especially for the mildest of traumatic brain injuries, have plagued the field from its inception," and have led to varying opinions about sport-related concussion reflected in current guidelines and statements from the and the , they added.

In the three-part BASICS (Biomarkers Assessed in Collegiate Student-Athletes) study, Asken and colleagues looked at levels of beta-amyloid peptide 42, total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 29,39-cyclic-nucleotide 3'-phosphodiesterase (CNPase). It followed student athletes over time to look for changes at both the group and individual level.

In the , an analysis of 415 healthy college athletes who played football, basketball, lacrosse, or soccer showed strong variability in S100B and UCH-L1 concentrations at baseline: men had higher levels than women, and black athletes had higher levels than white athletes. In the , biomarkers in these same 415 athletes showed no consistent association with concussion history, or cumulative exposure to collision sports.

The studied 29 college athletes who had sport-related concussions during the study and found that 67% had elevated levels of S100B after a concussion compared with baseline; that number rose to 88% when blood samples were collected within 4 hours of concussion.

When researchers compared blood samples of 36 athletes who had concussion within 4 hours with those of 86 athletes who did not have concussion, they saw that 75% of concussed athletes had higher levels of total tau, 81% had higher levels of beta-amyloid peptide 42, and 88% had higher levels of S100B than the median levels of non-concussed athletes. Neither absolute serum biomarker concentrations nor changes from baseline correlated with clinical outcomes, including symptom severity, sport-related concussion test scores, or duration of clinical recovery.

"The takeaway from this, at least in sport-related concussion, is that a serum biomarker may detect injury, yet not relate in meaningful ways to current motor, neurobehavioral, and neurocognitive outcome measures," observed Bigler and Deibert. While this research "does provide Class III evidence that some serum biomarkers are elevated or higher than controls after sport-related concussion, their diagnostic accuracy depends on which reference group method is used and time post-injury," they added.

The concussions studied in BASICS were sport-related only and did not require emergency department care, Asken and colleagues noted. Unmeasured factors also may have influenced the serum concentrations of biomarkers in athletes.