DOI: 10.1177/03635465231221782 ISSN: 0363-5465

Optimizing Concussion Care Seeking: Connecting Care-Seeking Behaviors and Neurophysiological States Through Blood Biomarkers

Christopher D’Lauro, Johna K. Register-Mihalik, Timothy B. Meier, Zachary Yukio Kerr, Kristen Knight, Steven P. Broglio, Daniel Leeds, Robert C. Lynall, Emily Kroshus, Michael A. McCrea, Thomas W. McAllister, Julianne D. Schmidt, Christina Master, Gerald McGinty, Jonathan C. Jackson, Kenneth L. Cameron, Thomas Buckley, Thomas Kaminski, Jason P. Mihalik,
  • Physical Therapy, Sports Therapy and Rehabilitation
  • Orthopedics and Sports Medicine


Timely and appropriate medical care after concussion presents a difficult public health problem. Concussion identification and treatment rely heavily on self-report, but more than half of concussions go unreported or are reported after a delay. If incomplete self-report increases exposure to harm, blood biomarkers may objectively indicate this neurobiological dysfunction.


The purpose of this study was to compare postconcussion biomarker levels between individuals with different previous concussion diagnosis statuses and care-seeking statuses. It was hypothesized that individuals with undiagnosed concussions and poorer care seeking would show altered biomarker profiles.

Study Design:

Cohort study; Level of evidence, 3.


Blood samples were collected from 287 military academy cadets and collegiate athletes diagnosed with concussion in the Advanced Research Core of the Concussion Assessment, Research and Education Consortium. The authors extracted each participant’s self-reported previous concussion diagnosis status (no history, all diagnosed, ≥1 undiagnosed) and whether they had delayed or immediate symptom onset, symptom reporting, and removal from activity after the incident concussion. The authors compared the following blood biomarkers associated with neural injury between previous concussion diagnosis status groups and care-seeking groups: glial fibrillary acidic protein, ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light chain (NF-L), and tau protein, captured at baseline, 24 to 48 hours, asymptomatic, and 7 days after unrestricted return to activity using tests of parallel profiles.


The undiagnosed previous concussion group (n = 21) had higher levels of NF-L at 24- to 48-hour and asymptomatic time points relative to all diagnosed (n = 72) or no previous concussion (n = 194) groups. For those with delayed removal from activity (n = 127), UCH-L1 was lower at 7 days after return to activity than that for athletes immediately removed from activity (n = 131). No other biomarker differences were observed.


Individuals with previous undiagnosed concussions or delayed removal from activity showed some different biomarker levels after concussion and after clinical recovery, despite a lack of baseline differences. This may indicate that poorer care seeking can create neurobiological differences in the concussed brain.

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