Abstract
Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose. To investigate acute blood protein levels in military cadets after combative training-associated concussions. This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Concussion incurred during combative training. Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.
Highlights
Mild traumatic brain injuries (TBIs) or concussions are a substantial public health problem, occurring with peak incidence in adolescence and young adulthood.[1]
This study’s findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training–associated concussions among military service academy cadets
Out-of-sport concussions that were not associated with combative training were excluded (1 concussion was associated with snowboarding, 6 concussions were associated with unorganized sports, and the cause of 1 concussion was undetermined). These exclusions produced a final sample of 103 cadets; of those, 67 cadets were in the concussion group
Summary
Mild traumatic brain injuries (TBIs) or concussions are a substantial public health problem, occurring with peak incidence in adolescence and young adulthood.[1]. Military service academy (MSA) cadets represent a group of young, healthy individuals who have a higher risk of incurring mild TBI in the setting of combative training. Cadets are required to participate in combative training exercises, which, in the context of this study, were defined to include boxing, self-defense, martial arts, and other military training, all of which may result in head impacts. It is essential that studies of combative training–associated concussions have an active control group of cadets who are undergoing the same combative training exercises but have not incurred concussions (defined as a contact-control group). Symptom burdens associated with the stress of combative training may overlap with those of concussion, and the potential for incurring subconcussive impacts as part of combative training needs to be considered.[3] Data indicate that aerobic activity in the absence of head injuries has implications for blood biomarkers of concussion.[4,5]
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