Research Letter: Relationship of Blood Biomarkers of Inflammation With Acute Concussion Symptoms and Recovery in the CARE Consortium.

Abstract

Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion. Multicenter study in National Collegiate Athletic Association member institutions including military service academies. Four hundred twenty-two participants with acute concussion. Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12hours, 12-36hours, and 36-60hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12hours; exploratory analyses were conducted with false discovery rate correction. For prespecified analyses, IL-1RA at 0 to 12hours in female participants was positively associated with more errors on the SAC (B(standard error, SE)=0.58(0.27), P <.05) and worse SCAT symptom severity (B(SE)=0.96(0.44), P <.05). For exploratory analyses, higher levels of IL-1RA at 12 to 36hours were associated with higher global (B(SE)=0.55(0.14), q<0.01), depression (B(SE)=0.45(0.10), q <0.005), and somatization scores on the BSI (B(SE)=0.46(0.12), q <0.01) in participants with concussion; Higher TNF at 12 to 36hours was associated with fewer errors on the SAC (B(SE)=-0.46(0.14), q <0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12hours was associated with slower RTP in female participants (OR=14.47; 95% confidence interval, 2.96-70.66, q <0.05); no other associations with recovery were observed. Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.