Meier Timothy B, Huber Daniel L, Goeckner Bryna D, Gill Jessica M, Pasquina Paul, Broglio Steven P, McAllister Thomas W, Harezlak Jaroslaw, McCrea Michael A
Author Affiliations: Department of Neurosurgery (Dr Meier, Mr Huber, and Dr McCrea), Department of Biomedical Engineering (Dr Meier), Department of Biophysics (Ms Goeckner), Department of Cell Biology, Neurobiology and Anatomy (Dr Meier), Department of Neurology (Dr McCrea), Medical College of Wisconsin, Milwaukee, Wisconsin; National Institute of Nursing Research (Dr Gill), National Institutes of Health, Bethesda, Maryland, USA; Johns Hopkins School of Nursing and Medicine (Dr Gill), Baltimore, MD; Department of Physical Medicine and Rehabilitation (Dr Pasquina), Uniformed Services University of the Health Sciences, Bethesda, Maryland; Michigan Concussion Center (Dr Broglio), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry (Dr McAllister), Indiana University School of Medicine, Indianapolis, IN; and Department of Epidemiology and Biostatistics (Dr Harezlak), School of Public Health-Bloomington, Indiana University, Bloomington, Indiana.
J Head Trauma Rehabil. 2025;40(1):E23-E28. doi: 10.1097/HTR.0000000000000956. Epub 2024 May 31.
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 (0-12 hours, 12-36 hours, and 36-60 hours 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 12 hours; exploratory analyses were conducted with false discovery rate correction.
For prespecified analyses, IL-1RA at 0 to 12 hours 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 36 hours 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 36 hours 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 12 hours 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.
确定炎症生物标志物与脑震荡参与者的临床指标及恢复情况之间的关联。
在包括军事院校在内的美国国家大学生体育协会成员机构中进行的多中心研究。
422名急性脑震荡参与者。
在受伤前以及脑震荡后的多次访视（受伤后0 - 12小时、12 - 36小时和36 - 60小时）时完成临床检查和血液采集。临床指标包括运动性脑震荡评估工具（SCAT）症状严重程度、平衡误差评分系统、脑震荡标准化评估（SAC）、简明症状量表18项版（BSI - 18）评分、开始逐步恢复比赛（RTP）方案的时间以及恢复比赛的时间。检测血清中的白细胞介素（IL）-6、IL - 10、IL - 8、IL - 1受体拮抗剂（RA）、肿瘤坏死因子（TNF）、C反应蛋白和血管内皮生长因子（VEGF）。预先设定的分析聚焦于0至12小时的IL - 6和IL - 1RA；采用错误发现率校正进行探索性分析。
对于预先设定的分析，女性参与者在0至12小时时的IL - 1RA与SAC上更多的错误（B（标准误，SE）= 0.58（0.27），P <.05）以及更差的SCAT症状严重程度（B（SE）= 0.96（0.44），P <.05）呈正相关。对于探索性分析，脑震荡参与者在12至36小时时较高水平的IL - 1RA与BSI上更高的总体评分（B（SE）= 0.55（0.14），q < 0.01）、抑郁评分（B（SE）= 0.45（0.10），q < 0.005）和躯体化评分（B（SE）= 0.46（0.12），q < 0.01）相关；12至36小时时较高的TNF与SAC上更少的错误相关（B（SE）= - 0.46（0.14），q < 0.05）。亚组分析显示男性参与者和运动员参与者有类似结果。在非运动员学员中未发现关联。女性参与者在0至12小时时较高的IL - 8与较慢的恢复比赛相关（OR = 14.47；95%置信区间，2.96 - 70.66，q < 0.05）；未观察到与恢复的其他关联。
外周炎症标志物与脑震荡后的临床症状相关，并且可能代表受伤后观察到的心理症状的一种机制。目前的结果并未为这些标志物的潜在预后作用提供有力支持。
