From the Departments of Clinical and Health Psychology (B.M.A., R.M.B., A.M.S., G.H.), Neurology (R.M.B., S.T.D., J.R.C.), and Community Health and Family Medicine (J.R.C.), and University Athletic Association (J.K.B., D.N.D., J.R.C.), University of Florida, Gainesville; and Banyan Biomarkers, Inc. (R.L.H.), Alachua, FL.
Neurology. 2018 Dec 4;91(23):e2133-e2143. doi: 10.1212/WNL.0000000000006617. Epub 2018 Nov 7.
To evaluate changes in serum biomarker concentrations (β-amyloid peptide 42 [Aβ], total tau, ubiquitin carboxy-terminal hydrolyzing enzyme L1, S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], microtubule associated protein 2 [MAP2], and 2',3'-cyclic-nucleotide 3'-phosphodiesterase [CNPase]) after sport-related concussion (SRC) in a sample of collegiate athletes. Associations with clinical outcomes were also investigated.
Participants in this case-control study included 36 athletes (50% male, 61% white, aged 19.7 ± 1.0 years) with SRC. Twenty-nine also had baseline blood drawn, allowing for within-patient analyses of concentration changes. Between-group analyses incorporated 86 demographically matched controls (51% male, 63% white, aged 19.6 ± 1.1 years). Biomarker sensitivity/specificity for SRC vs controls and relative to standardized normative cutoffs was evaluated (receiver operating characteristics). We also analyzed associations between post-SRC clinical outcomes and both biomarker change from baseline and post-SRC concentrations.
The majority of blood samples had concentrations of GFAP, MAP2, and CNPase below limits of quantification. Within-patient analyses indicated elevated S100B after SRC ( = 0.003, 67% of patients elevated), especially for blood samples collected <4 hours post-SRC (88% of patients). Significant between-group differences were limited to blood draws <4 hours post-SRC: Aβ (81% of SRC > control median, area under the curve [AUC] = 0.75 [95% confidence interval 0.59-0.91]), total tau (75% SRC > control, AUC = 0.74 [0.56-0.79]), and S100B (88% SRC > control; AUC [specific to white race] = 0.82 [0.72-0.93]). Using standardized normative cutoffs ( > 1.0), specificity ranged from 79.1% to 89.3% while sensitivity was <70%. Biomarkers were not associated with clinical outcomes.
For SRC, diagnostic accuracy of serum biomarkers appears best if blood is collected within a few hours. Accurate blood marker identification of SRC appears somewhat dependent on the "healthy" comparison. Additional research must evaluate whether physiologic changes in the absence of clinical changes, or vice versa, are relevant for concurrent or future neurologic health.
This study provides Class III evidence that certain serum biomarkers are elevated from baseline and higher than demographically matched controls after sport-related concussion.
评估运动相关性脑震荡（SRC）后血清生物标志物浓度（β-淀粉样肽 42 [Aβ]、总 tau、泛素羧基末端水解酶 L1、S100 钙结合蛋白 B [S100B]、胶质纤维酸性蛋白 [GFAP]、微管相关蛋白 2 [MAP2]和 2'，3'-环核苷酸 3'-磷酸二酯酶 [CNPase]）在运动员样本中的变化。还研究了与临床结果的相关性。
本病例对照研究纳入了 36 名 SRC 运动员（50%为男性，61%为白人，年龄 19.7 ± 1.0 岁）。其中 29 名患者还进行了基线采血，允许进行患者内浓度变化的分析。组间分析纳入了 86 名年龄和性别匹配的对照者（51%为男性，63%为白人，年龄 19.6 ± 1.1 岁）。评估了 SRC 与对照者之间以及与标准化正常参考值相比的生物标志物敏感性/特异性（受试者工作特征）。我们还分析了 SRC 后临床结果与生物标志物从基线变化和 SRC 后浓度之间的相关性。
大多数血液样本的 GFAP、MAP2 和 CNPase 浓度低于定量下限。患者内分析表明 SRC 后 S100B 升高（ = 0.003，67%的患者升高），尤其是在 SRC 后 <4 小时采集的血液样本中（88%的患者）。组间显著差异仅限于 <4 小时内采集的血液样本：Aβ（81%的 SRC 高于对照中位数，曲线下面积 [AUC] = 0.75 [95%置信区间 0.59-0.91]）、总 tau（75%的 SRC 高于对照，AUC = 0.74 [0.56-0.79]）和 S100B（88%的 SRC 高于对照；白人种族特异性 AUC [specific to white race] = 0.82 [0.72-0.93]）。使用标准化正常参考值（>1.0），特异性范围为 79.1%至 89.3%，而敏感性<70%。生物标志物与临床结果无关。
对于 SRC，若在数小时内采集血液，则血清生物标志物的诊断准确性似乎最佳。准确识别 SRC 的血液标志物似乎在一定程度上取决于“健康”对照。需要进一步研究以评估生理变化是否与临床变化同时发生，或者相反，是否与当前或未来的神经健康相关。
这项研究提供了 III 级证据，表明运动相关性脑震荡后，某些血清生物标志物会从基线升高，且高于年龄和性别匹配的对照组。
