Mavroudis Ioannis, Petridis Foivos, Kazis Dimitrios, Ciobica Alin, Dăscălescu Gabriel, Petroaie Antoneta Dacia, Dobrin Irina, Novac Otilia, Vata Ioana, Novac Bogdan
Department of Neuroscience, Leeds Teaching Hospitals, NHS Trust, Leeds LS9 7TF, UK.
Third Department of Neurology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Brain Sci. 2025 May 28;15(6):581. doi: 10.3390/brainsci15060581.
Mild traumatic brain injury (mTBI), commonly known as concussion, is a major public health issue characterized by subtle neuronal damage that traditional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) often fail to detect. Fluid biomarkers have emerged as promising diagnostic and prognostic tools for mTBI.
This umbrella meta-analysis aims to evaluate the diagnostic accuracy and clinical utility of the key fluid biomarkers, S100B, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, neurofilament light chain (NfL)) and tau protein, in detecting mTBI and to clarify their roles as screening, confirmatory, and complementary indicators.
A systematic review was performed using PubMed, Web of Science, Scopus, and Cochrane to identify the published meta-analyses that assessed the biomarkers in mTBI. Sensitivity, specificity, and diagnostic odds ratios were then calculated using random-effects models. Heterogeneity was evaluated with the I statistic, and publication bias was assessed via funnel plots. The results of S100B demonstrated high sensitivity (91.6%) but low specificity (42.4%), making it an effective rule-out biomarker to minimize unnecessary CT scans. In contrast, GFAP exhibited moderate sensitivity (84.5%) with improved specificity (61.0%), supporting its role in confirming mTBI diagnoses. UCH-L1 revealed a sensitivity of 86.7% alongside low specificity (37.3%), indicating its potential as a complementary marker. Additionally, the NfL levels were notably elevated in sports-related concussions, while the diagnostic utility of tau protein remains inconclusive due to limited available data.
The findings underscore the clinical promise of fluid biomarkers in the management of mTBI. S100B and GFAP are particularly valuable as screening and confirmatory markers, respectively. Nonetheless, further standardization of biomarker thresholds and additional longitudinal studies are necessary to validate the roles of UCH-L1, NfL, and Tau protein. The integration of these biomarkers into a multimodal diagnostic panel may enhance mTBI detection accuracy and facilitate improved patient stratification and management.
轻度创伤性脑损伤（mTBI），通常称为脑震荡，是一个重大的公共卫生问题，其特征是存在细微的神经元损伤，而计算机断层扫描（CT）和磁共振成像（MRI）等传统成像技术常常无法检测到。体液生物标志物已成为有前景的mTBI诊断和预后工具。
本伞形荟萃分析旨在评估关键体液生物标志物S100B、胶质纤维酸性蛋白（GFAP）、泛素羧基末端水解酶L1（UCH-L1）、神经丝轻链（NfL）和tau蛋白在检测mTBI方面的诊断准确性和临床实用性，并阐明它们作为筛查、确诊和补充指标的作用。
使用PubMed、科学网、Scopus和Cochrane进行系统评价，以识别评估mTBI生物标志物的已发表荟萃分析。然后使用随机效应模型计算敏感性、特异性和诊断比值比。用I统计量评估异质性，并通过漏斗图评估发表偏倚。S100B的结果显示出高敏感性（91.6%）但低特异性（42.4%），使其成为一种有效的排除生物标志物，可尽量减少不必要的CT扫描。相比之下，GFAP表现出中等敏感性（84.5%）且特异性有所提高（61.0%），支持其在确诊mTBI诊断中的作用。UCH-L1的敏感性为86.7%，特异性较低（37.3%），表明其作为补充标志物的潜力。此外，在与运动相关的脑震荡中，NfL水平显著升高，而由于可用数据有限，tau蛋白的诊断效用仍不确定。
研究结果强调了体液生物标志物在mTBI管理中的临床前景。S100B和GFAP分别作为筛查和确诊标志物特别有价值。尽管如此，生物标志物阈值的进一步标准化以及更多的纵向研究对于验证UCH-L1、NfL和tau蛋白的作用是必要的。将这些生物标志物整合到多模式诊断面板中可能会提高mTBI检测的准确性，并有助于改善患者分层和管理。
