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Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting with Mild Head Injury to Emergency Departments: A Living Systematic Review and Meta-Analysis

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posted on 2021-06-24, 04:24 authored by Stefania Mondello, Abayomi Sorinola, Endre Czeiter, Zoltán Vámos, Krisztina Amrein, Anneliese SynnotAnneliese Synnot, Emma Donoghue, János Sándor, Kevin KW Wang, Ramon Diaz-Arrastia, Ewout W Steyerberg, David Menon, Andrew Maas, Andras Buki
Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE®, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.


This work was supported by the European Union FP 7th Framework program (CENTER-TBI; Grant number: grant 602150) and the Hungarian Brain Research Program (Grant No. KTIA 13 NAP-A-II/8).


Publication Date



Journal of Neurotrauma






21p. (p. 1086-1106)


Mary Ann Liebert



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