A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury

Introduction: Severe traumatic brain injury (TBI) presentation and late clinical outcomes are usually evaluated by the Glasgow Outcome Scale-Extended (GOS-E), which lacks strong prognostic predictability. Several blood biomarkers have been linked to TBI, such as Tau, GFAP, UCH-L1, S -100B, and NSE. Clinical values of TBI biomarkers have yet to be evaluated in a focused multi-study meta -analysis. We reviewed relevant articles evaluating potential relationships between TBI biomarkers and both early and 6-month outcomes. Methods: All PubMed article publications from January 2000 to November 2023 with the search criteria "Protein Biomarker " AND "Traumatic Brain Injury " were included. Amongst all comparative studies, the sensitivity means and range values of biomarkers in predicting CT Rotterdam scores, ICU admission in the early period, or predicting GOS-E < 4 at the 6-month period were calculated from confusion matrices. Sensitivity values were modeled for each biomarker across studies and compared statistically for heterogeneity and differences. Results: From the 65 articles that met the criteria, 13 were included in this study. Six articles involved earlyperiod TBI outcomes and seven involved 6-month outcomes. In the early period TBI outcomes, GFAP had a superior sensitivity to UCH-L1 and S -100B, and similar sensitivity to the CT Rotterdam score. In the 6-month period TBI outcomes, total Tau and NSE both had significant interstudy heterogeneity, making them inferior to GFAP, phosphorylated Tau, UCH-L1, and S -100B, all four of which had similar sensitivities at 75 %. This sensitivity range at 6-month outcomes was still relatively inferior to the CT Rotterdam score. Total Tau did not show any prognostic advantage at six months with GOS-E < 4, and phosphorylated Tau was similar in its sensitivity to other biomarkers such as GFAP and UCH-L1 and still inferior to the CT Rotterdam score. Conclusion: This data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes.