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

• Published in: Clinical neurology and neurosurgery 2024-07, Vol.242, p.108312, Article 108312
• Main Authors: Behzadi, Faraz, Luy, Diego D., Schaible, Peter A., Zywiciel, Joseph F., Puccio, Ava M., Germanwala, Anand V.
• Format: Article
• Language: English
• Subjects: Biomarkers; Biomarkers - blood; Blood Proteins - analysis; Brain Injuries, Traumatic - blood; Critical care; Glasgow Outcome Scale; Glial fibrillary acidic protein; Humans; Meta-analysis; Predictive Value of Tests; Prognosis; Protein gene product 9.5; Proteins; S100b protein; Science; Systematic review; Tau; tau Proteins - blood; Traumatic brain injury
• ISSN: 0303-8467; 1872-6968; 1872-6968
• DOI: 10.1016/j.clineuro.2024.108312

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. 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. From the 65 articles that met the criteria, 13 were included in this study. Six articles involved early-period 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. This data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes. •Much current research focuses on investigating the utility of biomarkers with TBI prognostication.•Blood protein biomarkers may provide more insight into cellular damage compared to GOS-E and imaging findings.•Blood protein markers provide validated sensitivities for ruling out unfavorable TBI outcomes within 6–12 months.•In this meta-analysis, the value of analyzed biomarkers was not superior to that from current non-invasive clinical predictors.•GOS-E and the CT Rotterdam score continue to remain u