Can the Association of the Biomarkers GFAP and UCH-L1 Predict Intracranial Injury After Mild Traumatic Brain Injury in Adults? A Systematic Review and Meta-Analysis.

Study Objectives: Brain biomarkers have been used to predict intracranial injury in both adults and children following mild traumatic brain injury (mTBI). Several biomarkers have been evaluated, including S100B, NfL, Tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1). The combined measurement of GFAP and UCH-L1 has recently been recommended by scientific societies, but no meta-analysis on the topic has been performed yet.

Methods: A meta-analysis was performed to assess the prognostic value of the association of GFAP and UCH-L1 blood levels in predicting intracerebral lesions in adults after mTBI. A protocol was designed and registered with PROSPERO (CRD42024562587). Studies were chosen if they included adults with mTBI who underwent GFAP and/or UCH-L1 measurement and cranial computed tomography scans. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Three databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) were consulted.

Results: Of the 379 articles screened, 16 were selected for inclusion. The overall pooled sensitivity (Se) and specificity (Spe) were 100% (95% confidence interval [CI] 99% to 100%) and 31% (95% CI 26% to 36%), respectively, for the association of GFAP and UCH-L1. For GFAP alone, the overall pooled Se and Spe were 94% (95% CI 91% to 97%) and 40% (95% CI 34% to 46%), respectively. For UCH-L1 alone, the overall pooled Se and Spe were 83% (95% CI 69% to 94%) and 51% (95% CI 40% to 63%), respectively. The areas under the curve were 88, 67, and 97%, respectively, for GFAP, UCH-L1, and the association GFAP/UCH-L1.

Conclusion: The combined measurement of GFAP and UCH-L1 allows the exclusion of intracranial injury after mTBI in adults with 100% Se and negative predictive value. Its routine use can theoretically reduce the number of cranial computed tomography scans by 31%. The different sampling times and techniques used in the studies did not allow us to make specific recommendations.