Abstract

Background Mild traumatic brain injury (mTBI) accounts for 80% of TBI cases. Although only 16% show intracranial lesions and <1% require neurosurgical intervention, CT overutilization remains common. Clinical decision rules like the Canadian CT Head Rule achieve high sensitivity (approximate to 100%) but poor specificity (28-65%). Serum biomarkers, particularly GFAP and UCH-L1, offer complementary diagnostic performance. Emerging evidence suggests combining both strategies may optimize diagnostic accuracy, though integrated approaches remain poorly characterized in the literature. Methods We conducted a narrative review of literature published January 2000-March 2025 across PubMed/MEDLINE, Google Scholar, and Scielo. Search terms included mTBI, biomarkers (GFAP, UCH-L1, S100B), clinical decision rules (Canadian CT Head Rule, New Orleans Criteria, NEXUS), and resource-limited settings. Inclusion criteria comprised observational cohorts, clinical trials, validation studies, systematic reviews, and meta-analyses focused on mTBI in emergency contexts. Results Combined strategies integrating clinical decision rules with biomarkers achieved superior diagnostic performance compared to either tool individually. The Canadian CT Head Rule demonstrated optimal performance across GCS 13-15 (sensitivity 93-100% and specificity 28-65% for intracranial lesions). GFAP demonstrated superior diagnostic performance compared with UCH-L1 and S100B. Although UCH-L1 did not provide meaningful incremental value beyond GFAP alone, all currently FDA- and CE-cleared platforms for clinical use (Abbott i-STAT, Alinity i; bioM & eacute;rieux VIDAS (R) TBI) measure both GFAP and UCH-L1 in combination, achieving sensitivities of 95.8-97.3% and specificities of 34.2-41.2%. Conclusion Integrating the Canadian CT Head Rule with GFAP-based biomarker testing may optimize CT utilization in mTBI. We propose a sequential diagnostic algorithm consisting of initial evaluation with the Canadian CT Head Rule, followed by biomarker testing in CCHR-positive cases, with CT reserved for biomarker-positive patients. This stepwise approach has the potential to support more efficient referral decisions and resource utilization in settings with limited access to neuroimaging, while reducing unnecessary brain CT use in centers with imaging availability, adapting to diverse healthcare contexts. Cost-effectiveness analyses and validation in resource-limited environments remain needed.