Biomarkers and clinical rules for the
management of mild traumatic brain injury:
a narrative review

Biomarkers and clinical rules for the
management of mild traumatic brain injury:
a narrative review

Keywords Brain injuries, Traumatic, Glial fibrillary acidic protein, Ubiquitin thiolesterase, Biomarkers, Clinical decision
rules, Multidetector computed tomography, Emergency service, Hospital, Unnecessary procedures

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 (≈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; bioMérieux VIDAS® 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,

Sebastián Salgado1,2,3, Vicente Saver1,2,3,8* , Ángel Sáenz1,2,3, Andrés Ferre1,2, Andrés Giglio1,2,4,5,6 and
Andrés Reccius1,2,7

https://doi.org/10.1186/s12245-025-01088-8

2026

peri irawan

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