Validation of Blood-Based Biomarkers After Mild Traumatic Brain Injury with GCS 15 in a Singapore Emergency...

Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) have emerged as possible adjuncts to head CT in evaluating mild TBI (mTBI). We aim to validate the performance of the Abbott Alinity i TBI test (UCH-L1 and GFAP) compared to head CT in an Asian cohort with mTBI and GCS 15. Materials and Methods: This prospective observational study was conducted at a tertiary academic medical center from 2 December 2024 to 19 March 2025. Patients aged 21 years and above who sustained head injury within 12 h of ED attendance had GCS of 15 and required head CT as per attending physician were eligible. Plasma was separated from whole blood within 10 min of collection and immediately stored at -20 °C. UCH-L1 and GFAP levels were analyzed in batches within 28 days of recruitment at the hospital central laboratory using the Alinity i TBI test. Results: Among 120 patients enrolled, there was predominance of males (55.8%, 67/120) and Chinese ethnicity (75.8%, 91/120). The median age was 73 (interquartile range [IQR] 56 to 79) years. Overall incidence of positive head CT was 9.2% (11/120); all 11 patients had positive Alinity i TBI tests. The sensitivity and negative predictive value of the biomarkers in our cohort were both 100% (95% confidence intervals [CIs] 71.5% to 100% and 78.2% to 100%, respectively), specificity 13.8% (95% CI 7.9% to 21.7%) and positive predictive value 10.5% (95%CI 5.4% to 18%). Exploratory post hoc analysis suggested that GFAP alone, at the prespecified assay threshold, was associated with modestly higher specificity [21.1% (95% CI 13.9% to 30.0%)] in this cohort. Conclusions: The Alinity i TBI test can safely rule out intracranial injury in patients with mTBI and GCS 15 presenting within 12 h of injury. However, specificity was low, limiting its ability to reduce head CT use in its current form. Exploratory post hoc analyses of the individual biomarkers, particularly GFAP alone, should be interpreted cautiously. Future studies should focus on optimizing specificity while maintaining a high degree of sensitivity.