Exclusion of intracranial lesions in mild traumatic brain injury using glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1: a European multicenter study

BACKGROUND: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are blood biomarkers that able to aid in the assessment of mild traumatic brain injury (mTBI) patients and reduce computed tomography (CT) overuse. OBJECTIVES: The aim of this study was to evaluate the predictive performance of individual biomarkers and their combination (i.e. mTBI assay) in detecting clinically significant intracranial injuries in mTBI. Furthermore, the influence of older age on the predictive performance of individual biomarkers and their combination was investigated. METHODS: This prospective multicenter study was conducted in 12 European healthcare centers. Adults with suspected mTBI presenting to the emergency department (ED) of each participating healthcare center within 12 h of head trauma were enrolled. GFAP and UCH-L1 were determined in blood samples collected from each participant. Head CT was considered as reference standard for the presence of intracranial injury. RESULTS: The mTBI assay yielded the highest sensitivity [95.5%, 95% confidence interval (CI): 89.9-98.5] and the highest negative predictive value (NPV) value (97.3%, 95% CI: 93.9-98.9) for the exclusion of intracranial lesions in mTBI. The sensitivities and NPVs of individual biomarkers were lower compared with the mTBI assay. In adults over 65 years, the individual biomarkers and the mTBI assay displayed the weakest diagnostic performances. After optimizing cutoff values for the mTBI assay for older adults, the following diagnostic accuracy measures were obtained: sensitivity 87.7%, 95% CI: 77.2-94.5 and NPV: 94.4%, 95% CI: 89.6-97.0 ( P < 0.001). CONCLUSION: The mTBI assay yielded high sensitivity and NPV for the exclusion of significant intracranial injuries in mTBI patients presenting to the ED within 12 h from injury, performing better than individual biomarkers. A significant age-dependent influence on the predictive performances of the individual biomarkers and the mTBI assay was demonstrated.