Ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein tandem brain biomarker test in the prediction of CT evident brain injury: A prospective evaluation in the emergency department

<b>Background:</b> Patients with features of mild traumatic brain injury (mTBI) frequently present to the emergency department (ED) and often meet recognized criteria for CT head imaging. Observational studies suggest that use of a tandem ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) brain biomarker test may significantly reduce need for CT scanning in this population, though data on patient flow are lacking.<b>Methods:</b> A prospective cohort evaluation of adult ED patients (≥18 years) with features of mTBI who met criteria for CT imaging within 12 hours of head injury had blood drawn for laboratory UCH-L1/GFAP testing. The diagnostic performance for CT-evident brain injury was expressed through the calculation of sensitivity and negative predictive value (NPV) with 95% confidence intervals (95% CI). Times from venepuncture to biomarker result availability, and from CT request to result availability were compared.<b>Results:</b> A laboratory UCH-L1/GFAP test identified 21 of 89 (24%) patients as low-risk for CT-evident TBI with a sensitivity of 100% (95% CI 76%-100%) and NPV of 100% (95% CI 85%-100%). The median time to biomarker and CT results were 88 minutes and 89 minutes, respectively. However, 68 (76%) of patients with a positive biomarker test would then progress to CT imaging, significantly prolonging ED length of stay, and restricting usefulness in adoption into clinical pathways.<b>Conclusion:</b> Evaluation of a laboratory UCH-L1/GFAP test in a UK population with mTBI demonstrates excellent performance for the exclusion of CT-evident brain injury. However, adoption into clinical patient pathways is likely to be limited until the test is available in whole blood at the point-of-care, and evidence of safe rationalization of CT imaging confirmed in randomized studies.