Increased specificity of the "GFAP/UCH-L1" mTBI rule-out test by age dependent cut-offs

Clin Chem Lab Med. 2024 Nov 27. doi: 10.1515/cclm-2024-1034. Online ahead of print.

Abstract

Objectives: Mild traumatic brain injury (mTBI) remains challenging to diagnose effectively in the emergency department. Abbott has developed the "GFAP/UCH-L1" mTBI test, to guide the clinical decision to perform a computed tomography (CT) head scan by ruling out the presence of mTBI. We evaluated the diagnostic accuracy of the "GFAP/UCH-L1" mTBI test in a Greek cohort and established age-dependent cut-offs.

Methods: A total of 362 subjects with suspected mTBI and admitted to the Emergency department of the KAT General Hospital of Athens, Greece were recruited for the study. All subjects underwent a CT head scan to establish the diagnosis of mTBI. GFAP and UCH-L1 were measured using Alinity I (Abbott). 163 healthy subjects served as controls.

Results: Using the manufacturer's cut-offs (35 ng/L for GFAP and 400 ng/L for UCH-L1), the "GFAP/UCH-L1" mTBI test had a sensitivity of 99.1 % and a specificity of 40.6 %. However, the specificity dropped to 14.9 % in patients older than 65 years old. By defining a new cut-off of 115 ng/L for GFAP and 335 ng/L specifically for patients older than 65 years, specificity was increased up to 30.6 % without changing test sensitivity and the number of CT head scans avoided was doubled in this subgroup.

Conclusions: The "GFAP/UCH-L1" mTBI test is an efficient "rule-out test" to exclude patients suffering from mTBI. By adjusting the cut-offs in patients older than 65 years old, we could significantly increase the number of CT head scans avoided without affecting the sensitivity. These new cut-offs should be externally validated.

Keywords: automated assay; brain concussion; glial fibrillary astrocyte protein (GFAP); mild traumatic brain injury (mTBI); ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1).