Evaluation of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Using a Rapid Point of Care Test for Predicting Head Computed Tomography Lesions After Mild Traumatic Brain Injury in a Dutch Multi-Center Cohort

Walid Chayoua; Koen Visser; Myrthe E de Koning; Albertus Beishuizen; Rein IJmker; Joukje van der Naalt; Johannes G Krabbe; Harm Jan van der Horn

doi:10.1089/neu.2023.0491

Evaluation of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Using a Rapid Point of Care Test for Predicting Head Computed Tomography Lesions After Mild Traumatic Brain Injury in a Dutch Multi-Center Cohort

J Neurotrauma. 2024 Feb 28. doi: 10.1089/neu.2023.0491. Online ahead of print.

Authors

Walid Chayoua^{1

2}, Koen Visser³, Myrthe E de Koning^{3

4}, Albertus Beishuizen⁵, Rein IJmker⁶, Joukje van der Naalt³, Johannes G Krabbe^{1

2}, Harm Jan van der Horn³

Affiliations

¹ Department of Clinical Chemistry and Laboratory Medicine, Medlon BV, Enschede, the Netherlands.
² Department of Clinical Chemistry and Laboratory Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.
³ Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands.
⁵ Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.
⁶ Department of Emergency Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.

PMID: 38326742
DOI: 10.1089/neu.2023.0491

Abstract

Mild traumatic brain injury (mTBI) is a common condition seen in emergency departments worldwide. Blood-based biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are recently U.S. Food and Drug Administration-approved for the prediction of intracranial lesions on head computed tomography (CT) scans in mTBI. We evaluated the diagnostic performance of GFAP and UCH-L1 in a Dutch cohort using the i-STAT TBI assay. In a multi-center observational study, we enrolled 253 mTBI patients. Head CT scans were scored using the Marshall classification system. Logistic regression models were used to assess the contribution of biomarkers and clinical parameters to diagnostic performance. Detection of UCH-L1 and GFAP resulted in a sensitivity of 97% and specificity of 19% for CT positivity in mTBI patients, along with a negative predictive value of 95% (88-100%) and a positive predictive value of 27% (21-33%). Combining biomarker testing with loss of consciousness and time to sample increased specificity to 46%. Combined testing of UCH-L1 and GFAP testing resulted in possibly more unnecessary CT scans compared with GFAP testing alone, with only limited increase in sensitivity. This study confirmed high sensitivity of GFAP and UCH-L1 for CT abnormalities in mTBI patients using the i-STAT TBI test. The results support the potential use of GFAP and UCH-L1 as tools for determining the indication for CT scanning in mTBI patients, possibly offering a cost- and time-effective approach to management of patients with mTBI. Prospective studies in larger cohorts are warranted to validate our findings.

Keywords: computed tomography (CT); glial fibrillary acidic protein (GFAP); mild traumatic brain injury (mTBI); point-of-care testing (POCT); ubiquitin carboxy-terminal hydrolase L1 (UCH-L1).