Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study

Ava M Puccio; John K Yue; Frederick K Korley; David O Okonkwo; Ramon Diaz-Arrastia; Esther L Yuh; Adam R Ferguson; Pratik Mukherjee; Kevin K W Wang; Sabrina R Taylor; Hansen Deng; Amy J Markowitz; Xiaoying Sun; Sonia Jain; Geoffrey T Manley

doi:10.1089/neu.2023.0186

Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study

J Neurotrauma. 2024 Mar 14. doi: 10.1089/neu.2023.0186. Online ahead of print.

Authors

Ava M Puccio¹, John K Yue^{2

3}, Frederick K Korley⁴, David O Okonkwo¹, Ramon Diaz-Arrastia⁵, Esther L Yuh^{3

6}, Adam R Ferguson^{2

3}, Pratik Mukherjee^{3

6}, Kevin K W Wang⁷, Sabrina R Taylor^{2

3}, Hansen Deng¹, Amy J Markowitz^{2

3}, Xiaoying Sun⁸, Sonia Jain⁸, Geoffrey T Manley^{2

3}

Affiliations

¹ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
² Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
³ Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, USA.
⁴ Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
⁷ Center for Neurotrauma, Multiomics and Biomarkers, Morehouse School of Medicine, Atlanta, Georgia, USA.
⁸ Biostatistics Research Center, Herbert Wertheim School of Public Health and Longevity Science, University of California San Diego, San Diego, California, USA.

PMID: 38251868
DOI: 10.1089/neu.2023.0186

Abstract

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to a United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. The GFAP provided good discrimination in the overall cohort at days 1 (AUC = 0.82) and 14 (AUC = 0.72), and in the hospitalized subgroup at days 1 (AUC = 0.84), 3 (AUC = 0.88), 5 (AUC = 0.82), and 14 (AUC = 0.74). The UCH-L1, NSE, and S100B did not perform well (AUC = 0.51-0.57 across time points). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h time frame in patients with TBI who have a GCS 13-15.

Keywords: biomarker; diagnosis; glial fibrillary acidic protein; medical decision-making; neuroimaging; point-of-care testing; traumatic brain injury.