Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility

OBJECTIVE Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomark-ers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored.METHODS Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis.RESULTS A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome.CONCLUSIONS UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome. https://thejns.org/doi/abs/10.3171/2022.5.JNS22638 KEYWORDS serum; biomarker; traumatic axonal injury; fractional anisotropy; outcome; trauma; traumatic brain injury

Automated summary

This study explores the potential role of serum biomarkers in assessing traumatic axonal injury (TAI). By extracting blood and performing imaging assessments on traumatic brain injury (TBI) patients, it was found that the concentrations of biomarkers were significantly higher in TBI patients compared to the control group. Among these biomarkers, UCH-L1 and NfL appear to be more specific markers for detecting TAI. Furthermore, the combination of NfL and the fractional anisotropy (FA) of the corpus callosum (CC) can help predict long-term outcomes.