Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI

Abstract

Objectives: To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI).

Methods: Study participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology.

Results: Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90-0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70-0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69-0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT.

Conclusion: Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials.

Classification of evidence: Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.

Figure 1. Box-and-whisker plots of tau (A), NFL (B), GFAP (C) and UCH-L1 (D) concentrations in the different diagnostic groups

The black horizontal line in each box represents the median, with the boxes representing the interquartile range. Significant differences are indicated with *p < 0.05, **p < 0.01, and ***p < 0.001. GFAP = glial fibrillary acidic protein; NFL = neurofilament light chain; and UCH-L1 = ubiquitin carboxyl-terminal hydrolase L1.

Figure 2. Receiver operating characteristic curves age-adjusted for NFL, tau, and GFAP and “model” which includes all biomarkers (NFL, tau, and GFAP)

(A) ROC stratifying controls vs patients with mTBI, (B) ROC stratifying patients with mTBI with and without CT imaging findings, (C) ROC stratifying patients with mTBI with and without MRI findings, (D) ROC stratifying patients with mTBI who have CT negative findings, both with and without MRI findings. GFAP = glial fibrillary acidic protein; mTBI = mild traumatic brain injury; NFL = neurofilament light chain; and ROC = receiver operating curve.