Early Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein in Predicting the Outcome of Mild Traumatic Brain Injury

Abstract

The purpose of this study was to correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). 107 patients with mTBI [Glasgow Coma Scale (GCS) ≥13] having the blood samples for GFAP and NF-L available within 24 hrs from arrival were included. Patients with mTBI were divided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) vs. incomplete (GOSE <8), and favorable (GOSE 5-8) vs. unfavorable (GOSE 1-4). GFAP and NF-L concentrations in blood were measured using ultrasensitive single molecule array technology. Patients with incomplete recovery had significantly higher levels of NF-L compared to those with complete recovery (p=0.005). The levels of GFAP and NF-L were significantly higher in patients with unfavorable outcome than in patients with favorable outcome (p=0.002 for GFAP and p <0.001 for NF-L). For predicting favorable outcome, the area under the ROC curve for GFAP and NF-L was 0.755 and 0.826, respectively. In a multivariate logistic regression model, the level of NF-L was still a significant predictor for complete recovery

Neurofilaments: The C-Reactive Protein of Neurology

“…In severe TBI, both CSF and serum NF-L sharply increase over the first 2 weeks compared to healthy controls and appear to be reliable predictors of poor outcome [56][57][58]. Similar predictions may be possible from serum NF-L in mild traumatic injury although care must be taken when patients are over 60 years old or have preexisting neurological disorders [59,60].…”

“…Such symptomatic controls may not represent the true levels of NF in the general population. Second, many studies also show an age-dependent correlation with NFs [59,60,98]. This is most likely caused by the well-described physiological age-related brain atrophy [162,163].…”

“…TBI can be classified as mild, moderate, or severe, typically using the Glasgow Coma Scale (GCS) [145][146][147], with mild traumatic brain injury (GCS score [14][15] being the most common. There is a need for biomarkers that can assess severity and outcome in TBI as well as the risk of developing chronic traumatic encephalopathy due to repeated exposure to head trauma [59,60].…”

Serum SNTF, a Surrogate Marker of Axonal Injury, Is Prognostic for Lasting Brain Dysfunction in Mild TBI Treated in the Emergency Department

“…However, studies of tau and NFL as prognostic markers for mTBI treated in the emergency department included complicated TBI cases with intracranial lesions discernable on non-contrast head CT scan, which may be prognostic for worse long-term outcomes (29). Thus far, neither marker has shown utility in this setting for the prognosis of uncomplicated mTBI (30)(31)(32). Biomarkers tied to brain elements other than the axon also have been investigated as candidates for mTBI.…”

“…Peripheral blood levels of a tandem of the astrocyteenriched glial fibrillary acidic protein (GFAP) and the neuronenriched ubiquitin C-terminal hydrolase-L1 (UCH-L1) identify cases of complicated TBI with intracranial lesions and distinguish them with high fidelity from cases of mTBI (33)(34)(35)(36)(37). However, these and other well studied proteins such as S100β and neuronspecific enolase have yet to demonstrate prognostic utility in the much larger uncomplicated mTBI patient population (27,31,37).…”