The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis

Abstract

Background: Several studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.

Methods: PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded.

Results: Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66-0.80) for unfavorable outcome and 0.76 (95% CI, 0.62-0.90) for mortality.

Conclusions: Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.

Figure 1. Identification process for eligible studies.

Of the 296 studies initially identified from our electronic search, 16 met the inclusion criteria and were included in this meta-analysis.

Figure 2. Risk of bias and applicability concerns of included studies examining role of NSE concentrations in prognosis in patients with traumatic brain injury.

Figure 3. Association between NSE (shown as mean (SD) in transformed concentration) and mortality in patients with traumatic brain injury.

Figure 4. Association between NSE (shown as mean (SD) in transformed concentration) and unfavourable outcome in patients with traumatic brain injury.

Figure 5. Funnel plot for the studies included to analysis the association between NSE concentration and mortality in patients with traumatic brain injury.

Figure 6. Funnel plot for the studies included to analysis the association between NSE concentration and unfavourable outcome in patients with traumatic brain injury.

Figure 7. The pooled sensitivity and specificity to predict unfavourable outcome in patients with traumatic brain injury.

Figure 8. The pooled sensitivity and specificity to predict mortality in patients with traumatic brain injury.

Figure 9. The pooled positive predictive value (PPV) and negative predictive value (NPV) to predict mortality in patients with traumatic brain injury.

Figure 10. The pooled positive predictive value (PPV) and negative predictive value (NPV) to predict unfavourable outcome in patients with traumatic brain injury.

Figure 11. The hierarchical summary receiver operating characteristic (HSROC) curves of NSE to predict mortality in patients with traumatic brain injury.

Figure 12. The hierarchical summary receiver operating characteristic (HSROC) curves of NSE to predict unfavourable outcome in patients with traumatic brain injury.