Serum Neuron-Specific Enolase Thresholds for Predicting Postcardiac Arrest Outcome

Abstract

Background and ObjectivesTo determine thresholds of serum neuron-specific enolase (NSE) for prediction of poor outcome after cardiac arrest with >95% specificity using a unique method of multiple thresholds meta-analysis.MethodsData from a systematic review by the European Resuscitation Council (ERC 2014) were updated with literature searches from PubMed, Cochrane, and Scopus until August 2020. Search terms included the MeSH terms “heart arrest” and “biomarkers” and the text words “cardiac arrest,” “neuron specific enolase,” “coma” and “prognosis.” Cohort studies with comatose cardiac arrest survivors aged >16 years undergoing targeted temperature management (TTM) and NSE levels within 96 hours of resuscitation were included. Poor outcome was defined as cerebral performance category 3–5 at hospital discharge or later. Studies without extractable contingency tables were excluded. A multiple thresholds meta-analysis model was used to generate summary receiver operating characteristic curves for various time points. NSE thresholds (and 95% prediction intervals) for >95% specificity were calculated. Evidence appraisal was performed using a method adapted from the American Academy of Neurology grading criteria.ResultsData from 11 studies (n = 1,982) at 0–24 hours, 21 studies (n = 2,815) at 24–48 hours, and 13 studies (n = 2,557) at 48–72 hours was analyzed. Areas under the curve for prediction of poor outcomes were significantly larger at 24–48 hours and 48–72 hours compared to 0–24 hours (0.82 and 0.83 vs 0.64). Quality of evidence was very low for most studies because of the risk of incorporation bias—knowledge of NSE levels potentially influenced life support withdrawal decisions. To minimize falsely pessimistic predictions, NSE thresholds at the upper 95% limit of prediction intervals are reported. For prediction of poor outcome with specificity >95%, upper limits of the prediction interval for NSE were 70.4 ng/mL at 24–48 hours and 58.6 ng/mL at 48–72 hours. Sensitivity analyses excluding studies with inconsistent TTM use or different outcome criteria did not substantially alter the results.ConclusionsNSE thresholds for highly specific prediction of poor outcome are much higher than generally used. Future studies must minimize bias by masking treatment teams to the results of potential predictors and by prespecifying criteria for withdrawal of life support.

Development of a strategy for assessing blood-brain barrier disruption using serum S100 calcium-binding protein B and neuron-specific enolase in early stage of neuroemergencies: A preliminary study

“…This reflects findings of a previous study that suggested a certain cutoff value of serum NSE with respect to evaluating neurological outcomes in patients with OHCA (based on the lower limit of the 95% CI for serum NSE obtained within 24 hours of OHCA). [ 18 ] The subgroup analysis in the current study showed numerically improved AUROC values for serum S100B with respect to predicting BBB disruption (AUROC, 0.718–0.836) and a 0% false-positive ratio for predicting abnormal Qa. Moreover, we found an approximately 3.5-fold increase in the coefficient of determination between serum S100B and Qa (R 2 , 0.110–0.382).…”

“…Thus, we performed a subgroup analysis in patients with serum NSE levels of <40.8 ng/mL measured simultaneously with S100B, as suggested according to the lower limit of the 95% confidence interval (CI) for serum NSE obtained within 24 hours following cardiac arrest within a recent meta-analysis. [ 18 ] We performed this subanalysis to estimate the relationship between serum S100B and BBB status after excluding the confounding effects of established neuronal cell injury.…”

Septic encephalopathy in the elderly – biomarkers of potential clinical utility

“…We suggest that it may be advantageous to also determine neuron-specific enolase (NSE) in plasma/serum. When hemolytic samples are excluded, NSE already established as a prognostic marker in hypoxic brain injury ( Sharma et al, 2022 ; Kim et al, 2023 ) probably is a valuable tool for the quantification of neuronal injury in septic encephalopathy of older persons.…”

Neurocritical Care Updates in Cerebrovascular Disease

“…A post hoc analysis of the Targeted Temperature Management trial revealed that neurofilament levels were 13× higher in patients with malignant versus benign electroencephalographic patterns, and the extent of brain injury was more strongly related to background rather than superimposed discharges. 15 Imaging (eg, magnetic resonance-spectroscopy 16 ) and serological (eg, neuron-specific enolase 17 ) biomarkers for neuroprognostication are also valuable. Ultimately a multimodal approach will likely facilitate deep phenotyping enabling more robust neuroprognostication and targeted treatment strategies.…”