Neuron-Specific enolase as a marker for acute ischemic stroke: A systematic review

Abstract

Study objectives: Neuron-specific enolase (NSE) is a glycolytic enzyme that is found mainly in the cytoplasm of neurons and cells of neuroendocrine origin. To date, the majority of the work delineating the usefulness of NSE as a marker for acute ischemic stroke has been inconclusive and on a limited number of patients. We determine whether serum NSE correlates with time of onset of stroke symptoms, volume of infarct, stroke severity, functional outcome, or hospital length of stay. We determine whether serial NSE levels are useful as a marker for ongoing brain ischemia. We determine if NSE levels are significantly higher for patients with stroke compared with controls at various intervals. Methods: All abstracts and published full reports identified as potentially relevant by the literature search were independently assessed for inclusion in the review by each of the reviewers. This was a qualitative analysis. Results: Twelve studies satisfying the entry criteria were identified. Four studies examined time of onset of stroke symptoms versus earliest time NSE levels were detectable. NSE levels were found to be higher ranging from 4 to 8 hours postinfarct. Seven studies found increased NSE levels to be associated with increased size of stroke. Two studies found no correlation. Two studies examined stroke severity versus NSE levels. Higher NSE levels generally indicated worse outcome, but with low NSE levels, the results were equivocal. Seven of the 12 included studies examined functional outcome at discharge and follow-up versus NSE levels. Four of these 7 studies found no correlation between serum NSE and functional outcome. No correlation was found when using the Scandinavian Stroke Scale, Activities of Daily Living Scale, or the Glasgow Outcome Score. There was a correlation with Barthel index, modified Rankin Score at 90 days, admission and day 7 National Institutes of Health Stroke Scale, and a trend with the Lindley score. No trial correlated hospital length of stay with NSE levels without the confounding influence of increased volume of infarct leading to increased length of stay. Three studies found a relationship between NSE levels and time; however, 3 studies did not. Seven studies reported statistically significant differences between NSE levels in patients with stroke compared with control groups. One study reported that patients with total anterior cerebral strokes had statistically elevated levels of NSE compared with controls. However, patients with partial anterior cerebral stroke did not reach statistical significance with regard to NSE levels. Conclusion: Overall, according to the data for these 597 patients, it is possible to state that serum NSE level does in fact seem to be higher in stroke patients compared with controls and does appear to correlate with volume of infarct. However, it does not appear to correlate with functional outcome, and its relationship to stroke severity is unclear.