Background: To date, most work delineating the usefulness of neuron-specific enolase (NSE) as a marker for acute ischemic stroke has been inconclusive. This study had the following objectives: (1) to determine whether serum concentrations of NSE correlate with time of onset of stroke symptoms, volume of infarcted tissue, stroke severity, functional outcome, or length of hospital stay; (2) to determine whether serial measurements of NSE levels are useful markers for ongoing brain ischemia, and (3) to determine whether NSE levels at various time intervals are significantly higher in patients with stroke than in controls. 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 reviewer. Twelve studies (including 597 patients) satisfied the entry criteria for this qualitative analysis. Results: In 4 studies, time of onset of stroke symptoms was compared with time of first detectable NSE levels, which ranged from 4 to 8 h after stroke onset. In 7 studies, NSE levels increased with increased size of stroke, but in 2 studies there was no correlation. In the 2 studies that compared stroke severity with NSE levels, high NSE levels generally indicated worse outcome, but at low NSE levels the results were equivocal. In 7 studies, functional outcome at hospital dismissal and follow-up was compared with NSE levels; in 4, there was no correlation. Conclusions: The serum level of NSE does seem to be higher in stroke patients than in controls, and it does appear to correlate with volume of infarcted tissue. However, it does not appear to correlate with functional outcome, and its relationship to stroke severity is unclear. This may be explained at least in part by the disparity in sampling times because the NSE level has been shown to peak after 24 h in most studies. Hence, the more delayed the sampling, the greater the correlation with stroke severity.

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