Correlation of Levels of Neuronal and Glial Markers with Radiological Measures of Infarct Volume in Ischaemic Stroke: A Systematic Review

Background: A blood test that quantified the extent of brain damage following ischaemic stroke might be a useful surrogate outcome measure in trials of acute stroke treatments. Measures of neuronal and glial damage, such as neuron-specific enolase (NSE), glial fibrillary acidic protein, tau-protein, myelin-basic protein and S100-beta are potential candidate biomarkers. Aim: We systematically reviewed the relevant literature to find studies that correlated blood levels of neuronal and glial damage markers with imaging measures of infarct volume. Methods: We identified studies with a comprehensive search of databases and the reference lists of relevant studies. We included studies that: (1) measured the highest level, or area under the curve (AUC) over time of markers of cerebral damage, (2) calculated infarct volume, and (3) correlated the two measures. Results: Seventeen studies met the criteria for the systematic review. There were sufficient data to provide summary estimates for S100-beta and NSE. The peak level and AUC over time of both markers correlated with subacute infarct volume. Measurements of S100-beta later than 24 h after stroke were better correlated with subacute infarct size than earlier measurements. However, scan times varied, and none was later than 8 days after stroke. Conclusion: Peak and AUC levels of NSE and S100-beta levels correlated with subacute infarct volume. Correlations of S100-beta with infarct volume were stronger when measured after 24 h than closer to admission. Exploratory studies within clinical trials are necessary before blood markers of cerebral tissue damage can be recommended as surrogate endpoints. Copyright (c) 2011 S. Karger AG, Basel