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BackgroundA 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-β are potential candidate biomarkers.AimWe systematically reviewed the relevant literature to find studies that correlated blood levels of neuronal and glial damage markers with imaging measures of infarct volume.MethodsWe 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.ResultsSeventeen studies met the criteria for the systematic review. There were sufficient data to provide summary estimates for S100-β and NSE. The peak level and AUC over time of both markers correlated with subacute infarct volume. Measurements of S100-β 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.ConclusionPeak and AUC levels of NSE and S100-β levels correlated with subacute infarct volume. Correlations of S100-β 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.

Original publication




Journal article


Cerebrovascular diseases (Basel, Switzerland)

Publication Date





47 - 54


Division of Clinical Neurosciences, Bramwell Dott Building, Western General Hospital, Edinburgh, UK.


Brain, Neuroglia, Neurons, Humans, Brain Ischemia, Glial Fibrillary Acidic Protein, Phosphopyruvate Hydratase, Nerve Growth Factors, S100 Proteins, tau Proteins, Nerve Tissue Proteins, Tomography, X-Ray Computed, Magnetic Resonance Imaging, Prognosis, Predictive Value of Tests, Time Factors, Stroke, Myelin Basic Protein, S100 Calcium Binding Protein beta Subunit, Biomarkers