title: Correlation of levels of neuronal and glial markers with radiological measures of infarct volume in ischaemic stroke: a systematic review.
abstract: 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-β are potential candidate biomarkers.
  
  
  OBJECTIVE
  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-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.
  
  
  CONCLUSIONS
  Peak 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.
authors: Division of Clinical Neurosciences, Bramwell Dott Building, Western General Hospital, Edinburgh, UK.
authors: Omar
authors: O
authors: Ahmad
authors: Joanna
authors: J
authors: Wardlaw
authors: William N
authors: WN
authors: Whiteley
mesh_terms: D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D004676:Myelin Basic Protein / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D009419:Nerve Tissue Proteins / Q000097:blood*; D009457:Neuroglia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016875:tau Proteins / Q000097:blood
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; C054369:MAPT protein, human; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase