Early biomarkers of stroke.
BACKGROUND
The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (<33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests.


METHODS
ELISAs for >50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke.


RESULTS
The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset.


CONCLUSIONS
A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.
D000208:Acute Disease; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood / Q000175:diagnosis; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D009414:Nerve Growth Factors; D011379:Prognosis; D012044:Regression Analysis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D020521:Stroke / Q000097:blood* / Q000175:diagnosis; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D001798:Blood Proteins; D019208:Brain-Derived Neurotrophic Factor; D018932:Chemokine CCL2; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014841:von Willebrand Factor; D020780:Matrix Metalloproteinase 9