title: Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location.
abstract: OBJECTIVE
  The cause of ischemic stroke remains unclear, or cryptogenic, in as many as 35% of patients with stroke. Not knowing the cause of stroke restricts optimal implementation of prevention therapy and limits stroke research. We demonstrate how gene expression profiles in blood can be used in conjunction with a measure of infarct location on neuroimaging to predict a probable cause in cryptogenic stroke.
  
  
  METHODS
  The cause of cryptogenic stroke was predicted using previously described profiles of differentially expressed genes characteristic of patients with cardioembolic, arterial, and lacunar stroke. RNA was isolated from peripheral blood of 131 cryptogenic strokes and compared with profiles derived from 149 strokes of known cause. Each sample was run on Affymetrix U133 Plus 2.0 microarrays. Cause of cryptogenic stroke was predicted using gene expression in blood and infarct location.
  
  
  RESULTS
  Cryptogenic strokes were predicted to be 58% cardioembolic, 18% arterial, 12% lacunar, and 12% unclear etiology. Cryptogenic stroke of predicted cardioembolic etiology had more prior myocardial infarction and higher CHA(2)DS(2)-VASc scores compared with stroke of predicted arterial etiology. Predicted lacunar strokes had higher systolic and diastolic blood pressures and lower National Institutes of Health Stroke Scale compared with predicted arterial and cardioembolic strokes. Cryptogenic strokes of unclear predicted etiology were less likely to have a prior transient ischemic attack or ischemic stroke.
  
  
  CONCLUSIONS
  Gene expression in conjunction with a measure of infarct location can predict a probable cause in cryptogenic strokes. Predicted groups require further evaluation to determine whether relevant clinical, imaging, or therapeutic differences exist for each group.
authors.affiliation: Department of Neurology and MIND Institute, University of California at Davis, Sacramento, CA 95817, USA. gcjickling@ucdavis.edu
authors.forename: Glen C
authors.initials: GC
authors.lastname: Jickling
authors.forename: Boryana
authors.initials: B
authors.lastname: Stamova
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhan
authors.forename: Dazhi
authors.initials: D
authors.lastname: Liu
authors.forename: Shara-Mae
authors.initials: SM
authors.lastname: Sison
authors.forename: Piero
authors.initials: P
authors.lastname: Verro
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000368:Aged; D002533:Cerebral Angiography; D002539:Cerebral Arterial Diseases / Q000150:complications* / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D006331:Heart Diseases / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D006333:Heart Failure / Q000150:complications; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000235:genetics*; D059409:Stroke, Lacunar / Q000175:diagnosis* / Q000235:genetics*; D013923:Thromboembolism / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography