Signatures of cardioembolic and large-vessel ischemic stroke
Article first published online: 28 OCT 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 5, pages 681–692, November 2010
How to Cite
Jickling, G. C., Xu, H., Stamova, B., Ander, B. P., Zhan, X., Tian, Y., Liu, D., Turner, R. J., Mesias, M., Verro, P., Khoury, J., Jauch, E. C., Pancioli, A., Broderick, J. P. and Sharp, F. R. (2010), Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol., 68: 681–692. doi: 10.1002/ana.22187
- Issue published online: 28 OCT 2010
- Article first published online: 28 OCT 2010
- Manuscript Accepted: 30 JUL 2010
- Manuscript Revised: 9 JUL 2010
- Manuscript Received: 27 MAY 2010
- NIH National Institutes of Neurological Disorders and Stroke. Grant Numbers: NS056302, PO21040N635110
- American Heart Association Bugher Foundation
The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group.
A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large-vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross-validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors.
A 40-gene profile differentiated cardioembolic stroke from large-vessel stroke with >95% sensitivity and specificity. A separate 37-gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large-vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation.
Gene expression signatures distinguish cardioembolic from large-vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies. Ann Neurol 2010;68:681–692