Extracellular Micrornas in Blood Differentiate Between Ischemic and Hemorrhagic Stroke Subtypes

Background: Rapid identification of patients suffering from cerebral ischemia, while excluding intracerebral hemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs (ex-miRNAs) predictive of major stroke subtypes using clinical samples from subjects with intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), and ischemic stroke due to cerebral vessel occlusion. Methods: We collected blood from patients presenting with IPH (n=19), SAH (n=17) and ischemic stroke (n=21). We isolated extracellular vesicles from plasma, extracted RNA cargo, sequenced the small RNAs, and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Findings: 67 miRNAs were significantly variant across the stroke subtypes. A subset of ex-miRNAs differed between hemorrhagic and ischemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.97 +/- 0.002. Further analyses predicted miRNA classifiers that stratify IPH from ischemic stroke with accuracy of 0.81 +/- 0.004 and distinguish hemorrhagic from ischemic stroke with accuracy of 0.81 +/- 0.003. Interpretations: Blood-based, ex-miRNAs have predictive value, capable of distinguishing between major stroke subtypes. Such a biomarker may serve as point-of-care tests to rapidly and reliably differentiate between major stroke subtypes and aid with the triage of patients to expand the pool eligible for chemical and mechanical revascularization. Funding: This work was funded by the NIH-National Center for Translational Sciences (1UH2TR000891/1UH3TR000891). SK was also supported by Texas A&M System Chancellor's Research Initiative for the Center for Computational Systems Biology at Prairie View A&M University. Declaration of Interest: KVKJ is a member of the scientific advisory board at Dyrnamix Ethical Approval: This study was approved by the institutional review boards of St. Joseph’s Hospital and Medical Center (13BN094) and WIRB (#20120512).