title: Embolic strokes of undetermined source: the case for a new clinical construct.
abstract: Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.
authors.affiliation: McMaster University and Population Health Research Institute, Hamilton, ON, Canada. Electronic address: robert.hart@phri.ca.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.affiliation: University Duisburg-Essen, Essen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: University of Calgary, Calgary, AB, Canada.
authors.forename: Shelagh B
authors.initials: SB
authors.lastname: Coutts
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, USA.
authors.forename: J Donald
authors.initials: JD
authors.lastname: Easton
authors.affiliation: Duke University, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: National University of Ireland Galway, Galway, Ireland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: O'Donnell
authors.affiliation: Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.affiliation: McMaster University and Population Health Research Institute, Hamilton, ON, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
mesh_terms: D006801:Humans; D020521:Stroke / Q000209:etiology*; D013923:Thromboembolism / Q000150:complications*