Long-Term Outcomes of Ischemic Stroke of Undetermined Mechanism: A Population-Based Prospective Cohort

Background and Purpose: Little is known about the short- and long-term outcomes of ischemic stroke of undetermined mechanism (ISUM). Methods: Subjects were recruited from the Mashhad Stroke Incidence Study. Ischemic stroke (IS) was classified on the basis of the TOAST criteria. We further categorized patients with ISUM into ISUMneg (negative clinical/test results for large artery, small artery) and ISUMinc (incomplete investigations). Cox proportional hazard models and the competing-risk regression model were used to compare 1 and 5 years mortality (all-causes) and recurrent rate among IS subtypes. Results: Overall, 1-year mortality was higher in those with ISUMinc than in ISUMneg (adjusted hazard ratio [aHR] 1.6, 95% CI 1.01–2.8; p = 0.04) and in other stroke subtypes. Cardioembolic stroke was associated with the greatest risk of stroke recurrence at one year (aHR 4.9, 95% CI 1.8–12.9; p = 0.001) and 5 years (HR 2.1, 95% CI 1.1–3.7; p = 0.01) as compared to ISUMneg. Conclusions: The classification of ISUM as a single group may lead to over- or underestimation of mortality and recurrence in this major category of IS. A better definition of ISUM is necessary to predict death and recurrence accurately.