Embolic Stroke of Undetermined Source: Gateway to a New Stroke Entity?

Embolic stroke of unknown source (ESUS) is currently thought to represent a subpopulation of cryptogenic strokes defined by its embolic stroke pattern on imaging, and if after a carefully performed diagnostic evaluation, a specific, well-recognized cause of stroke has not been identified. The concept was primarily established to justify and enable the conduct of the ESUS trials, such as Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RESPECT-ESUS) and New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus aspirin to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS). With both studies having neutral results, the question arises if the ESUS concept is misleading or rather a gateway for a modern understanding of stroke etiology. This review will analyze the background of the ESUS concept, overview the results and the impact of the recent multicenter trials and cohort studies, and discuss the definition, etiology, and diagnosis of ESUS.