Cryptogenic stroke is not uncommon. In 2014, embolic stroke of undetermined source (ESUS) was advocated, two clinical trials for ESUS comparing the efficacy of direct oral anticoagulants (DOACs) and aspirin have failed to show any benefits of DOACs over aspirin, possibly due to heterogeneous embolic mechanisms in ESUS. Transesophageal echocardiography (TEE) is useful to screen for potential embolic sources such as patent foramen ovale, atrial septal aneurysm, and aortic arch plaques in ESUS/cryptogenic stroke. The Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke (CHALLENGE ESUS/CS) registry is a multicenter registry enrolling consecutive patients with CS who underwent TEE among 8 hospitals in Japan between April 2014 and December 2016. Inclusion criteria were: 1) ≥ 20 years of age within 7 days of stroke onset; 2) non-lacunar stroke on neuroradiological imaging; 3) absence of arterial stenosis ≥ 50% or occlusion in a corresponding large artery; 4) absence of major embologenic cardiac diseases; and 5) absence of other determined stroke etiologies. In this paper, results from CHALLENGE ESUS/CS are reviewed, and the pathomechanisms of cryptogenic stroke are discussed.
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