Embolic stroke of undetermined source: The role of the nonstenotic carotid plaque

Cryptogenic stroke, or stroke of undetermined cause, presents a remarkably challenging dilemma for the treating physician as there are limited therapeutic options to prevent recurrence. Roughly one third of transient ischemic attacks (TIAs) and ischemic strokes are classified as cryptogenic, with an even greater proportion in young patients. While classification systems have been successfully used in trials to refine therapeutic approaches specific to subtype, there has been little progress made in secondary prevention of cryptogenic stroke. The cryptogenic stroke/ESUS International Working Group recently proposed a new entity under the realm of cryptogenic stroke called embolic stroke of undetermined source (ESUS). This clinical construct emerged from data suggesting thromboembolism as the primary etiology of cryptogenic strokes. While current trials are addressing covert atrial fibrillation as a significant source of embolism, more recent population data has called this hypothesis into question and illustrated the heterogeneity, and often multiplicity, of embolic sources. The importance of carotid artery plaques which do not cause significant stenosis as a source of emboli to the brain has generally been ignored given the long-standing focus of using percent stenosis measurements as the primary criterion for defining high-risk carotid atherosclerotic disease. As part of the required diagnostic workup to define ESUS, vascular imaging, and advances therein, provides a unique opportunity to prospectively determine a subset of patients who may benefit from aggressive medical therapy or endovascular interventions in the prevention of recurrent ESUS. Here we review the role of the nonstenotic, and potentially vulnerable, carotid plaque in ESUS.