Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review

Abstract

Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.ABBREVIATIONS: ESUS ¼ embolic stroke of undetermined source; IPH ¼ intraplaque hemorrhage; LRNC ¼ lipid-rich necrotic core; SyNC ¼ symptomatic nonstenotic carotid artery disease; US ¼ ultrasound U p to one-third of strokes have no established mechanism and are considered to be cryptogenic. 1 In 2014, the term "embolic stroke of undetermined source" (ESUS) was established as a clinical entity in patients with nonlacunar cryptogenic stroke in which an embolic source was thought to be most likely, despite an appropriate diagnostic evaluation with negative findings (Fig 1). 2 This term (along with "cryptogenic stroke") has also been used to define patients who may have multiple, competing stroke etiologies in which a definitive source cannot be determined. Patients with ESUS have been estimated to have a .4% risk of recurrent stroke per annum despite being on antiplatelet medication. 1 Subsequent thought was directed to the idea that anticoagulation may be beneficial in such patients, given the likelihood that emboli originated from various nonevident atheroembolic sources. 3 This premise provided the impetus for 2 large clinical trials that compared anticoagulation with aspirin alone in patients with ESUS. 4,5 Despite this plausible theory, no benefit of anticoagulation was observed. These results spurred continued interest in additional

Lessons from autopsy: Topographical variability of atherosclerosis plaques

“… 5 These elements, along with other biological processes, significantly impact the development, severity, distribution, and advancement of atherosclerotic plaques. 6 , 7…”

“…5 These elements, along with other biological processes, significantly impact the development, severity, distribution, and advancement of atherosclerotic plaques. 6,7 Atherosclerosis presents another layer of complexity with the preferential localization of plaques in specific arterial systems within the same individual. This selective vulnerability remains puzzling and suggests a range of genetic, environmental, and lifestyle factors, including fetal programing, which interact in ways that are not fully understood yet.…”

Clinical Features, Radiological Findings, and Outcome in Patients with Symptomatic Mild (<50%) Carotid Stenosis: A MUSIC Study

“…3 With advances in imaging technology, however, there is an increasing evidence that a certain subgroup of medically treated patients with mild carotid stenosis may have at higher risk to repeat ischemic stroke when their plaque is vulnerable. [5][6][7] Thus, it may be no further sufficient to assess the stenosis degree alone to predict the future risk of ischemic events in patients with symptomatic mild carotid stenosis 5 .…”