Symptomatic non - stenotic carotid disease (SyNC) in ESUS (embolic stroke of undetermined source) patients: A prospective observational study

Objectives: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischemic strokes. Increasing evidence suggests that non-stenotic carotid plaques with high-risk morphological features may act as embolic sources in ESUS, leading to the concept of symptomatic nonstenotic carotid disease (SyNC). However, data on the prevalence and clinical relevance of SyNC in Indian populations remain limited. The objective of the study is to determine the frequency of SyNC in patients with ESUS and to compare the clinico-radiological characteristics and outcome between ESUS patients with and without SyNC. Materials and Methods: In this prospective observational study conducted at a tertiary care center, consecutive patients aged >12 years presenting with acute ischemic stroke or transient ischemic attack were screened between October 2023 and May 2025. Patients fulfilling ESUS criteria involving the anterior circulation were included. All patients underwent standardized neuroimaging and computed tomography angiography (CTA). Non-stenotic carotid plaques (<50% stenosis) were evaluated for high-risk features. SyNC was defined as the presence of an ipsilateral non-stenotic carotid plaque with at least one high-risk feature. Clinical characteristics, imaging findings, and outcomes at three months (modified Rankin scale [mRS]) were compared between SyNC and non-SyNC groups. Results: Of 251 patients screened, 69 met ESUS criteria and were included. SyNC was identified in 20 patients (29.0%). Baseline demographics and vascular risk factors were similar between groups, although SyNC patients had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (14.2 ± 6.8 vs. 10.9 ± 4.9; p = 0.028). Middle cerebral artery territory infarcts predominated in both groups, with a higher proportion of watershed infarcts in the SyNC group. At three months, poor outcome (mRS 4–6) was more frequent in SyNC patients compared with non-SyNC patients (45.0% vs. 21.27%; p = 0.049). Conclusion: SyNC was present in nearly one-third of ESUS patients and was associated with higher baseline stroke severity; however, its independent impact on functional outcome remains uncertain after adjustment for potential confounding factors. These findings highlight the potential clinical relevance of carotid plaque vulnerability in ESUS and support the need for larger studies to refine risk stratification and preventive strategies.