Embolic Stroke of Undetermined Source (ESUS): Prevalence, Risk Factors, and Diagnostic Insights from a Prospective German Cohort

BACKGROUND AND OBJECTIVES: Embolic stroke of undetermined source (ESUS) was introduced to standardize the classification of cryptogenic strokes with presumed embolic origin. However, ESUS comprises a heterogeneous group with diverse clinical and diagnostic features. This study aimed to characterize ESUS within a prospective stroke cohort and compare it with other defined ischemic stroke subtypes. METHODS: In this prospective, single-center study, patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled over 6 months. Stroke etiology was classified according to established criteria, including ESUS definitions based on the exclusion of major cardioembolic sources, ≥50% large-artery stenosis, and small-vessel disease. All patients underwent neuroimaging, vascular diagnostics, and cardiological workup, including echocardiography and rhythm monitoring. RESULTS: Of 714 patients, 98 (13.7%) met ESUS criteria. ESUS patients were younger (median 67 vs. 74 years), predominantly male (61.2%), and had fewer prior strokes or TIAs (11.2% vs. 27.6%, P < 0.001) than nonESUS patients. Hypertension (72.2%) and obesity (54.2%) were common. Stroke severity at discharge was lower in ESUS (National Institutes of Health Stroke (NIHSS) 1.9 ± 2.3) compared to cardioembolic (4.8 ± 3.7) and atherosclerotic strokes (3.5 ± 3.1) ( P < 0.05), and no in-hospital deaths occurred in the ESUS group ( P = 0.02). While overall diagnostic imaging rates were similar across groups, transesophageal echocardiography was performed more frequently in ESUS (38.8%). CONCLUSIONS: ESUS accounted for 18% of ischemic strokes and represents a distinct, clinically relevant subgroup with unique demographic and outcome profiles. These findings support the refinement of ESUS classification and the need for individualized diagnostic and secondary prevention strategies.