Shifting Outcomes: Superior Functional Recovery in Embolic Stroke of Undetermined Source Compared to Cardioembolic Stroke

Background/Objectives: Embolic Stroke of Undetermined Source (ESUS) is a subtype of ischemic stroke characterized by a non-lacunar infarct in the absence of a clearly identifiable embolic source, despite comprehensive diagnostic evaluation. While ESUS patients are typically younger, have fewer cardiovascular comorbidities, and experience milder strokes than those with cardioembolic strokes (CE), their long-term functional recovery remains underexplored. Methods: We retrospectively analyzed data from 317 ischemic stroke patients (n = 37 ESUS, n = 280 CE) admitted to the Department of Neurology, University of Pécs, between February 2023 and September 2024. Functional recovery was assessed using the modified Rankin Scale (mRS), adjusted for baseline differences (adjusted mRS-shift). Independent predictors of mRS-shift were identified using Firth penalized regression and extreme gradient boosting (XGBoost). Results: ESUS patients were significantly younger (53.8 ± 13.5 years vs. 75.1 ± 11.3 years, p <0.001), had lower pre-morbid modified Rankin Scale (pre-mRS) scores (0.22 ± 0.75 vs. 0.81 ± 1.23, p <0.001), were less likely to have hypertension (70.3% vs. 86.1%, p = 0.027), and presented with milder strokes at admission (National Institutes of Health Stroke Scale [NIHSS] score 5.5 ± 3.6 vs. 8.1 ± 6.3, p <0.001) and 72 hours post-stroke (2.8 ± 3.7 vs. 6.5 ± 6.3, p <0.001) compared to CE patients. After adjusting for baseline differences, ESUS patients had significantly better functional recovery (adjusted mRS-shift 1.30 ± 1.71 vs. 2.27 ± 2.17, p <0.001). Conclusions: ESUS patients showed superior functional recovery compared to CE patients, even after adjusting for baseline differences. These findings highlight the need for further research into the pathophysiology and optimal treatment for ESUS.