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

Background/Objectives: An 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 (CEs), their functional recovery remains underexplored. Methods: We retrospectively analyzed data from 374 ischemic stroke patients (n = 94 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). Propensity score matching (PSM) was performed to balance the baseline characteristics, and the mRS-shift was compared between groups. Independent predictors of mRS-shift were identified using Huber regression and extreme gradient boosting (XGBoost). Results: The ESUS patients were significantly younger (60.7 ± 13.8 years vs. 75.1 ± 11.3 years, p < 0.001), had lower pre-morbid modified Rankin Scale (pre-mRS) scores (0.34 ± 0.91 vs. 0.81 ± 1.23, p < 0.001), were less likely to have hypertension (75.5% vs. 86.1%, p = 0.027) and diabetes (23.4% vs. 36.8%, p = 0.024), and presented with milder strokes (National Institutes of Health Stroke Scale [NIHSS] score at admission: 5.4 ± 4.5 vs. 8.1 ± 6.3, p < 0.001, and 72 h post-stroke: 3.0 ± 4.4 vs. 6.5 ± 6.3, p < 0.001) compared to the CE patients. After adjusting for baseline differences, the ESUS patients demonstrated significantly greater functional recovery than the CE patients (adjusted mRS-shift: 1.84 ± 1.14 vs. 2.53 ± 1.69, p = 0.022). Age, pre-mRS score, and NIHSS score at 72 h post-stroke were the strongest predictors of mRS-shift, with an older age, a higher pre-mRS score, and a greater stroke severity significantly decreasing the odds of recovery. Conclusions: The ESUS patients showed superior functional recovery compared to the CE patients, even after accounting for baseline differences. These findings highlight the need for further research into the pathomechanisms underlying ESUSs and the development of optimal treatment strategies to improve patient outcomes.