ORIGINAL RESEARCH article
Front. Neurol.
Sec. Applied Neuroimaging
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1620772
Association Between Glymphatic Dysfunction and Cryptogenic Stroke Risk in Patients with Patent Foramen Ovale: A Retrospective Cross-Sectional Study
Provisionally accepted
Fengfeng Wang*
Qun Li- Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
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Abstract Background: Patent foramen ovale (PFO) is strongly associated with cryptogenic stroke (CS), but the underlying mechanisms remain incompletely understood. The glymphatic system plays a crucial role in central nervous system homeostasis, and its dysfunction has been implicated in various neurological disorders. This study aimed to evaluate the association between glymphatic dysfunction, assessed by the ALPS (Analysis Along the Perivascular Space) index, and the risk of cryptogenic stroke in patients with PFO. Methods: This retrospective, single-center cross-sectional study enrolled 208 PFO patients, including 52 with cryptogenic stroke and 156 without a history of stroke. All participants underwent brain MRI with diffusion tensor imaging (DTI) to calculate the ALPS index. Clinical data, laboratory tests, and echocardiographic parameters were collected. Multivariate logistic regression was used to identify independent predictors of cryptogenic stroke, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of the ALPS index. Results: Patients with cryptogenic stroke exhibited significantly lower ALPS index values compared to controls (1.31 ± 0.18 vs. 1.52 ± 0.21, p < 0.001). Multivariate analysis demonstrated that a lower ALPS index (OR = 0.126, 95% CI: 0.059–0.273, p < 0.001) was independently associated with cryptogenic stroke after adjusting for confounders. The ALPS index showed excellent diagnostic performance, with an AUC of 0.916 (95% CI: 0.876–0.956), yielding a sensitivity of 90.7% and specificity of 82.2% at the optimal cut-off value. Conclusion: In PFO patients, impaired glymphatic function, as indicated by a lower ALPS index, was independently associated with an increased risk of cryptogenic stroke. The ALPS index may serve as a promising non-invasive imaging biomarker for stroke risk stratification in this high-risk population.
Keywords: patent foramen ovale, cryptogenic stroke, Glymphatic system, ALPS index, Diffusion Tensor Imaging, risk stratification
Received: 19 May 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fengfeng Wang, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
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