Independent Association of Severe Venous Sinus Hypoplasia with Enlarged Perivascular Spaces: A Retrospective Cohort Study

Background : Perivascular spaces (PVSs) are integral to the brain's glymphatic system, serving as lymphatic drainage channels that mediate cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and waste clearance. Enlarged perivascular spaces (EPVSs) may result from metabolic waste accumulation in PVSs or CSF-ISF circulationdysfunction. The lateral dural sinus wall not only forms venous sinuses but also serves as a distribution area for meningeal lymphatic vessels (MLVs). However, the relationships among glymphatic drainage, CSF circulation, idiopathic intracranial hypertension (IIH), and venous sinus flow remain unclear. This study retrospectively collected patients who underwent venous lateral sinus Magnetic Resonance Venography (MRV) and routine brain Magnetic Resonance Imaging (MRI) to investigate the correlation between venous sinus hypoplasia and the severity of EPVSs. Methods : A total of 261 patients underwent venous sinus imaging analysis and assessment of EPVSs degree, and their clinical characteristics were documented. The development of the lateral venous sinus was classified as normal, mild hypoplasia, or severe hypoplasia. EPVSs were categorized into the basal ganglia (BG) region and the white matter (WM) region, both of which were classified into four degrees. Univariate analysis was used to analyze the differences between groups, and multivariate ordinal logistic regression and Spearman correlation analysis were employed to assess associations. The multivariate ordinal logistic regression was conducted in three models. Prioritized the intergroup analysis of venous sinus hypoplasia in Model I. Variables with P<0.01 entered Model II, those with P<0.05 entered Model III. Results : Univariate analysis showed that age, venous sinus dysplasia, hypertension, hyperlipidemia, diabetes, Alzheimer's disease (AD), and Parkinson's disease (PD) were statistically significant differences among the BG-EPVS. Similarly, age, venous sinus dysplasia, hypertension, AD, and PD were statistically significant differences among the WM-EPVSs. In the ordinal multivariate regression model, ‌age‌ (OR=1.19, P <0.001 in BG; OR=1.02, P =0.022 in WM) and ‌severe lateral sinus hypoplasia‌ ( P <0.001) were independently and positively correlated with EPVSs degree in both BG-EPVSs and WM-EPVSs. Furthermore, PD‌ was independently and positively associated with ‌BG-EPVSs‌ (OR=3.67, 95% confidence interval [CI]=1.11-12.15, P =0.033 ), whereas ‌hypertension‌ (OR=1.99, 95% CI=1.03-3.85, P =0.04), ‌AD‌ (OR=4.57, 95% CI=1.13-18.56, P =0.033), and ‌male gender‌ (OR=1.90, 95% CI=1.16-3.11, P =0.011) were independently and positively correlated with ‌WM-EPVSs load. Conclusion : Age and severe venous sinus hypoplasia were independent risk factors for both BG-EPVSs and WM-EPVSs. Additionally, hypertension, AD, and male gender all showed independent positive correlations with the load of WM-EPVSs, whereas PD was independently associated with BG-EPVSs.