Early Cerebral Edema Subtypes and Functional Outcome in Patients With Cerebral Venous Thrombosis: Insights From the CLOT-VENUS Registry

Abstract

Background and Objectives – Cerebral edema is a common yet poorly defined neuroimaging feature in cerebral venous thrombosis (CVT), and its influence on downstream clinical outcomes has not been fully elucidated. We aimed to characterize cerebral edema subtypes and evaluate their effect on functional outcomes in patients with CVT. Methods – We conducted a retrospective analysis using the CLOT-VENUS (Collaboration on Cerebral Venous Thrombosis) registry, an international cohort of patients with acute CVT treated at 2 major stroke centers in the United States and Mexico between 2004 and 2024. Admission neuroimaging (MRI and/or CT) was independently reviewed to classify cerebral edema into 3 subtypes: global cerebral edema, cytotoxic edema, and vasogenic edema. The primary outcome was the 6-month modified Rankin Scale (mRS) score, which was assessed as an ordinal shift. Secondary outcomes included ordinal mRS score at discharge, poor functional outcome (mRS 3–6 vs 0–2 and mRS 2–6 vs 0–1), in-hospital mortality, 6-month mortality, and length of hospital stay (LOS). Multivariable models adjusted for prespecified baseline confounders were used to estimate the effect of cerebral edema on these outcomes. Results – We included 394 patients with CVT (mean age was 42.7 ± 16.9 years; 65.5% female). Cerebral edema was identified in 220 patients and classified as cytotoxic edema (32.5%), global cerebral edema (25.6%), or vasogenic edema (24.9%). At discharge, global cerebral edema (adjusted odds ratio [aOR]: 2.79; 95% CI 1.83–4.27; p < 0.001) and cytotoxic edema (aOR: 1.89; 95% CI 1.27–2.80; p = 0.002) increased the odds of worse mRS scores. Similarly, at 6-month follow-up, both global cerebral edema (aOR: 1.83; CI 1.19–2.81; p = 0.006) and cytotoxic edema (aOR: 1.92; CI 1.28–2.88; p = 0.002) had a direct effect on higher odds of mRS scores. In addition, cytotoxic edema increased the risk of in-hospital mortality (aOR: 3.17; 95% CI 1.22–8.96; p = 0.021). Global cerebral edema led to a prolonged LOS (+2.00 days at median; p = 0.014). Discussion – Our results suggest that cytotoxic and global cerebral edema independently worsened 6-month functional outcomes in patients with CVT, with cytotoxic edema also increasing the risk of in-hospital mortality. Prospective studies should evaluate whether early cerebral edema subtypes can serve as critical entities that could potentially stratify patients for adjunctive therapies beyond anticoagulation.