Acute-phase clinical phenotyping stratifies long-term cognitive and functional outcomes in cerebral venous sinus thrombosis

Background Current prognostic models for cerebral venous sinus thrombosis (CVST) inadequately predict long-term cognitive and functional outcomes, focusing primarily on survival. We aimed to develop and validate a simple, acute-phase clinical phenotyping system to stratify the risk of these disabling sequelae. Methods In this retrospective cohort study, consecutive adult CVST patients between 2014 and 2024 were included. Patients were classified into three acute-phase phenotypes: Benign Intracranial Hypertension, Focal Brain Injury, and Diffuse Brain Injury. Long-term outcomes (cognitive impairment, depressive symptoms, return to work) were assessed at a median of 1 year post-onset via telephone interview. Multivariable logistic regression analyses adjusted for key confounders were used to determine independent associations. Results Among 110 patients, the prevalence of the Benign, Focal, and Diffuse Brain Injury phenotypes was 33.6% ( n = 37), 38.2% ( n = 42), and 28.2% ( n = 31), respectively. A significant gradient of worsening outcomes was observed across the three phenotypes based on the dominant clinical syndrome of isolated intracranial hypertension, focal, or diffuse brain injury. The prevalence of cognitive impairment (MoCA<26) was 27.0, 59.5, and 90.3% ( p < 0.001), and the rate of return to work was 89.2, 66.7, and 32.3% ( p = 0.002), respectively. After adjustment, both the Focal (aOR = 3.26, 95% CI: 1.18–9.01) and Diffuse Brain Injury (aOR = 9.21, 95% CI: 2.84–29.87) phenotypes were independent predictors of cognitive impairment versus the Benign phenotype. The Diffuse Brain Injury phenotype was also independently associated with depressive symptoms (aOR = 4.85, 95% CI: 1.67–14.09) and an 85% reduced odds of returning to work (aOR = 0.15, 95% CI: 0.05–0.43). Conclusion A simple, bedside-accessible clinical phenotyping system effectively stratifies long-term risk in CVST patients. The Diffuse Brain Injury phenotype warrants early, multidisciplinary intervention to mitigate its multifaceted poor prognosis.