Venous Architecture Predicts Hemorrhage Risk in Sporadic CCM With DVA

BACKGROUND: To prospectively validate an imaging-based classification system for cerebral cavernous malformation (CCM) associated with developmental venous anomaly (DVA) in a multicenter cohort, and to evaluate the association between DVA subtypes and hemorrhage risk. METHODS: This prospective multicenter cohort study was conducted as part of the Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy (CRESS) study at 2 tertiary neurosurgical centers in China. Patients with sporadic CCM and coexisting DVA were consecutively enrolled and prospectively followed for data collection between September 2019 and March 2024. Eligible patients had a single sporadic CCM with a coexisting DVA, confirmed by contrast-enhanced magnetic resonance imaging or susceptibility-weighted imaging, and provided written informed consent for scheduled follow-up. Patients were classified into 3 subtypes (Groups A, B, and C) based on DVA morphology and its anatomic relationship with the CCM by 2 independent neuroradiologists blinded to outcomes. Clinical, demographic, and imaging data were collected, and patients were followed at scheduled intervals. The primary outcome was symptomatic hemorrhage. Outcomes were assessed throughout the follow-up period from enrollment until the first occurrence of symptomatic hemorrhage or censoring. Kaplan-Meier survival analysis and multivariable Cox regression were used to assess hemorrhage risk across subtypes. RESULTS: Of the 237 patients, 37.6% were classified as Group A, 13.5% as Group B, and 48.9% as Group C. Over a median follow-up of 51.4 months, 75 (31.5%) patients experienced hemorrhagic events. Group C showed a markedly higher annual hemorrhage incidence (17.2 per 100 patient-years) compared with Group A (4.1 per 100 patient-years) and Group B (2.2 per 100 patient-years). Multivariable analysis confirmed that Group C was independently associated with increased hemorrhage risk compared with Group A (adjusted hazard ratio, 4.51 [95% CI, 2.42–8.40]). Other significant predictors included infratentorial location (hazard ratio, 2.67 [95% CI, 1.61–4.49]), history of previous hemorrhage (hazard ratio, 2.04 [95% CI, 1.24–3.35]), and Zabramski type I lesions (hazard ratio, 1.94 [95% CI, 1.02–3.72]). CONCLUSIONS: CCM located at the distal branches of DVA with radially converging veins (Group C) carries a significantly higher risk of symptomatic hemorrhage. This imaging-based classification offers a practical framework for risk stratification and may inform individualized surveillance strategies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04076449.