Hemorrhage Risk of Untreated Isolated Cerebral Cavernous Malformations

OBJECTIVE: Predicting future hemorrhage risk may allow better selection of patients with cerebral cavernous malformations (CCMs) who will likely benefit from treatment. In this study, we sought to identify predictors of CCM hemorrhage, and to compare subsequent symptomatic hemorrhage risks between patients with and without previous hemorrhage. METHODS: We performed a retrospective review of consecutive CCM patients at our institution between 1982 and 2017. Patients with diffuse or familial CCM syndromes, and those without follow-up data were excluded. The primary endpoint was acute symptomatic hemorrhage causing transient or permanent neurological symptoms. Primary endpoint incidences were compared between patients with and without previous hemorrhage. RESULTS: The study cohort comprised 84 patients with 90 CCMs. Previous hemorrhage was the only significant predictor for the primary endpoint (P = 0.003). CCMs with previous hemorrhage had a higher risk of symptomatic hemorrhage in follow-up than those without previous hemorrhage (26.9 vs. 1.5 symptomatic hemorrhages per 1000 CCM-months, P < 0.001). CCMs with and without previous hemorrhage had annual hemorrhage rates of 2.7% and 0.15%, respectively. Symptomatic hemorrhage-free survival rates were significantly lower in CCMs with previous hemorrhage (log-rank test, P < 0.001). Actuarial hemorrhage-free survival rates for CCMs with previous hemorrhage were 75%, 60%, 60%, and 60% at 1, 2, 3, and 4 years, respectively, compared with rates of 95%, 95%, 95%, and 84% for CCMs without previous hemorrhage. CONCLUSIONS: Previous hemorrhage is a predictor of subsequent symptomatic hemorrhage in CCMs. Compared with CCMs without previous hemorrhage, those with prior hemorrhage have a significantly higher risk of future symptomatic hemorrhage.