Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system

OBJECTIVE: Hemorrhages from cerebral cavernous malformations (CMs) sometime s seem to occur in closely spaced "clusters" interspersed with long hemorrh age-free intervals. Clustering of hemorrhages could affect retrospective as sessments of radiosurgery efficacy in prevention of CM rehemorrhage. Howeve r, this empirical observation had not been tested quantitatively. To test w hether CM hemorrhages tend to cluster, we reviewed pretreatment rebleeding rates after a first symptomatic hemorrhage in CM patients who later underwe nt surgery or radiosurgery. METHODS: We performed a retrospective review of 141 patients with CMs who p resented with clinically overt hemorrhage, and who subsequently underwent s urgery or proton beam radiosurgery during an 18-year period. Statistical mo dels were used to analyze all events per person and identify potential vari ation in rebleeding risk with time after a previous hemorrhage. RESULTS: Sixty-three of 141 patients experienced a second hemorrhage before treatment; 16 had additional hemorrhages. Five hundred thirty-eight patien t years elapsed between first hemorrhages and treatment. The cumulative inc idence of a second hemorrhage after the first CM hemorrhage was 14% after 1 year and 56% after 5 years. During the first 2.5 years after a hemorrhage, the monthly rehemorrhage hazard was 2%. The risk then decreased spontaneou sly to less than 1% per month, which represents a 2.4-fold decline (P < 0.0 01). Rehemorrhage rates were higher in younger patients (P < 0.01), but not in females or in patients with deep lesions. Shorter intervals between suc cessive hemorrhages did not predict higher subsequent rehemorrhage risk. CONCLUSION: The rehemorrhage rate from untreated CMs is high initially, and it decreases 2 to 3 years after a previous hemorrhage. This hazard pattern generates the observed temporal clustering of hemorrhages from untreated C Ms.