title: Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system.
abstract: OBJECTIVE
  Hemorrhages from cerebral cavernous malformations (CMs) sometimes seem to occur in closely spaced "clusters" interspersed with long hemorrhage-free intervals. Clustering of hemorrhages could affect retrospective assessments of radiosurgery efficacy in prevention of CM rehemorrhage. However, this empirical observation had not been tested quantitatively. To test whether CM hemorrhages tend to cluster, we reviewed pretreatment rebleeding rates after a first symptomatic hemorrhage in CM patients who later underwent surgery or radiosurgery.
  
  
  METHODS
  We performed a retrospective review of 141 patients with CMs who presented with clinically overt hemorrhage, and who subsequently underwent surgery or proton beam radiosurgery during an 18-year period. Statistical models were used to analyze all events per person and identify potential variation 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 patient years elapsed between first hemorrhages and treatment. The cumulative incidence 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 spontaneously to less than 1% per month, which represents a 2.4-fold decline (P < 0.001). Rehemorrhage rates were higher in younger patients (P < 0.01), but not in females or in patients with deep lesions. Shorter intervals between successive hemorrhages did not predict higher subsequent rehemorrhage risk.
  
  
  CONCLUSIONS
  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 CMs.
authors: Neurosurgical Service, Massachusetts General Hospital, Boston 02114, USA. barker@helix.mgh.harvard.edu
authors: F G
authors: FG
authors: Barker
authors: S
authors: S
authors: Amin-Hanjani
authors: W E
authors: WE
authors: Butler
authors: S
authors: S
authors: Lyons
authors: R G
authors: RG
authors: Ojemann
authors: P H
authors: PH
authors: Chapman
authors: C S
authors: CS
authors: Ogilvy
mesh_terms: D000293:Adolescent; D000328:Adult; D002426:Cavernous Sinus / Q000002:abnormalities*; D020785:Central Nervous System Vascular Malformations / Q000150:complications*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors