Natural history of cerebral cavernous malformations

To determine the natural history of brain cavernous malformations, the authors entered patients referred to their center into a prospective registry between 1987 and 1993. All patients underwent magnetic resonance imaging, which showed the typical appearance of this lesion, and conservative management was recommended in all. Patients or their referring physicians were contacted for follow-up data. The purpose of the study was to define the rate of symptomatic hemorrhage and to determine the outcome in those patients who had suffered seizures. Follow-up data were available for 122 patients with a mean age at entry of 37 years (range 4-82 years). The malformation was located in the brainstem in 43 cases (35%), the basal ganglia/thalamus in 20 (17%), and a hemispheric area in 59 (48%). Fifty percent of patients had never had a symptomatic hemorrhage, 41% had one bleed, 7% had two, and 2% had three. Seizures were reported in 23% of patients and headaches in 15%. Lesions were solitary in 80% of patients and multiple in 20%. The retrospective annual hemorrhage rate (61 bleeds/4550.6 patient-years of life) was 1.3%. The mean prospective follow-up period was 34 months. There were nine bleeds during this time, six with new neurological deficits. In patients without a prior bleed, the prospective annual rate of hemorrhage was 0.6%. In contrast, patients with prior hemorrhage had an annual bleed rate of 4.5% (p = 0.028). Patient sex (p = 0.97) or the presence of seizures (p = 0.11), headaches (p = 0.06), or solitary versus multiple lesions (p = 0.15) were not significant predictors of later hemorrhage. There was no difference in the rate of bleeds between brain locations. Four patients with seizures became seizure-free and four patients without seizures later developed seizures; only one patient developed intractable seizures. Fourteen patients (11%) underwent surgery (two after hemorrhage, five with seizures, and seven with progressive deficits), and five had radiosurgery. No patient died in the follow-up period. This study indicates that conservative versus operative management strategies may need to be redefined, especially in patients who present with hemorrhage and who appear to have a significantly increased risk of subsequent rehemorrhage.