Researchers at the Mayo Clinic, Rochester, MN reviewed the records and radiograph data of 292 patients (47.3% male) seen between 1989 and 1999 with a diagnosis of intracerebral cavernous malformation (ICM). The mean age at diagnosis was 45.8 years (range 3.5-88.9 years). Seventy-four patients presented with hemorrhage, 108 with seizure or focal deficit (symptoms not related to hemorrhage), and 110 were asymptomatic. The overall annual rate of hemorrhage at follow-up in the patients grouped according to presenting symptoms was 6.19%, 2.18%, and 0.33%, respectively. The median length of follow-up was 7.3 years (range 0-25 years); 68 patients underwent surgical excision. Patients who presented initially with symptomatic hemorrhage were at higher risk for future hemorrhage (p<0.001), and hemorrhage risk decreased with time; 81% were free of prospective hemorrhage at 10.6 years. Of 32 patients with prospective symptomatic hemorrhage, 19 (59%) initially presented with hemorrhage. The annual statistically significant risk factors for prospective hemorrhage included younger age (p=0.02) (without adjustment for gender etc.), male gender (p=0.02), infratentorial location (p=0.015), initial presentation as hemorrhage (p<0.001), and multiplicity of ICMs (p=0.01). Pregnancy was not a risk factor. The median time from first to second hemorrhage was 8 months. 
COMMENT. In an editorial, Salman and Murray question whether a risk of re-bleeding of 10-20% in the first 2 years of follow-up of cavernous malformations warrants early neurosurgical excision . This question is addressed in the following studies in Switzerland.
In a multicenter study of 79 pediatric patients with cerebral cavernous malformation (CCM) treated by surgical resection at University Hospital, Zurich, 77.3% became seizure free. Resection was the treatment of choice if lesions caused medically refractory epilepsy or other persistent symptoms . Mean age at presentation was 9.7 years, and mean age at operation was 11.3 years. One-quarter of all CCMs affect children.
In a study of outcome of 20 children with CCM treated in Berne, Switzerland, average age at presentation was 8.5 years (range 7 months to 16 years). Presentation was acute hemorrhage in 17 (85%), seizures in 9 (45%), focal neurologic symptoms in 5 (25%), and headache only in 3 (15%). Location was supratentorial in 15 (75%). Treatment was conservative in 10 and surgical in 10. Neurological sequelae at follow-up (0.5-10 years) occurred in 6 (30%) patients. 
A study of the natural history of CCM in 92 children and young adults at the University of Michigan, Ann Arbor, found the imaging prevalence of CCM increased with advancing age (p=0.002). Multiple CMs occurred in 28 (30%) patients. Thirty patients presented with hemorrhage, and the hemorrhage rate was 8% per patient-year in the symptomatic group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute hemorrhage (p=0.02). 
A prospective, Scotland, population-based cohort study of 139 adults with CCM, radiologically validated, found the risk of recurrent intracranial hemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, greater for women than for men (p=0.01), and declines over 5 years from 9.8% in year 1 to 5.0% in year 5 . The increased risk in women in this study of adults only is different from that in the Mayo Clinic study showing a preponderant risk in males.