J Neurosurg 80:422-432, 1994 The natural history of familial cavernous malformations: results of an ongoing study JOSEPH M. ZABRAMSKI, M.D., THOMAS M. WASCHER, M.D., ROBERT F. SPETZLER, M.D., BLAKE JOhnSON, M.D., JOaN GOLrINOS, M.D., BURTON P. DRAYER, M.D., BEN BROWN, M.D., DANIEL RIGAMONTI, M.D., AND GERALDINE BROWN, R.N., M.S. Divisions of Neurological Surgery and Neuroradiolo83; Barrow Neurological Institute, St. Joseph's Hospital, Phoenix, Arizona; Division of Neuroradiology, Kaiser Permanente Hospital, Portland, Oregon; and Division of Neurological Surgery, University of Maryland Hospital, Baltimore, Maryland ~" Cavernous malformations are congenital abnormalities of the cerebral vessels that affect 0.5% to 0.7% of the population. They occur in two forms: a sporadic form characterized by isolated lesions, and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance. The management of patients with cavernous malformations, particularly those with the familial form of the disease, remains a challenge because little is known regarding the natural history. The authors report the results of an ongoing study in which six families afflicted by familial cavernous malformations have been prospectively followed with serial interviews, physical examinations, and magnetic resonance (MR) imaging at 6- to 12-month intervals. A total of 59 members of these six families were screened for protocol enrollment; 31 (53%) had MR evidence of familial cavernous malformations. Nineteen (61%) of these 31 patients were symptomatic, with seizures in 12 (39%), recurrent headaches in 16 (52%), focal sensory/motor deficits in three (10%), and visual field deficits in two (6%). Twenty-one of these 31 patients underwent at least two serial clinical and MR imaging examinations. A total of 128 individual cavernous malformations (mean 6.5 -+ 3.8 lesions/patient) were identified and followed radiographically. During a mean follow-up period of 2.2 years (range 1 to 5.5 years), serial MR images demonstrated 17 new lesions in six (29%) of the 21 patients; 13 lesions (10%) showed changes in signal characteristics, and five lesions (3.9%) changed significantly in size. The incidence of symptomatic hemorrhage was 1.1% per lesion per year. The results of this study demonstrate that the familial form of cavernous malformations is a dynamic disease; serial MR images revealed changes in the number, size, and imaging characteristics of lesions consistent with acute or resolving hemorrhage. It is believed that the de novo development of new lesions in this disease has not been previously reported. These findings suggest that patients with familial cavernous malformations require careful follow-up monitoring, and that significant changes in neurological symptoms warrant repeat MR im- aging. Surgery should be considered only for lesions that produce repetitive or progressive symptoms. Pro- phylactic resection of asymptomatic lesions does not appear to be indicated. KEY WORDS cavernous malformation 9 angioma 9 cerebrovascular malformation 9 familial malformation 9 hereditary disorder magnetic resonance imaging c EREBROVASCULAR malformations are develop- mental abnormalities that affect the blood ves- sels supplying the brain. They include venous malformations, arteriovenous malformations (AVM's), 43 cavernous malformations, and telangiectases. The results of postmortem studies suggest that approxi- mately 4% of the population harbor such lesions. 27,z9,3~ Although cavernous malformations make up only 8% to 15% of cerebrovascular malformations reported in postmortem studies, they are responsible for a dis- proportionately larger percentage of the clinical symptomatology caused by this group of vascular 1e- 12 23 27 30 4 3 sions. , , , , Symptomatic lesions usually present with evidence of recent hemorrhage in association with seizures when located above the tentorium, and with focal neurological deficits (or much more rarely, death) when located in the posterior f o s s a . 10,15,24,26,4~,49,50 They are the second most common vascular malformation identified in reviews of surgical pathology, being out- numbered only by AVM's? 3 Cavernous malformations occur in two forms: a spo- radic or nonhereditary form, in which patients tend to have a single isolated lesion, and a familial form char- acterized by the presence of multiple lesions and an autosomal dominant pattern of inheritance. Prior to the introduction of magnetic resonance (MR) imaging, fa- 422 3. Neurosurg. / Volume80 / March, 1994