The natural history of cavernous malformations: a prospective study of 68 patients

OBJECTIVE: Cavernous malformations are angiographically occult cerebrovascular malformations found in approximately 0.5% of the population. To help further understand the natural history of these lesions, we prospectively followed 68 patients harboring cavernous malformations. METHODS: The 68 patients in this study were all diagnosed radiographically (67 patients) or surgically (1 patient) and were entered into a patient database. Age, sex, clinical symptoms, seizure frequency, focal neurological deficits, and presence or absence of extralesional hemorrhage were all recorded at presentation. Patients were then followed prospectively to determine the rate of hemorrhage and new-onset seizures. RESULTS: The mean follow-up per patient was 5.2 years, and the total follow-up was 352.9 patient-years. There was an average of 3.4 lesions per patient. Thirteen of the patients (19%) had familial cavernous malformations. Patients with familial disease were more likely to have multiple lesions than patients with sporadic disease (85% versus 25%, respectively [P = 0.001]). Initial presentation included headache (65%), seizures (49%), and focal neurological deficit (46%). Eleven symptomatic, radiologically proven, extralesional hemorrhages occurred during the 352.9 patient-years of follow-up for an overall hemorrhage rate of 3.1% per patient-year. Female patients had a significantly higher prospective hemorrhage rate (4.2% per patient-year versus 0.9% per patient-year [P = 0.04]). A history of hemorrhage at presentation was not a risk factor for subsequent hemorrhage during follow-up. The rate of new-onset seizures was 2.4% per patient-year. CONCLUSION: The clinical presentation and prospective hemorrhage rate reported here agree well with findings of other prospective studies. This information, combined with our new-onset seizure rate, should aid clinicians caring for patients with cavernous malformations.

A longitudinal study of patients with venous malformations: documentation of a negligible hemorrhage risk and benign natural history.

BACKGROUND: The natural history of cerebral venous malformations has not been well documented, and the clinical significance of these common lesions remains controversial. OBJECTIVE: The objective of this study was to follow longitudinally the clinical course of patients with cerebral venous malformations to document the natural history of the lesion. METHODS: Ninety-two patients with radiographically confirmed venous malformations were entered into the study between 1987 and 1996. Annual follow-up was maintained by clinic visits and/or phone interviews. Sixty-three patients (25 men and 38 women) with more than 1 year of follow-up were analyzed. McNemar's test and logistic regression analysis was applied to prevalence of presenting symptoms over time. An average per patient follow-up of 4.2 years yielded 2,721 retrospective and 301 prospective lesion-years for analysis. RESULTS: Average age at diagnosis was 39.1 years (SD, 18.7 years; range, 2 to 73 years). The most frequent lesion locations included the frontal lobe (55.6%, n=35) and the cerebellum (27%, n=17). The most frequent presentations included headache (50.8%, n=32), focal neurologic deficits (39.7%, n=25), and seizure (30.2%, n=19). Prevalence of headache (p=0.048) and seizure (p=0.016) decreased over time without treatment of the lesion. A second cerebrovascular lesion was identified in 12 patients (19%). Two patients had a symptomatic intracerebral hemorrhage attributable to their venous malformation. Risk of hemorrhage was 0.15% per lesion-year (95% CI, 0.06 to 0.38%). CONCLUSIONS: This study establishes that the natural history of venous malformations is benign, that the risk of hemorrhage from these lesions is negligible, and that conservative therapy is warranted.

Cerebral cavernous malformations. Incidence and familial occurrence.

We studied 24 patients with histologically verified cerebral cavernous malformations, reviewing the familial occurrence and presenting signs, symptoms, and radiographic features of the disorder. Eleven patients had no evidence of a heritable trait and had negative family histories. Thirteen patients were members of six unrelated Mexican-American families. Sixty-four first-degree and second-degree relatives were examined, and family pedigrees were established. Most relatives (83 percent) were asymptomatic; 11 percent had seizures. Magnetic resonance imaging was performed in 16 relatives (5 of whom were asymptomatic). Fourteen of the 16 studies revealed cavernous malformations; 11 studies identified multiple lesions. As compared with computerized tomography and angiography, magnetic resonance imaging was far more accurate in detecting cavernous malformations. We conclude that cavernous malformations are more prevalent than previously reported, and that a familial form of the disorder exists that is more common than expected, with a high incidence of multiple lesions and an increased frequency of occurrence among Mexican-American families. Magnetic resonance imaging is the radiographic technique of choice for the identification and follow-up of these lesions.