Solitary Sporadic Cerebral Cavernous Malformations: Risk Factors of First or Recurrent Symptomatic Hemorrhage and Associated Functional Impairment

Objective: To quantify the risk of a first or recurrent hemorrhage and the associated functional impairment in patients with sporadic solitary cerebral cavernous malformations (CCMs) and to investigate the potential risk factors.

Methods: We undertook an observational study (n = 199) of consecutive patients with the diagnosis of a single, sporadic CCM using clinical and magnetic resonance imaging follow-up to identify prospective hemorrhage events and associated functional impairment. We calculated the annual hemorrhage risk rates, calculated cumulative risks, and performed uni- and multivariate analysis to assess outcome predictors.

Results: There were 199 adults identified, and 712.5 person years of follow-up were analyzed. Overall annual rates of hemorrhage were 6.03%, 11.95%, and 1.03% in the complete cohort, in those presenting with previous hemorrhage, and in those without, respectively. The 5-year risk of hemorrhage was higher in those presenting with previous hemorrhage than those without (40.9%; 95% confidence interval [CI], 31.78-50.73 vs. 8.6%; 95% CI, 3.97-16.95; P < 0.0001) and in those with a brainstem CCM compared with nonbrainstem CCM (51.6%; 95% CI, 37.61-65.46 vs. 17.1%; 95% CI, 4.55-32.04; P < 0.0001). In the multivariate analysis, previous hemorrhage (odds ratio, 7.18; 95% CI, 1.8-28.11; P = 0.005), age less than 45 years (odds ratio, 2.61; 95% CI, 1.03-6.61; P = 0.042), and brainstem location (odds ratio, 7.44; 95% CI, 2.09-26.50; P = 0.002) increased the risk of hemorrhage. Of the patients, 30% showed a moderate or severe disability associated with a CCM hemorrhage (5-year risk of severe hemorrhage, 8.9%; 95% CI, 5.50-13.99).

Conclusions: This study provides an estimate of symptomatic hemorrhage risk and the associated disability in patients with sporadic solitary CCM and an investigation of risk factors.