Browse the corpus

Prospective untreated outcomes in patients with cerebral cavernous malformation. OBJECTIVE: The aim of this study was to elucidate the long-term morbidity associated with untreated cerebral cavernous malformation (CCM). METHODS: From a prospectively maintained database of patients with CCM, we assessed functional outcome as measured using the modified Rankin Scale (mRS) score at baseline and the last untreated follow-up evaluation. Disability was defined as an mRS score ≥ 3. Kaplan-Meier curves were used to assess the time to disability, and Cox proportional hazards models were used to determine risk factors for disability. Furthermore, the predictive performance of a previously published nomogram for morbidity in CCM was assessed. RESULTS: The cohort consisted of 332 patients (58.4% female, mean age at diagnosis 44.5 years), with 19.8% having the familial form and 28.0% having a CCM located in the brainstem. Of 48 patients who presented with symptomatic hemorrhage (SH) and who did not undergo surgery or have a prospective SH, 27.1% had an mRS score ≥ 3 at diagnosis. By 1 year and 5 years, this improved to 6.2% and 4.7%, respectively. Over a mean follow-up duration of 6.6 years, 103 of 332 patients (31.0%) had one prospective SH and 48 (14.5%) had multiple prospective SHs. Patients with brainstem-located CCM had an 18.8% 5-year and 35.4% 10-year risk of disability compared with 4.1% and 7.5%, respectively, in patients with a nonbrainstem location (p < 0.0001). Multivariate analysis showed that a brainstem location, history of self-reported psychiatric disorder, and ≥ 2 SHs were predictive of disability at the last follow-up. External validation of a published nomogram demonstrated high specificity but limited sensitivity for predicting disability, with an area under the receiver operating curve of 0.687 for mRS scores ≥ 2 and 0.783 for mRS scores ≥ 3. CONCLUSIONS: Most patients improved after a first hemorrhage, with the most improvement occurring in year 1. Disability increased with each SH. Disability was associated with 2 or more SHs, a brainstem location, and a self-reported psychiatric diagnosis. Ten-year disability risk with a nonbrainstem CCM location was < 8%.