Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.

Effects of medication intake on the risk of hemorrhage in patients with sporadic cerebral cavernous malformations.

Objective: Recurrent intracerebral hemorrhage (ICH) poses a high risk for patients with cerebral cavernous malformations (CCMs). This study aimed to assess the influence of medication intake on hemorrhage risk in sporadic CCMs. Methods: From a database of 1,409 consecutive patients with CCM (2003-2021), subjects with sporadic CCMs and complete magnetic resonance imaging data were included. We evaluated the presence of ICH as a mode of presentation, the occurrence of ICH during follow-up, and medication intake, including beta blockers, statins, antithrombotic therapy, and thyroid hormones. The impact of medication intake on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. The longitudinal cumulative 5-year risk for (re-)hemorrhage was analyzed using the Kaplan-Meier curves and the Cox regression analysis. Results: A total of 1116 patients with CCM were included. Logistic regression analysis showed a significant correlation (OR: 0.520, 95% CI: 0.284-0.951, p = 0.034) between antithrombotic therapy and ICH as a mode of presentation. Cox regression analysis revealed no significant correlation between medication intake and occurrence of (re-)hemorrhage (hazard ratios: betablockers 1.270 [95% CI: 0.703-2.293], statins 0.543 [95% CI: 0.194-1.526], antithrombotic therapy 0.507 [95% CI: 0.182-1.410], and thyroid hormones 0.834 [95% CI: 0.378-1.839]). Conclusion: In this observational study, antithrombotic treatment was associated with the tendency to a lower rate of ICH as a mode of presentation in a large cohort of patients with sporadic CCM. Intake of beta blockers, statins, and thyroid hormones had no effect on hemorrhage as a mode of presentation. During the 5-year follow-up period, none of the drugs affected the further risk of (re-)hemorrhage.