Background and Purpose: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. Methods: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage.Results: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases.Conclusions: FCCM patients with ICH at diagnosis are prone to develop rebleeding.During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

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OBJECTIVE The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM). METHODS The authors’ institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex. RESULTS Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03–1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%–29.38%) for the entire cohort, 31.41% (95% CI 23.26%–40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%–49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%–32.29%) for patients on statin medication, and 0% (95% CI 0%–30.13%) for patients on antithrombotic medication. CONCLUSIONS ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

Background and purpose The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10‐year period. Methods A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non‐missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow‐up. Kaplan–Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. Results Eighty‐nine patients with a CM of the CNS were included. Our results showed a non‐significant increased risk of hemorrhage during 10 years of follow‐up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86–5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71–14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10‐year risks of bleeding were observed: arterial hypertension 42.9% (18.8%–70.4%); diabetes 66.7% (12.5%–98.2%); hyperlipidemia 30% (8.1%–64.6%); active nicotine abuse 50% (24.1%–76%); and obesity 22.2% (4%–59.8%). Overall cumulative (10‐year) hemorrhage risk was 30.3% (21.3%–41.1%). Conclusions The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow‐up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.