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Background and Purpose: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Methods: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. Results: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15−8.63];P =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04−5.86];P =0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18−8.99];P =0.022 and odds ratio, 2.53 [95% CI, 1.07−5.98];P =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80−110.39];P =0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%−23.6%) for the entire cohort, 30.2% (20.2%−42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%−51.1%) for children with brain stem CCM.Conclusions: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study