Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study

Abstract

Purpose There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors. Methods We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and $$\ge$$ ≥ 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis. Results Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage. Conclusion The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.

Outcomes after surgical and nonsurgical treatment of pediatric cerebral cavernous malformation

“…Previous studies reported that the seizure outcomes were satisfied in 60%−90% of cases after surgical resection of CCM 13,24 . Resection of hemosiderin rim around the CCM and a shorter duration of seizure symptoms were reported to be associated with favorable seizure control after surgery 13,16,24 . In this study, pure lesionectomy was performed without the removal of a hemosiderin‐stained brain.…”

“…Considering the life‐long risk of hemorrhage and the unclear nature of the history of pediatric CCM, studies reporting the long‐term outcomes of pediatric patients managed by radiosurgery and/or conservative treatment with CCM are lacking 6,15,17,21,25 . Several authors have suggested that stereotactic radiosurgery can be administered to adult patients with high surgical risk and prior hemorrhage and can reduce the hemorrhage risk 16 . Other studies demonstrated that Gamma Knife radiosurgery can reduce the hemorrhage risk in pediatric CCM patients and suggested that radiosurgery can serve as a therapeutic alternative for pediatric CCM 15 .…”

“… 5 , 6 , 7 , 8 However, studies exclusively focused on pediatric CCM are limited, 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 and treatment experience is often extrapolated from adult populations. The natural history and long‐term outcomes of pediatric patients with CCM remain underreported, 13 , 14 , 16 particularly for children undergoing nonsurgical management. 15 , 16 , 17 This information is valuable for providing optimal treatment options to achieve favorable outcomes.…”

“…The natural history and long‐term outcomes of pediatric patients with CCM remain underreported, 13 , 14 , 16 particularly for children undergoing nonsurgical management. 15 , 16 , 17 This information is valuable for providing optimal treatment options to achieve favorable outcomes. Therefore, this study aimed to analyze the demographic characteristics, therapeutic methods, and long‐term outcomes of pediatric patients with CCM.…”

The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique

“…According to known statistics, we recommend CM surgical removal in patients with risk factors that increase the possibility of bleeding. These include previous symptomatic bleeding, a positive family history, gender, and age [ 37 , 39 ]. All our operated patients had suffered at least one acute or previous bleeding episode.…”