Related Experiment Video
Updated: Mar 31, 2026
Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
Published on: September 4, 2017
The natural history of cerebral cavernous malformations in children
Bradley A Gross1,2,3,4, Rose Du1,4, Darren B Orbach3,4
1Department of Neurological Surgery, Brigham and Women's Hospital.
Insights
Pediatric cerebral cavernous malformations (CMs) carry a 3.3% annual hemorrhage risk. Prior bleeding, brainstem location, and associated DVAs significantly increase this risk in children.
Area of Science:
- Neurology
- Pediatric Neurosurgery
- Vascular Malformations
Background:
- Cerebral cavernous malformations (CMs) cause significant neurological issues in children, including seizures and deficits.
- Limited natural history data exists for pediatric CMs compared to adults.
Purpose of the Study:
- To determine the natural history of untreated cerebral cavernous malformations in pediatric patients.
- To identify risk factors for symptomatic hemorrhage in children with CMs.
Main Methods:
- Retrospective review of hospital databases for pediatric patients with CMs and clinical/radiological follow-up.
- Calculation of annual hemorrhage rates and assessment of risk factors using Cox proportional hazards models.
Main Results:
- A cohort of 167 children with 222 CMs was analyzed; 62% presented with hemorrhage.
- The overall annual hemorrhage rate was 3.3%, with higher rates for previously hemorrhagic or brainstem lesions.
- Significant risk factors for hemorrhage included prior hemorrhage, brainstem location, and associated developmental venous anomalies (DVAs).
Conclusions:
- Prior hemorrhage, brainstem location, and associated DVAs are key risk factors for symptomatic hemorrhage in pediatric CMs.
- Hemorrhage clustering within 3 years of an initial bleed is a significant phenomenon requiring consideration in management and counseling.
Abstract:
OBJECT Cerebral cavernous malformations (CMs) are a source of neurological morbidity from seizures and focal neurological deficits due to mass effect and hemorrhage. Although several natural history reports exist for adults with CMs, similar data for pediatric patients are limited. METHODS The authors reviewed hospital databases to identify children with CMs who had not been treated surgically and who had clinical and radiological follow-up. Annual hemorrhage rates were calculated in lesion-years, and risk factors were assessed using the Cox proportional hazards model. RESULTS In a cohort of 167 patients with 222 CMs, the mean patient age at the time of diagnosis was 10.1 years old (SD 6.0). Ninety patients (54%) were male. One hundred four patients (62%) presented with hemorrhage from at least 1 CM, 58 (35%) with seizures with or without CM hemorrhage, and 43 (26%) with incidental lesions. Twenty-five patients (15%) had multiple CMs, 17 (10%) had a family history of CMs, and 33 (20%) had radiologically apparent developmental venous anomalies (DVAs). The overall annual hemorrhage rate was 3.3%. Permanent neurological morbidity was 29% per hemorrhage, increasing to 45% for brainstem, thalamic, or basal ganglia CM and decreasing to 15% for supratentorial lobar or cerebellar lesions. The annual hemorrhage rate for incidental CMs was 0.5%; for hemorrhagic CMs, it was 11.3%, increasing to 18.2% within the first 3 years. Hemorrhage clustering within 3 years was statistically significant (HR 6.1, 95% CI 1.72-21.7, p = 0.005). On multivariate analysis, hemorrhagic presentation (HR 4.63, 95% CI 1.53-14.1, p = 0.007), brainstem location (HR 4.42, 95% CI 1.57-12.4, p = 0.005), and an associated radiologically apparent DVA (HR 2.91, 95% CI 1.04-8.09, p = 0.04) emerged as significant risk factors for hemorrhage, whereas age, sex, CM multiplicity, and CM family history did not. CONCLUSIONS Prior hemorrhage, brainstem location, and associated DVAs are significant risk factors for symptomatic hemorrhage in children with CMs. Hemorrhage clustering within the first 3 years of a bleed can occur, a potentially important factor in patient management and counseling.
