The natural history of cerebral cavernous malformations in children

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>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.</jats:p></jats:sec>

Surveillance imaging for high‐grade childhood brain tumors: What to do 10 years after completion of treatment?

“…Despite an increase in size in 70% of cases, no patient suffered from acute bleeding during the follow‐up period. The hemorrhage rate in nonirradiated children is 3.3% and 1.6% per patient year . Other publications show a bleeding rate for radiation‐induced cavernoma of 10% .…”

Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling

“…The haemorrhage rate per patient-year has been reported to be significantly lower in incidentally discovered groups when compared to symptomatic groups [Washington et al, 2010;Al-Holou et al, 2012;Al-Shahi Salman et al, 2012;Gross et al, 2016;Horne et al, 2016;Akers et al, 2017]. In a single-centre cohort of 107 individuals with CCM as an incidental finding, the only patient in whom a prospective haemorrhage was definitively related to the cavernous malformation was in fact diagnosed as having a familial form of CCM.…”

“…Seizures are the predominant first symptom of supratentorial lobar CCMs, while brainstem lesions are primarily associated with cranial nerve palsy, hemiparesis, and other focal neurological deficits. Prior haemorrhage and brainstem location appear to confer a higher risk for symptomatic haemorrhage, while the annual re-hemorrhage rate has been reported to decline over time [AlHolou et al, 2012;Al-Shahi Salman et al, 2012;Gross et al, 2016;Horne et al, 2016;Gross and Du, 2017].…”

Pediatric Congenital Cerebrovascular Anomalies

“…CCMs in pediatric patients may remain asymptomatic for the lifetime of the patient, sometimes presenting as an incidental radiographic finding (26%), or can present with hemorrhage (62%), seizures (39%), headaches (52%), focal neurologic deficit (6%), and visual field deficits (6%). The overall risk for CCM hemorrhage in the pediatric population is approximately .5–1.1% per lesion per year . A history of prior hemorrhage is the most important risk factor with an overall annual hemorrhage risk of 11.3% .…”

“…In first‐degree relatives of patients with CCMs with two or more affected family members, brain MRI screening is indicated. DVAs are concomitant findings in up to 20% of patients with CCMs and have been suggested to confer an increased risk of hemorrhage …”