Incidence of Cerebral Cavernous Malformation-Related Epilepsy in Children: A Single Center Survey

Cerebral cavernous malformations (CCMs) are rare developmental cerebrovascular malformations. The risk of epilepsy is high in patients with CCMs, but the incidence of epilepsy has not been reported in a pure pediatric population. We herein present 14 pediatric cases of CCMs, including five with CCM-related epilepsy, and examine the incidence of CCM-related epilepsy in this pediatric population.  Methods: Pediatric patients with CCMs who visited our Hospital between November 1, 2001, to September 31, 2020, were retrospectively screened for inclusion, and 14 were enrolled.  Results: Fourteen enrolled patients were divided into two groups based on the presence or absence of CCM-related epilepsy. The "CCM-related epilepsy group" (n = 5) consisted of five males with a median age of 4.2 (range: 0.3-8.5) years at the first visit. The "non-epilepsy group" (n = 9) consisted of seven males and two females with a median age of 3.5 (range: 1.3-11.5) years at the first visit. The prevalence of CCM-related epilepsy at the time of the present analysis was 35.7%. Follow-up periods in CCM-related epilepsy and non-epilepsy groups were 19.3 and 24.9 patient-years, respectively: the incidence was 11.3% per patient-years. The frequency of seizures due to intra-CCM hemorrhage as the primary symptom was significantly higher in the CCM-related epilepsy group than in the non-CCM-related epilepsy group (p = 0.01). Other clinical characteristics, i.e., primary symptoms including vomiting/nausea and spastic paralysis, magnetic resonance imaging findings, including the number or maximum diameter of CCMs, cortical involvement, intra-CCM hemorrhage, and infratentorial lesions, surgical resection, and non-epileptic sequelae, such as motor disability and intellectual disability, did not significantly differ between the groups.  Discussion: The incidence of CCM-related epilepsy in the present study was 11.3% per patient year, higher than in adults. This discrepancy may be attributed to these studies including both adult and pediatric patients, whereas the present study examined a pure pediatric population. The presence of seizures due to intra-CCM hemorrhage as the initial symptom was a risk factor for CCM-related epilepsy in the present study. To elucidate the pathophysiology of CCM-related epilepsy or the reason for its higher incidence in children than in adults, further analyses of a large number of children with CCM-related epilepsy are warranted.