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

Introduction: 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.