Cerebral cavernous malformations increase risk for seizures

Individuals with familial cerebral cavernous malformation had a high incidence rate of seizures, according to study findings published in Neurology.

“Seizures related to a cerebral cavernous malformation (CCM) often begin in childhood, but seizure incidence rates in children with either sporadic or familial forms of CCM are not well described. In familial cases, a greater number of CCMs or genetic variations may influence the likelihood of a seizure or earlier seizure onset,” Christine Fox, MD, MAS, associate professor and director of the Pediatric Stroke and Cerebrovascular Disease Center at the University of California, San Francisco, and colleagues wrote. “We aimed to measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity in a cohort of children and adults with familial cerebral cavernous malformation (FCCM).”

In a retrospective and prospective longitudinal cohort study, the researchers analyzed 479 children and adults with FCCM from the Brain Vascular Malformation Consortium (median age, 42.7 years; 93 children; 292 women; 188 reported seizures prior to enrollment; 347 with CCM1 mutation) between June 2010 and August 2019.

Using standardized case report forms, Fox and colleagues conducted FCCM genotypes, brain MRIs and in-person interviews to determine seizure probability. Specifically, they evaluated whether CCM counts or genotype affected earlier seizure onset. Participants returned for annual visits to update reports. The researchers also used summary statistics to explain the cohort demographics and clinical characteristics.

Among the 479 participants, 202 experienced a seizure either before or during the study. Of the 393 with genotyping, the researchers identified mutations in participants as CCM1– Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%) and CCM3 mutations (2%).

Results showed cumulative incidence of a childhood seizure of 20.3% (95% CI 17 – 23.4), and the risk for a first seizure slowly increased with patient age. By age 80 years, the approximate cumulative incidence was 60.4% (95% CI, 54.2–63.3).

Study limitations included a small population of patients with CCM3 and the inability to truly analyze medications as seizure predictors.

“Our study suggests FCCM cases with seizures have more frequent ER visits and hospitalizations, contributing to increased health care costs, compared [with] those without seizures. These data may be particularly important for individuals with FCCM as new treatment strategies become available,” Fox and colleagues wrote. “Future studies are needed to determine the best practices to reduce the burden of seizures and epilepsy related to FCCM.”