Christine K Fox1,2, Jeffrey Nelson2, Charles E McCulloch2,3, Shantel Weinsheimer2,4, Ludmila Pawlikowska2,4, Blaine Hart5, Marc Mabray5, Atif Zafar6, Leslie Morrison7, Joseph M Zabramski8, Amy Akers9, Helen Kim2,3,9. 1. Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA, USA christine.fox@ucsf.edu. 2. Center for Cerebrovascular Research, University of California San Francisco, San Francisco, CA, USA. 3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. 4. Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA. 5. Department of Radiology, University of New Mexico, Albuquerque, NM, USA. 6. Department of Medicine, Division of Neurology, University of Toronto, Ontario, Canada. 7. Department of Neurology, University of New Mexico, Albuquerque, NM, USA. 8. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA. 9. Angioma Alliance, Durham, NC, USA.
Abstract
BACKGROUND AND OBJECTIVES: Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC). METHODS: Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset. RESULTS: The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 - 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 - 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 - 49.32) compared to patients without a seizure history. DISCUSSION: Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.
BACKGROUND AND OBJECTIVES: Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC). METHODS: Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset. RESULTS: The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 - 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 - 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 - 49.32) compared to patients without a seizure history. DISCUSSION: Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.
Authors: Christopher C Gibson; Weiquan Zhu; Chadwick T Davis; Jay A Bowman-Kirigin; Aubrey C Chan; Jing Ling; Ashley E Walker; Luca Goitre; Simona Delle Monache; Saverio Francesco Retta; Yan-Ting E Shiu; Allie H Grossmann; Kirk R Thomas; Anthony J Donato; Lisa A Lesniewski; Kevin J Whitehead; Dean Y Li Journal: Circulation Date: 2014-12-08 Impact factor: 29.690
Authors: Eugen Trinka; Hannah Cock; Dale Hesdorffer; Andrea O Rossetti; Ingrid E Scheffer; Shlomo Shinnar; Simon Shorvon; Daniel H Lowenstein Journal: Epilepsia Date: 2015-09-04 Impact factor: 5.864
Authors: J M Zabramski; T M Wascher; R F Spetzler; B Johnson; J Golfinos; B P Drayer; B Brown; D Rigamonti; G Brown Journal: J Neurosurg Date: 1994-03 Impact factor: 5.115
Authors: Felix Rosenow; Mario A Alonso-Vanegas; Christoph Baumgartner; Ingmar Blümcke; Maria Carreño; Elke R Gizewski; Hajo M Hamer; Susanne Knake; Philippe Kahane; Hans O Lüders; Gary W Mathern; Katja Menzler; Jonathan Miller; Taisuke Otsuki; Cigdem Ozkara; Asla Pitkänen; Steven N Roper; Americo C Sakamoto; Ulrich Sure; Matthew C Walker; Bernhard J Steinhoff Journal: Epilepsia Date: 2013-10-17 Impact factor: 5.864