Familial aggregation of status epilepticus in generalized and focal epilepsies
Judith L Z Weisenberg, Robert T Fitzgerald, John N Constantino, Melodie R Winawer, Liu Lin Thio, EPGP Investigators, Bassel Abou-Khalil, Brian Alldredge, Dina Amrom, Eva Andermann, Frederick Andermann, Jocelyn Bautista, Sam Berkovic, Judith Bluvstein, Alex Boro, Gregory D. Cascino, Damian Consalvo, Sabrina Cristofaro, Patricia Crumrine, Orrin Devinsky, Dennis Dlugos, Michael Epstein, Robyn Fahlstrom, Miguel Fiol, Nathan Fountain, Kristen Fox, Jacqueline French, Catharine Freyer-Karn, Daniel Friedman, Eric Geller, Tracy Glauser, Simon Glynn, Kevin Haas, Sheryl Haut, Jean Hayward, Sandra Helmers, Sucheta Joshi, Andres Kanner, Heidi Kirsch, Robert Knowlton, Eric Kossoff, Rachel Kuperman, Ruben Kuzniecky, Daniel Lowenstein, Shannon McGuire, Paul Motika, Gerard Nesbitt, Edward Novotny, Ruth Ottman, Juliann Paolicchi, Jack Parent, Kristen Park, Annapurna Poduri, Neil Risch, Lynnette Sadleir, Ingrid Scheffer, Renee Shellhaas, Elliott Sherr, Jerry J. Shih, Shlomo Shinnar, Rani Singh, Joseph Sirven, Michael Smith, Joe Sullivan, Liu Lin Thio, Anu Venkat, Eileen Vining, Gretchen Von Allmen, Judith Weisenberg, Peter Widdess-Walsh, Judith L Z Weisenberg, Robert T Fitzgerald, John N Constantino, Melodie R Winawer, Liu Lin Thio, EPGP Investigators, Bassel Abou-Khalil, Brian Alldredge, Dina Amrom, Eva Andermann, Frederick Andermann, Jocelyn Bautista, Sam Berkovic, Judith Bluvstein, Alex Boro, Gregory D. Cascino, Damian Consalvo, Sabrina Cristofaro, Patricia Crumrine, Orrin Devinsky, Dennis Dlugos, Michael Epstein, Robyn Fahlstrom, Miguel Fiol, Nathan Fountain, Kristen Fox, Jacqueline French, Catharine Freyer-Karn, Daniel Friedman, Eric Geller, Tracy Glauser, Simon Glynn, Kevin Haas, Sheryl Haut, Jean Hayward, Sandra Helmers, Sucheta Joshi, Andres Kanner, Heidi Kirsch, Robert Knowlton, Eric Kossoff, Rachel Kuperman, Ruben Kuzniecky, Daniel Lowenstein, Shannon McGuire, Paul Motika, Gerard Nesbitt, Edward Novotny, Ruth Ottman, Juliann Paolicchi, Jack Parent, Kristen Park, Annapurna Poduri, Neil Risch, Lynnette Sadleir, Ingrid Scheffer, Renee Shellhaas, Elliott Sherr, Jerry J. Shih, Shlomo Shinnar, Rani Singh, Joseph Sirven, Michael Smith, Joe Sullivan, Liu Lin Thio, Anu Venkat, Eileen Vining, Gretchen Von Allmen, Judith Weisenberg, Peter Widdess-Walsh
Abstract
Objective: To determine whether familial aggregation of status epilepticus (SE) occurs in a large cohort of familial common epilepsies.
Methods: We used the Epilepsy Phenome/Genome Project dataset, which consisted of 2,197 participants in 1,043 family units with ≥2 members having a common generalized or nonacquired focal epilepsy (NAFE). We identified participants with a history of traditionally defined SE (TSE) (seizures ≥30 minutes) and operationally defined SE (OSE) (seizures ≥10 minutes) by chart review. We assessed familial aggregation of TSE and OSE using χ2 analysis and generalized estimating equations (GEE).
Results: One hundred fifty-five (7%) participants in 1,043 families had ≥1 episodes of TSE. Two hundred fifty (11%) had ≥1 episodes of OSE. In a χ2 analysis, the number of family units with ≥2 members having TSE (odds ratio [OR] 4.79, 95% confidence interval [CI] 2.56-8.97) or OSE (OR 4.23, 95% CI 2.67-6.70) was greater than expected by chance. In GEE models adjusted for sex, broad epilepsy class (GE or NAFE), age at onset, and duration of epilepsy, TSE in a proband predicted TSE in a first-degree relative (OR 2.79, 95% CI 1.24-6.22), and OSE in a proband predicted OSE in a first-degree relative (OR 2.91, 95% CI 1.65-5.15). The results remained significant in models addressing epilepsy severity by incorporating the number of antiseizure medications used or epilepsy surgery.
Conclusions: TSE and OSE showed robust familial aggregation in a cohort of familial epilepsy independently of epilepsy severity or class, suggesting that genetic factors contribute to SE independently of the genetic cause of these epilepsies.
Clinicaltrialsgov identifier: NCT00552045.
© 2020 American Academy of Neurology.
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Source: PubMed