Familial aggregation of seizure outcomes in four familial epilepsy cohorts

Objective To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic–clonic seizures, and seizure control for individuals taking antiseizure medication. Methods We analyzed families containing...

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Vydáno v:Epilepsia (Copenhagen) Ročník 65; číslo 7; s. 2030 - 2040
Hlavní autoři: Ellis, Colin A., Tu, Danni, Oliver, Karen L., Mefford, Heather C., Hauser, W. Allen, Buchhalter, Jeffrey, Epstein, Michael P., Cao, Quy, Berkovic, Samuel F., Ottman, Ruth
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Wiley Subscription Services, Inc 01.07.2024
Témata:
Adolescent
Adult
Anticonvulsants - therapeutic use
Bayes Theorem
Bayesian analysis
Child
Cohort Studies
Convulsions & seizures
Data collection
Epilepsy
Epilepsy - drug therapy
Epilepsy - genetics
familial epilepsy
Female
genetics
Humans
Male
Meta-analysis
Middle Aged
Remission
Retrospective Studies
Risk factors
Seizures
Seizures - drug therapy
Seizures - genetics
Treatment Outcome
treatment response
Young Adult
genetics
familial epilepsy
meta‐analysis
treatment response
remission
ISSN:0013-9580, 1528-1167, 1528-1167
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Shrnutí:Objective To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic–clonic seizures, and seizure control for individuals taking antiseizure medication. Methods We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure‐free at last observation. Total number of tonic–clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed‐effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family‐specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta‐analysis using GLMMs. Results The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic–clonic seizures showed strong familial aggregation in three separate cohorts and meta‐analysis (ICC .28, 95% confidence interval [CI] .21–.35, Bayes factor 8 × 1016). Meta‐analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01–.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0–.35, Bayes factor 0.94), with heterogeneity among cohorts. Significance A history of ≥4 tonic–clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.
Bibliografie:EPGP Consortium and Epi4K Consortium members are listed in the Appendix
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CAE and RO contributed to study concept and design. All authors contributed to data acquisition and analysis, and to drafting of the manuscript and figures.
Author Contributions
ISSN:0013-9580
1528-1167
1528-1167
DOI:10.1111/epi.18004