Evidence map›Paper›PMID 38738647›Full record

ArticleEpilepsia2024

Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

Colin A Ellis, Danni Tu, Karen L Oliver, Heather C Mefford, W Allen Hauser, Jeffrey Buchhalter, Michael P Epstein, Quy Cao, EPGP Consortium, Epi4K Consortium and 2 more

Abstract read
In one paragraph

Article in Epilepsia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Colin A EllisDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0003-2152-8106
Danni TuDepartment of Biostatistics, Epidemiology, & Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Karen L OliverDepartment of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0001-5188-6153
Heather C MeffordDepartment of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID https://orcid.org/0000-0001-7188-522X
W Allen HauserDepartment of Neurology and Epidemiology, and the Gertrude H. Sergievsky Center, Columbia University Irving Medical Center, New York, New York, USA.
Jeffrey BuchhalterBuchhalter Consulting, PLLC, Phoenix, Arizona, USA.ORCID https://orcid.org/0000-0002-6807-8328
Michael P EpsteinDepartment of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Quy CaoDepartment of Biostatistics, Epidemiology, & Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
EPGP Consortium
Epi4K Consortium
Samuel F BerkovicDepartment of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.ORCID https://orcid.org/0000-0003-4580-841X
Ruth OttmanDepartment of Neurology and Epidemiology, and the Gertrude H. Sergievsky Center, Columbia University Irving Medical Center, New York, New York, USA.ORCID https://orcid.org/0000-0001-7074-242X

Funding

The Epilepsy Phenome/ Genome Project (EPGP)U01NS053998 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2007 to 2013
$26.4M
Genetic Epidemiology of Seizure Disorders In RochesterR01NS043472 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OTTMAN, RUTH · 2002 to 2006
$6.2M
GENETICS OF AD PARTIAL EPILEPSY WITH AUDITORY FEATURESR01NS036319 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OTTMAN, RUTH · 1997 to 2007
$3.7M
GENETIC EPIDEMIOLOGY OF FAMILIAL EPILEPSYR01NS020656 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI OTTMAN, RUTH · 1985 to 2001
$1.2M
Polygenic risk in familial epilepsyK23NS121520 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ELLIS, COLIN · 2021 to 2025
$1.1M
5 of 7 Epi4K: Multiplex Families & Pairs ProjectU01NS077367 · NINDS · UNIVERSITY OF MELBOURNE · PI BERKOVIC, SAMUEL FRANK, COSSETTE, PATRICK · 2011 to 2013
$1.0M
NHMRC APP1196637NINDS NIH HHS K23 NS121520NINDS NIH HHS K23NS121520NINDS NIH HHS R01 NS020656NINDS NIH HHS R01 NS036319NINDS NIH HHS R01 NS043472NINDS NIH HHS R01NS20656NINDS NIH HHS R01NS43472NINDS NIH HHS U01 NS053998NINDS NIH HHS U01NS053998NINDS NIH HHS U01 NS077367NINDS NIH HHS U01NS077367The American Academy of Neurology Susan S Spencer Clinical Research Training Scholarship
6 · The paper itself

Abstract

objectiveTo 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.

methodsWe 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.

resultsThe 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 × 10 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.

Indexed as

AnticonvulsantsSeizuresAdolescentAdultBayes TheoremChildCohort StudiesEpilepsyFemaleHumansMaleMiddle AgedRetrospective StudiesTreatment OutcomeYoung AdultAnticonvulsantsfamilial epilepsygeneticsmeta‐analysisremissiontreatment response

Identifiers

PMID38738647
PMCPMC11251848

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.