Evidence map›Paper›PMID 26311751›Full record

ArticleNeurology2015

Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial.

Shlomo Shinnar, Avital Cnaan, Fengming Hu, Peggy Clark, Dennis Dlugos, Deborah G Hirtz, David Masur, Eli M Mizrahi, Solomon L Moshé, Tracy A Glauser and 1 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00088452 (Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study), which is not on this map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 8% of its field
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.

NCT00088452 phase3completednot on this map

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

TypeinterventionalSponsorChildren's Hospital Medical Center, CincinnatiRan2004 to 2016Enrolled453ConditionsChildhood Absence Epilepsy, Petit Mal Epilepsy, Epilepsy, SeizuresArmsEthosuximide, Lamotrigine, Valproic acid
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.

  1. Lamotrigine add-on therapy for drug-resistant focal epilepsy.The Cochrane database of systematic reviews · 2023
    Pooled it
  2. Lamotrigine add-on therapy for drug-resistant focal epilepsy.The Cochrane database of systematic reviews · 2020
    Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Absence Seizures in Children: Usual and the Unusual.Indian journal of pediatrics · 2020
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. [Research advances in the role of vitamin D in autism spectrum disorders].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016
    Review
  13. Article
  14. Article
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

11 authors at 2 institutions in 1 country.

Shlomo ShinnarFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX. sshinnar@aol.com.
Avital CnaanFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Fengming HuFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Peggy ClarkFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Dennis DlugosFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Deborah G HirtzFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
David MasurFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Eli M MizrahiFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Solomon L MoshéFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Tracy A GlauserFrom Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.
Childhood Absence Epilepsy Study Group
Cincinnati Children's Hospital Medical Center · USChildren's National · US

Funding

Impact of Initial Therapy and Response on Long Term Outcome in Children with CAEU01NS045911 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI GLAUSER, TRACY A · 2003 to 2013
$31.1M
Consequences of Prolonged Febrile Seizures in ChildhoodR01NS043209 · NINDS · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI SHINNAR, SHLOMO · 2003 to 2012
$21.5M
NEUROIMAGING COREP30HD040677 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI VITTORIO GALLO, VITTORIO GALLO VITTORIO GALLO · 2001 to 2015
$15.9M
Consequences of Prolonged Febrile Seizures in ChildhoodR37NS043209 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SHINNAR, SHLOMO · 2013 to 2019
$11.4M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR031988 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI GUAY-WOODFORD, LISA MARIE · 2010 to 2011
$8.2M
RNA fidelity and protein function of Becker-like in-frame deletionsP50AR060836 · NIAMS · CHILDREN'S RESEARCH INSTITUTE · PI PARTRIDGE, TERENCE A · 2011 to 2015
$7.8M
AGE RELATED SEIZURE SUPPRESSIONR01NS020253 · NINDS · YESHIVA UNIVERSITY · PI MOSHE, SOLOMON L. · 1985 to 2011
$4.7M
N-carbamylglutamate in the treatment of hyperammonemiaR01HD058567 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI TUCHMAN, MENDEL · 2008 to 2016
$4.4M
Childhood Absence Epilepsy: Coordinating CenterU01NS045803 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI CNAAN, AVITAL · 2003 to 2008
$4.0M
2 of 7 EPI4K - Phenotyping Clinical Informatics Core U01NS077276 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2011 to 2015
$3.1M
Imaging the effect of centrotemporal spikes and seizures on language in childrenR01NS065840 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI VANNEST, JENNIFER J. · 2011 to 2015
$2.5M
Einstein Center for Excellence for Clinical Trials in NeuroscienceU10NS077308 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI LIPTON, RICHARD B., SHINNAR, SHLOMO · 2011 to 2017
$2.2M
NCRR NIH HHS UL1RR031988NIAMS NIH HHS P50AR060836NIAMS NIH HHS R01AR061875NICHD NIH HHS P30HD040677NICHD NIH HHS R01HD058567NINDS NIH HHS 1R01NS053998NINDS NIH HHS 2U01-NS045911NINDS NIH HHS NS20253NINDS NIH HHS NS 2R01-NS043209NINDS NIH HHS NS43209NINDS NIH HHS NS45911NINDS NIH HHS NS-78333NINDS NIH HHS P20 NS080181NINDS NIH HHS R01-NS043209NINDS NIH HHS R01-NS053998NINDS NIH HHS R01-NS062756NINDS NIH HHS R01-NS065840NINDS NIH HHS U01-NS045803NINDS NIH HHS U01 NS045911NINDS NIH HHS U01NS077276NINDS NIH HHS U10NS077308NINDS NIH HHS U10-NS077311NLM NIH HHS 1R01LM011124NLM NIH HHS R01-LM011124
6 · The paper itself

Abstract

objectiveTo determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE).

methodsOccurrence of GTCs was determined in 446 children with CAE who participated in a randomized clinical trial comparing ethosuximide, lamotrigine, and valproate as initial therapy for CAE.

resultsAs of June 2014, the cohort had been followed for a median of 7.0 years since enrollment and 12% (53) have experienced at least one GTC. The median time to develop GTCs from initial therapy was 4.7 years. The median age at first GTC was 13.1 years. Fifteen (28%) were not on medications at the time of their first GTC. On univariate analysis, older age at enrollment was associated with a higher risk of GTCs (p=-0.0009), as was the duration of the shortest burst on the baseline EEG (p=0.037). Failure to respond to initial treatment (p<0.001) but not treatment assignment was associated with a higher rate of GTCs. Among patients initially assigned to ethosuximide, 94% (15/16) with GTCs experienced initial therapy failure (p<0.0001). A similar but more modest effect was noted in those initially treated with valproate (p=0.017) and not seen in those initially treated with lamotrigine.

conclusionsThe occurrence of GTCs in a well-characterized cohort of children with CAE appears lower than previously reported. GTCs tend to occur late in the course of the disorder. Children initially treated with ethosuximide who are responders have a particularly low risk of developing subsequent GTCs.

Indexed as

Age FactorsAnticonvulsantsChildChild, PreschoolComorbidityEpilepsy, AbsenceEpilepsy, Tonic-ClonicFemaleFollow-Up StudiesHumansIncidenceMaleRandomized Controlled Trials as TopicRiskTreatment OutcomeAnticonvulsants

Identifiers

PMID26311751
PMCPMC4603882
OpenAlexW1657464758

What OpenQuestion holds

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Registered trials

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.