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. Moshe, Tracy A. Glauser

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: To determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE). Methods: Occurrence 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. Results: As 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. Conclusions: The 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.

Original languageEnglish (US)
Pages (from-to)1108-1114
Number of pages7
JournalNeurology
Volume85
Issue number13
DOIs
StatePublished - Sep 29 2015

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Absence Epilepsy
Ethosuximide
Seizures
Valproic Acid
Therapeutics
Electroencephalography
Randomized Controlled Trials
Incidence

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Shinnar, S., Cnaan, A., Hu, F., Clark, P., Dlugos, D., Hirtz, D. G., ... Glauser, T. A. (2015). Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial. Neurology, 85(13), 1108-1114. https://doi.org/10.1212/WNL.0000000000001971

Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial. / Shinnar, Shlomo; Cnaan, Avital; Hu, Fengming; Clark, Peggy; Dlugos, Dennis; Hirtz, Deborah G.; Masur, David; Mizrahi, Eli M.; Moshe, Solomon L.; Glauser, Tracy A.

In: Neurology, Vol. 85, No. 13, 29.09.2015, p. 1108-1114.

Research output: Contribution to journalArticle

Shinnar, S, Cnaan, A, Hu, F, Clark, P, Dlugos, D, Hirtz, DG, Masur, D, Mizrahi, EM, Moshe, SL & Glauser, TA 2015, 'Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial', Neurology, vol. 85, no. 13, pp. 1108-1114. https://doi.org/10.1212/WNL.0000000000001971
Shinnar, Shlomo ; Cnaan, Avital ; Hu, Fengming ; Clark, Peggy ; Dlugos, Dennis ; Hirtz, Deborah G. ; Masur, David ; Mizrahi, Eli M. ; Moshe, Solomon L. ; Glauser, Tracy A. / Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial. In: Neurology. 2015 ; Vol. 85, No. 13. pp. 1108-1114.
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AU - Cnaan, Avital

AU - Hu, Fengming

AU - Clark, Peggy

AU - Dlugos, Dennis

AU - Hirtz, Deborah G.

AU - Masur, David

AU - Mizrahi, Eli M.

AU - Moshe, Solomon L.

AU - Glauser, Tracy A.

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N2 - Objective: To determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE). Methods: Occurrence 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. Results: As 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. Conclusions: The 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.

AB - Objective: To determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE). Methods: Occurrence 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. Results: As 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. Conclusions: The 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.

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