Shlomo Shinnar1, Avital Cnaan2, Fengming Hu2, Peggy Clark2, Dennis Dlugos2, Deborah G Hirtz2, David Masur2, Eli M Mizrahi2, Solomon L Moshé2, Tracy A Glauser2. 1. From 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. 2. From 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.
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.
RCT Entities:
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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