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October 17, 2017; 89 (16) Article

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

Ruth C. Shinnar, Shlomo Shinnar, Avital Cnaan, Peggy Clark, Dennis Dlugos, Deborah G. Hirtz, Fengming Hu, Chunyan Liu, David Masur, Erica F. Weiss, Tracy A. Glauser, For the Childhood Absence Epilepsy Study Group
First published September 15, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004514
Ruth C. Shinnar
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
RN, MSN
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Shlomo Shinnar
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
MD, PhD
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Avital Cnaan
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
PhD
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Peggy Clark
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
DNP, PPCNP-BC
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Dennis Dlugos
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
MD
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Deborah G. Hirtz
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
MD
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Fengming Hu
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
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Chunyan Liu
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
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David Masur
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
PhD
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Erica F. Weiss
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
PhD
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Tracy A. Glauser
From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
MD
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From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD.
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Pretreatment behavior and subsequent medication effects in childhood absence epilepsy
Ruth C. Shinnar, Shlomo Shinnar, Avital Cnaan, Peggy Clark, Dennis Dlugos, Deborah G. Hirtz, Fengming Hu, Chunyan Liu, David Masur, Erica F. Weiss, Tracy A. Glauser, For the Childhood Absence Epilepsy Study Group
Neurology Oct 2017, 89 (16) 1698-1706; DOI: 10.1212/WNL.0000000000004514

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Abstract

Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE).

Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16–20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure.

Results: A total of 382 participants at baseline, 310 participants at the week 16–20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%–11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16–20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6–54.7]), externalizing problems (51.4 [98.3% CI 48.5–54.3]), attention problems (57.8 [98.3% CI 55.6–60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1–57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4–49.6]; 45.8 [98.3% CI 42.9–48.7]; 54.6 [98.3% CI 52.4–56.9]; 53.0 [98.3% CI 51.3–54.8]). Lack of seizure freedom and elevated week 16–20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6–60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1–56.9]).

Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE.

Clinicaltrials.gov identifier: NCT00088452.

Classification of evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.

GLOSSARY

ANCOVA=
analysis of covariance;
ANOVA=
analysis of variance;
CAE=
childhood absence epilepsy;
CBCL=
Child Behavior Checklist;
CI=
confidence interval;
CPT=
Continuous Performance Test;
DSM=
Diagnostic and Statistical Manual of Mental Disorders;
RCT=
randomized controlled trial

Footnotes

  • Coinvestigators are listed at Neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received November 25, 2016.
  • Accepted in final form July 26, 2017.
  • © 2017 American Academy of Neurology
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