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September 25, 2012; 79 (13) Articles

Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

A prospective cohort study

Anne T. Berg, Frank A. Zelko, Susan R. Levy, Francine M. Testa
First published September 12, 2012, DOI: https://doi.org/10.1212/WNL.0b013e31826c1b55
Anne T. Berg
From the Epilepsy Center (A.T.B.) and Department of Child and Adolescent Psychiatry (F.A.Z.), Ann and Robert H. Lurie Children's Hospital of Chicago, IL; and Departments of Neurology and Pediatrics (S.R.L., F.M.T.), Yale School of Medicine, New Haven, CT.
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Frank A. Zelko
From the Epilepsy Center (A.T.B.) and Department of Child and Adolescent Psychiatry (F.A.Z.), Ann and Robert H. Lurie Children's Hospital of Chicago, IL; and Departments of Neurology and Pediatrics (S.R.L., F.M.T.), Yale School of Medicine, New Haven, CT.
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Susan R. Levy
From the Epilepsy Center (A.T.B.) and Department of Child and Adolescent Psychiatry (F.A.Z.), Ann and Robert H. Lurie Children's Hospital of Chicago, IL; and Departments of Neurology and Pediatrics (S.R.L., F.M.T.), Yale School of Medicine, New Haven, CT.
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Francine M. Testa
From the Epilepsy Center (A.T.B.) and Department of Child and Adolescent Psychiatry (F.A.Z.), Ann and Robert H. Lurie Children's Hospital of Chicago, IL; and Departments of Neurology and Pediatrics (S.R.L., F.M.T.), Yale School of Medicine, New Haven, CT.
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Citation
Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes
A prospective cohort study
Anne T. Berg, Frank A. Zelko, Susan R. Levy, Francine M. Testa
Neurology Sep 2012, 79 (13) 1384-1391; DOI: 10.1212/WNL.0b013e31826c1b55

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Abstract

Objectives: Increasing evidence suggests that uncontrolled seizures have deleterious effects on cognition and behavior, particularly in the developing brain.

Methods: In a community-based cohort, 198 children, aged <8 years with new-onset epilepsy were followed prospectively and reassessed with the Wechsler Intelligence Scales for Children, Third Edition (WISC-III) 8–9 years later. Linear regression analyses with interactions between age at onset (age) and pharmacoresistance (PR) were used to test whether earlier onset conveyed greater vulnerability to the effects of uncontrolled seizures. Full-scale IQ (FSIQ) and the 4 subdomain scores were examined. Adjustment for adaptive behavior scores in a subset was performed. A dichotomous indicator for IQ <80 or ≥80 was used to permit inclusion of children who were not tested, particularly those who were untestable.

Results: FSIQ was not correlated with age. PR was associated with an 11.4 point lower FSIQ (p = 0.002) and similar decrements in each WISC-III domain. There were substantial age-PR interactions for FSIQ (p = 0.003) and 3 domain scores, indicating a lessening impact of PR with increasing age. The dichotomous IQ indicator was strongly correlated with age at onset in the pharmacoresistant group (p < 0.0001) and not in the non-pharmacoresistant group (p = 0.61). Adjustment for adaptive behavior measured near onset did not alter the conclusions.

Conclusions: Uncontrolled seizures impair cognitive function with effects being most severe in infancy and lessening with increasing age at onset. These findings further emphasize the need for early aggressive treatment and seizure control in infants and young children.

GLOSSARY

AED=
antiepileptic drug;
BECTS=
benign epilepsy with central temporal spikes;
CAE=
childhood absence epilepsy;
CBCL=
Child Behavior Checklist;
FSIQ=
full-scale IQ;
VABS=
Vineland Adaptive Behavior Scales;
WAIS-R=
Wechsler Adult Intelligence Scale−Revised;
WISC-III=
Wechsler Intelligence Scales for Children, Third Edition

Footnotes

  • Study funding: Supported by a grant from the National Institutes of Health (NINDS R37-NS31146).

  • Supplemental data at www.neurology.org

  • Received February 21, 2012.
  • Accepted May 8, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.
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  • Developmental disorders
  • Mental retardation
  • Natural history studies (prognosis)

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