Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a prospective cohort study

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.

Figure 1. Full-scale IQ (FSIQ) and age at onset by pharmacoresistance

Scatterplot and regression line for the association between age at onset and FSIQ in (A) children whose epilepsy was not pharmacoresistant and (B) children with pharmacoresistant epilepsy.

Figure 2. Full-scale IQ (FSIQ) ≥80 by age at onset and pharmacoresistance

Proportion of children with a FSIQ ≥80 by year of age at onset of epilepsy and by whether seizures were pharmacoresistant (PR+) or not pharmacoresistant (PR−). Children who did not participate in the cognitive testing battery were included in the data for this plot (N = 326 total).