Abstracts

Rationale: Cognitive impairment is a common comorbidity of childhood epilepsy. Especially important is the impact of epilepsy on executive abilities and the related consequences for day-to-day functional status and health-related quality of life. The anatomical substrate of executive dysfunction in childhood epilepsy remains to be fully characterized. This investigation focuses on a specific executive function, concept formation, and relates performance to measures of cortical thickness in order to understand the anatomical and maturational correlates of impaired executive function in new and recent onset childhood epilepsy. Methods: Research participants included children (ages 8-18) with new and recent onset localization-related (n=27) and idiopathic generalized (n=28) epilepsies who were seen and assessed within 12 months of diagnosis. Healthy controls (n=48) consisted of age- and gender-matched first-degree cousin controls. Executive function was assessed by the D-KEFS Sorting Test with the number of confirmed correct sorts serving as the primary dependent measure. Images were obtained at the University of Wisconsin Hospital on a 1.5-Tesla GE Signa MRI scanner. To investigate difference in cortical thickness, we performed a surface based group analysis using Freesurfer s statistical tool, QDEC 1.4. Subjects surface data were first smoothed with a 10 mm FWHM kernel to improve intersubject averaging. A general linear model was then applied at each vertex to test for group differences in cortical thickness with FDR correction. Results: Children with both idiopathic generalized and localization-related epilepsies exhibited significantly impaired (p <0.05) D-KEFS performance compared to controls, with no difference between the two epilepsy groups (p >.10). The top panel of Figure 1 depicts the link between executive function (D-KEFS sort test) and cortical thickness in the epilepsy group (p<0.05, corrected). Better performance in executive function was associated with decreased cortical thickness predominately in the bilateral dorsolateral prefrontal cortex. To determine whether delayed neurodevelopment may be a pertinent consideration, we examined age-related differences in cortical thinning. The bottom panel of Figure 2 provides the corrected map of age dependent cortical thickness differences between the epilepsy and control groups. Group differences were evident in the left frontal cortex characterized by delayed cortical thinning in the epilepsy group compared to controls. Conclusions: Children with localization-related and idiopathic generalized epilepsies exhibit abnormal executive function early in the course of the disorder. Performance in executive function is associated with the degree of neurodevelopmental maturation (cortical thinning) in the bilateral frontal lobes, a process that appears to be slowed in areas of frontal cortex in childhood epilepsy compared to healthy controls.