Abstracts

Rationale: Idiopathic generalized epilepsy (IGE) is a common pediatric epilepsy syndrome frequently associated with impairments in executive functions (EFs), which consist of attention, problem solving, planning, and inhibition. The etiology of these impairments remains to be clarified, but is likely affected by disruption of thalamofrontal circuitry. The thalamus and the frontal lobes have been identified in previous studies as demonstrating subtle morphometric differences from healthy controls and for being critical in IGE neuropathology. The relationship between EFs and this circuitry remains unexplored in IGE. It also remains unclear whether these impairments are present at diagnosis and/or worsen over time. This study combined volumetric MRI (qMRI), voxel-based morphometry (VBM), and diffusion tensor imaging (DTI) to examine global volumetrics, location of volumetric/density abnormalities, and microstructure of the thalamus and frontal lobes in children with recent onset IGE to determine their relationship to changes in EF development. Examination of recent onset IGE provides the unique opportunity to examine the initial impact of seizures and their potential influence during a critical period of development. Methods: 29 children with recent onset IGE (i.e., diagnosed within past 12 months) and 51 healthy controls (ages 8-18 years) underwent baseline assessment which included neuropsychological assessment and magnetic resonance imaging (MRI). Select subtests of the Delis-Kaplan Executive Functioning System (D-KEFS) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to assess executive functions. The collective usage of qMRI, VBM, and DTI provides related, but distinct, measures of thalamofrontal integrity. Results: Children with IGE had more impaired executive functioning than healthy controls on both the D-KEFS and BRIEF (p’s < .05). In addition, children with IGE were also found to have significantly more frontal lobe CSF (qMRI volume) than controls (p = .01). No regional thalamic volume or density differences were found in the thalamus using VBM. In contrast, VBM showed that the IGE group had increased fronto-temporal grey matter density, increased superior frontal gyrus grey matter volume, and decreased fronto-temporal white matter density (p’s < .001, uncorrected). No significant group differences were observed on thalamic or frontal DTI fractional anisotropy or mean diffusivity (all p’s > .05). No DTI measures were significantly related to executive functions in the IGE group. Frontal white matter volume and Verbal Fluency (Category Switching Accuracy) were significantly related in the IGE group. Conclusions: Subtle structural abnormalities of the frontal lobes and impairments in EF were observed in IGE within one year of seizure onset. Frontal, but not thalamic, integrity was related to executive functions. Abnormalities in prefrontal circuitry, both structural and functional, can be seen early in the course of IGE. Longitudinal data (two years after baseline) are currently being collected and will be available at the time of presentation.