Abstracts

Rationale: Individuals with chronic juvenile myoclonic epilepsy (JME) are known to exhibit subtle anomalies in cognition and brain structure. An important question is when these abnormalities develop in the course of the disorder. We, therefore, prospectively examined a cohort of children with new/recent-onset JME and normally developing children in order to characterize their cognitive development and brain maturational changes over two years. Further, we investigated whether divergences of intellectual progress in JME participants were associated with an altered trajectory of cortical development. Methods: Study participants included 22 children (age=13 3) with new/recent-onset JME and 62 healthy first-degree cousin controls (age=15 3); all underwent comprehensive neuropsychological testing at baseline and 2 years later. Within this cohort, 16 JME participants and 42 healthy controls received baseline and prospective MRI scans 2 years apart. Cognitive development from baseline to follow-up was analyzed using a mixed (group, time) two-way ANCOVA with age and gender as covariates. Prospective changes in cortical thickness and the relationship of changes in full-scale IQ to gray matter pruning were examined using the FreeSurfer longitudinal stream. Results: Both the JME and control groups improved their cognitive abilities over the 2 years, but significant group differences existed for baseline and follow-up scores as well as the rate of improvement for some measures (Figure 1). Full Scale IQ was not significantly different at baseline, but the JME group performed more poorly at follow-up with a significant group by time interaction (p=0.009). Response inhibition and psychomotor speed scores were lower at baseline and follow-up in the JME group with no group by time interaction. In terms of brain development, no significant prospective cortical thinning occurred in the JME group over the 2 year interval while dramatic thinning of the neocortex occurred in the healthy controls (> 3% gray matter loss in the bilateral frontal, temporal parietal and occipital regions; Figure 2). Importantly, decreased pruning of left middle temporal lobe and fusiform cortical thickness over 2 years was linked to greater gains in full scale IQ in JME participants but not in controls.Conclusions: For the first time, our study shows the dynamics of cognitive development and cortical maturation divergence between children with new/recent-onset JME and healthy controls. Distinguishing patterns of cognitive trajectories in children with JME emerged from the study, suggesting both antecedent (lower baseline with parallel developmental trajectory) and disease-related contributions (similar baseline but slower gain over time). Importantly, children with JME diverged from normally developing children in brain maturational patterns, with JME participants exhibiting reduced pruning in higher-order association areas. Finally, children with JME demonstrated a reorganization of brain and intellectual development in which reduced gray matter pruning in the left temporal lobe was associated with better cognitive abilities.