Extrafrontal structural changes in juvenile myoclonic epilepsy: A topographic analysis of combined structural and microstructural brain imaging

PURPOSE An increasing amount of evidence has demonstrated that juvenile myoclonic epilepsy (JME) is associated with structural abnormalities in not only the thalamofrontal system but its adjacent regions such as temporal or parieto-occipital areas. The goal of this study was to systematically characterize morphological changes and the subsequent pathophysiological implications in JME patients using the combined structural and diffusion tensor MRI analysis. METHODS Comparisons of white matter (WM) water diffusivity and gray matter (GM) cortical thickness were analyzed with tract-based spatial statistics (TBSS) and a Constrained Laplacian-based Anatomic Segmentation with Proximity (CLASP) algorithm, respectively. Additionally, volumes of the bilateral thalami and hippocampi were obtained using manual volumetry (MV). RESULTS Compared with 22 normal controls, 18 patients with JME exhibited WM alterations in the antero-superior corona radiata, corpus callosum, both centro-parietal regions, and the left temporal lobe. JME patients also had reduced GM thickness (right paracentral lobule, precuneus, dorsolateral parietal and inferior temporal cortex; left dorsolateral frontal and anterior temporal areas). Furthermore, MV analyses revealed a significant volume reduction in the bilateral thalami and hippocampi. CONCLUSIONS In addition to structural changes in the thalamofrontal system, there was a conspicuous alteration of WM diffusivity in widespread extra-frontal areas and an associated decreased GM thickness in temporoparietal regions, including a significant reduction of hippocampal volume. These findings suggest that the pathophysiology of JME may be not confined to the thalamofrontal circuit but may also involve extensive areas of the extra-frontal network which encompasses temporo-parietal regions.