Abstracts

Rationale: Genetic generalized epilepsy (GGE) is by definition non-lesional but continually described with cognitive impairments. A higher incidence of photosensitivity has been reported in GGE compared to other epilepsies. However, the underlying mechanisms of structural alterations remain elusive. An increasing amount of quantitative MRI studies have addressed consistent grey matter structural differences in GGE. Only a small number of studies characterized white matter (WM) alterations and reported conflicting results. In this study, we propose to utilise an automated probabilistic reconstruction approach to determine WM alterations in patients with GGE. Methods: 3D T1-weighted and diffusion tensor imaging (DTI) were acquired for 35 patients with GGE and 39 healthy controls. Whole brain segmentation and automated WM tractography were conducted using Freesurfer and TRActs Constrained by UnderLying Anatomy (TRACULA; Yendiki et al., Front Neuroinform, 2011;5:23)(Figure 1). Tract DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed and analyzed. Group comparisons were performed using a MANCOVA in SPSS 25, controlling for age, sex, and motion. We corrected for multiple comparisons using the false discovery rate (FDR) method. Results: All the following group comparison results are presented in Table 1. Patients exhibited a significant decrease in FA of the right and a trend-level decrease in FA of the left inferior longitudinal fasciculus (ILF) relative to controls. Furthermore, compared to controls, patients showed a significant concomitant increase in MD values of the right ILF and a trend towards increased MD in the left ILF. RD values of right and left ILF were significantly increased in patients relative to controls. A significantly increased RD and trend-level increased MD and decreased FA were identified in the corpus callosum forceps major in patients compared to controls. Moreover, the AD in the right anterior thalamic radiation and right superior longitudinal fasciculus parietal division was significantly reduced. However, a trend of decrease in MD values was observed in the same structures. Finally, the left superior longitudinal fasciculus temporal division revealed significantly lower FA values in patients relative to controls. Conclusions: Our results suggested bihemispheric WM disruption in GGE, particularly of association pathways. The ILF appears to be dominantly affected, with changes showing as bilaterally decreased FA and increased MD and RD relative to controls. Increased RD but unchanged AD has been shown to reflect dysmyelination (Song et al. 2002, NeuroImage 17, 1429–1436). It is therefore possible that microstructural alterations of association tracts are linked to dysmyelination and cognitive impairments in GGE. Funding: UK Medical Research Council (Grant numbers MR/S00355X/1 & MR/K023152/1)