Objectives Idiopathic generalized epilepsy (IGE) arises from paroxysmal dysfunctions of the thalamo-cortical network. is definitely to investigate WM microstructural abnormalities in individuals with IGE using diffusional kurtosis imaging (DKI). Materials & methods We acquired DKI and volumetric T1-weighted images from 14 individuals with IGE and 25 matched healthy settings. Using tract-based spatial statistics we performed voxel-wise group comparisons in the parametric maps generated from DKI: imply diffusivity (MD) fractional anisotropy (FA) and imply kurtosis (MK) and in probabilistic maps of WM volume generated by voxel-based morphometry. Results We observed that standard microstructural actions (MD and FA) exposed WM abnormalities in thalamo-cortical projections whereas MK disclosed a broader pattern of WM abnormalities including thalamo-cortical and cortical-cortical projections. Conclusions Even though IGE is definitely TAK-632 traditionally regarded as a “non-lesional” form of epilepsy our results shown pervasive thalamo-cortical WM microstructural abnormalities. Particularly WM abnormalities demonstrated by MK further prolonged into cortical-cortical projections. This suggests that the degree of microstructural abnormalities in thalamo-cortical projections in IGE may be better assessed through the diffusion metrics provided by DKI. Keywords: Diffusional kurtosis imaging diffusion tensor imaging idiopathic generalized epilepsy MRI tract-based spatial statistics voxel-based morphometry 1 Intro Idiopathic generalized epilepsy (IGE) is definitely defined by recurrent generalized seizures such as absence myoclonic and generalized tonic-clonic seizures (1). During the ictal and interictal phases the electroencephalogram (EEG) of individuals with IGE typically demonstrate a generalized epileptiform discharges in symmetrically distributed multiple channels without consistent localization or lateralization (2). The TAK-632 mechanisms underlying ictogenesis in IGE remain unclear but it has been postulated that seizures arise from paroxysmal dysfunction of thalamo-cortical networks (3-5). By definition IGE is definitely associated with no epileptogenic structural abnormalities on routine diagnostic MRI. Occasionally medical MRI scans may demonstrate additional structural abnormalities such as subcortical microangiopathy or arachnoid cysts but these are regarded as incidental findings without relevance to the pathogenesis of IGE. Therefore some epileptologists do not regularly perform MRI studies on patients having a classical history seizure semiology and EEG findings of IGE given the high probability of a normal study. The concept of “MRI-negative” IGE has been challenged by recent studies using quantitative MRI techniques. Tissue volume studies have shown structural abnormalities in thalamo-cortical networks in individuals with IGE (6-11). However these results have not been fully consistent. For example some morphometric studies observed an increase in tissue NOS3 volume in frontal lobes (6-8). Additional studies showed decreased tissue volume TAK-632 (9 10 or no changes (11) in thalamus and frontal lobes. Diffusion tensor imaging (DTI) studies also reported multiple regional white-matter (WM) abnormalities in thalamo-cortical networks (12-16). These inconsistent findings TAK-632 of structural abnormalities in IGE have been attributed to heterogeneous genetic backgrounds (17) and different sub-syndromes of IGE (6 18 We hypothesized that IGE is definitely associated with a complex pattern of microstructural changes that may not be completely detectable using standard DTI methods. Given its difficulty minor variations in study design may lead to inconsistent findings. Hence a biomarker that is sensitive to complex microstructure architecture may better assess the degree of structural abnormalities in IGE. With this study we investigate WM microstructural abnormalities in individuals with IGE using diffusional kurtosis imaging (DKI) (19). Compared to standard DTI (with b = 1000 s/mm2) DKI employs multiple b-values (up to b = 2000 s/mm2) to quantify non-Gaussian water diffusion which may be associated with membrane permeability (20-22) and heterogeneity in cell compartments (20). Earlier studies have shown that DKI may better characterize epilepsy-related cells changes (23 TAK-632 24 We also study WM volumetric abnormalities in IGE using voxel-based morphometry (VBM). We performed voxel-wise comparisons between individuals with IGE and healthy controls. We assessed the relationship between microstructural abnormalities in IGE and the patients’ clinical variables. 2 Materials & methods 2.1.