Altered Structural Brain Networks in Refractory and Nonrefractory Idiopathic Generalized Epilepsy

Introduction: Idiopathic generalized epilepsy (IGE) is a collection of generalized nonlesional epileptic network disorders. Around 20-40% of patients with IGE are refractory to antiseizure medication, and mechanisms underlying refractoriness are poorly understood. Here, we characterize structural brain network alterations and determine whether network alterations differ between patients with refractory and nonrefractory IGE.Methods: Thirty-three patients with IGE (10 nonrefractory and 23 refractory) and 39 age- and sex-matched healthy controls were studied. Network nodes were segmented from T1-weighted images, while connections between these nodes (edges) were reconstructed from diffusion magnetic resonance imaging (MRI). Diffusion networks of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and streamline count (Count) were studied. Differences between all patients, refractory, nonrefractory, and control groups were computed using network-based statistics. Nodal volume differences between groups were computed using Cohen's d effect size calculation.Results: Patients had significantly decreased bihemispheric FA and Count networks and increased MD and RD networks compared with controls. Alterations in network architecture, with respect to controls, differed depending on treatment outcome, including predominant FA network alterations in refractory IGE and increased nodal volume in nonrefractory IGE. Diffusion MRI networks were not influenced by nodal volume.Discussion: Although a nonlesional disorder, patients with IGE have bihemispheric structural network alterations that may differ between patients with refractory and nonrefractory IGE. Given that distinct nodal volume and FA network alterations were observed between treatment outcome groups, a multifaceted network analysis may be useful for identifying imaging biomarkers of refractory IGE. Impact statementAlthough it is accepted that epilepsy is a network disorder, few studies have prospectively recruited patients with clear refractory and nonrefractory idiopathic generalized epilepsy (IGE) with a goal to identify magnetic resonance imaging (MRI) markers of pharmacoresistance. By showing that patients with refractory and nonrefractory IGE have different patterns of diffusion MRI networks and nodal volume alterations with respect to controls, we suggest that imaging analysis of structural networks may have the potential to identify unique biomarkers of treatment outcome. Reliable imaging markers of pharmacoresistance could inform the treatment pathway for many patients with epilepsy.