Neurometabolite abnormalities and associations with epilepsy duration and cognition in patients with idiopathic generalized epilepsies

Abstract Objective This study investigated whether idiopathic generalized epilepsies (IGEs) are associated with neuroinflammation by measuring neurometabolite levels and brain temperature using whole‐brain magnetic resonance spectroscopy imaging (MRSI). We compared patients with IGEs to healthy controls (HCs), and in IGEs examined relationships with seizure control, MRSI markers, epilepsy duration, and cognitive performance. Methods Seventeen patients with IGEs and 15 HCs underwent 3T‐MRI scans. IGEs were also administered the Montreal Cognitive Assessment (MoCA) and Flanker test. Whole‐brain 1 H‐MRSI provided metabolite and water maps. Levels for myo‐inositol (MI; glial marker), glutamate‐glutamine complex (Glx), and N‐acetylaspartate (NAA) were normalized to creatine (Cr) levels. Brain temperature was obtained by frequency difference between water and Cr. IGEs were stratified into seizure‐free (IGE−) and treatment‐resistant (IGE+) groups. Group analyses were performed using permutation‐based threshold‐free cluster enhancement (TFCE) within bilateral regions of interest: anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), hippocampus, parietal cortex, and thalami. Results Compared with HCs, IGEs showed higher MI/Cr in the parietal cortex, PCC, and thalamus; higher hippocampus Glx/Cr; and lower parietal cortex NAA/Cr. Brain temperature did not differ between groups. IGE− exhibited higher hippocampal NAA/Cr and better MoCA scores than IGE+. Longer epilepsy duration was associated with lower NAA/Cr in the ACC and PCC, and parietal cortex, as well as lower Glx/Cr in the ACC, PCC, parietal cortex, and hippocampus. Lower NAA/Cr in the ACC, PCC, hippocampus, and thalamus, together with higher thalamus MI/Cr, was associated with lower MoCA scores in IGEs. Lower NAA/Cr in the ACC, thalamus, and hippocampus was associated with poorer Flanker performance in IGEs. Significance We provide novel evidence of neurometabolic abnormalities in IGEs. The associations between metabolite levels and clinical and cognitive variables suggest potential biomarkers for disease progression and treatment response. Furthermore, these results highlight the roles of abnormal glial activation, neuronal loss, and hyperexcitability in IGE pathophysiology. Plain Language Summary We compared patients with idiopathic generalized epilepsies (IGEs) to healthy controls (HCs) to investigate brain chemistry and temperature differences and their relationships to seizure control, epilepsy duration, and cognitive performance. We found group differences in brain N‐acetylaspartate (NAA; neuronal marker), myo‐inositol (MI; glial cell marker), and glutamate/glutamine (Glx; excitatory neurotransmission) levels, but not in brain temperature. Longer epilepsy duration was associated with brain chemistry levels. In IGEs, lower NAA levels and higher MI levels were associated with worse cognitive performance. This study highlights the roles of abnormal glial activation, neuronal loss, and hyperexcitability in epilepsy duration and cognition in IGEs.