Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy

Abstract

Summary Purpose: To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network. Methods: Sixty patients with JME were submitted to multi‐voxel proton spectroscopy (1H‐MRS) at 1.5 T over medial prefrontal cortex (MPC), primary motor cortex (PMC), thalamus, striatum, posterior cingulate gyrus (PCG), and insular, parietal, and occipital cortices. We determined ratios for integral values of N‐acetyl‐aspartate (NAA) and glutamate‐glutamine (GLX) over creatine‐phosphocreatine (Cr). The control group (CTL) consisted of 30 age‐ and sex‐matched healthy volunteers. Results: The NAA/Cr ratio, a measure of neuronal injury, was reduced in PMC, MPC, and thalamus among patients. In addition, they had an altered GLX/Cr ratio, which is involved in excitatory activity, on PMC, MPC, and PCG, where it was reduced, whereas it was increased on insula and striatum. Multiple regression analysis revealed the strongest correlation between thalamus and MPC, but the thalamus was also correlated with insula, occipital cortex, and striatum among patients. Lower NAA/Cr was observed with advancing age and duration of epilepsy, regardless of frequency of seizures and antiepileptic drug therapy in thalamus and frontal cortex. Discussion: The identification of a specific network of neurochemical dysfunction in patients with JME, with diverse involvement of particular structures within the thalamocortical circuitry, suggests that cortical hyperexcitability in JME is not necessarily diffuse, supporting the knowledge that the focal/generalized distinction of epileptogenesis should be reconsidered. Furthermore, evidence is provided toward progressive neuronal dysfunction in JME.

Hippocampal metabolic dysfunction in juvenile myoclonic epilepsy: 3D multivoxel spectroscopy study

“…This may partly be attributed to restrictions imposed by the single voxel size used in our analysis. In addition to recent data suggesting neurochemical dysfunction in different brain areas in patients with JME [6], we found evidence of metabolic disturbances in the hippocampi of our patients. Moreover, our data further corroborate the hypothesis that focal brain regions in patients with "predominantly generalized" epilepsy are more innately epileptogenic than controls [15].…”

“…However, there is a consistent body of data that has accumulated with the advancement of neuroimaging techniques that challenge the current hypothesis of JME as a condition with no anatomic substrate. A magnetic resonance spectroscopy (MRS) study in patients with JME gave evidence for a specific network of neurochemical dysfunction affecting particular brain structures including primary motor and medial prefrontal cortex and thalamus [6]. Furthermore, serotonin 1A receptor binding potential (BP) measured with positron emission tomography (PET) revealed reduction in dorsolateral prefrontal cortex, raphe nuclei and hippocampus that is not related to atrophy [7].…”

Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy

“…A more recent study investigating a large network of regions implicated in JME using MRS, including the medial prefrontal cortex, primary motor cortex, occipital cortex, and posterior cingulate cortex, further demonstrated decreased NAA in primary motor cortex, medial prefrontal cortex, and reduced GLX to creatine-phosphocreatine ratios (a proxy measure of neuronal excitability) in the posterior cingulate, overlapping with the regions reported here in the VBM analyses. 35 In line with the guidelines of Pell and colleagues 36 on maximization of detection power in group comparison VBM, our control group size varied across analyses. However, a subset of participants was kept constant across all 3 analyses.…”

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

“…For example, studies using voxel-based analyses found topographical abnormalities in frontal cortical gray matter (GM) concentration and volume [3][4][5]. Moreover, studies using diffusion tensor imaging (DTI) or magnetic resonance spectroscopy (MRS) analyses observed changes in white matter (WM) and GM connectivity that indicated abnormal function within the thalamofrontal network in JME patients [6,7]. An emphasis on abnormal function in the frontal lobe of JME patients Seizure 30 (2015) [124][125][126][127][128][129][130][131] was reinforced by findings from neuropsychological testing [8] and EEG analyses [9], but several recent studies have also identified extra-frontal, focal cortical, and regional abnormalities [4,10].…”