Gray Matter Changes in Juvenile Myoclonic Epilepsy. A Voxel-Wise Meta-Analysis

Abstract

Background and Objectives. Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome, with a genetic basis clinically identified by myoclonic jerks of the upper limbs upon awaking, generalized tonic-clonic seizures and less frequent absences. Although the brain magnetic resonance imaging (MRI) is by definition normal, computer-based Voxel-Based morphometry studies have shown a number of volumetric changes in patients with juvenile myoclonic epilepsy. Thus, the aim of the present Voxel-Wise Meta-Analysis was to determine the most consistent regional differences of gray matter volume between JME patients and healthy controls. Materials and Methods. The initial search returned 31 studies. After excluding reviews and studies without control groups or without detailed peak coordinates, 12 studies were finally included in the present meta-analysis. The total number of JME patients was 325, and that of healthy controls was 357. Results. Our study showed a statistically significant increase of the gray matter in the left median cingulate/paracingulate gyri, the right superior frontal gyrus, the left precentral gyrus, the right supplementary motor area and left supplementary motor area. It also showed a decrease in the gray matter volume in the left thalamus, and in the left insula. Conclusions. Our findings could be related to the functional deficits and changes described by previous studies in juvenile myoclonic epilepsy. In this way, the volumetric changes found in the present study could be related to the impaired frontal lobe functions, the emotional dysfunction and impaired pain empathy, and to the disrupted functional connectivity of supplementary motor areas described in JME. It additionally shows changes in the volume of the left thalamus, supporting the theory of thalamocortical pathways being involved in the pathogenesis of juvenile myoclonic epilepsy.

Valproate use associated with frontal and cerebellar gray matter volume reductions: A voxel‐based morphometry study

“…The study did not incorporate the influence of ASMs in the statistical analysis, raising concerns about the possibility of confounding due to the long‐term use of VPA that is the most commonly used ASM for patients with IGE. Of interest, meta‐analytic studies have reported GM volume increases in the medial frontal cortex/anterior cingulate cortex but no volume changes in the cerebellum in JME patients compared to controls 15,16 . Therefore, GM volume reductions in the medial frontal cortex/anterior cingulate cortex and cerebellum observed in our study are likely to be specifically related to VPA use rather than pathophysiological changes underlying IGE.…”

“…Of interest, meta-analytic studies have reported GM volume increases in the medial frontal cortex/anterior cingulate cortex but no volume changes in the cerebellum in JME patients compared to controls. 15,16 Therefore, GM volume reductions in the medial frontal cortex/ anterior cingulate cortex and cerebellum observed in our study are likely to be specifically related to VPA use rather than pathophysiological changes underlying IGE. The clinical significance of frontal structural changes remains unknown but may provide a mechanistic understanding of reported frontal cognitive dysfunctions that are associated with VPA use.…”

Brain functional network changes in patients with juvenile myoclonic epilepsy: a study based on graph theory and Granger causality analysis

“…DCG.L is part of the cingulate gyrus and is involved in behavior, motor, and somatosensory functions, especially in emotion, information transmission, and cognitive processing ( Oane et al, 2020 ). Voxel-based morphometric analysis revealed that changes in gray matter volume occurred in DCG.L in patients with JME, which could lead to impaired cognitive function in these patients ( Kazis et al, 2021 ). Node efficiency quantitatively describes the importance of a node in the whole network, the higher the node efficiency, the more important the node is and the more likely it is to become a hub node.…”

Midbrain structure volume, estimated myelin and functional connectivity in idiopathic generalised epilepsy

“…The importance of these interconnected white matter tracts for movement has been evidenced by their role in the deep brain stimulation of the SubTN in Parkinson’s disease (Vanegas-Arroyave et al ., 2016). The superior frontal gyrus has been found to be impaired in patients with IGE, with previously reported volumetric (Deng et al ., 2019; Kazis et al ., 2021) and microstructural alterations (Focke et al ., 2014), and epileptiform discharges (Jun et al ., 2019). Therefore, abnormal connectivity between the SubTN and superior frontal gyrus may be related to altered networks contributing to the motor manifestations of seizures in IGE.…”