Juvenile Myoclonic Epilepsy Shows Potential Structural White Matter Abnormalities: A TBSS Study.
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ABSTRACT:
SUBMITTER: Domin M
PROVIDER: S-EPMC6033991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients.MethodsSixty-seven patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features.ResultsThe gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected P < 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (P < 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (P < 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (P = 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (P < 0.05).ConclusionThe JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.
| S-EPMC9149597 | biostudies-literature
Project description:ObjectiveThe aim of this study was to determine if there were focal cortical abnormalities in juvenile myoclonic epilepsy (JME) using neuropsychological investigations and MRI.MethodsTwenty-eight patients with JME and a large sample of healthy controls were assessed using a series of neuropsychological tests as well as structural and diffusion tensor MRI (DTI). DTI measures assessed fractional anisotropy (FA) within a white matter skeleton.ResultsNeuropsychological testing indicated subtle dysfunctions in verbal fluency, comprehension, and expression, as well as nonverbal memory and mental flexibility. Utilizing whole-brain voxel-based morphometry for gray matter MRI data and tract-based spatial statistics for white matter diffusion MRI data, we found reductions in gray matter volume (GMV) in the supplementary motor area and posterior cingulate cortex and reductions in FA in underlying white matter of the corpus callosum. Supplementary motor area FA predicted scores in word naming tasks and expression scores. Posterior cingulate cortex GMV and FA predicted cognitive inhibition scores on the mental flexibility task.ConclusionsThe neuropsychological, structural, and tractography results implicate mesial frontal cortex, especially the supplementary motor area, and posterior cingulate cortex in JME.
| S-EPMC3030222 | biostudies-literature
Project description:Juvenile myoclonic epilepsy is the most common idiopathic generalized epilepsy, characterized by frequent myoclonic jerks, generalized tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease. Given its presumed thalamo-cortical basis, we investigated thalamo-cortical structural connectivity, as measured by diffusion tensor imaging, in a cohort of 28 participants with juvenile myoclonic epilepsy and detected changes in an anterior thalamo-cortical bundle compared with healthy control subjects. We then investigated task-modulated functional connectivity from the anterior thalamic region identified using functional magnetic resonance imaging in a task consistently shown to be impaired in this group, phonemic verbal fluency. We demonstrate an alteration in task-modulated connectivity in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle, and overlapping with the supplementary motor area. Further, we show that the degree of abnormal connectivity is related to disease severity in those with active seizures. By integrating methods examining structural and effective interregional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo-cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the functional abnormalities in this idiopathic epilepsy.
| S-EPMC3525058 | biostudies-literature
Project description:BackgroundWidespread structural and functional brain network changes have been shown in Juvenile Myoclonic Epilepsy (JME) despite normal clinical neuroimaging. We sought to better define these changes using magnetoencephalography (MEG) and source space connectivity analysis for optimal neurophysiological and anatomical localisation.MethodsWe consecutively recruited 26 patients with JME who underwent resting state MEG recording, along with 26 age-and-sex matched controls. Whole brain connectivity was determined through correlation of Automated Anatomical Labelling (AAL) atlas source space MEG timeseries in conventional frequency bands of interest delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (40-60 Hz). We used a Linearly Constrained Minimum Variance (LCMV) beamformer to extract voxel wise time series of 'virtual sensors' for the desired frequency bands, followed by connectivity analysis using correlation between frequency- and node-specific power fluctuations, for the voxel maxima in each AAL atlas label, correcting for noise, potentially spurious connections and multiple comparisons.ResultsWe found increased connectivity in the theta band in posterior brain regions, surviving statistical correction for multiple comparisons (corrected p < 0.05), and decreased connectivity in the beta band in sensorimotor cortex, between right pre- and post- central gyrus (p < 0.05) in JME compared to controls.ConclusionsAltered resting-state MEG connectivity in JME comprised increased connectivity in posterior theta - the frequency band associated with long range connections affecting attention and arousal - and decreased beta-band sensorimotor connectivity. These findings likely relate to altered regulation of the sensorimotor network and seizure prone states in JME.
| S-EPMC7684644 | biostudies-literature
Project description:Patients with juvenile myoclonic epilepsy (JME) often present with risk-taking behavior, suggestive of frontal lobe dysfunction. Recent studies confirm functional and microstructural changes within the frontal lobes in JME. This study aimed at characterizing decision-making behavior in JME and its neuronal correlates using functional magnetic resonance imaging (fMRI).We investigated impulsivity in 21 JME patients and 11 controls using the Iowa Gambling Task (IGT), which measures decision making under ambiguity. Performance on the IGT was correlated with activation patterns during an fMRI working memory task.Both patients and controls learned throughout the task. Post hoc analysis revealed a greater proportion of patients with seizures than seizure-free patients having difficulties in advantageous decision making, but no difference in performance between seizure-free patients and controls. Functional imaging of working memory networks showed that overall poor IGT performance was associated with an increased activation in the dorsolateral prefrontal cortex (DLPFC) in JME patients. Impaired learning during the task and ongoing seizures were associated with bilateral medial prefrontal cortex (PFC) and presupplementary motor area, right superior frontal gyrus, and left DLPFC activation.Our study provides evidence that patients with JME and ongoing seizures learn significantly less from previous experience. Interictal dysfunction within "normal" working memory networks, specifically, within the DLPFC and medial PFC structures, may affect their ability to learn.
| S-EPMC4209120 | biostudies-literature
Project description:It is not known whether patients with juvenile myoclonic epilepsy (JME) differ from healthy people in decision making under risk, i.e., when the decision-making context offers explicit information about options, probabilities, and consequences already from the beginning. In this study, we adopted the Game of Dice Task-Double to investigate decision making under risk in a group of 36 patients with JME (mean age 25.25/SD 5.29?years) and a group of 38 healthy controls (mean age 26.03/SD 4.84?years). Participants also underwent a comprehensive neuropsychological assessment focused on frontal executive functions. Significant group differences were found in tests of psychomotor speed and divided attention, with the patients scoring lower than the controls. Importantly, patients made risky decisions more frequently than controls. In the patient group, poor decision making was associated with poor executive control, poor response inhibition, and a short interval since the last seizure episode. Executive control and response inhibition could predict 42% of variance in the frequency of risky decisions. This study indicates that patients with JME with poorer executive functions are more likely to make risky decisions than healthy controls. Decision making under risk is of major importance in every-day life, especially with regard to treatment decisions and adherence to long-term medical therapy. Since even a single disadvantageous decision may have long-lasting consequences, this finding is of high relevance.
| S-EPMC5879545 | biostudies-literature
Project description:Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criteria. 87/168 identified JME patients were seizure-free at last follow-up including 61 drug-responsive patients (group NDR). Seventy-eight patients were not seizure-free including 26 drug-resistant patients (group DR). Valproate was the most efficacious AED. The JME diagnosis was revised in 7 patients of group DR including 6 in whom the diagnosis had already been questioned or revised during clinical follow-up. One of these was finally diagnosed with PME (genetically confirmed Lafora disease) based on genetic testing. She was initially reviewed at age 29 yrs and considered to be inconsistent with PME. Intellectual disability (p = 0.025), cognitive impairment (p < 0.001), febrile seizures in first-degree relatives (p = 0.023) and prominent dialeptic seizures (p = 0.009) where significantly more frequent in group DR. Individuals with PME are rarely found among drug-resistant alleged JME patients in a tertiary epilepsy center. Even a very detailed review by experienced epileptologists may not identify the presence of PME before the typical features evolve underpinning the need for early genetic testing in drug-resistant JME patients.
| S-EPMC6746890 | biostudies-literature
Project description:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
| S-EPMC7567169 | biostudies-literature
Project description:ObjectiveJuvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas.MethodsUsing diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients.ResultsNeuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance.ConclusionsOur findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.
| S-EPMC4299970 | biostudies-literature
Project description:Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.
| S-EPMC8861057 | biostudies-literature