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INTRODUCTION: We conducted a multilayer network analysis in patients with juvenile myoclonic epilepsy (JME) and healthy controls, to investigate the gray matter layer using a morphometric similarity network and analyze the white matter layer using structural connectivity. METHODS: We enrolled 42 patients with newly diagnosed JME and 53 healthy controls. Brain magnetic resonance imaging (MRI) using a three-tesla MRI scanner, including T1-weighted imaging and diffusion tensor imaging (DTI) were performed. We created a gray matter layer matrix with a morphometric similarity network using T1-weighted imaging, and a white matter layer matrix with structural connectivity using the DTI. Subsequently, we performed a multilayer network analysis by applying graph theory. RESULTS: There were significant differences in network at the global level in the multilayer network analysis between the groups. The average multiplex participation of patients with JME was lower than that of healthy controls (0.858 vs. 0.878, p = 0.007). In addition, several regions showed significant differences in multiplex participation at the nodal level in the multilayer network analysis. Multiplex participation in the right entorhinal cortex was lower, whereas multiplex participation in the right supramarginal gyrus was higher at the nodal level in the multilayer network analysis of patients with JME compared to healthy controls. CONCLUSION: We demonstrated differences in network at the global and nodal levels in the multilayer network analysis between patients with JME and healthy controls. These features may be associated with the pathophysiology of JME and could help us understand the complex brain network in patients with JME.
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Imagen de Difusión Tensora , Epilepsia Mioclónica Juvenil , Sustancia Blanca , Humanos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Masculino , Femenino , Adulto , Imagen de Difusión Tensora/métodos , Sustancia Blanca/diagnóstico por imagen , Estudios de Casos y Controles , Imagen por Resonancia Magnética/métodos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Adolescente , Adulto JovenRESUMEN
Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC-FC coupling of rich-club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.
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Epilepsia Mioclónica Juvenil , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Relación Estructura-ActividadRESUMEN
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.
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Epilepsia Mioclónica Juvenil , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Epilepsia Mioclónica Juvenil/diagnóstico por imagenRESUMEN
OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.
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Cognición/fisiología , Hipercinesia/diagnóstico por imagen , Hipercinesia/fisiopatología , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/fisiopatología , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Estudios Transversales , Endofenotipos , Femenino , Humanos , Hipercinesia/psicología , Masculino , Persona de Mediana Edad , Epilepsia Mioclónica Juvenil/psicología , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with juvenile myoclonic epilepsy (JME) compared to healthy controls. METHODS: We enrolled 50 patients with JME and 42 healthy controls. We obtained structural volumes of the individual thalamic nuclei based on T1-weighted imaging and performed intrinsic thalamic network analysis using graph theoretical analysis. We analyzed the differences of thalamic nuclei volumes and intrinsic thalamic networks between the patients with JME and healthy controls. RESULTS: In the patients with JME, there were significant alterations of thalamic nuclei volumes compared to healthy controls. Right laterodorsal and left suprageniculate nuclei volumes were significantly increased (0.0019% vs 0.0014%, P < .0001; 0.0011% vs 0.0008%, P = .0006, respectively), whereas left ventral posterolateral, left ventromedial, and left pulvinar inferior nuclei volumes (0.0572% vs 0.0664%, P = .0001; 0.0013% vs 0.0015%, P = .0002; 0.0120% vs 0.0140%, P < .0001, respectively) were decreased in the patients with JME. Furthermore, the intrinsic thalamic network of the patients with JME was significantly different from that of the healthy controls. The modularity in the patients with JME was significantly increased over that in healthy controls (0.0785 vs 0.0212, P = .039). CONCLUSION: We found that there were significant alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with JME compared to healthy controls. These findings might contribute to the underlying pathogenesis of in JME.
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Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Núcleos Talámicos/diagnóstico por imagen , Adolescente , Adulto , Conectoma , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.
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Hipocampo/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/genética , Hermanos , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: The objective of the study was to identify the relationship between subcortical gray matter (GM) volumes and juvenile myoclonic epilepsy (JME). METHODS: We analyzed the brain magnetic resonance imaging (MRI) scans that were performed during the time of the diagnosis of epilepsy by using voxel-based morphometry (VBM) method. The volumetric three-dimensional sequence was used for structural investigation. The volumes of the thalamus, caudate nucleus, pallidum, and putamen were measured in both hemispheres of patients with JME, patients with generalized tonic-clonic seizures alone (GTCS) (as a disease control group) and healthy controls (HCs). All patients were drug-naïve, and treatment had been started after evaluating MRI results. RESULTS: Fifteen patients with JME (9 females, mean ageâ¯=â¯16.1⯱â¯3.2), 18 patients with GTCS (10 females, mean ageâ¯=â¯15.5⯱â¯2.9), and 43 HCs (24 females, mean ageâ¯=â¯15.9⯱â¯2.8) were included in the analysis. No significant difference was found for relative globus pallidus, caudate, and putamen volumes among the groups with JME, GTCS, and the HC group. The relative left and right thalamic volumes were significantly different between groups (Kruskal-Wallis rank test, pâ¯=â¯0.007, pâ¯=â¯0.001). In pairwise comparisons, both right and left relative thalamic volumes were lower in patients with JME than in HCs (right thalamus: means: 0.521⯱â¯0.066 vs. 0.597⯱â¯0.058, pâ¯<â¯0.001; left thalamus: means: 0.526⯱â¯0.088 vs. 0.605⯱â¯0.057, pâ¯<â¯0.001, Bonferroni post hoc corrections) and in patients with JME than in patients with GTCS (right thalamus: means: 0.521⯱â¯0.066 vs. 0.578⯱â¯0.066, pâ¯=â¯0.03; left thalamus: means: 0.526⯱â¯0.088 vs. 0.592⯱â¯0.068, pâ¯=â¯0.01, Bonferroni post hoc corrections), whereas there was no significant difference between the HCs and patients with GTCS (right thalamus: means: 0.597⯱â¯0.058 vs. 0.578⯱â¯0.066, pâ¯=â¯0.8; left thalamus: means: 0.605⯱â¯0.057 vs. 0.592⯱â¯0.068, pâ¯=â¯0.999, Bonferroni post hoc corrections). CONCLUSION: This study allowed us to know that microstructural abnormalities exist from the disease onset, and the thalamus might play a critical role in the pathogenesis of JME.
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Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Putamen/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adolescente , Electroencefalografía/métodos , Femenino , Sustancia Gris/fisiopatología , Humanos , Masculino , Epilepsia Mioclónica Juvenil/fisiopatología , Putamen/fisiopatología , Tálamo/fisiopatologíaRESUMEN
OBJECTIVES: We aimed to evaluate structural and functional connectivity of patients with newly diagnosed juvenile myoclonic epilepsy (JME) compared to healthy subjects. METHODS: We enrolled 36 patients with a diagnosis of JME, who were newly diagnosed and drug-naïve. They underwent T1-weighted imaging, and structural volumes were calculated using FreeSurfer software. In addition, EEG data were obtained from all of them. Structural and functional connectivity matrices were estimated by calculating the structural volumes and EEG amplitude correlation, respectively. Then, the connectivity measures were calculated using the BRAPH program. We also enrolled healthy subjects to compare its structural and functional connectivity with the patients with JME. RESULTS: We observed that patients with JME exhibited significantly different functional and structural connectivity compared to healthy control subjects. In the global structural connectivity, global efficiency, and local efficiency, and small-worldness index were decreased, whereas characteristic path length was increased in patients with JME. Betweenness centrality of cingulate, precentral, superior parietal, and superior frontal cortex was increased in patients with JME whereas that of hippocampus was decreased. In the functional connectivity, the betweenness centrality of the fronto-central electrodes was significantly increased. CONCLUSIONS: This study reports that the structural connectivity and functional connectivity in patients with JME are significantly different from those in healthy control subjects, even those with newly diagnosed drug-naive state. The patients with JME exhibited disrupted topological disorganization of the global brain network and hub reorganization in structural and functional connectivity. These alterations are implicated in the pathogenesis of JME and suggestive of network disease.
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Encéfalo/fisiopatología , Epilepsia Mioclónica Juvenil/fisiopatología , Vías Nerviosas/fisiopatología , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagenRESUMEN
OBJECTIVE: Altered thalamocortical network has been proposed to play a pivotal role in the principal pathophysiology underlying juvenile myoclonic epilepsy (JME). Recently, resting-state fMRI studies have provided converging evidence for thalamocortical dysconnectivity in patients with JME. Herein, we investigated the amplitude and spatial distribution of spontaneous low-frequency oscillations using analysis of fractional amplitude of low-frequency fluctuation (fALFF) in a large group of JME patients in comparison with controls. METHODS: Volumetric MRI and resting-state fMRI were acquired in 75 patients with JME and 62 matched controls. After preprocessing of MRI data, fALFF was computed and then Z-transformed for standardization. fALFF was compared between controls and patients, and correlation analysis between regional fALFF and clinical parameters were performed in patients. RESULTS: Compared with controls, JME patients revealed significant fALFF increases in the bilateral medial thalamus, insular cortex/inferior frontal gyrus, and cerebellum vermis (false discovery rate-corrected P < 0.05). There was no region of fALFF reduction in JME patients relative to controls. No significant correlation was observed between regional fALFF and disease duration or cumulative number of generalized tonic-clonic seizures. CONCLUSIONS: We have shown alterations of low-frequency oscillations in the thalamus, insular cortex/inferior frontal gyrus, and cerebellum in patients with JME, implicating cerebello-thalamocortical network abnormality in the pathophysiology underlying JME. Our results could further support the recent concept that JME is a network epilepsy involving specific cortical and subcortical structures, especially the cerebello-thalamocortical network.
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Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adolescente , Adulto , Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Estudios Transversales , Femenino , Humanos , Masculino , Epilepsia Mioclónica Juvenil/fisiopatología , Estudios Prospectivos , Tálamo/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: Structural and functional magnetic resonance imaging (MRI) studies have consistently documented cortical and subcortical abnormalities in patients with juvenile myoclonic epilepsy (JME). However, little is known about how these structural abnormalities emerge from the time of epilepsy onset and how network interactions between and within cortical and subcortical regions may diverge in youth with JME compared to typically developing children. METHODS: We examined prospective covariations of volumetric differences derived from high-resolution structural MRI during the first 2 years of epilepsy diagnosis in a group of youth with JME (n = 21) compared to healthy controls (n = 22). We indexed developmental brain changes using graph theory by computing network metrics based on the correlation of the cortical and subcortical structural covariance near the time of epilepsy and 2 years later. RESULTS: Over 2 years, normally developing children showed modular cortical development and network integration between cortical and subcortical regions. In contrast, children with JME developed a highly correlated and less modular cortical network, which was atypically dissociated from subcortical structures. Furthermore, the JME group also presented higher clustering and lower modularity indices than controls, indicating weaker modules or communities. The local efficiency in JME was higher than controls across the majority of cortical nodes. Regarding network hubs, controls presented a higher number than youth with JME that were spread across the brain with ample representation from the different modules. In contrast, children with JME showed a lower number of hubs that were mainly from one module and comprised mostly subcortical structures. SIGNIFICANCE: Youth with JME prospectively developed a network of highly correlated cortical regions dissociated from subcortical structures during the first 2 years after epilepsy onset. The cortical-subcortical network dissociation provides converging insights into the disparate literature of cortical and subcortical abnormalities found in previous studies.
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Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Epilepsia Mioclónica Juvenil/patología , Adolescente , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Estudios de Casos y Controles , Niño , Progresión de la Enfermedad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagenRESUMEN
The aim of this study was to investigate the structural and functional connectivity (FC) of juvenile myoclonic epilepsy (JME) using resting state functional magnetic resonance imaging (rs-fMRI). High-resolution T1-weighted magnetic resonance imaging (MRI) and rs-fMRI data were collected in 25 patients with JME and in 24 control subjects. A FC analysis was subsequently performed, with seeding at the regions that demonstrated between-group differences in gray matter volume (GMV). Then, the observed structural and FCs were associated with the clinical manifestations. The decreased GMV regions were found in the bilateral anterior cerebellum, the right orbital superior frontal gyrus, the left middle temporal gyrus, the left putamen, the right hippocampus, the bilateral caudate, and the right thalamus. The changed FCs were mainly observed in the motor-related areas and the cognitive-related areas. The significant findings of this study revealed an important role for the cerebellum in motor control and cognitive regulation in JME patients, which also have an effect on the activity of the occipital lobe. In addition, the changed FCs were related to the clinical features of JME patients. The current observations may contribute to the understanding of the pathogenesis of JME.
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Encéfalo/patología , Encéfalo/fisiopatología , Epilepsia Mioclónica Juvenil/patología , Epilepsia Mioclónica Juvenil/fisiopatología , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Adulto JovenRESUMEN
Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsies (IGEs) and is characterized by myoclonic jerks, tonic-clonic seizures and infrequent absence seizures. The network notion has been proposed to better characterize epilepsy. However, many issues remain not fully understood in JME, such as the associations between discharge-affecting networks and the relationships among resting-state networks. In this project, eigenspace maximal information canonical correlation analysis (emiCCA) and functional network connectivity (FNC) analysis were applied to simultaneous EEG-fMRI data from JME patients. The main findings of our study are as follows: discharge-affecting networks comprising the default model (DMN), self-reference (SRN), basal ganglia (BGN) and frontal networks have linear and nonlinear relationships with epileptic discharge information in JME patients; the DMN, SRN and BGN have dense/specific associations with discharge-affecting networks as well as resting-state networks; and compared with controls, significantly increased FNCs between the salience network (SN) and resting-state networks are found in JME patients. These findings suggest that the BGN, DMN and SRN may play intermediary roles in the modulation and propagation of epileptic discharges. These roles further tend to disturb the switching function of the SN in JME patients. We also postulate that emiCCA and FNC analysis may provide a potential analysis platform to provide insights into our understanding of the pathophysiological mechanism of epilepsy subtypes such as JME. Hum Brain Mapp 37:3515-3529, 2016. © 2016 Wiley Periodicals, Inc.
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Encéfalo/fisiopatología , Epilepsia Mioclónica Juvenil/fisiopatología , Adolescente , Adulto , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Encéfalo/diagnóstico por imagen , Electroencefalografía , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Dinámicas no Lineales , Descanso , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.
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Imagen por Resonancia Magnética/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Electroencefalografía , Epilepsia Tipo Ausencia/diagnóstico por imagen , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Pulvinar/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto JovenRESUMEN
Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients. Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results. We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease.
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Encéfalo/patología , Cognición/fisiología , Epilepsia Mioclónica Juvenil/patología , Epilepsia Mioclónica Juvenil/psicología , Sustancia Blanca/patología , Adolescente , Anisotropía , Encéfalo/diagnóstico por imagen , Niño , Imagen de Difusión Tensora/métodos , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Pruebas Neuropsicológicas , Tamaño de los Órganos , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVE: The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.
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Anticonvulsivantes/uso terapéutico , Encéfalo/fisiopatología , Epilepsia Mioclónica Juvenil/diagnóstico , Convulsiones/diagnóstico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Niño , Preescolar , China , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Epilepsia Mioclónica Juvenil/fisiopatología , Convulsiones/diagnóstico por imagen , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Adulto JovenRESUMEN
Our aim in this research is investigating the hypothesis of biochemical changes in frontal cortex and thalamocortical pathways in juvenile myoclonic epilepsy (JME) and the interaction between the biochemical changes and cortical functions. Magnetic resonance spectroscopy (MRS) was applied to 20 JME patients and 20 controls for measuring N-acetyl aspartate (NAA), N-acetyl aspartate to creatine ratio (NAA/Cr), Glutamine and Glutamate (GLX), Glutamine-Glutamate to creatine (GLX/Cr), Choline containing compounds (Cho) and Choline to creatine (Cho/Cr) levels. Neuropsychological cognitive tests for linguistic and visual attention, linguistic and visual memory, visuospatial and executive functions were applied to all participants. NAA and NAA/Cr concentrations were found lower in bilateral frontal and thalamic regions in JME group as compared with the control group (p < 0.05). There was no difference in frontal and thalamic GLX, GLX/Cr, Cho, Cho/Cr levels in between JME patients and controls (p > 0.05). JME patients were found more unsuccessful than the controls in attention, memory, visuospatial function, verbal fluency, Trail B test and executive functions, stroop test, clock drawing test and Trail A test (p < 0.05). Prefrontal NAA/Cr level was positively related to visual attention, memory, stroop test and thalamic NAA/Cr level was positively related to linguistic memory and Wisconsin card sorting test in JME patients. This research highlights regional brain changes and cognitive decline in JME patients and suggests that MRS may be a sensitive technique for showing subclinical cognitive changes.
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Encéfalo/diagnóstico por imagen , Cognición , Espectroscopía de Resonancia Magnética/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/psicología , Pruebas Neuropsicológicas , Adulto , Encéfalo/metabolismo , Cognición/fisiología , Trastornos del Conocimiento/diagnóstico por imagen , Humanos , Epilepsia Mioclónica Juvenil/metabolismoRESUMEN
INTRODUCTION/BACKGROUND: Juvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. METHODS: This study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. RESULTS: In the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. CONCLUSIONS: Our results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.
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Epilepsia Mioclónica Juvenil , Sustancia Blanca , Humanos , Imagen de Difusión Tensora/métodos , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Cuerpo CallosoRESUMEN
INTRODUCTION: There are rising evidences that subcortical structures, including the basal ganglia, are affected in patients with epilepsy. These structures are thought to influence the modulation and phenotypic expression of epileptic seizures. Our study aimed to evaluate the presence of structural abnormalities in subcortical structures in patients with juvenile myoclonic epilepsy (JME). METHODS: This cross-sectional study included 51 patients who were diagnosed with JME and who were monitored on an outpatient basis at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade from January 1985 to October 2017. All patients underwent transcranial parenchymal sonography (TCS) from October 2015 to October 2017. Relation of clinical parameters (seizure control andcognitive functioning,) with TCS results was assessed. RESULTS: Hyperechogenicity of the substantia nigra (SN) was detected in 37.2% of JME subjects and it was significantly more common in patients with JME than in the control group. The marked echogenicity of the red nucleus (RN) was detected in 17.6% of cases, while 11.8% of subjects had hyperechogenic RN. The presence of hyperechogenic RN (both right and left) was significantly more frequent in the group of patients with JME compared to the control group. The third ventricle diameter was larger in patients with JME than in controls. CONCLUSION: Structural changes of certain subcortical structures, primarily SN and RN, detected in JME patients indicate additional non-lesional abnormalities of the basal ganglia and midbrain structures in these patients.
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Epilepsia Mioclónica Juvenil , Humanos , Masculino , Femenino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Estudios Transversales , Adolescente , Adulto , Adulto Joven , Ultrasonografía Doppler Transcraneal/métodos , Niño , Sustancia Negra/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Núcleo Rojo/diagnóstico por imagenRESUMEN
INTRODUCTION: This study aimed to investigate the presence of sarcopenia in patients with juvenile myoclonic epilepsy (JME) and the association between sarcopenia and response to anti-seizure medication (ASM) in patients with JME. METHODS: We enrolled 42 patients with JME and 42 healthy controls who underwent brain magnetic resonance imaging with three-dimensional T1-weighted imaging. We measured the temporal muscle thickness (TMT), a radiographic marker for sarcopenia, using T1-weighted imaging. We compared the TMT between patients with JME and healthy controls and analyzed it according to the ASM response in patients with JME. We also performed a receiver operating characteristic (ROC) curve analysis to evaluate how well the TMT differentiated the groups. RESULTS: The TMT in patients with JME did not differ from that in healthy controls (9.630 vs. 9.956 mm, p = .306); however, ASM poor responders had a lower TMT than ASM good responders (9.109 vs. 10.104 mm, p = .023). ROC curve analysis revealed that the TMT exhibited a poor performance in differentiating patients with JME from healthy controls, with an area under the ROC curve of .570 (p = .270), but good performance in differentiating between ASM good and poor responders, with an area under the ROC curve of .700 (p = .015). CONCLUSION: The TMT did not differ between patients with JME and healthy controls; however, it was reduced in ASM poor responders compared to ASM good responders, suggesting a link between ASM response and sarcopenia in patients with JME. TMT can be used to investigate sarcopenia in various neurological disorders.
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Epilepsia Mioclónica Juvenil , Sarcopenia , Humanos , Epilepsia Mioclónica Juvenil/complicaciones , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Sarcopenia/diagnóstico por imagen , Encéfalo , Imagen por Resonancia Magnética/métodos , CabezaRESUMEN
Background: This study investigated alterations in the intrinsic thalamic network of patients with juvenile myoclonic epilepsy (JME) based on an electroencephalography (EEG) source-level analysis. Materials and Methods: We enrolled patients newly diagnosed with JME as well as healthy controls. The assessments were conducted in the resting state. We computed sources based on the scalp electrical potentials using a minimum-norm imaging method and a standardized, low-resolution, brain electromagnetic tomography approach. To create a functional connectivity matrix, we used the Talairach atlas to define thalamic nodes and applied the coherence method to measure brain synchronization as edges. We then calculated the intrinsic thalamic network using graph theory. We compared the intrinsic thalamic network of patients with JME with those of healthy controls. Results: This study included 67 patients with JME and 66 healthy controls. EEG source-level analysis revealed significant differences in the intrinsic thalamic networks between patients with JME and healthy controls. The measures of functional connectivity (radius, diameter, and characteristic path length) were significantly lower in patients with JME than in healthy controls (radius: 2.769 vs. 3.544, p = 0.015; diameter: 4.464 vs. 5.443, p = 0.024; and characteristic path length: 2.248 vs. 2.616, p = 0.046). Conclusions: We demonstrated alterations in the intrinsic thalamic network in patients with JME compared with those in healthy controls based on the EEG source-level analysis. These findings indicated increased thalamic connectivity in the JME group. These intrinsic thalamic network changes may be related to the pathophysiology of JME.