RESUMO
Although the remission of self-limited epilepsy with centrotemporal spikes (SeLECTS) usually occurs by adolescence, deficits in cognition and behavior are not uncommon. Several functional magnetic resonance imaging (fMRI) studies have revealed connectivity disturbances in patients with SeLECTS associated with cognitive impairment. However, the disadvantages of fMRI are expensive, time-consuming, and motion sensitive. In the current study, we used a partial directed coherence (PDC) method to analyze electroencephalogram (EEG) for exploring brain connectivity in patients with SeLECTS. This study enrolled 38 participants (19 patients with SeLECTS and 19 healthy controls) for PDC analysis. Our results demonstrated that the controls had significantly higher PDC inflow connectivity in the F7, T3, FP1, and F8 channels than patients with SeLECTS. By contrast, the patients with SeLECTS demonstrated significantly higher PDC inflow connectivity than did the controls in the T5, Pz, and P4 channels. We also compared the PDC connectivity in different Brodmann areas between the patients with SeLECTS and the controls. The results revealed that the inflow connectivity in the BA9_46_L area was significantly higher in the controls than in the patients with SeLECTS, whereas the inflow connectivity in the MIF_L area 4 was significantly higher in the patients with SeLECTS than in the controls. Our proposed approach of combining EEG with PDC provides a convenient and useful tool for investigating functional connectivity in patients with SeLECTS. This approach is time-saving and inexpensive compared with fMRI, but it achieves similar results to fMRI.
Assuntos
Epilepsia Rolândica , Epilepsia , Adolescente , Humanos , Eletroencefalografia/métodos , Encéfalo , Córtex Cerebral , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Epilepsia Rolândica/patologiaRESUMO
BACKGROUND: Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS) is the most common form of idiopathic epilepsy in children, accounting for up to 23% of pediatric epilepsy. The pathogenesis of BECTS is unknown, but it is thought that genetic factors play a role in susceptibility to the disease. METHODS: To investigate the role of common genetic variants in BECTS pathogenesis, a 2-stage genome-wide association study (GWAS) was performed in 1,800 Chinese Han BECTS patients, and 7,090 healthy controls. Genetic findings were used in a Mendelian Randomization study in the UK Biobank dataset to investigate the potential role of smoking in BECTS. FINDINGS: Definitive evidence of a role for common-variant heritability was demonstrated, with heritability of BECTS of >10% observed even with conservative disease prevalence assumptions. Although no individual locus achieved genome-wide significance, twelve loci achieved suggestive evidence of association (5 × 10-8
Assuntos
Epilepsia Rolândica/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas do Tecido Nervoso/genética , Receptores Nicotínicos/genética , Adolescente , Povo Asiático/genética , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Pré-Escolar , Epilepsia Rolândica/patologia , Feminino , Regulação da Expressão Gênica/genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pediatria , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Childhood epilepsy with centrotemporal spikes, previously known as Benign Epilepsy with Centro-temporal Spikes (BECTS) or Rolandic Epilepsy, is one of the most common forms of focal childhood epilepsy. Despite its prevalence, BECTS is often misdiagnosed or missed entirely. This is in part due to the nocturnal and brief nature of the seizures, making it difficult to identify during a routine electroencephalogram (EEG). Detecting brain activity that is highly associated with BECTS on a brief, awake EEG has the potential to improve diagnostic screening for BECTS and predict clinical outcomes. For this study, 31 patients with BECTS were retrospectively selected from the BCH Epilepsy Center database along with a contrast group of 31 patients in the database who had no form of epilepsy and a normal EEG based on a clinical chart review. Nonlinear features, including multiscale entropy and recurrence quantitative analysis, were computed from 30-second segments of awake EEG signals. Differences were found between these multiscale nonlinear measures in the two groups at all sensor locations, while visual EEG inspection by a board-certified child neurologist did not reveal any distinguishing features. Moreover, a quantitative difference in the nonlinear measures (sample entropy, trapping time and the Lyapunov exponents) was found in the centrotemporal region of the brain, the area associated with a greater tendency to have unprovoked seizures, versus the rest of the brain in the BECTS patients. This difference was not present in the contrast group. As a result, the epileptic zone in the BECTS patients appears to exhibit lower complexity, and these nonlinear measures may potentially serve as a clinical screening tool for BECTS, if replicated in a larger study population.
Assuntos
Ondas Encefálicas/fisiologia , Eletroencefalografia/métodos , Epilepsia Rolândica/diagnóstico , Convulsões/diagnóstico , Encéfalo/fisiologia , Criança , Registros Eletrônicos de Saúde , Epilepsia Rolândica/patologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
The aim of this study is to evaluate the abnormal cortical structures associated with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS) patients and assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities. Newly diagnosed BECTS patients (nâ¯=â¯33, 23 males) and age-matched healthy controls (nâ¯=â¯48) were evaluated by surface and volumetric MRI. CAT12 toolbox (HYPERLINK "http://www.neuro.uni-jena.de/cat/"\t"_blank" http://www.neuro.uni-jena.de/cat/, version r1109), SPM12(HYPERLINK"http://www.fil.ion.ucl.ac.uk/spm/software/spm12/"\t"_blank"http://www.fil.ion.ucl.ac.uk/spm/software/spm12/, version 6225) and MATLAB (9.5, Mathworks, Natick, MA) were used to gather CT estimates. An additional comparison was performed between BECTS children with (nâ¯=â¯13) and without ADHD (nâ¯=â¯20). BECTS patients had significantly smaller volume in left postcentral gyrus when compared to healthy controls. BECTS patients with ADHD had significantly thinner superior-inferior frontal cortex, superior temporal cortex, left pericalcarine, lingual and fusiform cortex to healthy controls. Also BECTS without ADHD patients had thinner cortical areas when compared to healthy controls, however the significance was more relevant in the BECTS with ADHD. The left fusiform cortex of BECTS patients with ADHD patients was significantly thinner than BECTS patients without ADHD. Our results showed that BECTS affects frontal, temporal, parietal and occipital lobes by cortical thinning. Our study supports the need for better characterization of patients with BECTS so identification of different phenotypes can occur. Further studies are needed to investigate the relationship between BECTS and ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Córtex Cerebral/patologia , Epilepsia Rolândica/patologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Pré-Escolar , Comorbidade , Epilepsia Rolândica/complicações , Epilepsia Rolândica/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white-matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white-matter structural architecture, it cannot detect neural activity or white-matter functions. Recent studies demonstrated the functional organization of white-matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white-matter dysfunctions in BECT. Resting-state fMRI data were collected from 24 new-onset drug-naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white-matter functional networks were obtained using a clustering analysis on voxel-by-voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub-bands (Slow-5:0.01-0.027, Slow-4:0.027-0.073, Slow-3:0.073-0.198, and Slow-2:0.198-0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white-matter networks based on their correlations with multiple gray-matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency-specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow-3 and Slow-4. This study provided further support on the existence of white-matter functional networks which exhibited frequency-specific properties, and extended abnormalities of rolandic area from the perspective of white-matter dysfunction in BECT.
Assuntos
Epilepsia Rolândica/fisiopatologia , Rede Nervosa/fisiopatologia , Substância Branca/fisiopatologia , Criança , Epilepsia Rolândica/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/patologia , Substância Branca/patologiaRESUMO
OBJECTIVES: The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers. MATERIALS AND METHODS: To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated. RESULTS: Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS. CONCLUSION: A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.
Assuntos
Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Epilepsia Rolândica/psicologia , Adolescente , Córtex Cerebral/patologia , Criança , Eletroencefalografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Testes NeuropsicológicosRESUMO
Rolandic epilepsy (RE) is the most common focal epilepsy in childhood. To date no hypothesis-free exome-wide mutational screen has been conducted for RE and atypical RE (ARE). Here we report on whole-exome sequencing of 194 unrelated patients with RE/ARE and 567 ethnically matched population controls. We identified an exome-wide significantly enriched burden for deleterious and loss-of-function variants only for the established RE/ARE gene GRIN2A. The statistical significance of the enrichment disappeared after removing ARE patients. For several disease-related gene-sets, an odds ratio >1 was detected for loss-of-function variants.
Assuntos
Epilepsia Rolândica/genética , Mutação com Perda de Função , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Criança , Epilepsia Rolândica/patologia , Exoma , Feminino , Humanos , MasculinoRESUMO
Epilepsy is a neurological disorder characterized by abnormal electrical discharges in a group of brain cells. Benign childhood epilepsy, which affect children under the age of 12 years, has been reported to contribute to the cognitive impairment of these children, even in the absence of structural abnormalities. Functional connectivity models have been applied to provide a deeper understanding of the processes that control and regulate interictal activity of benign childhood epilepsy. These studies have shown regions of increased connectivity and activity, particularly at the epileptic zone, which is usually the central region around the sensorimotor cortex, and in the immediate regions surrounding the zone and reduced activity in distant regions, such as the frontal lobe and temporal regions. The present study was designed to identify the neural drivers involved in the initiation and propagation of epileptic activity and the causal relationships between brain regions with increased and decreased connectivity and functional activity. We used three different models to identify neural drivers and casual connectivity with dynamic causal modelling (DCM) of EEG data. All models showed that the central region, the source of the epileptic activity, is the major driver of the brain network during interictal discharges. Other regions include the temporoparietal junction and temporal pole. The central region also had influence on the frontal and contralateral hemisphere, which might explain the cognitive deficits observed in these patients.
Assuntos
Mapeamento Encefálico , Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Lobo Temporal/fisiopatologia , Teorema de Bayes , Criança , Eletroencefalografia , Feminino , Lateralidade Funcional , Humanos , Masculino , Vias Neurais/fisiopatologiaRESUMO
PURPOSE: Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to investigate sub-cortical morphological alterations in RE children with left, right, or bilateral hemispheric focus and its association with cognition. METHODS: Participants include 41 children with rolandic epilepsy and 38 healthy controls (age 8-14 years), recruited from CHU Sainte-Justine Montreal Children Hospital (N=40) and Basel's Children Hospital (N=39). Quantitative volumetric assessment of putamen and caudate structures was performed on T1-weighted MR scans along with the morphological analysis to test for differences between patients and controls. These analyses were performed considering the side of epilepsy focus in all participants. Correlations were investigated between the sub-cortical morphometry and cognitive indices such as intelligence quotient (IQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). RESULTS: Children with bilateral BECTS showed statistically significant volume reduction in right caudate (p<.05), while no statistically significant putamen volumetric changes were detected in BECTS participants compared to normal controls. According to a spectral-based groupwise shape analysis, regional alterations were found in both putamen and caudate structures of children with BECTS. In particular, children with left BECTS showed significant outward local deformity in left putamen and individuals with bilateral BECTS showed inward local group differences in both right putamen and right caudate. The correlation assessment showed positive association between the volume of the left caudate and cognitive indices in the group containing all BECTS participants. Negative correlation was found between putamen sub-regional shape alterations and cognition in individuals with right BECTS and in all BECTS participants. Negative associations between caudate sub-regional morphologies and cognitive indices were detected in left cohort. SIGNIFICANCE: We have confirmed putamen and caudate shape alterations in children with BECTS. However, our results further suggest that variations in sub-cortical shape affect cognitive functions. Importantly, we have demonstrated that shape alterations and their relation with cognition depend on the side of epilepsy focus. Our results point to different syndromic entities in the BECTS population.
Assuntos
Núcleo Caudado/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Epilepsia Rolândica/complicações , Epilepsia Rolândica/patologia , Putamen/diagnóstico por imagem , Adolescente , Criança , Transtornos Cognitivos/diagnóstico , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Estatística como AssuntoRESUMO
Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain's intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.
Assuntos
Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Encéfalo/fisiopatologia , Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Vias Neurais/fisiopatologia , Adolescente , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Criança , Simulação por Computador , Eletroencefalografia , Epilepsia Rolândica/diagnóstico por imagem , Epilepsia Rolândica/tratamento farmacológico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Oxigênio/sangue , Estatísticas não ParamétricasRESUMO
OBJECTIVE: The aim of our study was to investigate the neuronal networks underlying background oscillations of epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS). METHODS: Sleep electroencephalography (EEG) studies before and after the treatment were investigated in 15 patients with CSWS. To investigate functional and effective connectivity within the network generating the delta activity in the background sleep EEG, the methods of dynamic imaging of coherent sources (DICS) and renormalized partial directed coherence (RPDC) were applied. RESULTS: Independent of etiology and severity of epilepsy, background EEG pattern in patients with CSWS before treatment is associated with the complex network of coherent sources in medial prefrontal cortex, somatosensory association cortex/posterior cingulate cortex, medial prefrontal cortex, middle temporal gyrus/parahippocampal gyrus/insular cortex, thalamus, and cerebellum. The analysis of information flow within this network revealed that the medial parietal cortex, the precuneus, and the thalamus act as central hubs, driving the information flow to other areas, especially to the temporal and frontal cortex. The described CSWS-specific pattern was no longer observed in patients with normalized sleep EEG. In addition, frequency of spiking showed a strong linear correlations with absolute source power, source coherence strength, and source RPDC strength at both time points: (1) Spike and wave index (SWI) versus absolute source power at EEG1 (r = 0.56; p = 0.008) and at EEG2 (r = 0.45; p = 0.009); (2) SWI versus source coherence strength at EEG1 (r = 0.71; p = 0.005) and at EEG2 (r = 0.52; p = 0.006); and (3) SWI versus source RPDC strength at EEG1 (r = 0.65; p = 0.003) and at EEG2 (r = 0.47; p = 0.009). SIGNIFICANCE: The leading role of the precuneus and thalamus in the hierarchical organization of the network underlying the background EEG points toward the significance of fluctuations of vigilance in the generation of CSWS. This hierarchical network organization appears to be specific for CSWS as it is resolved after successful treatment.
Assuntos
Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Fases do Sono/fisiologia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Masculino , Rede Nervosa/fisiopatologia , Análise Espectral , Estatística como Assunto , Estatísticas não ParamétricasRESUMO
PURPOSE: To explore intrahemispheric, cortico-cortical EEG functional connectivity (EEGfC) in benign childhood epilepsy with rolandic spikes (BECTS). METHODS: 21-channel EEG was recorded in 17 non-medicated BECTS children and 19 healthy controls. 180s of spike- and artifact-free activity was selected for EEGfC analysis. Correlation of Low Resolution Electromagnetic Tomography- (LORETA-) defined current source density time series were computed between two cortical areas (region of interest, ROI). Analyses were based on broad-band EEGfC results. Groups were compared by statistical parametric network (SPN) method. Statistically significant differences between group EEGfC values were emphasized at p<0.05 corrected for multiple comparison by local false discovery rate (FDR). RESULTS: (1) Bilaterally increased beta EEGfC occurred in the BECTS group as compared to the controls. Greatest beta abnormality emerged between frontal and frontal, as well as frontal and temporal ROIs. (2) Locally increased EEGfC emerged in all frequency bands in the right parietal area. CONCLUSIONS: Areas of increased EEGfC topographically correspond to cortical areas that, based on relevant literature, are related to speech and attention deficit in BECTS children.
Assuntos
Mapeamento Encefálico , Eletroencefalografia , Epilepsia Rolândica/fisiopatologia , Descanso/fisiologia , Criança , Epilepsia Rolândica/patologia , Feminino , Humanos , Masculino , Tomógrafos ComputadorizadosRESUMO
Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic childhood epilepsy, which is often associated with developmental disorders in children. In the present study, we analyzed resting state EEG spectral changes in the sensor and source spaces in eight BECTS patients compared with nine age-matched controls. Using high-resolution scalp EEG data, we assessed statistical differences in spatial distributions of EEG power spectra and cortical sources of resting state EEG rhythms in five frequency bands: δ (0.5-3.5 Hz), θ (4-8 Hz), α (8.5-13 Hz), ß1 (13.5-20 Hz) and ß2 (20.5-30 Hz) under the eyes-closed resting state condition. To further investigate the impact of centrotemporal spikes on EEG spectra, we split the EEG data of the patient group into EEG portions with and without spikes. Source localization demonstrated the homogeneity of our population of BECTS patients with a common epileptic zone over the right centrotemporal region. Significant differences in terms of both spectral power and cortical source densities were observed between controls and patients. Patients were characterized by significantly increased relative power in θ, α, ß1 and ß2 bands in the right centrotemporal areas over the spike zone and in the right temporo-parieto-occipital junction. Furthermore, the relative power in all bands significantly decreased in the bilateral frontal and parieto-occipital areas of patients regardless of the presence or absence of spikes in EEG segments. However, the spectral differences between patients and controls were more pronounced in the presence of spikes. This observation emphasized the impact of benign epilepsy on cortical source power, especially in the right centrotemporal regions. Spectral changes in bilateral frontal and parieto-occipital areas may also suggest alterations in the default mode network in BECTS patients.
Assuntos
Ritmo alfa/fisiologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Epilepsia Rolândica/patologia , Descanso , Criança , Eletroencefalografia , Feminino , Análise de Fourier , Humanos , MasculinoRESUMO
OBJECTIVE: The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naïve Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data. METHODS: Resting state fMRI data was collected from three groups of children aged 6-13, including new onset drug naïve BECTS, chronic BECTS with medication, and HC; the data analyzed by ReHo method. Mandarin school exams scores were acquired and compared across groups. RESULTS: There were three main findings. Firstly, compared with HC, abnormally increased ReHo was observed in bilateral sensorimotor regions in new onset BECTS which normalized or even reversed in the chronic BECTS group. Secondly, enhanced ReHo was found in the left frontal language region in the two BECTS groups, with even higher ReHo value in the chronic group. Lastly, decreased ReHo was found in regions of the default mode network (DMN), bilateral occipital lobes and cerebellum in both the new onset and chronic BECTS groups, lower in chronic BECTS. Behavioral analyses of school scores showed the chronic BECTS group presented significantly lower scores compared to HC (p<.05). SIGNIFICANCE: The coherence of low frequency fluctuations is disrupted in sensorimotor, language and DMN-related regions in new-onset BECTS. Some of these effects seem to be selectively normalized in chronic BECTS, thus allowing us to explore possible chronicity and AED-induced effects on BECTS. Abnormal ReHo in left language and DMN regions could be responsible for impairments of cognitive function.
Assuntos
Encéfalo/irrigação sanguínea , Epilepsia Rolândica/patologia , Imageamento por Ressonância Magnética , Descanso , Idade de Início , Análise de Variância , Anticonvulsivantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Criança , Doença Crônica , Epilepsia Rolândica/tratamento farmacológico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Oxigênio/sangueRESUMO
Benign epilepsy with centrotemporal spikes (BECT) is the most common form of childhood idiopathic focal epilepsy syndrome. We investigated quantitative evidence regarding brain morphology and functional connectivity features to provide insight into the neuroanatomical foundation of this disorder, using high resolution T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI in 21 patients with BECT and in 20 healthy children. The functional connectivity analysis, seeded at the regions with altered gray-matter (GM) volume in voxel-based morphometry (VBM) analysis, was further performed. Then, the observed structural and functional alteration were investigated for their association with the clinical and behavior manifestations. The increased GM volume in the striatum and fronto-temporo-parietal cortex (striato-cortical circuit) was observed in BECT. The decreased connections were found among the motor network and frontostriatal loop, and between the default mode network (DMN) and language regions. Additionally, the GM of striatum was negatively correlated with age at epilepsy onset. The current observations may contribute to the understanding of the altered structural and functional feature of striato-cortical circuit in patients with BECT. The findings also implied alterations of the motor network and DMN, which were associated with the epileptic activity in patients with BECT. This further suggested that the onset of BECT might have enduring structural and functional effects on brain maturation.
Assuntos
Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Neuroimagem Funcional , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologiaRESUMO
PURPOSE: Rolandic epilepsy (RE) is a form of well-characterized childhood epilepsy whose focal electroencephalographic abnormalities affect the same well-delineated local brain regions. Little is known about how the focal electroencephalographic discharges interfere with the topological organization of whole-brain networks in RE patients. METHODS: Seventy-three patients RE patients and 73 healthy children underwent rsfMRI. The whole-brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based approaches. We used network-based statistics to evaluate functional connectivity. The correlations between the network properties and the clinical and cognitive characteristics were calculated. RESULTS: The global topologic organization of the functional brain network was disrupted in RE patients, as manifested by reduced clustering coefficient and local and global efficiency and increased characteristic path length. The RE patients exhibited less connectivity among the sensorimotor areas; this reduction in the mean functional connectivity in this network correlated to altered global small-world properties. The RE patients exhibited decreased nodal centralities, predominantly in the bilateral postcentral gyrus, in the frontal, parietal and temporal lobes around the rolandic fissure and in areas related to linguistics and attention control (p<0.05, FDR-corrected). The altered nodal centralities in the bilateral postcentral gyrus and the left posterior cingulate cortex were correlated with subscales in Child Behavior Checklist. CONCLUSIONS: These results support the hypothesis that RE is associated with systemic brain disorganization and that the functional defect in rolandic areas contribute to symptomatology and electrophysiology in RE. Nodal abnormalities appear to imply the disturbances in linguistics and attention observed in RE patients.
Assuntos
Conectoma , Epilepsia Rolândica/patologia , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Córtex Sensório-Motor/patologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Eletroencefalografia , Epilepsia Rolândica/complicações , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/irrigação sanguínea , Vias Neurais/irrigação sanguínea , Testes Neuropsicológicos , Oxigênio/sangue , Córtex Sensório-Motor/irrigação sanguíneaRESUMO
PURPOSE: The aim of this study was to investigate cortical thickness and gray matter volume abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS). We additionally assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities. METHODS: Surface and volumetric MR imaging data of children with newly diagnosed BCECTS (n = 20, 14 males) and age-matched healthy controls (n = 20) were analyzed using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu). An additional comparison was performed between BCECTS children with and without ADHD (each, n = 8). A group comparison was carried out using an analysis of covariance with a value of significance set as p < 0.01 or p < 0.05. RESULTS: Children with BCECTS had significantly thicker right superior frontal, superior temporal, middle temporal, and left pars triangularis cortices. Voxel-based morphometric analysis revealed significantly larger cortical gray matter volumes of the right precuneus, left orbitofrontal, pars orbitalis, precentral gyri, and bilateral putamen and the amygdala of children with BCECTS compared to healthy controls. BCECTS patients with ADHD had significantly thicker left caudal anterior and posterior cingulate gyri and a significantly larger left pars opercularis gyral volume compared to BCECTS patients without ADHD. CONCLUSION: Children with BCECTS have thicker or larger gray matters in the corticostriatal circuitry at the onset of epilepsy. Comorbid ADHD is also associated with structural aberrations. These findings suggest structural disruptions of the brain network are associated with specific developmental electro-clinical syndromes.
Assuntos
Encéfalo/patologia , Epilepsia Rolândica/patologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Epilepsia Rolândica/complicações , Feminino , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
OBJECTIVE: The mismatch negativity (MMN) is an objective measure of central auditory discrimination. MMN alterations have been shown in children with language and/or developmental disorders. In benign focal epilepsies, neuropsychological disorders are often reported and linked to interictal epileptic discharges (IEDs) during non-rapid eye movement (NREM) sleep. There are few studies reporting MMN in children with benign epilepsy with centrotemporal spikes (BECTS) and sleep IEDs. Moreover, no MMN recording has yet been reported in atypical BECTS children with continuous spike-and-wave during sleep (CSWS). We retrospectively compared MMN in typical and atypical BECTS children, particularly addressing the impact of NREM sleep IEDs on auditory discrimination. Moreover, we attempted a neuropsychological characterization of patients. METHODS: The MMN was recorded in 9 normal controls and 23 patients (14 typical BECTS and 9 atypical BECTS) in an oddball paradigm with syllable stimuli. MMN, sleep electroencephalography (EEG) and neuropsychological evaluation were realized in the same testing session. RESULTS: Measurable MMN responses to speech stimuli were identified in both the control and patient groups. A significant difference between control and atypical BECTS children was found with respect to amplitude (p = 0.0061). Atypical BECTS also showed a lower MMN amplitude with respect to typical BECTS, but this difference did not reach statistical significance (p = 0.0545). Statistical comparisons between groups revealed no differences in latency. Among the neuropsychological variables, academic difficulties were significantly more prominent in the patients with atypical BECTS (p = 0.04). SIGNIFICANCE: CSWS EEG pattern affects auditory discrimination and may have a long-lasting impact on academic skills acquisition, whereas in typical BECTS children with a lower degree of IED NREM sleep, plastic brain reorganization or the preservation of participating networks may prevent such difficulty. Early electrophysiologic identification of auditory discrimination deficits in epileptic children could be used in early rehabilitation, thereby reducing the risk of developing neuropsychological disorders.
Assuntos
Córtex Cerebral/fisiopatologia , Variação Contingente Negativa/fisiologia , Epilepsia Rolândica/patologia , Epilepsia Rolândica/fisiopatologia , Potenciais Evocados Auditivos/fisiologia , Fases do Sono/fisiologia , Estimulação Acústica , Adolescente , Criança , Cognição/fisiologia , Eletroencefalografia , Epilepsia Rolândica/classificação , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
OBJECTIVE: Herein we present a single-center retrospective study of patients who underwent epilepsy surgery for seizures arising from the sensorimotor (rolandic) cortex. The goal was to find prognostic factors associated with better seizure outcome and to evaluate both surgical and neurologic outcomes. PATIENTS, METHODS, AND MATERIALS: A total of 66 patients fulfilled eligibility criteria and were included in the study. Patients were divided into two groups for analysis: patients with resections within rolandic cortex (RO group; n = 46), and patients with resections in immediate perirolandic cortex and simultaneous sensorimotor multiple subpial transections (IPR group; n = 20). RESULTS: Favorable postoperative seizure outcome (International League Against Epilepsy [ILAE]; ILAE1-ILAE3) was achieved in 42 patients (64%), 39 (59%) of whom were completely seizure-free (ILAE1). The favorable seizure outcome in the RO group (72%) was better than in the IPR group (45%) (p = 0.04, relative risk [RR] 0.51 [0.28-0.94, 95% CI]). Eighteen patients (34%) had a postoperative permanent neurologic deficit. Independent predictors for excellent seizure outcome (ILAE1) after multivariate regression analysis were complete resection of the lesion (p < 0.001), pathology (p = 0.009), age at surgery (p = 0.03), and the absence of preoperative simple partial seizures (p = 0.01). SIGNIFICANCE: With a 64% favorable seizure outcome, surgery for intractable epilepsy arising from sensorimotor cortex is possible and can be worthwhile. The increased risk for postoperative neurologic deficits is higher than in other locations, and this must be discussed with patients in detail prior to surgery. Best postoperative results can be achieved in cases in which a complete resection is possible without damaging eloquent cortical areas.
Assuntos
Epilepsia Rolândica/cirurgia , Córtex Sensório-Motor/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Córtex Sensório-Motor/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Chemical RNA modifications are present in all kingdoms of life and many of these post-transcriptional modifications are conserved throughout evolution. However, most of the research has been performed on single cell organisms, whereas little is known about how RNA modifications contribute to the development of metazoans. In recent years, the identification of RNA modification genes in genome wide association studies (GWAS) has sparked new interest in previously neglected genes. In this review, we summarize recent findings that connect RNA modification defects and phenotypes in higher eukaryotes. Furthermore, we discuss the implications of aberrant tRNA modification in various human diseases including metabolic defects, mitochondrial dysfunctions, neurological disorders, and cancer. As the molecular mechanisms of these diseases are being elucidated, we will gain first insights into the functions of RNA modifications in higher eukaryotes and finally understand their roles during development.