Functional and structural connectivity in patients with focal epilepsy

Orientadores: Fernando Cendes, Ana Carolina CoanTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: Estudos recentes demonstram que as epilepsias são doenças relacionadas a alterações de redes neuronais. Técnicas de neuroimagem funcional e de difusão aliadas a avançados métodos de pós-processamento computacional permitem avaliações de conectividade funcional e estrutural do cérebro fornecendo informações sobre os padrões organizacionais das redes associadas. Este estudo visa avaliar a conectividade estrutural e funcional em pacientes com epilepsias focais, caracterizando as alterações de pacientes com epilepsia de lobo temporal mesial (ELTM) associada à esclerose hipocampal (EH) e comparando com outras epilepsias focais. Métodos: Instrumentações de software foram desenvolvidas para as análises realizadas: 1- de conectividade estrutural e 2- de conectividade funcional. Para avaliação da conectividade estrutural, foram selecionados três grupos de pacientes (ELTM-EH, ELT-não lesional [NL] e epilepsia de lobo frontal associada a displasia cortical focal [ELF-DCF]) e um grupo controle. Metodologia de tractografia semiautomática avaliou a anisotropia fracionada (FA), difusividade radial (RD) e axial (AD) de quatro fascículos: 1-uncinado; 2-fórnix; 3-fronto-occiptal inferior; 4-cíngulo. As análises de conectividade funcional foram realizadas comparando pacientes de ELTM-EH com lateralização à direita (D-ELTM) e à esquerda (E-ELTM) e um grupo controle. Setenta regiões de interesse representando 12 redes funcionais foram usadas para análise de criação das matrizes de adjacência. O segundo nível foi realizado comparando pacientes e controles. Resultados: Análise macroestrutural de substancia branca (SB) mostrou alterações (principalmente ipsilaterais) para ELTM-EH e ELF-DCF. A análise microstrutural mostrou alterações em parâmetros de difusão para os mesmos grupos. Os pacientes ELT-NL não apresentaram alterações em nenhuma das análises de integridade estrutural. Comparados ao grupo controle, os grupos D-ELTM e E-ELTM apresentaram alterações de conectividade funcional. Das 12 redes, apenas auditory e visual não apresentaram alterações em ambos os grupos. Para D-ELTM, a anterior salience e a sensorimotor também foram preservadas. Pacientes de E-ELTM apresentaram alterações mais difusas, afetando os dois hemisférios de forma mais evidente. Discussão e conclusão: Pacientes com epilepsias focais apresentam alterações de conectividade funcional e estrutural. Pacientes com ELTM-EH apresentaram piores resultados de alterações estruturais e vasta rede de alterações quando comparados a frontais ou não lesionais. Adicionalmente, apresentam complexa rede de alterações funcionais. Pacientes com E-ELTM apresentaram pior padrão de alterações funcionais comparados aos com D-ELTM. O desenvolvimento de toolboxes para as modalidades metodológicas propostas possibilitaram padronização e melhor eficiência da análise dos dadosAbstract: Introduction: Recent studies has shown that epilepsies are diseases related to neuro networks alterations. Functional and diffusion neuroimaging techniques explored by advanced computational methodologies, allows the functional and structural brain connectivity evaluation providing information regarding the brain networks behavior. This project aim to evaluate the functional and the structural connectivity in patients with temporal lobe epilepsy comparing its alteration patterns with other focal epilepsies. Methods: We developed software resources to perform the analysis: 1- Structural connectivity and 2- functional connectivity. For structural evaluations, three groups of patients were included (mesial temporal lobe epilepsy [MTLE] associated to hipocampal sclerosis [HS], non-lesional temporal lobe epilepsy [TLE-NL] and frontal lobe epilepsy associated to focal cortical dysplasia [FLE-FCD]) and a control group. We performed a semi-automatic tractography procedure to evaluate the fractional anisotropy (FA), the radial diffusivity (RD) and the axial diffusivity (AD) of four anatomic relevant fasciculi: uncinate, body of fornix, inferior fronto-occipital and body of cingulum. We performed functional connectivity analysis comparing patients with left and right MTLE-HS and controls. We used 70 regions of interest (ROIs) from 12 functional networks to compute the connectivity adjacency matrices and performed a second level analysis to compare patients and controls groups. Results: The macrostructural white matter (WM) analysis showed alterations (manly ipsilateral) on MTLE-HS and FLE-FCD. The microstructural WM analysis presented alterations on diffusion parameters for the same groups. Patients with TLE-NL showed no changes for both structural analysis. Compared to the control group, the R-MTLE and L-MTLE groups showed functional connectivity alterations. From the 12 studied networks, only the auditory and the visual networks were preserved on both groups. For the R-MTLE patients, the anterior salience and the sensorimotor networks were also not affected. Patients with L-MTLE showed more diffuse alterations, more evidently affecting both hemispheres. Discussion and conclusion: The study and the proposal methodology were effective for the identifications and characterization of functional and structural connectivity alterations in patients with focal epilepsies. The MTLE-HS showed worse widespread structural alterations compared to the FLE and TLE-NL. Additionally, they presented complex and widespread functional networks abnormalities. Patients with L-MTLE demonstrated worse and more bilaterally affected pattern of alterations when compared to R-MTLE. The development of toolboxes to perform the proposal methodology enabled the standardization and high data analysis efficiency, throughout clear proceduresDoutoradoFisiopatologia MédicaDoutor em Ciência

Does side of onset influence the pattern of cerebral atrophy in Parkinson's disease?

Imaging studies have revealed widespread neurodegeneration in Parkinson's disease (PD), but only a few considered the issue of asymmetrical clinical presentations. To investigate if the side of onset influences the pattern of gray matter (GM) atrophy in PD. Sixty patients (57.87 +/- 10.27 years) diagnosed with idiopathic PD according to the U.K. Brain Bank criteria, 26 with right-sided disease onset (RDO) and 34 with left-sided disease onset (LDO), were compared to 80 healthy controls (HC) (57.1 +/- 9.47 years). We acquired T1-weighted images on a 3 T scanner. Images were processed and analyzed with VBM8 (SPM8/Dartel) on Matlab R2012b platform. Statistic assessments included a two-sample test (family-wise error p < 0.05) with extent threshold of 20 voxels. Compared to HC, LDO patients had GM atrophy in the insula, putamen, anterior cingulate, frontotemporal cortex, and right caudate, while the RDO group showed atrophy at the anterior cingulate, insula, frontotemporal, and occipital cortex. This study revealed widespread GM atrophy in PD, predominantly in the left hemisphere, regardless of the side of onset. Future investigations should also consider handedness and side of onset to better characterize cerebral involvement and its progression in PD7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP74873/2010-22012/05286-

Padrões de controle de crises em pacientes com epilepsia de lobo temporal com ou sem esclerose hipocampal

Objective Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. Infrequent seizures was considered as up to three seizures per year and frequent seizures as any period of seizures higher than that. Results Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). Conclusion Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures.Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method: We evaluated 172 pat7327982FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2005/56578-4; 2009/54552-9SEM INFORMAÇÃOPacientes com epilepsia do lobo temporal mesial (ELTM) podem apresentar padrão instável de crises epilépticas. Nosso objetivo foi avaliar ocorrência de crises remitente-recorrentes em ELTM com (ELTM-EH) e sem (ELTM-NL) esclerose hipocampal. Método: Ava

Test-retest reproducibility of a multi-atlas automated segmentation tool on multimodality brain MRI

The increasing use of large sample sizes for population and personalized medicine requires high-throughput tools for imaging processing that can handle large amounts of data with diverse image modalities, perform a biologically meaningful information reduction, and result in comprehensive quantification. Exploring the reproducibility of these tools reveals the specific strengths and weaknesses that heavily influence the interpretation of results, contributing to transparence in science. We tested-retested the reproducibility of MRICloud, a free automated method for whole-brain, multimodal MRI segmentation and quantification, on two public, independent datasets of healthy adults. Results The reproducibility was extremely high for T1-volumetric analysis, high for diffusion tensor images (DTI) (however, regionally variable), and low for resting-state fMRI. Conclusion In general, the reproducibility of the different modalities was slightly superior to that of widely used software. This analysis serves as a normative reference for planning samples and for the interpretation of structure-based MRI studies.910FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2107/13102-7; 2013/07559-

Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE. Keywords: Functional connectivity, Generalised epilepsy, Sleep, Thalamic reticular nucleus thalamu

Diffuse decreased gray matter in patients with idiopathic craniocervical dystonia: a voxel-based morphometry study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: Recent studies have addressed the role of structures other than the basal ganglia in the pathophysiology of craniocervical dystonia (CCD). Neuroimaging studies have attempted to identify structural abnormalities in CCD but a clear pattern of alteration has not been established. We performed whole-brain evaluation using voxel-based morphometry (VBM) to identify patterns of gray matter (GM) changes in CCD. Methods: We compared 27 patients with CCD matched in age and gender to 54 healthy controls. VBM was used to compare GM volumes. We created a two-sample t-test corrected for subjects' age, and we tested with a level of significance of p < 0.001 and false discovery rate (FDR) correction (p < 0.05). Results: Voxel-based morphometry demonstrated significant reductions of GM using p < 0.001 in the cerebellar vermis IV/V, bilaterally in the superior frontal gyrus, precuneus, anterior cingulate and paracingulate, insular cortex, lingual gyrus, and calcarine fissure; in the left hemisphere in the supplementary motor area, inferior frontal gyrus, inferior parietal gyrus, temporal pole, supramarginal gyrus, rolandic operculum, hippocampus, middle occipital gyrus, cerebellar lobules IV/V, superior, and middle temporal gyri; in the right hemisphere, the middle cingulate and precentral gyrus. Our study did not report any significant result using the FDR correction. We also detected correlations between GM volume and age, disease duration, duration of botulinum toxin treatment, and the Marsden-Fahn dystonia scale scores. Conclusion: We detected large clusters of GM changes chiefly in structures primarily involved in sensorimotor integration, motor planning, visuospatial function, and emotional processing.Recent studies have addressed the role of structures other than the basal ganglia in the pathophysiology of craniocervical dystonia (CCD). Neuroimaging studies have attempted to identify structural abnormalities in CCD but a clear pattern of alteration ha5FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2010/11085-9]2010/11085-

PREVALÊNCIA DE LESÕES DA MUCOSA ORAL EM UMA POPULAÇÃO IDOSA INSTITUCIONALIZADA DA CIDADE DE ANÁPOLIS/GO PREVALENCE OF ORAL LESIONS IN INSTITUTIONALIZED ELDERLY IN ANÁPOLIS/GO

Objetivo: Avaliar a prevalência de lesões da mucosa oral em uma população idosa institucionalizada da cidade de Anápolis/GO.  Métodos: O estudo tratou-se de uma amostra de conveniência, a população abordada foi de 42 internos de três casas de repouso localizadas da cidade de Anápolis. Para a investigação da prevalência de lesões bucais na população estudada foram realizados exames clínicos e uma breve entrevista acerca do estado de saúde geral dos pacientes e possíveis queixas de cunho odontológico. Os dados coletados nos instrumentos de pesquisa foram tabulados e sumarizados em planilhas do programa computacional Microsoft Excel, expressos em forma de porcentagem e acompanhados de dados como média. Resultados: Dos 42 idosos analisados 66,67% eram do sexo feminino e 33,33% masculino. Sendo 92,86% edêntulos masculino e 75% feminino. As alterações mais prevalentes na mucosa oral foram língua saburrosa 52,38% candidose 11,90%, xerostomia 90,47% hiperplasia fibrosa 4,76% Conclusões: Os dados colhidos neste estudo revela a necessidade de medidas específicas e de saúde bucal com esse grupo de indivíduos, além de mais promoções em saúde que visam melhorar a condição de vida desses idosos

Influência do exercício físico no processo inflamatório crônico do organismo idoso

Com o envelhecimento populacional, tem se observado o aumento da prevalência de doenças crônicas, tais como doenças cardiovasculares, diabetes do tipo 2 e obesidade. O processo de envelhecimento é imuno-mediado por diversas citocinas anti e pró-inflamatórias, com uma maior prevalência dos processos inflamatórios, que acabam por levar o corpo do idoso a um quadro de inflamação crônico basal, esse, denominado de Inflammaging. Assim, tem-se como objetivo do estudo a dosagem da citocina inflamatória mais comumente associada a esse processo de imunossenescência. O projeto será realizado grupo de 30 idosos, de ambos os sexos, participantes do programa UniATI, da Universidade Evangélica De Goiás, em Anápolis-GO. De início uma palestra a respeito do estudo, relacionado com a importância do exercício fisico, ministrada pela equipe pesquisadora, acompanhados de um profissional da área da educação física, a fim de esclarecer acerca dos benefícios das atividades físicas, estimulando seu início. Após essa introdução, os participantes responderão inicialmente por um questionário e avaliação antropométrica. Após esse processo inicial, será realizado a coleta de uma amostra saliva de todos os participantes, para realização de um teste ELISA de dosagem da IL-1β, que se trata de um teste de imunoabsorção ligado a enzimas Sandwich. Após 12 meses do primeiro encontro, os participantes serão novamente submetidos ao questionário de atividade física, avaliação antropométrica e nova dosagem da citocina pesquisada, assim como realizado no início do estudo. Assim, como resultado esperado, deseja-se notar uma significante melhora no perfil inflamatório crônico desses idosos, que com base nos questionários, incrementaram sua prática física diária

Prior exercise training and experimental myocardial infarction: A systematic review and meta-analysis

Exercising prior to experimental infarction may have beneficial effects on the heart. The objective of this study was to analyze studies on animals that had exercised prior to myocardial infarction and to examine any benefits through a systematic review and meta-analysis. The databases MEDLINE, Google Scholar, and Cochrane were consulted. We analyzed articles published between January 1978 and November 2018. From a total of 858 articles, 13 manuscripts were selected in this review. When animals exercised before experimental infarction, there was a reduction in mortality, a reduction in infarct size, improvements in cardiac function, and a better molecular balance between genes and proteins that exhibit cardiac protective effects. Analyzing heart weight/body weight, we observed the following results - Mean difference 95% CI - -0.02 [-0.61,0.57]. Metaanalysis of the infarct size (% of the left ventricle) revealed a statistically significant decrease in the size of the infarction in animals that exercised before myocardial infarction, in comparison with the sedentary animals -5.05 [-7.68, -2.40]. Analysis of the ejection fraction, measured by echo (%), revealed that animals that exercised before myocardial infarction exhibited higher and statistically significant measures, compared with sedentary animals 8.77 [3.87,13.66]. We conclude that exercise performed prior to experimental myocardial infarction confers cardiac benefits to animals