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- ItemAcesso aberto (Open Access)Amyotrophic lateral sclerosis in Brazil: 1998 national survey(Academia Brasileira de Neurologia - ABNEURO, 2000-09-01) Dietrich-neto, Flávia; Callegaro, Dagoberto; Dias-Tosta, Elza; Silva, Helga Cristina Almeida da [UNIFESP]; Ferraz, Maria Elizabeth [UNIFESP]; Lima, José Mauro Braz de; Oliveira, Acary Souza Bulle [UNIFESP]; Aventis Pharma; Universidade de São Paulo (USP); Hospital de Base do Distrito Federal Head of Neurology Unit; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio de Janeiro Neurological InstituteOBJECTIVES: To assess the epidemiologic characteristics of amyotrophic lateral sclerosis (ALS) in Brazil in 1998. METHOD: Structured Clinical Report Forms (CRFs) sent to 2,505 Brazilian neurologists from January to September 1998 to be filled with demographic and clinical data regarding any ALS patient seen at any time during that year. RESULTS: Five hundred and forty CRFs were returned by 168 neurologists. Data on 443 patients meeting the criteria of probable or definite ALS according to El Escorial definition were analysed: 63 probable (14.2%) and 380 definite (85.8%). Two hundred and fifty-nine (58.5%) of the patients were male, mean age of onset was 52. Spinal onset occurred in 306 patients (69%); bulbar onset in 82 (18.5%), and both in 52 (11.7%). Twenty-six (5.9%) had a family history of ALS. Two hundred and fifty-nine (58.6%) were seen by private practitioners, and 178 (40.2%) at a hospital clinic. Age-ajusted incidence shows a peak incidence at the 65-74 years old range. CONCLUSIONS: The disease's characteristics are similar to those described in international studies, except for age of onset (Brazilian patients are younger). This difference is not confirmed when figures are age-adjusted.
- ItemAcesso aberto (Open Access)Análise da função de receptores da imunidade inata no desenvolvimento da esclerose lateral amiotrófica experimental(Universidade Federal de São Paulo, 2021-10-25) Silva, Denise Correia [UNIFESP]; Barboza, Renato [UNIFESP]; http://lattes.cnpq.br/4251443655560947; http://lattes.cnpq.br/6537772227638526A neuroinflamação é um processo que desempenha papel importante na progressão de doenças neurodegenerativas como a Esclerose Lateral Amiotrófica (ELA), que é caracterizada pela morte de neurônios motores e progressiva paralisia muscular. Dados da literatura têm mostrado que mutações observadas na doença, levam à má formação de proteínas, como a Superóxido Dismutase 1 (SOD1), que pode servir como fator desencadeador do processo neuroinflamatório. Este processo é mediado pela ativação de receptores da imunidade inata, como os receptores tipo Toll (TLR) e os receptores tipo Nod (NLR); estes que são capazes de formar complexos proteicos, conhecidos como Inflamassomas. É de grande importância o entendimento desses processos, visto que, os mecanismos da neuroinflamação na ELA ainda não foram totalmente esclarecidos. Nesse sentido, o objetivo central deste trabalho foi analisar a função dos TLRs e Inflamassomas (NLRP1, NLRP3 e AIM2) no curso da doença. Além disso, avaliamos o efeito do Parthenolide, um sesquiterpeno lactano derivado da Tanacetum parthenium, que possui reconhecida atividade anti-inflamatória sobre vias de ativação relacionadas aos receptores da imunidade inata. Para estes fins, utilizamos um modelo murino de ELA, com camundongos transgênicos para a proteína SOD1 humana constitutiva ou mutante SOD1G93A. Obtivemos amostras da medula espinhal destes animais, com 120 e 140 dias de vida, período em que os sinais característicos da doença se tornam evidentes. Após, avaliamos a expressão de marcadores envolvidos nestes processos. Os resultados sugerem aumento de mRNAs para os receptores NLRP1, NLRP3 e os TLR2 e 4; na medula espinhal dos camundongos SOD1 mutantes, em relação aos controles. Bem como, maior presença de proteínas pró-inflamatórias nos tecidos desses animais. Além disso, os dados sugerem a diminuição dos níveis destes mRNAs para o gene NLRP3 na medula espinhal dos camundongos SOD1 mutantes tratados com Parthenolide, em relação aos SOD1 mutantes não tratados. Espera-se que os resultados deste trabalho possam auxiliar no entendimento dos mecanismos inflamatórios mediados por receptores da imunidade inata, que estão envolvidos com os processos de neurodegeneração.
- ItemAcesso aberto (Open Access)Aplicação de toxina botulínica tipo A para reduzir a saliva em pacientes com esclerose lateral amiotrófica(ABORL-CCF Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, 2005-10-01) Manrique, Dayse [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)AIM: To demonstrate the effect of local application of Botox® in patients with amyotrophic lateral sclerosis (ALS), following our 2002 institutional protocol of sialorrhea treatment. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Five patients with ALS assisted at Clinic of Otolaryngology of AACD (Associação de Assistência à Criança Deficiente). They were all submitted to local application of Botox® in salivary glands and followed up for a year. The protocol consisted of clinical questionnaire about the inability of swallowing saliva and its repercussions in quality of life. Patients were submitted to previous odontological treatment, had intolerance to the adverse effects of anti-cholinergic agents and had not used Botox® for at least six months. The application was guided by ultrasound and the doses were 30U in one point for submandibular gland, and 20U in two points for each parotid gland, after topic anesthetic with prilocaine. RESULTS: Five patients with ALS with sialorrhea, aged 45 to 59 years, were submitted to Botox® salivary glands application. We observed that the symptoms of sialorrhea changed dramatically in four patients. Three patients stayed almost four months without complaints with repercussion in quality of life. No patient presented local or systemic effects with local injection of Botox®.
- ItemAcesso aberto (Open Access)Esclerose Lateral Amiotrófica e as diversidades das distribuições das variantes (SNPs, indel) das enzimas de cadeia respiratória relacionadas à neuroproteção/neurodegeneração nas populações dos haplogrupos mitocondriais: uma análise de 1000 GENOME PROJECT(Universidade Federal de São Paulo (UNIFESP), 2019-09-26) Mehrpour, Sheida [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; Briones, Marcelo [UNIFESP]; http://lattes.cnpq.br/0018992452321910; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/3656019291521709; Universidade Federal de São Paulo (UNIFESP)Amyotrophic Lateral Sclerosis (ALS) is a disease characterized by the degeneration of motor neurons in the brain and spinal cord, causing progressive, irreversible and incapacitating motor paralysis. Regarding the etiology of ALS, several factors have been included: acquired nuclear enzyme abnormalities, glutamate toxicity, oxidative stress, defective axonal transport, neurofilament abnormalities, genetic factors, viral infections, and mitochondrial dysfunction. There is strong evidence that mitochondria are one of the main targets of impairment in motor neurons, with changes in the electron transport complexes of the mitochondrial chain, affecting the final production of ATP. The impaired function of mitochondrial respiratory complexes has been linked to the quantitative and / or qualitative defects of these components. Previous studies have shown that some of the mitochondrial respiratory chain enzymes, including Riboflavin kinase (RFK), flavin adenine dinucleotide synthetase (FAD), Succinate dehydrogenase B subunit (SDHB), and Cytochrome C1 (CYC1) are associated with several mechanisms of neuroprotection and dysfunctions of these enzymes are related to neurodegeneration. In addition, there is evidence that these enzymes having quanitative defects are compromised in ALS patients. Considering that several studies have demonstrated an intimate relationship between mitochondria and ALS, we have proposed to rigorously analyze the information collected at the ENSEMBLE GENOME BROWSER 91 website (updated site of 1000 GENOME PROJECT, updated in December 2017), with variant description of the genes of these enzymes including RFK, FAD, SDHB, and CYC1, of the 2.540 individuals from 26 different populations of the five places of the world belong to the different mitochondrial haplogroups, identifying the distributions of the variants of these enzymes in the different populations of the mitochondria haplogroups. The study is based on the Hardy-Weinberg equilibrium calculation. Deviation of the Hardy-Weinberg equilibrium in the control group may reflect an expectation about the development of a disease or a clinical disorder or susceptibility to a disease. We were able to identify the diversity of the distributions of the mitochondrial respiratory chain enzymes variants including RFK, FAD, SDHB, and CYC1 in mitochondrial haplogroup populations by deviation of the equilibrium of certain variants of these enzymes, confirming the susceptibility of different haplogroup populations about ALS disease and through this information we can apply prognostic, diagnostic and therapeutic antioxidant strategies for ALS patients. This finding reflects how we conduct clinical trials in the individualized therapeutic determination of each ALS patient depending on the patient haologroup and the compromised enzyme.
- ItemSomente MetadadadosEstudo do efeito in vitro do parthenolide sobre a modulação das vias de ativação dos receptores TLR e NLR induzida por SOD1G93A(Universidade Federal de São Paulo (UNIFESP), 2021) Castro, Patricia Oliveira De [UNIFESP]; Barboza, Renato [UNIFESP]; Universidade Federal de São PauloAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. The disease progresses gradually, leading to muscle atrophy, paralysis and even death from respiratory failure. Among the causes of familial ALS is the presence of mutations in the protein Superoxide Dismutase 1 (SOD1), an enzyme responsible for dismuting superoxide into oxygen. Its toxicity is associated with several mechanisms such as: abnormal accumulation of protein inclusions, mitochondrial damage, and endoplasmic reticulum stress. In this disorder, neuroinflammation plays a crucial role, characterized by chronic activation of glial cells mediated by pattern recognition receptors. Among them are the Toll-like receptores, which are responsible for the translocation of the NF-κB transcription factor; and the inflammasomes, which are protein complexes that, when activated, cleave pro-caspase, which results in the maturation of pro-inflammatory cytokines transcribed by NF-κB, and which will mediate inflammation and the innate immune response. In this work we use an in vitro model of neuroinflammation in BV2 cells induced by SOD1WT and SOD1G93A proteins in their soluble and aggregated state. We found an increase in factors linked to neuroinflammation such as TNF-α, IL-6, NLRP3, RAGE and HMGB1. To modulate inflammation, we used the NF-κB translocation inhibitor, Parthenolide. We found evidence to suggest the presence of SOD1 in a soluble or aggregated state in relation to the period of disease progression and directly associated with neuroinflammatory processes. The SOD1G93A protein in its soluble state may act as a first signal via the TLR in the inflammatory cascade, while in its aggregated state it corroborates the chronicity of inflammation and perpetuation of inflammasome activation. In addition, Parthenolide showed a decrease in TNF-α levels, but further studies are needed to analyze its pharmaceutical potential.
- ItemSomente MetadadadosIMPROVING THE REPRODUCIBILITY OF MOTOR UNIT NUMBER INDEX(Wiley, 2017) Escorcio-Bezerra, Marcio Luiz [UNIFESP]; Bulle Oliveira, Acary Souza [UNIFESP]; De Oliveira Braga, Nadia Iandoli [UNIFESP]; Manzano, Gilberto Mastrocola [UNIFESP]Introduction: Reproducibility is an important aspect of any method intended to be a marker of disease progression. In this study we investigated approaches for improving motor unit number index (MUNIX) reproducibility. Methods: We used the intraclass correlation coefficient (ICC) and the coefficient of variation (CV) to study reproducibility in healthy subjects. We tested reproducibility between test and retest of a single MUNIX from 3 different muscles (S-MUNIX) and also of the mean of a set of 3 measurements from these same muscles (M-MUNIX). Results: M-MUNIX was more reproducible than S-MUNIX. The CV showed a greater improvement than the ICC in all 3 muscles. Conclusions: M-MUNIX may be a valuable approach for following motor unit loss, because it is more replicable than MUNIX. This may be especially relevant in amyotrophic lateral sclerosis patients, in whom MUNIX variability is higher than in healthy individuals.
- ItemSomente MetadadadosMUNIX: Reproducibility and clinical correlations in Amyotrophic Lateral Sclerosis(Elsevier Ireland Ltd, 2016) Escorcio-Bezerra, Marcio Luiz [UNIFESP]; Abrahao, Agessandro [UNIFESP]; de Castro, Isac; Troccoli Chieia, Marco Antonio [UNIFESP]; de Azevedo, Lyamara Apostolico [UNIFESP]; Pinheiro, Denise Spinola [UNIFESP]; de Oliveira Braga, Nadia Iandoli [UNIFESP]; Bulle de Oliveira, Acary Souza [UNIFESP]; Manzano, Gilberto Mastrocola [UNIFESP]Objective: To study the reproducibility, diagnostic yield to detect denervation, and clinical correlations of the Motor Unit Number Index (MUNIX) in subjects with Amyotrophic Lateral Sclerosis (ALS). Methods: MUNIX evaluation was performed in three muscles twice on the same day to assess reproducibility. Cut-off values for the MUNIX were based on data from 51 healthy subjects (controls) to evaluate the sensitivity of the technique to detect denervation in 30 subjects with ALS. Results: The method had good reproducibility. The variability was greater in the ALS group. In 23 ALS subjects (77%), low MUNIX values were detected. Most of the muscles with low MUNIX had also low compound muscle action potential (CMAP) and strength, but these parameters were normal in 9% of muscles. According to ROC curve analysis, MUNIX was generally accurate (AUC = 0.9504) for discriminating between healthy individuals and subjects with at least one denervated muscle. Conclusions: MUNIX variability was higher in the ALS group. The method showed good diagnostic performance for the detection of denervation in a sample of patients with ALS. Significance: This study demonstrated that in addition to being a quantitative tool MUNIX can detect denervation in subjects with ALS. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
- ItemSomente MetadadadosWhy averaging multiple MUNIX measures in the longitudinal assessment of patients with ALS?(Elsevier Ireland Ltd, 2017) Escorcio-Bezerra, Marcio Luiz [UNIFESP]; Abrahao, Agessandro [UNIFESP]; Santos-Neto, Denizart [UNIFESP]; de Oliveira Braga, Nadia Iandoli [UNIFESP]; Bulle Oliveira, Acary Souza [UNIFESP]; Manzano, Gilberto Mastrocola [UNIFESP]Objective: To assess the impact of averaging multiple MUNIX trials on the follow-up of patients with amyotrophic lateral sclerosis (ALS).& para;& para;Methods: We determined the percent relative change (%RC) of MUNIX, in healthy subjects and patients with ALS, by subtracting the MUNIX value in the second visit from the first. Both the mean of a set of three MUNIX (mean-MUNIX) and the first MUNIX sample (single-MUNIX) were evaluated. Then, we studied the sensitivity to detect relative changes over time and the statistical dispersion of the %RC from these two parameters.& para;& para;Results: We found that the mean-MUNIX %RC has lower mean coefficient of variation than the single-MUNIX %RC in all muscles. The mean-MUNIX also resulted in more ALS patients with significant %RC, i.e., outside reference limits.& para;& para;Conclusion: The mean-MUNIX resulted in less dispersed values of %RC in patients with ALS and thus, increased the precision of the technique. The mean-MUNIX resulted also in an increase in the sensitivity to track changes over time in these patients.& para;& para;Significance: The mean-MUNIX should be considered in any ALS follow-up study as a more reliable approach and as a way of potentially reducing the sample size needed for the study. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.