Les progrès de la recherche et de la prise en charge des maladies neuromusculaires de l’enfance ont prolongé la survie des patients. L’évaluation s’impose donc pour le suivi des patients et aussi en recherche clinique car les premiers essais cliniques tant attendus commencent à paraître. Une métrologie rigoureuse et adaptée est alors indispensable parce qu'il n'est possible ni de se contenter d’une quantification approximative ni d'utiliser des outils non adaptés à des pathologies évolutives. Nous résumons l’état des connaissances sur la métrologie appliquée à l’évaluation fonctionnelle motrice des patients atteints de maladies neuromusculaires et proposons une revue de la littérature sur les outils disponibles avec des analyses précises de leurs propriétés métrologiques. La Mesure de Fonction Motrice, développée à partir de 1998, présente des qualités intéressantes en termes de validité et de fiabilité. Nous avons analysé sa sensibilité au changement dans différentes populations de patients adultes et enfants. Nous proposons ensuite, une classification en grades de sévérité d’atteinte fonctionnelle motrice, le NM-score. Les études de validation ont confirmé son intérêt, sa facilité d'utilisation, sa validité et sareproductibilité. Le NM-Score permet de décrire précisément et de façon discriminante les patients en termes de fonction motrice pour la position debout et les transferts, la motricité axiale ou proximale et la motricité distale. S’intéresser à l’évaluation et à la mesure en médecine, c’est faire preuve d’une rigueur indispensable aux décisions de soins touchant des personnes vulnérables aux besoins spécifiques. / Advances in the research and treatment of childhood neuromuscular diseases have led to longer patient survivals. Evaluation is thus required not only in clinical practice for patient follow-up but also in medical research because the results of long-awaited clinical trials are beginning to emerge. A rigorous and appropriate metrology is then necessary because rough estimates or the use of improper assessment tools are no more satisfactory. We summarize here the current knowledge on the metrology applied to motor function assessment of patients with neuromuscular diseases. We propose a review of the literature on the tools available to monitor motor function with detailed analyses of their metrological properties. Developped since 1998, the Motor Function Measure presents interesting properties in terms of validity and reliability. We analyzed its sensitivity to change in different patient populations of adults and children. We then propose, the NM-Score, a classification in levels of severity of motor function decline.Validation studies have confirmed the interest of this score as well as its ease of use, validity,and reproducibility. The NM-Score is able to describe the patients precisely and discriminantly in terms of motor function for standing position and transfers, axial / proximal motor function and distal motor function. Being interested in evaluation and measurement in medicine is a sign of rigor necessary for decision-making regarding vulnerable persons with special need.

Chez les patients avec maladies neuromusculaires (MNM) ou lésions médullaires, les modifications musculaires et squelettiques perturbent le mécanisme de toux. Les in-exsufflations mécaniques (IE-M) et les hyper-insufflations (H-I) constituent une aide instrumentale pour avoir une toux plus efficace. En France, ces dispositifs médicaux (DM) sont remboursés via des forfaits de location avec prestations de services. Cette thèse a pour objectif d'étudier le bénéfice clinique des IE-M et H-I par l'évaluation : 1) du niveau de preuve disponible via une revue systématique, 2) de leurs modalités de remboursement en France, via la constitution d'un groupe de travail, puis à l'international, via une enquête auprès du réseau international des agences d'évaluation, et, 3) des populations éligibles à ces DM via l'exploitation des bases administratives. Notre revue systématique souligne l'absence de donnée fiable disponible sur les IE-M utilisées chez les patients avec MNM. Elle rend compte de la particularité française d'utiliser des H-I. Malgré le faible niveau de preuves, le contraste avec la pratique des professionnels de santé qui considèrent ces DM efficaces et souhaitent le maintien du remboursement, peut s'expliquer par le peu d'alternatives disponibles et la possibilité d'utiliser ces DM non invasifs à domicile. Il s'agit de la seule évaluation de ces DM menée par une agence. La population éligible aux IE-M et H-I a été estimée à 3 100 par an. Ce travail encourage d'autres recherches pour assurer le meilleur traitement pour les patients comme les essais contrôlés randomisés (bien que difficiles en population rare) ou d'explorer d'autres modèles (essais randomisés par groupes) / Patients with neuromuscular disease (NMD) or spinal cord injury suffered from muscle and skeletal changes which impair cough mechanism. Mechanical in-exsufflations (MI-E) and Intermittent Positive Pressure Breathing (IPPB) are instrumental methods used for having a more effective cough. In France, theses medical devices (MD) are available to rent on a weekly fee schedule including associated services.This thesis aimed to study the clinical benefit of MI-E and IPPB by assessing: 1) the level of evidence available through a systematic review, 2) reimbursement arrangements in France, through the set-up of a multidisciplinary working group, and then internationally, through a survey of the International Network of Agencies for Health Technology Assessment, and, 3) the patient population treated with these MD through public databases’ queries.Our systematic review points lack of reliable data available on the use of MI-E in patients with NMD. It highlights the French particularity of using IPPB. The scientific evidence does not support the use of these MD but healthcare professionals are faced with the reality of medical practice. They consider these MD effective and want to keep their refund. This can be explained by the few available alternatives and the home-used possibility of these non-invasive MD. This is the only assessment of these MD conducted by an agency. The patient population treated with MI-E and IPPB has been estimated at 3 100 per year.This work stresses the need for further research to ensure best treatment for the patients such as randomized controlled trials (although difficult in a rare population) or explore other designs (cluster randomized trials).

Contextualização - A distrofia muscular de cinturas tipo 2A ou calpainopatia é uma desordem causada pelas mutações no gene CAPN3 (15q15.1) que codifica a calpaína. Entender como ocorre a perda de força muscular, da mobilidade articular e suas relações com a função nestes pacientes pode auxiliar na melhor compreensão da evolução da doença e indicar os biomarcadores pertinentes para o acompanhamento desta doença. Objetivo - Descrever e correlacionar a força muscular, a amplitude de movimentos articulares (ADM) e a função de um grupo de pacientes brasileiros com distrofia muscular de cinturas tipo 2A (calpainopatia). Método - Trata-se de um estudo transversal. A população estudada foi composta por 50 pacientes acompanhados no Centro de Pesquisa sobre o Genoma Humano e Células Tronco (CEGH-CEL) do Instituto de Biociências da Universidade de São Paulo, São Paulo, Brasil. Foram coletados os dados de força muscular (Medical Research Council - MRC), amplitude de movimento, escala de Vignos, escala de Medida de Independência Funcional (MIF), teste de caminhada de 10 metros (TC10m) e Escala Egen Klassifikation (EK). Para análise de correlação entre a força muscular e função foram utilizados os testes de correlação de Pearson e de Spearman. Resultados - Houve correlação positiva forte entre o índice de força muscular de cotovelo e o escore da Escala de Medida de independência funcional total (MIFT) (rho=0.70) e correlação negativa forte entre a Escala de Vignos e escore da MIFT (rho= -0.90). No teste de caminhada de 10 metros, a média do tempo utilizado pelos participantes foi de 17.82 segundos. Os resultados mostraram correlação negativa moderada entre o escore da escala EK e o índice de força muscular (MRC) dos segmentos corporais do cotovelo (rho= -0.51) e punho (r= -0.40) para o subgrupo cadeirantes. A amplitude de movimento não é um biomarcador pertinente para o acompanhamento da doença, pois não apresentou correlação com as demais variáveis deste estudo. A maioria dos pacientes apresentou limitações articulares na região de joelho e tornozelo, condizentes com outras pesquisas. A comparação da força muscular entre os músculos extensores dos joelhos direito e esquerdo mostrou diferença significativa (p < 0.02). Conclusão - Amostra brasileira apresentou incidência similar com os países do continente europeu (32%). Os escores de força muscular mostraram correlação com a função motora. Nossos achados permitem determinar, com melhor embasamento, os biomarcadores funcionais força muscular e função como os mais indicados na prática clínica e de pesquisa / Contextualization - Limb-girdle muscular dystrophy type 2A or calpainopathy is a disorder caused by mutation in the CAPN3 gene (15q15.1) that codes for calpain. Understanding how loss of muscular strength, joint mobility and their relationship with the function in these patients can help in better understanding the evolution of the disease and indicate the biomarkers pertinent to the follow-up of this disease. Objective - To describe and correlate muscle strength, range of joint movements (ROM) and function of a group of Brazilian patients with limb-girdle muscular dystrophy type 2A (calpainopathy). Method - This is a cross-sectional study. The studied population was composed for 50 patients at the Center for the Study of the Human Genome (CSHG) of the Institute of Biosciences of the University of São Paulo, São Paulo, Brazil. The data recorded were muscle strength (Medical Research Council - MRC), range of motion, Vignos scale, Functional Independence Measure (FIM), 10-meter walk test and Egen Klassifikation scale (EK). Para análise de correlação entre a força muscular e função foram utilizados os testes de correlação de Pearson e de Spearman. Results - There was a strong positive correlation between MRC and FIM (rho=0.70) and negative correlation between the Vignos Scale and FIM (rho= -0.90). The 10-meter walk test, the mean time used by participants was 17.82 seconds. The results showed a moderate negative correlation between the EK scale score and the MRC of the elbow (rho = -0.51) and wrist (r = -0.40) for the wheelchair subgroup. The range of motion is not a biomarker pertinent to the disease follow-up, since it did not present a correlation with the other variables of this study. The patients had contractures around the knee and ankle, is in keeping with what other studies. The comparison of muscle strength between the extensor muscles of the right and left knees showed a significant difference (p < 0.02). Conclusion - Brazilian sample had an incidence similar with the countries of the European continent (32%). The scores of muscle strength and motor function showed correlation. Our findings allow us to determine, with better foundation, functional biomarkers muscle strength and function as the most indicated in clinical practice and research

INTRODUÇÃO. As crianças dependentes de ventilação mecânica constituem um dos grupos de pacientes que mais utilizam de recursos de saúde em pediatria. Uma de suas características é o longo tempo de permanência hospitalar, o que diminui a disponibilidade de leitos para novas internações, principalmente em unidades de terapia intensiva. Neste trabalho descrevemos o perfil desta população através do conceito de criança com complexidade médica. Analisamos a potencial disponibilização de leitos em unidades de terapia intensiva decorrente da transferência de pacientes para unidades para pacientes dependentes de ventilação mecânica. MÉTODOS: A população de estudo foi constituída por pacientes internados na unidade de pediatria do Hospital Auxiliar de Suzano, e os critérios de inclusão foram: estar internado entre janeiro de 2001 e dezembro de 2010, e estar em ventilação mecânica por um período de pelo menos de três meses, após falha no desmame. Foram levantadas as suas características de acordo os quatro domínios do conceito de criança com complexidade médica, que são: doença crônica grave, limitações funcionais (mensuradas pelo índice de Barthel), utilização de recursos de saúde (medida em tempo de permanência), e necessidades das famílias devido à condição da criança (mensurada pela necessidade de benefício financeiro pelo estado). RESULTADOS: Foram contabilizadas 65 internações, correspondentes a 54 pacientes. Identificaram-se 30 doenças de base, sendo que as mais frequentes foram: encefalopatia hipóxico-isquêmica, atrofia muscular espinhal tipo I e hidrocefalia. A maioria das internações foi proveniente de unidades de terapia intensiva (54%). As faixas etárias com maior número de crianças foram as menores de 1 ano e entre 1 e 4 anos. A mediana do tempo de permanência hospitalar do grupo foi de 194 dias. Na avaliação das limitações funcionais pelo índice de Barthel, foi detectado que 50 pacientes apresentam pontuação zero (total dependência de cuidados) e quatro apresentaram 40 pontos (num máximo de 100). Foram levantados dados sociais de 31 famílias de pacientes (57%). Dez famílias receberam a concessão do benefício de prestação continuada (32%). A renda média destas famílias foi de 1,7 salários-mínimos, enquanto que a das famílias que não receberam era de 5 salários-mínimos. As internações ocuparam 26.751 pacientes/dia na unidade de pediatria, sendo que 14.445 pacientes/dia correspondem a internações provenientes de unidades de terapia intensiva. Isto possibilitou nestas unidades a disponibilização em potencial de 120 leitos/dia por mês, ou 18 internações/mês, em média, durante dez anos. CONCLUSÕES: As crianças dependentes de ventilação mecânica consomem grande volume de recursos, o que é expresso pelo longo tempo de permanência hospitalar. Isto afeta o atendimento de outros pacientes, ao diminuir a disponibilidade de leitos para internação. Fatores que influenciam este longo tempo de permanência são a sua elevada utilização de recursos, suas limitações funcionais, e o perfil socioeconômico das famílias. A transferência destes pacientes para unidades para dependentes de ventilação mecânica melhora a disponibilidade de leitos nas unidades de terapia intensiva, porém sua capacidade de atendimento é limitada. Políticas de saúde, como programas de cuidado domiciliar, podem provavelmente reduzir este problema / INTRODUCTION: Children who are dependent on mechanical ventilation are a group of patients with one of the highest health resource utilization in pediatrics. One of their features is the long hospital stays, which reduces bed availability for new admissions, especially in intensive care units. In this study the characteristics of this group are described, through the concept of children with medical complexity. We analyze potential bed availability in intensive care units as a consequence of transferring these patients to a unit for mechanical ventilation dependent patients. METHODS: The population of study was constituted by patients from the pediatric unit of Hospital Auxiliar de Suzano, and the criteria for admission to the study were: to be hospitalized between January/2001 to December/2010, and to be in mechanical ventilation for at least three months, after fail to wean. Their characteristics were studied according to the four domains of the concept of children with medical complexity, which are: severe chronic disease, severe functional limitations (measured by the Barthel Index), high health resource utilization (measured by length of stay), e family necessities due to the child\'s condition (measured by necessity of state financial aid). RESULTS: We counted 65 admissions, due to 54 patients. Thirty different diseases were identified, of which the most frequent were: hypoxic-ischemic encephalopathy, spinal muscular atrophy type I, and hydrocephalus. Most of admissions came from intensive care units (54%). The age groups with greatest number of children children were those bellow 1 year and those between 1 and 4 years. The median of the length of stay was 194 days. Functional limitation assessment through Barthel index found that 50 patients had zero points (total care dependency), and four had 40 points in that scale (maximum was 100). It was possible to access social data from 31 families (57%). Ten families received a state financial aid (32%). The average income from these families was 1.7 minimum salaries, while the average income from families which did not receive that aid was 5 minimum salaries. The admissions occupied 26751 patient-days in the pediatric unit, from which 14445 patient-days were related to admissions which came from intensive care units. These admissions have made possible the potential availability of 120 bed-days per month in the intensive care units, or an average of 18 new admissions per month, during ten years. CONCLUSION: Children dependent on mechanical ventilation needs a great amount of health resources, which is expressed by their long length of stay in hospitals. This situation affects the care of other children by reducing bed availability for new admissions. The factors that influence this length of stay are their high resource utilization, their functional limitations, and the social and economical profile of their families. The transfer of these children to units for mechanical ventilation dependent patients improves bed availability in intensive care units, but their capacity is limited. Health policies, like home care programs, can probably reduce these problems

INTRODUÇÃO. As crianças dependentes de ventilação mecânica constituem um dos grupos de pacientes que mais utilizam de recursos de saúde em pediatria. Uma de suas características é o longo tempo de permanência hospitalar, o que diminui a disponibilidade de leitos para novas internações, principalmente em unidades de terapia intensiva. Neste trabalho descrevemos o perfil desta população através do conceito de criança com complexidade médica. Analisamos a potencial disponibilização de leitos em unidades de terapia intensiva decorrente da transferência de pacientes para unidades para pacientes dependentes de ventilação mecânica. MÉTODOS: A população de estudo foi constituída por pacientes internados na unidade de pediatria do Hospital Auxiliar de Suzano, e os critérios de inclusão foram: estar internado entre janeiro de 2001 e dezembro de 2010, e estar em ventilação mecânica por um período de pelo menos de três meses, após falha no desmame. Foram levantadas as suas características de acordo os quatro domínios do conceito de criança com complexidade médica, que são: doença crônica grave, limitações funcionais (mensuradas pelo índice de Barthel), utilização de recursos de saúde (medida em tempo de permanência), e necessidades das famílias devido à condição da criança (mensurada pela necessidade de benefício financeiro pelo estado). RESULTADOS: Foram contabilizadas 65 internações, correspondentes a 54 pacientes. Identificaram-se 30 doenças de base, sendo que as mais frequentes foram: encefalopatia hipóxico-isquêmica, atrofia muscular espinhal tipo I e hidrocefalia. A maioria das internações foi proveniente de unidades de terapia intensiva (54%). As faixas etárias com maior número de crianças foram as menores de 1 ano e entre 1 e 4 anos. A mediana do tempo de permanência hospitalar do grupo foi de 194 dias. Na avaliação das limitações funcionais pelo índice de Barthel, foi detectado que 50 pacientes apresentam pontuação zero (total dependência de cuidados) e quatro apresentaram 40 pontos (num máximo de 100). Foram levantados dados sociais de 31 famílias de pacientes (57%). Dez famílias receberam a concessão do benefício de prestação continuada (32%). A renda média destas famílias foi de 1,7 salários-mínimos, enquanto que a das famílias que não receberam era de 5 salários-mínimos. As internações ocuparam 26.751 pacientes/dia na unidade de pediatria, sendo que 14.445 pacientes/dia correspondem a internações provenientes de unidades de terapia intensiva. Isto possibilitou nestas unidades a disponibilização em potencial de 120 leitos/dia por mês, ou 18 internações/mês, em média, durante dez anos. CONCLUSÕES: As crianças dependentes de ventilação mecânica consomem grande volume de recursos, o que é expresso pelo longo tempo de permanência hospitalar. Isto afeta o atendimento de outros pacientes, ao diminuir a disponibilidade de leitos para internação. Fatores que influenciam este longo tempo de permanência são a sua elevada utilização de recursos, suas limitações funcionais, e o perfil socioeconômico das famílias. A transferência destes pacientes para unidades para dependentes de ventilação mecânica melhora a disponibilidade de leitos nas unidades de terapia intensiva, porém sua capacidade de atendimento é limitada. Políticas de saúde, como programas de cuidado domiciliar, podem provavelmente reduzir este problema / INTRODUCTION: Children who are dependent on mechanical ventilation are a group of patients with one of the highest health resource utilization in pediatrics. One of their features is the long hospital stays, which reduces bed availability for new admissions, especially in intensive care units. In this study the characteristics of this group are described, through the concept of children with medical complexity. We analyze potential bed availability in intensive care units as a consequence of transferring these patients to a unit for mechanical ventilation dependent patients. METHODS: The population of study was constituted by patients from the pediatric unit of Hospital Auxiliar de Suzano, and the criteria for admission to the study were: to be hospitalized between January/2001 to December/2010, and to be in mechanical ventilation for at least three months, after fail to wean. Their characteristics were studied according to the four domains of the concept of children with medical complexity, which are: severe chronic disease, severe functional limitations (measured by the Barthel Index), high health resource utilization (measured by length of stay), e family necessities due to the child\'s condition (measured by necessity of state financial aid). RESULTS: We counted 65 admissions, due to 54 patients. Thirty different diseases were identified, of which the most frequent were: hypoxic-ischemic encephalopathy, spinal muscular atrophy type I, and hydrocephalus. Most of admissions came from intensive care units (54%). The age groups with greatest number of children children were those bellow 1 year and those between 1 and 4 years. The median of the length of stay was 194 days. Functional limitation assessment through Barthel index found that 50 patients had zero points (total care dependency), and four had 40 points in that scale (maximum was 100). It was possible to access social data from 31 families (57%). Ten families received a state financial aid (32%). The average income from these families was 1.7 minimum salaries, while the average income from families which did not receive that aid was 5 minimum salaries. The admissions occupied 26751 patient-days in the pediatric unit, from which 14445 patient-days were related to admissions which came from intensive care units. These admissions have made possible the potential availability of 120 bed-days per month in the intensive care units, or an average of 18 new admissions per month, during ten years. CONCLUSION: Children dependent on mechanical ventilation needs a great amount of health resources, which is expressed by their long length of stay in hospitals. This situation affects the care of other children by reducing bed availability for new admissions. The factors that influence this length of stay are their high resource utilization, their functional limitations, and the social and economical profile of their families. The transfer of these children to units for mechanical ventilation dependent patients improves bed availability in intensive care units, but their capacity is limited. Health policies, like home care programs, can probably reduce these problems

Tension-Type Headache (TH) is highly prevalent and associated with significant personal and social cost. The causes of TH are unclear, precluding optimal treatment or prevention at present. Stress is a well-documented correlate and trigger of TH activity, however the causal significance has not been experimentally demonstrated to date. Similarly, the mechanisms by which stress contributes to TH, if in fact it does, are not clearly understood. Findings of increased pain sensitivity in TH sufferers suggests TH pathophysiology may involve dysfunction in peripheral and/or central nervous system processing of pain. Studies on animals and healthy humans demonstrate that stress can increase pain sensitivity by affecting peripheral and central pain mechanisms proposed as dysfunctional in TH. It has therefore been proposed that stress may contribute to TH through aggravating already increased pain sensitivity in TH sufferers. However, this hypothesis has not been adequately examined in TH sufferers to date. Addressing the above issues, the present project conducted seven studies examining relationships between stress, pain sensitivity, and headache activity in TH sufferers. The aim was to test the hypothesis that stress contributes to TH by aggravating already increased pain sensitivity in TH sufferers. Studies 1 and 2 demonstrated increased general arousal and complex temporal relationships between general arousal and headache activity in the natural environment in Episodic TH (ETH) sufferers. In Study 3, experimentally induced stress of brief duration increased pressure pain sensitivity at the head in Chronic TH (CTH) sufferers more than in healthy controls. Study 4 found CTH sufferers to have increased levels of daily stress, increased pericranial muscle tenderness, and reduced pain thresholds, which were inter-related. Both daily stress and pain sensitivity were predictive of prospective daily headache activity. In Study 5, an experimental model demonstrated that stress-induced headache was associated with stress-induced increase in pericranial muscle tenderness and reduction in pressure pain thresholds at head and hand. Additionally, induced stress reduced pain tolerance and increased pain intensity ratings to cold pressor more in TH sufferers than in healthy controls (Study 7). Finally, TH sufferers were found to have abnormal temporal summation of pressure pain and impaired noxious inhibition of temporal summation compared to healthy controls, however neither temporal summation nor noxious inhibition of temporal summation were affected by induced stress (Study 6). Together, the results support the hypotheses: 1) Stress contributes to both ETH and CTH, and 2) Stress contributes to CTH through aggravating already increased pain sensitivity in CTH sufferers. Impaired pain inhibition and increased wind-up may be underlying abnormalities contributing to increased pain sensitivity in CTH sufferers.

Orientadores: Mônica Corso Pereira, Ilma Aparecida Paschoal, Ivete Alonso Bredda Saad / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T19:56:31Z (GMT). No. of bitstreams: 1 Ferraresso_Amanda_M.pdf: 1661408 bytes, checksum: 4e7bfa4f33f4937d9eb361e7a9a60e42 (MD5) Previous issue date: 2013 / Resumo: A Esclerose Lateral Amiotrófica (ELA) é uma desordem progressiva que envolve a degeneração dos neurônios motores em todos os níveis. A falência respiratória é a principal causa de morte nos pacientes com ELA e está diretamente relacionada com a disfunção muscular respiratória, em geral será tardia e precipitada por uma infecção respiratória. Objetivos: (1) Avaliar clínica e funcionalmente o comprometimento respiratório dos indivíduos portadores de esclerose lateral amiotrófica (ELA) e sua evolução com um programa de exercícios respiratórios e orientações domiciliares. (2) Traduzir para a língua portuguesa e avaliar a reprodutibilidade mediata da aplicação do questionário Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), em pacientes com ELA nascidos no Brasil. (3) Buscar a detecção precoce de distúrbios da deglutição por meio de questionários específicos e do exame salivograma. (4) A partir da análise dos desfechos clínicos (pacientes sem suporte pressórico, ventilação invasiva (VI) ou óbito), avaliar se alguma das medidas como capacidade vital forçada (CVF), pressões respiratórias máximas (PImax= pressão inspiratória máxima e PEmax= pressão máxima expiratória), pico de fluxo de tosse (PFT), questionários doença-específicos: amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) e amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-40), ajudariam na previsão do prognóstico da doença. Metodologia: foi realizado um estudo de coorte prospectivo, não controlado. No período de maio de 2010 a dezembro de 2011, todos os pacientes com diagnóstico de ELA, que frequentavam o ambulatório de doenças neuromusculares foram considerados para participar do estudo. O questionário ALSFRS-R foi aplicado no início da pesquisa e após 15 dias, para o processo de tradução e avaliação do instrumento. Foram avaliadas trimestralmente as variáveis de CVF (sentado ? supino), PImax, PEmax, PFT, SpO2 e questionários doença-específicos (ALSFRS-R e ALSAQ-40), ao longo de um período de 18 meses, exceto o radiograma de tórax e salivograma, avaliados somente ao início da pesquisa. Na evolução dos pacientes que participaram do programa de exercícios respiratórios, os pacientes foram separados em dois grupos (F1 e F2), com maior e menor número de sessões de fisioterapia, respectivamente. Resultados: Foram considerados para inclusão na pesquisa 32 pacientes, sendo incluídos 14 indivíduos efetivamente. A um nível de 5% foi encontrada significativa correlação entre as notas obtidas no questionário ALSFRS-R (p=0,001) nos dois momentos, o que permitiu a validação da versão na língua portuguesa. Das variáveis comparadas entre os grupos F1 e F2 apenas o PFT foi diferente entre os grupos, com valores de 125 e 225 L/min respectivamente (p=0,03). O PFT também foi a única variável que mostrou diferença entre o grupo de VI ou óbito vs pacientes sem suporte pressórico, com valores de 140 e 225 L/min, respectivamente (p= 0,007). Conclusões: O PFT, um exame simples, de fácil manuseio entre os clínicos e de baixo custo, pode ter um papel na avaliação do prognóstico destes doentes, além de auxiliar a traçar condutas que poderiam beneficiá-los em uma fase de maior comprometimento funcional / Abstract: The Amyotrophic Lateral Sclerosis (ALS) is a progressive disorder involving degeneration of motor neurons at all levels. Respiratory failure is the leading cause of death in patients with ALS and is directly related to respiratory muscle dysfunction, usually late and will be precipitated by a respiratory infection. Objectives : ( 1 ) To evaluate the clinical and functional respiratory impairment of individuals with amyotrophic lateral sclerosis (ALS ) and its evolution with a program of breathing exercises and guidance at home; ( 2 ) Translate to Portuguese and to assess the mediated reproducibility of the Amyotrophic Lateral Sclerosis Functional Rating Scale -Revised ( ALSFRS -R ) questionnaire, in patients with ALS born in Brazil; ( 3 ) Search for the early detection of swallowing disorders through specific interviews and salivagram examination; ( 4 ) iii) From the analysis of clinical outcomes data to assess whether lung function and disease specific questionnaires may help predict the prognosis of patients with ALS. Methods: we conducted a prospective cohort study, not controlled. From May 2010 to December 2011, all patients diagnosed with ALS, who attended the outpatient neuromuscular diseases were considered for the study. The ALSFRS -R questionnaire was administered at baseline and after 15 days for the translation process and evaluation of the instrument. Were evaluated quarterly variables FVC ( sitting / supine) , MIP, MEP , PCF , SpO2 and disease-specific questionnaires ( ALSFRS - R and ALSAQ - 40 ) over a 18 month period , except the chest X-ray and salivagram, evaluated only the beginning of research. The outcome of patients who participated in the program of breathing exercises, patients were separated into two groups (F1 and F2), with the highest and lowest number of physiotherapy sessions, respectively. Results: We considered for inclusion in the study 32 patients, including 14 individuals effectively. At a level of 5 % was found significant correlation between the scores obtained in the ALSFRS -R questionnaire (p = 0.001) in the two periods, which allowed the validation of the Portuguese version. Variables compared between groups F1 and F2 only the PFT was different between groups , with values of 125 and 225 L / min, respectively ( p = .03 ) . The PFT was also the only variable that showed a difference between the VI group of patients without or death vs. pressure support , with values of 140 and 225 L / min, respectively (p = 0.007). Conclusions : The PFT , a simple test , easy handling between the clinical and cost , may have a role in assessing the prognosis of these patients , and help to trace behaviors that could benefit them in a stage of greater functional impairment / Mestrado / Clinica Medica / Mestra em Ciências

Nous avons généré des souris déficientes pour les gènes codant pour les échangeurs Na/Ca de type I (NCX1) et de type III (NCX3) afin d'étudier, in vivo, le rôle de ces deux protéines.<p>L‘analyse phénotypique des souris adultes totalement déficientes pour le gène Ncx1 (Ncx1-/-) n'a pu être menée étant donné que ces souris décèdent au cours du développement embryonnaire.<p>Les souris déficientes pour le gène Ncx3 (Ncx3-/-) sont viables et fertiles. Nous avons analysé l'effet de l'inactivation du gène Ncx3 dans le muscle squelettique et plus particulièrement au niveau de la jonction neuromusculaire.<p>L'analyse histologique des muscles squelettiques de souris Ncx3-/- a révélé des altérations des fibres musculaires caractérisées par la présence de foyers de fibres nécrotiques et d'infiltrats de cellules mononuclées.<p>L'analyse électromyographique classique a montré un électromyogramme anormal du muscle gastrocnémien de souris Ncx3-/-, révélant une affection neuromusculaire pré- et post-synaptique caractérisée par (i) la petitesse de l'amplitude de la réponse M au repos, (ii) le décrément après stimulation répétitive à basse fréquence, (iii) l'incrément après stimulation répétitive à haute fréquence et (iv) la facilitation post-exercice. L'électromyographie à fibre unique a révélé une MCD élevée et des blocages anormaux de la transmission neuromusculaire, reflétant une atteinte post-synaptique de la jonction neuromusculaire chez les souris Ncx3-/-. L'ensemble de ces anomalies électromyographiques sont les caractéristiques du syndrome myasthénique de Lambert-Eaton.<p>Finalement, pour déterminer les conséquences de l'inactivation du gène Ncx3 sur l'activité physique des souris Ncx3-/-, nous avons réalisé des tests comportementaux sur ces souris. Ces tests ont permis de détecter un épuisement et une faiblesse musculaire accrus à l'effort chez ces souris.<p>En conclusion, nos observations montrent que les souris Ncx3-/- présentent des anomalies électromyographiques similaires à celles du syndrome myasthénique de Lambert-Eaton. Ces résultats suggèrent que l'échangeur NCX3 est peut-être impliqué dans la pathogenèse de certaines formes de cette maladie.<p>Des études supplémentaires afin de confirmer notre hypothèse devront donc être réalisées.<p>/<p>We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein which mediates cellular Ca2+ efflux (forward mode) or Ca2+ influx (reverse mode) and thus controls intracellular Ca2+ concentration. NCX3-deficient mice (Ncx3-/-) present a skeletal muscle fiber necrosis and a defective neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of the muscle fibers and at the neuromuscular junction. The defective neuromuscular transmission is characterized by the presence of electromyographic abnormalities including low compound muscle action potential amplitude, a decremental response at low frequency nerve stimulation, an incremental response and a prominent post-exercise facilitation at high frequency nerve stimulation as well as neuromuscular blocks. The analysis of quantal transmitter release in Ncx3-/- neuromuscular junctions revealed an important facilitation superimposed on the depression of synaptic responses and an elevated delayed release during high frequency nerve stimulation. It is suggested that Ca2+ entering nerve terminals is cleared relatively slowly in the absence of NCX3, thereby enhancing residual Ca2+ and evoked and delayed quantal transmitter release during repetitive nerve stimulation. Our findings indicate that NCX3 plays an important role in vivo in the control of Ca2+ concentrations in the skeletal muscle fibers and at the neuromuscular junction.<p> / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

Objetivo: Determinar a responsividade do domínio subir e descer escada da escala de avaliação funcional em distrofia muscular de Duchenne (DMD), no período de um ano. Método: Participaram do estudo 26 pacientes com DMD. A análise utilizou o Tamanho do Efeito (ES) e a Média Padronizada de Resposta (SRM). Resultados: Atividade de subir escada: o ES mostrou responsividade baixa nos intervalos de avaliação de 3 meses (0,26; 0,35; 0,13; 0,17), baixa a moderada em 6 meses (0,58, 0,48; 0,33), moderada em 9 meses (0,70; 0,68) e alta em 1 ano (0,88). A análise com SRM mostrou responsividade baixa nos intervalos de avaliação de 3 meses (0,29; 0,38; 0,18 e 0,19), baixa a moderada em intervalos de 6 meses (0,59 e 0,51, 0,36), moderada em 9 meses (0,74 e 0,70) e alta em 1 ano (0,89). Atividade de descer escada: O ES apresentou responsividade baixa nos intervalos de avaliação de 3 meses (0,16; 0,25; 0,09; 0,08) e 6 meses (0,48; 0,35; 0,18), baixa a moderada em 9 meses (0,59, 0,44) e moderada em 1 ano (0,71). Análise com SRM mostrou responsividade baixa nos intervalos de 3 meses (0,25; 0,35; 0,12 e 0,09) e 6 meses (0,47; 0,38 e 0,21), moderada a baixa em 9 meses (0,62, 0,49) e moderada em 1 ano (0,74). Conclusão: A avaliação da atividade de subir escada, por meio da FES-DMD-D3, deve ser realizada em intervalos a partir de 9 meses, pois a responsividade é de moderada a alta. A avaliação do descer escadas deve ser realizada anualmente, pois houve responsividade moderada somente a partir de 12 meses / Objective: To determine the responsiveness of the domain up and down stair Functional Evaluation Scale for Duchenne Muscular Dystrophy (DMD) in one year follow-up. Method: The study included 26 patients with DMD. The analysis used the Effect Size (ES) and Standardized Response Mean (SRM) tests. Results: Climbing stairs activity: the ES test showed low responsiveness in the 3-month evaluation intervals (0.26; 0.35; 0.13; 0.17), low to moderate at 6 months (0.58, 0 48; 0.33), moderate in 9 months (0.70, 0.68) and high in one year (0.88). The SRM analysis showed low response in the 3 month evaluation interval (0.29, 0.38, 0.18 and 0.19), moderate to low every 6 months (0.59 and 51, 0, 36), moderate in 9 months (0.74 and 0.70) and high in one year (0.89). Down stairs activity: The ES test showed low responsiveness in the 3 month evaluation intervals (0.16; 0.25; 0.09; 0.08) and 6 months (0.48, 0.35, 0, 18), low to moderate at 9 months (0.59, 0.44) and moderate in 1 year (0.71). SRM Analysis showed low response at intervals of 3 months (0.25; 0.35; 0.12 and 0.09) and 6 months (0.47, 0.38 and 0.21), low to moderate 9 months (0.62, 0.49) and moderate in 1 year (0.74). Conclusion: The assessment of stair climbing up should be performed in 9 months or longer intervals, when responsiveness is moderate to high. Going down stairs assessment should be performed annually, because moderate responsiveness was observed in 1 year interval

A Distrofia Muscular Congênita (DMC) se caracteriza clinicamente por hipotonia e fraqueza muscular, retardo do desenvolvimento motor e retrações fibrotendíneas. Instrumentos de avaliação clínica, como as escalas funcionais, motoras e de qualidade de vida, têm como objetivo quantificar o impacto da doença sobre as atividades diárias da vida do paciente, além de auxiliarem na caracterização de grupos de estudo heterogêneos. Sendo a DMC altamente heterogênea, traçar o perfil funcional dos pacientes com diferentes subtipos seria útil para caracterizar padrões funcionais e auxiliar no tratamento em equipe multidisciplinar. Objetivos: Caracterizar o perfil de funcionalidade e qualidade de vida de pacientes com DMC de diferentes subtipos e correlacioná-lo com a força muscular e grau de amplitude de movimento. Metodologia: Em uma amostra de 18 pacientes com DMC com idade de 12 + 3,2 anos e 13 pacientes com outras miopatias congênitas com idade de 13 + 2,6 anos foram aplicados em três visitas (V1, V2 e V3) os questionários SF-36 e Índice de Barthel (IB), além de realizada avaliação físico-motora (goniometria, força muscular) seguido de correlação com a escala funcional MFM-32 (Medida de Função Motora). Resultados: Houve significativa queda na qualidade de vida em pacientes Merosina (-) e em outras formas de DMC. O índice de Barthel (IB) apontou \"grave dependência\" final em pacientes merosina (-) e \"moderada dependência\" em outras formas de DMC. A goniometria mostrou diminuição da movimentação global em todos os grupos articulares avaliados em pacientes com merosina (-). Em outras formas de DMC, houve exceção de diminuição apenas em articulação distal de membros superiores. A força de todos os grupos musculares é significativamente afetada em ambos os grupos. Pacientes merosina (-) mostram diminuição significativa de funcionalidade nas três dimensões da escala MFM-32 (D1, D2 e D3), e em outras formas de DMC, apenas diminuição em D2 e D3. Houve moderada correlação positiva entre força muscular e D1 da escala MFM-32, forte correlação positiva entre goniometria e D2 e D3 em pacientes com merosina (-), não havendo correlação entre nenhuma variável e MFM-32 em outras formas de DMC. Conclusão: Pacientes com DMC apresentaram perfil funcional \"gravemente dependente\", com diminuição da qualidade de vida, observada em cinco de oito quesitos do questionário SF-36. A força muscular e a amplitude de movimento articular foram afetadas de forma generalizada em ambos os grupos de pacientes. Pacientes com merosina (-) mostraram-se mais afetados funcionalmente em posturas eretas e transferências, sendo correlacionada positivamente com a força muscular dos grupos dessa tarefa / Congenital Muscular Dystrophy (CMD) is characterized by hypotonia and weakness, motor development delay and muscular contractures. Instruments of clinical assessment, such as functional motor and quality of life scales are essential to quantify the impact of the disease on daily activities of the patient\'s life in addition to helping in the characterization of heterogeneous study groups. As the DMC highly heterogeneous, trace the functional profile of patients with different subtypes would be useful to characterize functional patterns and aid in the treatment by a multidisciplinary team. Objectives: To characterize the functionality and quality of life of children with different subtypes of DMC and to correlate them with the degree of muscle strength and range of motion. Methods: In a sample of 18 patients with CMD (aged 12 + 3.2 years) and 13 patients with other congenital myopathies (aged 13 ± 2.6 years) were applied in three visits (V1, V2 and V3) the SF-36 and Barthel Index (BI), and performed physical-motor assessment (goniometry, muscle strength) followed by correlation with functional scale MFM-32 (motor Function Measure. ). Results: There was a significant decrease in the quality of life in patients Merosin (-) and other forms of CMD. IB indicated \"severe dependence\" final in Merosin patients (-) and \"moderate dependence\" in other forms of CMD. Goniometry showed a decrease of the overall joint movement in all groups evaluated in patients with merosin (-).In other forms of DMC was decreased joint movement in all joint groups, except for the distal joint of the upper limbs. The strength of each muscle group was significantly affected in both groups. Patients merosin (-) show a significant decrease in the functionality on the 3 dimensions of MFM-32 scale (D1, D2, D3) in patients with other forms of DMC only reduction in D2 and D3. There was a moderate positive correlation between muscle strength and D1 of the SF-32 scale, strong positive correlation between goniometry and D2 and D3 in patients with Merosin (-), there was no correlation between this variable and MFM-32 in other forms of CMD. Conclusion: Patients with CMD showed functional profile \"severely dependent\" to low quality of life observed in five of eight areas of the SF-36 questionnaire. Muscle strength and range of motion were affected in a generalized manner in both patient groups. Patients with Merosin (-) are even more affected functionally in standing and transfers being positively correlated with muscle strength of the groups of this task postures