Homage to Paula Coutinho ­ a pioneer in portuguese and worldwide neurogenetics / Homenagem a Paula Coutinho ­ uma pioneira da neurogenética portuguesa e mundial

This is a tribute to an outstanding Portuguese neurologist and researcher, Paula Coutinho (1941-2022), who specialized in the care and study of people with familial amyloidotic polyneuropathy and Machado-Joseph disease which she helped define. As a result, she collaborated with the inauguration of the Centro de Estudos de Paramiloidose Antônio Rodrigues de Mello (CEPARM) founded in 1984 at the University Hospital of the Federal University of Rio de Janeiro. Since then, we admire her commitment to science and patients.

Esta é uma homenagem a uma notável neurologista e pesquisadora portuguesa, Paula Coutinho (1941-2022), que se especializou no cuidado e estudo de pessoas com polineuropatia amiloidótica familiar e doença Machado-Joseph, que ela ajudou a definir. Como resultado, colaborou com a inauguração do Centro de Estudos de Paramiloidose Antônio Rodrigues de Mello (CEPARM) fundado em 1984 no Hospital Universitário da Universidade Federal do Rio de Janeiro. Desde então, admiramos o seu compromisso com a ciência e os pacientes.

Effect of speech therapy on quality of life in patients with spinocerebelar ataxia type 3 / Efeito da terapia fonoaudiológica na qualidade de vida de pacientes com ataxia espinocerebelar tipo 3

Abstract Background Individuals with spinocerebellar ataxia type 3 (SCA3) present communication and swallowing disorders, and consequent deterioration in quality of life (QOL). Objective To evaluate the impact of a speech therapy rehabilitation program on the QOL of patients with SCA3. Methods All participants were randomly assigned to two groups, an intervention group receiving speech therapy (STG) and a control group (CG). The International Cooperative Ataxia Rating Scale scores were 32.4 ± 20.2, and the Scale for the Assessment and Rating of Ataxia scores were 11.8 ± 8.0. The intervention consisted of a 12-session speech therapy rehabilitation program with oral, pharyngeal, and laryngeal strengthening exercises—the so-called ATAXIA-Myofunctional Orofacial and Vocal Therapy (A-MOVT). They all were submitted to pre- and postintervention evaluations using the World Health Organization's Quality of Life (WHOQOL-BREF) assessment, as well as the Living with Dysarthria (LwD), Quality of Life in Swallowing Disorders (SWAL-QOL), and Food Assessment Tool (EAT-10). Results The study sample consisted of 48 patients with SCA3 (STG = 25; CG = 23), mean age was 47.1 ± 11.4 years; mean age at symptom onset was 36.9 ± 11.3 years; disease duration was 11.9 ± 13.3 years. After the 3-month intervention, there were significant changes in the QOL in the STG compared with the CG, when assessed by the LwD (179.12 ± 62.55 vs. 129.88 ± 51.42, p < 0.001), SWAL-QOL (869.43 ± 153.63 vs. 911.60 ± 130.90, p = 0.010), and EAT-10 (5.16 ± 7.55 vs. 2.08 ± 3.85, p = 0.018). Conclusions Patients with SCA3 should receive continuous speech therapy as part of the A-MOVT program, because therapy helps to improve difficulty swallowing and dysarthria.

Resumo Antecedentes Indivíduos com ataxia espinocerebelar tipo 3 (AEC3) apresentam distúrbios da comunicação e deterioração da deglutição e, consequentemente, na qualidade de vida (QV). Objetivo Avaliar o impacto de um programa de reabilitação fonoaudiológica na QV em pacientes com AEC3. Métodos Todos os participantes foram alocados aleatoriamente em dois grupos, um grupo intervenção que recebeu terapia fonoaudiológica (GTF) e um grupo controle (GC). As pontuações das escalas: International Cooperative Ataxia Rating Scale (ICARS) foram 32,4 ± 20,2 e da Scale for the Assessment and Rating of Ataxia (SARA) foram 11,8 ± 8,0. A intervenção consistiu em um programa de reabilitação fonoaudiológica de 12 sessões composto por exercícios de fortalecimento oral, faríngeo e laríngeo - denominados ATAXIA - Terapia Miofuncional Orofacial e Vocal (A-TMOV). Todos foram submetidos a avaliações pré e pós-intervenção por meio dos protocolos World Health Organization's Quality of Life (WHOQOL-BREF), Vivendo com Disartria (VcD), Quality of Life in Swallowing Disorders (SWAL-QOL) e Food Assessment Tool (EAT-10). Resultados A amostra foi composta por 48 pacientes com AEC3 (25 no GTF e 23 no GC), média de idade 47,1 ± 11,4anos; média de idade de início dos sintomas 36,9 ± 11,3anos; duração da doença 11,9 ± 13,3anos. Após intervenção de três meses, houve mudanças significativas na QV no GTF em comparação com o GC quando avaliado pelo VcD (179,12 ± 62,55 versus129,88 ± 51,42, p < 0,001), SWAL-QOL (869,43 ± 153,63 versus 911,60 ± 130,90, p = 0,010), EAT-10 (5,16 ± 7,55 versus 2,08 ± 3,85, p = 0,018). Conclusões Pacientes com AEC3 devem receber terapia fonoaudiológica contínua como parte do programa A-TMOV, pois a terapia ajuda a melhorar a dificuldade de deglutição e a disartria.

Eficácia de terapia de fala em grupo para pacientes com a doença de Machado Joseph: uma série de casos / Effectiveness of group speech therapy for patients with Machado Joseph Disease: a series of cases / Eficiencia de la terapia del habla en grupo para pacientes con Enfermedad de Machado Joseph: una serie de casos

Objetivo: Verificar o benefício de terapia fonoaudiológica em grupo na inteligibilidade de fala de pacientes com Doença de Machado Joseph (DMJ). Método: Realizou-se uma série de casos, com pacientes atendidos em um ambulatório de fonoaudiologia para adultos neurodegenerativos em um hospital de referência no sul do Brasil. Foram incluídos pacientes com o diagnóstico molecular de DMJ. Realizaram-se coletas de fala pré e pós-intervenção. Posteriormente, os trechos de fala passaram por análise perceptiva-auditiva por 3 fonoaudiólogas treinadas e calibradas a um índice Kappa ≥ 0.90, cegas às coletas de fala e por análise acústica no software Praat. A terapia fonoaudiológica foi realizada em grupo, composta por quatro sessões semanais de cinquenta minutos. Cada sessão foi dividida entre exercícios de fala e orientação sobre estratégias para otimizar a comunicação. Resultados: A amostra foi composta por 5 pacientes com média de idade de 39,8 anos (±16,51) e tempo de doença de 10 anos (±8,15). Quatro (80%) participantes receberam diagnóstico fonoaudiológico inicial de disartria leve e um (20%) de disartria moderada. Após a intervenção, não houve melhora no diagnóstico de disartria, contudo verificou-se que 60% (n=3) dos participantes apresentaram melhora na articulação, 40% (n=2) na prosódia e ressonância e 40% (n=2) apresentaram piora na respiração. Na análise acústica observou-se melhora no tempo máximo de fonação (TMF) em 3 (60%) dos 5 pacientes. Conclusão: Verificou-se melhora na funcionalidade da fala através da análise perceptiva auditiva, porém com pouca melhora em parâmetros específicos da análise acústica.

Objective: To verify the benefit of group speech therapy in speech intelligibility of patients with Machado Joseph's disease (MJD). Methods: A series of cases was carried out, with patients seen in a speech therapy clinic for neurodegenerative adults in a referral hospital in southern Brazil. Patients with the molecular diagnosis of MJD were included. Speech recordings were performed before and after the intervention. Subsequently, the speech excerpts underwent auditory-perceptual analysis by 3 trained speech therapists and calibrated to a Kappa index ≥ 0.90, blind to speech collections and acoustic analysis in the Praat software. Speech therapy was performed in a group, consisting of four weekly sessions of fifty minutes. Each session was divided between speech exercises and guidance on strategies to optimize communication. Results: The sample consisted of 5 patients with a mean age of 39.8 years (± 16.51) and disease duration of 10 years (± 8.15). Four (80%) participants received an initial speech therapy diagnosis of mild dysarthria and one (20%) of moderate dysarthria. After the intervention, there was no improvement in the diagnosis of dysarthria, however it was found that 60% (n = 3) of the participants showed improvement in the speech motor bases: articulation, 40% (n = 2), prosody and resonance and 40% (n = 2) worsened in breathing. The acoustic analysis showed an improvement in maximum phonation time (MPT) in 3 (60%) of the 5 patients. Conclusion: Despite the little improvement in specific parameters of the acoustic analysis, there was an improvement in speech functionality from the auditory perceptual analysis, improving the speech intelligibility of this sample.

Objetivo: Verificar el beneficio de la logopedia grupal en la inteligibilidad del habla de pacientes con enfermedad de Machado Joseph (EMJ). Metodos: Se realizó una serie de casos, con pacientes atendidos en una clínica de logopedia para adultos neurodegenerativos en un hospital de referencia en el sur de Brasil. Se incluyeron pacientes con diagnóstico molecular de EMJ. Se realizaron grabación del habla antes y después de la intervención. Posteriormente, los extractos del habla se sometieron a un análisis auditivo-perceptivo por 3 logopedas capacitados y calibrados con un índice Kappa ≥ 0,90, ciegos a las grabación del habla y al análisis acústico en el software Praat. La logopedia se realizó en grupo, consistente en cuatro sesiones semanales de cincuenta minutos. Cada sesión se dividió entre ejercicios de habla y orientación sobre estrategias para optimizar la comunicación. Resultados: La muestra estuvo formada por 5 pacientes con una edad media de 39,8 años (± 16,51) y una duración de la enfermedad de 10 años (± 8,15). Cuatro (80%) participantes recibieron un diagnóstico inicial de terapia del habla de disartria leve y uno (20%) de disartria moderada. Tras la intervención, no hubo mejoría en el diagnóstico de disartria, sin embargo se encontró que el 60% (n = 3) de los participantes mostró mejoría en las bases motoras del habla: articulación, 40% (n = 2), prosodia y resonancia. y el 40% (n = 2) empeoró en la respiración. El análisis acústico mostró una mejora en el tiempo máximo de fonación (TMF) en 3 (60%) de los 5 pacientes. Conclusion: A pesar de la pequeña mejora en los parámetros específicos del análisis acústico, hubo una mejora en la funcionalidad del habla a partir del análisis de percepción auditiva, mejorando la inteligibilidad del habla de esta muestra.

Nystagmus may be the first neurological sign in early stages of spinocerebellar ataxia type 3 / Nistagmo pode ser o primeiro sinal neurológico nos estágios precoces da ataxia espinocerebelar tipo 3

Abstract Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant spinocerebellar ataxia worldwide. Almost all patients with SCA3 exhibit nystagmus and/or saccades impairment. Objective: To investigate the presence of nystagmus as an early neurological manifestation, before ataxia, in some patients with SCA3 in the first six months of the disease. Methods: We evaluated a series of 155 patients with clinically and molecularly proven SCA3 between 2013 and 2020. Data regarding sex, age, age at onset, disease duration, CAG repeat expansion length, first symptom, presence of ataxia, scores on SARA and ICARS scales, and presence and characteristics of nystagmus were collected. Results: We identified seven patients with symptomatic SCA3 who presented with isolated nystagmus. In these seven individuals the age at onset ranged from 24 to 57 years, and disease duration from four to six months. Conclusions: Our study showed that nystagmus may be the first neurological sign in SCA3. This clinical observation reinforces the idea that the neurodegenerative process in SCA3 patients may start in vestibular system connections or in flocculonodular lobe. This study adds relevant information about pre-symptomatic features in SCA3 that may work as basis for a better understanding of brain degeneration and for future therapeutic clinical trials.

RESUMO Antecedentes: A ataxia espinocerebelar tipo 3 (SCA3) é a ataxia espinocerebelar de herança autossômica dominante mais comum em todo o mundo. Quase todos os pacientes com SCA3 têm nistagmo e/ou comprometimento das sácades. Objetivo: Investigar a presença de nistagmo como manifestação neurológica precoce, antes do surgimento da ataxia, em alguns pacientes com SCA3 nos primeiros seis meses de doença. Métodos: Foram avaliados 155 pacientes com diagnóstico clínico e molecular de SCA3, entre 2013 e 2020, em relação a sexo, idade, idade de início, duração da doença, expansão da repetição CAG, primeiro sintoma, presença de ataxia, pontuações nas escalas SARA e ICARS, e presença e caracterização de nistagmo. Resultados: Identificamos sete pacientes com SCA3 que apresentavam nistagmo isolado. A idade de início da doença nesses pacientes variou de 24 a 57 anos e a duração da doença variou de quatro a seis meses. Conclusões: O nosso estudo mostrou que o nistagmo pode ser o primeiro sinal neurológico na SCA3. Essa observação clínica reforça a ideia de que o processo neurodegenerativo nos pacientes com SCA3 pode se iniciar nas conexões do sistema vestibular ou no lobo floculonodular. Este estudo adiciona informações relevantes sobre características pré-sintomáticas na SCA3 e que podem servir de base para melhor entendimento da degeneração cerebral e para futuras terapias.

Atuação fonoaudiológica na doença de Machado-Joseph: relato de caso / Effect of speech-language therapy in Machado-Joseph disease: case report

RESUMO A doença de Machado-Joseph é a forma de ataxia espinocerebelar de maior prevalência no Brasil e tem como alguns dos principais sinais clínicos a disfagia e a disartria. Este relato de caso objetivou verificar os efeitos da intervenção intensiva fonoaudiológica em um paciente com a doença de Machado-Joseph. A coleta de dados foi realizada a partir de protocolos de avaliação de fala e deglutição e protocolos de autoavaliação de qualidade de vida, em relação à deglutição e comunicação. Também foram realizadas avaliações quantitativas de parâmetros acústicos. A intervenção foi administrada por meio do método Lee Silverman, programa intensivo que visa ao aumento da intensidade vocal. A partir das avaliações clínicas e instrumentais, os resultados demonstraram melhora em todas as bases motoras de fala, respiratória, fonatória, ressonantal, articulatória e a prosódia, além da diminuição dos sinais disfágicos. Na qualidade vocal, houve diminuição de rouquidão e instabilidade, regularização de jitter e shimmer, aumento da intensidade vocal, melhora na coordenação de palavras e frases por expiração e, ainda, melhora discreta da diadococinesia. Após intervenção, a autoavaliação de qualidade de vida relacionada à deglutição apresentou valores iguais ou maiores nos domínios diretamente ligados à alimentação, porém, os domínios emocionais diminuíram. O paciente relatou satisfação em todos os domínios da qualidade de vida em voz e foram obtidos valores maiores em todos os domínios. Concluiu-se que a intervenção intensiva beneficiou o participante e impactou positivamente sua qualidade de vida.

ABSTRACT Machado-Joseph disease is the most prevalent form of spinocerebellar ataxia in Brazil, and has dysphagia and dysarthria among its main clinical signs. This case report aims to ascertain the effects of intensive speech-language intervention in a patient with Machado-Joseph disease. Data collection was performed based on speech and swallowing assessment protocols and self-assessment protocols specific to swallowing-related and communication-related quality of life. Quantitative assessments of acoustic parameters were also performed. The intervention was administered through the Lee Silverman method, which is an intensive program aimed at increasing vocal intensity. The results of clinical and instrumental evaluations showed improvement in all motor parameters of speech (respiration, phonation, resonance, articulation, and prosody), besides a reduction in dysphagic signs. Regarding vocal quality, there was a decrease in hoarseness and instability, regularization of jitter and shimmer, increased vocal intensity, and improved coordination of words and phrases by expiration, as well as slight improvement of diadochokinesis. After intervention, self-assessment of swallowing-related quality of life was unchanged or improved in the domains directly related to food, but reduced in emotional domains. The patient reported satisfaction in all domains of voice-related quality of life, and scores were increased in all domains. We conclude that intensive intervention was beneficial for the participant and positively impacted their quality of life.

Assessment of Bone Mineral Density of Patients with Spinocerebellar Ataxia Type 3

OBJECTIVE: Machado-Joseph disease (MJD) is a spinocerebellar ataxia, and osteoporosis is a multifactor disease that may affect patients with neurologic conditions. The frequency of osteoporosis among MJD patients, however, has not been studied. The purpose of this study is to evaluate bone mineral density (BMD) and identify correlations between clinical factors and frequency of vertebral fractures in patients with MJD. METHODS: Clinical data, lumbar X-rays and BMD data were obtained in 30 patients with MJD. RESULTS: Ten patients (33.3%) showed low BMD in at least one of the sites studied based on Z-scores. The Z-score correlated directly with body mass index, and the femoral neck Z-score was inversely correlated with cytosine-adenine-guanine (CAG) expansion. There was no correlation between BMD and other clinical factors. Forty-three percent of the patients reported previous pathologic fractures. Five patients (16.7%) had at least one fracture detected by lumbar X-ray. CONCLUSION: Low BMD and fractures are frequent among MJD patients, and careful management of BMD may be beneficial for these patients.

Características clínicas de 63 pacientes con ataxia / Clinical features of 63 patients with ataxia

Background: Ataxia can be classified as genetic, sporadic or acquired. Aim: To report the clinical features of a group of patients with ataxia. Material and Methods: Review of medical records of patients consulting in a specialized center in movement disorders. Those records in which the diagnosis of "ataxia" or "ataxic syndrome" appeared, were selected for the review. Results: Of 4,282 records surveyed, the diagnosis of ataxia appeared in 95. After eliminating repeated or incomplete records, 63 were reviewed. Results: Ataxia was sporadic, genetic and acquired in 27, 22 and 14 patients, respectively. The mean age at presentation for genetic, acquired and sporadic ataxia was 24, 46 and 53 years respectively. All autosomal dominant ataxias were type 3 spinocerebellar ataxia (SCA). Friedrich's ataxia was the most common recessive form. Most sporadic forms of ataxia were multiple system atrophy with predominant cerebellar ataxia (MSA-C) subtype. Conclusions: Considering the heterogeneity of patients with ataxia, we propose a method to approach them.

Doença de Machado-Joseph no contexto da pessoa/família que a vivencia: alterações cotidianas e expectativas futuras / Enfermedad de Machado-Joseph en el contexto de la persona/familia que la vive: alteraciones cuotidianas y expectativas futuras / Machado-Joseph disease in the context of the person/familythat experiences it: daily changes and future expectations

Objetivo: conhecer as principais alterações cotidianas e as expectativas futuras vivenciadas pela pessoa/família com a doença de Machado-Joseph (DMJ). Métodos: Pesquisa exploratória, descritiva de abordagem qualitativa, realizada com uma pessoa com a DMJ e com cinco familiares, em uma cidade do Rio Grande do Sul. Os dados coletados durante uma visita domiciliar realizada no mês de abril de 2016, por meio de entrevista semiestruturada e observação participante, foram submetidos à análise de conteúdo. Resultados: Emergiram cinco categorias: (des)conhecimento da doença antes do diagnóstico; conhecimento da doença após o diagnóstico; dificuldades do diagnóstico; alterações vivenciadas após o diagnóstico; e expectativas para o futuro com a DMJ. Conclusão: Torna-se necessário mais investimento por parte dos profissionais da saúde, especialmente dos enfermeiros, na realização de estudos voltados a buscar auxiliar as pessoas/familiares que convivem com a DMJ.

Objective: to know the main daily changes and future expectations experienced by the person/family with Machado-Joseph disease. Methods: Exploratory, descriptive study of qualitative approach, carried out with a person with Machado-Joseph disease and with five relatives, in a city of Rio Grande do Sul. The data collected during a home visit conducted in April 2016 by. through semi-structured interviews and participant observation were subjected to content analysis. Results: Emerged five categories: (Des)knowledge of the disease before diagnosis; Knowledge of disease after the diagnosis; Difficulties of diagnosis; experienced changes after diagnosis; Expectations for the future with Machado-Joseph disease. Conclusion: It is necessary, more investment by health professionals, especially nurses, in conducting studies aimed to seek help people / families living with Machado-Joseph disease.

Objetivo: conocer las principales alteraciones cuotidianas y las expectativas futuras vividas por la persona/familia con la enfermedad de Machado-Joseph. Metodología: Investigación exploratoria, descriptiva de enfoque cualitativo, realizada con una persona con la enfermedad de Machado-Joseph y cinco miembros de la familia, en una ciudad del estado del Rio Grande do Sul (Brasil). Los datos recogidos durante una visitación domiciliar realizada en el mes de abril/2016, por medio de entrevista semiestructurada y observación participante, fueron sometidos al análisis de contenido. Resultados: Surgieron cinco categorías: (des)conocimiento de la enfermedad antes del diagnóstico; conocimiento de la enfermedad después del diagnóstico; dificultades del diagnóstico; alteraciones vividas después del diagnóstico; expectativas para el futuro con la enfermedad de Machado-Joseph. Conclusión: Es necesario más inversión por parte de los profesionales de la salud, especialmente de los enfermeros, en la realización de estudios direccionados al auxilio a las personas/familiares que conviven con la enfermedad de Machado-Joseph.

Paula Coutinho's outstanding contribution to the definition of Machado-Joseph disease / A excepcional contribuição de Paula Coutinho na definição da doença de Machado-Joseph

ABSTRACT Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is the most common form of autosomal dominant ataxia in the world. Paula Coutinho, a highly-regarded Portuguese neurologist worldwide, had a seminal participation in the definition of this disease, more than 40 years ago.

RESUMO A doença de Machado-Joseph, também conhecida como ataxia espinocerebelar tipo 3 (SCA3), representa a forma mais comum de ataxia hereditária autossômica dominante no mundo. Paula Coutinho, neurologista portuguesa de reputação mundial, teve participação fundamental na definição desta doença há mais de 40 anos.

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

El papel del psicólogo clínico en el contexto del consejo genético incluye brindar apoyo a los sujetos en riesgo en el proceso de toma de decisiones, independientemente de la decisión adoptada por el sujeto (conociendo o no el resultado de las pruebas genéticas). El estudio que se informa aborda la motivación para realizar las pruebas pre-sintomáticas (PPS) de sujetos en situación de riesgo para tres enfermedades: polineuropatía amiloide familiar (PAF), la enfermedad de Huntington (EH) y la enfermedad de Machado-Joseph (EMJ) y comparar con la motivación para realizar las PPS para hemocromatosis (HH). La muestra consistió en 213 sujetos portugueses que tenían riesgo genético para contraer las tres enfermedades y 31 sujetos en situación de riesgo genético para contraer hemocromatosis. Ellos fueron evaluados con una entrevista para obtener datos sociodemográficos y debían responder a una pregunta sobre la motivación para llevar a cabo las pruebas pre-sintomáticas. Se obtuvieron siete categorías principales y las siguientes son las más significativas para PAF, EH y EMJ: razones relacionadas con el futuro, razones relacionadas con los demás y razones relacionadas con la curiosidad y la necesidad de conocer. Para hemocromatosis, las más importantes resultaron ser razones relacionadas con los demás y las relacionadas con las características de la enfermedad. La motivación para realizar el test pre-sintomático (PST) de la PAF, EH y EMJ es externa y sin relación con la enfermedad, mientras que la motivación de los sujetos en situación de riesgo para la HH está relacionada con la enfermedad. Las razones relacionadas con los demás es una motivación común en ambos grupos. A los sujetos también les preocupa la posibilidad de transmitir la enfermedad a sus hijos.

The role of the clinical psychologist in the context of genetic counseling includes support for the process of decision-making for subjects at-risk, regardless of the decision that was made. For this, it is important to know the motivations behind these decisions. What may be considered advant-ageous and justifiable reasons to perform the PST for genetic diseases from the medical and public point of view, i.e., planning for the future, helping in the choice of a profession, family planning, improving quality of life and contributing to health, may not be recognized as such by the individual seeking the PST. This study addresses the motivation to perform the presymptomatic testing (PST) of subjects at-risk for three diseases, Familial Amyloid Polyneuro pathy (FAP), Huntington's disease (HD), and Machado-Joseph disease (MJD), compared with the motivation to perform the PST for Hemochromatosis (HH). FAP, HD and MJD are three genetic (monogenic) autosomal dominant late-onset diseases (LON-Ds) with no cure. FAP is a progressive sensorimotor and autonomic neuropathy of adult hood. HD is characterized by a triad of clinical symptoms of chorea (motor, cognitive and psychiatric symptoms), emotional distress and cognitive decline. MJD is characterized by slowly progressive clumsiness in the arms and legs, a staggering lurching gait, sometimes mistaken for drunkenness, difficulty with speech and swallowing, involuntary eye movements, and may be accompanied by double vision or bulging eyes, and lower limb spasticity. HH is a disease in which too much iron accumulates in parenchymal organs, leading to iron overload and subsequent organ toxicity and failure. The study participants consisted in 213 subjects at genetic risk for FAP, HD, and MJD and 31 subjects at genetic risk for HH, that were assessed through an interview to obtain sociodemographic data and the answer to one question about motivation to perform PST: "Which were the reasons that led you to perform the predictive test? "This study was carried out in Center for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Porto (Portugal). This research used a mixed-method, since qualitative and quantitative techniques of data analysis were used. Before deciding to seek genetic counseling and to know their genetic status, subjects at-risk have naturally considered their motives and it was probably the pro-counseling reasons the ones dictating the motivation to perform the PST. This may suggest that in fact there is a prior self-selection to the test, i.e. only those considering to have emotional skills to go through the process, performing the test. Seven major categories were obtained. The most significant ones for FAP, HD and MJD were reasons related to the future, reasons related to others and reasons related to curiosity and to the need to know. For HH, the most important ones were reasons related to others and reasons related to the characteristics of the disease. The motivation of subjects at-risk to perform the PST for FAP, HD and MJD is external and unrelated to the disease, while the motivation of subjects at-risk to perform the PST for HH is related to the disease. Reasons related to others area common motivation: as subjects at-risk for FAP, HD and MJD, subjects at-risk for HH also chose reasons related to others as one of the most important motivations to carry out the PST. These subjects also care about the fact that they can transmit the disease to their children and care about other family members which are already ill. The category reasons related to others includes sub-categories that identify the person and the situation that led to the decision to perform a PST. Subjects at-risk are also concerned about the fact that they have to decide whether or not to have children and its economic implications.

Value of 1H-MRS on SCA3/MJD diagnosis and clinical course / 中南大学学报(医学版)

Objective:To investigate the value of proton magnetic resonance spectroscopy (1H-MRS) on the diagnosis of SCA3/MJD,and to calculate the correlation between 1H-MRS ratio and the clinical score.Methods:Sixteen patients with SCA3/MJD and 19 healthy volunteers were scanned with 1H-MRS.The data of N-acetyl aspartate,creatine,choline-containing compounds,myoinositol,NAA/Cr,Cho/Cr,and mI/Cr ratio were collected,which were grouped for comparative study.The onset patients with SCA3/MJD were evaluated with the International Cooperative Ataxia Rating Scale and Scale for the Assessment and Rating of Ataxia,the correlation between NAA/Cr,Cho/Cr or mI/Cr ratio and the clinical score was calculated.Results:The NAA/Cr in the pons and cerebellar dentate nucleus from the onset patients with SCA3/MJD was significantly reduced compared to that in the normal control group.The NAA/Cr in the cerebellar dentate nucleus of onset patients with SCA3/MJD was obviously correlated with ICARS.Conclusion:SCA3/MJD lesions are mainly located in the cerebellum and brainstem,where gray and white mater are also involved.The cerebellar dentate nucleus may be the earliest involved area.There is a correlation between the ICARS and the cerebellar lesion degree.The ICARS reflects the severity of clinical manifestations.1H-MRS is useful in the diagnosis of SCA3/MJD.

Augmented movement strategies for postural control in patients with spinocerebellar ataxia type 3: a case-control study / Estratégias aumentadas de movimento para controle postural em pacientes com ataxia espinocerebellar tipo 3: caso-controle

INTRODUCTION: This study investigated the movement strategies for postural control in patients with spinocerebellar ataxia type 3 (SCA3). METHODS: This case-control study enrolled 5 patients with SCA3 (aged 41 to 51 years) and 5 healthy participants group-matched by age, body mass and body height.Participants performed 3 trials lasting 30 s each of postural tasks characterized by: feet apart or together; eyes open or closed. Center of pressure (CoP) data was quantified using three-dimensional (3D: number of high-density and high-speed regions, average and maximal distances among regions), two-dimensional (2D: elliptical area, average velocity) and one-dimensional (1D: standard deviation, velocity) parameters. RESULTS: Analysis of variance revealed significant interaction effect between group*task for 1D (F12,238=3.496, p<0.001), 2D (F6,184=11.472, p<0.001), and 3D parameters (F12,238=2.543, p=0.004). Significant univariate effects for postural task were observed for all parameters, with higher body sway values under visual and biomechanical constraints, either separated or combined. CONCLUSIONS: Patients with SCA3 presented augmented movement strategiescompared with healthy subjects, characterized by increasing body sway under more demanding biomechanical and/ or visual constraints. Three-dimensional kinematic mapping revealed either random movement strategies or a unique movement strategy characterized by a stochastic CoP distribution, with high CoP speed to correct for large body sway deviations.

INTRODUÇÃO: Este estudo investigou as estratégias de movimento para controle postural em pacientes com ataxia espinocerebelar tipo 3 (SCA3). MÉTODOS: Este estudo de caso-controle incluiu cinco pacientes com SCA3 (idade 41 a 51 anos) e cinco participantes saudáveis, agrupados por idade, massa corporal e altura corporal. Os participantes realizaram três ensaios 30 s cada uma das tarefas posturais caracterizadas por: pés separados ou juntos; olhos abertos ou fechados. Os dados do centro de pressão (CoP) foram quantificados usando tridimensional (3D: número de alta densidade e alta velocidade regiões, distâncias médias e máximas entre regiões), bidimensional (2D: área elíptica, velocidade média) e unidimensional (1D: Desvio padrão, velocidade). RESULTADOS: Análise de variância Revelou um efeito de interação significativo entre a tarefa * grupo 1D (F12.238 = 3.496, p <0.001), 2D (F6.184 = 11.472, p <0.001) e os parâmetros 3D (F12,238 = 2,543, p = 0,004). Efeitos univariados significativos foram observados para todos os parâmetros, com maiores valores de balanço corporal sob restrições visuais e biomecânicas, separadas ou combinados. CONCLUSÕES: Os pacientes com SCA3 apresentaram estratégias de movimento comparadas com indivíduos saudáveis, aumentando o balanço do corpo sob condições biomecânicas e / ou restrições visuais. O mapeamento cinemático tridimensional revelou estratégias de movimento aleatório ou uma estratégia de movimento caracterizada por uma distribuição estocástica de CoP, com alta velocidade de correção para os grandes desvios.

Itajaí, Santa Catarina - Azorean ancestry and spinocerebellar ataxia type 3 / Itajaí, Santa Catarina - descendência açoriana e ataxia espinocerebelar tipo 3

ABSTRACT The authors present a historical review of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the most common form of spinocerebellar ataxia in Brazil, and consider the high frequency of cases in families from Itajaí, a city on the coast of the state of Santa Catarina with a large population of Portuguese/Azorean descent.

RESUMO Os autores apresentam uma revisão histórica sobre a ataxia spinocerebelar tipo 3/doença de Machado-Joseph (SCA3/DMJ), que representa a forma de SCA mais comum em nosso país, considerando a alta frequência de casos oriundos de famílias da cidade de Itajaí, no litoral de Santa Catarina, cidade com ascendência portuguesa-açoriana.

Qualidade de vida em pacientes com doença de Machado-Joseph sob acompanhamento fonoaudiológico para disfagia / Therapy speech impact in quality of life in patients with Machado-Joseph disease

RESUMO A doença de Machado-Joseph é uma doença degenerativa e atualmente considerada a ataxia espinocerebelar mais frequente. O processo degenerativo da doença afeta diferentes regiões e funções do sistema nervoso central e/ou periférico. A disfagia é um dos sintomas presentes na doença de Machado-Joseph, sendo responsável pelas complicações clínicas e pela pneumonia aspirativa, sua principal causa de morte. O objetivo deste trabalho é verificar o impacto da terapia fonoaudiológica na qualidade de vida em pacientes com doença de Machado-Joseph. Participaram da pesquisa quatro pacientes diagnosticados com a doença, três do sexo feminino e um do sexo masculino, com média de idade de 46,5 anos (±18) e queixa de disfagia. Na primeira sessão, todos os pacientes responderam ao questionário de Avaliação da Qualidade de Vida em Disfagia, SWAL-QOL, foram avaliados quanto aos aspectos estruturais e funcionais da deglutição e classificados de acordo com a Escala Funcional de Ingestão por Via Oral (FOIS). Após seis sessões de tratamento fonoaudiológico, realizaram nova avaliação clínica da deglutição, novamente classificados de acordo com a escala FOIS e responderam o SWAL-QOL. Conclusões: Após a intervenção fonoaudiológica, todos os pacientes apresentaram melhor conceito nos domínios medo de alimentar-se, alimentação como um fardo e fadiga, podendo-se inferir que houve uma melhora na satisfação com o processo alimentar e, consequentemente, qualidade de vida dos sujeitos acompanhados.

ABSTRACT The Machado-Joseph disease is a degenerative disease, currently considered the most frequent spinocerebellar ataxia. The degenerative process of the disease affects several regions and functions of the central and/or peripheral nervous system. The dysphagia is one of the symptoms of Machado-Joseph disease, being responsible for the clinical complications and for the aspiration pneumonia, its main cause of death. The goal of this paper is to verify the impact of the speech-language therapy in the quality of life of the Machado-Joseph disease patients. Four patients diagnosed with Machado-Joseph disease attended to the research, three female and one male, with age average in 46,5 years-old (± 18), and complaining about dysphagia. In the first session, all patients answered the protocol of quality of life in dysphagia assessment of Quality of Life in Dysphagia, SWAL -QOL were assessed for structural and functional aspects of swallowing and classified according to Functional Intake Scale for Oral (FOIS). After six speech therapy sessions conducted a new clinical evaluation of swallowing, again classified according to FOIS and answered the SWAL -QOL. Conclusions: After speech therapy, all patients showed better concept in the field fear of eating, food as a burden and fatigue, which can be inferred that there was an improvement in satisfaction with food processes and hence the quality of life accompanied subjects.

Caracterização do equilíbrio, risco de quedas e qualidade de vida em pessoas com doença de Machado-Joseph / Characterization of balance, accidental falls and quality of life in patients with Machado-Joseph disease

Introdução: A doença de Machado-Joseph (DMJ) é uma doença neurodegenerativa bastante incapacitante que afeta principalmente os sistemas motores dos sujeitos acometidos, ocasionando uma redução da autonomia e das atividades de vida diária devido à predisposição ao risco de quedas, o que pode gerar complicações emocionais, isolamento social e uma interferência na qualidade de vida. Objetivo: Avaliar e correlacionar o equilíbrio, risco de quedas e qualidade de vida de sujeitos com Doença de Machado-Joseph. Material e métodos: Estudo de abordagem quantitativa, do tipo descritiva correlacional, que avaliou sete sujeitos com DMJ, de ambos os sexos, com idade média de 46,28 anos, residentes em Santa Maria/ RS. Os instrumentos utilizados foram ficha de avaliação, escala de equilíbrio de Berg, Dynamic Gait Index (DGI) e Questionário SF-36. Resultados: A percepção geral sobre a qualidade de vida foi moderadamente baixa, com ênfase nos domínios de função física. Os resultados evidenciaram um prejuízo do equilíbrio estático e dinâmico desses sujeitos, além de um risco aumentado a quedas apresentando correlação significativa, o que demostra que quanto maior o desequilíbrio mais propenso a quedas estão esses sujeitos. O aspecto capacidade funcional da qualidade de vida apresentou correlação significativa com o equilíbrio dos sujeitos avaliados. Conclusão: Tendo em vista a importância da fisioterapia no tratamento de sujeitos com DMJ, faz-se necessário uma avaliação completa e precisa para que se possam estabelecer estratégias satisfatórias de intervenção no âmbito da promoção da saúde. (AU)

Introduction: The Machado-Joseph disease (MJD) is a disabling neurodegenerative disease which affects the motor systems of the affected subjects, causing a reduction of autonomy and activities of daily living due to the predisposition to risk of falls. It can generate emotional complications, social isolation and interference in quality of life. Objective: To assess and correlate the balance, risk of falls and quality of life of subjects with Machado-Joseph disease. Methods: This is a quantitative study, descriptive correlational, which evaluated seven subjects with MJD, of both sexes, with mean age 46.28 years old, residents in Santa Maria/RS. The instruments used were the evaluation form, Berg Balance Scale, Dynamic Gait Index (DGI) and Questionnaire SF-36. Results: The general perception about quality of life was moderately low, with emphasis in the areas of physical function. The results showed a loss of static and dynamic balance of these subjects, as well as an increased risk factor for falls, showing significant correlation, which demonstrates that greater the imbalance, more prone to falls the patients are. The functional capacity aspect of quality of life showed significant correlation with the balance of the subjects evaluated. Conclusion: In view of the importance of physical therapy in the treatment of subjects with MJD, it is required a full assessment and needs so that satisfactory intervention strategies in health promotion can be established. (AU)

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients / Ataxia espinocerebelar do tipo 3: subfenótipos em uma coorte de pacientes brasileiros

Spinocerebellar ataxia type 3 (SCA3) involves cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems with strong phenotypic heterogeneity, that lead us to classify the disorder into different clinical subtypes according to the predominantly affected motor systems. Method The series comprises 167 SCA3 patients belonging to 68 pedigrees, studied from 1989-2013. These patients were categorized into seven different subphenotypes. Results SCA3 cases were clustered according to the predominant clinical features. Three most common forms were subphenotype 2, characterized by ataxia and pyramidal symptom was observed in 67.5%, subphenotype 3 with ataxia and peripheral signs in 13.3%, and subphenotype 6 with pure cerebellar syndrome in 7.2%. Conclusion Our study was the first to systematically classify SCA3 into seven subphenotypes. This classification may be particularly useful for determination of a more specific and direct phenotype/genotype correlation in future studies. .

A ataxia espinocerebelar do tipo 3 (AEC3) envolve os sistemas cerebelar, piramidal, extrapiramidal, do neurônio motor e oculomotor, com uma grande heterogeneidade fenotípica, o que nos levou a classificar essa desordem em diferentes subtipos clínicos de acordo com o sistema predominantemente afetado. Método Nossa série compreende 167 pacientes com AEC3, pertencentes a 68 famílias, avaliados de 1989 a 2013. Esses pacientes foram classificados em 7 diferentes subtipos. Resultados Os pacientes com AEC3 foram agrupados de acordo com as características clínicas predominantes. As três formas mais comum foram o subfenótipo 2, caracterizado por ataxia e sintomas piramidais, observado em 67,5% dos pacientes, subfenótipo 3 com ataxia e sinais periféricos, em 13,3%, e subfenótipo 6 com síndrome cerebelar pura, em 7,2%. Conclusão Nosso estudo foi o primeiro a classificar sistematicamente AEC3 em sete subtipos. Esta classificação pode ser particularmente útil para correlacionar fenótipo/genótipo com mais especificidade em futuros estudos. .

Amplio espectro fenotípico de la SCA-3: paraparesia espástica hereditaria / The broad phenotypic spectrum of SCA-3: hereditary spastic paraplegia

La ataxia espinocerebelosa tipo 3 o enfermedad de Machado-Joseph (SCA-3/EMJ) es la forma más frecuente de ataxia espinocerebelosa autosómica dominante. Se caracteriza por una marcada variabilidad fenotípica, pudiendo causar formas no cerebelosas de presentación. En base a algunos casos comunicados, se ha propuesto una forma de presentación clínica similar a la de una paraparesia espástica hereditaria, con la presencia de signos de disfunción piramidal predominantes como la manifestación clínica inicial. Presentamos dos nuevos casos de SCA-3/EMJ con un cuadro clínico inicial sugerente de paraparesia espástica hereditaria y una revisión de los casos clínicos similares previamente informados. Nuestros hallazgos apoyan la propuesta de un subtipo de SCA-3/EMJ caracterizado por la presencia de marcada disfunción piramidal como manifestación inicial, simulando un cuadro clínico de paraparesia espástica hereditaria.

Machado-Joseph disease (MJD) is the most frequent dominantly inherited spinocerebellar ataxia. A marked phenotypic variability is a characteristic of this disorder that could involve non-cerebellar presentations. Based on several case reports describing pyramidal dysfunction as the main symptom at onset, a clinical form resembling hereditary spastic paraplegia has been proposed. We report here two further cases of MJD patients whose initial clinical presentation suggested hereditary spastic paraplegia, and a summary of the main findings of previously similar published reports. Our findings lent support to the proposal of a MJD subtype distinguished by a marked pyramidal dysfunction at onset, simulating a clinical picture of hereditary spastic paraplegia.

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias / Relevância clínica do "bulging eyes" para o diagnóstico diferencial das ataxias espinocerebelares

Objective To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. Methods Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. Results BE was detected in 123 patients with SCA (33.3%), namely 109 of the 167 SCA3 patients (65.3%) and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients). Conclusion BE was detected in the majority of patients with SCA3 (65.3%) and could be used with a clinical tool for the differential diagnosis of SCA. .

Objetivo Investigar a relevância do achado clínico de bulging eyes (BE) em uma grande amostra brasileira de pacientes com ataxias espinocerebelares (AEC), para avaliar sua importância no diagnóstico diferencial entre as AEC. Métodos Foram avaliados 369 pacientes de 168 famílias brasileiras com AEC através de exame neurológico e testes de genética molecular. BE foi caracterizado pela presença de retração palpebral. AEC3 foi determinada geneticamente em 167 pacientes, AEC10 em 68 pacientes, AEC2 em 20, AEC1 em 9, AEC7 em 6 e AEC6 foi encontrada em 3 pacientes. Resultados BE foi detectado em 123 pacientes com AEC (33,3%), correspondendo a 109 dos 167 pacientes com AEC3 (65,3%) e 5 pacientes com outras AEC (1 paciente com AEC10, 2 AEC1 e 2 pacientes com AEC2). Conclusão BE foi detectado na maioria dos pacientes com AEC3 (65,3%) e poderia ser usado com uma ferramenta clínica para o diagnóstico diferencial das AEC. .

Magnetic resonance spectroscopy of the cerebellum in patients with spinocerebellar ataxia type 3/Machado-Joseph disease / 中南大学学报(医学版)

Objective To evaluate the metabolite pattern and the severity in patients with spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by 1H magnetic resonance spectroscopy (1H-MRS) on different cerebellar regions, including cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum. Methods Thirty-six SCA3/MJD patients, and 27 sex, age-matched healthy controls were scanned with 1H-MRS for N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum as the region of interests (ROI), and finally got access to NAA/Cr, Cho/Cr, and NAA/Cho ratios. We also examined the CAG repeat numbers of MJD1 gene, scored the 36 patients by the scale for the assessment and rating of ataxia (SARA), analyzed the differences in ratios between SCA3/MJD patients and the control group, and explored whether relevance existed between these ratios and duration of the disease, age of onset, CAG repeat times, and SARA scores respectively. Results The ratio of NAA/Cr in SCA3/MJD patients showed a significant reduction in the cerebellar cortex, dentatum, cerebellar vermis and medipeduncle (P<0.01) compared with the controls. The ratio of NAA/Cho also showed significant reduction in the dentatum and cerebellar vermis (P<0.01). A number of correlations were found between the metabolite ratios of 1H-MRS and duration of the disease, age of onset, expanded CAG and SARA score in SCA3/MJD patients. Conclusion 1H-MRS, which shows the neural metabolic changes in the cerebella of SCA3/MJD patients, provides useful information about the severity of SCA3/MJD.