Social, professional and neuropsychiatric outcomes in patients with myasthenia gravis.

BACKGROUND: Recent medical advances have enabled the control of neurological symptoms and increased survival of patients with myasthenia gravis (MG). However, MG has many veiled consequences that may be underestimated by neurologists. Our aim was to clarify the social, professional, and neuropsychiatric issues of MG patients. METHODS: We carried out a cross-sectional cohort study with MG patients from a university-affiliated referral hospital. We registered clinical and sociodemographic data, and patients were classified according the MGFA classification. Clinical severity was assessed with Myasthenia Gravis Composite (MGC) scale. Trained and blind investigators analyzed social and professional outcomes. Neuropsychiatric symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS) and the social support with the Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: We enrolled 49 patients with MG. The mean age was 45.3 ± 18.1 years and 39 (79.6%) were women. There were 19 (38.8%) patients who become unemployed, 23 (46.9%) who had to retire prematurely, 31 (63.3%) that reported a significant reduction in work performance, and 23 (46.9%) who had a reduction in monthly income after the diagnosis of MG. Only 16 (32.6%) received any financial support and 24 (48.9%) patients had the perception of receiving a satisfactory social support. The practice of physical activity is a habit in only 10 patients (20.4%). Neuropsychiatric symptoms were present in 26 (53.1%) patients. CONCLUSION: Patients with MG are vulnerable to social, professional, and mental disadvantages. Therapeutic success in MG goes beyond symptom relief and inevitably depends on a personalized approach to the patient.

Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research.

Amyotrophic lateral sclerosis (ALS) is a multifactorial and progressive neurodegenerative disease of unknown etiology. Due to ALS's unpredictable onset and progression rate, the search for biomarkers that allow the detection and tracking of its development and therapeutic efficacy would be of significant medical value. Considering that alterations of energy supply are one of ALS's main hallmarks and that a correlation has been established between gene expression in human brain tissue and peripheral blood mononuclear cells (PBMCs), the present work investigates whether changes in mitochondrial function could be used to monitor ALS. To achieve this goal, PBMCs from ALS patients and control subjects were used; blood sampling is a quite non-invasive method and is cost-effective. Different parameters were evaluated, namely cytosolic calcium levels, mitochondrial membrane potential, oxidative stress, and metabolic compounds levels, as well as mitochondrial dynamics and degradation. Altogether, we observed lower mitochondrial calcium uptake/retention, mitochondria depolarization, and redox homeostasis deregulation, in addition to a decrease in critical metabolic genes, a diminishment in mitochondrial biogenesis, and an augmentation in mitochondrial fission and autophagy-related gene expression. All of these changes can contribute to the decreased ATP and pyruvate levels observed in ALS PBMCs. Our data indicate that PBMCs from ALS patients show a significant mitochondrial dysfunction, resembling several findings from ALS' neural cells/models, which could be exploited as a powerful tool in ALS research. Our findings can also guide future studies on new pharmacological interventions for ALS since assessments of brain samples are challenging and represent a relevant limited strategy. Graphical abstract.

Regressão do depósito amiloide e normalização da função ventricular em paciente com amiloidose de cadeias leves tipo Kappa / Regression of amyloid deposit and normalization of ventricular function in a patient with Kappa-type light chain amyloidosis

INTRODUÇÃO: A amiloidose por depósito de cadeias leves (AL) é reconhecida como um tipo de amiloidose associado a quadro clínico devastador e prognóstico sombrio se diagnosticada tardiamente. É por este motivo considerada uma urgência médica, pelo fato do tratamento precoce modificar radicalmente a evolução. A presença de sintomas graves de cardiopatia geralmente empobrece o prognóstico e contraindica o transplante de medula óssea (MO). Descrevemos um caso de evolução favorável de amiloidose AL com tratamento medicamentoso. Caso Clínico: paciente de 83 anos, hígido, realizando atividade física intensa, apresentou subitamente piora significativa da capacidade funcional, evoluindo para dispneia aos pequenos esforços e em repouso, em 3 meses de evolução. Foi internado para compensação do quadro em UTI por duas ocasiões, em anasarca, necessitando drogas vasoativas. Realizou ecocardiograma que evidenciou espessura de septo de 19 mm e parede posterior de 17mm, fração de ejeção de 62%, relação E/e'19, e eletrocardiograma com ritmo sinusal e padrão de baixa voltagem no plano frontal. Relação kappa/lambda de 94,6 (valor de referência de 0,26 a 1,65). Foi submetido a biopsia de MO e de gordura abdominal, a imunohistoquímica da MO evidenciou infiltrado intersticialde células plasmocitárias monoclonais para cadeias leves kappae a de gordura abdominal corou com vermelho Congo. Foi submetido aovesquema CyBorD por 1 mês (Ciclofosfamida, Bortezomibe e Dexametasona) Ecocardiograma realizado após 1 ano, evidenciou diminuição significativa da espessura de paredes (septo de 13mm e parede posterior de 12mm). Em 1 ano e 6 meses, o ecocardiograma era normal, com espessura de septo e de parede posterior de 10mm, relação E/e'de 10. COMENTÁRIOS: O diagnóstico de amiloidose de cadeias leves é realizado de forma relativamente simples, com a dosagem da relação kappa/lambda quando esta está muito elevada. Neste caso, a evolução foi muito favorável, com regressão da cardiopatia provavelmente pelo diagnóstico ter sido precoce. O ecocardiograma foi o elemento determinante do diagnóstico e evolução. CONCLUSÃO: A amiloidose de cadeias livres leves tipo Kappa pode ter uma evolução extremamente favorável quando o diagnóstico é feito precocemente, portanto o reconhecimento desta patologia é fundamental para a melhora do prognóstico.

Medication adherence in patients with myasthenia gravis in Brazil: a cross-sectional study.

Advances in the treatment of MG have allowed most patients to effectively treat their disorder with oral medications. In parallel, non-adherence to medication treatment regimens is a worldwide health problem. Other chronic neurological disorders have already been associated with low adherence to treatment. However, the literature regarding adherence among patients with MG is definitely poor. The purpose of this study was to capture the prevalence and the associated factors of non-adherence to pharmacological treatment in patients with MG. We carried out a cross-sectional cohort study with 58 consecutive patients with MG from a university-affiliated referral hospital in São Paulo, Brazil. We registered clinical and sociodemographic data and patients were classified according to the MGFA classification. Clinical severity was assessed with myasthenia gravis composite (MGC) scale. Neuropsychiatric symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS) and quality of life with the 15-Item Quality Of Life Instrument for myasthenia gravis scale (MG-QOL15). Adherence to pharmacological treatment was evaluated using the 8-item Morisky Medication Adherence Scale (MMAS-8). There were 26 (44.8%) patients adherent to treatment. Low adherence was associated with poor educational attainment, longer time of disease and greater daily number of pills (p < 0.05). Patients with poor compliance to treatment presented worse quality of life and increased neuropsychiatric symptoms (p < 0.05). Adherence can be relatively challenging in patients with MG. Medical approach should recognize that therapeutic success in the treatment of MG goes through adherence to treatment.

Quantitative Myasthenia Gravis Score: a Brazilian multicenter study for translation, cultural adaptation and validation.

OBJECTIVE: To perform the translation, cross-cultural adaptation and validation of the Quantitative Myasthenia Gravis Score (QMGS) to Brazilian Portuguese in accordance with international ethical standards. METHODS: The following steps were taken: (1) implementation of the translation protocol and transcultural adaptation, (2) validation of the adapted content, and (3) assessment of reliability. To check intra- and inter-observer reproducibility, each patient underwent two interviews with interviewer-A and one with B. The QMGS was compared to the Myasthenia Gravis Composite Scale and Myasthenia-specific Quality of Life Questionnaire. RESULTS: Our study group consisted of 30 patients, with a mean age of 47.6±11.4 years and a mean duration of illness of 11.33±8.49 years. Correlation between the QMGS and MGC was very strong (r = 0.928; p < 0.001) and substantial between the QMGS and MG-QOL 15 (r = 0.737; p < 0.001). CONCLUSION: The Brazilian Portuguese translation, and validation of the QMGS was successfully performed.

Quantitative Myasthenia Gravis Score: a Brazilian multicenter study for translation, cultural adaptation and validation / Teste Quantitativo para Miastenia Gravis: estudo multicêntrico brasileiro para tradução, adaptação cultural e validação

ABSTRACT Objective To perform the translation, cross-cultural adaptation and validation of the Quantitative Myasthenia Gravis Score (QMGS) to Brazilian Portuguese in accordance with international ethical standards. Methods The following steps were taken: (1) implementation of the translation protocol and transcultural adaptation, (2) validation of the adapted content, and (3) assessment of reliability. To check intra- and inter-observer reproducibility, each patient underwent two interviews with interviewer-A and one with B. The QMGS was compared to the Myasthenia Gravis Composite Scale and Myasthenia-specific Quality of Life Questionnaire. Results Our study group consisted of 30 patients, with a mean age of 47.6±11.4 years and a mean duration of illness of 11.33±8.49 years. Correlation between the QMGS and MGC was very strong (r = 0.928; p < 0.001) and substantial between the QMGS and MG-QOL 15 (r = 0.737; p < 0.001). Conclusion The Brazilian Portuguese translation, and validation of the QMGS was successfully performed.

RESUMO Objetivo O objetivo foi realizar a tradução e validação do teste quantitativo para Miastenia Gravis (QMGS) para Português do Brasil, de acordo com as diretrizes internacionais. Métodos Foram realizadas as etapas de implementação do protocolo de tradução e adaptação transcultural, validação do conteúdo adaptado e avaliação da confiabilidade. Para verificar a reprodutibilidade intra e inter-observador cada paciente foi submetido a duas entrevistas por um entrevistador-A e um B. O QMGS foi comparado ao MG Composite Scale e Myasthenia-specific Quality of Life Questionnaire. Resultados O estudo inclui 30 pacientes, com a média de idade de 47,6±11,4 anos e tempo médio de doença de 11,33±8,49 anos. A correlação entre QMGS e MGC apresentou-se muito forte (r = 0,928; p < 0,001) e substancial entre QMGS e MG-QOL 15 (r = 0,737; p < 0,001). Conclusão A tradução, e validação do QMGS para o português do Brasil foi realizada com sucesso.

Sleep, lung function, and quality of life in patients with myasthenia gravis: A cross-sectional study.

The purpose of this study was to investigate the physiological variables of lung function, respiratory muscle strength, and sleep in clinically stable patients with myasthenia gravis. This was a prospective cross-sectional study conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Patients adhering to the eligibility criteria were consecutively recruited from the Research Department of Neuromuscular Diseases at the Federal University of Sao Paulo and the Department of Neurology at Santa Casa de Misericordia of Sao Paulo and were referred to the Nove de Julho University Sleep Laboratory (Sao Paulo, Brazil). The study included 25 patients (21 female) with a mean age of 45.28 ± 12.33 years. Only one patient exhibited a restrictive ventilatory pattern. The maximum ventilatory pressures observed were considerably reduced in most patients as compared to reference values. In sleep studies, the patients exhibited significantly reduced oxygen saturation, reduced rapid eye movement sleep time, increased non-rapid eye movement stage 3 sleep, and considerable apnoea/hypopnoea indexes. Clinically stable patients with myasthenia gravis exhibit a high prevalence of sleep-disordered breathing, significant reductions in maximum ventilatory pressures, and impairment of health-related quality of life.

Brazilian-Portuguese translation, cross-cultural adaptation and validation of the Myasthenia Gravis Composite scale. A multicentric study.

OBJECTIVE: To perform the translation, cultural adaptation and validation of the Myasthenia Gravis Composite (MGC) scale in Brazil. METHODS: The study was conducted at three neuromuscular disease research centers in accordance with the international ethical standards, following a multi-modal approach and was conducted in three steps consisting of translation, cultural adaptation, and validation according to international guidelines. The final version of the MGC was applied in a sample of 27 MG patients and the total score was compared to a Portuguese version of the MG-QOL-15. RESULTS: The internal consistency verified by Cohen's Kappa test was excellent (0.766). The correlation between the MGC and MG-QOL-15 was strong (R = 0.777; p = 0.000). No significant differences were found between the responses of patients in the first and second applications of the MGC. CONCLUSION: The MGC scale, validated into Brazilian Portuguese, has proven to be a reliable instrument that is easy to use, and is highly reproducible.

Brazilian-Portuguese translation, cross-cultural adaptation and validation of the Myasthenia Gravis Composite scale. A multicentric study / Tradução, adaptação cultural e validação da escala composta de Miastenia Grave para a lingua portuguesa do Brasil. Estudo multicêntrico

ABSTRACT Objective To perform the translation, cultural adaptation and validation of the Myasthenia Gravis Composite (MGC) scale in Brazil. Methods The study was conducted at three neuromuscular disease research centers in accordance with the international ethical standards, following a multi-modal approach and was conducted in three steps consisting of translation, cultural adaptation, and validation according to international guidelines. The final version of the MGC was applied in a sample of 27 MG patients and the total score was compared to a Portuguese version of the MG-QOL-15. Results The internal consistency verified by Cohen’s Kappa test was excellent (0.766). The correlation between the MGC and MG-QOL-15 was strong (R = 0.777; p = 0.000). No significant differences were found between the responses of patients in the first and second applications of the MGC. Conclusion The MGC scale, validated into Brazilian Portuguese, has proven to be a reliable instrument that is easy to use, and is highly reproducible.

RESUMO Objetivo Realizar a tradução e a adaptação transcultural da escala composta de Miastenia Grave (ECMG) Myasthenia Gravis Composite (MGC) no Brasil. Métodos O estudo foi realizado em três centros de investigação em doenças neuromusculares, de acordo com as normas éticas internacionais, consistindo em tradução, adaptação cultural e validação de acordo com as diretrizes internacionais. A versão final do MGC ECMG foi aplicada em vinte e sete pacientes com MG e a pontuação total foi comparada ao questionário MG-QOL 15. Resultados A consistência interna verificada pelo teste Kappa de Cohen foi excelente (0,766) e a correlação entre o a ECMG MGC e MG-QOL 15 foi positiva (R = 0,777; p = 0,000). Não foram encontradas diferenças entre as respostas dos pacientes na primeira e segunda aplicação da MGC. Conclusão A ECMG escala MGC validada para o Português do Brasil provou ser um instrumento confiável, de fácil aplicação e altamente reprodutível.

Imaging diagnosis of upper motor neuron compromising in a patient with Chiari 1 malformation.

We report a case of a typical MRI from a patient with bulbar-onset sporadic amyotrophic lateral sclerosis associated with Chiari type 1 malformation. Our report reinforces the conventional neuroimaging appearance associated with each condition and the associated abnormalities on a clinical and advanced imaging techniques basis. The MRI signal intensity was useful for detecting upper motor neuron degeneration based on corticospinal tract signal intensity, while diffusion tensor imaging parameters were limited to this purpose. Our description reinforces the relevance of the T1 magnetisation transfer sequence to demonstrate corticospinal tract degeneration and corroborate an amyotrophic lateral sclerosis diagnosis in an individual participant, when there is a potential concurrent 'amyotrophic lateral sclerosis mimic syndrome'. To our knowledge, this is the first description of the non-conventional MR techniques applicability to distinguish the impact of amyotrophic lateral sclerosis from Chiari 1 malformation.

Cross-cultural adaptation and validation of als Functional Rating Scale-Revised in Portuguese language.

The aim of this study is the cross-cultural, as well as to validate in Portuguese language the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). We performed a prospective study of individuals with amyotrophic lateral sclerosis (ALS) clinically defined. The scale, after obtaining the final version in Portuguese, was administered in 22 individuals and three weeks after re-applied. There were no significant differences between the application and reapplication of the scale (p=0.069). The linear regression and internal consistency measured by Pearson correlation and alpha Conbrach were significant with r=0.975 e alpha=0.934. The reliability test-retest demonstrated by intraclass correlation coefficient was strong with ICC=0.975. Therefore, this version proved to be applicable, reliable and easy to be conducted in clinical practice and research.

Cross-cultural adaptation and validation of als Functional Rating Scale-Revised in Portuguese language / Adaptação transcultural e validação da als Functional Rating Scale-Revised para a língua portuguesa

The aim of this study is the cross-cultural, as well as to validate in Portuguese language the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). We performed a prospective study of individuals with amyotrophic lateral sclerosis (ALS) clinically defined. The scale, after obtaining the final version in Portuguese, was administered in 22 individuals and three weeks after re-applied. There were no significant differences between the application and reapplication of the scale (p=0.069). The linear regression and internal consistency measured by Pearson correlation and alpha Conbrach were significant with r=0.975 e α=0.934. The reliability test-retest demonstrated by intraclass correlation coefficient was strong with ICC=0.975. Therefore, this version proved to be applicable, reliable and easy to be conducted in clinical practice and research.

O objetivo deste estudo foi realizar a adaptação transcultural, bem como validar na língua portuguesa a Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). Foi realizado um estudo prospectivo com indivíduos com esclerose lateral amiotrófica clinicamente definida. A escala, após a obtenção da sua versão final em português, foi aplicada em 22 indivíduos em dois momentos com intervalo de três semanas. Não foram observadas diferenças significativas entre a aplicação e reaplicação da escala (p=0,069). A fidedignidade e a consistência interna mensuradas pela correlação de Pearson e alfa de Conbrach foram significativos com r=0,975 e α=0,934, respectivamente. A confiabilidade evidenciada pelo coeficiente de correlação intraclasse foi forte com ICC=0,975. Portanto, a versão em português da ALSFRS-R demonstrou ser reprodutível, confiável, de fácil aplicação e compreensão para prática clínica e pesquisa.

Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery.

Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery / Polineuropatia axonal aguda com acometimento proximal predominante: manifestação neurológica incomum de cirurgia bariátrica

Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

A cirurgia bariátrica é freqüentemente indicada no tratamento da obesidade mórbida. Complicações previamente não relatadas têm sido associadas a essa cirurgia; dentre estas, as complicações neurológicas têm recebido destaque. Relatamos o caso de um homem de 25 anos de idade submetido a cirurgia gástrica para tratamento de obesidade mórbida que desenvolveu, dois meses após a cirurgia, fraqueza de predomínio proximal nos membros inferiores, de instalação aguda. A eletroneuromiografia demonstrou polineuropatia periférica axonal nos membros inferiores, de predomínio proximal. Após tratamento com imunoglobulina e suplementação vitamínica, apresentou rápida melhora clínica e neurofisiológica. Descrevemos as características clínicas e eletroneuromiográficas desse caso, destacando a dificuldade diagnóstica inicial, particularmente com relação ao diagnóstico diferencial com síndrome de Guillain-Barré. Discutimos a importância de acompanhamento nutricional e a eventual indicação de suplementação vitamínica de rotina nesses pacientes.

[Neural conduction in hand nerves and the physiological factor of age]. / Condução nervosa em nervos da mão e o fator fisiológico idade.

Many researchers have established the influence of physiological factors as age, for the parameters of the study of the motor and sensitive conduction. The objective of this study was to analyze the influence of the variable age in the study of the motor and sensitive nervous conduction of the median and ulnar nerves. The data were collected from 92 volunteers: 61 women and 31 men. Their age was from 13 to 74 years old, with a mean of 36.3 years. Most of them were employees at Santa Casa de São Paulo. It was observed that a reduction in the velocity of sensitive and motor nervous conduction takes place with the age. This reduction is associated with a reduction in the amplitude of the evoked potential.

Condução nervosa em nervos da mão e o fator fisiológico idade / Neural conduction in hand nerves and the physiological factor of age

Muitos pesquisadores têm estabelecido a influência do fator fisiológico idade nos parâmetros do estudo da condução nervosa sensitiva e motora, e que estas alterações podem levar a erros diagnósticos. O objetivo deste estudo foi estabelecer as alterações dos parâmetros do estudo da condução nervosa sensitiva e motora dos nervos mediano e ulnar em relação à idade. Os dados foram coletados de 92 voluntários, na sua maioria funcionários da Santa Casa de São Paulo: 61 mulheres e 31 homens, em faixa etária dos 13 aos 74 anos, com média de 36,3 anos. Em nosso estudo foi observado que, com o envelhecimento, ocorre diminuição da velocidade de condução nervosa sensitiva e motora associada a redução da amplitude do potencial evocado.