Sit to stand test and handgrip strength in men and women with post-COVID-19 syndrome without invasive ventilator support: insights from a Brazilian observational study

Two valid tests have been used in patients with post-COVID-19 syndrome (coronavirus disease 2019) due to their fast application, feasibility, and accessible procedures, facilitating data collection in large groups: the 1-minute sit-to-stand test (STS) and handgrip strength (HGS) dynamometry. The present study aimed to: i) assess the STS and HGS in men and women with post-COVID-19 syndrome who did not require invasive ventilator support; ii) correlate STS repetitions and HGS with time since the COVID-19 diagnosis. Six hundred and twenty-two men and women with post-COVID-19 syndrome who did not require invasive ventilatory support performed the STS and HGS tests at the beginning of the rehabilitation process at a Reference Hospital Centre. Women over 55 years presented significantly lower results compared to participants under 55 years. For the HGS, the median ranged from 42 to 48 kg and 70 to 81 kg for the female and male groups, respectively. The correlations of time since COVID-19 diagnosis with STS and HGS ranged from -0.16 to 0.02 (p>0.05) for women and men, respectively.The test results could be used for the initial analysis of normality ranges and comparisons with other populations. Although STS repetitions and HGS presented low and non-significant correlations with time since the COVID-19 diagnosis, some COVID-19 sequelae were not measured, so these data should be interpreted with caution

Análise do perfil clínico, neurofisiológico e genético de pacientes com Doença de Charcot Marie Tooth de herança autossômica recessiva

Este estudo teve como objetivo descrever as características clínicas, genéticas e epidemiológicas das formas recessivas da doença de Charcot-Marie-Tooth (AR-CMT) em pacientes avaliados em um centro de referência brasileiro e compará-las com os achados publicados na literatura. Entre fevereiro de 2015 e dezembro de 2020, foram avaliados 503 indivíduos (94 famílias e 192 indivíduos não relacionados), com diagnóstico de CMT. Os dados clínicos e de exames complementares foram obtidos de prontuários eletrônicos e as amostras de sangue foram utilizadas para análises genéticas. A amplificação multiplex de sonda dependente de ligação (MLPA) foi utilizada para avaliar duplicações / deleções no PMP22. O sequenciamento pelo método Sanger do GJB1 foi realizado em casos de suspeita de CMT desmielinizante. O sequenciamento através de painel de genes foi usado para os casos desmielinizantes negativos restantes e todos os casos de CMT axonal e intermediário. Variantes patogênicas ou provavelmente patogênicas foram identificadas em 197 casos-índice, sendo que 23 apresentavam alterações em genes relacionados a formas de AR-CMT. Os genes causadores mais comuns de AR-CMT entre os probandos foram: GDAP1 (n = 3, 2,03%), SBF2 (n = 3, 1,52%) e SH3TC2 (n = 3, 1,52%). Outras variantes identificadas foram responsáveis por ≤ 1% dos casos-índice. A primeira década de vida foi o período mais comum de aparecimento da doença nas formas recessivas. Em 7 dos 8 indivíduos com AR-CMT que puderam ter os resultados da espirometria avaliados, foi identificado padrão ventilatório restritivo. Este trabalho fornece mais dados sobre a frequência de subtipos de AR-CMT em uma população clínica de um centro de referência para desordens neuromusculares no Brasil e destaca a importância de variantes mais raras na prática clínica. Também chamamos a atenção para os aspectos respiratórios relacionados à AR-CMT.This study aimed to describe the clinical, genetic and epidemiological characteristics of recessive forms of Charcot-Marie-Tooth disease (AR CMT) in patients evaluated in a Brazilian reference center and compare them with the findings published in the literature. Between February 2015 and December 2020, 503 patients (94 families and 192 unrelated individuals) diagnosed with CMT were evaluated. Clinical data and complementary tests were obtained from electronic medical records and blood samples were used for genetic analysis. Multiplex binding-dependent probe amplification (MLPA) was used to assess duplications/deletions in PMP22. Sequencing by the Sanger method of the GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal and intermediate CMT cases. Pathogenic or probably pathogenic variants were identified in 197 index cases, 23 of which had alterations in genes related to forms of AR-CMT. The most common causative genes of AR-CMT among the probands were: GDAP1 (n = 3, 2.03%), SBF2 (n = 3, 1.52%) and SH3TC2 (n = 3. 1.52%). Other variants identified accounted for ≤ 1% of index cases. The first decade of life was the most common period for the onset of the disease in recessive forms. In 7 of the 8 individuals with AR-CMT who could have their spirometry results evaluated, a restrictive ventilatory pattern was identified. This study provides further data on the frequency of AR-CMT subtypes in a clinical population from a referral center for clinical neuromuscular disorders in Brazil and highlights the importance of rarer variants in clinical practice. We also draw attention to the respiratory aspects related to AR-CMT.138 f

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives

Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies

Consenso brasileiro sobre distrofia muscular de Duchenne, Parte 1 : diagnóstico, corticoterapia e perspectivas

Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD) took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1) genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2) patients diagnosed with DMD should have steroids prescribed; 3) lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.Avanços na compreensão e no manejo da distrofia muscular de Duchenne (DMD) ocorreram desde a publicação de diretrizes internacionais em 2010. Nosso objetivo foi elaborar um consenso nacional baseado em evidências de cuidado multidisciplinar dos pacientes com DMD no Brasil. Utilizamos a técnica de Delphi combinada com revisão sistemática da literatura de 2010 a 2016 classificando níveis de evidência e graus de recomendação. Nossas recomendações foram divididas em duas partes. Apresentamos aqui a parte 1, descrevendo a metodologia utilizada e conceitos gerais da doença, e fornecemos recomendações sobre diagnóstico, tratamento com corticosteroides e novas perspectivas de tratamentos medicamentosos. As principais recomendações: 1) testes genéticos deveriam ser a primeira linha para confirmação de casos suspeitos; 2) pacientes com diagnóstico de DMD devem receber corticosteroides; 3) por enquanto, a falta de publicações de resultados dos ensaios clínicos de fase 3, dificulta recomendações de uso medicamentos que “saltam exons” ou “passam” por código de parada prematura

Consenso brasileiro sobre distrofia muscular de Duchenne, Parte 1 : diagnóstico, corticoterapia e perspectivas

Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD) took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1) genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2) patients diagnosed with DMD should have steroids prescribed; 3) lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.Avanços na compreensão e no manejo da distrofia muscular de Duchenne (DMD) ocorreram desde a publicação de diretrizes internacionais em 2010. Nosso objetivo foi elaborar um consenso nacional baseado em evidências de cuidado multidisciplinar dos pacientes com DMD no Brasil. Utilizamos a técnica de Delphi combinada com revisão sistemática da literatura de 2010 a 2016 classificando níveis de evidência e graus de recomendação. Nossas recomendações foram divididas em duas partes. Apresentamos aqui a parte 1, descrevendo a metodologia utilizada e conceitos gerais da doença, e fornecemos recomendações sobre diagnóstico, tratamento com corticosteroides e novas perspectivas de tratamentos medicamentosos. As principais recomendações: 1) testes genéticos deveriam ser a primeira linha para confirmação de casos suspeitos; 2) pacientes com diagnóstico de DMD devem receber corticosteroides; 3) por enquanto, a falta de publicações de resultados dos ensaios clínicos de fase 3, dificulta recomendações de uso medicamentos que “saltam exons” ou “passam” por código de parada prematura

Update of the Brazilian consensus recommendations on Duchenne muscular dystrophy

In the last few decades, there have been considerable improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy. International guidelines have been published and recently reviewed. A group of Brazilian experts has developed a standard of care based on a literature review with evidence-based graded recommendations in a two-part publication. Implementing best practice management has helped change the natural history of this chronic progressive disorder, in which the life expectancy for children of the male sex in the past used to be very limited. Since the previous publication, diagnosis, steroid treatment, rehabilitation, and systemic care have gained more significant insights with new original work in certain fields. Furthermore, the development of new drugs is ongoing, and some interventions have been approved for use in certain countries. Therefore, we have identified the need to review the previous care recommendations for Brazilian patients with DMD. Our objective was to create an evidence-based document that is an update on our previous consensus on those topics