PTC Therapeutics.

Objective: During the transitional phase (ambulatory to non-ambulatory), synergies characterize the evolution of Duchenne muscular dystrophy (DMD). This study was performed to describe and quantify compensatory movements while sitting down on/rising from the floor and climbing up/down steps. Method: Eighty videos (5 children × 4 assessments × 4 tasks) were recorded quarterly in the year prior to gait loss. Compensatory movements from the videos were registered based on the Functional Evaluation Scale for DMD. Results: The most frequently observed compensatory movements were upper limb support on lower limbs/floor/handrail during all the tasks and lumbar hyperlordosis, trunk support on handrail, equinus foot, increased base of support, non-alternated descent, and pauses while climbing up/down steps. Conclusion: Climbing up/down steps showed a higher number of compensatory movements than sitting down on/rising from the floor, which seemed to be lost before climbing up/down steps in ambulatory children with DMD.Keywords: Duchenne muscular dystrophy, evaluation, scales. RESUMOObjetivo: Durante a fase de transição (deambulador -não-deambulador), sinergias musculares caracterizam a evolução da distrofia muscular de Duchenne (DMD). Este estudo visou descrever e quantificar os movimentos compensatórios durante o sentar/levantar do solo, subir/descer degraus. Oitenta vídeos (5 crianças × 4 avaliações × 4 tarefas) foram gravados trimestralmente durante o ano que antecedeu a perda da marcha. Método: Os movimentos compensatórios dos vídeos foram registrados utilizando a Escala de Avaliação Funcional para DMD. Resultados: Os movimentos compensatórios mais frequentemente observados foram apoio de membros superiores nos membros inferiores/solo/corrimão durante todas as tarefas funcionais e hiperlordose lombar, apoio de tronco no corrimão, pés equinos, aumento da base de suporte, descida não alternada e pausas ao subir/descer degraus. Subir/descer degraus apresentou um número maior de movimentos compensatórios do que sentar/levantar do solo. Conclusão: Sentar/levantar do solo foram habilidades perdidas antes de subir/descer degraus em crianças com DMD.Palavras-chave: distrofia muscular de Duchenne, avaliação, escalas.

Objective:The relationship between functional dependence and quality of life (QOL) in Duchenne muscular dystrophy (DMD) patients and burden and QOL in caregivers is not clear. This study investigated possible relationships between functional dependence/QOL of DMD patients and QOL/burden of caregivers. Method: This study included 35 boys (6-17 years) and respective caregivers (above 21 years). Caregivers answered to World Health Organization Quality of Life and Zarit Burden Interview questionnaires. Patients were assessed with the Motor Function Measure and the Autoquestionnaire Qualité de vie Enfant Imagé. Spearman correlations and linear regressions were run to investigate relationships between the variables. Results: The occurrence of lower QOL and higher burden among the caregivers of patients with Duchenne muscular dystrophy was evidenced. The functional dependence of patients was not considered a determinant factor. Higher caregivers' burden was related to lower caregivers' QOL and to higher patients' ages.Keywords: Duchenne muscular dystrophy, behavior, quality of life, motor activity. RESUMOObjetivo: A relação entre qualidade de vida e função motora de pacientes com distrofia muscular de Duchenne (DMD) e sobrecarga e qualidade de vida (QV) dos cuidadores não está clara na literatura. Esse estudo investigou possíveis relações entre dependência funcional/ QV de pacientes e sobrecarga/QV dos cuidadores em 35 meninos (6-17 anos) com DMD e respectivos cuidadores (acima de 21 anos). Método: Cada cuidador respondeu ao questionário de QV da Organização Mundial de Saúde e de sobrecarga de Zarit e o paciente foi avaliado com a medida de função motora e o Autoquestionnaire Qualité de vie Enfant Imagé. Correlações de Spearman e regressões lineares investigaram possíveis relações entre as variáveis. Resultados: A ocorrência de menor QV e maior sobrecarga entre cuidadores foi evidenciada, enquanto a dependência funcional dos pacientes não foi considerada fator

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.Keywords: muscular dystrophy, Duchenne; practice guideline; consensus; diagnosis; genetic testing; drug therapy; glucocorticoids; utrophin. RESUMOAvanços 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.

BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of SMN gene (SMN1) and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene (SMN2). The SMN2 mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene. One of these drugs is the valproic acid (VPA), a histone deacetylase inhibitor.MethodsTwenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC), the Hammersmith Functional Motor Scale (HFMS), and the Barthel Index.ResultsAfter 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period.ConclusionTreatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease.Trial RegistrationClinicalTrials.gov: NCT01033331