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Introducción: La Distrofia Muscular de Duchenne (DMD) y la Atrofia Muscular Espinal (AME) son enfermedades neuromusculares genéticas poco comunes pero graves en la población pediátrica con alta carga de morbilidad y mortalidad. A pesar de avances en su comprensión y búsqueda de opciones terapéuticas dirigidas, persisten vacíos en la detección oportuna, caracterización, seguimiento de pacientes, búsqueda activa de portadores y en algunos países de Latinoamérica sin tamización neonatal. Objetivo: Caracterizar clínica, paraclínica, imagenológica y molecularmente pacientes con diagnóstico presuntivo y confirmado de distrofia muscular de Duchenne (DMD) y Atrofia Muscular Espinal (AME) atendidos en un centro pediátrico de referencia y excelencia del Suroccidente Colombiano. Materiales y Métodos: Estudio observacional de corte transversal en pacientes menores de 18 años con diagnósticos CIE-10 relacionados con DMD y AME. Los datos se exportaron a una matriz de Excel en Office 365 versión 2403, y luego a IBM SPSS versión 29 para realizar un análisis univariado, se emplearon medidas de tendencia central y dispersión para variables numéricas, considerando su distribución, y frecuencias absolutas y porcentajes para variables cualitativas. Resultados: Tras revisar 954 historias clínicas pertenecientes a un centro de atención pediátrica en el Suroccidente Colombiano entre los años 2015 - 2021, se identificaron 422 casos relacionados a Distrofia Muscular de Duchenne (DMD) y Atrofia Muscular Espinal (AME); excluyendo duplicados y registros no relacionados, de estos, se seleccionaron aleatoriamente 99 casos para un análisis exhaustivo utilizando OpenEpi versión 3.01, distribuidos en dos grupos: AME (n=23) y DMD (n=76). Los pacientes confirmados con Distrofia Muscular de Duchenne (DMD) mostraron un inicio de síntomas a los 54,5 ± 29,0 meses y un diagnóstico a los 98,8 ± 34,9 meses, siendo más común en varones con hipotonía y niveles elevados de creatin quinasa (CK), el 54,5% presentaba trastorno cognitivo y el 88.2% tenía antecedentes familiares, en la Atrofia Muscular Espinal (AME), el inicio de síntomas fue a los 28,9 ± 37,7 meses y el diagnóstico a los 37,9 ± 38,2 meses, siendo predominante en mujeres con arreflexia y fasciculaciones, no hubo registros de la función cognitiva en los pacientes confirmados, y el 21,7% tenía antecedentes familiares de AME, además de ligeras elevaciones de CK. En el grupo AME, 9 casos se confirmaron molecularmente y 3 se respaldaron con registros médicos; en contraste, en el grupo de DMD, 22 casos tuvieron confirmación molecular, pero 9 contaban con anotaciones en los registros médicos, aunque estos informes eran incompletos. Conclusiones: La sospecha y diagnóstico temprano de estas enfermedades neurodegenerativas progresivas que se caracterizan por altas tasas de morbilidad y mortalidad es fundamental para impactar en el abordaje holístico que deben recibir los pacientes. Dado al continuo avance en métodos diagnósticos y opciones terapéuticas innovadoras y dirigidas ( medicina de la hiperpersonalización ), se hace necesario crear registros y "big data" médicos- clínicos completos, que cuenten con todas las herramientas actuales disponibles (opciones diagnósticas multimodales) que faciliten el re-contacto de pacientes, seguimiento y poderles ofrecer una atención personalizada, de precisión, que mejore la calidad de vida de ellos, sus familias, contribuyendo en la generación de políticas públicas integradas y dirigidas. (provisto por Infomedic International)

Introduction: Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) are rare but severe genetic neuromuscular diseases in the pediatric population with high burden of morbidity and mortality. Despite advances in their understanding and search for targeted therapeutic options, there are still gaps in timely detection, characterization, patient follow-up, active search for carriers and in some Latin American countries no neonatal screening. Objective: To characterize clinically, paraclinically, imaging and molecularly patients with presumptive and confirmed diagnosis of Duchenne muscular dystrophy (DMD) and Spinal Muscular Atrophy (SMA) attended in a pediatric center of reference and excellence in Southwestern Colombia. Materials and Methods: Observational cross-sectional study in patients under 18 years of age with ICD-10 diagnoses related to DMD and SMA. Data were exported to an Excel matrix in Office 365 version 2403, and then to IBM SPSS version 29 to perform a univariate analysis, measures of central tendency and dispersion were used for numerical variables, considering their distribution, and absolute frequencies and percentages for qualitative variables. Results: After reviewing 954 medical records belonging to a pediatric care center in Southwestern Colombia between 2015 - 2021, 422 cases related to Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) were identified; excluding duplicates and unrelated records, from these, 99 cases were randomly selected for a comprehensive analysis using OpenEpi version 3.01, distributed in two groups: SMA (n=23) and DMD (n=76). Patients confirmed with Duchenne Muscular Dystrophy (DMD) showed symptom onset at 54.5 ± 29.0 months and diagnosis at 98.8 ± 34.9 months, being more common in males with hypotonia and elevated creatin kinase (CK) levels, 54.5% had cognitive impairment and 88. 2% had family history, in Spinal Muscular Atrophy (SMA), the onset of symptoms was at 28.9 ± 37.7 months and diagnosis at 37.9 ± 38.2 months, being predominant in females with areflexia and fasciculations, there were no records of cognitive function in confirmed patients, and 21.7% had family history of SMA, in addition to slight elevations of CK. In the SMA group, 9 cases were molecularly confirmed and 3 were supported by medical records; in contrast, in the DMD group, 22 cases had molecular confirmation, but 9 had annotations in medical records, although these reports were incomplete. Conclusions: Early suspicion and diagnosis of these progressive neurodegenerative diseases characterized by high morbidity and mortality rates is critical to impact the holistic approach patients should receive. Given the continuous advance in diagnostic methods and innovative and targeted therapeutic options (hyperpersonalization medicine), it is necessary to create complete medical-clinical registries and big data, which have all the current tools available (multimodal diagnostic options) to facilitate patient re-contact, follow-up and to be able to offer personalized, precision care that improves the quality of life of patients and their families, contributing to the generation of integrated and targeted public policies. (provided by Infomedic International)

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La atrofia muscular espinal (AME) 5q es una de las enfermedades neuromusculares de mayor incidencia en la infancia. Sin embargo, la prevalencia de AME tipo 1, su forma más severa de presentación, es menor debido a muertes prematuras evitables antes de los dos años por insuficiencia ventilatoria subtratada. La irrupción de nuevos tratamientos modificadores de la enfermedad pueden cambiar dramáticamente este pronóstico y es una oportunidad para actualizar el manejo respiratorio, a través de cuidados estandarizados básicos, preferentemente no invasivos, abordando la debilidad de los músculos respiratorios, la insuficiencia tusígena y ventilatoria, con un enfoque preventivo. La siguiente revisión literaria entrega estrategias para evitar la intubación y la traqueostomía usando soporte ventilatorio no invasivo (SVN), reclutamiento de volumen pulmonar (RVP) y facilitación de la tos. Se analizan en detalle los protocolos de extubación en niños con AME tipo 1.

Spinal muscular atrophy (SMA) 5q is one of the neuromuscular diseases with the highest incidence in childhood. Nevertheless, the prevalence of its most severe form SMA1 is lower due to premature preventable deaths before two years of age related to ventilatory insufficiency undertreated. The emergence of new disease-modifying treatments can dramatically change this prognosis and is an opportunity to update respiratory management, through basic standardized care, mostly non-invasive, addressing respiratory muscles pump weakness, cough and ventilatory insufficiency with a preventive approach. This literature review provides consensus recommendations for strategies to avoid intubation and tracheostomy using noninvasive ventilatory support (NVS), lung volume recruitment (LVR), and cough facilitation. Extubation protocols in children with SMA type 1 are analyzed in detail.

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La atrofia muscular espinal (AME) de presentación temprana representa la variante más severa, con una expectativa de vida generalmente no mayor a dos años sin soporte ventilatorio, debido a la insuficiencia respiratoria y la dificultad para toser. Tradicionalmente, el manejo respiratorio en muchos países ha incluido la traqueostomía para proporcionar asistencia ventilatoria invasiva de manera continua. No obstante, la introducción de medicamentos de precisión ha modificado la progresión natural de la enfermedad, evidenciando mejoras significativas en los hitos motores y beneficiando también la función respiratoria. A pesar de estas mejoras, en muchos casos sigue siendo necesaria la ventilación intermitente y/o continua, además de la facilitación de la tos. Estas necesidades pueden abordarse de forma no invasiva mediante el soporte ventilatorio no invasivo (SVN), la in-exsuflación mecánica (IEM) y el reclutamiento de volumen pulmonar (RVP), que son considerados pilares del tratamiento respiratorio en enfermedades neuromusculares. Estas estrategias promueven el desarrollo y mantenimiento de la función respiratoria, reduciendo el riesgo de exacerbaciones respiratorias que podrían llevar a intubaciones evitables. Comúnmente, los pacientes con AME experimentan intentos fallidos de extubación siguiendo protocolos tradicionales, siendo catalogados como no extubables y potenciales candidatos a traqueostomía. No obstante, existen protocolos de extubación específicos para AME que emplean SVN e IEM con un alto porcentaje de éxito, evitando traqueostomías innecesarias que pueden complicar la progresión de la enfermedad y afectar la calidad de vida. El enfoque respiratorio no invasivo es una opción de manejo segura tanto en el hospital como en el hogar, ofreciendo una mejor calidad de vida para los pacientes y sus familias.

Early-onset spinal muscular atrophy (SMA) is the most severe variant, with a life expectancy generally not exceeding two years without ventilatory support due to respiratory insufficiency and difficulty in coughing. Traditionally, respiratory management in many countries has included tracheostomy to provide continuous invasive ventilatory support. However, the introduction of precision medicine has altered the natural progression of the disease, showing significant improvements in motor milestones and also benefiting respiratory function. Despite these improvements, many cases still require intermittent and/or continuous ventilation, as well as cough facilitation. These needs can be addressed non-invasively through non-invasive ventilatory support (NIV), mechanical insufflation-exsufflation (MIE), and lung volume recruitment (LVR), which are considered the pillars of respiratory treatment in neuromuscular diseases. These strategies promote the development and maintenance of respiratory function, reducing the risk of respiratory exacerbations that could lead to avoidable intubations. Commonly, SMA patients experience failed extubation attempts following traditional protocols, being labeled as non-extubatable and potential candidates for tracheostomy. Nevertheless, there are specific extubation protocols for SMA that employ NIV and MIE with a high success rate, avoiding unnecessary tracheostomies that can complicate disease progression and impact quality of life. The non-invasive respiratory approach is a safe management option both in the hospital and at home, offering a better quality of life for patients and their families.

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OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the onasemnogene abeparvovec in relation to nusinersen and risdiplam in the treatment of spinal muscular atrophy type 1 from the perspective of the Brazilian Unified Health System. METHODS: A Markov model was built on a lifetime horizon. Short-term data were obtained from clinical trials of the technologies and from published cohort survival curves (long term). Costs were measured in current 2022 local currency (R$) values and benefits in quality-adjusted life-years (QALYs). Utility values were derived from type 1 spinal muscular atrophy literature, whereas costs related to technologies and maintenance care in each health state were obtained from official sources of reimbursement in Brazil. Deterministic and probabilistic, as well as scenario, sensitivity analyses were performed. RESULTS: Compared with the less costly strategy (nusinersen), the use of onasemnogene abeparvovec resulted in an incremental cost of R$2.468.448,06 ($975 671.169 - purchasing power parity [PPP]) and a 3-QALY increment and incremental cost-effectiveness ratio of R$742.890,92 ($293 632.774 - PPP)/QALY. Risdiplam had an extended dominance from other strategies, resulting in an incremental cost-effectiveness ratio of R$926.586,22 ($366 239.612 - PPP)/QALY compared with nusinersen. Sensitivity analysis showed a significant impact of the follow-up time of the cohort and the cost of acquiring onasemnogene abeparvovec. CONCLUSIONS: Over a lifetime horizon, onasemnogene abeparvovec seems to be a potentially more effective option than nusinersen and risdiplam, albeit with an incremental cost. Such a trade-off should be weighed in efficiency criteria during decision making and outcome monitoring from the perspective of the Brazilian Unified Health System.

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Abstract Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes.

Resumo Atrofia muscular espinhal ligada ao cromossomo 5 (AME-5q) é uma doença genética de herança autossômica recessiva causada por mutações no gene SMN1. A AME-5q cursa com degeneração progressiva dos motoneurônios medulares e bulbares, acarretando grave comprometimento motor e respiratório com redução da sobrevida, especialmente nas suas formas clínicas mais graves. Nos últimos anos, terapias modificadoras da doença altamente eficazes, ou que atuam regulando o splicing do exon 7 do gene SMN2 ou adicionando uma cópia do gene SMN1 via terapia gênica, têm surgido, proporcionando uma mudança drástica na história natural da doença. Dessa forma, o desenvolvimento de guias terapêuticos e de consensos de especialistas torna-se importante no sentido de direcionar o uso dessas terapias na prática clínica. Este consenso, preparado por especialistas brasileiros, teve como objetivos revisar as principais terapias modificadoras de doença disponíveis, analisar criticamente os resultados dos estudos clínicos dessas terapias e prover recomendações para seu uso na prática clínica para pacientes com AME-5q. Aspectos relativos ao diagnóstico, aconselhamento genético e seguimento dos pacientes em uso das terapias também são abordados nesse consenso. Assim, esse consenso promove valiosas informações a respeito do manejo atual da AME-5q auxiliando decisões terapêuticas na prática clínica e promovendo ganhos adicionais nos desfechos finais.

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Abstract Background The Hammersmith Functional Motor Scale Expanded (HFMSE) has been widely used to assess the motor function of patients with spinal muscular atrophy (SMA) older than 2 years, with the ability to sit and/or walk. Objective To translate, cross-culturally adapt and validate the HFMSE to Brazilian Portuguese. Methods The translation process and cross-cultural adaptation followed international guidelines recommendations. The reliability and applicability of the Brazilian version consisted of the application of the HFMSE (in Brazilian Portuguese) to 20 patients with types 2 and 3 SMA. Two examiners assessed the participants for interrater reliability, through the analysis of Kappa reliability agreement (k) and intraclass correlation coefficient (ICC). Results The HFMSE was successfully translated and cross culturally adapted to Brazilian Portuguese. Twenty participants with types 2 and 3 SMA were enrolled in the study (type 2 = 6; type 3 = 14). The ICC for the total score showed very high reliability (ICC =1.00), and the reliability of each of the items individually was considered excellent (Kappa > 0.80). Conclusion The Brazilian version of the HFMSE proved to be valid and reliable for the evaluation of SMA patients older than 2 years with the ability to sit and/or walk.

Resumo Antecedentes A Hammersmith Functional Motor Scale Expanded (HFMSE) tem sido amplamente utilizada para avaliar a função motora de pacientes com atrofia muscular espinhal (AME) maiores de dois anos, com capacidade de sentar e/ou andar. Objetivo Traduzir, adaptar transculturalmente e validar a HFMSE para o português brasileiro. Métodos A tradução e a adaptação transcultural seguiram as diretrizes internacionais. A confiabilidade e a aplicabilidade da versão brasileira consistiram na aplicação da HFMSE (em português brasileiro) em 20 pacientes com AME tipos 2 e 3. Dois examinadores avaliaram os participantes quanto à confiabilidade interexaminadores, por meio da análise da concordância de confiabilidade Kappa (k) e do coeficiente de correlação intraclasse (intraclass correlation coefficient [ICC]). Resultados O processo de tradução e adaptação transcultural da HFMSE para o português brasileiro foi concluído com sucesso. Vinte participantes com AME tipos 2 e 3 foram incluídos no estudo (tipo 2 = 6; tipo 3 = 14). O ICC para o escore total apresentou confiabilidade alta (ICC = 1.00) e a confiabilidade de cada um dos itens individualmente foi considerada excelente (K > 0,80). Conclusão A HFMSE (PT-BR) mostrou-se válida e confiável para a avaliação de pacientes com AME, com mais de dois anos de idade e com capacidade de sentar-se independentemente e/ou andar.

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ABSTRACT OBJECTIVE To investigate the costs and profile of patients who have filed a lawsuit against the Ministry of Health for the treatment of spinal muscular atrophy (SMA) with the onasemnogene abeparvovec (Zolgensma®). METHODS This is a cross-sectional, descriptive study with a census design, based on records of lawsuits filed against the Ministry of Health between January 2019 and September 2022. Data was requested from the Ministry of Health via the Access to Information Act. Information was extracted on the epidemiological profile of the beneficiaries of the lawsuits, as well as the expenses spent by the Ministry of Health in cases where the requests were granted. RESULTS 136 lawsuits were identified, of which 113 (83%) were favorable to patients at a cost of R$ 944.8 million in the period analyzed. Demographic (gender and age), clinical (SMA subtypes, use of ventilatory or nutritional support), and lawsuit (type of legal service) characteristics were not associated with the granting of lawsuits. Prior use of medication (nusinersena or ridisplam) was associated with the dismissal of lawsuits. Of the 113 lawsuits granted in favor of patients, only six (5.3%) would meet the criteria currently established by the National Committee for Health Technology Incorporation - Conitec (children up to six months without ventilatory and nutritional support). R$ 146 million was spent on supplying Zolgensma to children over the age of two, which is outside the recommendation contained in the drug's package leaflet. CONCLUSIONS The Ministry of Health incurs a high cost with the judicialization of Zolgensma for SMA, representing 2.45% of total spending on medicines in the Unified Health System, including spending by the three administrative spheres. Some of the lawsuits have been granted in disagreement with the criteria established by health technology assessment agencies and the drug manufacturer's recommendations.

RESUMO OBJETIVO Investigar os custos e o perfil dos pacientes que demandaram judicialmente o onasemnogene abeparvoveque (Zolgensma®) para o tratamento da atrofia muscular espinhal (AME) no Ministério da Saúde. MÉTODOS Estudo transversal, de natureza descritiva e desenho censitário, com base em registros de ações judiciais movidas contra o Ministério da Saúde no período de janeiro de 2019 a setembro de 2022. Os dados foram solicitados ao Ministério da Saúde, via Lei de Acesso à Informação. Foram extraídas informações sobre o perfil epidemiológico dos beneficiários das ações judiciais, bem como os gastos dispendidos pelo Ministério da Saúde nos casos de deferimento das solicitações. RESULTADOS Foram identificados 136 processos judiciais, dos quais 113 (83%) foram favoráveis aos pacientes ao custo de R$ 944,8 milhões no período analisado. Características demográficas (sexo e idade), clínicas (subtipos da AME, uso de suporte ventilatório ou nutricional) e do processo judicial (tipo de serviço advocatício) não foram associadas com o deferimento das ações judiciais. O uso prévio de medicamento (nusinersena ou ridisplam) foi associado com o indeferimento dos processos judiciais. Das 113 ações judiciais concedidas em favor dos pacientes, apenas seis (5,3%) atenderiam aos critérios estabelecidos atualmente pela Comissão Nacional de Incorporação de Tecnologias - Conitec (crianças com até seis meses sem suporte ventilatório e nutricional). Houve dispêndio de R$ 146 milhões com o fornecimento do Zolgensma para crianças com idade superior a dois anos, que está fora da recomendação contida na bula do medicamento. CONCLUSÕES O Ministério da Saúde incorre em um alto custo com a judicialização do Zolgensma para AME, representando 2,45% do gasto total com medicamentos no Sistema Único de Saúde, incluindo gastos das três esferas administrativas. Parte das demandas judiciais tem sido deferida em divergência com os critérios estabelecidos por agências de avaliação de tecnologias em saúde e recomendações do fabricante do medicamento.

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Abstract Neuromuscular diseases (NMD) include a broad group of medical conditions with both acquired and genetic causes. In recent years, important advances have been made in the treatment of genetically caused NMD, and most of these advances are due to the implementation of therapies aimed at gene regulation. Among these therapies, gene replacement, small interfering RNA (siRNA), and antisense antinucleotides are the most promising approaches. More importantly, some of these therapies have already gained regulatory approval or are in the final stages of approval. The review focuses on motor neuron diseases, neuropathies, and Duchenne muscular dystrophy, summarizing the most recent developments in gene-based therapies for these conditions.

Resumo Doenças neuromusculares (DNM) compõem um grupo amplo de doenças de causa tanto adquiridas quanto genéticas. Nos últimos anos, importantes avanços ocorreram quanto ao tratamento das DNM de causa genética e grande parte desses avanços se deve à implementação de terapias voltadas para a modificação gênica. Dentre essas terapias, destacam-se as terapias de reposição gênica, uso de RNA de interferência, uso de antinucleotídeos antisense, entre outras. E, mais importante, algumas dessas terapias já se tornaram realidade na prática médica e já foram aprovadas, ou estão a poucos passos da aprovação, por órgãos governamentais regulatórios. Esta revisão aborda aspectos mais recentes quanto ao uso das terapias genéticas avançadas para algumas das formas mais comuns de DNM, em especial para doenças do neurônio motor (esclerose lateral amiotrófica e atrofia muscular espinhal), neuropatias e distrofia muscular de Duchenne.

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INTRODUCCIÓN: La ecografía muscular es una herramienta válida para monitorizar la pérdida de masa muscular de personas críticamente enfermas. El nivel de experiencia es clave para la precisión de las mediciones. Objetivo: Evaluar la confiabilidad interobservador de evaluadores experimentados y novatos midiendo grosor y eco-intensidad del cuádriceps y tibial anterior. Métodos: Estudio observacional transversal. Participaron 24 kinesiólogos de cuidados críticos; 5 experimentados (> 4 años de experiencia ecográfica) y 19 novatos (sin experiencia previa, por lo que recibieron entrenamiento de 16 horas). De forma estandarizada, cada evaluador midió ecográficamente el grosor (centímetros) del cuádriceps y tibial anterior de 10 modelos sanos y jóvenes usando equipos portátiles (transductores lineales y convexos). Se calculó el Coeficiente de Correlación Intraclase y el Cambio Mínimo Detectable (95% intervalo de confianza). Además, los novatos calificaron la eco-intensidad de 19 ecografías musculares de personas críticamente enfermas con la escala Heckmatt (calificación visual cualitativa) y se midió el acuerdo con los experimentados (Spearman Rho). RESULTADOS: Se realizaron 960 mediciones de grosor muscular (experimentados = 200 y novatos = 760). La media del grosor del cuádriceps y tibial anterior fue 4,4 ± 0,77 y 2,4 ± 0,35 centímetros para los experimentados y 4,2 ± 0,80 y 2,2 ± 0,39 centímetros para los novatos, respectivamente. La confiabilidad de cuádriceps y tibial anterior fue 0,82 y 0,86 para los experimentados y 0,76 y 0,41 para los novatos. El Cambio Mínimo Detectable osciló entre 0,14-0,33 centímetros. La puntuación media de Heckmatt fue 2,6 ± 0,83 puntos, con una confiabilidad de 0,68 y una concordancia con los experimentados de 0,78 [p < 0,001]. CONCLUSIONES: La confiabilidad interobservador de los experimentados fue excelente y la de los novatos moderada a buena. El nivel de experiencia podría determinar los resultados de confiabilidad.

BACKGROUND: Muscle ultrasound is a valid tool to monitor muscle mass loss in critically ill patients. The level of experience is essential to the accuracy of the measurements. Aim: To evaluate the interobserver reliability of experienced and novice raters measuring muscle thickness and echo intensity of the quadriceps and tibialis anterior. MATERIAL AND METHODS: Cross-sectional observational study. Twenty-four critical care physiotherapists participated (5 experienced and 19 novice). Following a standardized ultrasound protocol, each rater measured the thickness (centimeters) of the quadriceps and tibialis anterior of 10 healthy and young models using linear and convex probes of portable devices. The Intraclass Correlation Coefficient and the Minimal Detectable Change (95% confidence interval) were calculated. Additionally, the novices scored the echo intensity of 19 muscle ultrasound images of critically ill patients using the Heckmatt score (qualitative assessment). The agreement with experienced raters was evaluated (Spearman Rho). Results: 960 muscle thickness measurements were performed (experienced = 200 and novice = 760). The mean thickness of the quadriceps and tibialis anterior was 4.4 ± 0.77 and 2.4 ± 0.35 centimeters for the experienced and 4.2 ± 0.80 and 2.2 ± 0.39 centimeters for the novices, respectively. Quadriceps' and tibialis' anterior reliability were 0.82 and 0.86 for experienced and 0.76 and 0.41 for novices, respectively. The Minimal Detectable Change ranged from 0.14-0.33 centimeters. The mean Heckmatt score was 2.6 ± 0.83 points, with a reliability of 0.68 and an agreement with the experimenters of 0.78 [p < 0.001]. CONCLUSIONS: Interobserver reliability was excellent for experienced raters and moderate to good for novice raters. The level of experience could determine the reliability of the results.

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Abstract Background Spinal muscular atrophy (SMA) is a rare genetic disease that causes progressive muscle weakness and impacts motor function. The type I is the most severe presentation and affects infants before 6 months old. In addition, the instruments available for assessing motor function have limitations when applied to infants with neuromuscular diseases and significant muscle weakness. Objective To translate, cross-culturally adapt, and validate the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) to Brazilian Portuguese. Methods The present study comprised the translation, synthesis of translations, backtranslation, consolidation by a committee of experts, and test of the final version of the CHOP INTEND in 13 patients with SMA type I. We also assessed the content validity and reliability of the translated version. Results The scale was translated considering semantic, structural, idiomatic, and cultural aspects. All agreement rates were > 0.8, the overall content validity index of the instrument was 0.98, and inter-rater reliability using the intraclass correlation coefficient was 0.998. Conclusion The Brazilian version of the CHOP INTEND met semantic and technical equivalence criteria with the original version and was valid and reliable for patients with SMA type I.

Resumo Antecedentes A atrofia muscular espinhal (AME) é uma doença genética rara que provoca fraqueza muscular progressiva com impacto sobre a motricidade dos pacientes. A AME tipo I é considerada o tipo mais grave e acomete lactentes antes dos 6 meses de idade. As escalas disponíveis para avaliação das aquisições motoras mostram limitações para uso com crianças pequenas com doenças neuromusculares e fraqueza importante. Objetivo Realizar a tradução, adaptação transcultural e validação para a língua portuguesa do Brasil da Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND, na sigla em inglês). Métodos O presente estudo seguiu as etapas de tradução, síntese das traduções, retrotradução, consolidação por comitê de especialistas e teste com 13 pacientes com AME tipo 1. Foi avaliada a validade de conteúdo e a confiabilidade do instrumento. Resultados A escala foi traduzida considerando os aspectos semânticos, estruturais, idiomáticos e culturais. Todas as taxas de concordância foram > 0,8. O índice de validade de conteúdo geral do instrumento foi de 0,98. A confiabilidade interavaliadores analisada através do coeficiente de correlação intraclasse (ICC, na sigla em inglês) demonstrou um valor de ICC = 0,998. Conclusão A versão da CHOP INTEND em português atende aos critérios de equivalência semântica e técnica em relação à versão original e apresenta validade de conteúdo e confiabilidade para seu uso na população de pacientes com AME tipo I.

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Introducción. Con las nuevas terapias, el diagnóstico temprano de la atrofia muscular espinal (AME) es esencial. El objetivo de este estudio es analizar los distintos componentes que influyen en el retraso diagnóstico. Población y métodos. Se incluyeron pacientes con un diagnóstico molecular de AME tipo I, II y III. Se estudiaron varios parámetros, como la edad al momento de la aparición del primer signo, qué signo fue y el intervalo entre este y el diagnóstico confirmado. Neurólogos especialistas realizaron entrevistas que se complementaron con la revisión de historias clínicas cuando fue necesario. Resultados. Se entrevistaron 112 pacientes. AME I n = 40, AME II n = 48, AME III n = 24. La mediana de edad en meses al momento del reporte del primer signo fue AME I: 1,5 (R 0-7), AME II: 9 (R 2-20), AME III: 18 (R 8-180). Los primeros signos fueron reconocidos por los padres en el 75 % al 85 % de las veces en todos los subtipos. La mediana del tiempo transcurrido entre el primer signo y la primera consulta médica fue menor a un mes en los tres tipos. La mediana de tiempo transcurrido en meses entre el primer signo y el diagnóstico molecular confirmado fue en AME I: 2 (R 0-11), en AME II: 10 (3-46) y en AME III: 31,5 (R 4-288). Conclusiones. Existe un significativo retraso en el diagnóstico de la AME relacionado fundamentalmente a la falta de sospecha clínica. La demora es menor en AME I y mayor en AME III. Otros factores incluyen deficiencias en el sistema de salud.

Introduction. News treatments, make early diagnosis of spinal muscular atrophy (SMA) critical. The objective of this study is to analyze the different factors that influence delay in diagnosis. Population and methods. Patients with a molecular diagnosis of types I, II, and III SMA were included. Several parameters were studied, such as age at onset of first sign, what sign it was, and the time from recognition of first sign to confirmed diagnosis. Neurologists specialized in SMA conducted interviews, supported by the review of medical records when deemed necessary. Results. A total of 112 patients were interviewed. SMA I n = 40, SMA II n = 48, SMA III n = 24. The median age in months at the time of reporting the first sign was SMA I: 1.5 (R: 0­7), SMA II: 9 (R: 2­20), SMA III: 18 (R: 8­180). In all subtypes, first signs were identified by parents from 75% to 85% of the times. The median time from first sign to first medical consultation was less than a month in all 3 types. The median time in months, from first sign to confirmed molecular diagnosis in SMA I was: 2 (R: 0­11), in SMA II: 10 (R: 3­46), in SMA III: 31.5 (R: 4­288). Conclusions. There is a significant delay in SMA diagnosis mainly related to the absence of clinical suspicion. The delay is shorter in SMA I and longer in SMA III. Other factors include deficiencies in the health care system.

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ABSTRACT Quantitative assessments of rotator cuff muscle changes after successful tendon repair are scarce. On the other hand, semiquantitative and subjective assessments are more abundant, but their findings are controversial. One hypothesis about this divergence is that there is an immediate decrease in the proportion of fatty infiltration after surgical repair. Objective: Reassess fatty infiltration and muscle trophism of the rotator cuff after ten years of repair. Methods: Prospective comparison study. A total of 10 patients diagnosed with rotator cuff injury underwent repair of the lesion, and MRI of the affected shoulder was performed in the preoperative, immediate postoperative, and late postoperative periods (ten years). A comparative study was performed at every moment. Results: At 5% significance level, the mean of the immediate postoperative period was higher for the variable trophism and true muscle percentage. Fatty infiltration showed no difference in the three periods observed. Conclusion: Fatty infiltration does not change in the three periods evaluated and muscle trophism is greater in the immediate postoperative period. After ten years of rotator cuff repair, muscle trophism and fatty infiltration remain with statistically significantly equal results when compared to the preoperative period. Level of Evidence II, Prospective Comparison Study.

RESUMO Avaliações quantitativas das mudanças musculares do manguito rotador após reparos bem-sucedidos são escassas. Em contrapartida, avaliações semiquantitativas e subjetivas são mais abundantes, porém com achados controversos. Uma hipótese sobre essa discrepância é que a diminuição imediata na proporção de gordura que ocorre logo após o reparo. Objetivo: Reavaliar a infiltração gordurosa e o trofismo muscular do manguito rotador passados dez anos do reparo. Métodos: Estudo prospectivo comparativo realizado com dez pacientes diagnosticados com lesão do manguito rotador que foram submetidos a reparo da lesão e exames de ressonância magnética do ombro acometido no pré-operatório, no pós-operatório imediato e no pós-operatório tardio (dez anos), a fim de comparar as mudanças musculares em cada momento. Resultados: Ao nível de significância de 5%, a média do pós-operatório imediato foi superior para as variáveis trofismo e porcentagem muscular verdadeira. A infiltração gordurosa não apresentou diferença nos três períodos observados. Conclusão: A infiltração gordurosa não se altera nos três períodos avaliados, e o trofismo muscular é maior no pós-operatório imediato. Após dez anos do reparo do manguito rotador, o trofismo muscular e a infiltração gordurosa se mantêm com resultados estatísticos significativamente iguais quando comparados com o pré-operatório. Nível de Evidência II, Estudo Prospectivo Comparativo.

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Introducción. La polineuropatía, la miopatía y la polineuromiopatía son condiciones debilitantes que afectan a pacientes críticamente enfermos. Sin embargo, poco se conoce acerca de los factores relacionados con estos desenlaces en pacientes hospitalizados en las unidades de cuidado intensivo (UCI) y con hospitalización prolongada en el contexto clínico colombiano. Objetivo. Evaluar los factores asociados al desarrollo de polineuropatía, miopatía y polineuromiopatía en pacientes críticos con hospitalización prolongada. Métodos. Estudio analítico, observacional, de casos y controles apareados realizado en 192 pacientes (64 casos y 128 controles) atendidos en una clínica de tercer nivel de atención de Cali, Colombia. Se analizaron diferentes factores de riesgo como falla multiorgánica, sepsis, desnutrición, nutrición parenteral, uso de corticoides, uso de relajantes musculares, entre otros. Se evaluó si los días de estancia en UCI es un modificador del efecto de la relación entre estos factores y los desenlaces. Resultados. Se encontró que la falla multiorgánica (OR: 6,32, IC95%: 2,15-18,58), la desnutrición (OR: 2,25, IC95%: 1,01-5,0) y el uso de relajantes musculares (OR: 2,68, IC95%: 1,04-6,87) estuvieron asociados con el desarrollo de polineuropatía y miopatía. Así mismo, se observó que la asociación entre la falla multiorgánica y estas condiciones se vio afectada por la duración de la estancia en UCI (p<0,05). En pacientes sin falla multiorgánica, el riesgo aumentó mínimamente con cada día adicional de estancia en UCI (OR: 1,004, IC95%: 0,97-1,04); sin embargo, en pacientes con falla multiorgánica, el riesgo se incrementó en un 5% por cada día adicional de estancia en UCI. Conclusiones. Los resultados del presente estudio destacan la importancia de factores como la falla multiorgánica, la desnutrición y el uso de relajantes musculares en el desarrollo de la polineuropatía, la miopatía y la polineuromiopatía en pacientes críticos con hospitalización prolongada.

Introduction. Polyneuropathy, myopathy, and polyneuromyopathy are debilitating conditions that affect critically ill patients. However, little is known about the factors related to these outcomes in patients hospitalized in intensive care units (ICUs) and with prolonged hospitalization in the Colombian clinical context. Objective. To assess the factors associated with the development of polyneuropathy, myopathy and polyneuromyopathy in critically ill patients with prolonged hospitalization. Methods. Analytical, observational, matched case-control study conducted in 192 patients (64 cases and 128 controls) treated at a tertiary care clinic in Cali, Colombia. Different risk factors such as multi-organ failure, sepsis, malnutrition, parenteral nutrition, use of corticosteroids, use of muscle relaxants, among others, were analyzed. We assessed whether the length of stay in the ICU is a modifier of the effect of the relationship between these factors and the outcomes. Results. It was found that multiorgan failure (OR: 6.32, 95%CI: 2.15-18.58), malnutrition (OR: 2.25, 95%CI: 1.01-5.0) and the use of muscle relaxants (OR: 2.68, 95%CI: 1.04-6.87) were associated with the development of polyneuropathy and myopathy. Likewise, it was observed that the association between multi-organ failure and these conditions was affected by the length of stay in the ICU (p<0.05). In patients without multi-organ failure, the risk increased minimally with each additional day of stay in the ICU (OR: 1.004, 95%CI: 0.97-1.04); however, in patients with multi-organ failure, the risk increased by 5% for each additional day of stay in the ICU. Conclusions. The results of the present study highlight the importance of factors such as multi-organ failure, malnutrition and the use of muscle relaxants in the development of polyneuropathy, myopathy and polyneuromyopathy in critically ill patients with prolonged hospitalization.

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El síndrome de Down (SD) es la anomalía cromosómica más frecuente entre los recién nacidos vivos. La atrofia muscular espinal (AME), por su parte, es una enfermedad neuromuscular caracterizada por la degeneración progresiva de las motoneuronas del asta anterior de la médula espinal que produce atrofia muscular, debilidad y parálisis. Presentamos el caso de una niña de 6 años con síndrome de Down derivada a nuestro centro para estudio por cuadro de debilidad muscular generalizada de evolución crónica con falta de adquisición de la marcha. Realizamos una revisión bibliográfica enfocándonos en el compromiso neurológico esperable en el síndrome de Down, la evolución de los hitos del desarrollo motor grueso estipulado para este grupo de pacientes y en los hallazgos que deben sugerir la presencia de una enfermedad neuromuscular.

A case of a 6-year-old girl with Down's syndrome is presented. She was referred to our center due to a history of generalized muscle weakness of chronic evolution, associated to her inability to walk. Her mother claimed that the girl's muscle weakness always called her attention as well as the difficulties to the development of motor skills shown by her daughter compared to other children, whether they were healthy or with Down's syndrome. There was information in her medical record and physical exam that strongly suggested the possibility of suffering a neuromuscular disorder. We asked for a molecular study that confirmed the spinal muscular atrophy diagnosis. We carried out a bibliographical revision focusing on the expected neurological impairment in Down's syndrome, the retardation of the gross motor skills development determined for this kind of patients and on the findings that must suggest a neuromuscular disorder.

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Objetivo: Realizar o acompanhamento de crianças e adolescentes com Atrofia Muscular Espinhal (AME) e Distrofia Muscular de Duchenne (DMD) em um centro de referência, por meio de avaliações de parâmetros respiratórios e motores. Métodos: Conduziu-se 3 avaliações em um período de 24 meses, em pacientes até 15 anos, com DMD e AME. Avaliações respiratórias incluíram: parâmetros cardiorrespiratórios, força muscular respiratória, pico de fluxo de tosse e espirometria. Analisou-se a função motora por meio de escalas especificas: 1) Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) para crianças até 2 anos; 2) Medida da Função Motora (MFM-32) acima de 6 anos; 3) versão reduzida (MFM-20) para 2 a 6 anos. A análise estatística incluiu o teste de Shapiro-Wilk e utilizou-se ANOVA com Post Hoc de Bonferroni ou Friedman, e aplicou-se os coeficientes de Spearman ou Pearson. Resultados: Participaram 16 pacientes com mediana de idade de 6,5 anos, 12 com AME e 4 DMD. Houve diferença entre dados antropométricos, a frequência de crianças que não realizava fisioterapia reduziu (12,5%X6,3%) e houve aumento na adesão para técnica de empilhamento de ar (37,5%X43,8%). Uso de ventilação não invasiva se manteve igual, assim como parâmetros respiratórios e escalas motoras. Verificou-se forte correlação entre valor predito da capacidade vital forçada e escores MFM-20 e MFM-32. Conclusão: O acompanhamento ambulatorial de crianças com AME e DMD evidenciou relativa manutenção em parâmetros respiratórios e de função motora, o que pode ser atribuído a melhora na adesão de rotinas terapêuticas e aos cuidados em um centro de referência.

Objective: The aim of this study was to monitor children and adolescents with Spinal Muscular Atrophy(SMA) and Duchenne Muscular Dystrophy (DMD) at a referral center, through assessments of respiratory and motor parameters. Methods: 3 evaluations were conducted over a period of 24 months, in patients up to 15 years old, with DMD and SMA. Respiratory assessments included: cardiorespiratory parameters, respiratory muscle strength, peak cough flow and spirometry. Motor function was analyzed using specific scales: 1) Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for children up to 2 years old; 2) Measurement of Motor Function (MFM-32) over 6 years; 3) reduced version (MFM-20) for 2 to 6 years. The statistical analysis included the Shapiro-Wilk test and ANOVA with Bonferroni or Friedman's Post Hoc was used, and the Spearman or Pearson coefficients were applied. Results: 16 patients with a median age of 6.5 years, 12 with SMA and 4 DMD participated. There was a difference between anthropometric data, the frequency of children who did not undergo physical therapy decreased (12.5%X6.3%) and there was an increase in adherence to the air stacking technique (37.5%X43.8%). Use of non-invasive ventilation remained the same, as did respiratory parameters and motor scales. There was a strong correlation between the predicted value of forced vital capacity and scores MFM-20 and MFM-32. Conclusion: Outpatient follow-up of children with SMA and DMD showed a relative maintenance of respiratory and motor function parameters, which can be attributed to the improvement in adherence to therapeutic routines and care in a reference center.

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RESUMO Objetivo: Verificar a relação entre área de secção transversa do reto femoral e excursão diafragmática com sucesso no desmame da ventilação mecânica em pacientes críticos crônicos com traqueostomia. Métodos: Este foi um estudo de coorte observacional prospectivo. Incluímos pacientes críticos crônicos (aqueles submetidos à colocação de traqueostomia após 10 dias de ventilação mecânica). A área de secção transversa do reto femoral e a excursão diafragmática foram obtidas por ultrassonografia realizada dentro das primeiras 48 horas após a traqueostomia. Medimos a área de secção transversa do reto femoral e a excursão diafragmática para avaliar sua associação com o desmame da ventilação mecânica, incluindo sua capacidade de prever o sucesso no desmame e a sobrevida durante toda a internação na unidade de terapia intensiva. Resultados: Foram incluídos 81 pacientes. Quarenta e cinco pacientes (55%) foram desmamados da ventilação mecânica. A mortalidade foi de 42% e 61,7% na unidade de terapia intensiva e hospitalar, respectivamente. O grupo que falhou em relação ao grupo que obteve sucesso no desmame apresentou menor área transversa do reto femoral (1,4 [0,8] versus 1,84 [0,76]cm2, p = 0,014) e menor excursão diafragmática (1,29 ± 0,62 versus 1,62 ± 0,51cm, p = 0,019). Quando a área de secção transversa do reto femoral ≥ 1,80cm2 e a excursão diafragmática ≥ 1,25cm era uma condição combinada, apresentava forte associação com sucesso no desmame (RC ajustada de 20,81; IC95% 2,38 - 182,28; p = 0,006), mas não com sobrevida na unidade de terapia intensiva (RC ajustada de 0,19; IC95% 0,03 - 1,08; p = 0,061). Conclusão: O sucesso no desmame da ventilação mecânica em pacientes críticos crônicos foi associado a medidas maiores de área de secção transversa do reto femoral e da excursão diafragmática.

ABSTRACT Objective: To verify the relationship between the rectus femoris cross-sectional area and diaphragmatic excursion with successful weaning from mechanical ventilation in chronic critically tracheostomized patients. Methods: This was a prospective observational cohort study. We included chronic critically ill patients (those who underwent tracheostomy placement after 10 days under mechanical ventilation). The rectus femoris cross-sectional area and diaphragmatic excursion were obtained by ultrasonography performed within the first 48 hours after tracheostomy. We measured rectus femoris cross-sectional area and diaphragmatic excursion to assess their association with weaning from mechanical ventilation, including their potential to predict successful weaning and survival throughout the intensive care unit stay. Results: Eighty-one patients were included. Forty-five patients (55%) were weaned from mechanical ventilation. The mortality rates were 42% and 61.7% in the intensive care unit and hospital, respectively. The fail group in relation to the success group at weaning presented a lower rectus femoris cross-sectional area (1.4 [0.8] versus 1.84 [0.76]cm2, p = 0.014) and lower diaphragmatic excursion (1.29 ± 0.62 versus 1.62 ± 0.51cm, p = 0.019). When rectus femoris cross-sectional area ≥ 1.80cm2 and diaphragmatic excursion ≥ 1.25cm was a combined condition, it had a strong association with successful weaning (adjusted OR = 20.81, 95%CI 2.38 - 182.28; p = 0.006) but not with intensive care unit survival (adjusted OR = 0.19, 95%CI 0.03 - 1.08; p = 0.061). Conclusion: Successful weaning from mechanical ventilation in chronic critically ill patients was associated with higher measurements of rectus femoris cross-sectional area and diaphragmatic excursion.

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A case of a 6-year-old girl with Down's syndrome is presented. She was referred to our center due to a history of generalized muscle weakness of chronic evolution, associated to her inability to walk. Her mother claimed that the girl's muscle weakness always called her attention as well as the difficulties to the development of motor skills shown by her daughter compared to other children, whether they were healthy or with Down's syndrome. There was information in her medical record and physical exam that strongly suggested the possibility of suffering a neuromuscular disorder. We asked for a molecular study that confirmed the spinal muscular atrophy diagnosis. We carried out a bibliographical revision focusing on the expected neurological impairment in Down's syndrome, the retardation of the gross motor skills development determined for this kind of patients and on the findings that must suggest a neuromuscular disorder.

El síndrome de Down (SD) es la anomalía cromosómica más frecuente entre los recién nacidos vivos. La atrofia muscular espinal (AME), por su parte, es una enfermedad neuromuscular caracterizada por la degeneración progresiva de las motoneuronas del asta anterior de la médula espinal que produce atrofia muscular, debilidad y parálisis. Presentamos el caso de una niña de 6 años con síndrome de Down derivada a nuestro centro para estudio por cuadro de debilidad muscular generalizada de evolución crónica con falta de adquisición de la marcha. Realizamos una revisión bibliográfica enfocándonos en el compromiso neurológico esperable en el síndrome de Down, la evolución de los hitos del desarrollo motor grueso estipulado para este grupo de pacientes y en los hallazgos que deben sugerir la presencia de una enfermedad neuromuscular.

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Abstract A 26-year-old previously healthy patient who, at the age of 18 years, began progressive loss of distal strength, rest tremor, and muscle atrophy in the left upper limb. Upon examination, the patient presented moderate distal atrophy, degree 4 in muscular strength, and minipolymioclonus. Electromyoneurography revealed (EMNG) chronic preganglionic bilateral involvement of bilateral C7/C8/T1, worse on the left, with signs of active C8/T1 denervation. A cervical spine magnetic resonance imaging (MRI) scan showed spondylodiscal degenerative changes with central protrusions in C4-C5, C6-C7, and right central in C5-C6, which touched the dural sac. The anteroposterior diameter of the medulla in neutral position, in the C5-C6 plane, was of 5.1 mm. There was a reduction of the spinal cord caliber to 4.0 mm after the dynamic maneuver of forced flexion of the spine, as well as signal increase in the anterior horns. The clinical findings and those of the complementary tests were compatible with Hirayama disease (HD), a rare benign motor neuron disease that affects cervical spinal segments and is most prevalent in men, with onset in the early 20s. Unilateral and slowly progressive weakness is typical, but self-limited. Sensory disturbances, and autonomic and upper motor neuron signals are rare. Management is usually conservative, with the use of a soft cervical collar. Although rare, HD should be considered in young patients with focal asymmetric atrophy in the upper limbs. The early diagnosis of HD depends on the degree of suspicion, as well as on the cooperation and communication among the various specialties involved in the investigation.

Resumo Paciente de 26 anos, previamente hígido, que, aos 18 anos, iniciou perda progressiva de força distal, tremor de repouso, e atrofia muscular no membro superior esquerdo. Ao exame, apresentou atrofia moderada, distal, força muscular de grau 4, e minipolimioclonus. A eletroneuromiografia (ENMG) revelou comprometimento pré-ganglionar crônico de C7/C8/T1 bilateral pior à esquerda, com sinais de desnervação ativa em C8/T1. A ressonância magnética (RM) de coluna cervical mostrou alterações degenerativas espondilodiscais com protrusões centrais em C4-C5, C6-C7, e central direita em C5-C6, que tocavam o saco dural. O diâmetro anteroposterior da medula na posição neutra, no plano de C5-C6, era de 5,1 mm. Houve redução do calibre da medula para 4,0 mm após a manobra dinâmica de flexão forçada da coluna, e aumento de sinal nos cornos anteriores. Os achados clínicos e os dos exames complementares eram compatíveis com doença de Hirayama (DH), uma doença benigna rara dos neurônios motores, que afeta os segmentos espinhais cervicais e é mais prevalente em homens e de início próximo aos 20 anos. É típica a fraqueza unilateral e lentamente progressiva, porém autolimitada. Perturbações sensoriais, sinais autonômicos e do neurônio motor superior são raras. O manejo geralmente é conservador, com uso de colar cervical macio. Apesar de rara, a DH deve ser considerada em pacientes jovens que apresentam atrofias assimétricas focais de membros superiores. O diagnóstico precoce de DH depende do grau de suspeição, e da cooperação e comunicação entre as diversas especialidades envolvidas na investigação.

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SUMMARY: To describe the physical therapy protocols used in critically ill patients to attenuate skeletal muscle atrophy. We conducted a search in PubMed and Embase from inception to November 2020. Observational or experimental studies published in English or Spanish that evaluated the effect of physical therapy protocols on the attenuation of skeletal muscle atrophy in critically ill patients through muscle strength or mass measurement were considered eligible. Studies were only included if they reported a detailed description of the dosing of the interventions. Seventeen studies met the eligibility criteria. We included randomised clinical trials (n = 16) and observational studies (n = 1). The total population of the included studies was 872 critically ill patients. The studies aimed to evaluate the reliability, safety or effectiveness of neuromuscular electrical stimulation (n = 10) protocols, early mobilisation (n = 3), ergometer training (n = 2), transfers in tilt table (n = 1), and blood flow restriction (n = 1). Physical therapy protocols are part of the critically ill patient's integral management. Strategies such as passive mobilisation, in-bed and out-of-bed transfers, gait training, ergometer training, and neuromuscular electrical stimulation substantially impact critically ill patients' prognoses and quality of life after hospital discharge.

RESUMEN: Describir los protocolos de terapia física usados en pacientes críticos para atenuar la atrofia muscular esquelética. Realizamos una búsqueda en PubMed y Embase desde el inicio hasta noviembre de 2020. Se consideraron los estudios observacionales o experimentales publicados en inglés o español que evaluaron el efecto de los protocolos de terapia física en la atenuación de la atrofia del músculo esquelético en pacientes críticos a través de la medición de la fuerza o la masa muscular. Los estudios solo se incluyeron si informaron una descripción detallada de la dosificación de las intervenciones. Diecisiete estudios cumplieron los criterios de elegibilidad. Se incluyeron ensayos clínicos aleatorizados (n = 16) y estudios observacionales (n = 1). La población total de los estudios incluidos fue de 872 pacientes en estado crítico. Los estudios tuvieron como objetivo evaluar la confiabilidad, seguridad o efectividad de los protocolos de estimulación eléctrica neuromuscular (n = 10), movilización temprana (n = 3), entrenamiento con ergómetro (n = 2), transferencias en mesa basculante (n = 1) y restricción del flujo sanguíneo (n = 1). Los protocolos de terapia física forman parte del manejo integral del paciente crítico. Es- trategias como la movilización pasiva, los traslados dentro y fuera de la cama, el entrenamiento de la marcha, el entrenamiento con ergómetro y la estimulación eléctrica neuromuscular tienen un impacto sustancial en el pronóstico y la calidad de vida de los pacientes críticos después del alta hospitalaria.

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Abstract Monogenic neuromuscular disorders are potentially treatable through gene therapy. Using viral vectors, a therapeutic transgene aims to restore normal levels of a protein not produced by the defective gene, or to silence a gene whose expression leads to toxic effects. Spinal Muscular Atrophy (SMA) is a good example of a monogenic disease that currently has an AAV9-based vector gene therapy as a therapeutic option. In this review, we intend to discuss the viral vectors and their mechanisms of action, in addition to reviewing the clinical trials that supported the approval of gene therapy (AVXS-101) for SMA as well as neuromuscular diseases that are potentially treatable with gene replacement therapy.

Resumo Doenças neuromusculares monogênicas são potencialmente tratáveis através de terapia gênica. Utilizando-se de vetores virais, um transgene terapêutico objetiva repor os níveis normais de uma proteina não produzida pelo gene defeituoso ou silenciar um gene cuja expressão leva a efeitos tóxicos. A Atrofia Muscular Espinhal (AME) é um bom exemplo de doença monogenica que atualmente tem uma terapia gênica com vetor viral AAV9 como opção terapêutica. Nesta revisão, pretendemos discutir os vetores virais e macanismos de ação utilizados, além de revisar os ensaios clínicos que embasaram a aprovação da terapia gênica (AVXS-101) para AME, assim como doenças neuromusculares potencialmente tratáveis com terapia de reposição gênica.