Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil / Miopatia por deficiência de carnitina palmitoiltransferase II: atualizando os aspectos genéticos da primeira publicação no Brasil

Abstract Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Resumo Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.

Intramuscular Hemangioma: A Rare Cause of Omalgia / Hemangioma intramuscular: Uma causa rara de Omalgia

Abstract Intramuscular hemangiomas (IHs) are benign soft-tissue tumors that represent less than 1% of all hemangiomas. This clinical entity is rarely considered as a differential diagnosis in cases of musculoskeletal pain. A healthy 38-year-old woman presented to our office with complaint of left omalgia, with 8 months of evolution, limiting her daily activities. She reported the appearance of tumefaction in the previous 4 months. She was medicated with analgesic and antiinflammatory drugs with no clinical improvement. The objective examination showed limitation of left shoulder abduction (0-90°). The patient underwent a magnetic resonance imaging (MRI), in which a well-circumscribed nodular formation was detected in the deltoid muscle. Then, she underwent a biopsy, which confirmed the diagnosis of hemangioma. The patient was referred for sclerotherapy. Intramuscular hemangiomas are usually observed in young patients. The gold-standard examination for diagnosis is MRI, which often forestalls the need for a biopsy. In many cases, IHs are asymptomatic and tend to involute over time. Despite the low frequency of this clinical entity, it is important to place it as a diagnostic hypothesis in cases of chronic pain of the limbs in young patients with poor therapeutic response to antiinflammatory drugs and analgesia.

Resumo Os hemangiomas intramusculares (HIs) são tumores benignos de tecidos moles que representam menos de 1% de todos os hemangiomas. Esta entidade clínica raramente é considerada como diagnóstico diferencial nos casos de dor musculoesquelética. Uma paciente do sexo feminino, de 38 anos de idade, saudável, se apresentou ao nosso consultório com queixa de omalgia esquerda, com 8 meses de evolução, que limitava suas atividades diárias. Ela relatou o aparecimento de tumefação 4 meses antes da consulta. A paciente estava medicada com analgésico e antiinflamatório sem melhoria clínica. Ao exame objetivo, ela apresentava limitação da abdução do ombro esquerdo (0-90°). A paciente foi submetida a uma ressonância nuclear magnética (RNM) na qual foi detectada uma formação nodular bem circunscrita no músculo deltoide,. Em seguida, foi realizada uma biópsia que confirmou o diagnóstico de hemangioma. A paciente foi então encaminhada para a realização de escleroterapia. Os HIs normalmente são observados em pacientes jovens. O exame padrão-ouro para o diagnóstico é a RNM, que muitas vezes torna a realização de biópsia desnecessária. Em muitos casos, os HIs são assintomáticos e tendem a involuir com o tempo. Apesar da baixa frequência desta entidade clínica, é importante colocá-la como hipótese de diagnóstico em casos de dor crônica dos membros em pacientes jovens com má resposta terapêutica a antiinflamatórios e analgesia.

Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review / Experiência de um único centro em distrofia muscular de cinturas do tipo autossômica recessiva: série de casos e revisão de literatura

Abstract Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.

Resumo A distrofia muscular de cinturas (DMC) é um grupo de miopatias que leva à fraqueza muscular progressiva, e envolvendo predominante as cinturas escapular e pélvica. A DMCtem uma etiologia genética heterogênea, com variação na prevalência de subtipos de acordo com as origens étnicas e geográficas das populações. O objetivo deste estudo foi analisar uma série de pacientes com DMC do tipo autossômico recessivo (DMC-R) para contribuir para uma melhor caracterização da doença e encontrar a proporção relativa dos diferentes subtipos em uma coorte do Sul do Brasil. A população amostral foi composta por 36 pacientes com DMC-R. O painel de sequenciamento de nova geração com 9 genes revelou variantes em 23 pacientes com DMC (64%), e identificou calpainopatia (DMC-R1) em 26%, disferlinopatia (DMC-R2) em 26%, sarcoglicanopatias (DMC-R3-R5) em 13%, teletoninopatia (D-MCR7) em 18%, distroglicanopatia (D-MCR9) em 13%, e anoctaminopatia (DMC-R12) em 4% dos pacientes. Nesses 23 pacientes com DMC, havia 27 variantes diferentes nos genes ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG e TCAP. Foram encontradas diferentes variantes em diferentes éxons desses genes, com exceção do gene TCAP, para o qual todos os pacientes eram portadores da variante p.Gln53*, e do gene FKRP, que apresentou recorrência da variante p.Leu276Ile. As características fenotípicas, genotípicas e imuno-histoquímicas musculares desta coorte do Sul do Brasil foram analisadas.

Musculoskeletal disorders in university professors who telework due to COVID-19 pandemic / Trastornos musculoesqueléticos en docentes universitarios que realizan teletrabajo en el marco de la pandemia con COVID-19

Introduction: Teaching virtually can cause symptoms related to muscle pain due to bad postures when working with computers. Objective: To determine the presence of musculoskeletal disorders in university professors who telework during the COVID-19 pandemic. Materials and methods: Analytical cross-sectional study in professors from health programs at a northeastern Colombian university. The validated Spanish version of the Nordic Kuorinka questionnaire was used (Cronbach's alpha 0.8-0.9). Using non-probabilistic sampling and an instrument applied virtually, 68 professors were included in the study. The dependent variable was presence of musculoskeletal disorder, whereas the independent ones were the sociodemographic conditions related to telework. The Fisher or were used for qualitative variables. Comparison of means were carried out through Student's t test. p<0.05 values were interpreted as statistical association. Results: 67.7% of participants reported musculoskeletal disorder in at least one anatomical site, being the neck the one mostly affected. Female gender and seniority in teaching practice showed an association with the disorder (p<0.05). Conclusion: Working conditions triggered by teleworking during the pandemic are associated with the presence of musculoskeletal disorders in professors.

Introducción: El ejercicio de la docencia en modalidad virtual puede desencadenar síntomas relacionados con dolor muscular debido a las malas posturas frente al computador. Objetivo: Determinar la presencia de trastornos musculoesqueléticos en docentes universitarios que realizan teletrabajo durante la pandemia por COVID-19. Materiales y métodos: Estudio analítico de corte transversal en docentes de programas de salud de una universidad del nororiente colombiano. Se usó el cuestionario Nórdico Kuorinka, validado y adaptado al español Aalfa de Cronbach 0,8-0,9], a partir de muestreo no probabilístico se incluyeron 68 docentes mediante instrumento aplicado en formato virtual. La variable dependiente fue la presencia del trastorno musculoesquelético y variables independientes las sociodemográficas y relacionadas con teletrabajo. Se usó el Test de Fisher en variables cualitativas. La comparación de medias se hizo con prueba t de Student. Se interpretó como asociación estadística valores de p<0,05. Resultados: El 67,6% manifestó trastorno musculoesquelético en al menos un sitio anatómico; el cuello fue el área más afectada. El sexo femenino y la antigüedad en el ejercicio de la docencia mostraron asociación con el trastorno (p<0,05). Conclusión: Las condiciones laborales generadas por el teletrabajo durante la pandemia se asocian con la presencia de trastornos musculoesqueléticos en docentes.

Treatment of Muscle Injury with Stem Cells - Experimental Study in Rabbits / Tratamento da lesão muscular com células-tronco - Estudo experimental em coelhos

Abstract Objective Histological and macroscopic evaluation of the healing process of acute lesions of the femoral rectus muscle using stem cells derived from adipose tissue-derived stem cells (ADSCs). Method An experimental study was conducted with 18 hind legs of New Zealand rabbits, which were divided into three study groups according to the intervention to be performed. In group I, no surgical procedure was performed; in group II—SHAN, the experimental lesion was performed without any additional intervention protocol; in group III—Intervention, the addition of ADSCs was performed in the same topography of the experimental lesion. After the proposed period, 2 weeks, the material was collected and submitted to macroscopic and histological evaluation. Results The quantitative analysis showed that the addition of ADSCs is related to the reduction of inflammatory cells in the 2-week evaluation (164.2 cells in group II - SHAN to 89.62 cells in group III - ADSC). The qualitative analysis of the slides with Picrosirius red, noticed an increase in orange/yellow fibers in group III - ADSC, which evidences a final healing process. The macroscopic evaluation found no difference between the groups. Conclusion The use of ADSCs in the treatment of acute muscle injury presented histological advantages when compared to their non-use.

Resumo Objetivo Avaliação histológica e macroscópica do processo de cicatrização das lesões agudas do músculo reto femoral, com utilização de células-tronco derivadas de tecido adiposo (ADSCs, na sigla em inglês). Método Foi realizado um estudo experimental com 18 patas traseiras de coelhos Nova Zelândia, que foram divididos em três nos grupos de estudo de acordo com a intervenção a ser realizada. No grupo I não foi realizado procedimento cirúrgico; no grupo II - SHAN foi realizado a lesão experimental sem nenhum protocolo de intervenção adicional; e no grupo III - Intervenção foi realizado a adição de ADSCs na mesma topografia onde foi realizada a lesão experimental. Após o período proposto, 2 semanas, o material foi coletado, submetido a avaliação macroscópica e histológica. Resultados A análise quantitativa demonstrou que a adição de ADSCs está relacionada com a diminuição de células inflamatórias na avaliação com 2 semanas (164,2 células no grupo II - SHAN para 89,62 células no grupo III - ADSC). A análise qualitativa das lâminas coradas com Picrosírius red demonstrou um aumento das fibras de cor laranja/amarela no grupo III - ADSC, o que evidencia um processo final de cicatrização. A avaliação macroscópica não encontrou diferença entre os grupos. Conclusão A utilização de ADSCs no tratamento de lesão muscular aguda apresentou vantagens histológicas quando comparada a sua não utilização.

Zebrafish: an emerging model for hereditary muscle disease research / 中华神经科杂志

With the advances in molecular genetic techniques, especially next-generation sequencing technologies, genetic testing is now a widely applied procedure in diagnosing hereditary muscle diseases. However, there remain many challenges to assessing the pathogenicity of genetic variants, understanding disease pathogenesis, and developing therapeutic strategies in hereditary muscle diseases. The zebrafish model system is a powerful tool to address these issues, thanks to conserved vertebrate genetics, the ease of genetic manipulation, and various assessment approaches for muscle function. Given the limited use of zebrafish model organisms on muscle disease research in China, this article mainly focuses on the advantages, applications, and limitations of zebrafish as a model of hereditary muscle disease.

Effects of apelin-13 on ferroptosis of the C2C12 skeletal muscle cell line in a high-iron environment / 中华老年医学杂志

Objective:To examine the effects of apelin-13 on ferroptosis of the C2C12 skeletal muscle cell line induced by a high-iron environment and explore potential underlying mechanisms.Methods:C2C12 cells were cultured in Dulbecco's Modified Eagle Medium(DMEM)and divided into a control group, a ferric citrate(FAC)group, an apelin-13 group, an FAC+ apelin-13 group, a ferroptosis inducer RSL3 group and an FAC+ apelin-13+ RSL3 group.Cell viability was detected by the 3-(4, 5-dimethyl thiazole-2)-2, 5-diphenyl thiazolyl blue(MTT)assay.The intracellular concentrations of total iron and divalent iron were measured by colorimetry; the levels of glutathione(GSH), malondialdehyde(MDA)and intracellular reactive oxygen species(ROS)in cells were detected by an enzyme-linked immunosorbent assay, visible spectrophotometry and a chemifluorescence method, respectively.The ultrastructure of C2C12 cells was examined by transmission electron microscopy.The protein expression of glutathione peroxidase 4(GPX-4), ferritin heavy chain 1(FTH-1), heme oxygenase 1(HO-1)and nuclear factor E2-related factor 2(Nrf-2), were detected by Western blotting.Results:Compared with the FAC group, the FAC+ Apelin-13 group had significantly elevated cell viability(optical density: 0.52±0.06 vs.0.28±0.04, t=7.837, P=0.007)and higher concentrations of GSH(2.41±0.35 vs.0.91±0.12 μmol/g Pro, t=9.778, P=0.003), but significantly decreased levels of ROS(22.06±5.79 vs.52.71±7.28 a. u./mg Pro, t=8.064, P=0.006), MDA(4.63±0.51 vs.9.11±0.84 mmol/mg Pro, t=8.642, P=0.006), total iron(1.53±0.24 vs.3.17±0.55 μmol/g Pro, t=6.135, P=0.013)and divalent iron(0.75±0.08 vs.1.94±0.36 μmol/g Pro, t=5.068, P=0.027), as well as reduced intracellular iron deposition.In the control group and the apelin-13 group, the morphology of the mitochondria was clear and normal.In contrast, the mitochondria in the FAC group had increased membrane density, membrane shrinkage and rupture, vacuolar degeneration, and obvious mitochondrial damage, which were consistent with the morphological characteristics of ferroptosis.Compared with the FAC group, the FAC+ apelin-13 group showed significant improvement in mitochondrial damage.Moreover, compared with the FAC+ apelin-13 group, the cell viability of the FAC+ apelin-13+ RSL3 group was significantly decreased(optical density: 0.23±0.04 vs.0.48±0.06, t=7.642, P=0.007). Compared with the FAC group, the FAC+ apelin-13 group had significantly up-regulated cellular expression of GPX-4(relative expression: 0.96±0.14 vs.0.31±0.07, t=7.712, P=0.008), FTH-1(0.57±0.08 vs.0.27±0.05, t=6.944, P=0.011), and HO-1(0.49±0.07 vs.0.28±0.05, t=6.472, P=0.012), as well as increased nuclear expression of Nrf-2(relative expression: 0.42±0.04 vs.0.19±0.05, t=7.114, P=0.008)with a higher ratio of nuclear expression over total cellular expression[(58.36±5.24)% vs.(36.58±5.32)%, t=5.858, P=0.015]and a higher level of HO-1 protein expression(relative expression: 0.49±0.07 vs.0.28±0.05, t=6.472, P=0.012). Conclusions:Apelin-13 inhibits ferroptosis induced by a high iron environment in C2C12 cells, and the underlying molecular mechanisms may be related to the Nrf-2/HO-1 signaling pathway.

Vasculitis with a neuromuscular presentation and associated cancer revealed by autopsy

Peripheral neuropathy is common, but rarely due to vasculitis. This report is the case of a 74-year-old woman with systemic vasculitis who presented with progressive arm and leg weakness associated with numbness. Autopsy revealed a colon cancer, which may have triggered the vasculitis. This case illustrates the association between vasculitis and malignancy. The best treatment of vasculitis in patients with cancer-associated vasculitis is usually treatment of the cancer, which often yields remission of the vasculitis. This case also illustrates the difficulty of suspecting vasculitis since the symptoms and signs are nonspecific and protean. It is important not to miss a diagnosis of vasculitis. It is often life-threatening. It is treatable. The critical step in the diagnosis of vasculitis is to think of it.

Duchenne muscular dystrophy: an historical treatment review / Distrofia muscular de Duchenne: revisão histórica do tratamento

ABSTRACT In this review, we discuss the therapies used in the treatment of patients with Duchenne muscular dystrophy since the first description of the disease. A short description is given of the various theories based on disease pathogenesis, which give the substrates for the many therapeutic interventions. A brief review of the methods of evaluation used in therapeutic trials is made. Of all the treatments, the only drugs that are still considered able to modify the course of the disease are the corticosteroids (prednisone/prednisolone/deflazacort). Other drugs (coenzyme Q10 and creatine) have had a little effect in a few functions without adverse reactions. Idebenone seems to improve the respiratory function in the long term. The trials with mRNA transcription, through nonsense mutations or exon 51 skipping, show some beneficial results in a few functional tests, but they are limited to a small set of DMD patients.

RESUMO Nesta revisão são discutidas as terapêuticas empregadas no tratamento da distrofia muscular de Duchenne desde a descrição da doença. Apresentamos as diversas teorias que fundamentaram as intervenções terapêuticas, com uma breve descrição dos tipos de avaliação empregados nos ensaios terapêuticos. Dentre todos os tratamentos, a única medicação que até agora modificou o curso da doença foram os corticosteroides (prednisona/prednisolona/deflazacort). A coenzima Q10 e creatina tiveram algum efeito pequeno em algumas funções e evolução da doença sem efeitos colaterais. O idebenone mostrou efeito benéfico na função respiratória em longo prazo. As tentativas de intervir no gene da distrofina utilizando técnicas de transcrição do mRNA através das mutações sem sentido e técnicas que pulam o exon 51 mostram resultado muito discreto em algumas provas funcionais e limitado a uma parcela pequena de casos.

Diaphragm quantitative electromyography in difficult-to-treat asthmatic patients / Eletromiografia quantitativa do diafragma em pacientes com asma de difícil controle

ABSTRACT Quantitative electromyography is an important tool to evaluate myopathies, and some difficult-to-treat asthmatic patients may have a subclinical corticosteroid myopathic process, using only inhaled corticosteroid, according to some studies. In this report, diaphragm quantitative electromyography was used to evaluate asthmatic difficult-to-treat patients, comparing them with a control group. Significant differences were obtained in amplitude, duration and size index of motor unit action potentials, with lower parameters in the asthmatic patients, which may indicate a myopathic process.

RESUMO Eletromiografia quantitativa é uma ferramenta importante para a avaliação de miopatias, e alguns pacientes asmáticos de difícil controle podem ter um processo miopático subclínico, mesmo usando apenas corticosteroides inalatórios, de acordo com alguns artigos. Nesse artigo a eletromiografia quantitativa do diafragma foi usada para avaliar os pacientes asmáticos de difícil controle, comparando com um grupo controle. Diferenças significativas nas amplitudes, durações e índices de tamanho dos potenciais de unidades motoras foram encontradas, com parâmetros mais baixos nos pacientes asmáticos, o que pode indicar um processo miopático.

Musculoskeletal "don't touch" lesions: pictorial essay / Lesões musculoesqueléticas do tipo "não toque": ensaio iconográfico

Abstract Focal bone lesions are not uncommon findings in the daily practice of radiology. Therefore, it is essential to differentiate between lesions with aggressive, malignant potential that require action and those that have no clinical significance, many of which are variants or benign lesions, sometimes self-limited and related to reactive processes. In some cases, a diagnostic error can have catastrophic results. For example, a biopsy performed in a patient with myositis ossificans can lead to an incorrect diagnosis of sarcomatous lesions and consequently to mutilating surgical procedures. The present study reviews the main radiological aspects of the lesions that are most commonly seen in daily practice and have the potential to be confused with aggressive, malignant bone processes. We also illustrate these entities by presenting cases seen at our institution.

Resumo O achado de lesões ósseas focais não é incomum no dia-a-dia do radiologista. É, portanto, imprescindível saber discernir as lesões com potencial maligno agressivo, que requerem ação, das desprovidas de significado clínico, muitas destas sendo variantes da normalidade ou processos reativos benignos, às vezes, autolimitados. Em alguns casos, a confusão diagnóstica pode ter resultados catastróficos, como a realização de biópsia em casos de miosite ossificante, que pode levar ao diagnóstico incorreto de lesões de origem sarcomatosa e a cirurgias mutilantes. O presente estudo faz uma revisão dos principais aspectos radiológicos das lesões que mais comumente são vistas no dia-a-dia e que possuem potencial para causar confusão com processos ósseos malignos e agressivos. Ilustramos, ainda, essas lesões, apresentando casos do nosso serviço.

Critical illness polyneuromyopathy in septic patients: Is it possible to diagnose it in a bedside clinical examination? / Polineuromiopatia do doente crítico em pacientes sépticos: É possível diagnosticar em um exame clínico à beira do leito?

ABSTRACT Objective: To determine the sensitivity and specificity of peripheral and respiratory muscle strength tests in diagnosing critical illness polyneuromyopathy (CIPNM), compared with an electrophysiological examination. Methods: Fifty septic patients who required mechanical ventilation for at least five days, and without a previous history of muscle weakness, were included. Peripheral muscle strength was assessed using the Medical Research Council (MRC) score, handgrip strength by dynamometry, and respiratory muscle strength with maximum respiratory pressures. Diagnosis of CIPNM was either confirmed or rejected by an electrophysiological examination. Receiver operating characteristic curve analysis was performed to determine the cut-off values with the best sensitivity (SN) and specificity (SP) of the studied variables in the presence or absence of CIPNM. Results: Patients with CIPNM were older, more critical (APACHE IV/SAPS 3), had a longer hospitalization, required mechanical ventilation for longer, and had a higher rate of intensive care unit readmission. Cutoff values identified CIPNM patients using MRC scores, dynamometry according to sex, maximal expiratory and inspiratory pressures, as well as being confirmed by the electrophysiological examination, with good sensitivity and specificity: < 40 (SN: 0.893; SP: 0.955); < 7 kg (SN: 1; SP: 0.909) for men, < 4 kg (SN: 0.882; SP: 1) for women; < 34 cmH2O (SN: 0.808; SP: 0.909) and > −40 cmH2O (SN: 0.846; SP: 0.909), respectively. Conclusion: The MRC score, dynamometry or maximum respiratory pressures can be used to identify patients with CIPNM at the intensive care bedside assessment. The healthcare professional can choose any of the methods studied to evaluate the patient, based on his experience and the resource available.

RESUMO Objetivo: Determinar a sensibilidade (SN) e especificidade (SP) dos testes de força muscular periférica e respiratória no diagnóstico da Polineuromiopatia do Doente Crítico (PNDC) em comparação com o estudo eletrofisiológico. Métodos: Foram incluídos 50 pacientes sépticos, em ventilação mecânica (VM) durante pelo menos cinco dias e sem história prévia de fraqueza muscular. A força muscular foi avaliada utilizando o escore Medical Research Council (MRC), a força de preensão palmar e as pressões respiratórias máximas. O diagnóstico de PNDC foi confirmado ou excluído pelo estudo eletrofisiológico. A análise da curva ROC foi realizada para determinar os valores de corte com a melhor SN e SP. Resultados: Os pacientes com PNDC eram mais velhos, mais graves, tiveram hospitalização mais longa, necessitaram de VM por mais tempo e apresentaram maior taxa de readmissão na Unidade de Terapia Intensiva. Os valores de corte identificaram os pacientes com PNDC usando o MRC, a dinamometria de acordo com o sexo, as pressões expiratórias e inspiratórias máximas, também confirmado pelo estudo eletrofisiológico, com boa sensibilidade e especificidade: < 40 (SN: 0.893; SP: 0.955), < 7 kg (SN: 1; SP: 0,909) para homens, < 4 kg (SN: 0,882; SP: 1) para mulheres, <34 cmH2O (SN: 0,808; SP: 0,909) e > −40 cmH2O (SN: 0,846; SP: 0,909), respectivamente. Conclusão: Tanto o MRC, a dinamometria quanto as pressões respiratórias máximas podem ser usadas para identificar pacientes com PNDC na avaliação à beira do leito, podendo o profissional de saúde escolher qualquer um dos métodos baseado em sua experiência e no recurso disponível.

Progresses of ultrasound in diagnosis of hemophilia muscular diseases / 中国医学影像技术

Hemophilia is a recessive hereditary hemorrhagic disease linked with sex chromosomes. The main clinical manifestations of hemophilia are repeated bleeding of muscles and joints. Hemophilia muscular diseases can cause acute compartment syndrome, pseudotumor formation, muscular atrophy and ossifying myositis. Ultrasonography has advantages of real-time, noninvasive, simple, quick, strong repeatability and high resolution, which has been widely used in diagnosis of hemophilia muscular diseases. The application progresses of ultrasound in diagnosis of hemophilia muscular diseases were reviewed in this article.

The screening and genetic analysis of primary carnitine deficiency in the minority municipalities in Hainan Province / 中华检验医学杂志

Objective To investigate the incidence of neonatal carnitine deficiency (PCD) in eight minority autonomous cities and counties in Hainan Province (Changjiang, Ledong, Dongfang, Baoting, Baisha, Qiongzhong, Wuzhishan and Lingshui). Methods A total of 18, 701 cases of newborn filter paper dried blood samples were collected from August 1, 2017 to July 31, 2018 in eight minority autonomous cities and counties in Hainan Province, including 10051 male infants and 8650 female infants. Tandem mass spectrometry and the non-derivatized multi-amino acid, carnitine and succinylacetone assay kits produced by PE were used to detect free carnitine (C0) and acylcarnitine (C2, C3, C16, C18, etc.).The carnitine spec-trum was reexamined with the recall of mothers and infants whose C0 was less than 10μmol/L. Blood sam-ples from those who were still low were sent to the Beijing McKinnon gene for genetic diagnosis, and the urine samples were sent to the Guangzhou Golden Field for urine gas chromatography. Results Among the 18701 newborns, 5 cases were diagnosed with PCD. The incidence of neonatal PCD was 2.67/10000 (5/18701). Two cases of Li mutation c.388GA, two cases of Han mutation P.R254X and one case of Miao mutation P. Y84N were confirmed by gene detection. The confirmed children were treated with L-carnitine to avoid metabolic disorders or myocardial and skeletal muscle damage. Conclusions The incidence of neonatal PCD is high in eight cities and counties in Hainan Province. The mutation sites of neonatal PCD are different in Li and Han. The tandem mass spectrometry screening of PCD can guarantee the quality of the birth population.

Acute kidney injury induced by hypothyroidism myopathy: a clinical analysis of 24 cases / 中华全科医师杂志

Clinical data of 24 patients with acute kidney injury (AKI) induced by hypothyroidism myopathy admitted in our hospital from January 2014 to December 2016 were analyzed retrospectively.There were 9 patients classified as AKI stage Ⅰ and 15 patients as AKI stage Ⅱ according to the Kidney Disease Improving Global Outcomes (KDIGO),21 hypothyroidism myopathy patients without AKI were selected as control group.ANOVA and chi-square test were used to compare the general data and laboratory results among three groups;artificial neural network analysis and multi-factor stepwise regression method were used to analyze the factors related to AKI.There were significant differences in serum creatinine (Scr) (F=34.3,P＜0.01),BUN(F=29.1,P＜0.01),ALB(F=5.27,P=0.01),CK(F=8.61,P=0.01),creatin kinase isoenzyme(CK-MB)(F=33.1,P＜0.01),LDH(F=7.78,P=0.01),ALT(F=34.3,P＜0.01) and AST (F=28.1,P＜0.01) among three groups.Artificial neural network analysis showed that myoglobin was closely related to serum creatinine,suggesting its importance for AKI in patients with primary hypothyroidism myopathy.Multivariate regression analysis showed that serum creatinine was correlated with CK-MB(B=2.10,SE=0.38,β=0.96,t=5.52),LDH(B=0.18,SE=0.06,β=0.34,t=3.00)and AST(B=0.16,SE=0.09,β=0.32,t=2.62).This study indicates that hypothyroidism myopathy may be one of the causes of AKI,and the severity of AKI might be closely related to the severity of hypothyroidism myopathy.

Paying attention to the study of proteomics in muscular diseases / 中华神经科杂志

Although myopathy has obvious heterogeneity in clinic,the exact mechanism of myopathy is not fully understood,and there is no effective biomarker,and there are one or some protein changes in the basic pathogenesis of myopathy.Proteomics is a discipline that explores the composition,expression and modification of proteins at a holistic level and is widely used in various fields of life sciences.The study of differential proteomics provides more scientific basis for explaining the pathogenesis of diseases,searching for new diagnostic markers and potential therapeutic targets.The application of proteomics in the study of muscular diseases deserves more attention from neurologists.

Dermatomiositis. Presentación de un caso: Case presentation / Dermatomiositis

Se presenta el caso clínico de una paciente femenina de 30 años, quien comenzó a finales de enero del 2017 con síntomas de dolores musculares intensos en los músculos proximales de las 4 extremidades, que le impedían realizar sus actividades diarias, debilidad muscular y astenia que se agravaron progresivamente. Además se recogieron en el interrogatorio antecedentes de lesiones cutáneas, molestias al deglutir, disnea a los esfuerzos medianos que desaparecía con el reposo, tos escasa con expectoración blanquecina, ageusia, dolor en la región cervical y ligera pérdida de peso. Fue ingresada en el servicio de Medicina Interna donde se constataron cifras elevadas de CPK y otras enzimas. Se realizó electromiografía, biopsia muscular y biopsia de piel. Además se inició tratamiento con esteroides e inmunosupresores que lograron una notable mejoría clínica. Como resultado de la investigación la paciente se le diagnosticó dermatomiositis, una de las formas más frecuentes de miopatías  inflamatorias idiopáticas. Su evolución fue favorable, mejorando su sintomatología y egresando con seguimiento por consulta externa.

A Clinical case of a 30 year old female patient who started by the end of January  2017 with intense  pain in the muscles of the four limbs which impeded her from her daily routines , muscular weakness and asthenia which progressed severely.  In addition, on interviewing antecedents of cutaneous lesions, problems at deglutition, dyspnea on exertion which disappeared at rest, cough with scarce whitish expectoration, ageusia, cervical pain and slight weight loss. She was admitted at the Internal Medicine ward and high values of Creatinine and Phosphokinase and other enzymes. An electromyography and a muscle and skin biopsies were performed.  In addition, itwas started a treatment with steroids and inmmuno-depressors which had a noticeable clinical improvement. As a result of the study the patient was diagnosed with dermatomiositis, one of the most frequent forms of inflammatory idiopathic myopathies. It progressed favorably, improving the symptoms and she was discharged with follow up by outpatient consultation

Neutral lipid storage disease with distal weakness: report of one family / 中华神经科杂志

Objective To report the clinical and pathological features of one family with neutral lipid storage disease with distal weakness and review the literature , explore the diagnosis and differential diagnosis of the disease , and improve the understanding of the disease .Methods Clinical data of two patients of a family were collected , and next generation sequencing was performed after electrophysiological examination and pathological analysis of skeletal muscle biopsy .And related literature was reviewed .Results Two patients had similar presentations , both having symptoms after 30 years old.The main manifestations were weakness and atrophy of the distal limbs .The creatine kinase levels were increased ( 1067, 740 U/L) .Electromyography revealed myogenic lesions .Pathological analysis of skeletal muscle biopsy showed a large amount of lipid droplets deposition in most muscle fibers .Next generation sequencing revealed a homozygous splice mutation in PNPLA2 gene ( C.187 +1G >A) .Conclusions The two patients with neutral lipid storage disease with myopathy involve distal limbs , which should be distinguished with distal myopathy.The presence of large amounts of lipid droplets in the cytoplasm of muscle fibers can be used for the diagnosis of lipid storage myopathy .The next generation sequencing is helpful for the typing diagnosis of lipid deposition disease .

Clinical,pathological and molecular biological study of six patients with collagen type Ⅵ related myopathies / 中华神经科杂志

Objective Clinical, pathological and molecular biological data of six cases with molecular diagnosis of collagen type Ⅵ related myopathies were retrospectively analyzed to improve the recognition of collagen protein Ⅵrelated myopathy.Methods Clinical and pathological data of six patients diagnosed as collagen protein Ⅵ related myopathy by next generation sequencing and molecular biologic analysis during 2010-2017 were summarized.Results All of the six patients presented early childhood onset ((2.00 ±0.75) years old), and delayed motor growth after birth.There were six cases of proximal muscle weakness , one with distal muscle weakness; three cases with osteoarthropathy; one case of severe skin scar.The creatine kinase levels (187-380 U/L) of three patients were slightly elevated .Three cases showed myogenic damage , two with mild neurogenic lesions , one with myogenic and neurogenic damages . Next generation sequencing showed four cases with COL 6A1 gene heterozygous mutation ( a novel mutation and three had been reported), one with COL6A2 heterozygous mutation and one with COL6A1 and COL6A2 complex heterozygous mutation .The pathological analysis of skeletal muscle biopsy showed that the muscle fiber size was different , and the connective tissue elements were seriously increased .Some opaque fibers were observed.Six cases were found anti-collagen Ⅵ/Ⅳ protein monoclonal antibody immunofluorescence double stained , and sarcolemma Ⅵcollagen protein expression decreased to different degrees .Conclusions The clinical manifestations of the collagen protein Ⅵ related myopathy were found to be complex .Skeletal muscle biopsy pathological analysis was lack of specificity . Anti-collagen Ⅵ/Ⅳ monoclonal antibody immunofluorescence double staining showed collagen protein Ⅵ missing partly or completely . Immunofluorescence staining and the next generation sequencing can improve the diagnosis of collagen proteinⅥrelated myopathy.

Caveolin-associated myopathy: three cases with muscle rippling and a literature review / 中华神经科杂志

Objective To summarize the clinical , pathological and genetic characteristics of three patients with caveolin-3 associated myopathy and review the literatures .Methods The clinical data of three patients with caveolin-3 associated myopathy were investigated .With informed consent , we performed muscle biopsy and genetic analysis of CAV 3 and PTRF genes.Results All the three patients presented with percussion/pressure-induced rapid contraction , percussion-induced muscle mounding and mechanically induced muscle rippling.Besides, case 1 had weakness and atrophy of hand muscles .Case 2, who manifested with muscle hyperexcitability at onset , developed weakness and atrophy of distal part of lower limbs.Case 3 showed normal muscle strength and tone .All of them had myalgia or tenderness .Muscle biopsy revealed mild myogenic changes in two patients and a muscular dystrophic pattern in one . Immunohistochemical staining of caveolin-3 revealed an even deficiency in case 1 and a mosaic deficiency in cases 2 and 3.Gene analysis revealed a missense mutation ( c.80G>A, p.R27Q) in CAV3 gene of case 1. No mutations were identified in cases 2 and 3.Conclusions There is phenotypic variability in patients with caveolin-associated myopathy , including limb-girdle syndrome , rippling muscle disease , distal myopathy , muscle hypertrophy , idiopathic hyperCKemia and cardiomyopathy .Muscle biopsy and caveolin-3 staining should be performed for the above patients with muscle rippling .