Effect of the COVID-19 pandemic on patients with inherited neuromuscular disorders.

BACKGROUND: The COVID-19 pandemic has brought substantial challenges for current practices in treating hereditary neuromuscular disorders (hNMDs). However, this infection has not been the only concern for these patients. Social distancing has compromised multidisciplinary assistance and physical activity, and has brought about several mental health issues. We presented a follow-up on 363 patients with hNMDs at a Brazilian tertiary center during the peak of the COVID-19 pandemic. OBJECTIVE: We aimed to show the frequency and severity of SARS-CoV-2 infection among hNMD patients and to demonstrate the effects of the pandemic on life habits, disease progression and multidisciplinary supportive care status. METHODS: Three hundred and sixty-three patients (58% male and 42% female) were followed for three months through three teleconsultations during the peak of the COVID-19 pandemic in Brazil. RESULTS: There were decreases in the numbers of patients who underwent physical, respiratory and speech therapies. For several patients, their appetite (33%) and sleep habits (25%) changed. Physical exercises and therapies were interrupted for most of the patients. They reported new onset/worsening of fatigue (17%), pain (17%), contractions (14%) and scoliosis (7%). Irritability and sleep, weight and appetite changes, and especially diminished appetite and weight loss, were more frequent in the group that reported disease worsening. There was a low COVID-19 contamination rate (0.8%), and all infected patients had a mild presentation. CONCLUSION: The isolation by itself was protective from a COVID-19 infection perspective. However, this isolation might also trigger a complex scenario with life habit changes that are associated with an unfavorable course for the NMD.

Effect of the COVID-19 pandemic on patients with inherited neuromuscular disorders / Efeito da pandemia do COVID-19 em pacientes com doenças neuromusculares hereditárias

ABSTRACT Background The COVID-19 pandemic has brought substantial challenges for current practices in treating hereditary neuromuscular disorders (hNMDs). However, this infection has not been the only concern for these patients. Social distancing has compromised multidisciplinary assistance and physical activity, and has brought about several mental health issues. We presented a follow-up on 363 patients with hNMDs at a Brazilian tertiary center during the peak of the COVID-19 pandemic. Objective We aimed to show the frequency and severity of SARS-CoV-2 infection among hNMD patients and to demonstrate the effects of the pandemic on life habits, disease progression and multidisciplinary supportive care status. Methods Three hundred and sixty-three patients (58% male and 42% female) were followed for three months through three teleconsultations during the peak of the COVID-19 pandemic in Brazil. Results There were decreases in the numbers of patients who underwent physical, respiratory and speech therapies. For several patients, their appetite (33%) and sleep habits (25%) changed. Physical exercises and therapies were interrupted for most of the patients. They reported new onset/worsening of fatigue (17%), pain (17%), contractions (14%) and scoliosis (7%). Irritability and sleep, weight and appetite changes, and especially diminished appetite and weight loss, were more frequent in the group that reported disease worsening. There was a low COVID-19 contamination rate (0.8%), and all infected patients had a mild presentation. Conclusion The isolation by itself was protective from a COVID-19 infection perspective. However, this isolation might also trigger a complex scenario with life habit changes that are associated with an unfavorable course for the NMD.

RESUMO Antecedentes: A Pandemia por COVID-19 tem trazido desafios subtanciais para a prática clínica no tratamento das doenças neuromusculares hereditárias (DNMh). A infecção não tem sido a única preocupação para os pacientes. O distanciamento social tem comprometido a assistência multidisciplinar, atividade física e tem trazido problemas mentais em decorrência do próprio isolamento. Nós apresentamos aqui um seguimento de 363 pacientes com DNMh de um centro terciário Brasileiro durante o pico da Pandemia de Covid-19. Objetivos: Mostrar a frequência e gravidade da infecção por Sars-Cov-2 em pacientes com DNMh e demonstrar os efeitos da pandemia nos hábitos de vida, na progressão da doença e no cuidado multidisciplinary. Métodos Trezentos e sessenta e três pacientes (58% homens and 42% mulheres) foram acompanhados por 3 meses através de 3 teleconsultas durante o pico da Pandemia de Covid-19 no Brasil. Resultados Houve um decréscimo no número de pacientes que faziam terapia física, respiratória e fonoaudiológica. Em muitos pacientes, o apetite (33%) e hábitos do sono (25%) se alteraram. Exercícios físicos e terapias foram interrompidas pela maioria dos pacientes. Physical exercises and therapies were interrupted for most of the patients. Eles relataram piora ou aparecimento de fadiga (17%), dor (17%), retrações (14%), e escoliose (7%). Irritabilidade, mudanças no sono, peso e apetite, sendo principalmente diminuição do apetite e peso foram mais frequentemente encontrados em pacientes que apresentaram piora clinica da doença. Houve uma baixa taxa de contaminação por Covid-19 (0.8%), e todos os pacientes infectado apresentaram quadro clinico leve. Conclusão O isolamento por si só se mostrou protetor na perspectiva de infecção por Covid-19, mas pode desencadear um cenário complexo com mudanças nos hábitos de vida e curso desfavorável da doença de base.

Clinical, Histological, and Immunohistochemical Findings in Inclusion Body Myositis.

Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy aged over 50 years. The disease is characterized by a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in association with inflammation. The aim of this study was to present clinical and muscle histopathological findings, including immunostaining for LC3B, p62, α-synuclein, and TDP-43, in 18 patients with sIBM. The disease predominated in males (61%) and European descendants, with onset of clinical manifestations around 59 years old. The most common symptoms were muscle weakness, falls, dysphagia, and weight loss. Hypertension was the main comorbidity. Most of the cases presented with paresis predominantly proximal in lower limbs and distal in upper limbs. Immunosuppressive treatment showed to be not effective. Muscle histological findings included dystrophic changes, endomysial inflammation, increased lysosomal activity, and presence of rimmed vacuoles and of beta-amyloid accumulation, in addition to high frequency of mitochondrial changes. There was increased expression of LC3B, p62, α-synuclein, and TDP-43 in muscle biopsies. The sIBM has characteristic clinical and histological findings, and the use of degeneration and autophagic markers can be useful for the diagnosis.

Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy.

OBJECTIVE: To compare muscle strength (MS) and motor function in patients with Duchenne muscular dystrophy (DMD) receiving steroids for different times against the natural evolution of DMD described by Scott et al. METHOD: 90 patients with DMD (aged 5- 12 years), receiving steroids for one to seven years, were evaluated by Medical Research Council Scale (MRC) and Hammersmith motor ability score. The relation between MS and motor abilities measurement from our data and Scott's ones were ascertained statistically. RESULTS: The relation between patient's age and Hammersmith scores revealed decrease of 0.76 point per year for age against decrease of 2.23 points on Scott's study. The relation between MRC scale and patient's age showed decrease of 0.80 point per year of age against decrease of 3.65 points on Scott's study. CONCLUSION: In patients with DMD aged five to 12 years the progression of the disease is delayed by steroids and the motor function is less reduced than muscular strength.

Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy / Comparação da força e função motora em pacientes com distrofia muscular de Duchenne com ou sem corticoterapia

OBJECTIVE: To compare muscle strength (MS) and motor function in patients with Duchenne muscular dystrophy (DMD) receiving steroids for different times against the natural evolution of DMD described by Scott et al. METHOD: 90 patients with DMD (aged 5- 12 years), receiving steroids for one to seven years, were evaluated by Medical Research Council Scale (MRC) and Hammersmith motor ability score. The relation between MS and motor abilities measurement from our data and Scott's ones were ascertained statistically. RESULTS: The relation between patient's age and Hammersmith scores revealed decrease of 0.76 point per year for age against decrease of 2.23 points on Scott's study. The relation between MRC scale and patient's age showed decrease of 0.80 point per year of age against decrease of 3.65 points on Scott's study. CONCLUSION: In patients with DMD aged five to 12 years the progression of the disease is delayed by steroids and the motor function is less reduced than muscular strength.

OBJETIVO: Comparar força muscular e função motora de pacientes com distrofia muscular de Duchenne (DMD) em corticoterapia com a evolução natural da doença descrita por Scott et al. MÉTODO: Noventa pacientes, entre 5 e 12 anos de idade, em corticoterapia por um até sete anos, foram avaliados quanto à força muscular (FM) (escala MRC) e função motora (Hammersmith motor ability score). A relação entre idade, FM e função motora e a comparação com o estudo de Scott et al foram determinadas estatisticamente. RESULTADOS: a relação idade/escore Hammersmith diminuiu 0,76 pontos a cada ano de aumento da idade (2,23 pontos na história natural). A relação idade/MRC decresceu 0,80 pontos a cada ano de aumento da idade (3,65 pontos na história natural). CONCLUSÃO: Nos pacientes em corticoterapia, a progressão da doença é mais lenta que na evolução natural em todas as faixas etárias avaliadas, sendo a FM mais comprometida que a função motora.

Quantification of muscle strength and motor ability in patients with Duchenne muscular dystrophy on steroid therapy.

OBJECTIVE: An assessment protocol was applied to quantify and describe muscular strength and motor abilities of 32 patients with Duchenne muscular dystrophy (DMD), aged between 5 and 12 years on steroid therapy. METHOD: Assessments were made monthly for the first six months and with intervals of two months thereafter until the 14-month end point. The tests employed included: the Medical Research Council (MRC) scale; the Hammersmith motor ability score; maximum weight lift; timed rise from floor and nine-meter walk. RESULTS: The results showed that loss of muscular strength and motor abilities were slowed in comparison to that observed in the natural evolution of the disease according to the literature. CONCLUSION: We conclude that a swift and objective assessment may be performed using the MRC scale for lower limbs and trunk, the Hammersmith motor ability score, timed nine-meter walk and weight lifts.

Quantification of muscle strength and motor ability in patients with Duchenne muscular dystrophy on steroid therapy

OBJECTIVE: An assessment protocol was applied to quantify and describe muscular strength and motor abilities of 32 patients with Duchenne muscular dystrophy (DMD), aged between 5 and 12 years on steroid therapy. METHOD: Assessments were made monthly for the first six months and with intervals of two months thereafter until the 14-month end point. The tests employed included: the Medical Research Council (MRC) scale; the Hammersmith motor ability score; maximum weight lift; timed rise from floor and nine-meter walk. RESULTS: The results showed that loss of muscular strength and motor abilities were slowed in comparison to that observed in the natural evolution of the disease according to the literature. CONCLUSION: We conclude that a swift and objective assessment may be performed using the MRC scale for lower limbs and trunk, the Hammersmith motor ability score, timed nine-meter walk and weight lifts.

OBJETIVO: Um protocolo de avaliação foi aplicado com o objetivo de quantificar e descrever evolutivamente a força muscular e as habilidades motoras de 32 pacientes com distrofia muscular de Duchenne (DMD), com idades variando de 5 a 12 anos, em corticoterapia. MÉTODO: As avaliações foram aplicadas mensalmente durante os primeiros seis meses e bimensais até completar um período de 14 meses. Os testes empregados foram: escala da "Medical Research Council" (MRC); Hammersmith "motor ability score"; levantamento da carga máxima de peso; cronometragem do tempo para levantar-se do chão e percorrer nove metros. RESULTADOS: Os resultados demonstraram que a perda da força muscular e das habilidades motoras foi mais lenta do que a observada na evolução natural da doença, como descrito na literatura internacional. CONCLUSÃO: Concluímos que uma rápida e objetiva avaliação pode ser executada utilizando a escala MRC para membros inferiores e tronco, Hammersmith motor ability score, cronometragem do tempo para percorrer 9 metros.e o levantamento de peso.

Ullrich congenital muscular dystrophy and Bethlem myopathy: clinical and genetic heterogeneity.

UNLABELLED: Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observed. OBJECTIVE: To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen VI immunoreactivity on muscular biopsy. RESULTS: Among 60 patients with CMD, two had no expression of collagen V and their clinical involvement was essentially different: the first (3 years of follow-up) has mild motor difficulty; the second (8 years of follow-up) never acquired walking and depends on ventilatory support. A molecular study, performed by Pan et al. at the Thomas Jefferson University, demonstrated in the first a known mutation of Bethlem myopathy in COL6A1 and in the second the first dominantly acting mutation in UCMD and the first in COL6A1, previously associated only to Bethlem myopathy, with benign course and dominant inheritance. CONCLUSION: Bethlem myopathy should be considered in the differential diagnosis of UCMD, even in patients without fingers contractures; overlap between Ullrich and Bethlem phenotypes can be supposed.

Dystrophin-glycoproteins associated in congenital muscular dystrophy: immunohistochemical analysis of 59 Brazilian cases.

UNLABELLED: The congenital muscular dystrophies (CMD) are heterogeneous muscular diseases with early and dystrophic pattern on muscle biopsy. Many different subtypes have been genetically identified and most phenotypes not yet identified belong to the merosin-positive (MP) CMD subgroup. OBJECTIVE: To analyze the immunohistochemical expression of the main proteins of the dystrophin-glycoproteins associated complex in muscle biopsy of patients with different CMD phenotypes, for investigating a possible correlation with clinical and histopathological data. METHOD: Fifty-nine patients with CMD had clinical, histopathological and immunohistochemical data evaluated: 32 had MP-CMD, 23 CMD with merosin deficiency (MD-CMD), one Ullrich phenotype and three Walker-Warburg disease. RESULTS: Dystrophin and dysferlin were normal in all; among the patients with MD-CMD, merosin deficiency was partial in nine who showed the same clinical severity as those with total deficiency; the reduced expression of alpha-sarcoglycan (SG) and alpha-dystroglycan (DG) showed statistically significant correlation with severe MD-CMD phenotype. CONCLUSION: There is a greater relationship between merosin and the former proteins; among MP-CMD patients, no remarkable immunohistochemical/phenotypical correlations were found, although the reduced expression of beta-DG had showed statistically significant correlation with severe phenotype and marked fibrosis on muscular biopsy.

Schwartz-Jampel syndrome: report of five cases.

We describe five patients with Schwartz-Jampel syndrome (SJS) examined at the outpatient service for neuromuscular disorders at our Institution from 1996 to 1999 with the objective of emphasizing the characteristic dysmorphic phenotype of SJS and its different clinical forms. Two cases presented SJS-type 1A, two had SJS-type 1B and one manifested SJS-type 2. Two boys with 3 and 13 years of age had generalized stiffness and the characteristic facial as well as osteoarticular changes from birth. Other two boys with 11 and 7 years had less marked dysmorphic changes at birth and manifested myotonia, as a limiting factor, during the second year of age. A girl with two months of age had severe myotonia from birth leading to feeding difficulties. In all cases the diagnosis was based on dysmorphic features, and on electromyographic changes showing continuous electrical activity of muscle fibers. All were treated with carbamazepine, 20-30 mg/Kg since diagnosis. The four boys (all with normal intelligence) improved of myotonia in daily activities, markedly in three, and moderately in one. The girl did not improve and showed global development delay: by the last follow-up (at 20 months of age) she did not sit unsupported, and had mental retardation. Carbamazepine in SJS-type 1 improves general daily performance and psychological status of the patients.

King-Denborough Syndrome: report of two Brazilian cases.

We report on two boys aged 2 and 6 years-old respectively with dysmorphic face, ptosis, down-slanting palpebral fissures, hypertelorism, epicanthic folds, low-set ears, malar hypoplasia, micrognathia, high-arched palate, clinodactyly, palmar simian line, pectus excavatum, winging of the scapulae, lumbar lordosis and mild thoracic scoliosis who present congenital hypotonia, slightly delayed motor development, diffuse joint hyperextensibility and mild proximal weakness. The muscle biopsy revealed minimal but identifiable changes represented by size fiber variability, type I fiber predominance and atrophy, perimysial fibrous infiltration and some disarray of the intermyofibrillary network. These cases correspond to the first Brazilian reports of the King-Denborough syndrome and our objective is increasing the awareness of this disorder as these patients are predisposed to developing malignant hyperthermia.

Schwartz-jampel syndrome: report of five cases

We describe five patients with Schwartz-Jampel syndrome (SJS) examined at the outpatient service for neuromuscular disorders at our Institution from 1996 to 1999 with the objective of emphasizing the characteristic dysmorphic phenotype of SJS and its different clinical forms. Two cases presented SJS-type 1A, two had SJS-type 1B and one manifested SJS-type 2. Two boys with 3 and 13 years of age had generalized stiffness and the characteristic facial as well as osteoarticular changes from birth. Other two boys with 11 and 7 years had less marked dysmorphic changes at birth and manifested myotonia, as a limiting factor, during the second year of age. A girl with two months of age had severe myotonia from birth leading to feeding diffuculties. In all cases the diagnosis was based on dysmorphic features, and on electromyographic changes showing continuous electrical activity of muscle fibers. All were treated with carbamazepine, 20-30 mg/Kg since diagnosis. The four boys (all with normal intelligence) improved of myotonia in daily activities, markedly in three, and moderately in one. The girl did not improve and showed global development delay: by the last follow-up (at 20 months of age) she did not sit unsupported, and had mental retardation. Carbamazepine in SJS-type 1 improves general daily performance and psychological status of the patients

King-Denborough syndrome: report of two Brazilian cases

We report on two boys aged 2 and 6 years-old respectively with dysmorphic face, ptosis, down-slanting palpebral fissures, hypertelorism, epicanthic folds, low-set ears, malar hypoplasia, micrognathia, high-arched palate, clinodactyly, palmar simian line, pectus excavatum, winging of the scapulae, lumbar lordosis and mild thoracic scoliosis who present congenital hypotonia, slightly delayed motor development, diffuse joint hyperextensibility and mild proximal weakness. The muscle biopsy revealed minimal but identifiable changes represented by size fiber variability, type I fiber predominance and atrophy, perimysial fibrous infiltration and some disarray of the intermyofibrillary network. These cases correspond to the first Brazilian reports of the King-Denborough syndrome and our objective is increasing the awareness of this disorder as these patients are predisposed to developing malignant hyperthermia

Dor e fadiga muscular / Pain and muscle fatigue

Vem sendo bastante freqüente a procura de clínicas especializadas por pacientes com queixa de dor e(ou) fadiga muscular. Esses sintomas sao as duas maneiras pelas quais os músculos respondem a um stress metabólico, seja por trabalho excessivo, seja por incapacidade de produzir a energia necessária para realizar esforços mesmo leves. Na fibromialgia, síndrome miofascial, polimialgia reumática, síndrome de fasciculaçao e câimbra, síndrome do homem rígido e doença de Brody nao há fraqueza objetiva provocada por exercícios e o CPK é normal. Nas síndromes miálgica com internalizaçao de capilares e miálgica com eosinofilia, na fadiga crônica e nas doenças devidas a déficit na produçao de energia muscular econtramos fraqueza muscular induzida por exercícios, além de biópsia muscular alterada e(ou) CPK elevado. Sao feitas referências a cada uma das afecçoes acima relatadas, especialmente àquelas secundárias a alteraçoes do metabolismo das vias produtoras de energia muscular (ATP), quer sejam do metabolismo dos hidratos de carbono, quer da oxidaçao dos ácidos graxos, quer da reaçao desaminase. Sao feitas consideraçoes sobre diagnóstico clínico e provas laboratoriais, com particular ênfase sobre as dosagens do ácido láctico com ou sem isquemia, quociente respiratório e biópsia muscular. Sao feitas ainda referências com relaçao à terapêutica.

Miopatias associadas a agregados tubulares / Myopathies associated to tubular aggregates

Os autores relatam o caso de paciente de 58 anos de idade do sexo masculino, com quadro de características miastênicas tanto clínica como eletromiograficamente, no qual a biópsia muscular com histoquímica e microscopia eletrônica permitiu fazer o diagnóstico de miopatia associada a agregados tubulares. É chamada a atençäo para o fato de que as alteraçöes anátomo-patológicas encontradas podem estar presentes em um grupo heterogênero de pacientes com grande variedade de sintomas, näo havendo portanto motivo para considerar-se a existência de uma miopatia com agregados tubulares, já que os achados anátomo-patológicos säo inespecíficos e näo configuram moléstia específica

Miopatia centronuclear (miotubular): relato de caso / Centronuclear myopathy (myotubular): a case report

Os autores apresentam o caso de uma menina de cinco meses de idade com retardo acentuado do desenvolvimento neuromotor, tetraparesia flacida, hiporreflexia e semiptose palpebral bilateral, cuja biopsia muscular demonstrou grande numero de fibras com nucleos centrais, permitindo o diagnostico de miopatia centronuclear (miotubular). Sao analisadas e discutidas a dificuldade de caracterizacao histologica e a variabilidade do quadro clinico deste tipo de miopatia que admite formas de diferente gravidade.

Imunofluorescência direta em músculo esquelético de pacientes com doenças neuromusculares

Os autores investigam o valor diagnóstico do teste de imunofluorescência direta para detecçäo de depósitos de imunecomplexos no tecido muscular esquelético. Foram examinado 27 biopsias neuromusculares. Verificou-se depósitos de imunoglobulinas ou fraçäo C3 co complemento, individualmente ou em conjunto, nos vasos, sarcolema e intrafibra em todos os pacientes com polimiosite (sete casos), amiotrofia espinhal progressiva (três casos) e encefalomiopatia mitocondrial (um caso): e na grande maioria dos pacientes com distrofia muscular progressiva (11 de 13 casos) e com síndrome miastênica (dois de três casos). Estes achados sugerem que mecanismos imunológicos podem ser responsáveis pelas alteraçöes musculares tanto nas polimiosites como em outras doenças neuromuscular