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1.
Rheumatol Int ; 44(6): 1077-1087, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581449

RESUMO

Sporadic inclusion body myositis (sIBM) is a subgroup of idiopathic inflammatory myopathies characterised by progressive muscle weakness and skeletal muscle inflammation. Quantitative data on the myofibre morphology in sIBM remains scarce. Further, no previous study has examined fibre type association of satellite cells (SC), myonuclei number, macrophages, capillaries, and myonuclear domain (MD) in sIBM patients. Muscle biopsies from sIBM patients (n = 18) obtained previously (NCT02317094) were included in the analysis for fibre type-specific myofibre cross-sectional area (mCSA), SCs, myonuclei and macrophages, myonuclear domain, and capillarisation. mCSA (p < 0.001), peripheral myonuclei (p < 0.001) and MD (p = 0.005) were higher in association with type 1 (slow-twitch) than type 2 (fast-twitch) fibres. Conversely, quiescent SCs (p < 0.001), centrally placed myonuclei (p = 0.03), M1 macrophages (p < 0.002), M2 macrophages (p = 0.013) and capillaries (p < 0.001) were higher at type 2 fibres compared to type 1 fibres. In contrast, proliferating (Pax7+/Ki67+) SCs (p = 0.68) were similarly associated with each fibre type. Type 2 myofibres of late-phase sIBM patients showed marked signs of muscle atrophy (i.e. reduced mCSA) accompanied by higher numbers of associated quiescent SCs, centrally placed myonuclei, macrophages and capillaries compared to type 1 fibres. In contrast, type 1 fibres were suffering from pathological enlargement with larger MDs as well as fewer nuclei and capillaries per area when compared with type 2 fibres. More research is needed to examine to which extent different therapeutic interventions including targeted exercise might alleviate these fibre type-specific characteristics and countermeasure their consequences in impaired functional performance.


Assuntos
Miosite de Corpos de Inclusão , Regeneração , Humanos , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Macrófagos/patologia , Inflamação/patologia , Biomarcadores/análise , Músculo Esquelético/patologia , Células Satélites de Músculo Esquelético/patologia , Biópsia , Fibras Musculares de Contração Lenta/patologia , Fibras Musculares de Contração Rápida/patologia
2.
Sci Rep ; 12(1): 1082, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058512

RESUMO

Contractile activity is a fundamental property of skeletal muscles. We describe the establishment of a "feeder-supported in vitro exercise model" using human-origin primary satellite cells, allowing highly-developed contractile myotubes to readily be generated by applying electrical pulse stimulation (EPS). The use of murine fibroblasts as the feeder cells allows biological responses to EPS in contractile human myotubes to be selectively evaluated with species-specific analyses such as RT-PCR. We successfully applied this feeder-supported co-culture system to myotubes derived from primary satellite cells obtained from sporadic inclusion body myositis (sIBM) patients who are incapable of strenuous exercise testing. Our results demonstrated that sIBM myotubes possess essentially normal muscle functions, including contractility development, de novo sarcomere formation, and contraction-dependent myokine upregulation, upon EPS treatment. However, we found that some of sIBM myotubes, but not healthy control myotubes, often exhibit abnormal cytoplasmic TDP-43 accumulation upon EPS-evoked contraction, suggesting potential pathogenic involvement of the contraction-inducible TDP-43 distribution peculiar to sIBM. Thus, our "feeder-supported in vitro exercise model" enables us to obtain contractile human-origin myotubes, potentially utilizable for evaluating exercise-dependent intrinsic and pathogenic properties of patient muscle cells. Our approach, using feeder layers, further expands the usefulness of the "in vitro exercise model".


Assuntos
Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Células Satélites de Músculo Esquelético/fisiologia , Animais , Técnicas de Cultura de Células/métodos , Células Cultivadas , Estimulação Elétrica/métodos , Células Alimentadoras/metabolismo , Humanos , Camundongos , Modelos Biológicos , Fibras Musculares Esqueléticas/citologia , Mioblastos/citologia , Miosite de Corpos de Inclusão/fisiopatologia , Sarcômeros/fisiologia , Células Satélites de Músculo Esquelético/metabolismo
3.
Muscle Nerve ; 63(4): 497-505, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33432607

RESUMO

BACKGROUND: We evaluated the functional consequences of diaphragm involvement in patients with inclusion body myositis (IBM). METHODS: Ultrasound diaphragm thickening fraction (TFdi), lung function and dyspnea levels were compared between IBM patients and matched controls. Patients with IBM were grouped into "low" and "high" diaphragm activity based on TFdi values (with cutoff value being the lowest observed TFdi in the control group), and clinical characteristics were compared between groups. RESULTS: 20 IBM patients were included. TFdi was significantly lower in patients and correlated with time since symptom onset (rho = 0.74, P < .001). Patients had significantly lower forced vital capacity and higher dyspnea scores than controls. IBM patients with "low" diaphragm activity (n = 9) had lower 6-min walking distance, higher resting and exertional dyspnea and a larger positional decrease in vital capacity (all P ≤ .03) than patients with 'high' activity. Timed Up and Go time and St. George's Respiratory Questionnaire were not different between groups. CONCLUSIONS: Diaphragm involvement in IBM is related to disease duration and has detrimental effects on lung function, dyspnea and exercise capacity. Further studies are required to investigate its potential as a therapeutic target.


Assuntos
Diafragma/diagnóstico por imagem , Dispneia/diagnóstico por imagem , Miosite de Corpos de Inclusão/diagnóstico por imagem , Miosite de Corpos de Inclusão/fisiopatologia , Idoso , Dispneia/fisiopatologia , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Ultrassonografia/métodos
5.
Muscle Nerve ; 63(1): 89-95, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997375

RESUMO

We previously reported a new quantitative analysis of single-channel surface electromyography (EMG), the "clustering index method" (CI method), in the tibialis anterior muscle, which achieved sufficiently good sensitivity to detect neurogenic or myogenic abnormalities. The window width is a fundamental parameter of the CI method, and was arbitrarily set at 15 ms in that study. In this study, we searched for the most appropriate window width using expanded patient data. The data from our previous study were reanalyzed, and new patients were enrolled. Window width in the CI method was changed from 5 to 27.5 ms with a step of 2.5 ms. For each window width, Z-score values of individual subjects were calculated and the diagnostic yield was investigated. We enrolled 67 controls, 29 subjects with neurogenic disorders, and 39 with myogenic disorders. When the window width was set at 22.5 ms, the highest sensitivity was achieved both for neurogenic (97%) and myogenic (72%) disorders, with a specificity of 97%. Seven of 10 patients with inclusion body myositis were also abnormal. Reliable results were obtained by collecting 15 epochs per subject. There are two conflicting effects that appear to be best balanced at a window width of 22.5 ms: a wider width decreases the chance that a motor unit potential (MUP) is divided into two adjacent windows, and a narrower width reduces the possibility that an MUP firing at a low-frequency is counted twice by the differential sequences. CI is promising as a non-invasive method to diagnose neuromuscular disorders.


Assuntos
Neurônios Motores/fisiologia , Músculo Esquelético/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Doenças Neuromusculares/fisiopatologia , Adulto , Análise por Conglomerados , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neuromusculares/diagnóstico
6.
Rheumatology (Oxford) ; 60(2): 907-910, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33175137

RESUMO

OBJECTIVE: The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM). METHODS: An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population. RESULTS: Of the 608 participants (81.1% female, median (s.d.) age 57 (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic. CONCLUSION: This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.


Assuntos
Antirreumáticos/uso terapêutico , COVID-19 , Continuidade da Assistência ao Paciente , Miosite/terapia , Modalidades de Fisioterapia , Telemedicina , Tempo para o Tratamento , Adulto , Idoso , Dermatomiosite/fisiopatologia , Dermatomiosite/psicologia , Dermatomiosite/terapia , Progressão da Doença , Medo/psicologia , Feminino , Glucocorticoides/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/fisiopatologia , Miosite/psicologia , Miosite de Corpos de Inclusão/fisiopatologia , Miosite de Corpos de Inclusão/psicologia , Miosite de Corpos de Inclusão/terapia , Polimiosite/fisiopatologia , Polimiosite/psicologia , Polimiosite/terapia , SARS-CoV-2 , Inquéritos e Questionários , Reino Unido , Estados Unidos
7.
Muscle Nerve ; 62(6): 735-741, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32940356

RESUMO

BACKGROUND: Size index (SI) is a motor unit potential (MUP) parameter in concentric needle electromyography calculated from amplitude and area/amplitude, which can sensitively discriminate between control and neurogenic MUPs. In this study, we investigated the application of SI to myogenic MUPs based on expanded data. METHODS: MUPs were collected from the biceps brachii (BB) and tibialis anterior (TA) muscles. Muscles showing unequivocal neurogenic or myogenic changes by visual inspection were selected for patients. In addition to the original SI, a revised SI (rSI) was defined using the logarithmic scale for area/amplitude. The coefficient for area/amplitude was varied and that achieving the best sensitivity both for BB and TA was selected. RESULTS: Analyzed were 1619, 340, and 498 MUPs from the BB of 26, 10, and 14 subjects (control, neurogenic, and myogenic), respectively, and 1245, 536, and 473 MUPs from the TA of 23, 18, and 13 subjects (control, neurogenic, and myogenic), respectively. For neurogenic MUPs, the original SI and the newly defined rSIn were similarly sensitive (82.1% and 81.8% sensitivity for SI and rSIn, respectively, for BB, and 68.1% and 69.6% for TA), and were more sensitive than area (72.6% for BB and 57.6% for TA), the most sensitive parameter among conventional ones. For myogenic MUPs, the sensitivity of rSIm was 9.0% for BB and 24.5% for TA, which was not significantly different from duration (7.4% for BB and 21.8% for TA), the most sensitive parameter among conventional ones. CONCLUSIONS: SI, rSIn, and rSIm are promising as new MUP parameters.


Assuntos
Eletromiografia/métodos , Neurônios Motores , Fibras Musculares Esqueléticas , Músculo Esquelético/fisiopatologia , Doenças Neuromusculares/fisiopatologia , Adolescente , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Braço , Atrofia Bulboespinal Ligada ao X/fisiopatologia , Estudos de Casos e Controles , Miopatias Distais/fisiopatologia , Feminino , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Distrofia Muscular de Duchenne/fisiopatologia , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Miosite/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Distrofia Miotônica/fisiopatologia , Doenças Neuromusculares/diagnóstico , Síndrome Pós-Poliomielite/fisiopatologia , Estenose Espinal/fisiopatologia , Adulto Jovem
8.
Neuromuscul Disord ; 30(10): 807-814, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32928647

RESUMO

Inclusion body myositis is the most commonly acquired myopathy after the age of 45. The slowly progressive and heterogeneous disorder is a challenge for measuring clinical trial efficacy. One current method for measuring progression utilizes the Inclusion Body Myositis-Functional Rating Scale. We have found that the upper extremity domain scores in the Inclusion Body Myositis-Functional Rating Scale do not consistently change until there is extreme loss of grip and finger flexor strength. Therefore, we performed a cross-sectional observational study of 83 inclusion body myositis patients and 38 controls recruited at the 2019 Annual Patient Conference of The Myositis Association. We evaluated new Inclusion Body Myositis Patient-Reported Outcome measures for upper extremity function modified from the NIH Patient-Reported Outcomes Measurement Information System as well as pinch and grip strength. We found that Patient-Reported Outcome measures hand-function have a higher correlation with pinch and grip strength than the Inclusion Body Myositis-Functional Rating Scale.


Assuntos
Estado Funcional , Força da Mão/fisiologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força de Pinça/fisiologia
9.
Clin Neurophysiol ; 131(11): 2766-2776, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32928695

RESUMO

OBJECTIVE: Sporadic inclusion body myositis (sIBM) has been associated with neuropathy. This study employs nerve excitability studies to re-examine this association and attempt to understand underlying pathophysiological mechanisms. METHODS: Twenty patients with sIBM underwent median nerve motor and sensory excitability studies, clinical assessments, conventional nerve conduction testing (NCS) and quantitative thermal threshold studies. These results were compared to established normal controls, or results from a normal cohort of older control individuals. RESULTS: Seven sIBM patients (35%) demonstrated abnormalities in conventional NCS, with ten patients (50%) demonstrating abnormalities in thermal thresholds. Median nerve motor and sensory excitability differed significantly in sIBM patients when compared to normal controls. None of these neurophysiological markers correlated significantly with clinical markers of sIBM severity. CONCLUSION: A concurrent neuropathy exists in a significant proportion of sIBM patients, with nerve excitability studies revealing changes possibly consistent with axolemmal depolarization or concurrent neuronal adaptation to myopathy. Neuropathy in sIBM does not correlate with muscle disease severity and may reflect a differing tissue response to a common pathogenic factor. SIGNIFICANCE: This study affirms the presence of a concurrent neuropathy in a large proportion of sIBM patients that appears independent of the severity of myopathy.


Assuntos
Nervo Mediano/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Condução Nervosa/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia
11.
Muscle Nerve ; 62(4): 445-454, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32478919

RESUMO

Muscle disorders are characterized by differential involvement of various muscle groups. Among these, weakness predominantly affecting finger flexors is an uncommon pattern, most frequently found in sporadic inclusion-body myositis. This finding is particularly significant when the full range of histopathological findings of inclusion-body myositis is not found on muscle biopsy. Prominent finger flexor weakness, however, is also observed in other myopathies. It occurs commonly in myotonic dystrophy types 1 and 2. In addition, individual reports and small case series have documented finger flexor weakness in sarcoid and amyloid myopathy, and in inherited myopathies caused by ACTA1, CRYAB, DMD, DYSF, FLNC, GAA, GNE, HNRNPDL, LAMA2, MYH7, and VCP mutations. Therefore, the finding of finger flexor weakness requires consideration of clinical, myopathological, genetic, electrodiagnostic, and sometimes muscle imaging findings to establish a diagnosis.


Assuntos
Dedos/fisiopatologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Amiloidose/patologia , Amiloidose/fisiopatologia , Miopatias Distais/patologia , Miopatias Distais/fisiopatologia , Doença de Depósito de Glicogênio Tipo II/patologia , Doença de Depósito de Glicogênio Tipo II/fisiopatologia , Humanos , Músculo Esquelético/patologia , Doenças Musculares/patologia , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Distrofia Miotônica/patologia , Distrofia Miotônica/fisiopatologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia
12.
Neuromuscul Disord ; 30(4): 294-300, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32307229

RESUMO

Inclusion Body Myositis (IBM) is the most common acquired myopathy in older individuals with more than two thirds of patients experiencing impaired swallowing. There are currently no standardized exercise therapies to improve or sustain swallowing despite good evidence for exercise therapy in limb muscles. Reduced upper esophageal sphincter opening is a common abnormality associated with dysphagia in IBM. This pilot study recruited IBM patients with abnormal upper esophageal sphincter function and dysphagia into an exercise program. It was hypothesized that regular practice using the Expiratory Muscle Strength Trainer (EMST) device would improve hyolaryngeal movement by strengthening suprahyoid musculature and facilitate opening of the upper esophageal sphincter thereby improving swallowing and quality of life. Overall, IBM patients who used the EMST device demonstrated no improvement in swallowing function. Consistent with that result, there was also no change in measures of quality of life. However, further studies are needed to elucidate whether it has a preventative role in the development or progression of dysphagia in IBM as there is a suggestion that patients with a shorter duration of disease may have had some benefit. This research provides pilot data and recommendations that will guide future studies on exercise therapy and swallowing in this area.


Assuntos
Transtornos de Deglutição/reabilitação , Esôfago/fisiopatologia , Terapia por Exercício/instrumentação , Força Muscular/fisiologia , Miosite de Corpos de Inclusão/reabilitação , Avaliação de Resultados em Cuidados de Saúde , Músculos Respiratórios/fisiopatologia , Idoso , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Terapia por Exercício/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite de Corpos de Inclusão/complicações , Miosite de Corpos de Inclusão/fisiopatologia , Projetos Piloto
13.
Semin Neurol ; 40(3): 342-348, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32252099

RESUMO

The inflammatory myopathies comprise disorders of immune-mediated muscle injury. The histopathology and clinical features help distinguish them. Juvenile dermatomyositis (JDM) is the most common form of myositis in children and adolescents. Children with JDM present with proximal muscle weakness and characteristic rashes. The presentation is similar in children and adults, but JDM is a primary disorder and the adult form often is concerning for a paraneoplastic syndrome. Proximal muscle weakness occurs with dermatomyositis, polymyositis, and immune-mediated necrotizing myopathy, but the latter two conditions have no dermatologic findings or distinct tissue changes which set them apart from dermatomyositis. Inclusion body myositis, also included in the inflammatory myopathies, presents with more distal involvement, and microscopically exhibits identifiable rimmed vacuoles. We review key features of these disorders, focusing in more detail on JDM because it is more often encountered by the child neurologist.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Dermatomiosite , Inflamação , Miosite de Corpos de Inclusão , Adolescente , Adulto , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Criança , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Dermatomiosite/fisiopatologia , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/tratamento farmacológico , Miosite de Corpos de Inclusão/imunologia , Miosite de Corpos de Inclusão/fisiopatologia
14.
Muscle Nerve ; 61(6): 783-788, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32239702

RESUMO

INTRODUCTION: The diagnosis of inclusion body myositis (IBM) can be challenging, and its presentation can be confused with other forms of myositis or neuromuscular disorders. In this study we evaluate the ability of quantitative muscle ultrasound to differentiate between IBM and mimicking diseases. METHODS: Patients 50 years of age and older were included from two specialty centers. Muscle echogenicity and muscle thickness of four characteristically involved muscles in IBM were measured and compared with polymyositis (PM)/dermatomyositis (DM), other neuromuscular disorders, and healthy controls. RESULTS: Echogenicity was higher and muscle thickness generally lower in all four muscles in IBM compared with PM/DM and normal controls. When comparing IBM with the comparator groups, the flexor digitorum profundus was the most discriminative muscle. DISCUSSION: Ultrasound appears to be a good test to differentiate established IBM from PM/DM and neuromuscular controls, with value as a diagnostic tool for IBM.


Assuntos
Miosite de Corpos de Inclusão/diagnóstico por imagem , Miosite de Corpos de Inclusão/fisiopatologia , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neuromusculares/diagnóstico por imagem , Doenças Neuromusculares/fisiopatologia , Estudos Retrospectivos , Ultrassonografia de Intervenção/normas
15.
Muscle Nerve ; 62(1): 76-82, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134516

RESUMO

INTRODUCTION: Objective information on longitudinal disease progression in inclusion body myositis (IBM) is lacking. METHODS: Longitudinal dynamometry and functional status data were collated from a cohort of IBM patients. Annual change was calculated by means of linear modeling. Trajectories of change in grip, knee extension, IBM Functional Rating Scale (IBM-FRS) and Neuromuscular Symptom Score (NSS) were identified by means of latent growth mixture modeling. RESULTS: Data were collated from 75 IBM patients (348 person-years follow-up). Annual strength loss was greatest for pinch (-10%) and knee extension (-4%). Functional deterioration was greatest for males. Three distinct trajectory groups were identified. Rapid deterioration trajectory for grip strength was associated with younger diagnosis age. Rapid deterioration for knee extension strength was associated with older age of diagnosis. DISCUSSION: This study has quantified strength change in IBM and identified distinct trajectory groups, which will aid prognostication and stratification for inclusion into future clinical trials.


Assuntos
Progressão da Doença , Dinamômetro de Força Muscular/tendências , Força Muscular/fisiologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Força da Mão/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Estudos Prospectivos
16.
Neuromuscul Disord ; 30(3): 200-206, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32057637

RESUMO

Inclusion body myositis (IBM) is a slowly progressive and heterogeneous disorder that is a challenge for measuring clinical trial efficacy. The current methods of measuring progression of the disease utilizes the Inclusion Body Myositis Functional Rating Scale, grip strength by dynamometer, and finger flexor strength. One of the hallmarks of the disease is selective deep finger flexor weakness. To date, no adequate data has been available to determine how well the Functional Rating Scale relates to this hallmark physical exam deficit. Our study is the first to investigate the degree of correlation between items pertaining to hand function in the Functional Rating Scale with measured grip and finger flexor strength in IBM patients. We have found a lower than expected correlation with finger flexor strength and even lower with grip strength. The current Functional Rating Scale will benefit from optimization to measure clinical progression more accurately.


Assuntos
Força da Mão/fisiologia , Mãos/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Dedos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
Physiol Meas ; 41(1): 015003, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31935703

RESUMO

OBJECTIVE: Muscle strength is a critical clinical hallmark in both health and disease. The current study introduces a novel portable device prototype (MyoQuad) for assessing and monitoring maximal voluntary isometric knee extension torque (MVIT). APPROACH: Fifty-six patients with inclusion body myositis were studied. Knee extension weakness is a key feature in this inflammatory muscle disease. Cross-validation with an isokinetic dynamometer (Biodex System 3 Pro) was performed. Between-day reproducibility and ability to monitor changes in muscle strength over time compared to the gold standard method as a reference, were also investigated. MAIN RESULTS: The measurement was feasible even in the weakest patients. Agreement between methods was excellent (standard error of measurement (SEM) was 3.8 Nm and intra-class correlation coefficient (ICC) was 0.973). Least significant difference (LSD) was 4.9 and 5.3 Nm for the MyoQuad and the Biodex, respectively Measurements using the MyoQuad exhibited excellent between-day reproducibility (SEM was 2.4 Nm and ICC was 0.989 versus 2.6 Nm and 0.988 using the Biodex). Changes in MVIT at 6 and 12 months were similar between methods (timepoint × method interaction was not significant; all p  > 0.19); strength changes classified according to LSD at 6 and 12 months were consistent between methods (>70% consistent classification)). SIGNIFICANCE: The measurement of MVIT using the MyoQuad offers a cost-effective, portable and immediate alternative for the routine measurement of maximal voluntary isometric strength of the quadriceps. The MyoQuad offers a comfort and stability that cannot be provided by standard hand-held dynamometers. These results support quantitative muscle strength assessment using fixed yet flexible dynamometry within clinical routine and multicenter trials.


Assuntos
Contração Isométrica , Força Muscular , Miosite de Corpos de Inclusão/fisiopatologia , Dispositivos Eletrônicos Vestíveis , Idoso , Humanos , Articulação do Joelho/fisiologia , Pessoa de Meia-Idade , Dinamômetro de Força Muscular
19.
Clin Neurophysiol ; 131(2): 368-371, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31865137

RESUMO

OBJECTIVE: To assess the value of electrical impedance myography (EIM) in inclusion body myositis (IBM). METHODS: Patients with clinically defined IBM and healthy controls (HC) of similar age group were recruited. Each participant underwent manual muscle testing (MMT), 6-min walk test (6MWT), handgrip dynamometry, and IBM-functional rating scale assessment (IBM-FRS). EIM measurements were obtained from bilateral deltoid, biceps, forearm-flexors, quadriceps, tibialis anterior, and medial gastrocnemius. RESULTS: Fourteen IBM patients and 12 HCs with mean age 68.6 ± 6 and 67.4 ± 5.4 years were included in the final analysis. Averaged phase value at 50 kHz (EIM50) and ratio of phase value at 50 kHz/200 kHz (EIMPR) from six-muscles were significantly lower in IBM patients when compared to HC (5.23 ± 1.34 vs 7.88 ± 1.9, p-value 0.002, and 0.55 ± 0.09 vs. 0.68 ± 0.09, p-value 0.004, respectively). A strong correlation was noted between IBM-FRS, 6MWT, disease-duration and the averaged value of EIM50 and EIMPR in the IBM patients (Spearman |rho|>0.7, p-values < 0.01). CONCLUSIONS: EIM can differentiate between IBM patients and HCs and EIM parameters correlate with clinical outcome measures. SIGNIFICANCE: EIM may be a potential objective biomarker for IBM. A longitudinal validation study is warranted.


Assuntos
Miografia/métodos , Miosite de Corpos de Inclusão/fisiopatologia , Impedância Elétrica , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Miografia/normas , Miosite de Corpos de Inclusão/diagnóstico , Sensibilidade e Especificidade
20.
Arthritis Res Ther ; 21(1): 293, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852482

RESUMO

BACKGROUND: Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients. METHODS: Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis. RESULTS: Myocellular infiltration of CD3-/CD8+ expressing natural killer cells increased following BFRE (P < 0.05) with no changes in CON. No changes were observed for CD3+/CD8- or CD3+/CD8+ T cells in BFRE or CON. CD3+/CD244+ T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68+/CD206-) and M2 anti-inflammatory (CD68+/CD206+) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups. CONCLUSIONS: Low-load blood flow restriction exercise elicited an upregulation in CD3-/CD8+ expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.


Assuntos
Exercício Físico/fisiologia , Sistema Imunitário/imunologia , Músculo Esquelético/fisiologia , Miosite de Corpos de Inclusão/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Idoso , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Complexo CD3/imunologia , Complexo CD3/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Terapia por Exercício/métodos , Feminino , Humanos , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Receptor de Manose , Lectinas de Ligação a Manose/imunologia , Lectinas de Ligação a Manose/metabolismo , Pessoa de Meia-Idade , Força Muscular/imunologia , Força Muscular/fisiologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/imunologia , Miosite de Corpos de Inclusão/imunologia , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Fluxo Sanguíneo Regional/imunologia
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