A review of the evidence for the utility of physical activity monitor use in patients with idiopathic inflammatory myopathies.

Few proven therapies exist for patients with idiopathic inflammatory myopathies (IIMs), partly due to the lack of reliable and valid outcome measures for assessing treatment responses. The current core set measures developed by the International Myositis Assessment and Clinical Studies group were developed to standardize assessments of disease activity and treatment effect. None of the current measures address functional improvement in muscle weakness. Therefore, supplemental measures to more objectively assess physical activity levels and fatiguability in free-living settings are needed to assess disease activity more comprehensively. Validated physical activity monitors (PAMs) have the potential to serve as an objective functional outcome measure in clinical trials and observational studies. This review examines the current evidence for the use of body-worn PAMs in clinical settings with IIM patients. A practical overview of methods for PAM use in clinical patient populations (including measurement details and data processing) that focuses on IIM patients is also presented.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Quantification of left atrial strain in patients with idiopathic inflammatory myopathy using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Left atrial (LA) dysfunction is involved in idiopathic inflammatory myopathy (IIM). Multiparametric cardiovascular magnetic resonance (CMR) strain imaging is a feasible and reproducible tool for examining global and regional LA functions, as well as left ventricular (LV) function in IIM patients. AIM: The aim of this study was to evaluate the feasibility and reproducibility of LA strain occurrence and strain rate for LA function assessment using CMR in IIM cases. MATERIALS AND METHODS: A total of 36 IIM and 42 healthy control cases were included. Baseline ventricular function was comparatively assessed in both groups. LA strain occurrence and strain rate were examined by cine cardiac magnetic resonance imaging [MRI] utilizing an in-house semiautomated technique. LA global function indexes were quantitated, including reservoir, conduit, and booster-pump functions. RESULTS: A total of 78 participants were enrolled in this study. There was no significant difference in left/right ventricular routine functions between IIM patients and control individuals (p>0.05); the same results (p>0.05) was also observed between patients with high hs-cTnI and normal. However, LV mass index had significant difference (p1=0.003, p2<0.01). Compared with IIM patients and control individuals, only total strain (εs) (p4=0.046) and passive strain (εe) (p4=0.002) showed significant difference, and in cases with high hs-cTnI and normal hs-cTnI, there are differences for εs (p3=0.012) and εe (p4=0.047). The strongest association was found between εe and LV ejection fraction (LVEF) (r=0.581, p<0.01). CONCLUSION: IIM cases have altered LA reservoir and conduit functions, and LA strain could reflect LA function.

Hand-held dynamometry for assessment of muscle strength in patients with inflammatory myopathies.

OBJECTIVES: Muscle weakness in idiopathic inflammatory myopathies (IIMs) is conventionally assessed using manual muscle testing (MMT). However, more objective tools must be developed to accurately and reliably quantify muscle strength in myositis patients. Hand-held dynamometry (HHD) is a quantitative, portable device with reported reliability in neuromuscular disorders. Our aim was to assess the reliability, validity and responsiveness of HHD in myositis. METHODS: Myositis patients [DM, necrotizing myopathy (NM), PM and anti-synthetase syndrome] evaluated at the University of Pittsburgh myositis centre were prospectively enrolled. Each patient was assessed at 0, 3 and 6 months for validated outcome measures of myositis disease activity and physical function. At each visit, muscle strength was assessed using both MMT and HHD (Micro FET2, Hoggan Health Industries, Draper, UT, USA). The reliability, validity and responsiveness of the HHD was assessed using standard statistical methods. RESULTS: Fifty IIM patients (60% female; mean age 51.6 years; 6 PM, 9 NM, 24 DM and 11 anti-synthetase syndrome) were enrolled. HHD showed strong test-retest intrarater reliability (r = 0.96) and interrater reliability (r = 0.98). HHD correlated significantly with the MMT score (r = 0.48, P = 0.0006) and myositis disease activity and functional measures. Longitudinal analysis showed a significant and strong association between the HHD and MMT as well as 2016 ACR/EULAR myositis response criteria (r = 0.8, P < 0.0001) demonstrating responsiveness. The mean effect size and standardized response mean of HHD was large: 0.95 and 1.03, respectively. MMT had a high ceiling effect compared with HHD. CONCLUSION: HHD demonstrated strong reliability, construct validity and responsiveness in myositis patients. External validation studies are required to confirm these findings.

Sexual function in patients with idiopathic inflammatory myopathies: a cross-sectional study.

OBJECTIVES: To date, there is almost no information concerning the sexual health of patients with idiopathic inflammatory myopathies (IIM). This cross-sectional study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function. METHODS: In total, 122 women (61 with IIM, 61 age-matched HC) and 22 men (11 with IIM, 11 age-matched HC) aged 18-80 years completed gender-specific selection of 7 well-established and validated questionnaires assessing sexual health and function (Female Sexual Function Index, Brief Index of Sexual Function for Women, Sexual Function Questionnaire, Sexual Quality of Life Questionnaire-Female, International Index of Erectile Function, Male Sexual Health Questionnaire, Sexual Quality of Life Questionnaire-Male). Results were compared between patients and HC and correlated with selected disease-related features. RESULTS: The prevalence of sexual dysfunction in IIM was 59% in women (vs 40% in HC), and 64% (vs 9% in HC) in men. Men and women with IIM reported significantly impaired sexual function compared with sex-/age-matched HC. Decreased sexual function was associated with muscle weakness, disability, physical inactivity, fatigue, depression and decreased quality of life. CONCLUSIONS: Our results suggest that sexual dysfunction is common among IIM patients and more attention should be paid to this aspect of the disease.

Reliability, validity and responsiveness of physical activity monitors in patients with inflammatory myopathy.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) cause proximal muscle weakness, which affects the ability to carry out the activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity and potentially have clinical usefulness in the assessment of IIMs. We examined the psychometric characteristics for PAM outcomes in IIMs. METHODS: Adult IIM patients were prospectively evaluated (at baseline, 3 months and 6 months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/minute, peak 1-minute cadence, and vector magnitude/minute. Validated myositis core set measures (CSMs) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extramuscular disease activity (Ex-muscular global), HAQ-DI (HAQ disability index), muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSMs, using Pearson correlations and other appropriate analyses. RESULTS: A total of 50 adult IIM patients enrolled [mean (s.d.) age, 53.6 (14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r = -0.37 to -0.48), Pt global (r=-0.43 to -0.61), HAQ-DI (r = -0.47 to -0.59) and MMT (r = 0.37-0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal associations with MD global (r=-0.38 to -0.44), MMT (r = 0.50-0.57), HAQ-DI (r = -0.45 to -0.55) and functional tests (r = 0.30-0.65) were moderate to strong. PAM measures were responsive to MMT improvement ≥10% and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-minute cadence had the largest effect size and standardized response means. CONCLUSION: PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-minute cadence. PAMs are able to provide valid outcome measures for future use in IIM clinical trials.

COVID-19 and myositis - unique challenges for patients.

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.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

Predictors, outcome and characteristics of oropharyngeal dysphagia in idiopathic inflammatory myopathy.

INTRODUCTION: Oropharyngeal dysphagia is a clinical hallmark of idiopathic inflammatory myopathy (IIM). This study investigated predictors, outcome, and characteristics of oropharyngeal dysphagia in patients with different types of IIM. METHODS: Flexible endoscopic evaluation of swallowing (FEES) videos of 71 IIM patients were retrospectively analyzed for bolus spillage, penetration, aspiration, and pharyngeal residue. Based on these findings, dysphagia severity was rated. Regression analyses were performed to investigate demographic and disease-specific predictors of dysphagia severity and pneumonia as outcome-relevant complications of dysphagia. A score was developed to rate the quality of the endoscopic white-out as a surrogate marker for pharyngeal muscle weakness with consecutive residue. RESULTS: Our analysis revealed no independent predictors of dysphagia severity. Dysphagia severity, however, was an independent predictor for pneumonia, which occurred in 24% of patients. Pharyngeal residue with risk of postdeglutitive aspiration was the most common dysphagia pattern. Attenuation of the endoscopic white-out was related to residue severity. DISCUSSION: Dysphagia in IIM assessed with FEES is associated with relevant complications, such as aspiration pneumonia, and must be considered independently of peripheral muscle weakness and disease duration. Swallowing impairment mainly presents with pharyngeal residue. The quality of the white-out may serve as a semi-quantitative surrogate marker for pharyngeal contractility.

Sensitivity and specificity of single and combined clouds analyses compared with quantitative motor unit potential analysis.

INTRODUCTION: Turns-amplitude, number of small segments (NSS)-activity, and envelope-activity clouds are three methods of electromyography (EMG) interference pattern analysis. Our objective was to evaluate the sensitivity and specificity of each individual cloud analysis and combined clouds analysis to compare with that of quantitative motor unit potential (QMUP) analysis. METHODS: A total of 379 muscles from 100 patients were analyzed by both QMUP and clouds analyses. Calculation of sensitivity and specificity was based on the clinical diagnosis as the "gold standard." RESULTS: For discrimination of abnormal vs normal and neuropathic vs non-neuropathic, combined clouds analysis had greater sensitivity than QMUP analysis and any single cloud analysis, but there were no differences in specificity. For discrimination of myopathic vs non-myopathic, combined clouds analysis and single cloud analysis had greater sensitivity than QMUP analysis, but there were no differences in specificity. DISCUSSION: Combined clouds analysis was superior to QMUP and each single cloud analysis for distinguishing normal, myopathic, and neuropathic muscles.

COVID-19 and Myositis: What We Know So Far.

PURPOSE: Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era. RECENT FINDINGS: COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor-mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration - finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.

Characteristics and outcomes of overlap myositis: a comparative multigroup cohort study in adults from the MyoCite cohort.

Overlap myositis (OM), an important subset of idiopathic inflammatory myopathies (IIM), is being increasingly recognized with wider myositis-specific autoantibody (MSA) testing. We studied the differences in clinical characteristics and long-term outcomes of OM with Dermatomyositis (DM), Polymyositis (PM), anti-synthetase syndrome (ASSD), and Cancer-associated IIM (CAM). Data from the MyoCite registry (Dec2017-May2020), a prospective dataset of IIM was extracted for the clinical profile, and MSAs, immunosuppressants received, disease activity (relapses and incomplete response), and treatment-related (drugs ADRs and infections) adverse events (DRAE and TRAE) were collected and analyzed between groups. Of 214 adults (58-OM,89-DM,27-ASSD,33-PM,7-CAM), OM had a greater female preponderance (13.5:1). Raynaud's and sclerodactyly were the prime distinguishing features of OM. OM could be distinguished from PM by frequent arthritis (OR-3.2) and infrequent dysphagia (OR-0.17); DM with greater nephritis (OR-20), infrequent dysphagia (OR-0.24) and rashes (OR-0.02); and ASSD by infrequent ILD (OR-0.07), and mechanic's hand (OR-0.05). 50% fulfilled the classification criteria for ASSD in the absence of MSA testing. ANA was positive more often (PM/DM: OR-6.7) and anti-Ro52 (OR-4.5) frequent in OM. Baseline serum creatinine and acute phase reactants were higher. OM received lower glucocorticoids (0 mg/kg, p < 0.001). Overall, 90% and 84% of OM at 12 and 24 months, respectively, achieved remission, with similar DRAE and TRAE as other IIM subsets. OM can be misdiagnosed as ASSD in the absence of MSA testing. Raynaud's, sclerodactyly, and a positive ANA may identify OM and prevent overtreatment.

Clinical features of anti-synthetase syndrome associated interstitial lung disease: a retrospective cohort in China.

BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.

MR imaging findings of musculoskeletal involvement in microscopic polyangiitis: a comparison with inflammatory myopathy.

OBJECTIVE: The purpose of this study was to evaluate the importance of MR imaging findings of musculoskeletal involvement of the lower limbs in diagnosing microscopic polyangiitis (MPA) vs polymyositis (PM) or dermatomyositis (DM). MATERIALS AND METHODS: This study included 13 patients diagnosed with MPA clinically and through histologically, and 38 diagnosed with PM/DM, who underwent MR imaging of the lower limbs prior to treatment. Axial and coronal short tau inversion recovery (STIR) images were reviewed retrospectively. RESULTS: The sites affected by MPA were the lower legs in six (46%) patients and the thighs in seven (54%). Intramuscular hyperintensity and fascial hyperintensity were observed in all cases of MPA (100%). Fascial hyperintensity was more frequently encountered in MPA than in PM/DM (100% vs. 45%, p < 0.01). As the predominantly involved sites, the fascial regions were more frequently affected by MPA than by PM/DM (77% vs. 18%, p < 0.01). Diffuse subcutaneous fat hyperintensity was more frequently observed in MPA than in PM/DM (100% vs. 16%, p < 0.01). However, no significant differences in intramuscular hyperintensity (100% vs. 97%, p = 0.745) and subcutaneous fat hyperintensity (54% vs. 50%, p = 0.533) were found between MPA and PM/DM. CONCLUSION: Intramuscular hyperintensity and fascial hyperintensity have always been observed in MPA, and the predominantly affected sites were usually the fascial regions. Compared with PM/DM, fascial hyperintensity and diffuse subcutaneous fat hyperintensity were more frequent in MPA.

Cardiac involvement in inflammatory myopathies and inherited muscle diseases.

PURPOSE OF REVIEW: To examine recent developments relating to cardiac involvement in the adult idiopathic inflammatory myopathies (IIM) and those inherited muscle diseases which may present in adulthood and mimic IIM. RECENT FINDINGS: Cardiac involvement is a common feature of IIM and inherited muscle diseases. Frequency according to disease subtype varies, with serotype having particular influence in IIM, and genotype in the inherited muscle diseases. Innovative techniques for examining cardiac function have been investigated further, including speckle-tracking echocardiography and cardiac magnetic resonance tomography. The present work has highlighted a likely underestimate of the burden of cardiac disease to date. The complex relationship between IIM, atherosclerosis, and traditional cardiovascular risk factors has been further elucidated. Consensus recommendations for managing patients with inherited muscle diseases and prominent cardiac involvement have been recently published. In addition to supportive care, disease modifying treatments are increasingly becoming available for inherited muscle diseases which may also improve cardiac outcomes. SUMMARY: Cardiac involvement is associated with significant morbidity and mortality. We suggest having a low threshold for considering the possibility of cardiac involvement in all patients with muscle disease.

Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies.

OBJECTIVES: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis. METHODS: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-ß1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR. RESULTS: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls. CONCLUSION: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases.

Updated size index valid for both neurogenic and myogenic changes.

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.

An exploratory study of contractile force production in muscle fibers from patients with inflammatory myopathies.

INTRODUCTION: The mechanism by which weakness develops in idiopathic inflammatory myopathies (IIMs) is still unclear. In this study we investigated the maximum force of single muscle fibers from patients with IIMs. METHODS: Permeabilized single muscle fibers from patients with IIMs and healthy controls were subjected to contractility measurements. Maximum force and specific force production (maximum force normalized to fiber size) and fiber type were determined for each isolated fiber. RESULTS: A total of 178 fibers were studied from five patients with IIMs and 95 fibers from four controls. Specific force production was significantly lower in the IIM group for all fiber types. DISCUSSION: The findings from this exploratory study suggest that weakness in IIMs may, in part, be caused by dysfunction of the contractile apparatus. These findings provide a basis for further studies into the mechanisms underlying weakness in IIMs.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in myocardial and skeletal muscles in idiopathic inflammatory cardiomyopathy.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients. METHODS: Forty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests. RESULTS: At baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients. During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2-15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment. CONCLUSIONS: Both myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.

Associations between magnetic resonance imaging and EMG findings in myopathies.

OBJECTIVES: Magnetic resonance imaging (MRI) is a cornerstone in diagnosis of myopathies. The present study sought to elucidate possible associations between electromyography (EMG) findings and histogram parameters derived from clinical MRI in myositis and other myopathies. MATERIALS AND METHODS: Twenty six patients with myopathies were included in this retrospective study. Clinical MRI was performed with a 1.5T MRI scanner including T2- and T1-weighted images. EMG analysis was performed during clinical diagnostic workup. The histogram parameters of the MRI sequences were obtained of the same muscle, which was investigated with EMG. RESULTS: Several correlations were identified between mean duration of the motor unit potentials (MUP) and histogram parameters derived from T1- and T2-weighted images. The highest for T1-weighted images was mode (r = -.73, P < .0001) and for T2-weighted images was p25 (r = -.57, P = .022). There were significant differences for several histogram parameters between muscles with pathological spontaneous activity and without. So, for T1-weighted images, the best discrimination was achieved with mean (P = .096), and for T2-weighted images for p10 (P = .05). Mean SI values derived from T1-weighted images achieved an AUC of 0.84 with a sensitivity of 0.81 and a specificity of 0.86 to discriminate patients with and without pathological spontaneous activity (PSA). CONCLUSIONS: The present study identified strong associations between histogram analysis derived from morphological MRI sequences and the duration of the MUP derived from EMG in myopathies strengthening the fact that both diagnostic modalities can reflect disease state in a similar fashion. Histogram parameters can predict muscles with PSA.