Severe Muscle Weakness Research Articles

Severe Rhabdomyolysis in a Child With Multisystem Inflammatory Syndrome: An Autoimmune Mechanism?

Severe Rhabdomyolysis in a Child With Multisystem Inflammatory Syndrome: An Autoimmune Mechanism?

27395 ANCA-positive hemorrhagic vasculitis with severe myositis—Atypical presentation of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Patient history: A 41-year-old female with a past medical history of asthma presented to the emergency department for diffuse myalgias and a cutaneous eruption gradually worsening over two weeks. Physical examination showed symmetric violaceous papules and nodules on the dorsal arms and hemorrhagic vesicles overlying palpable purpura on the lower extremities. During admission she developed profound dysphagia and severe systemic muscle weakness.

Recovery from aortic valve surgery: the trajectory of muscle mass, strength, and quality, and health-related quality of life (HRQoL)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Barts Charity OnBehalf Queen Mary University of London (QMUL) and Barts Health NHS Trust Background/Introduction: The impact of intensive care unit-acquired weakness (ICUAW) is considerable and is associated with reduced physical function and impaired health-related quality of life (HRQoL). Patients’ undergoing elective cardiac surgery are known to lose significant muscle mass and strength in the first seven days after surgery, but little is known beyond that time. Purpose We sought to investigate the effect of cardiac surgery on ICUAW (including muscle mass, strength, muscle quality) and HRQoL (including anxiety and depression and reintegration into society) until out-patient follow-up. Methods Eligible patients included adults undergoing a surgical elective aortic valve replacement without any pre-existing causes of severe muscle weakness or wasting. Muscle mass was measured using ultrasound of the rectus femoris cross-sectional area (RFcsa). Muscle quality was calculated using histogram analysis, specifically pixel intensity (PI), whereby a lower value is indicative of healthier muscle tissue. Muscle strength was measured using hand-held dynamometry specifically grip strength. HRQoL (EQ5D), anxiety and depression (hospital anxiety and depression scale (HADS)) and reintegration to normal living (RNLI index) were also collected. Measurements were assessed preoperatively, at day 7 and at out-patient follow-up. Results Thirty-one patients were recruited, with 22 (70.9%) patients attending follow-up. Patients lost 6.5% RFcsa (p= <0.0001) in the first seven days post-surgery and 10.1% (p = 0.0014) between preoperative assessment and follow-up. Hand-held grip strength decreased significantly (10.6%, p= <0.0001) in the first seven days post-surgery, however, differing to RFcsa, recovered considerably between day 7 and follow-up (7.7%, p = 0.018). Decreased muscle quality was observed solely in the first seven days after surgery (8.3%, p = 0.0094). The EQ5D visual analogue scale and crosswalk index increased significantly from preoperative assessment to follow-up (10%, p = 0.0250; 17.6%, p = 0.022 respectively) and day 7 to follow-up (11.7%, p = 0.0311; 27.9%, p = 0.011 respectively). While depression scores significantly decreased between the same time points as the EQ5D, changes in anxiety and RNLI scores, were non-significant. Conclusion Patients undergoing surgical aortic valve replacements lose considerable muscle mass in hospital, failing to recover even at out-patient follow-up. Furthermore, muscle quality decreases in the first seven days after surgery in line with the acute muscle loss. However, the impact on strength is less extensive as patients appear to recover the loss by follow-up. Patients’ health scores, function index and depression scores also improve, suggesting that muscle mass is the only outcome to not recover at follow-up. Therefore, patients appear to recover well from AVR surgery even surpassing some of their preoperative results, with the exception of the RFcsa.

Maximum Tolerated Dose (MTD) and Safety Profile from Phase I Study of MT-3724 (CD20 targeted immunotoxin) in Relapsed/Refractory (R/R) Non-Hodgkin B-Cell Lymphoma (NHL)

Maximum Tolerated Dose (MTD) and Safety Profile from Phase I Study of MT-3724 (CD20 targeted immunotoxin) in Relapsed/Refractory (R/R) Non-Hodgkin B-Cell Lymphoma (NHL)

Statin-induced rhabdomyolysis in a 60-year-old woman with decompensated type 2 diabetes: a case report

Rhabdomyolysis is a very rare and most severe form of statin-induced muscle adverse event characterized by muscle pain, muscle necrosis with myoglobinemia and/or myoglobinuria with a very high risk of acute kidney injury and death. The article presents a case report of developing rhabdomyolysis in a middleaged female patient with hypertension, decompensated type 2 diabetes and albuminuria. A 60-year-old woman was admitted to the hospital for emergency indications with complaints of severe muscle weakness that began in the neck, which spread over several days to the upper and lower extremities, with a symptoms progression up to paresis. According to the appointment of a primary care physician, three months before hospitalization, the patient was switched from therapy with European generic brand-name rosuvastatin 20 mg to the Russian generic unbranded atorvastatin in the same dose (20 mg), which is not comparable in lipid-lowering effect. In a laboratory study, an increase in creatine phosphokinase level by 348 times (50462 U/L) of upper normal limit in combination with severe hypokalemia 1б7 mmol/L in the absence of renal dysfunction was recorded. Cancellation of statin, metformin and empagliflozin, intensive infusion therapy and treating electrolyte imbalance made it possible to prevent the development of acute renal damage, life-threatening arrhythmias and completely stop muscle complaints within a few days. The patient was discharged from the hospital on the 23rd day with reference clinical and laboratory values, including creatine phosphokinase.This case emphasizes the importance of maintaining clinical suspicion regarding rhabdomyolysis in patients receiving statin therapy in the presence of risk factors (in this case, female sex, hyperglycemia, chronic kidney disease, concomitant therapy), as well as the relevance of timely diagnosis and treatment of this condition.

X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy.

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

Long-term outcome in patients with juvenile dermatomyositis: A case series

BackgroundFollow-up of juvenile dermatomyositis (JDM) patients has demonstrated the impact of the disease on several organs in the long term. ObjectiveAs there is little information on the long-term outcome of JDM, we aimed to assess long-term outcomes in a series of JDM patients. MethodsAfter selection of JDM patients, a consultation with a dermatologist and a rheumatologist was held for each patient. Cutaneous, muscle, and disease damage was assessed using different validated scores including the abbreviated Cutaneous Assessment Tool (aCAT), 8-muscle Manual Muscle Testing (MMT8), Childhood Myositis Assessment Scale (CMAS), Myositis Damage Index (MDI), Childhood Health Assessment Questionnaire (CHAQ), and Health Assessment Questionnaire (HAQ). Long-term disease outcomes were recorded including growth and pubertal development, educational and vocational achievement, and development of comorbidities. ResultsSeven patients were included in the study. After a mean follow-up of 14.9±8.8 years, the mean aCAT score was 0.57±1.4 and only one patient had a positive aCAT activity score. The mean aCAT damage score was 1.4±1.3 and five (71%) patients had a score of ≥1. Five (71.4%) patients had normal muscle strength with an MMT8 score of >72, and none had severe muscle weakness (MMT8 ≤32, and CMAS<35). The mean total extent of damage according to the MDI was ≥1 in five (71%) patients and mainly involved the skin. Two (29%) patients had mild disability according to the CHAQ/HAQ disability index. In terms of quality of life, no patient had a score of<40 (1 SD below the mean for healthy controls). ConclusionsBased on validated cutaneous and musculoskeletal scores, our study demonstrated the good functional outcomes of JDM at long-term follow-up.

Critical Illness Myopathy in a Child with SARS-CoV-2 Infection

AbstractA variety of symptoms affecting the nervous system and/or skeletal muscle have been described during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Though largely unexplored in children, intensive care unit-acquired weakness (ICU-AW) is associated with significant comorbidities. No previous pediatric cases of ICU-AW associated with coronavirus disease 2019 have been reported. A 12-year-old boy with SARS-CoV-2 infection developed systemic inflammatory response syndrome. Seven days later, he developed severe muscle weakness, with a creatine kinase level of 402 U/L. Nerve conduction studies and electromyography revealed a myopathic pattern. Severe pediatric cases of SARS-CoV-2 infection may develop ICU-AW. Early diagnosis and rehabilitation may decrease comorbidity and improve quality of life.

Influence of simulated hip muscle weakness on hip joint forces during deep squatting

ABSTRACT This study aimed to determine the effects of simulated hip muscle weakness on changes in hip joint forces during deep squat motion. Ten healthy individuals performed squat motion at three different positions (0° foot angle [N-squat], 10° toe-in [IN-squat], and 30° toe-out [OUT-squat]). A scaled musculoskeletal model for each participant was used to calculate the muscle and hip joint forces. For each hip muscle, models of full strength, mild muscle weakness (15% decrease), and severe muscle weakness (30% decrease) were created. The muscles affecting the hip joint forces were identified, and the rate of change in the joint forces was compared among the three squat conditions. The anterior hip joint force was increased in the muscle weakness models of the inferior gluteus maximus (iGlutMax) and iGlutMax+deep external rotator (ExtRot) muscles. With 30% muscle weakness of these muscles, statistically significant differences in the rate of increase in the anterior joint force were observed in the following order: IN-squat (iGlutMax, 29.5%; iGlutMax+ExtRot, 41.4%), N-squat (iGlutMax, 18.3%; iGlutMax+ExtRot, 27.8%), and OUT-squat (iGlutMax, 5.6%; iGlutMax+ExtRot, 9.3%). OUT-squat may be recommended to minimize the increase in hip joint forces if accompanied by hip muscle weakness.

POS1224 RHEUMATIC MANIFESTATIONS IN COVID-19 PATIENTS - SINGLE-CENTER EXPERIENCE AMIDST THE PANDEMIC

Background:Recently evolved from a monochromic flu-like disease to a polysyndromic “spectrum of disease”, our understanding of coronavirus disease 2019 (COVID-19) is still far from being complete [1]. Hyperinflammation involving not only the lungs but also the musculoskeletal system, skin, cardiovascular, genitourinary systems is immune-mediated resembling the flares of a full-blown rheumatic disease [2,3].Objectives:To describe the prevalence and type of rheumatic manifestations in a cohort of COVID-19 patients hospitalized in the COVID-19 rheumatology department in University Hospital St. Marina, Varna, Bulgaria.Methods:In the present single-center cohort study, а retrospective database analysis was performed among all COVID-19 patients hospitalized from 1 Dec 2020 to 22 Jan 2021. All 243 patients (age 19 - 93 years) were treated for moderate or severe SARS-CoV-2 infection confirmed by laboratory tests, including positive polymerase chain reaction (PCR) test, and imaging modality. Inpatient treatment included antibiotics, dexamethasone, anticoagulants, and antiviral drug remdesevir (optional). Detailed disease history and clinical examination were carried out by a fully certified rheumatologist and/or specialist in internal medicine.Results:Among all 243 COVID-19 patients, those with prominent self-reported myalgia and arthralgia were 26% (n = 63) and 21.3 (n = 52), respectively. We had 4 (1.6%) cases of newly developed cutaneous vasculitis and 2 (0.8%) cases of severe Raynaud’s phenomenon after SARS-CoV-2 infection onset. Two patients experienced severe muscle weakness, had elevated creatine phosphokinase, and were diagnosed with inflammatory myopathy secondary to COVID-19. Lupus-like syndrome was observed in 2 (0.8%) patients.Conclusion:Rheumatic manifestations are part of the heterogeneous spectrum of COVID-19 disease. Amidst the COVID-19 crisis, each newly onset rheumatic manifestation warrants exclusion of SARS-CoV-2 infection. Therefore, a rheumatologist should be a part of a multidisciplinary approach towards the COVID-19 treatment.

A Case of Rhabdomyolysis in a Patient With Hashimoto’s Thyroiditis

Introduction: Hashimoto’s thyroiditis (HT) is an autoimmune disease that presents with musculoskeletal symptoms like proximal muscle weakness, stiffness, pain or cramps in the majority of patients. Rhabdomyolysis which is a breakdown of the skeletal muscles, is a rare but serious manifestation of hypothyroidism and if occurs, it is usually related to trauma, strenuous exercise or use of statins. We report a patient with unrecognized Hashimoto’s thyroiditis who presented with severe rhabdomyolysis without reported history of strenuous exercise, seizures or statin use and surprisingly, He did not have any complications from rhabdomyolysis like electrolytes abnormalities or acute kidney injury. Case Report: A 56-year-old man with no reported past medical history who presented with severe generalized weakness, bilateral leg pain, and recurrent falls for three months. He also reported constipation, fatigue and dry skin. Denied any prior personal or family history of thyroid disease, seizure disorder, statin use, trauma or tick bite. He was afebrile with a heart rate of 80 beats/minute, a blood pressure of 126/71mmHg. Initial laboratory testing showed normal metabolic panel, elevated thyroid stimulating hormone 30.6 uIU/mL (Range 0.27-4.2 uIU/mL), FT4 0.1 ng/dL (Range 0.93-1.7ng/dL), TPO Ab 300IU/mL (N<43IU/mL), Creatine Kinase (CK) level 10,000U/L (N<200U/L), ESR 27 mm/Hr (N<20mm/Hr) and Lactate Dehydrogenase 621U/L (N <225U/L). A muscle biopsy was done to rule out polymyositis as a cause of his severe muscle pain, weakness and tenderness and it was negative. Patient was diagnosed with HT with associated rhabdomyolysis after excluding other causes of rhabdomyolysis. Supportive treatment with intravenous fluids and Levothyroxine were initiated and resulted in dramatic clinical improvement. Conclusion: Rhabdomyolysis is a rare but potentially a serious complication of hypothyroidism. Screening for hypothyroidism in patients with elevated muscle enzymes should be considered, as early diagnosis and prompt treatment of hypothyroidism is essential to prevent rhabdomyolysis and its consequences like acute kidney disease and electrolytes abnormalities. Appropriate fluid resuscitation is the mainstay therapy for AKI prevention and should be initiated in a timely manner. Key Words: HT: Hashimoto’s Thyroiditis, ESR: Erythrocyte Sedimentation Rate, TPO Ab: Thyroid Peroxidase Antibody, TSH: Thyroid Stimulating Hormone, FT4: Free Thyroxine level, AKI: Acute Kidney Injury.

Sarcoplasmic Reticulum Ca 2+ Handling in Gastrocnemius Muscles from 10‐week‐old C57 and D2‐ mdx Mice

Background Duchenne Muscular Dystrophy (DMD) is an X-linked muscle wasting disease caused by an absence of dystrophin. Secondary mechanisms including elevated myoplasmic Ca2+ as a result of dysfunctional sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pumps and leaky ryanodine receptors (RyR) can perpetuate disease pathology. Although the widely used preclinical C57BL/10 (C57) mdx mouse model displays moderate muscle damage and weakness, this model falls short in its ability to recapitulate the more severe human phenotype. Conversely, the DBA/2J (D2) mdx mouse model displays severe and early-onset muscle weakness, damage and histopathology; and therefore, more closely mimics human DMD. To date, there has been no characterization of muscle Ca2+ handling in the D2-mdx mouse. Thus, we examined sarcoplasmic reticulum (SR) Ca2+ handling in both D2-mdx and C57-mdx mice. Methods Eight-week-old male C57-WT, C57-mdx, D2-WT and D2-mdx mice were purchased from Jackson Laboratories. All mice underwent a hangwire test and were temporarily housed (48 hr) in a Promethion Metabolic Cage System to measure energy expenditure and cage activity. At 10 weeks of age, mice were euthanized, and gastrocnemius muscles were collected to measure Ca2+ uptake and leak via an Indo-1 fluorimetric assay. Serum creatine kinase (CK) activity was measured using a commercially available kit. Results Consistent with previous literature, serum CK was elevated in both C57-mdx and D2-mdx mice compared with WT, but to a greater extent in the former (8.9-fold vs 3.3 fold, p = 0.04). While both C57-mdx and D2-mdx mice had lowered hangwire time, these impairments were more severe in the D2-mdx mouse (-30% in C57-mdx vs -50% in D2-mdx, p = 0.09). Similarly, while both C57-mdx (-15%) and D2-mdx (-33%) mice had lowered total cage activity, the D2-mdx mice were most affected (p = 0.03). Interestingly, metabolic cage analyses further revealed that D2-mdx (1.3-fold increase) but not C57-mdx mice, had significantly elevated daily energy expenditure compared to their respective WT groups. When examining SR Ca2+ uptake, we found that the D2-mdx mice had significantly elevated starting Ca2+ levels compared with D2-WT mice (5500 vs 2300 nM). When activated by ATP, there was significantly less removal of Ca2+ in the D2-mdx muscles compared with WT (2.6-fold greater area-under-the-curve). However, none of these effects were observed in the C57-mdx mice. Furthermore, when SERCA was inhibited with cyclopiazonic acid, the rate of SR Ca2+ leak (-50%) and the amount of SR Ca2+ released back into the cytosol (-48%) were significantly lowered in the D2-mdx but not in the C57-mdx mice. This is likely reflective of impaired SR Ca2+ uptake and filling. Conclusions Unlike the C57-mdx, the D2-mdx mice displayed early onset muscle weakness with lowered cage ambulation and hangwire time when compared with their respective WT groups. These findings were associated with impaired SR Ca2+ handling in the D2-mdx mice but not the C57-mdx mice. Together, the extensive muscle damage and impaired SR Ca2+ handling in the D2-mdx mice likely enhances their daily energy expenditure.

P035 Inflammatory myopathy and metabolic disorders causing myopathies

Abstract Background/Aims Myopathies due to inborn errors of metabolism can be difficult to differentiate from inflammatory myopathies. Careful history, examination and laboratory tests are required to establish the diagnosis. We present a case of Riboflavin Transport Deficiency (Brown-Vialetto-Van Laere syndrome) masquerading as an inflammatory myopathy. Methods A 37-year-old lady presented with severe proximal muscle weakness. She had background of sensory neuropathy and chronic anaemia. Notably, her sister had a history of similar symptoms. Creatine Kinase (CK) was 360 IU/L and lactate dehydrogenase (LDH) was 1700 IU/L. Inflammatory markers were normal. The Ro52 antibody was weakly positive. Electromyography showed evidence of a sensory neuropathy with myopathic features. There was symmetrical fatty infiltration and atrophy of the thigh muscles on magnetic resonance imaging (MRI). Positron emission tomography (PET-CT) scan showed widespread intense uptake in skeletal muscle groups. She was given 3 pulses of IV methyprednisolone followed by oral prednisolone which did not provide clinical benefit. Intravenous immune globulin was given when she developed bulbar weakness, with difficulty swallowing and breathing. She required non-invasive ventilation and nasogastric feed. There were necrotic and regenerative muscle fibres on the muscle biopsy, in keeping with rhabdomyolysis. Electron microscopy showed abundant lipid accumulation, suggestive of a metabolic disorder. Urinary organic acids were raised, triggering an acylcarnitines blood spot test, which were increased. This was compatible with riboflavin transport 'Brown-Vialetto-Van-Laere syndrome'. Riboflavin 500mg TDS was started resulting in significant clinical improvement. Prednisolone was weaned, genetic testing sent, and she was transferred for neurorehabilitation. Results Riboflavin Transport Deficiency (Brown-Vialetto-Van Laere syndrome) is an autosomal recessive neurodegenerative genetic disorder. It affects females and males equally. Symptoms can appear in infants as well as adults. These include hearing and visual loss, bulbar palsy leading to dysphagia and speech problems. Paralysis of diaphragm may cause breathing difficulty. Initially it affects the proximal muscles and then generalized muscle weakness. Molecular genetic testing is required to confirm diagnosis. Patients may have abnormal plasma levels of flavin or acylcarnitine. Acylcarnitines are biological intermediates, used in the diagnosis of fatty acid oxidation disorders. Treatment includes riboflavin supplementation and supportive measures. Response to treatment is variable. Conclusion This lady was initially managed as inflammatory myopathy but did not respond to high dose methylprednisolone. There were atypical features including normal inflammatory markers, MRI thighs showing predominantly fatty infiltration and muscle atrophy and the muscle biopsy with abundant lipid accumulation suggestive of a metabolic disorder. We are awaiting full results of genetic testing. This case is a reminder of the importance of tissue diagnosis and reassessing the initial diagnosis if the clinical picture changes or patients do not respond as expected to treatment. Disclosure M. Malik: None. A. Mason: None. B. Davidson: None. J. Furby: None.

Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature

BackgroundSARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure.Case presentationWe addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis.ConclusionWe wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.

Dermatomiositis y cáncer colorrectal: reporte de caso y revisión de la literatura

Los pacientes con dermatomiositis presentan un mayor riesgo de asociación con patología maligna subyacente, sin conocerse una causa precisa de esta relación. Son múltiples las posibles localizaciones anatómicas, entre las que se incluyen los ovarios, mamas, zona gástrica, zona colorrectal, sangre, pulmones y próstata. Se presenta el caso de una mujer de 58 años que durante el estudio de pérdida anormal de peso manifestó debilidad muscular grave y alteraciones dermatológicas asociadas con el hallazgo de adenocarcinoma del colon transverso.

Health related quality of life in COVID-19 survivors discharged from acute hospitals: results of a short-form 36-item survey

Background: Health-related quality of life (HRQL) is important for evaluating the impact of a disease in the longer term across the physical and psychological domains of human functioning. The aim of this study is to evaluate HRQL in COVID-19 survivors in Italy using the short form 36-items questionnaire (SF-36). Methods: This is an observational study involving adults discharged home following a coronavirus disease 2019 (COVID-19)-related hospital admission. Baseline demographic and clinical data including the Cumulative Illness Rating Scale (CIRS) and the Hospital Anxiety and Depression Scale (HADS) were collected. The validated Italian version of SF-36 was administered cross-sectionally. The SF-36 contains eight scales measuring limitations in physical and social functioning, the impact on roles and activities, fatigue, emotional well-being, pain and general health perception. Results: A total of 35 patients, with a mean age of 60 years, completed the SF-36. The results showed difficulties across the physical and psychological domains, particularly affecting the return to previous roles and activities. A higher burden of co-morbidities as well as a more severe muscle weakness was associated to a lower physical functioning. Younger age, rather than older, correlated to a perceived greater limitation in physical functioning and vitality. Conclusions: COVID-19 survivors particularly the ones of working age may need support for resuming their premorbid level of functioning and returning to work.

The pathophysiological effects of exercise in the management of idiopathic inflammatory myopathies: A scoping review.

Idiopathic inflammatory myopathy (IIM) is a term used for a heterogeneous group of diseases characterized by severe muscle weakness. In addition to pharmacological treatment options, non-pharmacological methods such as exercising are essential for proper management of myositis. The present article aimed to provide an insight into the potential pathophysiological mechanisms underlying exercise-related benefits in myositis. A systematic search was performed on PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using the following keywords and their combinations: "idiopathic inflammatory myopathy", "inflammatory myopathy", "myositis", "polymyositis", "dermatomyositis", "inclusion body myositis", and "exercise". Current literature indicates that exercising has impact on both immune and non-immune pathways in patients with IIM. Exercise-related benefits include (a) increased mitochondrial biogenesis/enzyme activity, (b) reconditioning of immune/inflammatory pathways, (c) decreased endoplasmic reticulum stress, (d) modulation of gene expression, (e) increased protein synthesis and cytoskeletal remodeling, and (f) decreased muscle fibrosis and non-muscle area infiltrates. With its certain benefits, exercise stands as a precious non-pharmacological treatment option for patients with IIM.

Successful treatment of intubation-induced severe neurogenic post-extubation dysphagia using pharyngeal electrical stimulation in a COVID-19 survivor: a case report

BackgroundA significant portion of critically ill patients with coronavirus disease 2019 (COVID-19) are at high risk of developing intensive care unit (ICU)-acquired swallowing dysfunction (neurogenic dysphagia) as a consequence of requiring prolonged mechanical ventilation. Pharyngeal electrical stimulation (PES) is a simple and safe treatment for neurogenic dysphagia. It has been shown that PES can restore safe swallowing in orally intubated or tracheotomized ICU patients with neurogenic dysphagia following severe stroke. We report the case of a patient with severe neurogenic post-extubation dysphagia (PED) due to prolonged intubation and severe general muscle weakness related to COVID-19, which was successfully treated using PES.Case presentationA 71-year-old Caucasian female patient with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection developed neurogenic dysphagia following prolonged intubation in the ICU. To avoid aerosol-generating procedures, her swallowing function was evaluated non-instrumentally as recommended by recently published international guidelines in response to the COVID-19 pandemic. Her swallowing function was markedly impaired and PES therapy was recommended. PES led to a rapid improvement of the PED, as evaluated by bedside swallowing assessments using the Gugging Swallowing Screen (GUSS) and Dysphagia Severity Rating Scale (DSRS), and diet screening using the Functional Oral Intake Scale (FOIS). The improved swallowing, as reflected by these measures, allowed this patient to transfer from the ICU to a non-intensive medical department 5 days after completing PES treatment.ConclusionsPES treatment contributed to the restoration of a safe swallowing function in this critically ill patient with COVID-19 and ICU-acquired swallowing dysfunction. Early clinical bedside swallowing assessment and dysphagia intervention in COVID-19 patients is crucial to optimize their full recovery. PES may contribute to a safe and earlier ICU discharge of patients with ICU-acquired swallowing dysfunction. Earlier ICU discharge and reduced rates of re-intubation following PES can help alleviate some of the pressure on ICU bed capacity, which is critical in times of a health emergency such as the ongoing COVID-19 pandemic.

Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed "Fab-arm exchange" in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

A COMPARATIVE AYURVEDIC REVIEW OF ETIOPATHOGENESIS OF DUCHENNE MUSCULAR DYSTROPHY (INHERITED DISORDER)

Duchenne muscular dystrophy (DMD) is an inherited disorder with severe progressive muscle weakness. In Ayurveda, Adibala Pravritta Vyadhi are also known as inherited diseases that caused by Matruja beeja dushti (Shonita) and Pitruja beeja dushti (Shukra). Duchenne muscular dystrophy (DMD) has been classified under Adibala Pravritta Vyadhi as per Ayurveda. The main objective of this article is to describe the various aspect of etiopathogenesis of Duchenne muscular dystrophy (DMD) as per Ayurvedic literature. This article will be helpful to making the Nidana (Diagnosis) as per Ayurveda and also help in the Chikitsa (Treatment) of Duchenne muscular dystrophy.