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Abstract: X-linked myopathy with excessive autophagy is a rare disorder caused by a mutation in the vacuolar ATPase assembly factor gene which causes slowly progressive early onset proximal weakness and loss of ambulation by the age of 50-70 years. Electrodiagnostic (EDx) testing usually shows widespread complex repetitive and myotonic discharges, even in muscles unaffected clinically. We report a 65-year-old man who presented with progressive proximal weakness since his teenage years. Extensive workup over 30 years revealed inconclusive EDx and muscle histopathology findings. The diagnosis was finally made with genetic testing. Subsequent neuromuscular ultrasound was more informative of disease severity than repeat EDx and directed a muscle biopsy that showed an autophagic vacuolar myopathy and the novel identification of vacuoles in capillary endothelial cells. Although genetic testing is required for confirmation, in milder cases of X-linked myopathy with excessive autophagy, neuromuscular ultrasound may aid in diagnosis even when EDx findings are inconclusive., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This update begins with a section on inflammatory myopathies covering inclusion body myositis in younger patients, the possibility of a pathogenic role for anti-cN1A antibodies, and a negative trial of arimoclomol in inclusion body myositis. The potential study of Janus kinase inhibitors in dermatomyositis is discussed as well as the possible role of targeted therapy for immune checkpoint inhibitor neuromuscular complications. Next, studies of disease-modifying or potential disease-modifying therapies for inherited myopathies are addressed including the encouraging follow-up study of gene replacement therapy for Duchenne muscular dystrophy (DMD), a negative trial of tamoxifen in DMD, and the complex topic of gene therapy for X-linked myotubular myopathy. A newly identified condition of muscular dystrophy from 3-hydroxy-3-methylglutaryl-CoA reductase mutations is addressed along with possible therapy. Other papers regarding GNE myopathy and long-term outcome of enzyme replacement therapy in infantile onset Pompe disease round out that section. Updates on the expanding spectra of anoctamin-5 myopathies, caveolinopathies, and congenital and mylagic myopathies from CACNA1S mutations follow as well as extensive discussion of Valosin containing protein proteinopathies, comprehensive management of Becker muscular dystrophy, and gastrointestinal complications in adult DMD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We cover intensive care unit-acquired neuromuscular disorders associated with coronavirus disease 2019. Outcomes may be worse than expected in these patients, and there is some evidence that coronavirus disease 2019 causes myopathy directly. Corticosteroid regimens in Duchenne muscular dystrophy are addressed including outcomes in pulmonary and cardiac function. A recent article notes a continued diagnostic delay in Duchenne muscular dystrophy. An interesting report of a Canary Islands cohort of patients with oculopharyngeal muscular dystrophy is discussed. Features and clinical pearls related to a series of patients with limb-girdle muscle dystrophy R12 (anoctaminopathy) and a misdiagnosis of idiopathic inflammatory myopathy are provided. The last section on autoimmune myopathy includes articles on clinical and pathologic features associated with myositis-specific antibodies and dermatomyositis, the epidemiology of immune-mediated necrotizing myopathies (IMNMs) in Olmsted County, Minnesota, and features of a German cohort of hydroxy-3-methylglutaryl coenzyme A reductase-associated IMNM. A recent article proposes the benefit of early intravenous immunoglobulin use for adults with IMNM. We also highlight a report of 2 unusual cases of antisignal recognition particle myopathy presenting with asymmetric distal weakness., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction/aims: Critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) are common disorders associated with substantial morbidity. Electrodiagnostic studies (EDx) are effective in diagnosing CIM/CIP and identifying mimicking conditions. We surveyed intensive care unit (ICU) providers to better understand their approach to ICU-acquired weakness (ICU-AW) and the perceived utility of EDx., Methods: This was a single health system, Web-based survey of ICU providers., Results: Survey responses were received from 52 providers with a response rate of 22.1%. Most providers were somewhat familiar with CIM/CIP and median perceived prevalence was 30-49%. The majority (92.3%) of providers had no standard evaluation approach for ICU-AW. Electrodiagnostic testing was commonly considered, but many providers obtained it infrequently in presumed CIM/CIP cases. Electrodiagnostic studies were used to rule out other causes of weakness or to confirm the diagnosis of CIM/CIP. Many providers ordered EDx within 1 wk of identifying weakness. Finally, EDx were overshadowed by personal experience as the most helpful management tool for ICU-AW., Discussion: Overall, ICU providers perceive that CIM/CIP are commonly encountered, but they may not have a standard approach to evaluation. Clinical experience increased familiarity of ICU-AW and is central to management. EDx results are usually thought to be helpful, albeit not often ordered, and more study is needed to determine when implementation is of most assistance. Increasing education and developing institutional standards may lead to increased awareness and improved evaluation of CIM/CIP, but more study is needed to determine if algorithmic approaches would change patient outcomes., (© 2022 Wiley Periodicals LLC.)

Background/objective: Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data., Methods: This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh. We assessed patients for improvement in core set measures, prednisone dose, adverse effects, and by the "limited" ACR/EULAR 2016 myositis response criteria. The mean differences in CK and manual muscle testing (MMT-8) were compared using a paired t test. A clinically significant response was defined as a >10% absolute improvement in the MMT-8 and a >50% absolute reduction in serum CK at 6 months of IVIg., Results: Intravenous immunoglobulin treatment was associated with marked improvement in IMNM patients, with 85% of patient meeting clinically significant response. The median (interquartile range) relative percent improvement in CK level was 96% (85%-98%) and in MMT was 29% (14%-36%) at 6 months.There was a significant reduction in the mean (SD) dose of prednisone at 6 months and had minimal adverse effects. In addition, with IVIg, most (13/14) patients had at least minimal improvement as per ACR/EULAR 2016 myositis response criteria., Conclusions: Based on objective, meaningful improvement in MMT-8 and CK as well as marked reduction in prednisone doses with acceptable tolerability, early implementation of IVIg should be considered in adult IMNM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This edition concentrates on inflammatory myopathies with reports of reclassification of polymyositis, cancer associations, evaluation of subclinical cardiac involvement, myositis-specific and -associated antibodies, and immune checkpoint inhibitor myositis. A number of reports address sporadic late-onset nemaline myopathy and point out its diagnostic difficulty and the importance of identifying an associated monoclonal gammopathy that is likely of clinical significance and may warrant aggressive immunotherapy. Finally, treatment of nondystrophic channelopathies is addressed., Competing Interests: The author reports no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This update begins with muscle manifestations of coronavirus 2019. They may include myalgias and elevations in serum creatine kinase. It is unknown whether there is direct muscle invasion and how often the critically ill have muscle sequelae. Regarding autoimmune myopathies, a retrospective study of statin-induced necrotizing myopathy is covered. A relatively large proportion of patients had normal strength at presentation. Examples of dermatomyositis associated with immune checkpoint inhibitors are provided including one with cytokine storm. A report of juvenile dermatomyositis with severe abdominal complications is noteworthy. Two articles address unusual associations with inclusion body myositis, namely, spinocerebellar ataxias and granuloma myositis. In the category of muscular dystrophies, a relatively large single center study of the outcome of scapulothoracic arthrodesis for facioscapulohumeral muscular dystrophy is discussed and a article on anoctaminopathies with pauci- or asymptomatic hyperCKemia.

In this issue, an article describing a newly defined entity, myoglobinopathy, is covered. This autosomal-dominant, adult-onset, proximal-predominant myopathy may be associated with cardiac involvement and is due to a mutation in MB. The presence of sarcoplasmic bodies is distinctive in muscle biopsy specimens. Next, variability in phenotypes and genotypes in patients with RYR1 and TTN mutations is described. Several articles address respiratory dysfunction in myotonic dystrophy type 1, reporting that its severity is associated with the CTG-repeat size, age, and degree of muscle weakness. Several articles focus on muscle pain, including myalgias in mitochondrial disorders and the presence of inflammation in muscle biopsy specimens from patients with myalgias and abnormal electrodiagnostic testing. Finally, a form of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy mimicking limb-girdle muscular dystrophy is highlighted.

We review the development of exon 51 skipping therapy with eteplirsen for Duchenne muscular dystrophy, including the recent report of long-term, sustained dystrophin production. Studies of the late-life health profile of patients with Duchenne muscular dystrophy, early detection of left ventricular systolic dysfunction, and caregiver burden are also covered. A study of skeletal muscle magnetic resonance imaging in dysferlinopathies provides an extensive, detailed map of the involved muscles and consistency across phenotypes. Regarding the category of autoimmune myopathies, we discuss an article on the clinical and laboratory features associated with PM/Scl antibodies in comparison with other autoimmune myopathy subgroups. Finally, the overall increase in mortality in inflammatory myopathies is highlighted in a recent report from Sweden.

This update covers the results of a randomized, placebo-controlled study that provides evidence that lamotrigine is effective in treating nondystrophic myotonias. Next, an overview of adverse effects of immune checkpoint inhibitors is provided, and the association of autoimmune myopathy and these monoclonal antibody therapies is discussed in light of recent reports. Last, the utility of electrodiagnostic testing in patients with intensive care unit weakness is addressed with emphasis on the high sensitivity and specificity of prolonged compound muscle action potential amplitudes in diagnosing critical illness myopathy.

Introduction: Since the late 1980s, critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) have been increasingly recognized in the intensive care unit (ICU). We explored whether these causes of ICU weakness were now more likely to lead to electrodiagnostic studies (EDX) at our institution than they were 19-20 years earlier., Methods: We reviewed 100 consecutive ICU patients who underwent EDX from 2009 to 2015 and compared them to a previously reported study population from 1990-1995., Results: Thirty-seven (39%) had CIM, CIP, or both versus 55% in the previous study (P = 0.04). Thirty-four (36%) were diagnosed with "traditional" pre-ICU causes of weakness, such as motor neuron disease or Guillain-Barre syndrome, versus 29% in the earlier study (P = 0.3)., Discussion: CIM and CIP continue to be common disorders that lead to ICU EDX, but their proportion declined compared with 19-20 years earlier, possibly due to the perceived role and selective use of EDX in the ICU. Muscle Nerve 57: 772-776, 2018., (© 2017 Wiley Periodicals, Inc.)

This review is focused on recent reports of sporadic inclusion body myositis (sIBM), myopathy in patients with human immunodeficiency virus type 1 (HIV) infection, and necrotizing autoimmune myopathy with antibodies to signal recognition particle. The sIBM articles cover associations with certain genetic polymorphisms, the possible pathogenic role of anti-cytosolic 5'-nucleotidase 1A antibody, and disease-related burden and health care costs. Another article addressed the possible pathogenic role of signal recognition particle antibody in necrotizing myopathy. A series of HIV patients with overlapping features of sIBM and polymyositis are highlighted as is a report of a patient with HIV and late-onset rod-body myopathy that may have improved with immunotherapy.

Electrodiagnostic testing is a useful component of the approach to a patient with suspected myopathy. It follows the history and is guided by the neurologic examination findings. Uncovering various electrodiagnostic patterns (eg, fibrillation potentials with short-duration motor unit potentials, short-duration motor unit potentials without fibrillation potentials, myotonic discharges, and short-duration motor unit potentials with complex repetitive discharges) can lead to more targeted laboratory testing and a refined differential diagnosis. Electromyography may also be used to detect subclinical myopathy, assess disease activity, and help select a suitable muscle for biopsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Neuromuscular disorders that are diagnosed in the intensive care unit (ICU) usually cause substantial limb weakness and contribute to ventilatory dysfunction. Although some lead to ICU admission, ICU-acquired disorders, mainly critical illness myopathy (CIM) and critical illness polyneuropathy (CIP), are more frequent and are associated with considerable morbidity. Approximately 25% to 45% of patients admitted to the ICU develop CIM, CIP, or both. Their clinical features often overlap; therefore, nerve conduction studies and electromyography are particularly helpful diagnostically, and more sophisticated electrodiagnostic studies and histopathologic evaluation are required in some circumstances. A number of prospective studies have identified risk factors for CIP and CIM, but their limitations often include the inability to separate CIM from CIP. Animal models reveal evidence of a channelopathy in both CIM and CIP, and human studies also identified axonal degeneration in CIP and myosin loss in CIM. Outcomes are variable. They tend to be better with CIM, and some patients have longstanding disabilities. Future studies of well-characterized patients with CIP and CIM should refine our understanding of risk factors, outcomes, and pathogenic mechanisms, leading to better interventions.

Hydroxychloroquine causes a vacuolar myopathy that is usually of mild to moderate severity. The myopathy may be underrecognized, especially in patients who receive multiple other medications for complex illnesses. We report two patients with connective tissue diseases and unusually severe, histopathologically proven hydroxychloroquine myopathy. Both had ventilatory failure; one also had primary pulmonary disease associated with scleroderma, but the other lacked a pulmonary etiology. The ventilatory failure and subsequent medical complications led to death despite discontinuation of hydroxychloroquine, thereby underscoring the potential severity of hydroxychloroquine myopathy and the need for its early recognition.

Despite major advances in molecular genetics, histopathologic evaluation of muscle biopsy specimens continues to provide important diagnostic information in patients with suspected muscle diseases and in patients with vasculitic neuropathies. Muscle biopsy specimens are used in diagnosing many inherited as well as inflammatory and toxic myopathies. Furthermore, the study of muscle histopathology can also enhance our understanding of disease pathogenesis.

Acute myopathy is a common problem in intensive care units. Those at highest risk for developing critical illness myopathy are exposed to intravenous corticosteroids and paralytic agents during treatment of various illnesses. Diffuse weakness and failure to wean from mechanical ventilation are the most common clinical manifestations. Serum creatine kinase levels are variable. Electrodiagnostic studies reveal findings of a myopathic process, often with evidence of muscle membrane inexcitability. Based on animal model studies, the loss of muscle membrane excitability may be related to inactivation of sodium channels at the resting potential. In addition, human and animal pathologic studies reveal characteristic loss of myosin with relative preservation of other structural proteins. In some patients, there is also upregulation of proteolytic pathways, involving calpain and ubiquitin, in conjunction with increased apoptosis. Fortunately, the disorder is reversible, but there may be considerable morbidity.

Uncovering the cause of a suspected myopathy may be challenging. However, a careful approach starts with utilizing the wealth of available information regarding the clinical and laboratory features of myopathy. Electrodiagnostic testing is then obtained (in most cases). Recognition of the pattern of EMG findings in light of the clinical and laboratory features should narrow the differential diagnosis and dictate the next steps in the evaluation. Histopathologic or molecular studies, or both may follow. Ultimately, this approach usually allows the clinician to make the correct diagnosis.

Less invasive, inexpensive, and minimally time-consuming muscle biopsy techniques are desirable if their diagnostic yield is similar to that of open muscle biopsy. This article reviews the technique of semi-automated percutaneous needle muscle biopsy and its utility in diagnosis of neuromuscular diseases. Although direct comparisons with open biopsy are not available, the data indicate that percutaneous needle biopsy is quite useful for diagnosis of inflammatory as well as other forms of myopathy. The specimens can also be utilized for molecular diagnostic studies and cell culture.

Acute myopathy is a cause of weakness and additional morbidity in a variety of critically ill patients, including transplant recipients. We report the incidence of and risk factors associated with acute myopathy after orthotopic liver transplantation (OLTx). One hundred consecutive adult patients were prospectively assessed for muscle weakness after OLTx. Electrodiagnostic studies and muscle biopsies were performed on consenting affected patients. Potential risk factors for myopathy were evaluated in patients with myopathy versus control subjects. Seven patients developed acute persistent weakness after OLTx. Electrodiagnostic studies were consistent with a necrotizing myopathy. Histopathologic evaluation in five revealed a necrotizing myopathy with loss of myosin thick filaments. A higher initial index of illness severity, dialysis requirement, and higher doses of glucocorticoids were associated with development of myopathy. Patients with myopathy subsequently remained in the intensive care unit (ICU) longer than unaffected patients. In conclusion, acute substantial weakness was a source of additional morbidity in 7% of patients after OLTx. Most had myopathy with loss of myosin thick filaments. Patients with greater severity of illnesses and renal failure requiring dialysis were more likely to be affected. The effect of reducing exposure to corticosteroids in high-risk patients warrants further investigation.

We evaluated 4 women with chronic fatigue and myalgias. Two had proximal weakness. All had elevated serum creatine kinase levels, but none was diagnosed with myopathy until electrodiagnostic studies revealed myotonic or complex repetitive discharges predominantly in paraspinal muscles. Histopathology of paraspinal muscles revealed vacuolar myopathies with glycogen storage; biochemical assays revealed phosphorylase deficiency in 1. Since vacuolar myopathies may affect paraspinal muscles more than limb muscles, electromyographic and histopathologic studies of paraspinal muscles may be required for diagnosis.

We undertook a retrospective clinicopathologic study to ascertain the spectrum of histopathologic muscle biopsy changes in the elderly thought to have a myopathy, and to determine the accuracy of clinical diagnosis of myopathy in the elderly compared with a younger control population. We compared muscle histology and case histories, as well as EMG and creatine kinase (CK) data, obtained over 10 years from 77 consecutive patients aged 65 years or older (75 +/- 6, mean +/- SD; group 1) with those from 104 patients aged 30 to 50 years (group 2). Prominent myopathic features were present in 42% (group 1) versus 51% (group 2) of all biopsies. Neurogenic changes (17% versus 9%, p < 0.04) and type II fiber atrophy (22% versus 6%, p < 0.0005) were more common in the elderly, whereas normal findings tended to be less frequent (19% versus 35%). In at least 68% of patients in both groups with the histologic diagnosis of myopathy, either the CK was elevated or the EMG was consistent with that diagnosis. Our study indicates that (1) the spectrum of histopathologic changes in the two groups differs because of a higher frequency of neurogenic change and type II atrophy in the elderly, and (2) the accuracy of clinical diagnosis of myopathy in the elderly approximates that in a younger population.

A 38-year-old woman developed acute, severe weakness during the treatment of status asthmaticus that included high-dose intravenous corticosteroids. A muscle biopsy and EMG indicated a myopathy, and nerve conduction studies disclosed a neuropathic component. In association with corticosteroid tapering, the clinical, EMG, and nerve conduction abnormalities resolved. In some patients, intensive treatment of status asthmaticus may cause a reversible, toxic disorder of muscle and nerve.