What Is in the Neuromuscular Junction Literature?

This update starts with an interesting series of children and adults with congenital myasthenic syndrome with a DOK7 variant. The next section is on autoimmune myasthenia gravis (MG) epidemiology, cost of care, and hospitalizations. A number of studies on the newer treatments are discussed including a phase 2 trial of nipocalimab and recommendations for using some of these drugs.

Succinate dehydrogenase-complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema.

Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes.

Diagnosing X-Linked Myopathy With Excessive Autophagy After 30 years: Genetic, Ultrasonographic, and Electrodiagnostic Findings.

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.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls.

Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement.

A meta-analysis of post-exercise outcomes in people with amyotrophic lateral sclerosis.

Objective: To systematically evaluate post-exercise outcomes related to function and quality of life in people with ALS.

Methods: PRISMA guidelines were used for identifying and extracting articles. Levels of evidence and quality of articles were judged based on and the Outcomes were analyzed with Comprehensive Meta-Analysis V2 software, random effects models, and Hedge's G.

What Is in the Myopathy Literature?

This update begins with the results of a positive trial of intravenous immunoglobulin in dermatomyositis and a study of molecular and morphologic patterns in inclusion body myositis that may explain treatment refractoriness. Single center reports of muscular sarcoidosis and immune-mediated necrotizing myopathy follow. There is also a report of caveolae-associated protein 4 antibodies as a potential biomarker and cause of immune rippling muscle disease.

What Is in the Myopathy Literature?

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.

Perceived utility of electrodiagnostic testing in critical illness myopathy and polyneuropathy: A survey of intensive care unit providers.

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.

What Is in the Myopathy Literature?

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.

Role of Intravenous Immunoglobulin in Necrotizing Autoimmune Myopathy.

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.

Neuronal mitochondrial dysfunction in sporadic amyotrophic lateral sclerosis is developmentally regulated.

Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Mitochondria are essential for neuronal survival but the developmental timing and mechanistic importance of mitochondrial dysfunction in sporadic ALS (sALS) neurons is not fully understood. We used human induced pluripotent stem cells and generated a developmental timeline by differentiating sALS iPSCs to neural progenitors and to motor neurons and comparing mitochondrial parameters with familial ALS (fALS) and control cells at each developmental stage.

Granulomatous Myositis Associated With Acetylcholine Receptor Antibodies Without Clinical Myasthenia.

Myasthenia gravis associated with concurrent inflammatory myopathy is a rare but well-described syndrome, most often seen in patients with thymoma. We present a case of biopsy-proven granulomatous myositis associated with positive acetylcholine receptor binding, blocking, and modulating and antistriated antibodies, without clear clinical symptoms of myasthenia gravis and in the absence of thymoma. In addition, we include rarely reported neuromuscular ultrasound findings of granulomatous myositis in a patient without sarcoidosis.

SDH Subunit C Regulates Muscle Oxygen Consumption and Fatigability in an Animal Model of Pulmonary Emphysema.

Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force generation capacity, which partially depends on fibers' oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of SDHC (succinate dehydrogenase subunit C) in association with lower oxygen consumption and fatigue tolerance in locomotor muscles.

Lambert-Eaton Myasthenic Syndrome and Dermatomyositis With Anti-TIF1-gamma Autoantibody: A Unique Association of Autoimmune Neuromuscular Conditions Without Malignancy.

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder, and dermatomyositis (DM) is an idiopathic inflammatory myopathy. LEMS and DM are uncommon conditions that can present similarly and are often associated with autoantibodies. Concomitant LEMS and DM have only been reported a few times, and most of those cases were paraneoplastic.

What Is in the Neuromuscular Junction Literature?

This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression.

Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial.

Background: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.

Methods: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).

What is in the Myopathy Literature?

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.