Inflammasome in Skeletal Muscle: NLRP3 Is an Inflammatory Cell Stress Component in Inclusion Body Myositis.

Inclusion body myositis (IBM) is a chronic, mostly treatment-resistant, inflammatory myopathy with a pathology that centers around specific interactions between inflammation and protein accumulation. The study aimed to identify the inflammasome as a key event in the complex network of pathomechanisms. Regulation of the inflammasome was assessed in a well-established pro-inflammatory cell culture model using human myoblasts and primary human myotubes.

Repeated oral sucrose dosing after the second wind is unnecessary in patients with McArdle disease: Results from a randomized, placebo-controlled, double-blind, cross-over study.

It is well-established that oral sucrose ingested shortly before exercise improves early exercise tolerance in individuals with McArdle disease. This is by supplying blood-borne glucose for muscle metabolism to compensate for the blocked glycogenolysis. The present study investigated if individuals with McArdle disease could benefit further from repeated sucrose ingestion during prolonged exercise.

Development of Continuum of Care for McArdle disease: A practical tool for clinicians and patients.

McArdle disease (glycogen storage disease type V; GSDV) is a rare genetic disease caused by the inability to break down glycogen in skeletal muscle due to a deficiency in myophosphorylase. Glycolysis is only partially blocked in GSDV, as muscle fibres can take up circulating glucose and convert it to glucose-6-phosphate downstream of the metabolic block. Because skeletal muscle predominantly relies on anaerobic energy during the first few minutes of transition from rest to activity, and throughout more intense activities, individuals with GSDV experience muscle fatigue/pain, tachypnea, and tachycardia during these activities.

Homozygous splice variant (c.1741-6G>A) of the COL6A1 gene in three patients with Ullrich congenital muscular dystrophy.

The three major collagen VI genes: COL6A1, COL6A2, and COL6A3 encode microfibrillar components of extracellular matrices in multiple tissues including muscles and tendons. Pathogenic variants in the collagen VI genes cause collagen VI-related dystrophies representing a continuum of conditions from Bethlem myopathy at the milder end to Ullrich congenital muscular dystrophy at the more severe end. Here we describe a pathogenic variant in the COL6A1 gene (NM_001848.

Neurodegeneration in the retina of motoneuron diseases: a longitudinal study in amyotrophic lateral sclerosis and Kennedy's disease.

Background: To what extent retinal atrophy in neurodegenerative diseases reflects the severity and/or the chronicity of brain pathology or is a local independent phenomenon remains to be clarified. Moreover, whether retinal atrophy has a clinical (diagnostic and prognostic) value in these diseases remains unclear.

Objective: To add light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis (ALS) and Kennedy's disease (KD).

Impact of social determinants of health on individuals living with generalized myasthenia gravis and implications for patient support programs.

Introduction: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access.

Methods: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers.

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.

Background And Objectives: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.

Diagnosis and management of metabolic myopathies.

Metabolic myopathies are a set of rare inborn errors of metabolism leading to disruption in energy production. Relevant to skeletal muscle, glycogen storage disease and fatty acid oxidation defects can lead to exercise intolerance, rhabdomyolysis, and weakness in children and adults, distinct from the severe forms that involve multiple-organ systems. These nonspecific, dynamic symptoms along with conditions that mimic metabolic myopathies can make diagnosis challenging.

Cost-Effectiveness of Newborn Screening for Spinal Muscular Atrophy in England.

Introduction: We sought to evaluate the cost-effectiveness of newborn screening (NBS) versus no NBS for 5q spinal muscular atrophy (SMA) in England.

Methods: A cost-utility analysis using a combination of decision tree and Markov model structures was developed to estimate the lifetime health effects and costs of NBS for SMA, compared with no NBS, from the perspective of the National Health Service (NHS) in England. A decision tree was designed to capture NBS outcomes, and Markov modeling was used to project long-term health outcomes and costs for each patient group following diagnosis.

Pilot Program of Newborn Screening for 5q Spinal Muscular Atrophy in the Russian Federation.

5q spinal muscular atrophy (5q SMA) is one of the most common autosomal recessive disorders in the Russian Federation. The first medication to treat 5q SMA was registered in the Russian Federation for treatment of all 5q SMA types in 2019, and the last of the three currently available in December 2021. We launched the pilot newborn screening (NBS) program for 5q SMA in Moscow, the Russian Federation, starting in 2019.

Progesterone: A Neuroprotective Steroid of the Intestine.

The enteric nervous system (ENS) is an intrinsic network of neuronal ganglia in the intestinal tube with about 100 million neurons located in the myenteric plexus and submucosal plexus. These neurons being affected in neurodegenerative diseases, such as Parkinson's disease, before pathological changes in the central nervous system (CNS) become detectable is currently a subject of discussion. Understanding how to protect these neurons is, therefore, particularly important.

Upper Limb Changes in DMD Patients Amenable to Skipping Exons 44, 45, 51 and 53: A 24-Month Study.

Introduction: The Performance of Upper Limb version 2.0 (PUL 2.0) is increasingly used in Duchenne Muscular Dystrophy (DMD) to study longitudinal functional changes of motor upper limb function in ambulant and non-ambulant patients.

Subjective Sleep Quality as it Relates to Cognitive and Physical Function in Spinal Muscular Atrophy Patients.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA (n = 21) patients and age-matched controls (n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery.

A Scoping Review Investigating the "Gene-Dosage Theory" of Mitochondrial DNA in the Healthy Skeletal Muscle.

This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA).

Quantitative Brain MRI Metrics Distinguish Four Different ALS Phenotypes: A Machine Learning Based Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose diagnosis depends on the presence of combined lower motor neuron (LMN) and upper motor neuron (UMN) degeneration. LMN degeneration assessment is aided by electromyography, whereas no equivalent exists to assess UMN dysfunction. Magnetic resonance imaging (MRI) is primarily used to exclude conditions that mimic ALS.

Progress in muscle research through the international congress of neuromuscular diseases (ICNMD): a narrative review.

Progress in muscle research has been through different phases over the past decades. Here are reviewed the advances presented at the International Congresses of Neuromuscular Diseases (ICNMD). In the '60 to '80 muscle physiology and interpretations of muscle biopsy were the major focuses, diagnosis of muscle disorders was advanced utilizing histochemical, and ultrastructural techniques, and the focus of first to IVth ICNMD was prevention and Muscle Disorders classification as major issues.

Myasthenic crisis.

Myasthenic crisis (MC) is a life-threatening manifestation of myasthenia gravis (MG) defined by respiratory insufficiency that requires the use of invasive or non-invasive ventilation. This is often the result of respiratory muscle weakness but can also be due to bulbar weakness with upper airway collapse. MC occurs in approximately 15%-20% of patients with MG usually within the first 2 to 3 y of the disease course.

-Associated Nuclear Envelopathies.

Human encodes LAP1, a nuclear envelope protein expressed in most human tissues, which has been linked to various biological processes and human diseases. The clinical spectrum of diseases related to mutations in is broad, including muscular dystrophy, congenital myasthenic syndrome, cardiomyopathy, and multisystemic disease with or without progeroid features. Although rare, these recessively inherited disorders often lead to early death or considerable functional impairment.

Effect of strength training on functional outcomes and strength in patients with polyneuropathy: A scoping review.

Polyneuropathy (PNP) is a chronic progressive disease that over time can lead to damage of sensory, motor and/or autonomic peripheral nerves. Symptoms vary from predominantly sensory to severe sensorimotor affection both proximally and distally. This can result in considerable functional impairments that affect activities of daily living.

Effectiveness of rituximab versus oral immunosuppressive therapies in neuromyelitis optica spectrum disorder in a racially diverse cohort of subjects: A single-center retrospective study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder characterized by severe relapses and high level of disability. In clinical trials of NMOSD, Black patients are under-represented, < 12%, compared to a relatively high prevalence of NMSOD in this population, 10/100,000. Despite the higher prevalence of NMOSD in Black and Asian patients, there is limited knowledge of the effectiveness of disease modifying treatments across racially diverse groups.

Oxymetazoline Hydrochloride Eye-Drops as Treatment for Myasthenia Gravis-Related Ptosis: A Description of Two Cases.

In this article, we described two patients with myasthenia gravis-related ptosis who experienced sustained improvement with the use of oxymetazoline hydrochloride ophthalmic solution 0.1%. Despite the commonly used treatments for ptosis in myasthenia gravis (MG), such as acetylcholinesterase inhibitors and corticosteroids, complete remission of ptosis is not always achieved, and these treatments are often accompanied by systemic side effects.

Neuromuscular ultrasound standardized scanning techniques and protocols: Expert panel recommendations.

Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis.