Different Patterns of Autoantibody Secretion by Peripheral Blood Mononuclear Cells in Autoimmune Nodopathies.

Background And Objectives: Autoimmune nodopathies with antibodies against the paranodal proteins show a distinct phenotype of a severe sensorimotor neuropathy. In some patients, complete remission can be achieved after treatment with rituximab whereas others show a chronic course. For optimal planning of treatment, predicting the course of disease and therapeutic response is crucial.

Inclusion body myositis-health-related quality of life and care situation during phases of the "patience journey" in Germany: results from a qualitative study.

Background: To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease.

Methods: An exploratory qualitative study was performed via in-depth semi-structured interviews.

Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis.

Introduction: We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.

Materials And Methods: Human primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13).

Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

Background: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far.

Methods: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences.

Isolation and Characterization of Primary DMD Pig Muscle Cells as an Model for Preclinical Research on Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is the most frequent genetic myopathy in childhood and leads to progressive muscle atrophy, weakness, and premature death. So far, there is no curative treatment available. Therapeutic development from bench to bedside takes time, and promising therapies need to be tested in suitable preclinical animal models prior to clinical trials in DMD patients.

Slowly Progressive Limb-Girdle Weakness and HyperCKemia - Limb Girdle Muscular Dystrophy or Anti-3-Hydroxy-3-Methylglutaryl-CoA-Reductase-Myopathy?

Background: Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-myopathy is a usually rapidly progressive form of immune-mediated necrotizing myopathy (IMNM). Rarer clinical courses show slow progression and resemble the phenotype of limb-girdle dystrophy (LGMD).

Objective: We demonstrate the difficulties in differentiating LGMD versus anti-HMGCR-myopathy.

The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review.

Background: Inclusion body myositis (IBM) is a rare neuromuscular disease (NMD) and effective therapies are not available. Thus, it is relevant to determine the health-related quality of life (HRQoL) in IBM patients including aspects of mental health and illnesses.

Objectives: To identify and summarize the assessment of HRQoL, mental health and illnesses in IBM, the major factors that determine and influence them as well as the respective influence of IBM in general and compared to other NMD as a systematic review.

Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis.

Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and is characterized by disease chronicity with musculoskeletal, dermatological and pulmonary manifestations. One of eight autoantibodies against the aminoacyl-transferase RNA synthetases (ARS) is detectable in the serum of affected patients. However, disease-specific therapeutic approaches have not yet been established.

A scalable, clinically severe pig model for Duchenne muscular dystrophy.

Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/- carriers.

Congenital myopathy and epidermolysis bullosa due to PLEC variant.

We report on an adult Turkish patient with mild myopathy with a fiber-type disproportion and mitochondrial disorganization caused by genetic variants in the plectin gene (PLEC). Molecular genetic panel testing revealed two homozygous variants in PLEC (NM_000445.4): c.

Late-onset neuromuscular disorders in the differential diagnosis of sarcopenia.

Background: Sarcopenia is the age-related loss of muscle mass and strength. Undiagnosed late-onset neuromuscular disorders need to be considered in the differential diagnosis of sarcopenia.

Aim: Based on emblematic case reports and current neuromuscular diagnostic guidelines for three common late-onset neuromuscular disorders, a differential diagnostic approach for geriatric patients presenting with a sarcopenic phenotype is given.

Health-related Quality of Life and Satisfaction with German Health Care Services in Patients with Charcot-Marie-Tooth Neuropathy.

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany.

Delivery of oligonucleotide-based therapeutics: challenges and opportunities.

Nucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues.

Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa.

Several inborn errors of metabolism show cutis laxa as a highly recognizable feature. One group of these metabolic cutis laxa conditions is autosomal recessive cutis laxa type 2 caused by defects in v-ATPase components or the mitochondrial proline cycle. Besides cutis laxa, muscular hypotonia and cardiac abnormalities are hallmarks of autosomal recessive cutis laxa type 2D (ARCL2D) due to pathogenic variants in ATP6V1A encoding subunit A of the v-ATPase.

Antisense-Mediated Skipping of Dysferlin Exons in Control and Dysferlinopathy Patient-Derived Cells.

Dysferlinopathies encompass a spectrum of progressive muscular dystrophies caused by the lack of dysferlin due to missense mutations in the dysferlin gene or mutations causing premature truncation of protein translation. Dysferlin is a modular protein, and dysferlins lacking one or more repetitive domains have been shown to retain functionality. As such, antisense-mediated exon skipping has been proposed as a therapy for dysferlinopathy.

Cost of illness in Charcot-Marie-Tooth neuropathy: Results from Germany.

Objective: To assess cost associated with the disease-specific need of patients diagnosed with Charcot-Marie-Tooth neuropathies (CMT) in Germany.

Methods: Patients with CMT were identified through the national patient registry and invited to complete a standardized questionnaire. The data collected include information about health care use, informal care, and other disease-related expenses as well as the working situation.

Assessment of disease progression in dysferlinopathy: A 1-year cohort study.

Objective: To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.

Methods: One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry.

The multifaceted clinical presentation of VCP-proteinopathy in a Greek family.

VCP-proteinopathy is a multisystem neurodegenerative disorder caused by mutations in valosin containing protein. Here, we report the first Greek case of VCP-proteinopathy in a 62 year old patient with a slowly progressing muscular weakness since his mid-40s and a severe deterioration during the last year. He also manifested dementia with prominent neuropsychiatric symptoms, including aggression, apathy, palilalia and obsessions.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

Background And Objective: Dysferlinopathies are a group of muscle disorders caused by mutations in the gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests.

Methods: We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies.

Rare diagnosis of telethoninopathy (LGMD2G) in a Turkish patient.

Telethoninopathy is one of the rarest forms of Limb-girdle muscular dystrophy (LGMD). So far, only a small number of LGMD type 2 G (LGMD2G) patients have been described, mostly patients from Brazil. Here we present a 35-year-old female patient of Turkish ethnicity with LGMD2G due to a novel homozygous frame-shift mutation c.

Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles.

Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress.