Efficacy of Intravenous Immunoglobulin for Systemic Manifestations of Dermatomyositis Beyond Muscular and Cutaneous: Sub-analysis of the ProDERM Study.

Introduction: Muscle and skin involvement are well defined in dermatomyositis but other symptoms contribute significantly to the disease burden and their treatment is not well characterized. This post hoc analysis of ProDERM assessed the effect of intravenous immunoglobulin (IVIg) treatment on other manifestations of dermatomyositis beyond muscular and cutaneous involvement.

Methods: ProDERM was a randomized, placebo-controlled study.

Predictors of response to intravenous immunoglobulin in patients with dermatomyositis: the ProDERM study.

Objectives: The phase 3 ProDERM study demonstrated intravenous immunoglobulin (IVIg) was safe and effective in patients with dermatomyositis (DM). This analysis assessed clinical and serological predictors of IVIg response in DM patients from ProDERM.

Methods: ProDERM was a prospective, randomized, placebo-controlled study of DM patients.

Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study.

Background: Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking.

Unusually severe muscular dystrophy upon in-frame deletion of the dystrophin rod domain and lack of compensation by membrane-localized utrophin.

Background: Utrophin, a dystrophin homolog, is consistently upregulated in muscles of patients with Duchenne muscular dystrophy (DMD) and is believed to partially compensate for the lack of dystrophin in dystrophic muscle. Even though several animal studies support the idea that utrophin can modulate DMD disease severity, human clinical data are scarce.

Methods: We describe a patient with the largest reported in-frame deletion in the DMD gene, including exons 10-60 and thus encompassing the entire rod domain.

Trial of Intravenous Immune Globulin in Dermatomyositis.

Background: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated.

Methods: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.

Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020.

Background And Purpose: The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany.

Methods: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment.

Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis ("ProDERM Study").

Introduction: Dermatomyositis (DM) is an inflammatory myopathy characterized by distinct skin manifestations and muscle weakness. Intravenous immunoglobulin (IVIg) has been used off-label as adjuvant therapy in DM, but is not indicated for DM, due to lack of proven efficacy in a large randomized controlled trial. The objective of the ProDERM (Progress in DERMatomyositis) study was to evaluate the efficacy, safety and long-term tolerability of IVIg (Octagam 10%) in patients with DM in a randomized, placebo-controlled, double-blind, Phase III study.

Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family.

Importance: New genomic strategies can now be applied to identify a diagnosis in patients and families with previously undiagnosed rare genetic conditions. The large family evaluated in the present study was described in 1966 and now expands the phenotype of a known neuromuscular gene.

Objective: To determine the genetic cause of a slowly progressive, autosomal dominant, scapuloperoneal neuromuscular disorder by using linkage and exome sequencing.

In vivo characterization of human myofibrillar myopathy genes in zebrafish.

Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally.

Novel recessive myotilin mutation causes severe myofibrillar myopathy.

We identified the first homozygous and hence recessive mutation in the myotilin gene (MYOT) in a family affected by a severe myofibrillar myopathy (MFM). MFM is a rare, progressive and devastating disease of human skeletal muscle with distinct histopathological pattern of protein aggregates and myofibrillar degeneration. So far, only heterozygous missense mutations in MYOT have been associated with autosomal dominant myofibrillar myopathy, limb-girdle muscular dystrophy type 1A and distal myopathy.

Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders.

FHL1 mutations have been associated with various disorders that include reducing body myopathy (RBM), Emery-Dreifuss-like muscular dystrophy, isolated hypertrophic cardiomyopathy, and some overlapping conditions. We report a detailed histochemical, immunohistochemical, electron microscopic, and immunoelectron microscopic analyses of muscle biopsies from 18 patients carrying mutations in FHL1: 14 RBM patients (Group 1), 3 Emery-Dreifuss muscular dystrophy patients (Group 2), and 1 patient with hypertrophic cardiomyopathy and muscular hypertrophy (Group 2). Group 1 muscle biopsies consistently showed RBs associated with cytoplasmic bodies.

Proteomic characterization of aggregate components in an intrafamilial variable FHL1-associated myopathy.

Myopathies associated with mutations in FHL1 are rare X-linked dominant myofibrillar myopathies. By clinical examination, histopathology, Sanger sequencing, and laser microdissection combined with quantitative mass spectrometry, we were able to identify the causative gene mutation and protein aggregate composition in two brothers with a late-onset X-linked scapulo-axio-peroneal myopathy. The severely progressive course of the disease revealed a remarkable intrafamilial variability of the clinical presentation.

Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial.

Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).

Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial.

Patient-specific protein aggregates in myofibrillar myopathies: laser microdissection and differential proteomics for identification of plaque components.

Myofibrillar myopathies (MFMs) are histopathologically characterized by desmin-positive protein aggregates and myofibrillar degeneration. While about half of all MFM are caused by mutations in genes encoding sarcomeric and extra-sarcomeric proteins (desmin, filamin C, plectin, VCP, FHL1, ZASP, myotilin, αB-crystallin, and BAG3), the other half of these diseases is due to still unresolved gene defects. The present study aims at the proteomic characterization of pathological protein aggregates in skeletal muscle biopsies from patients with MFM-causing gene mutations.

Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy.

Introduction: Mutations in the anoctamin 5 gene (ANO5) have been recently identified.They cause limb girdle muscular dystrophy (LGMD2L) and Miyoshi muscular dystrophy.

Methods: Clinical findings of four unrelated patients are reviewed.

Reducing body myopathy and other FHL1-related muscular disorders.

During the past 2 years, considerable progress in the field of four and a half LIM domain protein 1 (FHL1)-related myopathies has led to the identification of a growing number of FHL1 mutations. This genetic progress has uncovered crucial pathophysiological concepts, thus redefining clinical phenotypes. Important new characterizations include 4 distinct human myopathies: reducing body myopathy, X-linked myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, and scapuloperoneal myopathy.

Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial.

Background: Duchenne muscular dystrophy is a rare X-linked progressive disease characterised by loss of ambulation at about age 10 years, with death in early adulthood due to respiratory and cardiac insufficiency. Steroids are effective at slowing the progression of muscle weakness; however, their use is limited by side-effects, prompting the search for alternatives. We assessed the effect of ciclosporin A as monotherapy and in combination with intermittent prednisone for the treatment of ambulant patients with this disorder.

The p.G154S mutation of the alpha-B crystallin gene (CRYAB) causes late-onset distal myopathy.

Mutations in alpha-B crystallin gene (CRYAB) have been described to cause congenital cataracts, dilated cardiomyopathy and myofibrillar myopathy. For skeletal myopathy, only three different mutations have been reported within the last decade. Here we describe for the first time the missense mutation p.

Maturation of inhibitory and excitatory motor cortex pathways in children.

Objective: To study intracortical inhibition and facilitation with paired-pulse transcranial magnetic stimulation in children, adolescents and adults.

Methods: Paired-pulse transcranial magnetic stimulation (interstimulus intervals (ISI): 1, 3, 5, 10 and 20 ms) was applied over the primary motor cortex (M1) in 30 healthy subjects (range 6-30 years, median age 15 years and 8 months, SD 7,9) divided in three groups: adults (>or=18 years), adolescents (> 10 and < 18 years) and children (
Results: We observed significantly less intracortical inhibition (SICI) in children's M1 compared to that of adults.

Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.

We recently identified the X-chromosomal four and a half LIM domain gene FHL1 as the causative gene for reducing body myopathy, a disorder characterized by progressive weakness and intracytoplasmic aggregates in muscle that exert reducing activity on menadione nitro-blue-tetrazolium (NBT). The mutations detected in FHL1 affected highly conserved zinc coordinating residues within the second LIM domain and lead to the formation of aggregates when transfected into cells. Our aim was to define the clinical and morphological phenotype of this myopathy and to assess the mutational spectrum of FHL1 mutations in reducing body myopathy in a larger cohort of patients.

Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy.

Regulators of skeletal muscle mass are of interest, given the morbidity and mortality of muscle atrophy and myopathy. Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM). The normal function of FHL1 in muscle and how it causes myopathy remains unknown.

Role of GluR1 in activity-dependent motor system development.

Activity-dependent specification of neuronal architecture during early postnatal life is essential for refining the precision of communication between neurons. In the spinal cord under normal circumstances, the AMPA receptor subunit GluR1 is expressed at high levels by motor neurons and surrounding interneurons during this critical developmental period, although the role it plays in circuit formation and locomotor behavior is unknown. Here, we show that GluR1 promotes dendrite growth in a non-cell-autonomous manner in vitro and in vivo.

Predominant fiber atrophy and fiber type disproportion in early ullrich disease.

Ullrich disease (congenital muscular dystrophy type Ullrich, UCMD) is a severe congenital disorder of muscle caused by recessive and dominant mutations in the three genes that encode the alpha-chains of collagen type VI. Little is known about the early pathogenesis of this myopathy. The aim of this study was to investigate early histological changes in muscle of patients with molecularly confirmed UCMD.