A Novel MYH14 Variant Presenting as a New Phenotype of MYH14-Associated Neuromuscular Disorders-Clinicohistologic Findings and Review of the Literature.

Background: Pathogenic variants in the nonmuscle myosin, MYH14, have been associated with several pathologic conditions including a complex phenotype with peripheral neuropathy, myopathy, hoarseness, and hearing loss. Since its first description in a large Korean kindred, this rare neuromuscular disorder has further been characterized in 1 American and 1 Canadian pedigree.

Case Presentation: Here, we describe a German patient with atypical MYH14-related neuromuscular disorder.

Quantitative whole-body muscle MRI in idiopathic inflammatory myopathies including polymyositis with mitochondrial pathology: indications for a disease spectrum.

Objective: Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity.

Economic evaluation of Motor Neuron Diseases: a nationwide cross-sectional analysis in Germany.

Background And Objectives: Motor Neuron Diseases (MND) are rare diseases but have a high impact on affected individuals and society. This study aims to perform an economic evaluation of MND in Germany.

Methods: Primary patient-reported data were collected including individual impairment, the use of medical and non-medical resources, and self-rated Health-Related Quality of Life (HRQoL).

Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregivers' Lives.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients' informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives.

A Nation-Wide, Multi-Center Study on the Quality of Life of ALS Patients in Germany.

Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort.

Associations between apparent diffusion coefficient values and histopathological tissue alterations in myopathies.

Objectives: Diffusion-weighted imaging (DWI) can reflect histopathologic changes in muscle disorders. The present study sought to elucidate possible associations between histopathology derived from muscle biopsies and DWI in myositis and other myopathies.

Methods: Nineteen patients (10 women, 52.

Associations between histogram analysis parameters derived from morphological sequences and histopathological tissue alterations in myositis and other myopathies: a preliminary study.

Objectives: Magnetic resonance imaging (MRI) is a cornerstone in diagnosis of myopathies. Recently, imaging techniques, such as histogram analysis are used to obtain novel imaging biomarkers. The present study sought to elucidate possible associations between histopathology derived from muscle biopsies and histogram parameters derived from clinical MRI in myositis and other myopathies.

Associations between magnetic resonance imaging and EMG findings in myopathies.

Objectives: Magnetic resonance imaging (MRI) is a cornerstone in diagnosis of myopathies. The present study sought to elucidate possible associations between electromyography (EMG) findings and histogram parameters derived from clinical MRI in myositis and other myopathies.

Materials And Methods: Twenty six patients with myopathies were included in this retrospective study.

Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study.

Background: Nusinersen is approved for the treatment of 5q spinal muscular atrophy of all types and stages in patients of all ages. Although clinical trials have shown improvements in motor function in infants and children treated with the drug, data for adults are scarce. We aimed to assess the safety and efficacy of nusinersen in adults with 5q spinal muscular atrophy.

[Gene-specific treatment approaches in muscle diseases].

Gene-specific treatment for hereditary muscle diseases has made great progress in recent years. The pathomechanisms of many of these diseases could be decrypted using molecular genetic techniques, paving the way for disease-modifying treatment options. A milestone was undoubtedly the successful translation of the antisense oligonucleotide (ASO) technology into clinical practice, with gene-specific ASOs being approved for the first time in 2016 for the treatment of spinal muscular atrophy and Duchenne muscular dystrophy.

White matter lesions in treated late onset Pompe disease are not different to matched controls.

Introduction: Genetic deficiency of α-1,4-glucosidase leads to multi-systemic glycogen storage and causes muscular disorder known as classic infantile Pompe disease (CIOPD) and late onset Pompe disease (LOPD). Treatment with recombinant human alglucosidase alfa is available as enzyme replacement therapy (ERT). Recently progressive white matter lesions (WML) have been observed as a new phenotype in CIOPD patients on treatment with ERT.

Decreased outlet angle of the superior cerebellar artery as indicator for dolichoectasia in late onset Pompe disease.

Background: Lysosomal α-glucosidase deficiency (Pompe disease) not only leads to glycogen accumulation in skeletal muscle, but also in the cerebral arteries. Dolichoectasia of the basilar artery (BA) has been frequently reported. Therefore progression of BA dolichoectasia in late onset Pompe patients (LOPD) was studied.

Long-term observation of incremental response and antibodies to voltage-gated calcium channels in patients with Lambert-Eaton myasthenic syndrome: two case reports.

Introduction: Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder of neuromuscular transmission due to the presence of antibodies to presynaptic P/Q-type voltage-gated calcium channels. The gold standard of therapy is the potassium channel blocker 3,4-diaminopyridine. To the best of our knowledge, no clinical reports have been published to date about long-term follow-up outcomes in patients who discontinued 3,4-diaminopyridine therapy.

Limb girdle muscular dystrophy type 2L presenting as necrotizing myopathy.

Recessive mutations in the ANO5 gene, encoding anoctamin 5, cause proximal limb girdle muscular dystrophy (LGMD2L), Miyoshi-type distal myopathy (MM3) and asymptomatic hyper- CKemia. We report a woman with exertion-induced myalgia and weakness in the hip girdle manifesting at the age of 40. Creatine kinase (CK) was increased 20-fold.

Eosinophils in hereditary and inflammatory myopathies.

It is not known whether eosinophilic myositis is a specific histopathological feature of limb girdle muscular dystrophy 2A (LGMD2A). Number and location of eosinophils in skeletal muscle biopsies (n=100) was analysed by Giemsa and modified hematoxylin/eosin staining in patients with genetically confirmed myopathies (LGMD2A, LGMD2B, LGMD2L, facioscapulohumeral muscular dystrophy, dystrophinopathy), histologically confirmed idiopathic inflammatory myopathies (sporadic inclusion body myositis (sIBM), dermatomyositis (DM), polymyositis), amyotrophic lateral sclerosis (neurogenic control), and normal controls. The number of eosinophils/mm² was significantly higher in LGMD2A, PM, DM, and sIBM compared to controls but not significantly higher than other myopathies.

Mitochondrial abnormalities in myofibrillar myopathies.

Histological mitochondrial changes are generally found to be associated with late onset myofibrillar myopathies (MFMs). How these changes contribute to the pathogenesis of MFMs is unknown. Mitochondrial changes, including COX-deficient fibers (n = 8), biochemical activities of respiratory chain complexes (n = 7), and multiple mtDNA deletions by long-range PCR (n = 9) were examined in patients with genetically confirmed MFMs [MYOT (n = 2), DES (n = 1), ZASP (n = 2), FLNC (n = 4)] and compared with age and sex matched normal controls (n = 27) and patients with a mitochondrial disorder with multiple mtDNA deletions due to nuclear genetic defects (n = 8).

Respiratory function in late-onset Pompe disease patients receiving long-term enzyme replacement therapy for more than 48 months.

Respiratory impairment is the most important prognostic factor in patients with adult-onset Pompe disease. The effect of long-term enzyme replacement therapy (ERT) on pulmonary function remains unclear.Respiratory parameters (vital capacity (VCmax); forced expiratory volume (FEV1); peak expiratory flow (PEF); and blood gas analysis) were monitored every 6 months during a treatment period of 48-77 months of ERT in six patients with genetically and biochemically confirmed adult-onset Pompe disease.

Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study.

Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It is essential that the tests designed provide reliable measures of the process under investigation but most importantly that these are reproducible across both time and laboratories. For this reason, we devised and tested a set of SOPs to investigate mouse behavior.

Identification, molecular characterization and subcellular localization of a Theileria annulata parasite protein secreted into the host cell cytoplasm.

Intracellular leucoproliferative Theileria are unique as eukaryotic organisms that transform the immune cells of their ruminant host. Theileria utilize the uncontrolled proliferation for rapid multiplication and distribution into host daughter cells. The equal distribution of the schizont into the daughter cells is thought to be accomplished by a tight association with the host cell mitotic apparatus.

Identification of homologous genes of T. annulata proteins in the genome of Theileria sp. (China).

Homologues to previously described Theileria (T.) annulata genes (T. annulata surface protein [TaSP], putative T.

Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic.

Neurological and psychiatric disorders are among the most common and most serious health problems in developed countries. Transgenic mouse models mimicking human neurological diseases have provided new insights into development and function of the nervous system. One of the prominent goals of the German National Genome Research Network is the understanding of the in vivo function of single genes and the pathophysiological and clinical consequences of respective mutations.