Muscle Contractility in Hypokalemic Periodic Paralysis.

Introduction/aims: Primary hypokalemic periodic paralysis (HypoPP) can present with periodic paralysis and/or permanent muscle weakness. Permanent weakness is accompanied by fat replacement of the muscle. It is unknown whether the permanent muscle weakness is solely due to fat replacement or if other factors affect the ability of the remaining muscle fibers to contract.

Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle.

Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM.

Ocular versus generalized myasthenia gravis: a continuum associated with acetylcholine receptor antibody titers.

The aim of this study was to evaluate clinical and serological differences between the ocular myasthenia gravis (oMG) and generalized MG (gMG). This study is a retrospective chart review, in which data was collected from patients fulfilling 2 of 3 diagnostic MG criteria (positive antibodies, evidence of neuromuscular transmission defect on neurophysiological examination, positive effect of pyridostigmine treatment). 350 patients were included and data concerning demographics and MG medical history were collected.

Natural history of cardiac involvement in myotonic dystrophy type 1 - Emphasis on the need for lifelong follow-up.

Background: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols.

Methods: Patients with genetically confirmed DM1 were identified.

Hypokalemic periodic paralysis: a 3-year follow-up study.

Background And Objectives: Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP.

Abnormal myosin post-translational modifications and ATP turnover time associated with human congenital myopathy-related RYR1 mutations.

Aim: Conditions related to mutations in the gene encoding the skeletal muscle ryanodine receptor 1 (RYR1) are genetic muscle disorders and include congenital myopathies with permanent weakness, as well as episodic phenotypes such as rhabdomyolysis/myalgia. Although RYR1 dysfunction is the primary mechanism in RYR1-related disorders, other downstream pathogenic events are less well understood and may include a secondary remodeling of major contractile proteins. Hence, in the present study, we aimed to investigate whether congenital myopathy-related RYR1 mutations alter the regulation of the most abundant contractile protein, myosin.

Myositis-related autoantibody profile and clinical characteristics stratified by anti-cytosolic 5'-nucleotidase 1A status in connective tissue diseases.

Introduction/aims: Cytosolic 5'-nucleotidase 1A (cN-1A) autoantibodies have been recognized as myositis-related autoantibodies. However, their correlations with clinical characteristics and other myositis-specific and myositis-associated autoantibodies (MSAs/MAAs) are still unclear. We aimed to establish the prevalence and clinical and laboratory associations of cN-1A autoantibodies in a cohort of patients with connective tissue diseases.

Myositis-specific autoantibodies and QTc changes by ECG in idiopathic inflammatory myopathies.

Objectives: The aim of this study was to investigate cardiac involvement detected by ECG in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate possible associations between the autoantibody profile and ECG changes in these patients.

Methods: In a Scandinavian cross-sectional study, patients were included from two Danish centres and one Swedish centre. Resting 12-lead ECG was investigated in 261 patients with IIM compared with 102 patients with systemic sclerosis (SSc) and 48 healthy controls (HCs).

Axial muscle involvement in patients with limb girdle muscular dystrophy type R9.

Introduction/aims: Limb girdle muscular dystrophy type R9 (LGMDR9) is characterized by progressive weakness of the shoulder and hip girdles. Involvement of proximal extremity muscles is well-described whereas information about axial muscle involvement is lacking. It is important to recognize the involvement of axial muscles to understand functional challenges for the patients.

Muscle biopsy and MRI findings in ANO5-related myopathy.

Introduction/aims: Mutations in the anoctamin 5 (ANO5) gene are a common cause of muscular dystrophy. We aimed to investigate whether inflammatory changes in muscle are present in patients with ANO5 myopathy when assessed by muscle biopsy and muscle magnetic resonance imaging (MRI).

Methods: Adults with pathogenic variations in ANO5 known to cause muscular dystrophy were included in our study.

A novel homoplasmic mt-tRNA m.14701C>T variant presenting with a partially reversible infantile respiratory chain deficiency.

Background: Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial disorder associated with variable penetrance and partial to full remission of symptoms.

Objective: To describe features of maternally related individuals with a novel variant associated with RIRCD.

Materials And Methods: Nine maternally related individuals aged 23 months to 64 years are described through physical examinations, muscle biopsies, histochemical and biochemical analyses, genome sequencing, and cerebral imaging.

Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency.

Objective: Using magnetic resonance imaging (MRI) and stationary dynamometry, the aim was to investigate the muscle affection in paraspinal muscles and lower extremities and compare the muscle affection in men and women with anoctamin 5 (ANO5) deficiency.

Methods: Seventeen patients (seven women) with pathogenic ANO5-mutations were included. Quantitative muscle fat fraction of back and leg muscles were assessed by Dixon MRI.

Autophagy is affected in patients with hypokalemic periodic paralysis: an involvement in vacuolar myopathy?

Hypokalemic periodic paralysis is an autosomal dominant, rare disorder caused by variants in the genes for voltage-gated calcium channel Ca1.1 (CACNA1S) and Na1.4 (SCN4A).

Patients With Becker Muscular Dystrophy Have Severe Paraspinal Muscle Involvement.

Paraspinal muscles are important for gross motor functions. Impairment of these muscles can lead to poor postural control and ambulation difficulty. Little knowledge exists about the involvement of paraspinal muscles in Becker muscular dystrophy.

Cardiac arrest in anti-mitochondrial antibody associated inflammatory myopathy.

Insight into predictors of cardiac involvement in inflammatory myopathies is sparse. A negative prognostic role of anti-mitochondrial antibodies (AMA) has been noticed and is supported by the current case. We describe a male patient who at the age 40 suffered a cardiac arrest and over the following months experienced progressive heart failure, arrhythmias and proximal muscle weakness.

Progression or Not - A Small Natural History Study of Genetical Confirmed Congenital Myopathies.

Background: Clinical characteristics of patients with congenital myopathies (CM) are well known but there is a lack of knowledge about the natural history and course of disease of the different genetic subtypes. In 2010 we assessed the national cohort of Danish patients with CM to decide genetic diagnosing and describe genotype- phenotype relationships.AIM of this follow-up study was to evaluate the course of disease since the initial study and to evaluate the applicability of standard assessment methods to reflect change over time and patients own opinion on the course of disease.

Quantitative Muscle MRI as Outcome Measure in Patients With Becker Muscular Dystrophy-A 1-Year Follow-Up Study.

With the advent of emerging molecular therapies for muscular dystrophies, the need for knowledge about natural history course of such diseases is of utmost importance in the preparation for future trials. However, for Becker muscular dystrophy such knowledge is scarce. In this 1-year follow-up study, we examined disease progression in Becker muscular dystrophy by monitoring changes in MRI-assessed muscle fat fraction (FF) in axial and lower limb muscles and quantitative muscle strength of axial muscles.

Contractile properties are impaired in congenital myopathies.

The ratio between muscle strength and muscle cross-sectional area is called the specific force. Fatty replacement of muscles is seen in many myopathies, affecting the specific force, without necessarily affecting the ability of the remaining muscle fibers to contract. This ability is called the contractility and is the ratio between muscle strength and the lean muscle cross-sectional area, i.

Responsiveness of outcome measures in myotonic dystrophy type 1.

Objective: As myotonic dystrophy type 1(DM1) evolves slowly and interventional trials often have a short duration, responsive outcomes in DM1 are needed. The objective of this study was to determine the responsiveness of muscle strength, balance, and functional mobility measurements after a 1-year follow-up period in individuals with DM1.

Methods: Sixty-three adults with noncongenital DM1 completed the following assessments at baseline and at 1-year follow-up: Handheld dynamometry (lower limbs), stationary dynamometry (lower limbs), step test, timed-up-and-go test (TUG), modified clinical test of sensory integration and balance (mCTSIB), feet-together stance, tandem stance, one-leg stance, 10-meter walk test, and sit-to-stand test.

Permanent muscle weakness in hypokalemic periodic paralysis.

Objective: To map the phenotypic spectrum in 55 individuals with mutations in known to cause hypokalemic periodic paralysis (HypoPP) using medical history, muscle strength testing, and muscle MRI.

Methods: Adults with a mutation in known to cause HypoPP were included. Medical history was obtained.

Intrarater reliability and validity of outcome measures in myotonic dystrophy type 1.

Objective: To investigate intrarater reliability and concurrent and construct validity of muscle strength, balance, and functional mobility measures in individuals with noncongenital myotonic dystrophy type 1 (DM1).

Methods: Seventy-eight adults with noncongenital DM1 participated in visit 1, and 73 of the them participated in visit 2 separated by 1 to 2 weeks. The assessments consisted of muscle strength tests with handheld dynamometry (HHD) and stationary dynamometry in the lower limb.