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.

Quantitative Muscle MRI and Clinical Findings in Women With Pathogenic Dystrophin Gene Variants.

To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic variant, we prospectively examined 53 women, assuming that some of these women-despite of the recessive X-linked inheritance-manifested clinical symptoms. We performed a cross-sectional observational study using MRI and stationary dynamometry of lower extremities, extracted blood muscle biomarkers, and investigated subjective complaints. Results were compared with 19 healthy women.

Evaluation of inflammatory lesions over 2 years in facioscapulohumeral muscular dystrophy.

Objective: We followed up patients with facioscapulohumeral muscular dystrophy (FSHD) with sequential examinations over 2 years to investigate whether inflammatory lesions always precede fat replacement, if inflammation can be resolved without muscle degeneration, and if inflammatory lesions in muscle are always followed by fat replacement.

Methods: In this longitudinal study of 10 sequential MRI assessments over 2.5 years, we included 10 patients with FSHD.

A single c.1715G>C calpain 3 gene variant causes dominant calpainopathy with loss of calpain 3 expression and activity.

Recessively inherited limb girdle muscular dystrophy (LGMD) type 2A is the most common LGMD worldwide. Here, we report the first single missense variant in CAPN3 causing dominantly inherited calpainopathy. A 43-year-old proband, his father and two sons were heterozygous for a c.

MRI in Neuromuscular Diseases: An Emerging Diagnostic Tool and Biomarker for Prognosis and Efficacy.

There is an unmet need to identify biomarkers sensitive to change in rare, slowly progressive neuromuscular diseases. Quantitative magnetic resonance imaging (MRI) of muscle may offer this opportunity, as it is noninvasive and can be carried out almost independent of patient cooperation and disease severity. Muscle fat content correlates with muscle function in neuromuscular diseases, and changes in fat content precede changes in function, which suggests that muscle MRI is a strong biomarker candidate to predict prognosis and treatment efficacy.

Characteristic muscle signatures assessed by quantitative MRI in patients with Bethlem myopathy.

Using MRI, the main aim was to (1) map the pattern of muscle involvement by assessing fat fraction and (2) investigate frequency of target and sandwich signs in 42 muscles of patients with Bethlem myopathy (BM). Fifteen BM patients were included. Results were compared to findings in 8 healthy controls and 50 patients with four other types of muscular dystrophies.

A quantitative method to assess muscle edema using short TI inversion recovery MRI.

Muscle inflammation is an important component of disease pathophysiology in several muscular dystrophies. Hyperintensities on MRI sequences with short TI inversion recovery (STIR) reflect edema, or inflammation (STIR+). Conventionally, STIR evaluation has been done by visual inspection.

Natural history of limb girdle muscular dystrophy R9 over 6 years: searching for trial endpoints.

Objective: Limb girdle muscular dystrophy type R9 (LGMD R9) is an autosomal recessive muscle disease for which there is currently no causative treatment. The development of putative therapies requires sensitive outcome measures for clinical trials in this slowly progressing condition. This study extends functional assessments and MRI muscle fat fraction measurements in an LGMD R9 cohort across 6 years.

Muscle contractility in spinobulbar muscular atrophy.

Spinobulbar muscular atrophy (SBMA) is caused by a trinucleotide repeat expansion in the androgen receptor gene on the X chromosome. There is a toxic effect of the mutant receptor on muscle and neurons resulting in muscle weakness and atrophy. The weakness can be explained by wasting due to loss of muscle cells, but it is unknown whether weakness also relates to poor muscle contractility of the remaining musculature.

Relationship between muscle inflammation and fat replacement assessed by MRI in facioscapulohumeral muscular dystrophy.

Objective: Unlike most muscular dystrophies that progress symmetrically at a constant rate, facioscapulohumeral muscular dystrophy (FSHD) is characterized by stepwise, asymmetric progression of muscle wasting, and weakness. Muscle tissue is progressively replaced by fat; however, its relation to preceding inflammation is unclear. In this longitudinal study of FSHD, we assessed muscle inflammation and fat replacement and their relation quantitatively.

Refining the spinobulbar muscular atrophy phenotype by quantitative MRI and clinical assessments.

Objective: To investigate the phenotypic features, with emphasis on muscle, in 40 patients with spinobulbar muscular atrophy (SBMA) using quantitative MRI, stationary dynamometry, questionnaires, and functional tests.

Methods: Patients with genetically confirmed SBMA were included. MRI was used to describe muscle involvement and quantify muscle fat fractions of arm, back, and leg muscles.

Disease progression and outcome measures in spinobulbar muscular atrophy.

Objective: Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive disease with weakness of bulbar and extremity muscles. There is no curative treatment for the disease, but several clinical trials have been conducted over the past years. The results from these trials have uncovered a great need to develop quantitative, reliable outcome measures.

Muscle contractility of leg muscles in patients with mitochondrial myopathies.

Background: The primary disease mechanism underlying mitochondrial myopathies (MM) is impaired energy generation to support muscle endurance. Little is known about muscle contractility before energy becomes deficient during muscle contractions. We investigated muscle contractility in MM to uncover potentially fixed weakness aspects of the disorders.

Progressive fat replacement of muscle contributes to the disease mechanism of patients with single, large-scale deletions of mitochondrial DNA.

Muscle dysfunction in mitochondrial myopathy is predominantly caused by insufficient generation of energy. We hypothesise that structural changes in muscles could also contribute to their pathophysiology. The aims of this study were to determine fat fractions and strength in selected muscles in patients with chronic progressive external ophthalmoplegia (CPEO), and compare progression of muscle fat fraction with age in individuals with CPEO vs.

Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in fibroblasts.

Introduction: Mutation in the collagen XII gene (COL12A1) was recently reported to induce Bethlem myopathy. We describe a family affected by collagen XII-related myopathy in 3 generations.

Methods: Systematic interview, clinical examination, skin biopsies, and MRI of muscle were used.

MRI as outcome measure in facioscapulohumeral muscular dystrophy: 1-year follow-up of 45 patients.

There is no effective treatment available for facioscapulohumeral muscular dystrophy type 1 (FSHD1), but emerging therapies are under way that call for a better understanding of natural history in this condition. In this prospective, longitudinal study, we used quantitative MRI to assess yearly disease progression in patients with FSHD1. Ambulatory patients with confirmed diagnosis of FSHD1 (25/20 men/women, age 20-75 years, FSHD score: 0-12) were tested with 359-560-day interval between tests.

Dysphagia is prevalent in patients with CPEO and single, large-scale deletions in mtDNA.

Background: The aim of this study was to assess the frequency of subjective and objective dysphagia in patients with chronic progressive external ophthalmoplegia (CPEO) due to single, large-scale deletions (LSDs) of mitochondrial DNA (mtDNA).

Methods: Sixteen patients with CPEO and single LSDs of mtDNA were included in the study and compared to a control group of 12 patients with the m.3243A>G mtDNA mutation.

Fat Replacement of Paraspinal Muscles with Aging in Healthy Adults.

Purpose: The aims of this study were to investigate the age-related changes in fatty replacement and cross-sectional area (CSA) of cervical, thoracic, and lumbar paraspinal muscles versus leg muscles in healthy adults and to test for association between muscle fat fraction and lifestyle factors.

Methods: Fifty-three healthy adults (24-76 yr) were included. Dixon magnetic resonance imaging technique was used to determine CSA and to quantify the fat fraction of paraspinal and leg muscles.

Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders.

There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes.

Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy: RCT study.

Objective: To investigate the effect of regular aerobic training and postexercise protein-carbohydrate supplementation in patients with facioscapulohumeral muscular dystrophy (FSHD).

Methods: In this randomized, double-blind, placebo-controlled parallel study, we randomized untrained men (n = 21) and women (n = 20) with FSHD (age 19-65 years) to 2 training groups-training with protein supplement (n = 18) and training with placebo supplement (n = 13)-and a nonintervention control group (n = 10). We assessed fitness, walking speed, muscle strength, questionnaires, and daily activity levels before and after 12 weeks of interventions.

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.

Objective: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease.

Methods: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function.

Progression of cardiac involvement in patients with limb-girdle type 2 and Becker muscular dystrophies: a 9-year follow-up study.

Aim: To assess the degree and progression of cardiac involvement in patients with limb-girdle type 2 (LGMD2) and Becker muscular dystrophies (BMD).

Methods: A follow-up study of 100 LGMD2 (types A-L) and 30 BMD patients assessed by electrocardiogram (ECG) and echocardiography, supplemented by Holter-monitoring at follow-up.

Results: After a median of 8.

Severe paraspinal muscle involvement in facioscapulohumeral muscular dystrophy.

Objective: In this study, involvement of paraspinal muscles in 50 patients with facioscapulohumeral dystrophy (FSHD) was evaluated using MRI.

Methods: The Dixon MRI technique was used in this observational study to quantify muscle fat content of paraspinal and leg muscles. Muscle strength in the neck, back, and legs was assessed with a handheld dynamometer.

Muscle biopsies off-set normal cellular signaling in surrounding musculature.

Studies of muscle physiology and muscular disorders often require muscle biopsies to answer questions about muscle biology. In this context, we have often wondered if muscle biopsies, especially if performed repeatedly, would affect interpretation of muscle morphology and cellular signaling. We hypothesized that muscle morphology and cellular signaling involved in myogenesis/regeneration and protein turnover can be changed by a previous muscle biopsy in close proximity to the area under investigation.