Acta Myologica最新文献

Although performing exercise studies in patients with neuromuscular disorders (NMD) is difficult, the number of randomized controlled trials is steadily increasing. There is growing evidence for a positive effect of aerobic exercise in several NMD, on the other hand, the evidence for the effect of strength training is still scarce. Many NMD patients are captured in a vicious circle of physical inactivity, and it is important to let patients adhere to an active lifestyle, in order to prevent further chronic cardiovascular and muscle deconditioning and increased cardiovascular health risks. Exercise has to be prescribed as if it is medicine, in order to increase the adherence of patients and to optimize the efficacy of the intervention. Exercise in NMD is safe, although for some metabolic myopathies there is a contraindication for strenuous exercise. In NMD known to affect cardiac muscle, it is usually safe to exercise, but the consultation of a cardiologist is advised. Based on recent research, an increase in physical activity of moderate intensity and of sufficient duration, i.e. a physically active lifestyle, could be at least as effective and relevant as physical training. Underlying mechanisms of effect of exercise could be the influence of epigenetic mechanisms and the anti-inflammatory effect of exercise, but further studies are needed to confirm these hypotheses.

Late-onset Pompe disease (LOPD) is characterized by progressive muscle weakness, respiratory muscle dysfunction, and minor cardiac involvement. Although in LOPD, as in other neuromuscular diseases, controlled low impact sub-maximal aerobic exercise and functional ability exercise can improve general functioning and quality of life, as well as respiratory rehabilitation, the bulk of evidence on that is weak and guidelines are lacking. To date, there is no specific focus on rehabilitation issues in clinical recommendations for the care of patients with Pompe disease, and standard practice predominantly follows general recommendation guidelines for neuromuscular diseases. The Italian Association of Myology, the Italian Association of Pulmonologists, the Italian Society of Neurorehabilitation, and the Italian Society of Physical Medicine and Rehabilitation, have endorsed a project to formulate recommendations on practical, technical, and, whenever possible, disease-specific guidance on rehabilitation procedures in LOPD, with specific reference to the Italian scenario. In this first paper, we review available evidence on the role of rehabilitation in LOPD patients, particularly addressing the unmet needs in the management of motor and respiratory function for these patients.

Duchenne muscular Dystrophy (DMD) is a X-linked degenerative disorder affecting skeletal muscles and myocardium caused by mutations in the dystrophin gene, mainly deletions and duplications. Point-mutations account for 13% and stop codon mutations are even more unfrequent. A drug treatment for patients with DMD caused by stop codon gene mutations and still ambulant, has become recently available, based on the clear demonstration of its efficacy in slowing the course of the disease. The drug is able to read through the stop codon; furthermore it has the advantage of an oral administration and a better patient's compliance. We report a case of a still ambulant 27 year-old DMD symptomatic carrier with a stop-codon mutation in exon 53 (c.7792C > T; p.Gln2598Stop), who started the treatment with Ataluren at a dosage of 2,250 mg/die, reporting a prompt subjective improvement in muscle strength. Unfortunately two months after, the patient discontinued taking the drug for a traumatic femur fracture requiring surgical repair and prolonged rehabilitation. With the resumption of the drug intake in February 2018, the patient reported almost immediately an improvement in motor skills, including the possibility of recovering walking, first with support and then unsupported. These results seem even more encouraging, as Duchenne patients hardly recover the ability to walk following a fracture at this age and extend the possibility to treat with ataluren also the symptomatic Duchenne carriers who have nonsense dystrophin gene mutations. Furthermore the case here reported supports the concept that symptomatic DMD female carriers must enjoy the same therapeutic opportunities offered to males.

Desmoplakin is encoded by DSP gene, whose altered function leads to skin and hair abnormalities, and heart diseases. The whole triad of these traits characterizes the Carvajal syndrome (CS). CS is an autosomal recessive genetic disorder, mapping on chromosome 6q24 and caused by mutations in DSP gene. We report a patient with CS caused by two novel mutations in DSP gene, inherited from his parents, both asymptomatic. The same phenotype was present in his younger sister who showed skin abnormality and woolly hairs. The segregation analysis of the known loci in DSP gene performed by genetic testing, was able to established the trans position of the two mutations (c.6986T > C and c.7123G > C) in the patient and his sister. The first mutation has been inherited from the mother, the other one from the father. The resulting compound heterozygous mutation in the siblings, is likely the cause of the disease.

Myotonic dystrophy type 1 (DM1) or Steinert's disease is the most common muscular dystrophy in adult life with an estimated prevalence of 1:8000. Cardiac involvement, including arrhythmias and conduction disorders, contributes significantly to the morbidity and mortality of the disease. Mild ventricular dysfunction has also been reported associated with conduction disorders, but severe ventricular systolic dysfunction is not a frequent feature and usually occurs late in the course of the disease. Heart transplantation is currently considered the ultimate gold standard surgical approach in the treatment of refractory heart failure in general population. To date, considering the shortage of donors that limit the achievement of a greater number of heart transplants and the reluctance of the cardiac surgeons to transplant patients with dystrophic cardiomyopathy, little is known about the number of patients with DM1 transplanted and their outcome. We report the case of a 44 year old patient with Steinert disease who showed an early onset ventricular dysfunction refractory to optimal medical and cardiac resincronization therapy, and underwent to successful heart transplantation. At our knowledge, this is the second heart transplantation performed in a patient affected by Steinert disease after the one reported by Conraads et al in 2002.

Statin-induced necrotizing autoimmune myopathy (IMNM) is an autoimmune disorder induced by anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase (anti-HMGCR) antibodies. We performed a retrospective clinical, histological, and radiological evaluation of 5 patients with a 3-year therapeutic follow-up. All patients used statins and then experienced proximal weakness that persisted after drug cessation. Muscle biopsies revealed a primary necrotizing myopathy without inflammatory infiltrates. All patients required immunomodulant combination therapy to achieve clinical remission. Magnetic resonance imaging (MRI) showed the presence of edema in the medial gastrocnemius, posterior and central loggia of the thigh, posterior loggia of the arm, and the infraspinatus and subscapularis muscles, as well as extensive inflammation of the subcutaneous tissues and muscolaris fasciae. Serum analysis, muscle biopsy, and MRI are fundamental for IMNM diagnosis and follow-up. The growing use of statins in the general population raises the importance of acquaintance with this disease in clinical practice.

Objectives: metabolic syndrome (MetS) increases risk of cardiovascular diseases and diabetes mellitus type 2. Aim of this study was to investigate frequency and features of MetS in a large cohort of patients with DM2.

Materials & methods: this cross-sectional study included 47 DM2 patients. Patients were matched with 94 healthy controls (HCs) for gender and age. MetS was diagnosed according to the new worldwide consensus criteria from 2009.

Results: mean age of DM2 patients was 52 ± 11 years, 15 (32%) were males, and mean disease duration was 15 ± 14 years. MetS was present in 53% of DM2 patients and 46% of HCs (p > 0.05). All components of the MetS appeared with the similar frequency in DM2 and HCs, respectively: hypertension 64 vs 52%, central obesity 62 vs 74%, hypertriglyceridemia 49 vs 39%, hyperglycemia 42 vs 33% and low HDL cholesterol 30 vs 42% (p > 0.05). DM2 patients were more commonly on lipid lowering therapy compared to HCs (12 vs 3%, p = 0.05). Fifteen (32%) patients with DM2 and only one (1%) subject from control group had diabetes mellitus (p < 0.01). Insulin resistance was found in thirty (65%) patients with DM2. Presence of MetS was not associated with patient's gender, age, severity nor duration of the disease (p > 0.05).

Conclusions: more than half of DM2 subjects met the criteria for the MetS. We suppose that treatment of metabolic disturbances may reduce cardiovascular complications and improve quality of life in patients with DM2, which is progressive and still incurable disorder.

The aim of this study is to analyze the epidemiology of the clinical and genetic features of childhood-onset limb-girdle muscular dystrophies (LGMD) in the Aegean part of Turkey. In total fifty-six pediatric cases with LGMD followed in four different pediatric neurology departments in the Aegean region of Turkey were evaluated. Among them, LGMD2C was the most common followed by LGMD2A, LGMD2D, and LGMD2F with equal frequencies. In twenty-eight patients (50%) the diagnosis could be confirmed by genetic analysis, where SGCG proved to be disease-causing in most of the cases. About half of the patients were diagnosed with whole exome or targeted gene sequencing. A positive correlation between muscle biopsy and genetic findings were observed in 11% of the patients. We report one novel frameshifting mutation in TTN. Knowledge on frequencies of childhood-onset limb-girdle muscular dystrophies and related genes in Turkey will lead to a prompt diagnosis of these neuromuscular disorders.

Introduction: Periodic paralyses (PP) are recurrent episodes of flaccid limb muscle weakness. Next to autosomal dominant forms, sporadic PP (SPP) cases are known but their genetics are unclear.

Methods: In a patient with hypokalemic SPP, we performed exome sequencing to identify a candidate gene. We sequenced this gene in 263 unrelated PP patients without any known causative mutations. Then we performed functional analysis of all variants found and molecular modelling for interpretation.

Results: Exome sequencing in the proband yielded three heterozygous variants predicted to be linked to disease. These encoded p.Thr140Met in the Kir2.2 potassium channel, p.Asp229Asn in protein kinase C theta, and p.Thr15943Ile in titin. Since all hitherto known causative PP genes code for ion channels, we studied the Kir2.2-encoding gene, KCNJ12, for involvement in PP pathogenesis. KCNJ12 screening in 263 PP patients revealed three further variants, each in a single individual and coding for p.Gly419Ser, p.Cys75Tyr, and p.Ile283Val. All four Kir2.2 variants were functionally expressed. Only p.Thr140Met displayed relevant functional alterations, i.e. homo-tetrameric channels produced almost no current, and hetero-tetrameric channels suppressed co-expressed wildtype Kir2.1 in a dominant-negative manner. Molecular modelling showed Kir2.2 p.Thr140Met to reduce movement of potassium ions towards binding sites in the hetero-tetramer pore compatible with a reduced maximal current. MD simulations revealed loss of hydrogen bonding with the p.Thr140Met substitution.

Discussion: The electrophysiological findings of p.Thr140Met are similar to those found in thyrotoxic PP caused by Kir2.6 mutations. Also, the homologous Thr140 residue is mutated in Kir2.6. This supports the idea that Kir2.2 p.Thr140Met conveys susceptibility to SPP and should be included in genetic screening.

Myotonic dystrophy type 1 (DM1) is the most common form of adult muscular dystrophy. It is an autosomal dominant inherited disease with multisystemic involvement. Respiratory function is often affected and respiratory failure is the most common cause of death. Pulmonary embolism is a rare cause of respiratory failure in DM1 patients, so that the best anticoagulation strategy in these patients is still unclear. We describe the case of pulmonary embolism in a DM1 patient, in which pulmonary thrombus was completely resolved with oral dabigatran etexilate therapy.