Acta Myologica最新文献

Muscular dystrophy (MD) is a group of neuromuscular diseases characterized by progressive muscle weakness due to various mutations in several genes involved in muscle structure and function. The age at onset, evolution and severity of the different forms of MD can vary and there is often impairment of motor function and activities of daily living. Although there have been important scientific advances with regard to pharmacological therapies for many forms of MD, rehabilitation management remains central to ensuring the patient's psychophysical well-being. Here we report the results of an Italian consensus conference promoted by UILDM (Unione Italiana Lotta alla Distrofia Muscolare, the Italian Muscular Dystrophy Association) in order to establish general indications and agreed protocols for motor rehabilitation of the different forms of MD.

Dystrophinopathies are allelic conditions caused by deletions, duplications and point-mutations in the DMD gene, located on the X chromosome (Xp21.2). Mutations that prematurely interrupt the dystrophin protein synthesis lead to the most severe clinical form, Duchenne muscular Dystrophy, characterized by early involvement of muscle strength. There is no known cure for dystrophinopathies. In DMD, treatment with corticosteroids have changed the natural history and the progression of the disease, prolonging ambulation, and slowing the onset of respiratory and cardiac involvement and scoliosis by several years. In the last few years, new perspectives and options are deriving from the discovery of pharmacological approaches able to restore normal, full-length dystrophin and potentially reverse the course of the disease. Read-through (RT) of nonsense mutations, thanks to its ability to bypass the premature stop codon and to act on virtually any region of the dystrophin gene, independently of the location in which the mutation resides, is one of these promising approaches. This non-systematic review shows the different steps that, passing from yeast to humans, have made it possible to use this innovative successful approach to treat serious diseases such as Duchenne muscular dystrophy.

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).

Mechanical ventilation in recent years has benefited from the development of new techniques and interfaces. These developments allowed clinicians to offer increasingly personalised therapies with the combination of different complementary techniques for treating respiratory insufficiency in patients with neuromuscular diseases. The mouthpiece ventilation, intermittent abdominal pressure ventilator and the negative pressure ventilation can offer many patients alternative therapy options when ventilation is required for many hours a day. In this non-systematic review, we will highlight the use of alternative methods to non-invasive mechanical ventilation at positive pressure in neuromuscular patients, to ensure the optimal interface for each patient.

We report a family carrying a previously described truncating mutation, NM_001267550.2(TTN):c.107889del p.(Lys35963Asnfs*9) in exon 364, and a novel truncating mutation, NM_001267550.1:c.100704C > A p.(Tyr33568*) in exon 358 in the titin gene. The c.107889del mutation, which was maternally transmitted, has been previously described in patients from the Iberian Peninsula. The mother was of Peruvian descent suggesting a potential European ancestral origin of this mutation. In this family, a daughter, who is a compound heterozygote carrying both these mutations, developed a peripartum cardiomyopathy during her second pregnancy. Subsequently, she was diagnosed with a myopathy following electromyography testing and a muscle biopsy which showed fiber type disproportion. Her brother, who carries only the paternally inherited c.100704C > A mutation, developed a cardiomyopathy following a suspected viral illness. Their father, who transmitted this mutation, has no evidence of a cardiomyopathy. We hypothesize that the c.100704C > A mutation confers susceptibility to the development of cardiomyopathy which may be brought on by cardiovascular stress. Our study of this family expands the genotype and phenotype spectrum of disorders that can be associated with mutations in the titin gene.

Purpose: Myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) are two different diseases. The coexistence of both of them is extremely rare and represents a diagnostic challenge which requires thoughtful interpretation of clinical characteristics.

Case report: We present the case of a 46-year-old Bosnian male who developed ALS five months after MG. Diagnosis of MG was based on elevated titers of anti-AchR antibodies, positive edrophonium test, and decremental responses on a repetitive nerve stimulation test while the diagnosis of ALS was based on clinical and neurophysiological findings: upper motor neuron signs in the lumbar region, lower motor neuron signs in the bulbar and cervical regions, generalized fasciculations and muscle atrophy and progressive asymetric muscle weakness together with active and chronic denervation in the cervical and lumbosacral region determined by electromyoneurography.

Conclusions: The coexistence of MG and ALS is rare and request an adequate interpretation of clinical symptoms. The relationship between these two diseases in as interesting phenomen to present.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction which affects all striated muscles, resulting in fluctuating weakness. Approaching MG as a disease with subgroups having different clinical, serological and genetic features is crucial in predicting the progression and planning treatment. Three relatively less frequently seen subtypes of MG are the subject of this review: MG with anti-MuSK antibodies (MuSK MG), non-thymomatous late-onset MG (LOMG), and ocular MG (OMG). In addition to reviewing the literature, mainly from a clinical point of view, our experience in each of the subgroups, based on close to 600 patients seen over a 10 year period, is related. MuSK MG is a severe disease with predominant bulbar involvement. It is more common in women and in early-onset patients. With the use of high dose corticosteroids, azathioprine and more recently rituximab, outcome is favorable, though the patients usually require higher maintenance doses of immunosuppressives. LOMG with onset ≥ 50 years of age is more common in men and ocular onset is common. Frequency of anti-AChR and anti-titin antibodies are high. Although it can be severe in some patients, response to treatment is usually very good. OMG is reported to be more frequent in men in whom the disease has a later onset. Anti-AChR antibodies are present in about half of the patients. Generalization is less likely when symptoms remain confined to ocular muscles for 2 years. Low dose corticosteroids are usually sufficient. Thyroid disease is the most common autoimmune disease accompanying all three subgroups.

The term 'limb girdle muscular dystrophy' (LGMD) was first used in the seminal paper by Walton and Nattrass in 1954, were they identified LGMD as a separate clinical entity In LGMD description it is pointed out that the category of LGMD most likely comprises a heterogeneous group of disorders. After that the clinical entity was discussed but the LMGD nosography reached a permanent classification during two ENMC workshops held in 1995 and 2017, in the last one an operating definition of LGMD was agreed. This last classification included dystrophies with proximal or distal-proximal presentation with evidence at biopsy of fibre degeneration and splitting, high CK, MRI imaging consistent with degenerative changes, fibro-fatty infiltration present in individuals that reached independent walking ability. To be considered in this group at least two unrelated families should be identified. A review is done of the first genetic characterisation of a number of LGMDs during the late twentieth century and a historical summary is given regarding how these conditions were clinically described and identified, the progresses done from identification of genetic loci, to protein and gene discoveries are reported. The LGMD described on which such historical progresses were done are the recessive calpainopathy (LGMD 2A/R1), dysferlinopathy (LGMD 2B/R2), sarcoglycanopathy (LGMD 2C-2F/R3-R6) types and the dominant type due to TPNO3 variants named transportinopathy (LGMD 1F/D2). Because of new diagnostic techniques such as exome and genome sequencing, it is likely that many other subtypes of LGMD might be identified in the future, however the lesson from the past discoveries can be useful for scientists and clinicians.

In 2019-2020, the SARS-CoV-2 pandemic has shocked the world and most health care systems, and a "second wave" of the viral spread is ongoing in Europe and in Italy too. While, at the initial outbreak, the treatment of patients had focused on the respiratory symptoms, many diverse clinical manifestations of the disease have to date been reported. However, the complete course of the disease has not yet been fully clarified. In particular, several reports from the real-world clinical practice have highlighted the noxious effects of SARS-CoV-2 on skeletal muscles. In this brief review, we summarized the main current findings about muscular and neuromuscular damages that may be triggered by the virus or by the drugs used to treat COVID-19. Moreover, we underlined the need of attentive care and vigilance for patients with neuro-muscular disorders, who may be particularly susceptible to infection and at increased risk for severe COVID-19.