Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology最新文献

Objective: This case study aimed to evaluate the safety and efficacy of sleeve gastrectomy surgery in an obese patient with Late-onset Pompe disease (LOPD) and to explore the potential role of bariatric surgery in improving clinical outcomes and promoting a more physiological body composition when dietary and physical interventions fail.

Methods: We describe a case of an obese LOPD patient who underwent sleeve gastrectomy, with clinical follow-up conducted to monitor motor and respiratory functions, as well as patient-reported outcome measures (PROMs), over time.

Results: The surgery was well-tolerated without significant complications, and prolonged stability in motor and respiratory functions was observed. Furthermore, the patient reported improvements in quality of life and PROMs following weight loss.

Conclusion: This case suggests that bariatric surgery, specifically sleeve gastrectomy, may be a safe and effective complementary strategy for weight loss in LOPD patients, offering benefits in functional stability, and quality of life.

Objective: Myotonic dystrophy type 2 (DM2; PROMM) is characterized by myotonia and muscle dysfunction, episodic muscle pain, proximal and axial weakness of the neck flexors. We describe the case of a young woman affected with a clinically silent form of DM2 disclosed by her return to physical exercise, a 7 km walk, after Covid-19 lockdown.

Methods: The patient underwent neurological examination, serum CK dosage and electromyography after assessing the Emergency Room complaining of cramps and severe myalgia. Molecular screening for CNBP expansions was carried out on the patient and her family.

Results: Clinical signs were generalized muscle weakness, more evident in the lower limb-girdle, myotonia at hands and foot fingers and dramatic elevation in CK levels. DM2 genetic assay revealed a pathological expansion in intron 1 of CNBP gene, confirming the clinical suspicion.

Conclusions: The case we describe is the first, to our knowledge, addressing the impact of Covid pandemia on DM2 patients. In particular, we discuss the role of physical training in modulating the onset and the severity of clinical manifestations of DM2, since sustained regular exercise can mask the disease whereas prolonged suspension can cause massive muscle damage. Recent works investigate possible molecular mechanisms altered by forced physical inactivity, preventing skeletal muscle from adapting to the sudden, non-progressive training reactivation. Additional observations on DM2 patients, other myopathic subjects and elders will help clarify this important issue and provide useful behavioural advice.

Objectives: Pathogenic TRIM32 gene variant was first described in 1976 in the Hutterite population of North America, presenting a phenotype of Limb-girdle muscular dystrophy R8 (LGMDR8, formerly termed LGMD2H). In recent years, different pathogenic mutations in this gene have been reported, with a spectrum of phenotypic heterogeneity, causing sarcotubular myopathy (STM), Bardet-Biedl Syndrome (BBS) and scapuloperoneal dystrophy. The genotype-phenotype correlation of this disease has been poorly reported.

Methods: Here, we perform a literature review to analyze the genotype-phenotype correlation of the pathogenic variants in the TRIM32 gene. We also describe the clinical progression of two cases of STM in two patients presenting the D487N mutation in the TRIM32 gene.

Results: We define the variety of LGMDR8 phenotypes associated with the identified TRIM32 variants so far.

Conclusions: TRIM32 mutations are responsible for a broad spectrum of clinical phenotypes.

Introduction and aims: We describe a case of long-living COLQ-related congenital myasthenic syndrome (CMS) benefitting from ephedrine with an overall improvement quantified with functional measures.

Results: A 71-year-old man was referred with limb-girdle/axial myopathy and fatigability since infancy. In his thirties, a decremental response was observed at 3Hz-nerve stimulation, although testing seronegative for anti-neuromuscular junction antibodies. Later, whole exome sequencing (WES)identified a homozygous likely pathogenic variant in COLQ. After 6-month ephedrine treatment, the patient doubled the distance in the 6-minute-walk test and reached 10 metres in half of the time. His forced vital capacity (FVC) and first-second-forced expiratory volume (FEV1) increased, as well as all patient-reported outcomes. At the 12-month mark, the overall improvement remained consistent/further enhanced, except for a slight decrease in FVC.

Conclusions: This case confirms the efficacy of ephedrine treatment with global improvements in a COLQ-CMS in their late adulthood, demonstrated by quantitative outcome measures. Such indicators may be of interest in upcoming CMS therapeutical trials.

Objective: We investigated myosin heavy chain (MyHC) isoform expression at early postnatal stages of clinically and genetically confirmed spinal muscular atrophy type 1 (SMA1) patients, in order to study the muscle fibre differentiation compared to age-matched controls at single fibre level.

Methods: Open skeletal muscle biopsies were performed from the quadriceps muscle in four SMA1 patients and three age-matched controls. Standard techniques were used for immunohistochemistry of embryonic and foetal MyHCs. Type I, IIa and IIx MyHCs were assessed by applying quadruple immunofluorescence. Western blot was performed to analyse the amount of survival motor neuron (SMN) protein in the muscle samples.

Results: There were profound and early alterations in MyHC expression from 7 days of life compared to age-matched controls. The expression of type IIx MyHC was completely lost in SMA1 and instead developmental isoforms remained highly expressed. Foetal MyHC was still, at 3.5 months of age, expressed in the majority of muscle fibres in SMA1 patients, whereas it was completely downregulated in age-matched controls. The level of SMN protein was reduced in all SMN1 patients.

Conclusions: The abnormal pattern of MyHC expression in postnatal stages of SMA1 was observed early in the newborn period, which may have implications for the effects of gene therapy, since there are clear clinical benefits from early treatment. Whether such aberrant and delayed expression of MyHCs can be completely restored by postnatal gene therapy remains to be studied and may also have implications for new phenotypes that will evolve with new therapies.

Objectives: Duchenne Muscular Dystrophy (DMD) is a severe, progressive, X-linked disorder resulting in muscle wasting, progressive functional loss and cardiomyopathy. Therapeutic strategies feature glucocorticoid corticosteroids plus gene therapy/stop codon read-through, plus standards of care. Prolonged survival, delayed loss of ambulation (LoA), and innovative treatment prescriptions pose new clinical challenges, including identification of new outcome measures/targets and implementation of continuity of care.

Methods: We report on the results of an Italian experts' meeting held in Rome, Italy on 20^th April 2022. We aimed to: discuss challenges linked to transitioning from the ambulatory to the non-ambulatory phase, and from pediatric to adult care; collect experience on the importance of ongoing care and treatment in advanced disease stages and on the need to measure clinically relevant outcomes during disease progression after LoA.

Results: Following LoA the main management focus shifts to cardiac, respiratory, orthopaedics, nutrition and upper limbs function. More data on clinical needs, available treatments, standards of care, frequency of follow-up, and transition should be collected in order to facilitate management optimisation. Shared protocols should be developed, especially to improve patients' management in the acute setting.

Conclusions: Transition from paediatric to adult services and from the ambulatory to the non-ambulatory phase require a multidisciplinary approach and the Identification of clinically meaningful outcome measures, which should be described in long-term longitudinal studies.

Objectives: Focal myositis (FM) is a rare and restricted skeletal muscle inflammation, presenting as a solid mass with a typical lower leg localization and benign prognosis. In most cases the process solves spontaneously or after immunosuppressant therapy, but sometimes it recurs or progresses to a systemic inflammation. The basis of the disease are mostly unknown.

Methods: Hence, we provide an update of histopathological features of FM, in order to better define the underlying pathomechanisms of this disorder. A PubMed literature search was focused on the case reports published in English from July 1977 to December 2023.

Results: FM and other myositis may show similar morphological features. Emerging studies on MMP molecules and future eventual research on microRNAs (miRNAs) could help in differential diagnosis.

Conclusions: Clinical, laboratory, neurophysiological and imaging findings can allow a correct diagnosis. However, muscle biopsy seems to be the only diagnostic tool to differentiate among FM and other localized soft tissue masses.

Objectives: Duchenne muscular dystrophy (DMD) is a heritable disorder that causes a rapid and progressive loss of ambulatory skills. There is no curative therapy for this pathology, that is currently managed with a combination of physiotherapy and pharmacological interventions limiting the progression of the disease (e.g. corticosteroids, cardiac medications). However, a new opportunity is represented by gene therapy, a promising treatment that, however, requires significant expertise during the whole delivery of care and a solid organisational infrastructure. An organisational strategy that could effectively support its delivery to DMD patients in Italy is the hub-and-spoke model. However, an accurate portrait of the present network of DMD centres of expertise in Italy and of their readiness in the delivery of gene therapy is paramount, to facilitate access to this experimental medicine in the future.

Methods: In this context, the present study aimed to map the DMD centres of expertise in Italy and later evaluate their preparedness in terms of gene therapy delivery. For this purpose, a series of items was proposed to 30 centres in Italy, of which 20 responded.

Results: After assessing the readiness of the involved centres in terms of patient preparation, therapy infusion, close surveillance, and long-term follow-up, we proposed a suitable organizational model, namely a flexible hub-and-spoke model, for the delivery of gene therapy in the Italian DMD network and solutions to tackle the challenges emerged from the survey.

Conclusion: Overall, the present study detected an adequate readiness of the Italian DMD centres of expertise, despite observing a significant room for improvement in digital infrastructures, culture, and training.

Neuromuscular diseases (NMDs) comprise a heterogeneous group of conditions characterized by extreme progressive muscle weakness leading to respiratory failure. Noninvasive mechanical ventilation (NIV) has emerged as a cornerstone in the management of respiratory complications associated with NMDs. This review aims to elucidate the role of NMV in respiratory function, improving quality of life, and prolonging survival in individuals with NMD. The physiological basis of respiratory impairment in NMDs, principles of NMV application, evidence supporting its efficacy, patient selection criteria, and potential challenges in its application are discussed.