No abstract

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the expression of DUX4 in skeletal muscles. A number of therapeutic approaches are being developed to antagonize the events preceding and following DUX4 expression that leads to muscular dystrophy. Currently, the possibility to evaluate treatment response in clinical trials is hampered by the lack of objective molecular biomarkers connecting the disease cause to clinical performance. In this study we employed RNA-seq to examine gene expression in PAXgene tubes obtained from two independent cohorts of FSHD patients. Analysis of gene expression profiles did not lead to the identification of genes or pathways differentially expressed in FSHD patients, or associated with disease severity. In particular, we did not find evidence that the DUX4 and PAX7 signatures were differentially expressed. On the other hand, we were able to improve patient classification by including single genes or groups of genes in classification models. The best classifier was ROPN1L, a gene known to be expressed in testis, coincidentally the typical location of DUX4 expression. These improvements in patient classification hold the potential to enrich the FSHD clinical trial toolbox.

Neurologists are often asked for specific advice regarding patients with neuromuscular disease who require general anaesthesia. However, guidelines on specific neuromuscular disorders do not usually include specific guidelines or pragmatic advice regarding (regional and/or general) anaesthesia or procedural sedation. Furthermore, the medical literature on this subject is mostly limited to publications in anaesthesiology journals. We therefore summarise general recommendations and specific advice for anaesthesia in different neuromuscular disorders to provide a comprehensive and accessible overview of the knowledge on this topic essential for clinical neurologists. A preoperative multidisciplinary approach involving anaesthesiologists, cardiologists, chest physicians, surgeons and neurologists is crucial. Depolarising muscle relaxants (succinylcholine) should be avoided at all times. The dose of non-depolarising muscle relaxants must be reduced and their effect monitored. Patients with specific mutations in RYR1 (ryanodine receptor 1) and less frequently in CACNA1S (calcium channel, voltage-dependent, L type, alpha 1S subunit) and STAC3 (SH3 and cysteine rich domain 3) are at risk of developing a life-threatening malignant hyperthermia reaction.

No abstract

This study has formally assessed the diagnostic value of the non-ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non-traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

No abstract

The idiopathic inflammatory myopathies are a group of disorders characterized by acquired muscle weakness and presence of inflammatory infiltrates in skeletal muscle. 1,2 The three most common diseases within this group are dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Respiratory muscle weakness with respiratory failure is a well-recognized complication in PM and DM but has only rarely been reported in IBM.3,4 Symptomatic respiratory failure in IBM is considered to be secondary to coincidental pulmonary disease. 5 We report a patient with IBM who developed subacute respiratory failure caused by primary respiratory muscle weakness.Case report. A 58-year-old woman sought treatment for slowly progressive muscle weakness, dysphagia, and weight loss. Her medical history was unremarkable, and she did not use any myotoxic drugs. Physical examination revealed normal speech, mild facial weakness, dysphagia without aspiration, and generalized muscle weakness (Medical Research Council [MRC] score, 4) with asymmetric weakness of the forearm muscles (right, MRC 4; left, MRC 3). Muscle atrophy was most pronounced in the quadriceps muscles. Creatine kinase was mildly increased (285 U/L; normal, Ͻ180 U/L). Nerve conduction studies were normal. EMG demonstrated spontaneous activity and a mixed pattern of shortduration low-amplitude and long-duration high-amplitude motor unit potentials at submaximal voluntary contractions. By EMG, forearm flexor muscles were more involved than forearm extensor muscles. Muscle biopsy from the anterior tibial muscle revealed a small number of muscle fibers surrounded by collagen, fat cells, and inflammatory infiltrates. IBM was diagnosed according to established criteria, 6 and the patient was referred to a rehabilitation clinic.Eight months after initial presentation, she gradually developed shortness of breath on exertion. She subsequently experienced morning headaches, excessive daytime sleepiness, and confusion. One day she was found unconscious as a result of severe hypercapnia and hypoxemia and required intubation and mechanical ventilation. Arterial blood gas analysis after intubation showed elevated PCO 2 (7.9 kPa ϭ 806 mm H 2 O) and bicarbonate (33.7 mmol/L), reflecting chronic hypoventilation. Ancillary investigations showed no signs of cardiac disease or respiratory infection. Initially, nighttime apneas occurred lasting up to 45 seconds with hypercapnia (PCO 2 8.2 kPa ϭ 836 mm H 2 O) and elevated bicarbonate (34.8 mmol/L), after which mechanical ventilation was adjusted. Apparently, the respiratory drive in our patient was depressed during sleep. This probably resulted from bicarbonate retention and sleep deprivation caused by frequent arousals during REM sleep because of hypercapnia.7 Her general condition improved, and the need for daytime ventilatory support decreased. She underwent tracheotomy and thereafter required volume-regulated ventilation for 2 hours in the afternoon and at night. Two months after admission, she was discharged home on contin...

In short, reported mastication difficulties are prevalent in people with McArdle disease, most frequently in younger people. Therefore, awareness of mastication and oral motor problems is required.