207th ENMC Workshop on chronic respiratory insufficiency in myotonic dystrophies: Management and implications for research, 27–29 June 2014, Naarden, The Netherlands

Sansone, Valeria; Gagnon, Cynthia

doi:10.1016/j.nmd.2015.01.011

Cited by 73 publications

(80 citation statements)

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“…It has been correlated with CTG repeat size and may even exist in the absence of significant muscle weakness [48]. The respiratory dysfunction likely results from a combination of skeletal muscle weakness and central nervous system dysfunction [49,50]. Irregular breathing patterns, sleep breathing disorders, and the finding of reduced ventilatory response to CO 2 independent of respiratory muscle weakness all suggest that the central nervous system plays an important role in pathogenesis [50][51][52].…”

Section: Respiratorymentioning

confidence: 99%

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

2018

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Myotonic dystrophy is an autosomal dominant muscular dystrophy not only associated with muscle weakness, atrophy, and myotonia but also prominent multisystem involvement. There are 2 similar, but distinct, forms of myotonic dystrophy; type 1 is caused by a CTG repeat expansion in the DMPK gene, and type 2 is caused by a CCTG repeat expansion in the CNBP gene. Type 1 is associated with distal limb, neck flexor, and bulbar weakness and results in different phenotypic subtypes with variable onset from congenital to very late-onset as well as variable signs and symptoms. The classically described adult-onset form is the most common. In contrast, myotonic dystrophy type 2 is adult-onset or late-onset, has proximal predominant muscle weakness, and generally has less severe multisystem involvement. In both forms of myotonic dystrophy, the best characterized disease mechanism is a RNA toxic gain-of-function during which RNA repeats form nuclear foci resulting in sequestration of RNA-binding proteins and, therefore, dysregulated splicing of premessenger RNA. There are currently no disease-modifying therapies, but clinical surveillance, preventative measures, and supportive treatments are used to reduce the impact of muscular impairment and other systemic involvement including cataracts, cardiac conduction abnormalities, fatigue, central nervous system dysfunction, respiratory weakness, dysphagia, and endocrine dysfunction. Exciting preclinical progress has been made in identifying a number of potential strategies including genome editing, small molecule therapeutics, and antisense oligonucleotide-based therapies to target the pathogenesis of type 1 and type 2 myotonic dystrophies at the DNA, RNA, or downstream target level.

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Section: Respiratorymentioning

confidence: 99%

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

2018

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“…Weakness of the respiratory muscles is especially common among patients who have an acute or chronic neuromuscular disease (NMD), including amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome, spinal muscular atrophy, myotonic dystrophy type 1, Duchenne and other muscular dystrophies, and Pompe disease [1–3]. In patients with a NMD, irrespective of age, pathophysiological mechanisms that lead to the development of respiratory failure frequently include progressive weakness in the inspiratory muscles, predominantly the diaphragm, as indicated by respiratory patterns with low tidal volumes [4, 5].…”

Section: Introductionmentioning

confidence: 99%

“…In patients with NMD, hypoventilation during REM sleep may be an early marker of the functional impact of diaphragm weakness [12]. Lastly, expiratory muscle weakness leads to ineffective clearance of airway secretions, and depending on the severity of the muscle weakness, these patients are thus at a higher risk for aspiration (more so since such patients have concomitant swallowing difficulties), bronchitis, and pneumonia [3, 11]. …”

Section: Introductionmentioning

confidence: 99%

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Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature

Schöser

Fong

Geberhiwot

et al. 2017

Orphanet J Rare Dis

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Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.

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“…Studies have shown a parallel development of proximal limb weakness and respiratory muscle weakness in DM1, 28 but there is growing evidence that adult DM1 patients may require NIV despite their ability to ambulate unaided. 29 Because affected individuals may not bring their myotonia to medical attention, and the clinical myotonia may be overlooked, especially in the absence of a classic DM1 phenotype, the diagnosis may be delayed. This was the case in patient 17, who was diagnosed with DM1 at age 34 during an evaluation for headaches, which were the result of hypercapnic respiratory insufficiency.…”

Section: Discussionmentioning

confidence: 99%