Effect and impact of mechanical ventilation in myotonic dystrophy type 1: a prospective cohort study

Boussaïd, Ghilas; Prigent, Hélène; Laforêt, Pascal; Raphaël, Jean-Claude; Annane, Djillali; David, Olivier; Lofaso, Frédéric

doi:10.1136/thoraxjnl-2017-210610

Cited by 21 publications

(31 citation statements)

References 13 publications

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“…Although respiratory parameters are typically monitored upright, supine evaluation of pulmonary function may be more sensitive at detecting a restrictive ventilatory pattern [48]. With regard to supportive care, noninvasive ventilation for respiratory weakness has been shown to potentially improve survival in DM1 patients, but therapeutic adherence may be poor and requires close follow-up [53]. This is being explored further in an ongoing open label, multicenter randomized controlled trial assessing the utility of early nocturnal noninvasive ventilation versus annual monitoring (DYVINE; NCT01225614).…”

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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“…Improved understanding of the consequences of neuromuscular insufficiency, including for example the impact on nocturnal ventilation, has led to improved quality of life and survival [2] . New treatment paradigms offer even greater potential and, while the new genetic therapies may not cure, there is now good reason to hope they will extend and improve quality of life even further [3] .…”

Section: Introductionmentioning

confidence: 99%

A hospital based epidemiological study of genetically determined muscle disease in south western Norway

Husebye

Rebne

Stokland

et al. 2020

Neuromuscular Disorders

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We determined the prevalence of genetically determined neuromuscular diseases in adult Norwegian patients from Hordaland County. We identified patients using International Classification of Disease codes registered in our hospital database and reviewed patient notes to ensure diagnostic accuracy. To ensure maximal ascertainment, we screened both inpatient and outpatient contacts from two 5-year periods 01.01.2005 to 31.12.2009 and 01.01.2008 to 01.01.2013, and used the second data set to define prevalence.Myotonic dystrophy was the commonest adult muscle disorder with a minimum prevalence of 11.84/100,000 followed by facioscapulohumeral muscular dystrophy at 6.42/100,000. Genetically confirmed limb-girdle muscular dystrophies had a prevalence of 4.2/100,000 with CAPN3 mutations being the commonest followed by mutations in ANO5 and FKRP . Becker muscular dystrophy was rare (0.4/100,000). For the purposes of comparison, we also ascertained adults with spinal muscular atrophy (SMA) and found a prevalence of 4.42/100,000.The impact of neuromuscular disease is enormous both for the patient and for society. Progressive weakness and increasing dependency together with pulmonary and cardiac complications require specialised, multidisciplinary follow up. The provision of such care places substantial demands on health service resources. Thus, precise understanding of both type of neuromuscular disease and numbers of patients is essential in order to manage individuals appropriately and plan future health service needs.

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“…In sleep studies a cut-off point of at least 5 h is defined as good adherence [16]. In this study we use a cut-off point of at least 5 h use per night as a good adherence, compared to other DM1 studies [5, 6].…”

Section: Methodsmentioning

confidence: 99%

“…Long-term non-invasive ventilation, using bilevel positive airway pressure, further called home mechanical ventilation (HMV), may relieve respiratory failure symptoms, normalization of gas exchange, and may improve life expectancy in DM1 patients [5, 6]. However, HMV is a complex treatment in DM1 patients.…”

Section: Introductionmentioning

confidence: 99%

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New Insights in Adherence and Survival in Myotonic Dystrophy Patients Using Home Mechanical Ventilation

et al. 2021

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Background: Non-invasive home mechanical ventilation (HMV) is a complex treatment in myotonic dystrophy type 1 (DM1) patients, due to a presumed poor adherence, variable symptom improvement, and uncertainty regarding survival benefits. Objectives: We aimed to investigate indications, adherence to HMV and its effects on mortality in a large cohort of DM1 patients. Methods: In this retrospective cohort study, we evaluated 224 DM1 patients. Different groups based on hypercapnia and HMV treatment were compared. Cox regression analyses were performed to compare mortality between different defined groups. Results: 224 patients were analysed of whom 111 started non-invasive HMV. Indications were daytime hypercapnia (n = 75), only nocturnal hypercapnia (n = 33), or other reasons (n = 3). Adequate adherence (≥4 h/night) was found in 84.9% of patients. Adequate ventilation was reached in 86.5% of patients. In 33 patients (29.7%), HMV was stopped prematurely due to not reaching patients’ expectations on symptom relief or treatment burden (n = 22), or intolerance (n = 8), or other reasons (n = 3). HMV did not improve survival in daytime hypercapnic patients (p = 0.61) nor in nocturnal hypercapnia patients compared to daytime hypercapnia (p = 0.21). Significant survival benefits after starting HMV were found for patients with HMV adherence ≥5 h/24 h compared to patients who used HMV less. Conclusion: In this large cohort, daytime hypercapnia is the main reason for starting HMV, which is well tolerated and used. Mortality is not associated with the reason why HMV was started, but once started, patients with ≥5 h/24 h adherence have significantly better survival compared to patients who use it less.

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Effect and impact of mechanical ventilation in myotonic dystrophy type 1: a prospective cohort study

Cited by 21 publications

References 13 publications

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

A hospital based epidemiological study of genetically determined muscle disease in south western Norway

New Insights in Adherence and Survival in Myotonic Dystrophy Patients Using Home Mechanical Ventilation

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