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Primary and secondary causes of death in adult-onset myotonic dystrophy patients (n 70) Primary cause Secondary cause
Source publication
Myotonic dystrophy is a relatively common type of muscular dystrophy, associated with a variety of systemic complications. Long term follow-up is difficult because of the slow progression. The objective of this study was to determine survival, age at death and causes of death in patients with the adult-onset type of myotonic dystrophy. A register o...
Contexts in source publication
Context 1
... weak inverse correlation between the CTG repeat length and survival was found (r 0.50, P 0.08). Medical documents on the cause of death were available for 70 patients; of these, 73% of the patients died from a complication related to myotonic dystrophy (Table 3). Pneumonia was the most frequent primary cause of death (31%), and it was a secondary cause of death in eight patients (11%) (three with fractures, three with embolic events and two with postoperative complications). ...
Context 2
... cardiac complications as the primary or secondary cause of death were seen in 33% of patients. Pneumonias and cardiac complications were far more frequent primary causes of death than would be expected for this age group (expected 1% and 2%, respectively) ( Table 3). The proportion of all deaths attributed to malignancies was 10% in the myotonic dystrophy patients. ...
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Citations
... Myotonic dystrophy, an autosomal dominant disorder with CTG triplet repeat expansion in the myotonic dystrophy protein kinase gene, has two subtypes: DM1 and DM2. DM1, the more common form, is the primary adult-onset muscular dystrophy, while DM2, known as proximal myotonic myopathy, lacks DM1 molecular pathology [34][35][36]. The condition affects multiple organ systems, with the heart as the primary site of pathology, leading to cardiac manifestations, including arrhythmia, conduction disease, cardiomyopathy and mitral valve prolapse (13-40%), contributing to patient mortality [37,38]. ...
Purpose of Review
The main objective of this review article is to discuss the prevalence, utilization, and outcomes associated with advanced heart failure therapies among patients with neuromuscular disorders.
Recent Findings
Neuromuscular disorders often have multisystem involvement with a high prevalence of cardiovascular pathology. With the improvement in management of respiratory related complications, heart failure is now the leading cause of mortality in this patient population. Advanced heart failure therapies with durable left ventricular assist devices and heart transplantation have proven to be feasible and safe treatment options in selected patients.
Summary
Management of neuromuscular disease involves multidisciplinary team involvement given the systemic nature of the disease. Early recognition and close monitoring of these patients will allow for timely initiation of advanced heart failure therapies that can lead to successful outcomes.
... Pneumonia and cardiac arrhythmias are the most frequent primary causes of death. [35] SCD has an annual incidence of 0.53-1.16% [36,37], three-fold higher in MD1 patients than in age-matched healthy controls. ...
Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of myotonic dystrophy type 1 (MD1).
... Monitoring and treating cardiological DM1 manifestations is of enormous importance, as conduction disturbances and heart rhythm disorders are, alongside respiratory failure, the main cause of premature death in DM1 patients [78,79]. ECG should be performed annually regardless of the presence of cardiological symptoms [72•, 80]. ...
Purpose of review
This review aimed to summarize the clinical characteristics of myotonic dystrophy type 1 and to provide a comprehensive review of the current management options for DM1 patients.
Recent findings
Tremendous advances in understanding the molecular pathophysiology of the disease have led to the first successful preclinical or even clinical studies of disease-modifying therapies. Repurposed small molecules, such are metformin and tideglusib, are probably closest to receiving market authorization, although they showed limited clinical efficiency in treated patients. In the last decade, different synthetic therapeutic oligonucleotides (STO) able to degrade toxic DMPK mRNA were successfully tested in DM1 preclinical studies. Following the failure of the first clinical trial of an STO in DM1 due to poor peripheral drug biodistribution, clinical studies of two other STOs, namely, AOC 1001 and DYNE-101, have been initiated in the past 2 years. Preliminary results revealed successful drug delivery to the targeted tissues with significant clinical efficacy and a satisfactory safety profile. Furthermore, promising preclinical results have been disclosed for CRISPR-based genetic modifying therapy.
Summary
As there is currently no approved disease-specific therapy, a multidisciplinary approach and symptomatic therapy following recently proposed consensus-based care recommendations remain the pillars of good clinical practice managing DM1 patients. Nevertheless, significant breakthroughs in the field of oligonucleotide-based and gene therapy herald the exciting times of great potential for introducing the first causal therapy targeting the genetic cause of DM1.
... Although mortality studies have been mostly carried out in DM1 cohorts, it is plausible that cancer-related death in patients with DM2 is greater than currently recognized because respiratory and cardiac complications in this patient subgroup are less frequent, and because this myotonic dystrophy is often underdiagnosed. Table 1 summarizes the studies that investigated cancer-related deaths in DM [14][15][16][17][18][19]. ...
Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 (DM1) and 2 (DM2), respectively. These genetic defects lead to the abnormal splicing of different mRNA transcripts, which are thought to be responsible for the multiorgan involvement of these diseases. In ours and others’ experience, cancer frequency in patients with DM appears to be higher than in the general population or non-DM muscular dystrophy cohorts. There are no specific guidelines regarding malignancy screening in these patients, and the general consensus is that they should undergo the same cancer screening as the general population. Here, we review the main studies that investigated cancer risk (and cancer type) in DM cohorts and those that researched potential molecular mechanisms accounting for DM carcinogenesis. We propose some evaluations to be considered as malignancy screening in patients with DM, and we discuss DM susceptibility to general anesthesia and sedatives, which are often needed for the management of cancer. This review underscores the importance of monitoring the adherence of patients with DM to malignancy screenings and the need to design studies that determine whether they would benefit from a more intensified cancer screening than the general population.
... 5,8 Moreover, insufficient data are available on the life expectancy of patients with late-onset DM1, whereas patients affected by the adult subtype have been demonstrated to have a markedly reduced survival. 9 As a reduced lifespan in DM1 is most frequently the result of cardiac or respiratory complications, disease management focuses on early detection of organ involvement. 9 Yearly follow-up by a coordinating physician (neuromuscular neurologist) is advised, including an annual electrocardiogram (ECG) to detect possible cardiac conduction delay. ...
... 9 As a reduced lifespan in DM1 is most frequently the result of cardiac or respiratory complications, disease management focuses on early detection of organ involvement. 9 Yearly follow-up by a coordinating physician (neuromuscular neurologist) is advised, including an annual electrocardiogram (ECG) to detect possible cardiac conduction delay. 10,11 In the case of conduction disorders or cardiac symptoms, referral to a cardiologist is indicated. ...
Introduction/aims:
While the extent of muscle weakness and organ complications has not been well-studied in patients with late-onset myotonic dystrophy type 1 (DM1), adult-onset DM1 is associated with severe muscle involvement and possible life threatening cardiac and respiratory complications. This study aimed to compare the clinical phenotype of adult-onset versus late-onset DM1, focusing on the prevalence of cardiac, respiratory and muscular involvement.
Methods:
Data was prospectively collected in the Dutch DM1 registry.
Results:
275 adult-onset and 66 late-onset DM1 patients were included. Conduction delay on electrocardiogram was present in 123 out of 275 (45%) adult-onset patients, compared to 24 out of 66 (36%) late-onset patients (p=0.218). DM1 subtype did not predict presence of conduction delay (OR 0.706, CI 0.405-1.230, p=0.219). Subtype did predict indication for non-invasive ventilation (NIV) (late-onset vs. adult-onset, OR 0.254, CI 0.104-0.617, p=0.002) and 17% of late-onset patients required NIV compared to 40% of adult-onset patients. Muscular impairment rating scale (MIRS) scores were significantly different between subtypes (MIRS 1-3 in 66% of adult-onset vs. 100% of late-onset(p<0.001)), as were DM1-ActivC scores (67±21 in adult-onset vs. 87±15 in late-onset, p<0.001).
Discussion:
Although muscular phenotype was milder in late-onset compared to adult-onset DM1, the prevalence of conduction delay was comparable. Moreover, subtype was unable to predict the presence of cardiac conduction delay. Even though adult-onset patients had an increased risk of having an NIV indication, 17% of late-onset patients required NIV. Despite different muscular phenotypes, screening for multi-organ involvement should be equally thorough in late-onset as in adult-onset DM1. This article is protected by copyright. All rights reserved.
... Data in the literature regarding MDRO/XDRO infection in patients suffering with NMD and requiring hospitalisation, in particular, in a semi-intensive/sub-intensive care setting are scarce, with only a few studies describing pneumonia as one of the most common complications of this group of diseases [23,24]. Indeed, mortality due to pneumonia in amyotrophic lateral sclerosis and adult-onset myotonic dystrophy is shown to be near 30% [25,26]. Pneumonia was also the most common infectious syndrome in our cohort of patients, with 50% of them developing pneumonia during hospitalisation. ...
(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.
... 13 Only about 18% of DM1 patients live to the age of 65 compared to those with DM2 who tend to have a normal life expectancy. 12,18 ...
Majid Moshirfar,1– 3 Court R Webster,4 Tanner S Seitz,5 Yasmyne C Ronquillo,1 Phillip C Hoopes1 1Hoopes Vision Research Center, Hoopes Vision, Draper, UT, USA; 2John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA; 3Utah Lions Eye Bank, Murray, UT, USA; 4Michigan State University College of Osteopathic Medicine, East Lansing, MI, USA; 5Midwestern University, Glendale, AZ, USACorrespondence: Majid Moshirfar, Hoopes Vision Research Center, Hoopes Vision Research Center, Draper, UT, USA, Tel +1-801-568-0200, Fax +1-801-563-0200, Email cornea2020@me.comAbstract: Myotonic dystrophy is the most common inherited muscular dystrophy in adults and presents as two forms, type 1, and type 2. Ocular manifestations such as premature cataract formation, may be the first diagnostic sign or symptom of the disease, offering ophthalmologists a unique diagnostic role. Fuchs’ endothelial corneal dystrophy, ptosis and ocular melanoma are other possible findings. Systemic features can help providers better understand the disease and any accommodations to be made in clinical or surgical settings. Some patients with this disease may request evaluation of certain cataract or corneal refractive procedures. This article focuses on pertinent information for clinicians to utilize when evaluating and treating patients with myotonic dystrophy and specific surgical perspectives to consider prior to any ocular interventions. Hydrophobic intraocular lenses are still recommended in these patients with careful observation of capsular phimosis and posterior capsular opacities.Keywords: corneal endothelium, intraocular lens, IOL, laser assisted in situ keratomileusis, LASIK, small incision lenticule extraction, SMILE, yttrium aluminum garnet, YAG, capsulotomy
... Since as many as 50% of DM1 patients may experience cardiac involvement, and arrythmias are among the most frequent causes of death in the DM1 population, cardiac screening is a significant part of disease management. 1,4 Even though strict guidelines on the cardiac management of DM1 are still lacking, consensus-based care recommendations describe the necessity of annual screening through history taking and electrocardiogram (ECG). 5,6 Apart from ECG, routine cardiac imaging and 24 h Holter monitoring are commonly carried out, even though the exact role of Holter monitoring has not yet been validated. ...
Aims
To evaluate the clinical effectiveness of routine 24 h Holter monitoring to screen for conduction disturbances and arrhythmias in patients with myotonic dystrophy type 1 (DM1).
Methods and results
A retrospective two-centre study was conducted including DM1-affected individuals undergoing routine cardiac screening with at least one 24 h Holter monitoring between January 2010 and December 2020. For each individual, the following data were collected: Holter results, results of electrocardiograms (ECGs) performed at the same year as Holter monitoring, presence of cardiac complaints, and neuromuscular status. Holter findings were compared with the results of cardiac screening (ECG + history taking) performed at the same year. Cardiac conduction abnormalities and/or arrhythmias that would have remained undiagnosed based on history taking and ECG alone were considered de novo findings. A total 235 genetically confirmed DM1 patients were included. Abnormal Holter results were discovered in 126 (54%) patients after a mean follow-up of 64 ± 28 months in which an average of 3 ± 1 Holter recordings per patient was performed. Abnormalities upon Holter mainly consisted of conduction disorders (70%) such as atrioventricular (AV) block. Out of 126 patients with abnormal Holter findings, 74 (59%) patients had de novo Holter findings including second-degree AV block, atrial fibrillation/flutter and non-sustained ventricular tachycardia. Patient characteristics were unable to predict the occurrence of de novo Holter findings. In 39 out of 133 (29%) patients with normal ECGs upon yearly cardiac screening, abnormalities were found on Holter monitoring during follow-up.
Conclusion
Twenty-four hour Holter monitoring is of added value to routine cardiac screening for all DM1 patients.
... Myotonic dystrophy type 1 (DM1) is a multisystem disorder characterized by multiple organ involvement. 1 Respiratory failure, together with cardiac involvement, is the main cause of death in adult-onset DM1 and is associated with increased morbidity and poor quality of life perception. [2][3][4] Respiratory function in DM1 patients is characterized by progressive inspiratory and expiratory muscle weakness which causes a restrictive respiratory syndrome. 4,5 Several authors have specifically addressed respiratory dysfunction in DM1. ...
Introduction:
Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia and sleep disturbances, the prevalence of respiratory disease and indication for and effects of non-invasive ventilation (NIV) need to be further explored.
Objectives:
We aim to describe the respiratory function and the need for NIV at baseline and over time in a cohort of adult patients with DM1.
Methods:
One hundred and fifty-one adult patients with DM1 were subjected to arterial blood gas analysis, sitting and supine forced vital capacity (FVC), peak cough expiratory flow (PCEF), nocturnal oximetry, maximal inspiratory and expiratory pressures (MIP/PEP).
Results:
On first assessment 84 of 151 had normal respiratory function (median age 38 years, median BMI 23.9, median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, median disease duration: 14 years). After a median time of 3.85 years, 43 patients were lost to follow-up; 9 of 84 required NIV; only 17 of 67 with the new NIV prescription were adherent.
Conclusions:
We provide additional data on the natural history of respiratory function decline and treatment adherence in a relatively large cohort of well-characterized patients with DM1. A high proportion (28%) were lost to follow-up. A minority (11%) required NIV, and only 25% were treatment adherent, irrespective of specific demographics and respiratory features. Our results also confirm previous findings showing that age, disease duration and higher BMIs are predisposing factors for respiratory impairment.
... Myotonic dystrophy type 1 (DM1) is a multisystem disorder characterized by multiple organ involvement [1]. Respiratory failure, together with cardiac involvement, is the main cause of death in adult-onset DM1 and is associated with increased morbidity and poor quality of life perception [2][3][4]. Respiratory function in DM1 patients is characterized by progressive inspiratory and expiratory muscle weakness, which causes a restrictive respiratory syndrome [4,5]. flexor weakness has been associated with lower lung volumes [12]. ...
... ere is general consensus that DM1 is a slowly progressive disorder [1][2][3][4], but the rate of decline of the multiple organs involved still needs to be defined. During our observational period, respiratory parameters overall did not show a clinically meaningful change in the cohort taken as a whole, in line with other reports [5,6]. ...
Introduction:
Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus that these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia, and sleep disturbances, the prevalence of respiratory disease and indication for the effects of noninvasive ventilation (NIV) need to be further explored.
Objectives:
To describe respiratory function and need for NIV at baseline and over time in a cohort of adult patients with DM1.
Methods:
A total of 151 adult patients with DM1 were subjected to arterial blood gas analysis, sitting and supine forced vital capacity (FVC), peak cough expiratory flow (PCEF), nocturnal oximetry, and maximal inspiratory pressure and expiratory pressure (MIP/PEP).
Results:
On first assessment, 84 of 151 had normal respiratory function (median age: 38 years, median BMI: 23.9, and median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, and median disease duration: 14 years). After a median time of 3.85 years, 43 patients were lost to follow-up; 9 of 84 required NIV; only 17 of 67 with the new NIV prescription were adherent.
Conclusions:
We provide additional data on the natural history of respiratory function decline and treatment adherence in a relatively large cohort of well-characterized patients with DM1. A high proportion (28%) was lost to follow-up. A minority (11%) required NIV, and only 25% were treatment adherent, irrespective of specific demographics and respiratory features. Our results also confirm previous findings, showing that age, disease duration, and higher BMIs are predisposing factors for respiratory impairment.
