Original articleWhy are some patients with Duchenne muscular dystrophy dying young: An analysis of causes of death in North East England
Introduction
Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease in children. The incidence is between 1 and 2.8 cases per 10.000 newborns in the UK.1 It is an X-linked recessive condition although the spontaneous mutation rate is high, with new mutations in approximately one third of cases.2 DMD is caused by a mutation in the dystrophin gene, which leads to a relentless progression of muscle weakness and wasting of skeletal and cardiac muscle. Affected patients display the first signs of muscle weakness around preschool age, most become wheel chair users in their teens and respiratory and cardiac failure occurs in late teens/early twenties. Death is mostly due to end stage cardiac and/or respiratory failure.
The last 10 years have seen an exponential rise in scientific research to find disease-modifying drugs to alter the devastating course of DMD. Parallel to the scientific development has been continuous improvement in clinical care for DMD, based on early and long term use of corticosteroids and a comprehensive and anticipatory multidisciplinary approach to cardiac and respiratory impairment. Corticosteroids have been shown to prolong ambulation and delay the onset of respiratory complications in DMD.3 In addition, corticosteroids have been shown to have cardio protective properties and prevent or reduce the need for spinal (scoliosis) surgery.4, 5
All of these and other improvements are encapsulated in the NICE accredited International Care Recommendations for Duchenne muscular dystrophy6, 7; these provide a guideline for clinicians to optimise and standardise care for patients with DMD. At a time when new therapies are on the horizon patients remain ambulant for longer, develop cardiac and respiratory complications later and have an increased life expectancy with a net improvement of the survival curve and quality of life over the last decades.8, 9, 10, 11 The current mean age of survival in DMD is between 23 and 27.8 years of age.8, 9, 10, 11 However, despite the significant advances in the scientific and clinical fields, there are still a small number of patients with DMD who die younger than expected and from causes other than cardiorespiratory failure.
The John Walton Muscular Dystrophy Research Centre (Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust) is one of three MDUK recognised Centres for research and clinical excellence for neuromuscular disorders in the UK and part of the MRC Centre for Neuromuscular Diseases. Our current DMD population includes 163 patients (67% under 18 years of age).
The aim of this retrospective review is to gain a more detailed understanding of mortality in DMD. We reviewed the causes of death in our DMD population over the last 10 years and analysed the events leading up to these deaths. We focused particularly on patients who died younger than expected and in the absence of end stage cardiorespiratory failure to identify potential predictors of early mortality. The hope is that these predictors will help us to refine care in more vulnerable patients and improve life expectancy.
Section snippets
Methods
A retrospective case note review was performed. We reviewed all deaths that occurred in the DMD population in North East England between 2004 and 2014 and who were under our care at the time of death. We collected data from clinic letters (up to two years prior to death), hospital notes and intensive care notes and liaised closely with all subspecialities involved in their care. Patients who died were divided into two groups; Group 1 included patients who had known moderate to severely impaired
Results
In the 10-year period from 2004 to 2014 we identified a total of 24 deaths in our DMD population. Three patients were excluded from the analysis; they died in another hospital or at home, we had insufficient information regarding the events leading up to their death. Of the remaining 21 patients, all were non ambulant at the time of their death. Seventeen patients had known moderate to severe cardio-respiratory failure leading up to their death (group 1). In four patients the cardiorespiratory
Discussion
Both survival and mortality in DMD have changed significantly over the last 30 years. Prior to the introduction of mechanical ventilation in the 90's, the major cause of death in DMD was respiratory failure.8, 10 The introduction of non-invasive ventilation resulted in an increase in survival and a change in cause of death from predominantly respiratory failure to cardiac failure in ventilated patients, with cardiomyopathy being a primary cause of premature death in DMD.14 Survival in DMD
Conclusions
It is now well known that improved clinical care for patients with DMD has prolonged survival over the last 10 years. With the dissemination of the International Care Guidelines for DMD, we are hopeful life expectancy will continue to increase and quality of life to improve. End stage cardio-respiratory failure remains the most common cause of death in DMD but young and unexpected deaths still occur.
Our data show that particular attention needs to be paid to nutrition and respiratory function
Conflict of interest disclosures
There are no conflicts of interest to disclose.
Acknowledgement
The study was supported by the Medical Research Council UK (reference G1002274, grant ID 98482). We also thank the clinicians, physiotherapists, nurses and support staff at the John Walton Muscular Dystrophy Research Centre for their continuing commitment to patient care. We also acknowledge the vital contribution of the Cardiology Department and Respiratory Team at the Newcastle upon Tyne Hospitals NHS Foundation Trust.
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