Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy

Introduction

Respiratory failure is an inevitable consequence of the progression of DMD. In corticosteroid treated children, respiratory function improves, stabilizes and then declines at a rate of approximately 4–6.9% per year from 9 years of age [7, 8]. The onset of respiratory decline is delayed by treatment with corticosteroids, on average, by two years [7]. In adult services, only a minority of patients will require respiratory support at the time of transition from paediatric services, however, inevitably all patients will develop respiratory failure requiring ventilatory support, thereafter the trajectory of decline is the same, between 4–6.9% per year [7, 8]. Thus, services caring for adults with DMD must have access to a suitably skilled respiratory team, and either joint clinics or a clear referral pathway to a complex ventilation service should be in place. The objective is to anticipate deterioration to prevent, as far as possible, acute presentation to hospital, improve quality of life and prolong survival.

Causes of respiratory pathology in DMD

Measurement of respiratory function

Oxygen saturations

Resting oxygen saturations cannot be relied upon to confirm or rule out respiratory failure. However, oxygen saturations > 95% makes significant hypercapnia unlikely [7, 9].

Initiating non-invasive ventilation

Guidelines for the management of neuromuscular weakness in children have been produced by the British Thoracic Society [10] and there is some published international guidance for adults with neuromuscular weakness [10, 11]. Respiratory management of adults with DMD should be led by a multi-disciplinary team familiar with the appropriate investigation, treatment and long term follow up of DMD patients which must be experienced and skilled in discussing the options for support with patients, as the literature is still inconclusive in defining which physiological tests or parameters mandate initiating ventilatory support. Clinical experience indicates that treatment is unlikely to be tolerated if the patient does not experience an increase in overall wellbeing. Thus, a shared decision-making framework is important because respiratory support via mask or tracheostomy and mechanical insufflation/exsufflation may be burdensome and intrusive.

Patients with DMD should be referred to respiratory/home ventilation teams for consideration of non-invasive ventilation (NIV) at the onset of symptoms of nocturnal hypoventilation and/or when the FVC is <50% predicted.

Lung volume recruitment and cough augmentation

Other important aspects of care include lung volume recruitment (LVR) and cough augmentation. Respiratory muscle weakness leads to atelectasis and secretion retention as the inspiratory and expiratory muscles fail to generate effective inspiratory volumes and cough peak flows. LVR can be achieved via a ventilator, an LVR bag or Mechanical Insufflation/Exsufflation (MI-E). There are no clear values which predict ineffective cough in DMD, however a PCF > 270l/min when well, predicts an effective cough and low risk of developing respiratory failure during respiratory tract infections.

Historically, ‘glossopharyngeal breathing’ was used to facilitate lung recruitment. However, with the widespread availability of augmentation devices, this technique is now rarely used or taught.

An LVR bag can be used for recruitment or for secretion management. Its use in effectively mobilising chest secretions requires adequate expiratory muscle function.

Patients with DMD should be referred to respiratory/home ventilation teams for consideration of LVR or MI-E if they are experiencing chest infections, difficulty mobilising lower respiratory secretions or their PCF is <270l/min. An LVR bag is often used initially when PCF < 270l/min or when there is difficulty mobilising secretions. Every complex home ventilation multi-disciplinary team should have access to MI-E provision when an LVR bag is not effective or when expiratory muscle weakness prevents effective cough.

Other therapies

Oro-pharyngeal secretion management may be required with a suction machine. Sialhorroea can be managed with antimuscarinic agents such as transdermal hyoscine patch, oral atropine, glycopyronium, propantheline or injection of botulinum toxin to the salivary glands. With recurrent chest infections assessment by a speech and language therapist is essential to exclude recurrent aspiration. The use of long-term antibiotics may be also considered when chest infections occur frequently. In patients with asthma or bronchial-hyperreactivity nebulised bronchodilators, steroids and ipratropium together with sputum management using mucolytics such as carbocysteine may all need to be considered.

Oxygen is not a treatment for respiratory failure and may further suppress respiratory drive although sometimes oxygen is required to be entrained into ventilator circuits e.g. to treat acute chest infection. Oxygen saturation targets in adult patients with DMD receiving supplemental oxygen should be 88–92% when not ventilated. Acute arterial oxygen desaturation is commonly caused by sputum plugging and retention in patients with marked respiratory muscle weakness. Intensive physiotherapy with use of cough augmentation techniques and NIV can help. If bronchial secretions are not excessive, then further clinical examination and investigation with chest X ray and blood tests are required to determine the cause of acute decompensation which may be due to acute chest infection, pneumothorax or pulmonary oedema.

Respiratory multi-disciplinary team

A holistic approach to therapy must be taken, with a good understanding of the individual’s care arrangements and the impact on care provision that changes to their respiratory management (such as tracheostomy ventilation) might impose. The respiratory team should provide training for patients, families and carers including a competency assessment framework. A full range of ventilatory interfaces should be available including: nasal, full face, oronasal and mouthpiece. The multi-disciplinary team (MDT) should anticipate and manage treatment complications such as ill-fitting masks, skin breakdown and abdominal distension. Tracheostomy ventilation may need to be considered where mask ventilation fails or when non-invasive ventilatory support is required for more than 16 hours continuously and is not tolerated by the patient or when respiratory secretion management with non-invasive strategies fails. Regular assessment of efficacy of respiratory support is essential with clinical review, oximetry, blood gases and overnight TcCO₂ and SpO₂ measurement where clinically indicated. Symptom management including palliative medicine and psychological support is important throughout the clinical course of the individual receiving ventilator support.

The respiratory support team is also responsible for equipment maintenance and should provide an emergency replacement service and 24-hour helpline. Patients requiring ventilation for >16 hours per day should have 2 devices both with internal battery support to ensure patient safety. The respiratory team should understand the arrangement for medical and social funded care packages for complex discharge planning from hospital to home environment. There should also be in place close liaison with the paediatric home ventilation service and there should be robust arrangements for “transition of care” into adult services. In addition, liaison with local hospitals, local respiratory physicians and intensive care units (ITU) is important when patients become acutely unwell. Other requirements of the service include wheelchair equipment mounting and other biomedical adaptations to equipment. Flight assessment before travel and the provision of backup equipment for holidays is also important. An understanding of advance care planning and the role of palliative care in supporting withdrawal of ventilation if requested/ indicated, is an important aspect for the respiratory team in conjunction with the neuromuscular team.

Emergency admission to intensive care unit

Sometimes a chest infection precipitates acute respiratory failure leading to invasive ventilation on intensive care. This can occur either before the institution of long-term respiratory support, or as an acute deterioration in a chronically ventilated patient. The prognosis for recovery is usually good, although the intensive care stay can be long, and patients usually have an increased need for long-term ventilation after the ITU admission. Patients with DMD who are admitted to ITU should have their management and weaning plan discussed with a respiratory physician responsible for the complex home ventilation service. Progression from mask ventilation to tracheostomy ventilation can have a profound effect on quality of life and care provision and may result in an ITU stay of many months.

Emergency admissions can be particularly stressful for patients with DMD and their families, especially if the admitting team are not familiar with the condition. An emergency care plan can be a useful document for the patient to carry and present on admission.

Guidelines for perioperative care

In general patients with DMD can be safely anaesthetised but there are significant potential complications which are related to pre-existing cardiorespiratory disease and the choice of anaesthetic agent [13]. Although guidance for professionals is important in this challenging area of anaesthesia, in general the safest anaesthetic is usually that with which the operative anaesthetist is most familiar and rigid guidance about technique is not appropriate.

Where practicable (outside of an emergency setting) patients with DMD undergoing General Anaesthesia (GA) or Procedural Sedation (PS) should be managed at a centre with significant experience in managing such patients and where there are intensive care facilities. Other than surgical experience, additional specialist experience required includes but is not limited to: anaesthesia, domiciliary ventilation services, cardiology and dietetics. Any patient having elective GA or PS should be referred to such centres. In the emergency situation, where transfer to specialist centres is not possible, advice should be sought from these centres.

Pre-assessment

All patients should attend an anaesthetic pre-assessment appointment as soon as surgery has been decided upon. Important issues to be addressed include:

Intraoperative care

Airway management

Airway management during GA has been successfully managed with endotracheal intubation, Laryngeal Mask Airway (LMA) and face mask. Endotracheal intubation remains the commonest technique due to the better control of minute ventilation. LMA use during gastrostomy formation is associated with a significant failure rate [29].

For PS, NIV has been used safely in patients on chronic NIV for diverse procedures, but its use has been most frequently investigated in patients undergoing gastrostomy formation [30]. It is a safe and effective technique but experience from specialist teams is that air leak during endoscopic gastrostomy formation is a significant problem and requires careful interface selection and monitoring as for a GA.

Regional anaesthesia

An expanding area of anaesthetic practice has been Regional Anaesthesia (RA). The successful use of RA (either neuroaxial or peripheral nerve blocks) has been reported either as a sole technique or combined with GA in ophthalmic, distal limb and orchidopexy procedures [31–33]. Consideration should be given to these techniques for intraoperative management and for postoperative analgesia.

Cardiac output monitoring

Invasive arterial pressure monitoring is recommended for all but the most minor of procedures. In procedures where significant blood loss is anticipated, cardiac output monitoring is frequently used to guide fluid requirements and replacement.

Practical considerations

Practical considerations for the anaesthetist include difficulty with intravenous access and with positioning of patients who may have significant joint contractures.

Postoperative

Cardiac management of adults with DMD

This guidance builds on international standards of care [1–3] and the 238th international ENMC workshop for cardiac care [5] and has been adapted with an emphasis on the adult with DMD thus broadening the treatment options described in the SOC required to manage more advanced disease. Development of cardiomyopathy affects all DMD patients and most will have an established cardiomyopathy by 18 years of age [39]. Cardiomyopathy is one of the leading causes of morbidity and mortality [40]. Adults with DMD should be seen at least annually by a cardiologist with experience in the management of neuromuscular cardiomyopathy to monitor heart function, optimise drug therapies and provide feedback to patients. To achieve best long-term survival it is critical for paediatric and adult cardiology teams to liaise and agree thresholds for starting heart treatments, the drugs to be used and protocols for dosing. Cardiac care in adulthood cannot compensate for treatments not deployed appropriately prior to transition from pediatric services.

Assessment of cardiac symptoms in non-ambulatory DMD adults is often difficult and limited. Even when left ventricular dysfunction is severely reduced, most patients remain asymptomatic and when heart failure ensues, symptoms are often non-specific with anorexia, abdominal pain and fatigue more often than shortness of breath predominating. Therefore, treatment and dose optimisation should not be based on the presence or absence of symptoms but needs to be guided by the serial results of cardiac imaging investigations.

Annual assessment by a cardiologist with imaging such as echocardiogram (echo) or cMRI should be undertaken, cMRI is the test of choice because it is better able to identify sub-clinical myocardial fibrosis at an early stage [5]. However, cMRI may be technically difficult in the adult patient and image quality reduced due to artefact from metallic spinal rods and inability of patients to lie flat for the duration of the scan. N-Terminal pro-Brain Natriuetic Peptide (BNP) measurement seems only to become elevated in patients with DMD with the onset of cardiac failure. As such, it is not clinically useful in monitoring the progression of ventricular dysfunction in these adults.

There is evidence to support the early initiation of an Angiotensin Converting Enzyme-inhibitor (ACEi) can reduce the rate of decline of cardiac function. Current clinical practice recommends empiric initiation of an ACEi prophylactically from 10 years of age and/or at a younger age when abnormalities are first detected on cardiac imaging [1, 5, 41–43]. A prospective randomised placebo-controlled trial in DMD patients showed that the mineralocorticoid receptor blocker, eplerenone, further reduces the rate of decline of cardiac function when added to ACEi therapy and its initiation is recommended in addition in patients with cardiac dysfunction [44]. Beta-blockers are also appropriate to slow sinus tachycardia and later when there is evidence of left ventricular systolic dysfunction because of their generic benefits in heart failure of diverse etiologies. However, evidence to support the use of a beta-blocker prophylactically in the early stages before the appearance of systolic dysfunction is lacking.

Therefore, the most evidence-based regime for managing cardiomyopathy in DMD adults is the combination of an ACE-inhibitor (ACEi), mineralocorticoid inhibitor (eplerenone / spironolactone) and beta blocker (BB) [41]. Most patients are likely to be already taking some or all of these medications before transitioning to adult services. However, doses will need to be optimised in line with patient size, weight and age changes over time thereafter. This three-drug combination is generally well tolerated. Up-titration of doses may be limited by low blood pressure in DMD patients, which appears to be prevalent [44]. Renal function should be monitored with U&E and Cystatin C, especially, with the combination of an ACE-inhibitor and eplerenone [45, 46]. Patients need to be warned specifically about the need to always maintain an adequate fluid intake to avoid hypovolaemia, and especially so during periods of intercurrent illness [45, 46]. Renal failure due to acute kidney injury may occur in patients following addition of a diuretic to ACEi in the presence of dehydration [47]. Pragmatically, venesection is often difficult and may lead to delayed monitoring.

Unlike in most other forms of cardiomyopathy, glucocorticoid steroid therapy, used for skeletal muscle strengthening, delays the onset of cardiomyopathy by an average of two years. However, their role in treatment of cardiomyopathy in steroid-naïve patients is not advocated [48].

Ivabradine may be used in selected DMD patients to slow sinus heart rate, particularly when a BB is contraindicated (such as in severe asthma) or as an adjunct to low dose BB when usual doses are not tolerated. The aim is to achieve a heart rate of between 50–70bpm as recommended in current heart failure guidelines. The evidence for use of ivabradine in this patient population is limited with only small trials showing some benefits [49].

The combination of sacubitril/valsartan (‘Entresto’) has been shown to confer significant symptomatic and survival benefits over conventional ACE-inhibitor therapies in patients with severe systolic dysfunction of other aetiologies although dosing may be limited by hypotension [50]. Currently, both Entresto and very recently licenced newer agents (SGLT2 inhibitors) [51] the utility and tolerability in patients with DMD are unknown, but may be considered in selected patients.

Cardiac arrhythmias in DMD

Atrial and ventricular arrhythmias may occur in DMD-related cardiomyopathy including atrial fibrillation or flutter with tachycardia which may aggravate pre-existing ventricular dysfunction. Treatment should be the same as for other causes of these arrhythmias in patients with other disorders who have similar degrees of LV dysfunction. Slowing ventricular response rates is important in preventing acute deterioration in LV function, culminating in overt heart failure symptoms [52, 53]. Although procedurally challenging, catheter ablation may be undertaken safely in adults with DMD with appropriate anaesthetic and respiratory support. Similarly, direct-current cardioversion may be indicated to restore sinus rhythm in those with atrial fibrillation precipitated by an intercurrent illness.

In adults with DMD, ventricular arrhythmias tend to track with the degree of LV systolic dysfunction. As such their impact on overall survival is unclear. Sudden unexpected deaths are described in patients with DMD but the extent to which they are attributable to arrhythmias is currently unclear and in need of further study. When sudden death occurs in an adult patient with advanced DMD it could be explained by profound bradycardia due to unheralded AV-block with ventricular stand-still, sustained ventricular tachycardia/fibrillation, pulseless electrical disease or pulmonary embolus [5, 54–56].

Cardiac devices in DMD

Implantable cardioverter-defibrillators (ICD) are indicated in patients with DMD who present with sustained ventricular tachycardia or who have survived cardiac arrest [57, 58]. However, the benefit of prophylactic ICD insertion when there is severely reduced left ventricular function has not been established [59]. In addition, there is risk of complications at the time of device implant due to need for sedation or general anaesthesia and the extent of chest deformity, which increases the occurrence of pneumothorax, lead dislodgment, bleeding at access sites and infection [60]. Therefore, ICD use in adults with DMD should only be considered after thoughtful consideration and detailed discussion with the patient - involving carers/family. Ideally patients should be assessed and undergo operative intervention in high volume centres by an experienced operator.

Cardiac resynchronisation therapy with or without defibrillator capability (CRTP/D) should be considered in accordance with established guidelines, although the evidence for benefit in the context of DMD is only by extrapolation from randomised trials in cardiomyopathy of other aetiologies [61]. A registry of ICD or CRTP/D device implants in adults with DMD would help inform best practice in the long term.

Advanced heart failure treatment with mechanical support and heart transplantation is a theoretical option for patients presenting with severe heart failure. However, because of concomitant respiratory and skeletal muscle weakness, in practice, patients with DMD will rarely be assessed as eligible for these therapies. However, a small number with milder intermediate (BDMD) phenotypes have been transplanted in the USA.

Anticoagulation for systemic thrombo-embolic prophylaxis may be considered in patients with atrial tachyarrhythmias and in those with severe left ventricular systolic dysfunction to reduce their risk systemic thrombo-embolus. Those considered at particular risk of venous thrombosis with pulmonary embolism may also warrant anticoagulation. The use of novel oral anticoagulants (NOAC) is preferable to vitamin K antagonists for patient convenience, ease of dosing and to reduce the need for repeated INR (international normalized ratio) checking needed with warfarin.

Finally, timely initiation and optimisation of NIV is also supportive for the heart in DMD patients and is a key part of the overall strategy for improving cardiac outcomes cardiac outcomes [55].

Specific drugs & doses

There is lack of evidence on most appropriate doses of cardio-active medications to use in the early early subclinical stages of DMD-cardiomyopathy. At the stage, cardiac fibrosis may be seen on cMRI, global systolic function is usually still within the normal range. Studies on prophylactic use of ACE- inhibitors in this patients’ population have left dosing to the discretion of the clinicians. However, by extrapolation from the results from heart failure studies, it seems logical to up-titrate the doses to the maximum tolerated to achieve better results. For patients with reduced systolic function, generic guidelines for use of drugs blocking the renin-angiotensin-aldosterone system and beta-blockade in heart failure of commoner etiologies are appropriate. Drugs should be initiated and up-titrated as tolerated [62–67]. There is need for more experience in using sacubritil/ Valsartan, in place of either an ACEi or Angiotensin-receptor blocker and/or SGLT2 inhibitors in patients with DMD cardiomyopathy to make recommendations.

Renal and bladder management

Renal function can be compromised in adults with DMD, usually as a result of progressive cardiac failure and its treatment [56, 57]. Renal dysfunction is associated with a poor prognosis with 14% all-mortality from acute renal failure in DMD and was first reported in Japanese patients [68]. There is no specific guidance for managing renal complications in DMD in the published literature including international SOC [1–3]. The National Institute of Clinical Excellence (NICE) adult chronic heart failure guidelines recommend regular monitoring of renal function [56] as renal failure is an independent risk factor for mortality and adverse cardiovascular event in adults with heart failure [69].

Renal calculi

Renal calculi can be a troublesome problem affecting about 10% adults with DMD [77]. They probably occur secondary to increased urinary calcium excretion, although measurement of urine calcium creatinine ratio is impossible due to the low muscle mass and low serum creatine level. Patients affected with renal calculi may experience pain and hydronephrosis necessitating analgesia and drainage with nephrostomy, which in turn poses additional risks for the adult with DMD. Voluntarily limiting oral fluid intake is not uncommon in older DMD patients. It is important to assess fluid intake at every clinic visit and to encourage the patient to drink 1-2 litres of fluid each day. Currently, there is insufficient evidence to support annual renal ultrasound to screen for calculi.

Bladder dysfunction

Bladder dysfunction is also reported amongst people with DMD and can be a distressing symptom. A questionnaire survey showed that some patients had symptoms of daytime incontinence, urinary frequency, urgency, nocturnal enuresis, nocturia, stress incontinence and urinary hesitancy [78]. Urodynamic studies showed a small capacity, hyperreflexic bladder and detrusor sphincter dyssynergia [79]. Detailed history and examination are important to exclude other causes of urinary dysfunction. Postural changes may help with voiding, some patients reported that using a neoprene strap to reduce their lumbar lordosis helped them to micturate. If symptoms are suggestive of detrusor hyperreflexia, a pre and post micturition bladder ultrasound to ensure complete bladder emptying and a trial of oxybutynin or a similar medication can be considered. The use of chronic indwelling catheterisation has been practised for some patients, although infection and leakage may be troublesome.

Corticosteroid management, endocrine and bone health

The adult DMD population is heterogeneous including patients who are: a) steroid naive (defined as either no treatment or treatment < 1 year), b) previously steroid treated but discontinued (>1 year treatment) and c) those still taking steroids either daily or intermittently (10 days on 10 days off). If the DMD adult has benefitted from steroid treatment- as evidenced by comparison with age-matched steroid naïve peers, and benefit continues to outweigh potential harms, the patient should be given the choice to continue treatment. Such benefits might include: better muscle function (as evidenced by: ability to walk, stand, crawl or sit without support), positive effect on upper limb function and preservation of respiratory and cardiac function.

Adult patients who are taking steroids are at risk of steroid related complications that require regular monitoring which, as outlined in the standards of care [1–3] include: hypertension, cataracts, glucose intolerance, obesity, infections, short stature, friable skin, GI and bowel perforation and pubertal delay due to hypogonadism, osteoporosis, adrenal insufficiency and fat embolism as a consequence of osteoporotic fractures. If these complications outweigh any perceived benefit in the adult patient, then the patient should be given the option to wean and stop steroid treatment. Weaning should be done very slowly and the patient warned that he is at risk for adrenal insufficiency for at least 12 months post weaning.

Adult DMD patients on steroids who develop Herpes Zoster infections should be treated promptly with oral or IV acyclovir.

Pubertal delay and hypogonadism

One adverse consequence of steroid treatment is pubertal delay and hypogonadism. The majority of adolescents on corticosteroids especially daily regime will not commence puberty spontaneously and will require testosterone therapy to aid completion of pubertal development, improve linear growth and restore bone accrual closer to those of a healthy adolescent. Testosterone therapy is discontinued once pubertal development is complete. Some young men with DMD continue to have central hypogonadism (low testosterone levels, with normal or low LH and FSH). Untreated this may impact on bone health, fatigue and energy levels. Monitoring testosterone levels together with LH and FSH is recommended at least once every 2 years. Ideally, testosterone levels should be checked in the morning close to 9 am, if possible. Discussion with endocrinologist for treatment with testosterone therapy is indicated if low testosterone levels is identified on two occasions [1], and this should be managed with input from an endocrinologist.

Glucose intolerance and metabolic syndrome

There is limited but growing research evidence for abnormal glucose metabolism in DMD adults, this could be related to corticosteroid treatment and obesity, but might also be related to loss of muscle tissue that would otherwise be involved in glucose metabolism [94]. Clinical assessment should look for evidence of metabolic syndrome and the finding of acanthosis nigrans should prompt testing of HbA1 C and if abnormal appropriate treatment commenced under the guidance of an endocrinologist. Where there is evidence of metabolic syndrome metformin may be prescribed. Acute episodes of normoglycaemic ketoacidosis have been reported recently in adult DMD and should be managed with IV fluids [95]. Further prospective natural history data, as planned by the ANSN will add to our understanding of these rare metabolic complications in the future.

Transition

The transition process should begin in the pediatric service during adolescence to prepare the young person for adulthood, this is discussed in the international standards of care [1] and there are NICE guidelines which should be followed (https://www.nice.org.uk/guidance/ng43). There should be joint clinics between the pediatric and adult physicians to facilitate a smooth transition and transfer to adult services. There should be a transition coordinator to set goals with the young person and to support them during adolescence and teenage years. The young person should have a voice and be heard. Providing peer support through the service and/or directing the young person to a peer support group via a national charity is also advised.

Participation, psychosocial, and palliative care

Comprehensive multidisciplinary care of adults with DMD should include access to therapy services including: physiotherapy, speech and language therapy, occupational therapy, clinical psychology and a care advisor. A care advisor or equivalent (such as Clinical Nurse Specialist) can play a major role in supporting participation at all stages of the condition. At times, orthopaedic surgery and chronic pain teams may also need to be involved. Musculoskeletal pain can a frequent symptom in adults with DMD, strong opioid analgesics may exacerbate constipation and bowel issues. Gabapentin is a useful adjunct and may be considered but early referral to a pain team for localised injections can be very helpful.

The role of the care advisor is outlined in Table 1

Participation in activities of daily living for adults with Duchene Muscular Dystrophy (DMD)

A primary goal of the care of the adult with DMD should be to facilitate participation. Participation is defined as direct engagement in a life situation including activities of personal care, mobility, social relationship, education, recreation and leisure, spirituality and community life. It is considered a measurable outcome of health and is increasingly becoming a key focus of rehabilitation programs [96].

For the general neuromuscular population decisions about occupation and employment are often dictated by physical function, muscle strength, fatigue and type of neuromuscular condition [97]. Not surprisingly, unemployment and social isolation are frequent complaints [98, 99]. Qualitative studies examining barriers to meaningful occupation in adult DMD patients indicate lack of support and resources, social isolation, lack of motivation and depression in addition to medical challenges [100]. Fatigue, pain and affective disorders may be more prevalent in the older DMD population [101] and these likely further impact upon participation in adulthood.

It is likely there is an interaction between physical health, psychological factors and societal factors. For young men with DMD and their families the disease impacts on all three areas with dramatic changes in lifestyle and functional performance and increasing loss of physical function and independence. This follows a pattern observed in younger DMD patients [102].

Outcome measures for persons diagnosed with DMD have, over the years, been mainly focused on the assessment and monitoring of disease progression. The emphasis has naturally been to focus upon features such as muscle strength and contractures, respiratory and cardiac involvement and other important medical aspects. However, these clinical measures may not correlate directly with daily life activities and quality of life issues which an individual experiences and aspires towards. There is a need to establish a more complete assessment of participation in daily life activities and for disease management to be examined in the context of valued participation in real life situations.

To date, this has been studied mainly in the paediatric DMD population using for example the Children’s Assessment of Participation and Enjoyment (CAPE) and Paediatrics Quality of Life Inventory (PedsQL) scales [103] and the ACTIVLIM questionnaire [104]. Studies in the adult Duchenne population have used narrative interviews [100, 103], SF-36 and WHOQOL-BREF [105–107]. Scales used in the adult population focus predominantly on quality of life evaluation rather than actual detailed performance participation. There is a need to assess these aspects and impact on quality of life in order to address the needs of adult men with DMD including to: identify and evaluate scales used in adult patients with neuromuscular diseases and gain consensus on which scales to use. Currently available scales include: MAPA – The Meaningful Activity Participation Assessment which is a checklist-type survey of 28 diverse activity items assessing frequency of participation and degree of personal meaningfulness experienced with each activity, assessment of pain, ACTIVLIM, QoL: SF36, WHOQOL-BREF. Assessing factors that impact on participation and quality of life also need to be considered. These include assessing pain, fatigue and mood. The Fatigue Severity Scale is a 9 item scale with good psychometric properties [108]. The Hospital Anxiety and Depression Scale [109] is a well-known screening measure. Higher scores indicate ‘caseness’ for depression or anxiety and warrant further assessment by mental health professional or referral to psychological therapies. These measures can be used routinely by care advisors or clinical nurse specialists to flag up individuals who may need further intervention.

Psychological care

Evidence for cognitive impairment in young DMD patients is well established [110–113]. Deficits have been reported in verbal and visual memory, working memory, executive function and higher cognitive processes attentional processes. Neuropsychiatric disorders including ADHD, autism or autistic spectrum disorder and obsessive compulsive disorder (OCD) are also prevalent [114]. Whilst some cognitive difficulties may resolve with age [115] there is evidence that difficulties in general information processing persist into adulthood [116] as do autistic traits and/or Attention Deficit Hyperactivity Disorder (ADHD) and OCD [117].

Psychological disorders such as depression and anxiety are also associated with DMD with rates ranging from 17–29% for depression and/or anxiety [118, 119]. Depression and anxiety may become more prevalent in adulthood as the young person grapples with adjustment to a progressing health condition [118, 119].

Consideration also needs to be given to the impact of these changes on the support system and family. Parents face the burden of providing greater levels of care as well as the social and psychological support for their children [120]. Assessing carer burden and the presence of anxiety or depression in parents may also be helpful.

The adult DMD patient and their family face a number of challenges from the medical, social and psychological domains. The interaction of these different factors and how they are managed can have a bearing on treatment compliance; especially NIV use and/or cardiac medication which can have life-threatening complications.

A clinical neuropsychologist (or equivalent) should be part of the neuromuscular multi-disciplinary team (MDT) and play a role in screening and risk assessing individuals where appropriate. Anti-depressant and anxiolytic medication should be considered for those people with moderate to severe symptoms. Referral for psychological intervention may also be useful. Intervention can range from individual or group treatment for specific concerns such as anxiety and/or depression, adjustment. Neuropsychological review should also be considered to provide a baseline of cognitive function and highlight weaknesses that may impact on the patient’s ability to manage educational and work activities as well as self-care and decisions around their health condition and treatments.

Palliative care

This is a new group of patients for palliative care and the trajectory of their condition is not as clear cut as patients with other life-limiting diseases such as cancer for example. However, it does fit with the change in the palliative care ethos with an emphasis on patients with non-malignant conditions rather than cancer and an emphasis on symptom control as well as end of life care [121]. Any chronic condition, particularly when life-limiting, can lead to psychological adjustments and the fear of dying and how that process will happen [122].

There is a very limited body of literature on palliative care and ‘End of life’ discussions in adults with DMD and the majority highlight that good quality end of life discussions are not usually held by the clinical team; DMD men may have questions about what the end of life will be like [122]. In one study 85% of families had not heard of the palliative care team and hospice care only in 6%. Only 25% had any form of advance care directive document [123].

Involving a palliative medicine consultant in patient care is helpful. Palliative medicine consultants are often embedded within the hospital setting, where this is not the case a ‘hub and spoke model’ with the neuromuscular team should be considered. The palliative medicine consultant can be called upon to help with symptom control and in the utilisation of a local palliative care service. All patients should be able access a palliative care consultant at any time during the course of their condition. Advance care plans in general medical care are now widely used and accepted. The application within DMD is difficult- both for when and how to introduce this topic of discussion and by whom should this discussion be initiated. Current experience suggests that it is the team who knows the patient best who should do this. There is also a perception that advance care plans are only about end-of-life discussions when they should be recognised as a means of documenting the patient’s wishes in terms of ‘ceiling of care’ and priorities. A recent review by Hiscock et al. revealed that majority of DMD patients die without a formal end of life care plan in place [124]. There appeared to be a shared reluctance of patients, family carers and healthcare professionals to initiate these discussions. Discussing end of life issues is an uncomfortable area for doctor patient discussions, an ENMC workshop on adult DMD care heard from participating people with DMD that they did not wish to have end of life discussions [125]. On the other hand, in a study by Abbott, young DMD men expressed a desire for clinicians to be proactive in their approach to bring up these topics and discussions [123]. Such discussions should always be conducted sensitively, led by the neuromuscular consultant, who knows the patient well, and supported by a specialist nurse, care advisor and/or clinical neuropsychologist.

Close liaison with a palliative medicine consultant can really be helpful with ‘symptom control’ management, especially for those patients with distressing symptoms such as intractable pain, where standard treatment of secretion management has failed, withdrawal of NIV at the patient’s request or end stage cardiomyopathy [124–126]. A traffic light system is useful to identify those patients that are more at risk of dying and ensure that timely discussions are initiated and if reciprocated, the discussion taken further [127]. Few adults with DMD access hospice care, although many would have accessed children’s respite hospices. Children’s and adult’s hospices are very different organisations offering different types of care. Adult palliative care services tend to offer a managed ‘episode of care’ approach, including ‘hospice at home’ which may provide valuable support for dying patients. Close collaboration between the neuromuscular team and palliative care consultant may be hugely helpful, especially in terms symptom management in patients with more advanced disease.