Epidemiology

Duchenne muscular dystrophy (DMD) is a genetic disease mainly affecting boys. It affects between 1 in 3600 and 1 in 6000 live male births;^1–3 the prevalence is 5 in 100,000.⁴

Aetiology

Duchenne muscular dystrophy is caused by deletions, duplication or point mutations in a gene on the X chromosome.⁵ The gene codes for a protein, dystrophin, that links the cell’s cytoskeleton to a transmembrane complex. Absence of this protein causes disease in muscle cells and brain neurons. The precise mechanism is still uncertain.

Pathology

In muscle, pathological studies show a ‘dystrophic’ picture in which there are dying muscle cells and regenerating muscle cells, together with inflammatory cells and excess amounts of fat and connective tissue.^6,7 Clinically, this manifests as weakness, first of the larger skeletal muscles around the shoulders and hips, and later of all skeletal muscles in the limbs and trunk. With increasing age, this causes a progressive loss of functional abilities that affect mobility (going up stairs, walking, standing, sitting and transferring between objects such as a chair or bed), activities of daily living (dressing, bathing and eating) and eventually breathing. As the disease progresses, muscles and tendons become shorter. These ‘contractures’ then prevent the joints they operate from moving through their full range, because the muscle can no longer stretch as completely as it should. The calf and long finger muscles are often involved by the age of 5 years, causing an inability to bend the foot fully up towards the shin (dorsiflexion) or straighten the fingers back. If untreated, contractures become more severe with time. Later, weakness of the trunk muscles causes scoliosis or curvature of the spine. The heart muscle is increasingly affected with age, eventually leading to impaired function and cardiac failure. The smooth muscle of the bowel deteriorates, affecting bowel function. The lack of dystrophin subtypes in the brain increases the risk of non-progressive cognitive dysfunction, which is associated with communication difficulties.⁸

Prognosis

Untreated, half of boys will lose independent ambulation by the age of 9 years, and all will do so by the age of 12 years. Scoliosis and impaired heart function start in early adolescence, whereas breathing difficulty develops later in adolescence. In the 1960s, survival beyond mid-adolescence was unusual. With better therapies, survival increased to late adolescence in the 1970s to the 1990s. In the past two decades, the introduction of more effective respiratory support and heart treatment has increased survival into the early 30s, or longer. The more widespread use of corticosteroids from a young age has slowed disease progression; in those taking daily steroids, the average age at loss of ambulation has increased to 14 years.⁹

Significance in terms of ill health

Health-related quality of life for boys with DMD and their carers is lower than for the general population.^10,11 Although physical and psychosocial domains of health-related quality of life are comparatively low in boys with DMD, psychosocial quality of life is sometimes higher in adolescents than in school-age children, indicating the development of coping strategies.^12–14 The psychosocial well-being of parents is greatly impacted, particularly around the time of a boy’s transition to wheelchair use.^15,16 Parents, especially mothers, report high levels of anxiety, depression and guilt.^17,18 Early diagnosis and the resilience of the family unit, expressed as their commitment and control, were associated with improved psychological adjustment by the parent, resilience on the part of the boy and response from siblings.^18–22 Parents, and mothers in particular, report care activities, such as including help for bathing and toileting, as time-intensive and contributing to social isolation.²³

Health-care costs are associated with access to specialist paediatricians/physicians in neurology, respiratory, cardiac and endocrine fields, orthopaedic surgeons, psychologists, physiotherapists and occupational therapists. Boys will sometimes have care co-ordinators or advisors, dietitians or nutritionists, or speech/language/swallowing therapists. Young men older than most of those in our study are likely to make increased use of emergency and respite care. Outside the health services, older boys may access home help, personal assistants and transportation services. From around 8 years of age, the median age of boys entering our study, families will typically make investments in and reconstructions of the home, for instance making adaptations for wheelchair accessibility.²⁴ Adaptations may also be required to educational facilities. A systematic review of the cost of illness⁴ noted only three studies that reported cost-impact data, all of which were > 20 years old.^25–27 However, a questionnaire study²⁴ involving people with DMD in Germany, Italy, the UK and the USA provided per-patient annual costs of DMD in 2012 in international dollars. The questionnaire elicited information about hospital admissions, visits to health-care professionals, tests, assessments, medications, non-medical community services, aids, devices, alterations to the home and informal care. Mean per-patient annual direct cost was $23,920–54,270, which is between 7 and 16 times higher than the mean per-capita health expenditure. The total societal costs were $80,120–120,910 per patient per annum, increasing sharply with disease progression. Mean household costs were estimated at $58,440–71,900.²⁴

Pharmacological management and multidisciplinary care excluding physiotherapy

At diagnosis, a boy and his family will typically be seen by a paediatrician at their local hospital, often a district general hospital. They will then be referred to a specialist muscle clinic, usually involving a paediatric neurologist, in their regional teaching hospital.²⁸ Regular review and ongoing medical care is provided by these services. The boy and his family will also be seen by the regional genetics service. As part of this service provision they will also be referred to the local paediatric physiotherapy team for assessment and management (see Physiotherapy). If needed, they may be referred for occupational therapy advice as well. Educational services will also be involved. Some children and their families may also benefit from psychological support.

From the age of 3–4 years, most boys will start treatment with corticosteroids, which requires 6-monthly monitoring visits. If complications develop, extra visits and referrals may be needed. One frequent early complication is excess weight gain, which would lead to referral to dietetic services. Approximately one-third of the current population of ambulant boys is eligible for trials of newer treatments designed to increase the amount of the missing dystrophin protein in muscle cells, leading to a milder disease course. If successful, these treatments are likely to become generally available, and additional products are likely to be designed to expand the number of boys who could benefit.

Physiotherapy

Although physiotherapy has been a mainstay of treatment since the 1960s, there is relatively little evidence for its efficacy. There have been no generally accepted guidelines on what type or dose of physiotherapy intervention should be provided.^29,30 Many recommendations are based on animal studies in which contraction-induced muscle injury was observed in dystrophinopathy.³¹ A Muscular Dystrophy Campaign workshop²⁹ agreed that the main aims of physiotherapy in neuromuscular disease should be to:

1. maintain or improve muscle strength by exercise
2. maximise functional ability through the use of exercise and the use of orthoses
3. minimise the development of contractures by stretching and splinting.

The prevention of joint contractures is a multidisciplinary effort, involving specialist hubs and community spokes.³² Regional consultant neurologists and specialist neuromuscular physiotherapists review disease progress and treatment regimens at clinic visits, typically twice a year, and offer management suggestions to community physiotherapists.²⁸ While a boy is still able to walk, a community paediatric physiotherapist will monitor him for hip and ankle contractures until he becomes wheelchair dependent.³³ The community physiotherapist is responsible for tailoring a programme of stretches and exercises to the boy’s individual needs and tolerance levels,²⁸ and for training parents, carers, school staff or, occasionally, other health and social care staff to deliver the stretches.³³

Management should consist of a variety of treatment options aimed at maintaining the length and extensibility of affected muscle groups.³⁴ Although evidence to support interventions aimed at improving the range of movement is lacking, there are generally recognised principles that should be carried out to delay or, where possible, prevent the development of contractures.³⁵ These include the prescription of a regular targeted stretching regime and the use of specific orthotics (e.g. resting or night splints are generally recommended). Stretches are typically prescribed to be performed at home, in school or occasionally in community clinics, on a minimum of 4–6 days per week.²⁸ They are intended to maintain dorsiflexion and hip flexion range, among other targets, with a view to postponing the onset of contractures and prolonging the length of time the child can walk independently.³³ There are no clear guidelines to specific exercise prescription, but regular submaximal exercise is recommended to maintain existing muscle strength and avoid secondary disuse atrophy,^36,37 along with general advice on regular activity such as walking, cycling and swimming. Although there is still the need for further research, there is general agreement that exercise that contains a substantial eccentric component (such as trampolining, stair descending) should be avoided because of the risk of exacerbating muscle damage.³⁸

Physiotherapy plays its part in the holistic, multidisciplinary management of children with DMD, providing specialist assessment, physiotherapy prescription and ongoing monitoring and evaluation of a complex and progressive condition.²⁸ Liaison with other specialist services, such as orthotics, wheelchair services, social and housing services, and schools to ensure the provision of appropriate equipment and support in a timely manner to maximise function and independence wherever possible is key. Hyde et al.³⁹ recommend the use of night splints. Resting or night splints, generally ankle–foot orthoses, are provided for use in combination with a regular stretching regime to optimise the length of the tendo-Achilles complex and maintain ankle dorsiflexion at night.^28,33,39 Children who are losing the ability to walk may be provided with knee–ankle–foot orthoses and may have surgical intervention to release tendons with a view to maintaining joint motion and independent ambulation.^28,33 Postponing wheelchair use may also defer the more or less inevitable associated onset of spinal scoliosis.³³

Introduction

Exercise that is safe and controlled but still sufficiently intense to maintain physical function is a challenge for children with altered muscle tone, balance or motor control problems and severe contractures.⁴⁰ Warm water allows children with DMD to perform targeted stretches, exercises and function-based and play activities that are progressively lost to them on dry land.³³ An aquatic therapy (AT) pool may be the only setting in which these children can learn new postures or skills and maintain fitness without damaging their joints.

Although definitions sometimes overlap, common usage distinguishes hydrotherapy and ‘aquatic therapy’ and, especially, ‘aquatic exercise’, from ‘balneotherapy’, which denotes seated immersion or spa therapy without exercise.^41–43 The Aquatic Therapy Association of Chartered Physiotherapists (ATACP) defined aquatic physiotherapy as:

A physiotherapy programme utilising the properties of water, designed by a suitably qualified Physiotherapist. The programme should be specific for an individual to maximise function which can be physical, physiological, or psychosocial. Treatments should be carried out by appropriately trained personnel, ideally in a purpose built, and suitably heated pool.

ATACP⁴³

They permit the use of the term ‘aquatic therapy’ for water-based programmes, designed by a suitably qualified physiotherapist, but carried out by non-specialist physiotherapists, or by carers and teaching assistants without specialist knowledge of anatomy and physiology.

Theoretical basis

In addition to the theories underpinning land-based therapy (LBT) (see Physiotherapy), the theoretical bases for AT are our understanding of the physical properties of water and a learning theory that accounts for developmental aquatic readiness, a model of systematic desensitisation⁴⁴ and the biomechanical principles of the floating human body,⁴⁵ as encapsulated in the Halliwick Concept.⁴⁶

The physical properties of water that are relevant to physiotherapy are density and specific gravity, hydrostatic pressure, buoyancy, viscosity and thermodynamics.⁴⁷ For DMD, a musculoskeletal condition, immersion brings the following benefits. First, warm water may increase cardiac output away from the splanchnic beds to the skin and musculature.^48–50 Blood flow to the muscles may be enhanced at rest⁵¹ and during exercise.⁵² Second, body weight is offloaded with immersion, with the desired amount of loading variable by depth.⁵³ In musculoskeletal conditions, then, it is hypothesised that the hydrostatic effects and the warmth of the water, compared with cooler water in community swimming pools, make muscles more supple. The buoyancy and antigravity effects relieve pressure on joints, leading to a reduction in pain and an increase in joint mobility compared with strengthening and stretching exercises performed on dry land.⁴⁷ The metacentric or rotational effects, caused by altering the amount of the body that is immersed or the shape of the body in water so that the body is displaced requiring postural adjustments, are used to develop balance, core/proximal stability (stomach, shoulder and hip muscles) and to simulate function (transitions between positions – sit to stand, rolling over, going up steps, lying to sitting).

Systems such as Halliwick, which teach people with disabilities to return to a safe breathing position in water,⁴⁶ thereby producing confidence and safety, are essential for an AT/physiotherapy programme.⁵⁴ They combine two elements: first, the ‘Ten Point Program’, which covers aspects of mental adjustment (including water confidence and breath control), balance control and movement; and, second, a protocol for ‘Water Specific Therapy’, involving assessment and objective setting, based on which the therapist chooses appropriate exercise patterns and treatment techniques.⁴⁶

Intervention methods and materials

Aquatic therapy pools typically operate at temperatures of 32–36 °C, higher than the 28 °C of conventional swimming pools, with a greater level of disinfectant and more frequent microbial sampling.⁵⁵ Pool size varies, with a recommended minimum space of 2.5 m × 2.25 m per patient and a typical depth of 1–1.2 m, often on a gradient. The provision of changing rooms with adequate space and wide entrances is optimal, along with hoists, both in the changing rooms and to get in and out of the pool. An ATACP foundation programme for chartered physiotherapists is necessary for safe and effective treatment.⁵⁶ Subjective, Objective, Assessment and Plan (SOAP) record keeping is recommended.³³

Evidence for effectiveness

In an overview,⁴² three systematic reviews evaluating aquatic exercise against controls in adults with musculoskeletal conditions showed small post-intervention improvements in function [n = 648, standardised mean difference 0.26, 95% confidence interval (CI) 0.11 to 0.42], quality of life (n = 599, standardised mean difference 0.32, 95% CI 0.03 to 0.61) and mental health (n = 642, standardised mean difference 0.16, 95% CI 0.01 to 0.32).^57–59 They also found a 3% absolute reduction and a 6.6% relative reduction in pain, measured on a visual analogue scale (n = 638, standardised mean difference 0.19, 95% CI 0.04 to 0.35). The meta-analyses identified no differences for walking ability or stiffness.

Although annotated bibliographies on the use of AT in disabled children exist,^60,61 we are aware of only one relevant systematic review of aquatic interventions for children with neuromotor or neuromuscular impairments.⁶² It included one randomised controlled trial (RCT) and 10 observational studies. Only three studies, all with low levels of evidence, investigated neuromuscular disorders. Seven articles indicated improvements in physical function and activity level, and two out of four articles investigated levels of participation-indicated improvements. The review concluded that there was a lack of quality evidence on the effects of AT in this population.

Current aquatic therapy provision in the UK

Although many health professionals believe that AT can improve mobility, strength, flexibility and cardiopulmonary fitness,⁶³ and although AT is a routine part of care in other countries, access is uneven and restricted in the UK.⁶⁴ At the end of 2015, the charity Muscular Dystrophy UK (MDUK) identified 179 AT pools in the UK that people with muscle-wasting conditions could potentially use, but highlight that:

• many hydrotherapy pools are based in schools and are only open during school hours and terms
• privately-owned hydrotherapy pools can be expensive to access – often more than £75 for a half-hour session
• people have to travel long distances to get to a pool, and this is not sustainable
• hydrotherapy pools do not always have hoists, or accessible changing facilities.

Reproduced with permission from MDUK, Hydrotherapy in the UK: The Urgent Need for Increased Access⁶⁴

Muscular Dystrophy UK asserts that NHS-funded AT ‘is often restricted to patients whose improvements can be demonstrably measured’;⁶⁴ as such, functional improvements are difficult to demonstrate in degenerative conditions and funding is often absent or limited. In MDUK’s report, a young person with DMD is quoted as saying:

We have an ongoing need for hydrotherapy, which is not fulfilled by just being given a block of sessions for six weeks. This does not allow us to continue to maintain our condition because once our block of six sessions is over we struggle to be able to access hydrotherapy treatment anywhere else.

Reproduced with permission from MDUK, Hydrotherapy in the UK: The Urgent Need for Increased Access⁶⁴

The aspiration to access AT throughout the year, rather than in 4- to 6-week blocks, is confirmed by our patient and public involvement (PPI) author, James Parkin, who notes ‘If you have AT regularly, it improves self-esteem; self-esteem improves how you deal with self-management’. A long hiatus between sessions can decrease water confidence and result in a loss of skills. Our qualitative research (see Chapter 5, Environmental factors and Operational work) confirms that, where publicly funded AT is available, it often comes in blocks of 4 or 6 weeks, ≥ 6 months apart, and is not necessarily routine but may be contingent on a successful application. MDUK end their report by arguing that access to AT helps people with muscle-wasting conditions ‘to manage their condition and improve their quality of life by reducing pain and increasing mobility’.⁶⁴ They make an appeal to equity, proposing that access should not depend on where a person lives or their disposable income.⁶⁴

Rationale

The National Institute for Health Research (NIHR) published a commissioning brief (commissioning brief HTA 12/144) requesting a ‘feasibility study’ to evaluate the addition of ‘manualised hydrotherapy’ to ‘optimised land-based exercise’ for children and young people with DMD who still have some mobility. There are several ways in which we might have interpreted and responded to this brief so, at this point, it is worth taking the reader through the choices we made and why we made them. First, confusion about the definition of feasibility studies, which has since been widely acknowledged,^65,66 meant that a decision had to made on the primary objective of this study. The request for a control group, and the focus on the ability to recruit and randomise, led us to interpret the brief as requiring an external pilot RCT, sometimes defined as ‘a version of the main study run in miniature to determine whether the components of the main study can all work together’.⁶⁶ In other words, we interpreted the brief primarily as a study to understand the feasibility of a research protocol for a full-scale RCT, rather than of the feasibility of delivering manualised AT per se. As the reader will see, an understanding of both issues is likely to be important for future clinical decision-making and the commissioning of further research.

Primary objective

A future full-scale trial would test the hypothesis that AT in addition to LBT is more effective than LBT alone for the maintenance of functional, participation or quality-of-life outcomes. The primary objective of this external pilot RCT was to determine the feasibility of a full-scale trial, defined in terms of participant recruitment.

Secondary objectives

Secondary objectives were the identification of:

1. the best primary outcome for a full-scale trial
2. the consent rate among eligible boys with DMD who were approached about the study
3. why boys with DMD refuse consent
4. the proportion of boys who provide valid outcome data 6 months after entering the trial
5. reasons for attrition from the trial
6. the views of participants and their families on the acceptability of the research procedures and the AT intervention
7. the robustness of the intended data collection tools
8. the willingness of participating centres to provide an AT service and to recruit participants
9. the ability of participating physiotherapists to deliver the AT intervention faithfully in accordance with a manualised protocol
10. therapist views on the feasibility of the AT intervention and the acceptability of the research protocol.