THE DIAGNOSIS ANDMANAGEMENT OF DUCHENNE

MUSCULAR DYSTROPHYA guide for families

Contents

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1 Introduction 042 How to use this document 05

3 Diagnosis 114 Neuromuscular management - maintaining strength and function 14

5 Rehabilitation management - physical therapy and occupational therapy 256 Orthopedic management - help with bone and joint problems 29

7 Pulmonary management - looking after the breathing muscles 318 Cardiac management - looking after the heart 34

9 Gastrointestinal management - nutrition, swallowing and other gastrointestinal issues 36

10 Psychosocial management - help with behavior and learning 3911 Considerations for surgery 43

12 Emergency care considerations 46Abbreviations 48

List of terms that you may come across 49

DISCLAIMER

The information and advice published or made available in this booklet is not intended toreplace the services of a physician, nor does it constitute a physician-patient relationship. This

advice should be taken in conjunction with medical advice from your physician, whom youshould consult in all matters relating to your health, in particular with respect to symptoms that

may require diagnosis or medical attention. Any action on your part in response to theinformation provided in this booklet is at your own discretion.

This guide for families summarizes the resultsof an international consensus on the medicalcare of Duchenne muscular dystrophy (DMD).This effort was supported by the US Centersfor Disease Control and Prevention (CDC), incollaboration with patient advocacy groupsand the TREAT-NMD network. The maindocument is published in Lancet Neurology.

The recommendations are based on anextensive study by 84 international experts inDMD diagnosis and care chosen to represent abroad range of specialties. They independently“rated” methods of care used in themanagement of DMD to say how “necessary”,“appropriate” or “inappropriate” each onewas at different stages of the course of DMD. In total they considered more than 70,000different scenarios. This allowed them toestablish guidelines that the majority agreedrepresented the “best practice” for DMD care.

The experts stressed that the best managementof DMD requires a multidisciplinary approach,with the input of specialists in many differentareas, and that there must be a physician ormedical professional that coordinates theseefforts. Because everybody is different, theperson with DMD and his family should beactively engaged with a medical professionalwho will coordinate and individualize clinical care.

This document will provide you with basicinformation to allow you to participateeffectively in this process. The physician ormedical professional who coordinates caremust be aware of all potential issues in DMDand must have access to the interventions thatare the foundations for proper care and toinput from different specialties. The emphasisof interventions will change over time. Thisguide takes you through the different topics or domains of DMD care (Figure 1). Not all ofthese specialists will be needed at all stages ofthe condition, but it is important that they areaccessible if necessary and that the personcoordinating care has support in all these areas.

1 Introduction

04

This guide contains a lot of information. Youcan use it in two different ways. Some familiesprefer to concentrate on the stage of DMDthat their child has reached. Others like tounderstand as much as possible about everyaspect of DMD from the start.

In this section and in Figure 1 you can see howexperts think about the different stages ofDMD and how the care needs of someonewith DMD changes over that time. Then if youwant to go directly to the parts of thedocument which are relevant to you now, youshould be able to find them easily. At the endof the document, there are two sections thatmight be important to have as an easyreference: things to remember if surgery isplanned and things to consider in anemergency situation. We have color-codedthe different sections to match with the colorsin the figure. There is a glossary at the end ofthe booklet to help you to understand anydifficult terms that you find here or that yourcare team might use.

TAKING DMD STEP BY STEP (Figure 1)DMD is a condition that changes as time goesby. Physicians and others often recognize key“stages” in the progression of the condition.They use these key stages to guide theirrecommendations about care, though thesestages can be a rather artificial distinction.Still, it can be useful to use the stages toidentify the kind of interventions that arerecommended at any particular time and what you should expect of your care team at that time.

Presymptomatic

Most boys with DMD are not diagnosed duringthe PRESYMPTOMATIC stage unless there is a family history of the condition or unlessblood tests are done for other reasons.Symptoms of delayed walking or delayedspeech are present, but are typically subtleand are often unnoticed or unrecognized atthis stage.

2 How to use this document

05

“This is a guide to the ‘medical’aspects of DMD, but always bear in mind that the medical side isn’teverything. The idea is that byminimizing medical problems, yourson can get on with his life and you can get on with being a family.It’s good to remember that mostDuchenne boys are happy kids andmost families do very well after theinitial shock of the diagnosis.”

Elizabeth Vroom, United Parent Projects Muscular Dystrophy

REFERENCES FOR THE MAIN DOCUMENT:Bushby K, et al. The Diagnosis andManagement of Duchenne MuscularDystrophy, part 1: diagnosis, andpharmacological and psychosocialmanagement, Lancet Neurology 2010, 9(1) 77-93.

Bushby K, et al. The Diagnosis andManagement of Duchenne MuscularDystrophy, part 2: implementation ofmultidisciplinary care, Lancet Neurology 2010, 9(2) 177-189.

The main document can be downloaded free from http://www.treat-nmd.eu/diagnosis-and-management-of-DMD/

Early ambulatory

In the EARLY AMBULATORY (WALKING)stage, boys will be showing what are typicallyregarded as the “classical” signs of DMD – aGowers’ maneuver (which means that theyneed to support themselves with hands onthighs as they get up from the floor), waddlingtype walking (gait) and walking on their toes.They can still climb stairs, but typically bringthe second foot up to join the first rather thangoing foot over foot.

These two early stages are the time when thediagnostic process is likely to be underway(Section 3).

DIAGNOSIS: Specific tests will berecommended in order to identify the changein the DNA or genetic mutation that causedDMD. Input from specialists may be needed in order to interpret these tests and to discusshow the results may impact your son andother family members.

LEARNING AND BEHAVIOR: Boys who haveDMD have a higher chance of having problemsin these areas. Some are due to the effectDMD has on the brain, others to physicallimitations. Some medications such as steroidsalso play a role. Family support is essential,and input from specialists may be needed toaddress specific issues of learning andbehavior (Section 10).

PHYSICAL THERAPY: An introduction to thephysical therapy team (Section 5) at this earlystage will mean that exercise regimes can beintroduced gradually to keep muscles suppleand prevent or minimize tightness at thejoints. The physical therapy team can alsoadvise on appropriate exercise for school inorder to support participation.

STEROIDS: It is a good time to find out aboutoptions such as steroids (Section 4) which will be planned for when the boy’s gaining ofmotor skills starts to level out or “plateau”. Inplanning for the use of steroids, it is important

to check that all immunizations are completeand to find out if any risk factors for the sideeffects of steroids can be anticipated andminimized. Guidance on weight control forexample might be required.

HEART AND BREATHING MUSCLES: Typically,problems with the heart and breathingmuscles are not likely to be present at thisstage, but surveillance should be built into the regular follow-up clinic visits to establishthe baseline (what is ‘normal’ for your son).Cardiac monitoring is recommended atdiagnosis and then every two years up to age10. After the age of 10, monitoring should bemore frequent. It is also important that theboy has pneumococcal and influenzavaccinations (Section 7).

Late ambulatory

In the LATE AMBULATORY stage, walkingbecomes increasingly difficult and there aremore problems with climbing stairs andgetting up from the floor.

LEARNING AND BEHAVIOR: Continuedsupport from professionals will be necessaryto help with any learning and behavior issues,and specific help may be needed to addresscoping strategies for dealing with the loss of ability to walk (Section 10).

PHYSICAL THERAPY: Rehabilitation input willcontinue to focus on range of movement andindependence (Section 5). If joint tightnessbecomes too much of a problem for physicaltherapy interventions, assessment and inputfrom orthopedic specialists may be necessary.It is important to make sure that there areappropriate wheelchairs with supportiveseating to promote continued independenceand comfort.

STEROIDS: Ongoing management of steroidtreatment is important at this stage, withattention to the specific regime and dose used(Section 4) as well as attention to side effects.

06Twice yearly assessments to monitor strengthand function are important. Continuedattention to weight control needs to take intoaccount any tendency to be under or overweight with appropriate intervention if thereis a problem (Section 9).

HEART AND BREATHING MUSCLES: From arespiratory and cardiac point of view (Sections7 and 8 respectively), the low risk of obviousproblems remains but ongoing assessment ofthe heart and breathing muscles is necessary.Echocardiogram and other types of testsshould be done annually from the age of 10.The physician will recommend interventions if there are any changes observed on theechocardiogram.

Early non-ambulatory

In the EARLY NON-AMBULATORY phase theboy needs to use a wheelchair. To start withhe may be able to wheel the chair himself andtypically his posture is still good (Section 5).

LEARNING AND BEHAVIOR: Despite thebackdrop of the condition progressing, anincreasing emphasis on independence isnecessary to encourage normal participation inschool and fun activities through adolescence.

PHYSICAL THERAPY: Attention to tightness in the upper limbs (shoulders, elbows, wrist andfingers) becomes very important, as does theneed for supporting equipment to help keepyour son standing. Spinal curvature (scoliosis) isseen much less often with the widespread useof steroids, but monitoring for this is still veryimportant following the loss of ambulation. In some cases scoliosis progresses quite rapidly,often over a period of months (Section 6).Orthopedic input may also be needed to dealwith problems with foot posture which cancause pain or discomfort and limit the choice of footwear.

STEROIDS: Maintenance of steroid treatmentcontinues to be an important part of

management in this phase (Section 4) whetherstarted previously and continued into thisphase or started at this stage.

HEART AND BREATHING MUSCLES:Monitoring of cardiac function at yearlyintervals is still essential and any deteriorationshould be treated promptly (Section 8).Respiratory function is likely to begin to declineafter loss of independent walking and a stagedseries of interventions to help with breathingand to aid with coughing needs to beintroduced (Section 7).

Late non-ambulatory

In the LATE NON-AMBULATORY phase, upper limb function and maintenance of good posture is increasingly difficult andcomplications are more likely.

PHYSICAL THERAPY: It is important to discusswith the physical therapist what types ofequipment will best support independenceand participation. Other adaptations may beneeded to help with activities such as eating,drinking, toileting and transferring to andturning in bed.

STEROIDS: Decisions related to steroidregimens, nutrition and weight managementare reviewed and discussed with the careteam.

HEART AND BREATHING MUSCLES: Twiceyearly monitoring of heart and lung function is recommended and often more intensiveinvestigations and interventions may need to be implemented.

Many young men with DMD live fulfillingadult lives. It is important to proactively planfor a life as a supported but independent adultwith all of the opportunities and challengesthat this entails.

The following sections deal in turn with theten different domains of care for DMD asdescribed in Figure 1.

07

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Figure 1The different areas of carerequired at each stage of DMD

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11

Care at diagnosis

The specific cause of a medical disorder iscalled the diagnosis. It is very important toestablish the exact diagnosis when DMD issuspected by your physician. The aim of careat this time should be to provide an accuratediagnosis as quickly as possible. With promptdiagnosis, everyone in the family can beinformed about the general course of DMD,provided with genetic counseling and told of treatment options. Appropriate care can be put in place and ongoing support andeducation can be provided to the family.Ideally, diagnosis should be performed by aphysician who is a neuromuscular specialistand who can assess the child clinically andcan initiate and interpret investigationsproperly. Family follow-up and supportfollowing diagnosis will often besupplemented by support from geneticcounselors.

When to suspect DMD

The first suspicions are usually raised by oneof the following three signs (even when thereis no history of DMD in the family):

PROBLEMS WITH MUSCLE FUNCTION: It isoften a family member who notices somethingis wrong. Boys who have DMD walk later thanother boys their own age. They have enlargedcalf muscles and have trouble running,jumping or climbing stairs. They fall easily andmay have a tendency to walk on their toes.They may also have a speech delay. One of theclassic signs of DMD is what is known as the“Gowers’” maneuver or sign, where the boyhas to use his hands and arms to “walk” up hisbody in order to push himself to an uprightposition. This is due to weakness in the hipsand thigh muscles (see Figure 2).

HIGH LEVELS OF THE MUSCLE PROTEINCREATINE KINASE (CK) in a blood test. Thefinding of a high CK level should prompt anurgent referral to a neuromuscular specialistfor confirmation of the diagnosis. High levels of CK are seen in people with other kinds of muscle conditions and a high CK alone is not enough to confirm DMD.

HIGH LEVELS OF THE “LIVER ENZYMES” ASTAND ALT in a blood test. High levels of theseenzymes in the blood are often associatedwith liver disease, but muscular dystrophiescan also cause this elevation. Unexpectedlyhigh levels of these enzymes without anothercause should raise the suspicion that the CKwill be high as well and so a diagnosis ofmuscular dystrophy might be suspected. A liver biopsy is not recommended.

DELAYED SPEECH DEVELOPMENT: Childrenwith DMD often also have some delay in theirspeech development and sometimes that is thesymptom that is first noticed (see Section 10).

3 Diagnosis

IMPORTANT FACTS TO REMEMBER:

1. Getting a diagnosis is an important step sothat you and your physician can make plansfor your son’s care.

2. Physicians cannot diagnose DMD using only a CK test. If your son has elevated CKlevels, your physician will need to confirmthe diagnosis using genetic testing.

3. YOU ARE NOT ALONE. Reach out to yourphysician to answer any questions you mayhave and seek consultation from a geneticcounselor.

4. This is also a time when contact with asupport group or advocacy organizationcan be of particular help. You can find lists of contacts at www.treat-nmd.eu/dmdpatientorganisations

10 Figure 2 - Gowers' Maneuver

Confirming the diagnosis of DMD

DMD is a genetic disease – it is caused by amutation or change in the DNA for a genecalled the dystrophin or DMD gene. Thediagnosis has to be confirmed by genetictesting usually on a blood sample, but othertests are also sometimes performed as well.Some background about genetic testing isprovided in Box 1.

The tests

1) GENETIC TESTINGGenetic testing is always necessary even ifDMD is first confirmed by muscle biopsy.Different types of genetic tests are able toprovide specific and more detailed informationabout the change in the DNA or mutation.Having genetic confirmation of the diagnosis is important for several reasons. It will help to determine if the boy may be eligible for anumber of mutation-specific clinical trials andwill help the family with decisions related toprenatal diagnosis and future pregnancies.

Once the exact mutation or change in theDNA in the dystrophin gene is known,mothers should be offered the opportunity for genetic testing to check whether they are carriers or not. This information will beimportant for other female family memberson the mother’s side (sisters, daughters, aunts,cousins) to understand if they may be carriersas well.

Genetic testing and a referral to a geneticcounselor will help the family understand theresults of the testing and the potential impacton other family members (see Box 1).

2) MUSCLE BIOPSY ANALYSIS Your physician may recommend a musclebiopsy (taking a small sample of muscle foranalysis). The genetic mutation in DMD means the body cannot produce the proteindystrophin, or doesn’t produce enough of it.Tests on the muscle biopsy can provide

information on the amount of dystrophinpresent in the muscle cells (see Figure 3).

If confirmation of the diagnosis has alreadybeen achieved by genetic testing, a musclebiopsy may not be required. However, at somecenters, the diagnosis of DMD may be madeby muscle biopsy analysis. Genetic testingafter a positive biopsy diagnosis of DMD is stillessential to determine the specific change inthe DNA or genetic mutation causing DMD.

There are two types of tests normallyperformed on a muscle biopsy. They areimmunocytochemistry and immunoblottingfor dystrophin. These tests are done todetermine the presence or absence ofdystrophin and can help to distinguish DMDfrom a milder form of the condition.

123) OTHER TESTSIn the past, the tests known aselectromyography (EMG) and nerveconduction studies (needle tests) have been atraditional part of the assessment of a childwith a suspected neuromuscular disorder. The experts agree that these tests are NOTappropriate or necessary for the evaluation of DMD.

13

Why genetic confirmation isimportantGENETIC COUNSELING AND CARRIER TESTING:

• Sometimes the genetic mutation causing DMDarises by chance in the boy. This is considered aspontaneous mutation. In other cases, it hasbeen passed on by the boy’s mother.

• If the mother has the mutation, she is called a“carrier”, and she can pass the genetic mutationon to her other children. The boys she passes iton to will be affected by DMD, while the girlswill be carriers themselves. If the mother istested and is found to have the mutation, shecan make informed decisions about futurepregnancies, and her female relatives (sisters,aunts, daughters) can also be tested to see ifthey are also at risk of having a boy with DMD.

• Even when a woman is not a carrier, there is asmall risk to future pregnancies because themutation may occur in her ova or egg cells. Thisis called “germ line mosaicism”.

• A carrier also has a small risk of developing aweak heart or even leg weakness later in life.Knowing carrier status helps to identify this riskso the woman can get proper advice.

• You should have access to a genetic counselorwho can explain all this to you in more detail.

ELIGIBILITY FOR CLINICAL TRIALS: There are anumber of clinical trials underway in DMD that aretargeted to certain types of mutations. Genetictesting is important to understand whether yourboy is eligible to participate in these trials. To helpphysicians find the boys who might be eligible, youshould register in a patient registry.

The most important question you need to haveanswered is whether the genetic testingperformed was up to currently acceptedstandards, allowing the exact mutation to bedefined. If it was not, then further testing mightbe required. You should discuss this with yourphysician. The exact mutation is also needed toregister with one of the DMD registries. You canfind details of the kinds of tests that might bedone and how effective they are at detecting theabsolute detail of the mutation in the main document.

All of the national patient registries for DMD acrossthe world are listed at:www.treat-nmd.eu/patientregistries.

Please see this website for more details.

NORMAL DMD

Figure 3Muscle biopsy; Left: normal muscle showingdystrophin round the fibres, Right: dystrophicmuscle with absent dystrophin.

Box 1

What assessments should be done and why

Your son should have regular checkups with a specialist physician who has the expertize to monitor how things are going and tounderstand if there is anything unusual thatmight need additional evaluation. This isimportant in order to make decisions aboutnew treatments at the most appropriate timeand to anticipate and prevent problems to themaximum extent possible. It is recommendedthat your son sees the physician every 6 months and the specialist physical therapistand/or occupational therapist about every 4 months if possible.

Tests used in different clinics to followindividuals with DMD may vary. The mostimportant thing is that there is regular reviewso that interventions can be properlymonitored. This regular assessment shouldinclude tests that help show how thecondition is progressing, including:

STRENGTH: Strength may be measured in anumber of different ways to see if the forcethat can be generated at specific joints ischanging.

RANGE OF JOINT MOTION: This is done tomonitor if contractures or joint tightening is developing and to help to guide whatstretches or interventions will be most helpful.

TIMED TESTS: Many clinics routinely timeactivities such as the time to get up off thefloor, time to walk a certain distance, and timeto climb several steps. This gives importantinformation on how the condition is changingand how it is responding to treatment.

MOTOR FUNCTION SCALES: There are a largenumber of different scales, but your clinicshould routinely use the same one to monitor

the condition in a systematic way. Differentscales may be needed at different times.

ACTIVITIES OF DAILY LIVING: This allows theteam to tell if some additional help might beneeded to assist independence.

Drug treatments for musclesymptoms

There is a lot of research happening at themoment in the area of new drugs for DMD. In this document the experts only gaverecommendations where there is alreadysufficient evidence for a treatment. Theserecommendations will change in future whennew evidence (such as the results of clinicaltrials) becomes available. The guidelines willbe reviewed as new results become available.

Although it is expected that in future a widerrange of treatment options will be available,at the present time, the only drug treatmentfor the musculoskeletal symptoms of DMDthat the experts agreed there was sufficientevidence to be able to recommend is steroidtreatment. Steroids are discussed in detail in

this section. Drug treatments for other specificsymptoms of the disease, such as heartproblems, are discussed later.

Steroid treatment – a step by step guide

Steroids are used in many other medicalconditions and there is a lot of experience intheir use worldwide. There is no doubt theycan benefit many boys with DMD but thisbenefit needs to be balanced with proactivemanagement of possible side effects. Use ofsteroids is very important in DMD and shouldbe discussed with all families early.

THE BASICS• Steroids (also called glucocorticoids or

corticosteroids) are the only drugs knownto slow the decline in muscle strength andmotor function in DMD. The goal of steroiduse is to help the child walk independentlyfor longer to allow enhanced participationand to later minimize breathing, heart andorthopedic problems. They can also reducethe risk of scoliosis (curvature of the spine).

• Prevention and management of steroidside effects needs to be proactive andanticipatory. Interventions should be putin place EARLY in an effort to preventproblems and to make sure they do notbecome severe. Side effects associated withsteroid use vary and are listed in Table 1.

STARTING AND STOPPING STEROIDS • The optimal time for starting steroid

treatment is when motor function is in a“plateau phase” – when the boy’s motorskills have stopped improving, but have notyet started to get worse. This is normallysometime between the age of 4-6 years. It isnot recommended to start steroids inchildren who are still gaining motor skills,especially if they are under 2 years of age.

• The recommended national vaccinationschedule should be complete before

steroid treatment is started, and varicella(chicken pox) immunity should beestablished.

• Starting steroid treatment in boys/youngmen who are no longer walkingindependently is a matter for individualdecision and needs to be discussed withthe physician, taking into considerationthe effect of pre-existing risk factors. Inboys who used steroids when they werewalking, many experts recommendcontinuation of medication after loss ofambulation. The goal in the non-ambulatoryperson is to preserve upper limb strength,slow the progression of scoliosis, and delaythe decline of respiratory and cardiacfunction.

4 Neuromuscular management - maintaining strength and function

IMPORTANT FACTS TO REMEMBER:

1. Because your son does not have dystrophin,his muscles will gradually get weaker.

2. Some types of exercise and getting tiredcan make muscle damage worse.

3. The physician understands the progressionof muscle weakness and can help your songet ready for the next step.

4. It is important for the physician to knowhow your son’s muscles are working so thatthey can start the right therapy as early aspossible.

IMPORTANT FACTS TO REMEMBER:

1. Steroids are the only medicines known tohelp slow down muscle weakness.

2. Always tell physicians and other healthcareproviders that your son is taking steroids. It is especially important if he is havingsurgery or has an infection or injurybecause steroids can suppress the immunesystem.

3. Your son should never stop taking steroidssuddenly.

4. Your son should have regular visits with a physician who is skilled in managingsteroids. The physician will explain possibleside effects and tell you if your son is at riskof developing them.

14 15

The different steroid regimes

One of the potentially confusing things inDMD care is that different physicians anddifferent clinics often prescribe differentregimens of steroids, which means you willfind information about different drugs anddifferent regimes. These guidelines have triedto establish a clear route to use steroidseffectively and safely based on regularassessments of function and side effects (see Box 2).

• Prednisone (prednisolone) and deflazacortare the two types of steroids that are mainlyused in DMD. They are believed to worksimilarly. Neither one is clearly better.Planned trials of these drugs are importantand should help us understand them betterin future.

• The choice of which steroid to use dependsupon availability in a particular country, thecost to the family, the way the drug is taken,and the perceived side effects. Prednisonehas the advantage of being inexpensive and is available in both tablet and liquidformulation. Deflazacort may be preferredto prednisone for some individuals becausethere may be a slightly lower risk of weight gain.

• Starting with daily use of a steroid waspreferred by the experts to the alternativeregimes. Data from ongoing and futurestudies may modify this recommendation.

Doses for starting andmaintaining steroids• The recommended starting dose of prednisone

is 0.75 mg/kg/day and that of deflazacort is 0.9 mg/kg/day, given in the morning. Somechildren experience short-lived behavioral sideeffects (hyperactivity, mood swings) for a fewhours after the medication is given. For thesechildren, administration of the medication in the afternoon may alleviate some of thesedifficulties.

• For ambulatory individuals, the dosage iscommonly increased as the child grows until hereaches approximately 40 kg in weight. Themaximum dose of prednisone is usually cappedat approximately 30 mg/day, and that ofdeflazacort at 36 mg/day.

• Non-ambulatory teenagers maintained on long-term steroid therapy are usually above 40 kg inweight and the prednisone dosage per kg isoften allowed to drift down to the 0.3 to 0.6mg/kg/day range. While this dosage is less thanthe approximate 30 mg cap, it demonstratessubstantial benefit.

• Deciding on the maintenance dose of steroids is a balance between growth, how good theresponse to steroids is and the burden of sideeffects. So this decision needs to be reviewed atevery clinic visit based on the result of the testsdone and whether or not side effects are aproblem that can’t be managed or tolerated.

• In boys on a relatively low dosage of steroids(less than the starting dose per kg body weight)who start to show functional decline, it isnecessary to consider a “functional rescue”adjustment. The dosage of steroids is increasedto the target and the individual is then re-evaluated for any benefit in approximately twoto three months.

• There is no consensus on the optimal steroiddosage if initiated in the non-ambulatoryindividual. Nor is it known how effective steroid treatment is in preventing scoliosis or instabilizing cardiac or respiratory function in thissetting. This issue warrants further study.

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Box 2

Steroid management and side effects (Boxes 3 and 4 and Table 1)

Attentive management of steroid-related side effects is crucial once a boy has startedon long-term steroid therapy. While steroidtherapy is currently the mainstay ofmedication therapy for DMD, it should not be undertaken casually by the physician orfamily, and should be undertaken only byphysicians with appropriate expertize.

Management of steroidmedication• A dose reduction of approximately 1/4 to 1/3 is

suggested if intolerable or non-manageableside effects occur, with a reassessment byphone or clinical visit in one month to assesscontrol of side effects.

• If a daily dosing schedule results inunmanageable and/or intolerable sideeffects that do not improve when the dose is reduced, then it is appropriate to change to an alternative regime.

• Steroid therapy should not be abandonedeven if side effects are NOT manageableand/or tolerable until at least one dosagereduction and change to an alternativeregime have been pursued. Thisrecommendation holds for both ambulatoryand non-ambulatory individuals.

• Should adjustments to the steroid dosingand/or schedule regimens prove ineffectivein making any significant side effectssufficiently manageable and tolerable, then itis necessary to discontinue steroid therapy.These decisions need to be made individuallyin partnership with the child and family.Steroids should never be stopped suddenly.

Other drugs and dietarysupplementsThe experts considered a range of other drugs andsupplements that are known to be used in somecases for DMD treatment. They reviewed publisheddata on these substances to see if there wasenough evidence for their safety and efficacy to be able to make recommendations.

The experts concluded the following:

• The use of oxandrolone, an anabolic steroid, is not recommended.

• Safety in the use of Botox has not been studiedfor the treatment or prevention of contracturesin individuals with DMD and is notrecommended.

• There was no support for the systematic use ofcreatine. A randomized controlled trial of

creatine in DMD did not show a clear benefit. If a person is taking creatine and has evidence ofkidney problems, it is necessary to discontinuethis supplement.

• No recommendations can be made at this timeabout other supplements or other drugs that aresometimes used in DMD treatment, including co-enzyme Q10, carnitine, amino acids (glutamine,arginine), anti-inflammatories/anti-oxidants (fishoil, vitamin E, green tea extract, pentoxifylline),and others including herbal or botanical extracts.The experts concluded that there was notenough evidence in the published literature.

• The experts agreed that this is an area whereadditional research is needed. Activeinvolvement of families in activities that developfurther knowledge, such as patient registries andclinical trials, was encouraged.

Steroids are the only drugs that the expertshave agreed can be recommended. Thoughsome of the drugs mentioned in Box 4 arequite widely used, there is just not enoughevidence to say whether these othersupplements really work or not. It is importantto discuss all medication with your physicianbefore you think about adding or stoppingmedication.

Table 1 (overleaf) summarizes the main sideeffects of steroids that should be monitoredand useful interventions. Factors to take intoaccount in maintaining or increasing dose areresponse to therapy, weight and growth, andwhether side effects are present andmanageable.

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Box 3 Box 4

Table 1STEROID SIDE EFFECTS: RECOMMENDED MONITORING AND INTERVENTION

Some of the more common long-term side effects of high-dose steroid administration in growingchildren are listed here. It is important to note that different people will have very differentresponses to steroids. The key to successful steroid management is to be aware of the potentialside effects and work to prevent them or reduce them where possible. Reduction in steroid doseis necessary if side effects are unmanageable or intolerable. If this is unsuccessful, then furtherreduction or a change to another dosing regimen is necessary before abandoning treatmentaltogether.

STEROID SIDE EFFECT COMMENT AND RECOMMENDEDMONITORING

POINTS FOR YOU TO THINK ABOUT ANDTO DISCUSS WITH YOUR PHYSICIAN

General and cosmeticWeight gainObesity

Dietary advice needs to beprovided to all families beforestarting a steroid regimen. Theyshould be warned that steroidsincrease appetite.

It is important that the wholefamily eat sensibly in order toprevent excess weight gain. Lookfor advice for the entire familyregarding diet and nutrition.

Cushingoid features(“moon face”)

Fullness in the face and cheeksbecomes more noticeable overtime.

Careful monitoring of diet andrestricting sugar and salt intake will help with weight gain and may minimize Cushingoid features.

Excessive growth of hairon the body (hirsutism)

Clinical examination. This is not usually severe enough to warrant a change in medication.

Acne, Tinea, Warts More noticeable in teenagers. Use specific treatments (topicalprescription) and do not rush tochange the steroid regimen unlessthere is emotional distress.

Growth retardation Monitor height at least every 6months as part of general care(height tends to be small in DMDeven without steroid treatment.)

Ask if your son is concerned abouthis short stature. If so, you shoulddiscuss with your physician if heneeds an endocrine check up.

STEROID SIDE EFFECT COMMENT AND RECOMMENDEDMONITORING

POINTS FOR YOU TO THINK ABOUT ANDTO DISCUSS WITH YOUR PHYSICIAN

Delayed puberty Monitor development.

Identify any family history ofdelayed sexual maturation.

Encourage discussion aboutpuberty. Ask your son if he hasconcerns about any delay.

Discuss with your physician aboutgetting an endocrine evaluation ifyou or your son are concerned.

Adverse behavioralchanges

(There is a lot moreinformation about behaviorin Section 10 of theserecommendations)

Identify any baseline mood,temperament, and ADHD issues. Beaware that these often temporarilyworsen in the initial six weeks onsteroid therapy.

Consider if baseline issues shouldbe treated prior to starting steroidtherapy, e.g. ADHD counseling orprescription.

It may help to change the timing of steroid medication to later in the day – discuss this with yourphysician, who may also consider a behavioral health referral.

Immune / adrenalsuppression

Be aware of risk of seriousinfection and the need to promptlyaddress minor infections.

Inform all medical personnel thatthe child is on steroids, and carrysteroid alert card.

Ensure that the steroid is notstopped abruptly.

It is very important that someoneon chronic steroids does not misstheir dose for more than 24 hoursat the most, especially if they arealso unwell.

Obtain chicken pox immunizationprior to starting steroid therapy; ifnot done seek medical advice if incontact with chicken pox.

If there is a regional problem withTB, there may need to be specificsurveillance.

Discuss with your physician howyou would cope if there was abreak in taking steroids, forexample substituting prednisoneequivalent if deflazacort istemporarily unavailable, or howyou might need IV coverage duringillness or fasting.

Discuss use of intravenous (IV)“stress dose” methylprednisolonecoverage for surgery or majorillness.

Give IV coverage if fasting.

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STEROID SIDE EFFECT COMMENT AND RECOMMENDEDMONITORING

POINTS FOR YOU TO THINK ABOUT ANDTO DISCUSS WITH YOUR PHYSICIAN

Hypertension Monitor blood pressure (BP) ateach clinic visit

If BP is elevated, reducing saltintake and weight reduction can beuseful first steps.

If ineffective, your physician willneed to consider possible ACE orbeta-blocker medication.

Glucose intolerance Test urine for glucose with dipsticktest at clinic visits.

Enquire about increased passage ofurine or increased thirst.

Blood tests may be needed if urinetests are positive.

Gastritis/gastresophageal reflux

Look out for reflux symptoms(heartburn).

Avoid non-steroidal antiinflammatory drugs (NSAIDs) - suchas aspirin, ibuprofen, naproxen.

Drugs and antacid can be used ifsymptoms occur.

Peptic ulcer disease Report symptoms of stomach painas this can be a sign of damage tothe lining of the stomach.

Stool can be checked for blood ifanemic or suggestive history.

Avoid NSAIDs (aspirin, ibuprofen,naproxen).

Drugs and antacid can be used ifsymptomatic.

Seek gastrointestinal consultation.

Cataracts Annual eye exam. Consider switching fromdeflazacort to prednisone ifcataracts evolve that affect vision.

Seek ophthalmology consultation.Cataracts will only need to betreated if they interfere with vision.

STEROID SIDE EFFECT COMMENT AND RECOMMENDEDMONITORING

POINTS FOR YOU TO THINK ABOUT ANDTO DISCUSS WITH YOUR PHYSICIAN

Bone demineralizationand increased fracturerisk

Take careful fracture history.

Yearly DEXA to monitor bonedensity.

Yearly vitamin D blood level(ideally late winter in seasonalclimates) and supplement withvitamin D3 if levels are low.

Dietician assesses calcium andvitamin D intake.

Vitamin D supplements may beneeded depending on level inblood. Recheck vitamin D levelagain after 3 months on therapy.

Weight-bearing activities can behelpful.

Make sure that calcium intake isgood in the diet and if notsupplements may be needed.

Myoglobinuria

(Urine looks coca-colacolored because itcontains breakdownproducts of muscleproteins. This needs tobe tested for in ahospital lab.)

Enquire about abnormal colorationof urine after exercise – urinetesting.

Avoid vigorous exercise andeccentric exercises, such asrunning downhill or trampolining.

Good fluid intake is important.

Kidney investigations are needed ifit carries on.

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People with DMD need access to differenttypes of rehabilitation managementthroughout their lives. Much of this will be delivered by physical therapists andoccupational therapists, but other people may also need to help, including rehabilitationspecialists, orthotists, providers ofwheelchairs and other seating. Orthopedicsurgeons may also be involved.

Management of muscle extensibility and joint contractures is a key part ofrehabilitation management.

The goal of stretching is to preserve function and maintain comfort. The programof stretching will be monitored by thephysical therapist but needs to become part of the family’s daily routine.

There are many factors in DMD thatcontribute to the tendency for joints to gettight or “contracted”. These include themuscle becoming less elastic due to limiteduse and positioning or because the musclesaround a joint are out of balance (one strongerthan another). Maintaining good range ofmovement and symmetry at different joints is important. This helps to maintain the bestpossible function, prevent the development of fixed deformities, and prevent pressureproblems with the skin.

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5 Rehabilitation management - physical therapy and occupational therapy

Management of muscleextensibility and jointcontractures• The key contact for management of joint

contractures is your physical therapist. Ideallyinput from a local physical therapist will bebacked up by a specialist physical therapistabout every 4 months. Stretching should beperformed at least 4-6 times each week andshould become part of the daily routine.

• Effective stretching to counteract developmentof contractures may require different techniqueswhich your physical therapist will show you,including stretching, splinting and standingdevices.

• Regular stretching at the ankle, knee, and hip isimportant. Later on, regular stretching for thearms becomes necessary, especially the fingers,wrist, elbow and shoulder. Additional areas thatrequire stretching may be identified on individualexamination.

• Night splints (ankle-foot orthoses or AFOs) canbe used to help control contractures in the ankle.These need to be custom-made and not provided‘off the shelf’. After the loss of ambulation,daytime splints may be preferred, but daytimesplints are not recommended for boys who arestill walking.

• Long leg splints (knee-ankle-foot orthoses orKAFOs) may be useful around the stage whenwalking is becoming very difficult or impossible.KAFOs can be useful to help control jointtightness and to prolong ambulation and delaythe onset of scoliosis.

• Standing programs (in a standing frame or powerchair with stander) are recommended afterwalking becomes impossible.

• Resting hand splints are appropriate forindividuals with tight long finger flexors.

• Surgery can be offered in some situations in aneffort to prolong the period of walking.However, this approach must be strictlyindividualized. More information about thedifferent options is available in the maindocument.

Wheelchairs, seating and other equipment

• During the early ambulatory stage, ascooter, stroller or wheelchair may be usedfor long distances to conserve strength.When your son starts using a wheelchair forlonger periods, it becomes more importantthat posture is carefully looked at, andcustomization of the chair is usuallynecessary.

• As difficulty with walking increases, it isrecommended that a power wheelchair isprovided sooner rather than later. Ideally,the initial power wheelchair should beadapted and customized to optimizecomfort, posture and symmetry. Someexperts also recommend a power standingfeature if available.

• With time, arm strength becomes more of an issue. Physical therapists andoccupational therapists will be helpful inrecommending assistive devices to helpmaintain independence. It is best to thinkproactively about the kind of equipmentthat will best support independence andparticipation and plan ahead to provide it in as timely a manner as possible.

• Additional adaptations in the lateambulatory and non-ambulatory stages maybe needed to help with getting upstairs andtransferring, eating and drinking, turning inbed and bathing.

Pain managementIt is important to ask boys/young men with DMD ifpain is a problem so that it can be addressed andtreated properly. Unfortunately, very little iscurrently known about pain in DMD. More researchis needed. If your son is in pain you need to talk toyour physician and explain to them that this is aproblem.

• For effective pain management, it is importantto determine why there is pain so thephysicians can provide appropriate interventions.

• As a lot of pain results from problems withposture and difficulty getting comfortable,interventions include provision of appropriateand individualized orthoses (braces), seating,bedding, and mobility as well as standard drugtreatment approaches (e.g. muscle relaxants,anti-inflammatory medications). Interactionswith other medications (e.g. steroids and non-

steroidal anti-inflammatory drugs [NSAIDs]) andassociated side effects, especially those thatmight affect cardiac or respiratory function,should be considered.

• Rarely, orthopedic intervention might beindicated for pain that cannot be managed in anyother way but that might respond to surgery.Back pain, especially in people using steroids,means the physicians should check carefully forvertebral fractures, which respond well tobisphosphonate treatment.

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Box 5

Box 6

People with DMD who are not treated withsteroids have a 90% chance of developingprogressive scoliosis (a sideways curvature of the spine that gets worse as time goes on).Daily steroid treatment has been shown toreduce the risk of scoliosis or at least delay its onset.

Proactive management of the risk of scoliosisrequires:

Surveillance

• Spinal care should include monitoring forscoliosis. This is done by clinicalobservation throughout the ambulatoryphase and with a spinal X-ray only ifscoliosis is observed. In the non-ambulatoryphase, clinical assessment for scoliosis isessential at each clinic visit.

• Spinal radiography (X-ray) should be doneas a baseline assessment around the timeof becoming wheelchair-dependent.Special X-rays getting two views of the fullspine are needed. Follow up X-rays shouldbe done at least once per year if there is aproblem. Gaps of greater than one yearbetween X-rays have the risk of missing aworsening of scoliosis. After growth hasstopped X-rays are only needed if there isany change clinically.

Prophylaxis (preventive measures)

• Attention to posture at all times:prevention of asymmetrical contracturesin boys who are still walking, properseating system in the wheelchair givingsupport of spinal and pelvic symmetry andspinal extension. Spinal bracing is notappropriate to try and delay surgery butmay be used if surgery cannot be done or isnot the chosen option.

6 Orthopedic management - help with bone and joint problems

IMPORTANT FACTS TO REMEMBER:

1. Boys and young men with DMD have weakbones, especially if they are taking steroids.

2. It is important for your son to have theright amount of calcium and vitamin D tohelp keep his bones strong.

3. The physician should watch your son’sspine closely after he stops walking,especially while he is still growing, asscoliosis can change quickly.

4. Key to success of spinal surgery, if it isneeded, is the identification of anexperienced surgeon and proper attentionto the breathing muscles and heart.

5. If your son has back pain he should see thephysician.

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Treatment

• Surgery with posterior spinal fusion isindicated when the degree of the curve(known as the Cobb angle) is greater than20° in boys who have not yet stoppedgrowing and who are not taking steroids.The aim of surgery is to preserve the bestpossible posture for comfort and function.When boys are taking steroids, there is lessrisk of deterioration and the decision toproceed to surgery can be left until theCobb angle is greater than 40°.

• It is important to discuss what type ofoperation is needed with your surgeon andexpress any concerns you may have.

Bone health management

• Bone health is important in both theambulatory and non-ambulatory phases ofDMD. Boys with DMD at all ages have weakbones, especially if they are taking steroids.They have a lower bone mineral density andare at increased risk of fractures (brokenbones) compared to the general population.

Long bone fracture management

• A broken leg can be a significant threat to the continued ability to walk. This is why treatment with surgery should beconsidered to allow the boy with DMD toget back up on his feet as soon as possible.If a fracture does occur, make sure that yourphysical therapist is notified.

• If a boy who is still walking breaks his leg, internal fixation (that is surgery tostabilize the break as quickly as possible)is needed to resume walking and to havethe greatest possible chance to maintainambulation.

• In boys who are no longer walking, a brokenleg can be safely treated by splinting orcasting, taking into account the functionalposition of the limb and possibledevelopment of contractures.

Bone health in general

• Steroid treatment is known to add to the risk of low bone density and is alsoassociated with the risk of fractures of thespinal vertebrae. Fractures of the vertebraeare not usually seen in non-steroid treatedboys. Bone density may need to be assessedwith blood tests, bone scans and other X-rays (see Box 7). This is an area wherefurther research is needed to establish theparameters for best practice.

Usually boys do not have trouble breathing orcoughing while they are still walking. Becausethe breathing muscles become affected, asboys with DMD get older they are at risk ofchest infections, often due to an ineffectivecough. Later on they develop problems withtheir breathing when sleeping. When they areolder, they may require help with breathingduring the day as well. As this is a stagedprogression of problems, a planned andproactive approach to respiratory care is possible based around appropriatesurveillance, prophylaxis and interventions.The team must include a physician andtherapist with skill in looking after thedelivery of non-invasive ventilation andassociated techniques for increasing theamount of air that can enter the lungs (lungvolume recruitment), and manual andmechanically assisted cough.

Box 7Bone health managementUNDERLYING FACTORS FOR POOR BONEHEALTH ARE:

• Decreased mobility

• Muscle weakness

• Steroid therapy

POSSIBLE INTERVENTIONS:

• Vitamin D – needed if there is a realdeficiency, supplement should be consideredin children.

• Calcium – intake is best in the diet, butsupplementation should be considered if dietis not adequate with advice from a dietician.

• Bisphosphonates – IV bisphosphatesrecommended for vertebral fractures.

7 Pulmonary management - looking after the breathing muscles

IMPORTANT FACTS TO REMEMBER:

1. Keep a copy of your son’s latest breathingtests to show any physician who takes careof him.

2. Your son should never be given inhaledanesthesia or the drug succinylcholine.

3. Your son’s lung function should be checkedbefore surgery. It is good to pick up on silentproblems so that they can be treatedpromptly.

4. Your son will need help with coughing andantibiotics if he has a chest infection.

5. Symptoms of hypoventilation and weakcough should be monitored for and bereported to the medical caregivers so thattherapy can be initiated.

6. If your son’s oxygen level drops when he isill or injured, the physician must be verycareful giving him oxygen because this cancause a situation where his own urge tobreathe is decreased.

30 31

Surveillance

• While a boy with DMD is still walking,minimal assessment of pulmonary function(such as measurement of forced vitalcapacity [FVC] at least annually) allows the child to become familiar with theequipment and the team to assess themaximum respiratory function achieved.

• The main emphasis of pulmonaryassessment is after the loss of independentwalking, and should include FVCmeasurement and peak cough flow. Othermeasures may also be useful, includingstudies of oxygen levels during sleep, andshould be introduced as time goes by.Assessment frequency will depend on thestage of the condition, but at a minimumFVC measurement should be done at leastevery 6 months.

It is very important to look out for the kindsof signs that suggest your son may be havingtrouble breathing as he gets older. If youthink you are seeing any of these you need toreport them to your physician. Contact yourphysician if your son:

• is experiencing prolonged illness withapparently minor upper respiratoryinfections. For example, recovery fromcommon colds is slow, with coldsprogressing to chest congestion andbronchitis, often requiring antibiotictherapy;

• is more tired than usual;

• is short of breath, acts as if he cannot catch his breath or has difficulty finishingsentences;

• has headaches all the time or in themorning;

• is often sleepy for no reason;

• has trouble sleeping, wakes up a lot, hastrouble waking up or has nightmares;

• wakes up trying to catch his breath or sayshe can feel his heart pounding;

• has trouble paying attention.

Prevention of problems

• Immunization with pneumonia vaccine is indicated for persons two years of ageand older and may need to be repeatedaccording to local policy. Annualimmunization with influenza vaccine isindicated. Both can be given to individualstreated with steroids, though the immuneresponse to vaccination may be diminishedin those individuals. Up-to-date, detailedinformation on immunization indications,contraindications, and schedules can beobtained from various national sources. It is essential to keep up to date withvaccination policies as they can changeregularly according to new threats, such asthe emergence of H1N1 flu in 2009.

• If chest infection occurs, then in addition touse of manually and mechanically assistedcough, antibiotics should be considered.

Interventions (this requires specialexpertize)

• Interventions are dependent on diseasephase. First of all, it may be helpful to useways to increase the amount of air that canenter the lungs through deep breathing(lung inflation techniques). As DMDprogresses, coughing will become lesseffective, and ways to improve this can be very helpful, such as with manual andassisted cough techniques. With time,support will be needed initially forbreathing overnight and then later duringthe daytime (non-invasive nocturnal /daytime ventilatory support) as symptomslisted under the surveillance sectiondevelop. Support of breathing through the use of non-invasive ventilation is avery important way to maintain health.Ventilation may also be delivered via a surgically placed tube in the neck(tracheostomy tube) depending on localpractice (this is known as invasive

ventilatory support). All these interventionscan help to keep people healthy and avoidacute illnesses.

• Particular attention to the breathing isrequired around the time of planned surgery(see Section 11 regarding respiratoryconsiderations for surgery).

Box 8IMPORTANT - CAUTION• In the later stages of DMD supplemental

oxygen therapy should be used withcaution.

• While oxygen therapy can apparentlyimprove low oxygen levels, using oxygenwill mask the underlying cause, such as acollapsed lung or poor breathing.

• Oxygen therapy may reduce the drive tobreathe and lead to carbon dioxideretention.

• Manual and mechanically assisted coughand non-invasive ventilatory support arelikely to be necessary. Using oxygentherapy instead is not recommended andmay be dangerous.

• If oxygen is given, and it may sometimeshave to be, then there needs to be verycareful monitoring of the gases in the bloodand/or help with the breathing should begiven at the same time.

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The aim of cardiac management in DMD is early detection and treatment of thedeterioration of heart muscle function (usuallycardiomyopathy - involvement of heartmuscle, or rhythm problems leading, forexample, to palpitations) that commonlyaccompanies the overall progression of thedisease. As this often happens silently (that is without the development of significantsymptoms) it needs to be looked out for so it can be treated promptly. The key factors to consider in cardiac management aresurveillance and proactive management. Youneed to be sure that there is a cardiologistinvolved with the care team.

Surveillance

• Baseline evaluation of cardiac functionshould be performed at the confirmation ofthe diagnosis or at latest by the age of sixyears. Minimum evaluation should includean electrocardiogram (ECG) andechocardiogram.

• Evaluation of cardiac function shouldoccur at least once every two years untilthe age of ten. Yearly complete cardiacevaluations should begin at approximatelyten years of age or at the onset of cardiacsigns and symptoms, if earlier. If non-invasive cardiac tests show abnormalities,increased surveillance is required, at leastevery six months, and drug treatmentshould be initiated.

Treatment

• Angiotensin converting enzyme (ACE)inhibitors should be considered as first-linetherapy. Other medicines such as beta-blockers and diuretics are also appropriateand should follow published guidelines forthe management of heart failure. There is some evidence from clinical trials tosupport the prophylactic treatment ofcardiomyopathy with ACE inhibitors priorto any signs of abnormal functioning.Further studies are awaited to allow firmrecommendations in this regard.

• Abnormalities of heart rhythm should bepromptly investigated and treated. A fastheart rate is a commonly noted harmlessfeature of DMD, but can also be seen withheart problems. If it develops as a newfinding it should be investigated.

• Individuals undergoing treatment withsteroids need additional attention from the cardiovascular perspective, especiallymonitoring for hypertension (high bloodpressure). Steroid dose may requireadjustment or further treatment may needto be added (see Table 1).

8 Cardiac management - looking after the heart

IMPORTANT FACTS TO REMEMBER:

1. Your son’s heart should be checkedregularly starting from the time he isdiagnosed.

2. In DMD the heart may be already damagedbefore symptoms appear.

3. This means that your son may need to startheart medication even if he does not havesymptoms of heart problems.

4. It is good to pick up silent problems so thatthey can be treated promptly.

5. Keep a copy of your son’s latest heart teststo show any other physician who may seeyour son.

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Access to the following experts may beneeded at different stages: a dietician or nutritionist, a swallowing/speech and language pathologist, and agastroenterologist.

Nutritional management

• Thinking ahead to maintain goodnutritional status to prevent both undernutrition and overweight is essential fromdiagnosis throughout life. It is importantthat weight for age or body mass index forage is kept between the 10th and 85thpercentile on national percentile charts.Provide a well-balanced diet with a fullrange of food types. Information for thewhole family on eating a well-balanced dietcan be found from most national sources.

• Boys should be monitored regularly for theirweight and height (which can be calculatedfrom arm measurement in non-ambulatoryboys). The triggers for referral to an expertdietician/nutritionist are if a boy isoverweight or underweight, if he isexperiencing unintentional weight loss orgain, or poor weight gain, if major surgery is planned, if he has chronic constipationand/or if he has difficulty swallowing(dysphagia). Referral will also be made atdiagnosis and when starting steroids. Thediet should also be assessed for calories,protein, fluid, calcium, vitamin D, and othernutrients.

• It is recommended that people with DMDtake a daily multivitamin with vitamin Dand minerals.

• If there is weight loss, it is important to lookfor problems with swallowing. However itis important to note that complications in other systems, such as cardiac orrespiratory systems, may contribute toweight loss. If there is unexpected weightloss, it may be important to check outother areas as well.

Swallowing management

In later stages, weakness of the throat musclescan lead to swallowing problems (dysphagia),further accentuating nutritional issues. This canoften come on very gradually, meaning it canbe difficult to spot.

• Clinical and X-ray tests of swallowing are necessary when there are clinicalindicators of possible aspiration (gettingfood in the windpipe) and poor movementof the swallowing muscles (food feels like itis getting stuck in the throat). Suchindicators include unintentional weight lossof 10% or more, or insufficient weight gainin growing children, prolonged meal times(>30 minutes) or mealtimes accompanied byfatigue, drooling, coughing or choking.

• Pneumonia caused by fluid going down intothe lungs (aspiration pneumonia),unexplained decline in pulmonary function,or fever of unknown origin may be signs ofswallowing problems necessitatingassessment.

• In case of swallowing problems, a SpeechLanguage Pathologist should be involved to deliver an individualized treatment plan.The aim is to preserve good swallowingfunction.

• Gastric tube placement should be offeredwhen efforts to maintain weight and fluidintake by mouth do not help enough.Potential risks and benefits of the procedureshould be discussed carefully. A gastrostomymay be placed by endoscopic or opensurgery, taking into account anestheticconsiderations and family and personalpreference. A feeding tube provided at theright time can relieve a lot of pressure fromtrying to eat enough. Provided theswallowing muscles are OK, having a feedingtube doesn’t mean you can’t still eat the foodyou want to – just that you don’t have to relyon mealtimes to get the calories and othernutrients you need so you can enjoy thefood more.

Other areas of gastrointestinalmanagement

Constipation and gastresophageal reflux(which causes heartburn) are the two mostcommon gastrointestinal conditions seen inindividuals with DMD. Constipation typicallyoccurs at an older age and after surgery. Withincreasing survival, other complications arebeing reported, including gastric and intestinalswelling related to air swallowing due toventilator use.

• Laxatives and other medicines can beuseful. It is important that there is enoughfluid intake. Increasing fiber may makesymptoms worse especially if fluids are notincreased.

• Reflux is typically treated with appropriatedrugs. Acid blockers are commonlyprescribed to children on steroid therapy or oral bisphosphonates to avoidcomplications.

• Oral care is an important area, andalthough this was not included in thepublished International consensus on thecare and management of DMD, TREAT-NMDhave developed expert recommendationsfor oral care that are outlined in Box 9.

9 Gastrointestinal management - nutrition, swallowing and other gastrointestinal issues

IMPORTANT FACTS TO REMEMBER:

1. Your son’s height and weight should bechecked at every visit to the physician.

2. It is important for your son to have a well-balanced diet, especially one that includes theright amount of calcium and vitamin D.

3. Nutritionists and dieticians are importantmembers of your son’s healthcare team, whocan check your son’s diet and help him eatbetter.

4. Your son should be evaluated if he has signs ofswallowing problems.

5. Getting a gastrostomy tube is another optionafter trying other ways to maintain your son’sweight.

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People with DMD may have an increased riskof psychosocial difficulties, such as problemswith behavior and learning, and medical careis not complete without support forpsychosocial wellbeing. Difficulties in socialfunctioning may be due to specific challengesin particular skills, such as getting on withothers, judging social situations, andperspectives, while the consequences of DMD(such as physical limitations) may result insocial isolation, social withdrawal, andreduced access to social activities. For manyparents, the stress caused by the psychosocialproblems of the child and difficulties in gettingthem recognized and properly treated exceedsthe stress associated with the physical aspectsof the disease.

If you think your child has worries about hiscondition, openness and a willingness toanswer his questions can go a long way topreventing further problems. Boys with DMDoften understand more about their conditionthan their parents think. It is important toanswer questions openly, but be age-appropriate in your answers and just answerwhat is being asked. This can be very difficult,but the staff at your clinic can offer help andguidance about what has worked for otherfamilies, as can patient support groups.

Not everyone with DMD will havepsychosocial difficulties, but families shouldkeep an eye out for:

• Weaknesses in language development,comprehension, and short-term memory;

• Learning problems;

• Difficulty with social interactions and/ormaking friendships (i.e., social immaturity,poor social skills, withdrawal or isolationfrom peers);

• Anxiety/worry;

• Frequent arguing and temper tantrums;

• There is also increased risk ofneurobehavioral and neurodevelopmentaldisorders, including autism-spectrumdisorders, attention-deficit/hyperactivitydisorder (ADHD), and obsessive-compulsivedisorder (OCD);

• Problems may be encountered withemotional adjustment and depression.Anxiety may also be an issue and can bemade worse by deficits in mental flexibilityand adaptability (i.e. an overly-rigid thoughtprocess);

10 Psychosocial management - help with behavior and learning

IMPORTANT FACTS TO REMEMBER:

1. The psychosocial health of your son andyour family is important.

2. Your son may have a higher chance ofhaving psychosocial difficulties.

3. You and your family are at risk of someproblems such as depression.

4. The best way to manage psychosocialproblems is to identify them early and starttreatments.

5. Correct use of language may be a problem,as may continuing difficulties at school.These behaviors are often seen in DMD andcan be helped with proper assessment andinput.

6. Learning problems in DMD are notprogressive and most boys catch up whenthey receive good help.

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Oral care recommendations• Boys with DMD should see a dentist with

extended experience and detailed knowledge of the disease, preferably at a centralized orspecialist clinic. The dentist’s mission should beto strive for high-quality treatment, oral healthand wellbeing and to function as a resource forthe families and the boy’s own dentist in hishome community. This dentist should be awareof the specific differences in dental and skeletaldevelopment in boys with DMD and collaboratewith a well informed and experiencedorthodontist.

• Oral and dental care is to be based onprophylactic measures with a view tomaintaining good oral and dental hygiene.

• Individually adapted assistive devices andtechnical aids for oral hygiene are of particularimportance when the muscular strength of theboy’s hands, arms and neck begins to decrease.

Box 9

• This can also result in oppositional/argumentative behavior and temperproblems;

• In addition, increased rates of depression inparents of children who have DMDunderscore the need for assessment andsupport of the entire family.

The emphasis in psychosocial managementshould be strongly on prevention ofproblems and early intervention, as this willmaximize the potential outcome. In general,the psychosocial problems should be treatedwith the same effective, evidence-basedinterventions that are used in the generalpopulation. This means it is important to lookfor help if you think there are problems in this area.

Speech and languagemanagement – The details:• There is a well-documented pattern of speech

and language deficits in some children withDMD, including problems with languagedevelopment, short-term verbal memory, andphonological processing, as well as impaired IQand specific learning disorders. These do notaffect all children with DMD but should belooked out for and helped if they are present.

• Delay in attainment of early language milestonesis common in boys who have DMD compared tochildren of the same age. The differences ingaining and improving language may besomething that can be seen across childhood. Itis important that this problem is looked for andtreated. Evaluate and treat for delayed speechand language problems.

• Referral to a Speech Language Pathologist(SLP) for speech and language evaluation andtreatment is necessary if problems in this areaare suspected.

• Exercises for the muscles involved in speechand help with articulation are appropriate andnecessary for both young boys who have DMDwith difficulties in this area and in olderindividuals who have deteriorating oral musclestrength and/or impaired speech intelligibility.

• For older individuals, compensatory strategies,voice exercises, and speech amplifications areappropriate if it becomes difficult to understandthe person with DMD due to problems withrespiratory support for speech and vocalintensity. Voice Output Communication Aid(VOCA) assessment may be appropriate at allages if speech output is limited.

Assessments

Although the needs of each child will vary,crucial times to consider assessments includeat or near the time of diagnosis (a 6- to 12-month window for some evaluations may bebeneficial in order to allow for adjustmentfollowing diagnosis), prior to entering school,and following a change in functioning. Whilenot every clinic will have direct access to allof the assessments and interventions listed,these recommendations can serve as a guideto filling gaps in clinical staff and directingreferrals, where appropriate.

• Areas of emotional adjustment and coping,development in learning relative to age,speech and language development, thepossible presence of autism spectrumdisorders, and social support should beassessed. (A social services professional canhelp access financial resources, developsocial support networks, or provide mentalhealth support to the family as needed).

• The psychosocial wellbeing in the individualwith DMD, parents, and siblings should be aroutine part of care for DMD.

Interventions

Care and support interventions

• A care coordinator can be the crucialperson here: they can serve as a point ofcontact for families and become a trustedperson. This person needs to have sufficientknowledge and background inneuromuscular disorders to be able to meetroutine family information needs.

• Proactive intervention is essential to helpavoid social problems and the socialisolation that can occur in the context ofDMD. Examples of useful interventionsinclude increasing awareness and educationabout DMD in school and with peers,ensuring participation in appropriate sportsand camps, provision of service dogs andcontact with others via the internet andother activities.

A special individualized education planshould be developed to address potentiallearning problems and to modify activitiesthat might otherwise prove harmful to thechild’s muscles (e.g. physical education),reduced energy/fatigue (e.g. walking longdistances to/from lunch), safety (e.g.playground activities), and accessibility issues.

• Making sure the school is fully informedabout DMD is important. Share with themall the information you have and identifythe person at the school who is there tosupport children with additional needs. Aproactive approach is important to makesure that the child with DMD accesses thefull range of education he needs to developgood social interactions and prepare forfurther education and employment. So theschool needs to be on side!

• Promoting independence and involvementin decision making (in particular, as relatesto medical care) is necessary and ofsignificant importance to promoteautonomy and independence. This should

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Box 10

be part of a planned transition programfrom pediatric to adult care.

• Helping to develop social and learningskills will make it easier to find a job and bepart of normal daily life in adulthood. Boyswith DMD benefit from having support toreach their personal goals.

• Access to palliative care services isappropriate to relieve or prevent sufferingand to improve quality of life, as needed. Inaddition to pain management (Box 6),palliative care teams may also be able toprovide emotional and spiritual support,assist families in clarifying treatment goalsand making difficult medical decisions,facilitate communication between familiesand medical teams, and address issuesrelated to grief, loss, and bereavement.

Psychotherapy and druginterventions

Several well-known techniques exist to helpin various areas. These include training forparents in trying to cope with bad behaviorand conflicts, individual or family therapy andbehavioral interventions. Applied behavioranalysis may help with certain behaviorsrelated to autism.

Some children and adults may get benefit fromthe use of prescribed medicines to help withemotional or behavioral problems. Thesemedicines can be used under specializedsupervision and monitoring for depression,aggression, OCD or ADHD when theseproblems have been specifically diagnosed byspecialist physicians.

There will be a variety of situations, bothrelated to DMD (e.g. muscle biopsy, jointcontracture surgery, spinal surgery, orgastrostomy) and unrelated (e.g. acutesurgical events), where general anesthesiamay be needed. There are a number ofcondition-specific issues that need to be takeninto account for the planning of safe surgery.

• Surgery should be done in a hospitalwhere personnel involved in the operationand after care are familiar with DMD andwilling to work together to be sureeverything goes smoothly. In addition,consideration needs to be given to “stresssteroid” coverage during surgery, for peopletreated with steroids at home.

Anesthetic agents and otherconsiderations for safe operative care

• There are always risks with anesthetics andthere are special considerations in DMD toallow anesthetics to be given safelyincluding using total intravenousanesthetics and avoiding specific drugs.

• Minimizing loss of blood is importantespecially in major surgery such as spinalfusion. In this situation, the surgeon andanesthetist may decide to use specifictechniques to help with this.

• Full details are available in the maindocument.

11 Considerations for surgery

IMPORTANT FACTS TO REMEMBER:

1. There are always risks with anesthesia;however, special considerations in DMDcan allow anesthesia to be given moresafely, such as the use of a totalintravenous anesthesia technique andabsolute avoidance of the drugsuccinylcholine.

2. Proper assessments of the heart and lungsare important when planning for surgery.

3. Make sure that all physicians are properlyinformed about DMD and all interventions(medicines) your son is getting.

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Cardiac considerations

• An echocardiogram and electrocardiogramshould be performed prior to generalanesthesia. They should also be performedbefore undergoing conscious sedation orregional anesthesia if the last investigationwas more than one year previously, or ifthere had been an abnormalechocardiogram in the preceding 7-12months.

• For local anesthesia, an echocardiogramshould be performed if there had been anabnormal result obtained previously.

Respiratory considerations

• Even if someone with DMD already hasproblems with the breathing muscles,certain measures can make surgery safer,though there will still be an increased risk. A pre-operative assessment of breathingfunction in a center familiar with DMD isvery important. Pre-operative training in theuse of non-invasive ventilation and assistedcough, and specialized interventions may beneeded.

• Physical therapists should always beinvolved if someone with DMD is havingsurgery.

• Planning and proactive assessments andmanagement of risk is the key to safesurgery in DMD.

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Breathing problems

Try and keep a note of, or remember what the latest tests of breathing (e.g. forced vitalcapacity, FVC) were. This information can beuseful for the physicians assessing your son ifhe does become ill acutely.

The main risks with breathing problems comewhen FVC and coughing strength havereduced:

• Help with clearing the chest may be needed;

• It may be important to help with coughing;

• Antibiotics may be needed;

• Sometimes it may be necessary to givesupport with a ventilator;

• Risk of the breathing muscles needing extrasupport during an infection can be high inthose with borderline respiratory function.Care in the use of opiates and othersedating medication is essential, as is carein the use of oxygen without ventilationdue to the risk of rising carbon dioxide inpeople with compromised breathingmuscle strength;

• If nocturnal ventilation is already used, thenaccess to the ventilator is essential duringany acute event or intervention. For thosewho are already ventilated, the teaminvolved with the respiratory care should be involved as soon as possible.

If you have a ventilator (or similarequipment) it is a good idea to bring it with you to the hospital.

Heart function

Try and keep a note of what the latest testresults of heart function (e.g. left ventricularejection fraction, LVEF) were, and what, if any, heart medication your son is on andwhich cardiologist sees him. This will help theemergency physicians decide if it is likely thatthe problems they are seeing are due to aproblem with the heart.

• Awareness of the risk of heart rhythmproblems and cardiomyopathy isimportant.

Anesthetic risks (see Section 11) need to betaken into account at all times if surgery orsedation is needed.

If you find yourselves needing to go to thehospital in an emergency situation, there are arange of factors that should be taken intoaccount.

• The diagnosis of DMD, current medication,presence of any respiratory and cardiaccomplications and the people who areyour key medical input should be madeclear to the admitting unit.

• As many health professionals are not awareof the potential management strategiesavailable for DMD, the current lifeexpectancy and expected good quality oflife should also be explained.

Steroids

Chronic steroid use needs to be made clear.Tell the staff how long your son has beenusing steroids and if he has missed a dose. It is also important to let the physicians knowif your son used steroids in the past.

• Steroids can dampen the stress response soextra steroids may be needed if someone onchronic steroids is unwell.

• Steroids can increase the risk of stomachulceration.

• Rarely other complications can presentacutely.

Broken bones

Boys with DMD are at risk of broken bonesand breaking a leg bone can mean that it isdifficult to walk again if walking is alreadyvery difficult. Let your physical therapist andthe rest of the care team know if there is afracture so they can talk to the surgeons ifnecessary.

• Surgery is often a better option than a castfor a broken leg if someone is still walking.

• Input from a physical therapist is crucial tomake sure that the boy gets back on his feetas soon as possible.

• If the broken bone is one of the vertebrae(backbones) with a lot of pain in the back,input from a bone physician orendocrinologist is needed to provide theright treatment (see Section 6).

12 Emergency care considerations

IMPORTANT FACTS TO REMEMBER:

1. You are very likely to know more aboutDMD than the physicians in Accident andEmergency.

2. Advise the physician or healthcare staff ifyour son is taking steroids.

3. If your son has a broken bone, insist thatthey speak with your physician or physicaltherapist.

4. If you can, bring copies of your son’s mostrecent test results, such as FVC and LVEF.

5. If your son’s oxygen level drops, thephysician must be very careful about givinghim oxygen or sedating medication.

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ACE angiotensin converting enzyme(ACE inhibitors are used to controlcardiac problems and high bloodpressure)

ADHD attention deficit hyperactivitydisorder

ADL activities of daily living

AFOs ankle-foot orthoses (splints whichare used to control tightness atthe ankles)

ALT alanine aminotransferase

AST aspartate aminotransferase

BP blood pressure

CDC Centers for Disease Control andPrevention (the major publichealth body in the USA)

CK creatine kinase (an enzyme foundat high levels in the blood in DMDand other forms of musculardystrophy)

DEXA dual energy X-ray absorptiometry(a test done to look at thestrength of the bones). Alsoreferred to as DXA

DMD Duchenne muscular dystrophy

ECG electrocardiogram (the main testdone to look at heart rhythm)

FVC forced vital capacity (a test ofbreathing muscle strength)

GC glucocorticoid

IV intravenous (into the vein)

KAFOs knee-ankle-foot orthoses (long legsplints that can be used especiallyover the period that walking isbecoming impossible andthereafter to help prolongwalking)

kg kilogram

L liter

LVEF left ventricular ejection fraction(one of the main tests of heartfunction)

mg milligram

nmol nanomoles

NSAIDs non-steroidal anti-inflammatorydrugs (which are used for painrelief, the most common of whichare ibuprofen, diclofenac andnaproxen)

OCD obsessive-compulsive disorder

TA achilles tendon

TB tuberculosis

VOCA voice output communication aid

Abbreviations

AAnterior spinal fusiona way to correct scoliosis via an anteriorapproach

Aspiration pneumoniapneumonia caused by irritation or bacteriafrom stomach content entering lungs due tofaulty swallowing

Atelectasiscondition in which the lungs are not fullyinflated

BBaselinethe starting point to compare other tests

BiPAP bi – two way; PAP – positive air pressure. Used to maintain lung expansion

Body Mass Indexrelationship between weight and heightaccording to formula weight, in kg, divided by the square of length, in meters

CCardiomyopathydeterioration of heart muscle function - alsoknown as “heart muscle disease”

Cobb anglemeasurement of scoliosis angle from spinal X-ray

Contracturestightness round a joint leading to its becomingfixed in a particular position or having lessthan full range of motion at that joint

Cushingoid featuresterm used to describe the round or “moonlike”face that people on steroids may develop. (Thismay be prominent even if weight gain overall isnot an issue and can be hard to control withouta change in steroid or in the dosing schedule)

DDepolarising muscle relaxantsdrugs that decrease the muscle tone by actingon muscle receptors involved in depolarisation

DEXAsee abbreviations

Dysphagiaswallowing problems

Dystrophinopathythe term used to cover all the differentconditions caused by faults in the dystrophingene (Duchenne muscular dystrophy, Beckermuscular dystrophy, manifesting carriers ofone of these conditions and rare patients whohave only heart disease)

List of terms that you may come across

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EEccentric Exercisesexercises such as going downstairs ortrampolining that involve lengthening ratherthan contraction of the muscle

Electrocardiogram (ECG)methods used to assess the electrical activityof the cardiac muscle. The ECG involvesstickers placed on the chest to record heartsignals.

Echocardiogram (“echo”)method used to assess the structure of theheart. The Echo is also known as a “cardiacultrasound” and gives pictures of the beating heart

Electromyographya test that measures electrical signals from amuscle and can give a clue to whether a nerve or muscle disorder is present

Etiologycause

FForced Vital Capacitythe maximum volume of air that can beexhaled after maximum inhalation

GGastritis/gastresophageal refluxoccurs when the muscle joining the esophagus(swallowing tube from the mouth) to thestomach opens on its own, or does not closeproperly and stomach contents rise up intothe esophagus. Also called acid reflux or acidregurgitation, because digestive juices, calledacids, rise up with the food

Gastrostomysurgical opening into the stomach, in this case to insert a feeding tube. Sometimes referred to as a PEG

Germline mosaicismcondition in which the cells in the gonads that will develop into germ cells (ova andspermatozoa) are a mixture of two geneticallydifferent cell types

Glucose intolerance defines a pre-diabetic state associated withinsulin resistance

Gowers’ maneuver/signa sign of weakness in the muscles round the hips and upper part of the lower legs. It describes the way that someone withweakness in these muscles gets up of thefloor, needing to turn onto their front, keeptheir legs wide apart and using a hand on their thigh to rise. It is commonly seen in DMD but other conditions causing weaknessin the same muscle groups also cause aGowers’ maneuver

HHoltermethod used for continuous ambulatory 24 hrECG recording

Hypercapniatoo much carbon dioxide in the blood

Hypertensionhigh blood pressure

Hypoventilationreduced breathing efficiency of ventilatorycapacity

Hypoxemiadecreased oxygen levels in the blood

IImmunoblottinga way to measure the amount of dystrophin in the muscle

Immunocytochemistrya way to look at the muscle under themicroscope and see how much dystrophin is present

KKnee adductorsthe muscles that keep the knees together

Kyphoscoliosisabnormal curvature of the spine with bothsideward (scoliosis) and hunched forward orbackward (kyphosis)

MMalignant Hyperthermia-like reactiona response to anesthesia that causes ahigh temperature and can be life-threatening

Motor Function Scalestests which are used to assess activities ofmotor performance in a standardized way

Myoglobinuriapresence of myoglobin in the urine as a sign of breakdown of muscle (urine looks coca-cola colored because it contains breakdownproducts of muscle proteins)

OOsteopenia/osteoporosisdecrease in bone mineral density

Oximetrythe measurement of oxygen in the bloodstream using a machine to detect it throughthe skin

PPalpitationsawareness of abnormal heartbeats

Pelvic obliquitydescribes a condition in which the pelvis isuneven, such as being rotated downward onone side

Prophylaxisprevention

RRhabdomyolysisbreakdown of muscle

SScoliosiscurvature of the spine

TTanner stagedefines pubertal development based onexternal primary and secondary sexcharacteristics, such as the size of the breasts,genitalia and the development of pubic hair

Tenotomysurgical cutting of a tendon

Thrombolitic eventsformation of a clot (thrombus) in a bloodvessel that breaks loose and is carried by theblood stream to plug another vessel

Tineaa fungal skin infection

Tracheostomysurgical procedure on the neck to open adirect airway through an incision in thetrachea (the windpipe)

VVarusinward rotation of the foot due to animbalance of the foot muscles

Volume recruitmentincreasing the amount of air taken in by thelungs using a device to help inflate the lungs.Such devices include Ambu bags and in-exsufflators. Ventilators can also be used toincrease volume

Videofluoroscopic studyassessment tool to view and determine thenature and extent of an oropharyngealswallowing problem. A video X-ray is taken as the child swallows the food

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Photographs used in this guide were provided by Duchenne ParentProject Netherlands, MDA, PPMD, Parent Project Czech Republic andTREAT-NMD. We would like to thank all the boys and families whoallowed their photos to be used.

MDA, PPMD, TREAT-NMD and UPPMD have all been directly involvedin the writing and production of this guide.

If you have any comments or questions about the text of this guide,please contact any of the following organizations:

MDA: www.mda.orgPPMD: www.parentprojectmd.orgTREAT-NMD: www.treat-nmd.euUPPMD: www.uppmd.org