729.Full.pdf Diagnosis

8/4/2019 729.Full.pdf Diagnosis

1/8

Q J Med 2005; 98:729736 Advance Access publication 31 August 2005doi:10.1093/qjmed/hci113

Original papers

Analysis of an adult Duchenne musculardystrophy population

A.E. PARKER1, S.A. ROBB2, J. CHAMBERS3, A.C. DAVIDSON1, K. EVANS1,J. ODOWD1, A.J. WILLIAMS1 and R.S. HOWARD1,4

From the1Lane-Fox Unit, 3Department of Non-Invasive Cardiology and 4Department of Neurology,

St Thomas Hospital, and2Department of Paediatrics, Newcomen Centre, Guys Hospital,

Guys and St Thomas Trust, London, UK

Received 19 January 2005 and in revised form 26 July 2005

Summary

Background: Advances in management have ledto increasing numbers of patients with Duchennemuscular dystrophy (DMD) reaching adulthood.Older patients with DMD are necessarily severelydisabled, and their management presents particularpractical issues.Aim: To review the management of a late adolescent

and adult DMD population, and to identify areasin which the present service provisions may beinadequate to their needs.Design: Retrospective review.Methods: We studied 25 patients with DMDreferred to an adult neuromuscular clinic over a7-year period. Clinical details were obtained retro-spectively, from case notes or direct observations.Results: There were 24 males and one symptomaticfemale carrier. Nine patients died during theobservation period. There was no significant corre-lation between age of wheelchair confinementand age of death. Sixteen patients received non-invasive positive pressure support. Twelve attended

mainstream schools and 12, residential specialschools. All the patients lived at home for some orall of the time, when their main carers were eitherone or both of the parents. The most strikingdifficulties were with the provision of practicalaids, including appropriate hoists and belts, feedingand toileting aids, and the conversion of accom-

modation. Patients rarely wished to discuss the laterstages of their disease, and death was often moreprecipitate than expected. Death usually occurredoutside hospital and the final cause was oftendifficult to establish.Discussion: Adult patients with DMD developprogressive impairment, due to respiratory, ortho-paedic and general medical factors. However, theparticular areas of difficulty in this study oftenreflected inadequate and poorly directed socialand medical support, illustrating the need forimprovements in the structure, co-ordination andbreadth of rehabilitation services for adult patientswith DMD.

Address correspondence to Dr R.S. Howard, Department of Neurology, St Thomas Hospital, Guys andSt.Thomas Trust, London SE1 7EH. email: [email protected]

! The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians.All rights reserved. For Permissions, please email: [email protected]


2/8

IntroductionDuchenne muscular dystrophy (DMD) is the mostcommon childhood onset muscular dystrophy, withan incidence estimated to be 1:3500 live births.The condition is inherited in an X-linked manner,but one third of cases are due to a spontaneousmutation. The natural history is well understood,

presenting a relentless, progressive deteriorationin limb and trunk strength, confining the patient toa wheelchair around the age of 12, and leading todeath in the early 20s, usually due to respiratory orcardiac complications. The disease is characterizedby muscular weakness, but the expression ofdystrophin isoforms in heart and brain leads todisease manifestations in these organ systemsas well.13

Disease progression is inevitable, leading to astate of severe physical dependence. However, mostadults with DMD remain fully competent, and

maintain a robust approach to managing theirdisability. With increasing advances in respiratory,4

cardiac and orthopaedic care for muscular dystro-phy, survival with DMD may be increasing.5,6

Appropriate care for an adult patient with Duchennemuscular dystrophy demands attention to theorthopaedic, respiratory and cardiac systems, irre-spective of symptomatology, because deteriorationin any of these areas can advance rapidly overthe course of months. However, there is relativelylittle information concerning the management ofthe adult DMD population in the community. Inparticular, there is no clear understanding of the

difficulties in adapting to leaving school, seekingemployment or obtaining support appropriate to thelevel of disability.

We retrospectively reviewed 25 patients withDMD referred to an adult neuromuscular clinic,aiming to identify areas of difficulty in the manage-ment of DMD in hospital and community settings.

MethodsPatients with DMD (n25) were seen in theneuromuscular clinic at The Lane Fox Respiratory

Unit (LFRU) between 1996 and 2003, most beingreferred from the paediatric neuromuscular clinicbetween the ages of 16 to 20. Some of the patientshad been seen in the Lane Fox Unit before transferof their care, for respiratory assessments or for themanagement of respiratory complications. All thepatients were assessed by a consultant neurologist(RSH) during out-patient appointments and wereseen every 36 months; many were subsequentlyadmitted electively for assessment, or acutely for

treatment of medical complications. The number ofout-patient visits ranged from 6 to 27, and thenumber of admissions from 0 to 12. FVC measure-ments were undertaken on each attendance, withthe patient seated. This retrospective review wasinitially undertaken as an audit of the managementof DMD.

The diagnosis of DMD was made by a seniorpaediatric neurology consultant and confirmed byclinical and developmental progression consistentwith DMD. A mean of 8 years of clinical case noteswere reviewed. Initial diagnosis was made on thebasis of clinical phenotype, out-of-frame mutationin the dystrophin gene and/or complete absenceof dystrophin immunostaining on muscle biopsy.Consecutive patients were studied. Clinical detailswere obtained, retrospectively, from case notes orfrom direct observations by two of us (AP, RSH).We reviewed the developmental history, diagnosticcriteria, neurological presentation, symptomatic and

functional progression, social and educational pro-vision and disease course.The 25 patients represent a subgroup of patients

with DMD who were referred from a paediatricservice because they had reached the age of 16.Other patients were transferred to local services,and some patients were seen both locally and at theLFRU clinic. These referrals were made irrespectiveof the progression and nature of their disease,although most patients did require respiratorymanagement within the LFRU.

The LFRU provides a multidisciplinary base forassessment, with most patients being seen by

consultants in respiratory medicine, orthopaedics,cardiology and rehabilitation, as well as physio-therapists with considerable expertise in the manage-ment of neurological disability. There was closeliaison with the MDC-funded family care officer,who attended most clinics. A specialist nurse wasallocated to take particular responsibility for theDMD patients. The Lane Fox Unit is also a supra-regional respiratory care centre with access totraining, 24-h ventilatory support, and an in-patientunit for admission if necessary.

ResultsTwenty-four of the patients were male; one was asymptomatic female carrier. The results presentedbelow include only data from the male patients;the details of the female patient are describedseparately.

Nine patients died during the observation period.Mean age of death (SD) was 21.410.1 years(range 1926). The mean age of the 16 patients alive

730 A.E. Parker et al.


3/8

at the end of the study was 22.15.2 years (range1531). There were two sets of brothers.

Diagnosis

Mean age at diagnosis was 4.63.5 years (range19). Three patients had a known family history ofthe disease at the time of diagnosis, and they werediagnosed earlier (mean age 2.0 years, range 13).CK was elevated in all the patients at the timeof diagnosis, and was the basis of the diagnosis inthe patients with a family history. Fourteen patientshad muscle biopsies. These showed a characteristicappearance of scattered groups of regenerating andnecrotic muscle fibres, increased endomysial con-nective tissue and muscle fibre loss with fatreplacement. Dystrophin deficiency was confirmedafter straining muscles with dystrophin antibody.Four patients were noted to have had EMG exami-nations, all which showed myopathic changes.

Genetics

Genetic information was available for 15 patients.There were two sets of brothers affected. Ninepatients were found to have deletions of thedystrophin gene, five patients were negative andone had a base insertion in exon 21 which led toa reading-frame shift (Figure 1).

Pattern of original illness

Median age of first walking was 18 months (range

1124), Gowers manoeuvre was observed at amedian age of 5 years (range 1.57), calf hyper-trophy was evident at 5 years (range 37), a wad-dling gait at 6 years (range 39) and toe walkingat 7 years (range 211). Patients lost the ability towalk unaided at median age of 10 years (range513) and became totally wheelchair-dependentat a median age of 11 years (range 713). In ourpatient group, there was no significant correlationbetween age of wheelchair confinement and ageof death.

Early disease progression/orthopaedicdeterioration

All patients received physiotherapy aimed at appro-priate stretching; they were also offered night ankle-foot orthoses (AFOs) when they developed Achillestendon tightness.

Seven of the patient underwent Achilles tendonrelease and rehabilitation in ischial weight-bearingknee-ankle-foot orthoses (KAFO) to prolong ambu-lation (mean age 9 years, range 711). One of the

patients underwent repeat Achilles tendon releaseto improve foot posture at the age of 18.

Seven patients experienced significant fractures

(total 16); in five these were multiple, and onepatient had a hip dislocation. Nine of the fracturesinvolved the lower limb, and three were upper-limbfractures; details were not available for the remain-ing patients. Eight of the thirteen fractures occurredafter the patient was confined to a wheelchair.One of two patients had a lower-limb fracturewhile ambulant, and lost independent ambulationas a result.

Scoliosis developed in 20/24 patients, and spinalsurgery was recommended in fifteen. All recom-mendations were made between 14 and 16 years ofage. Nine of these patients underwent spinal surgery

and six refused. The details of the procedure areknown for six of the patients. Complications of theprocedure were noted in three patients. One patienthad a wound infection with persistent asepticdischarge, one experienced neuropathic bladderurinary symptoms that later resolved, and onepatient developed severe hip pain following theprocedure. There was inadequate data to demon-strate any improvement in FVC or survival afterspinal surgery, although all the patients who under-went surgery described that their seating positionbecame much more comfortable and easier toadjust.

Respiratory deterioration

There was a progressive fall in FVC in all thepatients. The rate of decline was variable, but inmost patients, the reduction was relatively consis-tent over several years. A sudden decline wasoccasionally precipitated by intercurrent eventssuch as worsening scoliosis or infective complica-tions linked to the development of hypoventilation.

1

2

3

4

5

6

7

8

9

10

11

0 5 10 1 5 2 0 25 3 0 3 5 40 4 5 50 5 5 6 0 65 7 0 7 5 80

Exon

Patient

Figure 1. Exons involved in our Duchenne musculardystrophy patients. Black bars, deleted exons. Dark greybars, exons potentially affected by confirmed out offrame mutations, Circle, exons affected by base insertions.Light grey bars, exons affected by heterozygosity in femalepatient.

Duchenne muscular dystrophy 731


4/8

In 20 patients, FVC fell below 1 l due to progressiverespiratory muscle weakness. This led to nocturnalhypoventilation in nine patients, daytime hypoxiaand diurnal type II respiratory failure in six, andrespiratory arrest in two. Bulbar weakness anddifficulty clearing secretions led to episodes ofaspiration and bronchopneumonia. Twelve patientsexperienced recurrent hospitalizations for respira-tory infections.

Overnight oximetry studies were undertaken ifthe FVC fell below 1 l, or if there were symptomssuggestive of sleep disordered breathing, includingdaytime hypersomnolence, lethargy or morningheadache. Results were available for 17 patients.Nine of the 17 patients had significant desaturationsduring the night ranging from 90% to 53%. Themajor patterns seen in the study were REM-associated desaturation, increased heart ratevariability suggestive of upper-airway-associateddisease, a combination of the first two, normal

studies, and highly disordered sleep breathing.The criteria used for commencing non-invasiveventilation were variable and depended upon thepresence and severity of symptoms (sleepiness andmorning headache), the absolute level of forcedvital capacity, the presence of nocturnal hypoventi-lation, arterial blood gases, scoliosis and the level ofhome support.

Sixteen of the 24 patients received nocturnalpositive pressure ventilation (NIV), beginning atages ranging from 13 to 26 years, with 10commencing between 14 and 16 years. Anotherpatient (at 16) started NIV at the end of the study.

Generally, when started, NIV was used for 810 hovernight but, in some patients, symptoms ofincreasing breathlessness occurred during the day,necessitating increased use of NIV, such thatfour patients required full-time ventilatory support.Six patients had ENT problems (i.e. rhinitis orulceration of the nasal bridge) using the facemask. Four patients were intubated and ventilatedduring episodes of respiratory failure; of these,one died but three were successfully extubated,and no patient had a tracheostomy. Sevenpatients were receiving NIV at the time of theirdeath.

Cardiac deterioration

Seven of the 18 patients with available data hadsinus tachycardia present on either ECG (4 patients)or 24-h ambulatory ECG (3 patients). Seven otherpatients had evidence of precordial abnormalities,which included tall R waves in anterior leads, rightventricular dominance, or right axis deviation;two of these met criteria for right ventricular

hypertrophy. ST elevations or T wave inversionwere seen in three patients, of whom one had STdepression at night on ambulatory ECG.

One patient was noted to have a conductiondelay, specifically a right-sided abnormality (RSR inV1/V2). Other conduction abnormalities includedbradycardia/tachycardia syndrome due to sino-atrialdisease in one patient, and VE or SVE on ambulatoryECG in two.

Echographic data were available for 21 patients.Findings were normal in 11. In the abnormal group,the most common finding was left ventricularwall motion abnormalities: seen in seven patients,this ranged from dyskinesis to complete akinesis,and three were predominantly in the posterioror inferior regions. Two patients had significantdilatation, and seven had a reduced ejectionfraction, from 50% to 25%. Four patients werereceiving angiotensin-converting enzyme (ACE)inhibitors.

Occupational and educational

Eight patients were documented to have associ-ated cognitive developmental disability, althoughdetailed cognitive assessment was only available fortwo patients. Four were described as having globaldevelopmental delay, two had mild learning dis-abilities, and two had late speech development.One additional patient had ongoing speech difficul-ties that were attributed to a language barrier, asBengali was his native tongue and the languagespoken at home.

Twelve attended mainstream schools with indi-vidual support workers and adaptations to deal withthe special educational needs caused by theirdisability and any cognitive difficulties. The levelof adaptation and the extent to which schools wereable to cope with the demands of severe disabilitywas highly variable. Eight patients left school orattended irregularly after the age of 12. Twelveattended residential special schools, including fiveof those with cognitive disabilities. In general,their integration was satisfactory, and these patientsfound their schooling successful. Six of the 24 boysachieved success in public examinations, with two

attending university, and three others, Colleges ofHigher Education. Only one patient was able tosustain employment in mainstream work, but twowere actively seeking employment at the end ofthe study.

Other health concerns

There were a number of other symptomaticcomplaints among the patients in our study.



5/8

The most common were gastrointestinal symptoms,

experienced by at least twelve patients. Six patients

experienced severe and intractable constipation,

four patients had dysphagia, and two patients

had gastro-oesophageal reflux. Six patients were

markedly overweight (BMI425), four were severely

underweight and one required percutaneous endo-

scopic gastroscopy. Three of the patients who wereseverely underweight required NIV. Eight patients

had urinary complaints, including frequency and

incontinence. They experienced considerable

difficulties in using a bottle. Co-existing disease

included epilepsy (n1), type II diabetes (n1),and thyrotoxicosis (n1). Two patients had hearing

difficulties.

Social supportAll the patients lived at home for some or all of the

time, at which time their main carers were eitherone or both of the parents; however, only four

patients were documented as also having support

from external carers. There were several reasonsfor inadequate external support: on occasions, local

social services failed to provide adequate assess-

ment or did not understand the complex needs ofpatients; in other circumstances, the patient or their

carers refused extra support.The most striking difficulties were with the provi-

sion of practical aids, including appropriate hoistsand belts, feeding and toileting aids and the conver-

sion of accommodation. The carers of all the patients

in this series expressed dissatisfaction concerning

the delay or failure in provision of simple aids

recommended by the appropriate therapist or from

the clinic, with a delay in the provision of more

complex needs, such as an appropriate bed, being

in excess of two years.All the patients had electric wheelchairs, but the

size of the chair and the seating arrangements were

a frequent cause for concern, as was the delay

experienced by many in obtaining modifications.

Other difficulties included adaptation of foot rests,

and table adjustment of hand controls. Three

patients were provided with environmental controlsystems (ECS). Most patients received full provision

of disability allowances, but full access to socialservices provision was inadequate, and often

depended on the input of the muscular dystrophy

key worker.All the patients had access to the local muscular

dystrophy care worker, who provided considerable

practical support in accessing available financial,

domiciliary and clinical information.

Preparation for death andcause of death

Patients and their families were aware of diseaseprogression and usually understood the naturalhistory of the condition. Nonetheless, and under-standably, patients rarely wished to discuss the laterstages of their disease. Death was often more

precipitate than expected, and usually a conse-quence of some sudden overwhelming respiratoryinfection or other intercurrent event. In some, therewas a clear progressive deterioration of ventilatoryfunction, with the gradual progression of CO2narcosis. Seven of the nine patients who died werereceiving NIV at the time of their death. In thesepatients, NIV was commenced at a slightly olderage (range 1721) and they had received support for13 years at the time of death. However, thereremains considerable uncertainty about the way inwhich these patients used NIV during the later stagesof their illness. Death usually occurred outsidehospital, and the final cause was often difficult toestablish. There were no cases in whom suddencardiac death was known to have occurred, but thiscannot be excluded.

Female carrier case

There was one symptomatic female carrier whopresented to the clinic. She is now 42 years old.She was diagnosed at age 7 on the basis of clinicalfeatures, EMG and muscle biopsy. Diagnosis wasconfirmed by the presence of a deletion of exons13 to 17 in one dystrophin allele. On gene dosage

analysis, her phenotype was attributed to non-random X inactivation. She became wheelchair-dependent at the age of 13 years, and at 31 shebegan nocturnal non-invasive positive pressureventilation.

Discussion

This study describes a retrospective review ofconsecutive patients with DMD seen in an adultclinic over a seven-year period. The data on somepatients were incomplete, as the patients were

evaluated at multiple centres during the course oftheir illness, or had missing notes. In particular,it was difficult to obtain details of death in thosewho had died outside hospital.

The Newcastle Muscle Centre7 looked at a seriesof 25 new diagnoses of DMD in the absence ofa family history. In this group, the mean age atdiagnosis was 4 years and 10 months, rangingfrom 16 to 99 months. Mean age of walking for the24 boys who did walk was 17.7 months, ranging



6/8

from 21 to 24 months. In the present series, age

of first walking and at diagnosis were not signifi-

cantly different from those in the Newcastle and

previous studies (18 months and 5 years, respec-

tively). Although there is evidence of longer

survival, particularly with the increased use of NIV

and better scoliosis management, the overall

progression of the condition has not changed. Thedemographic pattern and disease progression, in

the present series, is compatible with other series.

In the present series, the diagnostic criteria varied.

A striking elevation in CK reflects the primary

damage at the sarcolemmal membrane, with leakof CK out of muscle fibre, and is seen in all patients.

EMG is not needed to identify a myopathic processwhen the CK is high, but may be important to

excluding neurogenic cause. However, the definitive

diagnosis of DMD is made by muscle biopsy and

DNA analysis. In the present series, biopsy was

undertaken in 14 patients and was diagnostic.

Orthopedic deterioration

In the present series there was considerable physio-

therapy input, with at least 6-monthly review frompresentation until transfer to the adult clinic. This

aimed to maintain mobility and standing for as long

as possible, as well as preventing the development

of contractures. The transition from childhood to

adolescence is characterized by a loss of mobility

and an increasing dependence on assistive technol-

ogy to maintain independence and minimize the

need for assistance.Appropriate stretching of the Achilles tendon, ilio-

tibial bands, knee and hip extensors and flexors was

undertaken on a regular basis, where possible as a

home programme, to delay onset of contractures.

Night-time AFOs were used at the onset of Achilles

tendon shortening, and daytime AFOs once the

child was chair-dependent. Longitudinal studies

show that loss of strength, specifically in hip

extension and ankle dosiflexion, are the primarypredictors of loss of ambulation.8 Rehabilitation in

ischial weight-bearing KAFOs was considered in

all boys at loss of ambulation, but not taken up on

some because of personal/family preference, exten-sive contractures, or insufficient residual strength

(notably in the hip abductors), the latter often due to

delayed presentation following loss of ambulation.In the present series, fractures were very common

and often led to precipitate deterioration in

mobility, although only one patient were confined

to a wheelchair after the fracture. This contrasts with

another study looking at fracture prevalence, which

found that 20.9% of the 378 patients in the study

had experienced fractures, of which half wereamong independently ambulatory patients.9

Scoliosis develops early in nearly all childrenwith DMD,10 and is usually progressive, especiallywhen the patient becomes wheelchair-bound andduring the growth spurt. Early spinal stabilizationis indicated, which is associated with significantcomplications.1113 Scoliosis was common in thisseries, and spinal surgery was discussed with mostpatients in the present series but was rejected byseveral, who did not wish to consider an extensivesurgical procedure. Also, a number of patients werenot considered for such intervention becauserespiratory or cardiac involvement was alreadyadvanced.

While surgical correction of the curve clearlyimproves nursing care and quality of life by allowingmore comfortable wheelchair posture,14,15 its effectson pulmonary function and life expectancy arecontroversial.16,17 Several studies have shown no

change in the rate of decline of pulmonary functionfollowing curve correction,14,16 while Galasko, et al.(1992)17 described stabilization of pulmonary func-tion for up to 36 months after spinal surgery,and improved survival. In the present series, therewas no significant improvement in FVC followingsurgery, but patients all reported that seating wasmore comfortable.

Respiratory deterioration

Respiratory disease is an almost inevitable compli-cation in the adult patient, and is the underlying

cause of death in 70% of DMD patients. It isthe primary result of restrictive disease stemmingfrom inspiratory muscle weakness, severe scoliosis,reduced lung and chest wall compliance, anineffective cough due to respiratory muscle weak-ness, and obstructive sleep apnoea.10,1820

Non-invasive nasal ventilation (NIV) increasessurvival in hypercapnic patients with DMD21,22 andameliorates symptoms.23 Life expectancy is51 yearonce diurnal hypercapnia develops, but with NIV itincreases to 85% at 1 year, and 73% at 5 years.5,6

Furthermore patients who initially require invasiveIPPV part time often go on to use it full time for

a mean of 6.34.6 years.24 Importantly, mostpatients with DMD who receive chronic ventilatoryassistance express satisfaction with their quality oflife, despite the extent of their physical depen-dence.24 The relatively late occurrence of respira-tory failure, often in association with bulbarweakness, makes it desirable to avoid IPPV via atracheostomy, despite the advantages of providingairway access.25 In the present series, there was acharacteristic and predictable deterioration in FVC



7/8

with time, leading to nocturnal hypoventilation,daytime hypoxia and the development of type IIrespiratory failure. All the patients who developednocturnal hypoventilation were successfully treatedwith nocturnal NIV, leading to a marked improve-ment in their ventilatory function and quality of life.The patients used NIV for increasing times duringthe daytime as their respiratory function deterio-rated. In no patient was a tracheostomy undertaken.The use of NIV did not prevent the development ofaspiration and bronchopneumonia, which was theusual cause of death.

Cardiac deterioration

Cardiac complications are common in DMD.Cardiomyopathy is due to the progressive replace-ment of myocardial fibres by connective tissue,which tends to occur predominantly in theposteriobasal and lateral regions of the left ventricle,

sparing the right ventricle and atrium.

2630

In thepresent series, typical electrocardiographic findingsincluded tall right percordial R waves, an increasedR/S ratio and deep Q waves in leads I, aVL, andV5-6, reflecting posterior left ventricular damageresulting from the characteristic DMD cardiomyo-pathic changes described above.31 Echocardiog-raphy showed left ventricular abnormalities, withhypokinesis or dyskinesis in seven and dilatationin two.

The excessive weight of six DMD patients ledto severe management difficulties with both appro-priate chair provision and transferring. A further

three patients had further weight loss either as aconsequence of dysphagia or of poor appetite.Percutaneous endoscopic gastrostomy (PEG) wasnecessary in two.

In DMD, full-scale verbal and performance IQsare normally distributed, with means approximatelyone standard deviation below the normal popula-tion mean and non-progressive.32 There may beselectively poor performance on tests requiringcomprehension of complex verbal information,with other weakness in arithmetic and vocabularysubtests compared to other verbal, performance ormemory measures.33 In the present series, eight

patients were identified with significant cognitiveimpairment. Formal psychometric assessment isrecommended if learning difficulties are suspected,in order to maximize educational achievement.

Bushby, et al.34 observed that a higher thanexpected proportion of families with DMD werefrom socio-economically deprived backgrounds,even at the time of first diagnosis. In the presentseries, we did not systematically study socio-economic demography but it is our impression that

many families were from a socially deprived back-ground and our patients certainly experiencedsimilar difficulties in accessing the sustained, high-quality, specialised support necessary for thesuccessful management of the condition.

Parents and patients occasionally rejected offersof further support from carers. This was generallybecause they doubted that the carers would beadequately trained to cope with the needs of suchcomplex and severe disability. There was often areluctance from local health provision to supportthe funding of such carers. This emphasizes theimportance of both providing adequate funding forcarers but also of ensuring carers are appropriatelytrained in techniques of managing patients disabledby neuromuscular weakness.

Death was often relatively unexpected, usuallyas a consequence of some sudden overwhelmingrespiratory infection or other intercurrent event.In some, there was clearer progressive deterioration

of ventilatory function with the gradual progressionof CO2 narcosis. The management of patients in thelater stages of their disease and their parents is oftenextremely difficult and fraught. The level and natureof discussion must be tailored to the needs of theindividual family. The process of informing patientsand their families is long, and requires the supportof a multidisciplinary team including nurses,therapists and care workers, but the responsibilityfor ensuring that the family is fully informed and alltheir questions are answered ultimately lies with thephysician. The family must be prepared for thedevelopment of bronchopneumonia and ventilatory

failure, and they must have clear guidance about if,when and where the patient is to be admittedto hospital. The admitting unit must be aware ofthe policy discussions concerning ventilatory andpalliative management of the terminal stages. Inthe present series, this may be extremely difficultbecause patients often live a long way from the unitprimarily responsible for the management. It istherefore essential that local services, includingGP, carers and therapists are able to provide clearmanagement guidance if the patient is admitted to alocal A&E department as an emergency.

Advances in orthopaedic, respiratory and cardio-

logical care have led to a major change in the out-look for patients with DMD reaching adolescence.With appropriate support, they can continue tolive fulfilling and rewarding lives despite profoundneuromuscular weakness and consequent dis-ability. The present study suggests that, in the UK,society is lagging behind in its ability to provideappropriate support to allow these patients toremain independent in the community and toafford their families the necessary back-up. Vigorous



8/8

lobbying on behalf of these patients is alreadyundertaken by special interest organisations suchas The Muscular Dystrophy Association, but it isincumbent on all professionals involved in theircare to ensure that their non-clinical needs are alsoappropriately met.

References1. Emery A. The muscular dystrophies. Oxford, Oxford

University Press, 2001.

2. Emery AE. The muscular dystrophies. Lancet 2002;

359:68795.

3. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations:

one gene, several proteins, multiple phenotypes. Lancet

Neurol 2003; 12:73140.

4. American Thoracic Society. Respiratory care of the patient

with Duchenne Muscular5 Dystrophy. Am J Respir Crit Care

Med2004; 170:45665.

5. Simmonds AK, Muntoni F, Heather S, Fielding S. Impact

of nasal ventilation on survival in hypocapnic Duchenne

muscular dystrophy. Thorax 1998; 53:94952.6. Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R,

Bushby K. Survival in Duchenne muscular dystrophy:

improvements in life expectancy since 1967 and the

impact of home nocturnal ventilation. Neuromusc Disord

2002; 12:9269.

7. Bushby KMD, Hill A, Steele JG. Failure of early diagnosis in

symptomatic Duchenne Muscular Dystropky. Lancet 1999;

353:5578.

8. Bakker JPJ, de Groot IJM, Beelen A, Lankhorst GJ. Predictive

factors of cessation of ambulation in patients with Duchenne

muscular dystrophy. Am J Phys Med Rehab 2002; 81:90612.

9. MacDonald DG, Kinali M, Gallagher AC, Mercuri E,

Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. FracturePrevalence in Duchenne muscular dystrophy. Dev Med

Child Neurol 2002; 44:6958.

10. Smith AD, Koreska J, Moseley CF. Progression of scoliosis in

Duchenne Muscular Treatment. J Bone Joint Surg 1989;

71A:1197205.

11. Do T. Orthopaedic management of the muscular dystrophies.

Curr Opin Paediatrics 2002; 14:503.

12. Marsh A, Edge G, Lehovsky J. Spinal fusion in patients with

Duchennes muscular dystrophy and a low forced vital

capacity. Eur Spine J 2003; 12:50712.

13. Ramirez N, Richards S, Warren P, et al. Complications after

posterior Spinal Fusions in Duchenne Muscular Dystrophy.

J Paediatric Orthopaedics1997; 17:10913.

14. Miller RG, Chalmers AC, Dao H, Filler Katz A, Holman D,Bost F. The effect of spine fusion on respiratory function in

Duchenne Muscular Dystrophy. Neurology1991; 41:3840.

15. Shapiro F, Sethna N, Colan S, Wohl ME, Specht L. Spinal

fusion in Duchenne muscular dystrophy: a multidisciplinary

approach. Muscle Nerve 1992; 15:60414.

16. Declan Kennedy J, Staples AJ, Brook PD, Parsons DW,

Sutherland AD, Martin AJ, Stern LM, Foster BK. The effects

spinal surgery on lung function in Duchenne muscular

dystrophy. Thorax 1995; 50:11738.

17. Galasko CSB, Delaney C, Morris P. Spinal stabilization in

Duchenne Muscular Dystrophy. J Bone Joint Surg 1992;

74B:21014.

18. Smith PEM, Calverley PMA, Edwards RHT, Evans GA,

Campbell EJM. Practical problems in the respiratory care of

patients with muscular dystrophy. N Engl J Med 1987;

316:1197205.

19. Khan Y, Heckmatt JZ. Obstructive apnoeas 1. Duchenne

muscular dystrophy. Thorax 1994; 49:15761.

20. Hukins CA, Hillman DR. Daytime predictors of sleep

hypoventilation in Duchenne Muscular dystrophy.

Am J Respirat Crit Care Med 2000; 161:16670.

21. Raphael J-C, Chavret S, Chastang, et al. Randomised trial

of preventive nasal ventilation in Duchennes muscular

dystrophy. Lancet 1994; 343:16004.

22. Gomez-Merino E, Bach JR. Duchenne Muscular Dystrophy:

Prolongation of life by noninvasive ventilation and

mechanically assisted coughing. Am J Phys Med Rehabil

2002; 81:41115.

23. Howard RS, Wiles CM, Hirsch NP, Spencer GT. Respiratory

involvement in primary muscle disorders: assessment andmanagement. Q J Med 1993; 86:17589.

24. Bach JR, Ishikana Y, Kim H. Prevention of pulmonary

morbidity for patients with Duchenne Muscular dystrophy.

Chest 1997; 112:10248.

25. Howard RS, Davidson C. Long term ventilation in neurogenic

respiratory failure. J Neurol Neurosurg Psychiat 2003;

74(suppl. 3):iii 2430.

26. Melacini P, Vianello A, Villanova C, Fanin M, Miorim M,

Angelini C, Dalla Volta S. Cardiac and Respiratory involve-

ment in advanced stage Duchenne muscular dystrophy.

Neuromuscular Disorders1996; 6:36776.

27. Muntoni F. Cardiac complications of childhood myopathies.

J Child Neurol2003c; 18:191202.

28. Muntoni F. Cardiomyopathy in muscular dystrophies.Current Opinions in Neurology 2003b; 16:57783.

29. Perloff JK, Henze E, Schelbert HR. Alterations in regional

myocardial metabolism, perfusions, and wall motion in

Duchenne muscular dystrophy studied by radionucleotide

imaging. Circulation 1984; 69:3342.

30. Finsterer J, Stollberger C. The heart in human dystrophino-

pathies. Cardiology2003; 99:119.

31. Corrado G, Lissoni A, Beretta S, et al. Prognostic value of

electrocardiograms, ventricular late potentials, ventricular

arrhtymias, and left ventricular systolic dysfunction in

patients with Duchenne muscular dystrophy. Am J Cardiol

2002; 89:83841.

32. Cotton S, Voudouris N, Douglas J. Key findings from a

meta-analytical study on intellectual function in Duchennemuscular dystrophy. J Intellect Disab Res 2000; 44:248.

33. Hinton VJ, De Vivo DC. Poor verbal working memory

across intellectual level in boys with Duchenne dystrophy.

Neurology2000; 54:212732.

34. Bushby K, Simon R, ODonnell S, Steele JG. Social

deprivation in Duchenne Muscular dystrophy: a population-

based study. Br Med J 2001; 323:10356.


Documents

729.Full.pdf Diagnosis