DUCHENNE MUSCULAR

DYSTROPHYBy Grainne O’Keeffe

OVERVIEW Intro Aetiology Pathogenisis Incidence Diagnosis Family support Client’s case MDT Management

INTRODUCTION

An X linked neuromuscular disease characterised by rapidly progressing muscle weakness and wasting, (WHO, 2013).

Four phases Early phase (<6 yrs): clumsy, fall frequently, difficulty jumping or

running, enlarged muscles, contractures.

Transitional Phase (ages 6-9): Trunk weakness (Gowers manouvre), muscle weakness, heart problems, fatigue.

Loss of ambulation (ages 10-14): by 12 yrs most boys use a powered wheelchair. Scoliosis due to constant sitting and back weakness, UL weakness make ADL’s difficult (retain use of fingers).

Late stage (15+): life threatening heart and respiratory problems more prevalent, dyspnea, oedema of the LL’s. Average age of death is 19 yrs in untreated DMD but due to improvements in clinical care in many centres the average age of death is the late twenties or beyond, (Bushby et al, 2005).

AETIOLOGY

Sex linked: X-linked genetic recessive disorder Inherited by the carrier mother/sporadic mutation in

the mothers egg cell (1/3 of cases).

Results in an abnormality in the genetic code for the protein dystrophin resulting in lack of dystrophin.

(Nowak and Davies, 2004)

AETIOLOGY The dystrophin gene is the largest in the human genome

and is prone to mutation. 60% of dystrophin mutations are large insertions or

deletions that lead to frame shift errors downstream, whereas approximately 40% are point mutations/duplications or small frame shifts/ rearrangements (Hoffman, 2001).

PATHOGENISIS Dystrophin links the muscle cells to

the extracellular matrix stabilising the membrane and protecting the sarcolemma from the stresses that develop during muscle contraction.

Mechanically induced damage through eccentric contractions puts a high stress on fragile membranes and provokes micro-lesions that could eventually lead to loss of calcium homeostasis, and cell death. 

Imbalance between necrotic and regenerative processes: early phase of disease.

Later phases the regenerative capacity of muscle fibers are exhausted and fibers are gradually replaced by connective tissue and adipose tissue.

(Deconinck and Dan, 2007)

INCIDENCE Incidence: 1 in 3600-6000 (Emery, 1991), (Bushby et al, 2010),

Bradley & Parsons, 1998)

Between 1 February 1993 to 30 June 1994 – DMD incidence was 1 in 12,200 in Northern Ireland (Hughes et al, 1996).

1 in 4200 – The Netherlands (Essen et al, 1992).

1 in 5,600 to 1 in 7,700 DBMD males through 5-24 years in four states in the U.S.A. 1982-2002. (Ciafoloni et al, 2009)

  First symptoms noticed on average at 3.6 years (MDSTARnet,

2007)

DIAGNOSIS Mean age of diagnosis in cases without family hx is >4 ½ years (bushby et al,

2005). Delay in diagnosis of 2 ½ yrs (Bushby et al, 2005), (Parsons et al, 2004)

(Bushby et al, 2010)

FAMILY SUPPORT

Family support is NB at this time: provide contact with a named member of staff and provide details of parental support groups .

http://www.parentprojectmd.org www.dfsg.org.uk http://www.mdi.ie/index.html http://www.informingfamilies.ie/

CLIENT’S DETAILS Age: 5 ½ years.

PC: rare Xp21 mutation with Point mutation of exon 7 of the dystrophin gene resulting in complete absence of dystrophin.

Presentation: (Early ambulatory stage ) - Ambulant, weight – 50th %, hypertrophy of the calves, +ve Gower's sign, mild lordosis.

Problem List: Poor attention, Speech delay (uses pecs), ?hyperactivity(reported by mother), proximal weakness of lower and upper limbs and neck flexors, epistaxis, poor balance, gait-waddle/flat footed, muscle spasm of calves.

PMHX: Initially presented with developmental delays before he was diagnosed.

CURRENT PLAN Corticosteroids: prednisolone 20 mg daily. Splinting for prevention of contractures at night time. Check ups with neurologist every 6 months. Physiotherapy

LTG’s Improve upper limb strength Improve lower limb strength Improve balance Improve participation in play

STG’s Increase throwing distance of bean bag from 1 meter to 1 ¼ meters in 3 weeks. Increase kicking distance of soccer ball while on gym matt from 1 meter to 1 ½ meter in 3

weeks. Improve one legged stance to 2 seconds in 3 weeks.

Other

Family Support and services

SLT

Psychology

OT

(Bushby et al, 2010)

MDT MANAGEMENT

(Bushby et al, 2010)

REHABILITATION Management of muscle extensibility and joint

contractures: stretching and positioning, assistive devices for MSK MGT (orthoses, standing devices), surgical mgt for LL contractures (Triple arthrodesis).

Improvement, maintenance and support of muscle strength and function: Recommendations for physical activity - regular submaximum (gentle) functional strengthening/activity, including a combination of swimming-pool exercises and recreation-based exercises in the community.

Steroid prescription and management

(Fowler et al 2002), (Fowler, 1982), (Bushby et al 2010)

CORTIOCOSTERIODS

Currently best treatment available Improve Muscle Strength and function Significantly slow the progression of muscle

weakness Prolong ambulation Delsy the onset of respiratory and/or cardiac

dysfunction Use with caution as side effects include weight gain,

reduced bone density, hyperactivity, failure to gain height.

Pednisone/prednisolone – 0.75 mg/kg/day Deflazacort – 0.9 mg/kg/day

ORTHOPAEDIC MGT 90 % of boys with DMD are likely to develop a clinically

significant scoliosis.

Surgery has shown to be effective in correcting scoliosis and Success rates are likely to be highest and complication rates lowest if surgery is performed when the spine is still mobile at a Cobb angle of 20–40% (Cervellati et al, 2004) .

Spinal bracing for those unable for surgery.

Triple arthrodesis may be required

Bone health: Fractures (long bone and vertebral)Osteopenia, Osteoporosis Kyphoscoliosis, Bone pain, Reduced QOL – DEXA scans, serum/urine tests, spine readiograph – Vit D, Calcium, Biphosphonates.

SCOLIOSIS MGT

(Eagle et al, 2007) Kaplan–Meier survival plot to show the impact of spinal surgery and ventilation on survival. Survival curves are significantly different p = 0.0001.

CARDIAC DYSFUNCTION + MGT Death is due to cardiac dysfunction in 10% of cases

(Gulatie et al, 2005). Dilated cardiomyopathy: A condition in which the heart

becomes weakened and enlarged. As a result, the heart cannot pump enough blood to the rest of the body.

Death due to cardiomyopathy is expected to rise now that life expectancy increases, (Bushby et al, 2003).

It is estimated that 20–30% of DMD boys have left ventricular impairment on echocardiography by age 10 years (Bushby et al, 2005).

Cardiac mgt should be implemented at diagnosis as clinical symptoms appear later than initial cardiac dysfunction, echocardiogram & electrocardioram – at 6 yrs, every 2 yrs up to age 10 and annually after 10 yrs +.

ACE and beta blockers

(American academy of Paediatrics, 2005)

Respiratory MGT

Panel 1: Respiratory interventions indicated in patients with Duchenne muscular dystrophyStep 1: volume recruitment/deep lung infl ation technique Volume recruitment/deep lung infl ation technique (by self-infl ating manual ventilation bag or mechanical insuffl ation–exsuffl ation) when FVC <40% predictedStep 2: manual and mechanically assisted cough tech• Respiratory infection present and baseline peak cough fl ow <270 L/min* • Baseline peak cough fl ow <160 L/min or maximum expiratory pressure <40 cm water • Baseline FVC <40% predicted or <1·25 L in older teenager/adult

Step 3: nocturnal ventilation Nocturnal ventilation† is indicated in patients who have any of the following: • Signs or symptoms of hypoventilation (patients with FVC <30% predicted are at especially high risk)• A baseline SpO2 <95% and/or blood or end-tidal CO2 >45 mm Hg while awake• An apnoea–hypopnoea index >10 per hour on polysomnography or four or more episodes of SpO2 <92% or drops in SpO2 of at least 4% per hour of sleepOptimally, use of lung volume recruitment and assisted cough techniques should always precede initiation of non-invasive ventilation

Step 4: daytime ventilation In patients already using nocturnally assisted ventilation, daytime ventilation‡ is indicated for:• Self extension of nocturnal ventilation into waking hours• Abnormal deglutition due to dyspnoea, which is relieved by ventilatory assistance• Inability to speak a full sentence without breathlessness, and/or • Symptoms of hypoventilation with baseline SpO2 <95% and/or blood or end-tidal CO2>45 mm Hg while awakeContinuous non-invasive assisted ventilation (with mechanically assisted cough) can facilitate endotracheal extubation for patients who were intubated during acute illness or during anaesthesia, followed by weaning to nocturnal non-invasive assisted ventilation, if applicable

Step 5: tracheostomy Indications for tracheostomy include:• Patient and clinician preference§ • Patient cannot successfully use non-invasive ventilation• Inability of the local medical infrastructure to support non-invasive ventilation• Three failures to achieve extubation during critical illness despite optimum use of non-invasive ventilation and mechanically assisted cough• The failure of non-invasive methods of cough assistance to prevent aspiration of secretions into the lung and drops in oxygen saturation below 95% or the patient’s baseline, necessitating frequent direct tracheal suctioning via tracheostomy

PSYCHOSOCIAL MGTPsychosocial AXEmotional adjustment/copingNeurocognitiveAutism spectrum disordersSocial work

Psychosocial InterventionsPsychotherapyPharmacological interventionsEducational interventionsSocial interaction interventionsCare/support interventions

OTHER MDT ROLES

Nutritionist/dietician: to guide the patient to maintain good nutritional status to prevent both under nutrition/malnutrition and being overweight/obese, and to provide a well-balanced, nutrient-complete diet.

SLT: To monitor and treat swallowing problems, to prevent aspiration and weight loss, and to assess and treat delayed speech and language problems.

Clinical Nurse specialist: Family Support and Services

OT: Continue previous measures Provision of appropriate wheelchair and seating, and aids and adaptations to allow maximum independence in ADL, function, and participation.

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/Becker muscular dystrophy among males aged 5-24 years - four states, 2007. MMWR Morb Mortal Wkly Rep. 2009 Oct 16;58(40):1119-22.

Deconinck, N., & Dan, B. (2007). Pathophysiology of duchenne muscular dystrophy: current hypotheses. Pediatric neurology, 36(1), 1-7.

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Hughes, M. I., Hicks, E. M., Nevin, N. C., & Patterson, V. H. (1996). The prevalence of inherited neuromuscular disease in Northern Ireland.Neuromuscular Disorders, 6(1), 69-73.

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Cervellati S, Bettini N, Moscato M, Gusella A, Dema E, Maresi R. Surgical treatment of spinal deformities in Duchenne muscular dystrophy: a long term follow-up study. Eur Spine J 2004;13(5):441–8.

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DEVELOPMENTAL PROGRESS(Parsons et al, 2004)Milestone Late/never

achieved(%) case numbers

Median age (rangeachieved) (months)

Walking alone (89%) 16/18 16 (13–27)

Sitting alone (67%) 12/18 8 (5–16)

Meaningful sentences

(53%) 9/17 29 (20–43)

Single words (47%) 8/17 13 (9–24)