Download Duchenne Muscular Dystrophy

DNIPROPETROVSK MEDICAL INSTITUTE
OF
TRADITIONAL AND NON-TRADITIONAL MEDICINE
UKRAINE
DEPARTMENT OF PEDIATRICS & MEDICAL
GENETICS
SPECIAL PRESENTATION
ON
MUSCULAR DYSTROPHY
 Intro
 Aetiology
 Pathogenesis
 Incidence
 Diagnosis
MDT
Management

 Muscular
Dystrophy (MD) is a group of
inherited diseases in which the voluntary
muscles progressively weaken overtime.
 Heart and other organs can also be affected.
 MD affects more than 50,000 Americans.
 9 major types:

Duchenne, Myotonic, Becker, Limb-girdle,
Facioscapulohumeral, Congenital,
Oculopharyngeal, Distal, and Emery-Dreifuss
 Can
occur at any age
 Most common in young males.
 Type is based on what age the individual is
when muscular dystrophy appears
 Also
depends on how severe the disease is,
which muscles it affects, rate of progression,
and the way it appears.
 Some types of muscular dystrophy only affect
males.
 Some individuals with this disease experience
mild symptoms, while others suffer from
severe muscle weakness, dying at an early
age.

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).

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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)

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).

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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 microlesions 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: 1 in 3600-6000 males (Emery, 1991), (Bushby et al, 2010),
Bradley & Parsons, 1998)

Between 1 February 1993 to 30 June 1994 – DMD incidence was 1 in
12,200males in Northern Ireland (Hughes et al, 1996).

1 in 4200 males – 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)

Mean age of diagnosis in cases without family hx is >4 ½ years (bushby et al,
2005).

The diagnosis of muscular dystrophy is based on the results of muscle biopsy,
increased creatine
phosphokinase (CpK3),electromyography, electrocardiography and DNA
analysis.

A physical examination and the patient's medical history will help the doctor
determine the type of muscular dystrophy. Specific muscle groups are affected
by different types of muscular dystrophy.

Often, there is a loss of muscle mass (wasting), which may be hard to see
because some types of muscular dystrophy cause a buildup of fat and
connective tissue that makes the muscle appear larger. This is
called pseudohypertrophy.

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

There is no known cure for muscular dystrophy, although significant headway is being
made with antisense oligonucleotides.[13] Physical therapy, occupational therapy,
orthotic intervention (e.g., ankle-foot orthosis), speech therapy and orthopedic
instruments (e.g., wheelchairs, standing frames and powered mobile arm supports) may
be helpful. Inactivity (such as bed rest, sitting for long periods) andbodybuilding efforts
to increase myofibrillar hypertrophy can worsen the disease.
There is no specific treatment for any of the forms of muscular
dystrophy. Physiotherapy, aerobic exercise, low intensity anabolic
steroids,prednisone supplements may help to prevent contractures and maintain muscle
tone. Orthoses (orthopedic appliances used for support) and corrective orthopedic
surgery may be needed to improve the quality of life in some cases. The cardiac
problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular
dystrophy may require apacemaker. The myotonia (delayed relaxation of a muscle after
a strong contraction) occurring in myotonic muscular dystrophy may be treated with
medications such as quinine, phenytoin, or mexiletine, but no actual long term
treatment has been found.
Occupational therapy assists the individual with MD to engage in activities of daily living
(such as self-feeding and self-care activities) and leisure activities at the most
independent level possible. This may be achieved with use of adaptive equipment or the
use of energy conservation techniques. Occupational therapy may implement changes to
a person's environment, both at home or work, to increase the individual's function and
accessibility. Occupational therapists also address psychosocial changes and cognitive
decline which may accompany MD, as well as provide support and education about the
disease to the family and individual.[14]
High dietary intake of lean meat, seafood, pulses, olive oil, antioxidants such as leafy
vegetables and bell peppers, and fruits like blueberry and cherry is advised. Decreased
intake of refined food, trans fats, and caffeinated and alcoholic beverages is also
advised, as is a check for any food allergies.[15]
After diagnosis, medical care may include services in neurology, nutrition,
gastroenterology, respiratory care, cardiac care, orthopedics, psychosocial,
rehabilitation, and oral care.

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However corticosteroids could be prescribed as some
countries approve.
Improve Muscle Strength and function
Significantly slow the progression of muscle weakness
Prolong ambulation
Delay 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
(Bushby et al, 2010)

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

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.
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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 dystrophy
Step 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% predicted
Step 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 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 awake
Continuous 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 noninvasive assisted
ventilation, if applicable
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 sleep
Optimally, use of lung volume recruitment and assisted
cough techniques should always
precede initiation of non-invasive ventilation
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

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(speech language therapist): 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

Occupation Therapist: Continue previous measures Provision of
appropriate wheelchair and seating, and aids and adaptations to
allow maximum independence in ADL, function, and
participation.
(Parsons et al, 2004)
Milestone
Walking alone
Late/never achieved
(%) case numbers
(89%) 16/18
Median age (range
achieved) (months)
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)

Centers for Disease Control and Prevention (CDC).Prevalence of Duchenne/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.

Hoffman EP, Dressman D (2001) Molecular pathophysiology and targeted therapeutics for muscular
dystrophy. Trends Pharmacol Sci 22: 465–470

Nowak, K. J., & Davies, K. E. (2004). Duchenne muscular dystrophy and dystrophin: pathogenesis
and opportunities for treatment. EMBO reports, 5(9), 872-876.

Ouyang L, Grosse SD, Kenneson A. Health Care Utilization and Expenditures for Children and Young
Adults With Muscular Dystrophy in a Privately Insured Population. J Child Neurol. 2008 Aug;23
(8):883-8.

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.