Lecture 35 - Muscular Dystrophies - Clinical Challenges Flashcards Preview

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Flashcards in Lecture 35 - Muscular Dystrophies - Clinical Challenges Deck (42):

Describe the make up of the multidisciplinary team that looks after DMD

What are the goals of this team?

• Genetic counsellor
• Physicians
• Physiotherapists
• Palliative care
• Speech pathologist
• Occupational therapist

• Genetic counsellor
• Maintenance of ambulation
• Prevention and treatment of contractures
• Anticipatory monitoring for DMD complications
• Medical therapy
• Palliative care


Describe Genetic counselling and its role in DMD
• Commencement
• Aim

• Commences at the time of diagnoses

Aim: disease prevention
• Allow carriers to have normal boys
• Reassurance of those who aren't carriers


1/3rd of mutations causing DMD are...

De novo


Antenatal diagnosis is most accurate with ...



Describe the importance of maintenance of ambulation

What happens when there is loss?

• As long as the child with DMD is ambulant, he can live a reasonably independent existence and cope with most daily activities
• Less tendency to develop contractures and scoliosis when ambulant

Loss of ambulation:
• Loss of independence
• Prone to increasing complications:
- Contractures
- Scoliosis


How is ambulation maintained?

• Weight control
- Diet
- Exercise
• Prevention of contractures
• Physiotherapy
• Corticosteroid therapy


Describe the observation of joint contractures in DMD

Which joints are affected?

Why do they arise?

• Achilles tendon contractures & muscle weakness → toe walking

Progressive contractures:
• Hips
• Knees
• Elbows
• Wrists

Arise because of:
• Static positioning in position of flexion
• Muscle imbalance around joint
• Fibrotic changes in muscle tissue


How can contractures be prevented?

Describe in detail surgical release

• Maintenance of ambulation
• Passive stretching (someone stretches for you)
• Active stretching (performed oneself)
• Physiotherapy
• Night time splints and braces

Surgical release of contractures
• Variable, depending on the individual
- Tendon Achilles releases
- Anterior hip releases
• Can prolong ambulation for 1-3 years
• Bracing required post-operatively
• Important to mobilise boys immediately post-operatively


Describe the importance of exercise in DMD

Which exercise is most beneficial?

What are the benefits?

Can exercise be harmful?

Sub-maximal aerobic exercise has a number of benefits on:

• Cardiovascular health
• Maintenance of muscle strength and raise of motion
• Avoidance of disuse atrophy
• Weight control
• Quality of life

e.g. Swimming:
• Aerobic
• Uses respiratory muscles
• Can be continued by the non-ambulant

Important to avoid:
• Over-exertion
• Eccentric / high-resistance strength training


Describe anticipatory monitoring in DMD

Monitoring of expected or common complications of DMD
• Learning problems
• Scoliosis
• Respiratory muscle weakness
• Cardiomyopathy


Describe management of learning disability in DMD

Early intervention strategies:
• Speech therapy
• Physiotherapy
• Occupational therapy

Assessment of skills and weaknesses
• Formal neuropsychological assessment in school age children
• Tailored school programme
• Provision of aide in classroom

Appropriate careers counselling


Describe the risk of scoliosis in DMD and how it can be attenuated

What about vertebral fractures?

Without steroids:
• 90% chance of developing scoliosis
• Small chance of vertebral compression fractures from osteoporosis

With steroids:
• Less risk of scoliosis
• Greater risk of vertebral fractures


Describe spinal monitoring in DMD

When is surgery performed?

Ambulatory phase: clinical observation sufficient

Non-ambulatory phase: annual X-rays

Guidelines of surgery:
• Spinal curve > 25 degrees
• Vital capacity > 30% of predicted
• No active infection
• No significant cardiomyopathy


What is Spinal Fusion?
What role does it play?

Spinal fusion is the surgical joining of vertebrae

aka Spondylodesis

• Straightens the spine
• Improves seated posture and comfort
• Prevents further worsening
• Eliminates pain due to vertebral fracture
• Slows rate of respiratory decline
• Prevents progression of scoliosis

Drawbacks / potential complications
• Doesn't restore lost pulmonary function
• Post-operative pain
• Loss of muscle conditioning and strength with immobilisation
• Loss of arm use
• Decreased spinal motility
• Complications of anaesthesia:
- Malignant hyperthermia
- Respiratory problems
- Cardiac arrhythmias


Describe the effect of spinal fusion (Spondylodesis) on respiratory function

Can slow the rate of respiratory decline, but cannot restore lost function


Compare Spinal fusion with spinal bracing

Spinal fusion: the surgery
• Stops scoliosis progression

Spinal bracing:
• Rigid plastic brace worn on the outside
• Suitable for those unfit for surgery
• Does not stop scoliosis progression


Describe the various complications due to anaesthesia

What is specifically that it that brings about these complications?


1. Malignant hyperthermia
• Exposure to anaesthetic agents → predisposition to high fever and muscle breakdown

2. Acute hyperkalaemia

3. Profound hyper-CK-aemia

4. Acute cardiac decompensation
• Arrhythmias

5. Respiratory decompensation

Brought about by:
Triggering anaesthetics:
• Halothane
• Succinylcholine


Describe respiratory function in DMD

What is the progression seen during sleep?

Weak intercostal muscles → restrictive deficit

Early years:
• Vital capacity increases as normal

Early teens:
• Vital capacity plateaus
• Decline: 5-10% / year

Late teens / early 20's
• Respiratory failure

Sleep disordered breathing → Nocturnal hypoventilation → Daytime hypoventilation


Describe how nocturnal hypoventilation can be treated

Nocturnal assisted ventilation

• Relieves symptoms
• Reduces hospitalisations
• ? Prolongs life


Describe how respiratory monitoring in DMD is carried out

What is the frequency?

Pulmonary function tests (Spirometry)
• Annual

Annual sleep study
• Desaturations
• Hypercapnia indicates decreased respiratory reserve

Peak cough flow test
• Annual
• Low PCF: risk of respiratory infections / failure

The frequency of the various tests is based on the age and progression of the DMD in the individual:
• Ambulatory and aged 6 or older: at least annually

• Non-ambulatory: At least every 6 months

• Non-ambulatory + suspected hypoventilation / FVC <50% predicted, use of assisted ventilation: At least annually


What is the best predictor of survival in DMD?

Pulmonary function tests


What is the implication of the following:
• Vital capacity <1L

< 1L: 100% mortality > 3 years if not ventilated*


Describe non invasive ventilation in children

NIV: Non-invasive ventilation

Mask strapped on, worn at night

Provides positive pressure to better inflate the lungs and alveoli

1. Ventilatory provides air at positive pressure via mask

2. Improved lung expansion

3. Improved alveolar ventilation

4. Reduced work of breathing and respiratory muscle fatigue


Describe cardiac involvement in DMD:
• Age of onset
• Presentation
• Treatment

Involvement may begin by 10, invariable by 18

• Sinus tachycardia
• Dilated cardiomyopathy (enlargement of heart)
• Arrhythmias
• Cardiomyopathy

Progression can be slowed by:
• ACE inhibitors
• Beta blockers


Describe how cardiac involvement in DMD is monitored, and how it is managed

• Baseline assessment by 6 years

• Regular ECG and echocardiography

• Hypertension monitoring in boys on steroids

• Treatment of signs and symptoms
• Cardiac transplantation (if dilated cardiomyopathy is severe)


Describe medical therapy of DMD

Drug therapy:
• Corticosteroids
(the only medical treatment shown to be effective in DMD)

Nutrition and dietary supplements

Endocrine treatment
• For delayed puberty


Describe the use of corticosteroids in DMD
• Mechanism of action
• Effects
• When it is offered
• Drawbacks

Mechanism of action:
• Unknown
Positive effect on myogenesis
• Anabolic effect on muscle → increased muscle mass
• Stabilisation of muscle fibre membranes (sarcolemmas)
• Attenuation of muscle necrosis
• Immunosuppression (because there is inflammation in muscle during the early stages)

• Rapid increase in strength
• Measurable effect in 10 days
• Slowed progression of muscle weakness
• Prolonged independent ambulation by 2-3 years
• Preservation of respiratory muscle function
• Delayed onset of cardiomyopathy and scoliosis
• Prolonged survival

When is it offered:
• At time of decline and frequent falls (4-6yr)
• Would be earlier, but there are some nasty side effects
• Continued at least until ambulation is lost

Side effects
• Cushingoid features
• Growth failure
• Weight gain
• Bone complications
- Avascular necrosis
- Osteoporosis
• Myopathy
• Diabetes
• Skin: acne, striae
• Hypertension
• Psychosis, mood disturbance
• Eye: cataracts, glaucoma
• Infections
• Adrenal suppression


Describe the role of nutrition and diet in DMD over the years

Young boys:
• Energy requirements with DMD unknown
• (Being investigated)

Middle stage:
• Obesity is common
• Decreased energy expenditure
• Reduced voluntary activity
• Steroid side-effects

Older boys:
• Inconclusive data as to energy requirements

Late stage:
Swallowing difficulties

• Poor oral intake
• Weight loss
• Constipation, Gastro-oesophageal reflux common


Describe the role of micronutrients in DMD

Which micronutrients are supplemented?

due to
Steroidal suppression of bone formation and increased bone resorption

→ Increased fracture risk

• Dietary calcium and vitamin D supplementation


Describe bone health status in DMD:
• Contributing factors
• Complications

Contributing factors:
• Decreased mobility
• Muscle weakness
• Steroid use

Complications of poor bone health:
• Fractures
• Osteoporosis
• Osteopaenia
• Scoliosis
• Bone pain


Describe how bone health in DMD is assessed

1. Blood tests
• Ca
• Phosphate
• Alkaline phosphatase
• Vitamin D

2. Bone density scans

3. Spine X-rays


Describe fractures in DMD
• Prevalence
• When
• Significance

• Long bone fractures: 20-45% of boys
• Vertebral fractures: 30% of boys

• Peak in late childhood
• Due to falling out of the wheelchair

• Causes significant pain and disability
• Boys may lose the ability to walk
• Can predispose to scoliosis


List 'adult' and psychiatric issues associated with DMD

Life expectancy continues to extend, so there are more and different issues being encountered:

• Delayed puberty
• Adult neurologists (i.e. neurologists who look after adults) have limited experience with DMD

Psychiatric issues:
• Social isolation
• Depression

Social issues:
• Idependence
• Sexuality
• Employment
• Cognitive issues may complicate transition to adult services
• Employment: in IT is common


Describe palliative and psychiatric care in DMD

In end-stage DMD, death should be prepared for earlier rather than later

Common problems:
• Depression
• Anxiety
• Social withdrawal

These things can be anticipated and treated

Aims of palliative care:
• Maximising quality of life for as long as possible
• Minimising stress and fear for families
• giving young men choices and control over their death


What complications do steroids help to prevent?


However, on steroids there is a greater risk of vertebral fractures


What is the Cobb angle?

Curvature of the spine


Is respiratory decline in DMD restrictive or obstructive?

What does this mean for the pulmonary function tests?

Restrictive: due to the weakness of intercostals

VC: decreased
FEV: not affected


By what age will boys with DMD invariably have cardiomyopathy?



What do the following tests provide information about:
• Echocardiogram

ECG: electrical function: rhythm of heart beat

Echocardiogram: structure and function of the pumping of the heart


What about cardiac function in carriers?

They do have some cardiomyopathy

They also have ECG and echo every 5 years after the age of 16


Which drugs have shown to be effective in DMD?

Only steroids have shown to be effective


What are Cushingoid features?

Features associated with prolonged use of cortisol / steroids

Central obesity:
• Face
• Trunk