Lecture 35 - Muscular Dystrophies - Clinical Challenges Flashcards
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 etc.
Goals:
• 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 …
Deletions
Describe the importance of maintenance of ambulation
What happens when there is loss?
Importance:
• 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
Purpose: • 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?
Complications:
- Malignant hyperthermia
• Exposure to anaesthetic agents → predisposition to high fever and muscle breakdown - Acute hyperkalaemia
- Profound hyper-CK-aemia
- Acute cardiac decompensation
• Arrhythmias - 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
Benefits:
• 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
Mechanism:
1. Ventilatory provides air at positive pressure via mask
- Improved lung expansion
- Improved alveolar ventilation
- 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
Presentation: • Sinus tachycardia • Dilated cardiomyopathy (enlargement of heart) • Arrhythmias • Cardiomyopathy
Treatment:
Progression can be slowed by:
• ACE inhibitors
• Beta blockers
Describe how cardiac involvement in DMD is monitored, and how it is managed
Monitoring:
• Baseline assessment by 6 years
- Regular ECG and echocardiography
- Hypertension monitoring in boys on steroids
Management:
• 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
Theories:
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)
Effects:
• 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
Drawbacks: 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?
Osteoporosis:
due to
Steroidal suppression of bone formation and increased bone resorption
→ Increased fracture risk
Treatment:
• 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
- Bone density scans
- Spine X-rays
Describe fractures in DMD
• Prevalence
• When
• Significance
Prevalence:
• Long bone fractures: 20-45% of boys
• Vertebral fractures: 30% of boys
When:
• Peak in late childhood
• Due to falling out of the wheelchair
Significance:
• 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?
Scoliosis
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?
18
What do the following tests provide information about:
• ECG
• 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
