Lecture 34 - Clinical Management of DMD Flashcards
Type of treatment for DMD
Multidisciplinary
Goals of DMD treatment 1) 2) 3) 4) 5) 6)
1) Genetic counselling
2) Maintaining ambulation
3) Prevention and treatment of contractures
4) Anticipatory monitoring for DMD complications
5) Medical therapy of DMD
6) Palliative care
Areas of DMD multidisciplinary treatment 1) 2) 3) 4) 5) 6) 7) 8)
1) Diagnostics
2) Rehabilitation management
3) Orthopaedic management
4) Psychosocial management
5) Cardiac management
6) Pulmonary management
7) GI, speech, swallowing management
8) Cortocosteroid management
DR POP CGC
What is germinal mosaicism?
Where a mutation is present in germline cells in the ovaries, but not in the blood.
Makes it hard to test for mutations in the mother.
When does DMD genetic counselling begin?
At diagnosis
Aim of DMD genetic counselling
1)
2)
3)
1) Disease prevention
2) Allow carriers to have normal boys
3) Allow those who aren’t carriers to stop worrying
How often is a deletion present in DMD patients?
2/3 of the time
Proportion of DMD mutations that are de novo
1/3
Why is maintaining ambulation in DMD important?
1)
2)
3)
1) Maintain independence, cope with most daily activities
2) Less chance of scoliosis, contractures when ambulant
3) Loss of ambulation leads to loss of independence, increased risk of complications
Ways to maintain ambulation 1) 2) 3) 4)
1) Weight control (diet, exercise)
2) Prevent contractures
3) Physiotherapy
4) Corticosteroid therapy
Type of walking that is common in early DMD
Toe walking
Why do contractures arise in DMD?
1)
2)
3)
1) Static positioning in a position of flexion
2) Muscle imbalances around joint
3) Fibrotic changes in muscle
How can contractures be prevented? 1) 2) 3) 4)
1) Maintain ambulation
2) Passive, active stretching
3) Night-time splints or braces
4) Surgery (tendo-Achilles releases, anterior hip releases)
How long can surgery for contractures prolong ambulation for?
1-3 years
Important post-operative thing to do after surgery for contractures
Mobilise patient immediately after surgery
Exercise that is good for DMD patients
Sub-maximal aerobic exercise
Things to avoid in exercise for DMD patients
1)
2)
1) Over-exertion
2) Eccentric or high-resistance weight training
Positive aspects of exercise for DMD 1) 2) 3) 4)
1) Cardiovascular health
2) Maintain muscle strength, range of motion, avoid disuse atrophy
3) Weight control
4) Quality of life
Complications monitored for in DMD 1) 2) 3) 4)
1) Learning problems
2) Scoliosis
3) Respiratory muscle weakness
4) Cardiomyopathy
How to manage DMD learning disabilities 1) 2) 3) 4)
1) Early intervention with speech pathology, physiotherapy, occupational therapy
2) Assessment of skills and weaknesses (often have verbal learning problems)
3) Use formal neuropsychological testing to determine skills and weaknesses, tailor school program, provide class aide
4) Appropriate careers counselling
Chance of boys with DMD not on steroids developing scoliosis
90%
Scoliosis in DMD
1)
2)
1) Reduced chance if treated with steroids
2) Steroids increase risk of vertebral fractures
Guidelines for surgery in DMD 1) 2) 3) 4)
1) Cobb angle (spinal curvature) is over 25 degrees
2) Vital capacity below 30% of predicted
3) No active infection
4) No significant cardiomyopathy
Once not ambulatory, how often are X-rays performed on spine?
Once per year
Average age of spinal fusion surgery
14 years
What does spinal bracing not prevent?
Scoliosis progression
Purposes of spinal fusion surgery 1) 2) 3) 4) 5) 6)
1) Straightens the spine
2) Improves seated posture and comfort
3) Prevents worsening of deformity
4) Eliminates pain due to fractures from osteoporosis
5) Slows the rate of respiratory decline
6) Doesn’t restore lost respiratory function
What doesn’t spinal fusion surgery restore?
Lost respiratory function
Potential complications of spinal fusion surgery 1) 2) 3) 4)
1) Complications of anaesthesia
2) Post-operative pain
3) Loss of muscle conditioning
4) Loss of arm use
Why can a patient lose the use of his arms after spinal fusion surgery?
Decreased spinal mobility restricts movement of the upper limbs
Anaesthetic risks in DMD 1) 2) 3) 4) 5)
1) Need to avoid triggering anaesthetics
2) Malignant hyperthermia
3) Hyperkalaemia without hyperthermia
4) Profound hyper creatine kinaeaemia
5) Acute cardiac and respiratory decompensation
Malignant hyperthermia
Pharmaco-genetic predisposition to high fever, muscle breakdown after exposure to some anaesthetics
Triggering anaesthetics
1)
2)
1) Halothane
2) Succinylcholine
Respiratory issues in DMD
Restrictive deficit from weak intercostal muscles
When does respiratory failure often occur in DMD?
Late teens, early twenties
Progression of respiratory problems in DMD
1)
2)
3)
1) Sleep-disordered breathing
2) Nocturnal hypoventilation
3) Diurnal hypoventilation
Way to help with nocturnal hypoventilation
Nocturnal assisted ventilation
Helps with symptoms, reduces hospitalisations
Not clear if it extends life
Best predictor of lifespan in DMD
Pulmonary function tests
Predictions of different vital capacity measurements
1)
2)
3)
1) Vital capacity under 60% - Risk of sleep-disordered breathing
2) Vital capacity under 40% of predicted - Risk of nocturnal hypoventilation
3) Vital capacity under 1L - 100% risk of mortality in 3 years if not ventilated
In an annual sleep study, what indicates decreased respiratory reserve?
Hypercapnia, desaturation
Why is peak cough flow checked annually?
Low peak cough flow increases infection risk
Recommended respiratory tests for an ambulant patient 6 years or older
Sitting FVC, at least annually
Recommended respiratory test for non-ambulant patients 1) 2) 3) 4)
1) Oxyhaemoglobin saturation
2) Sitting FVC
3) Peak cough flow
4) Maximum inspiratory and expiratory pressures
Recommended respiratory test for non-ambulant patient who is suspected of hypoventilation, FVC under 50% predicted or currently using assisted ventilation
Awake end-tidal CO2 measurement by capnography
Mechanism of action of non-invasive ventilation 1) 2) 3) 4)
1) Ventilator provides air at a positive air pressure through mask
2) Improves lung expansion
3) Improves alveolar function
4) Reduces work of breathing and muscle fatigue
What can hyperkalaemia from triggering anaesthetics lead to?
Irregular heartbeat
Cardiac involvement in DMD at different stages of life
1)
2)
3)
1) Sinus tachycardia seen early in life
2) Arrhythmias seen late in life
3) Heart problems can begin at ten, inevitable by eighteen
Common heart problem in DMD
Dilated cardiomyopathy
Dilated cardiomyopathy in DMD
1)
2)
3)
1) Affects pump function
2) Sometimes preceded by localised hypertrophy, conduction defects
3) Onset can be insidious. Symptoms masked by muscle weakness
What slows the progression of heart problems in DMD?
1)
2)
1) Angiotensin-converting enzyme
2) Beta blockers
Management of cardiac involvement in DMD 1) 2) 3) 4)
1) Baseline assessment by 6 years
2) Regular echocardiogram, echocardiography
3) Monitor for hypertension in boys on corticosteroids
4) Treat signs and symptoms of cardiac dysfunction
Management of cardiac involvement in BMD 1) 2) 3) 4) 5)
1) Baseline assessment by 6 years
2) Regular echocardiogram, echocardiography
3) Monitor for hypertension in boys on corticosteroids
4) Treat signs and symptoms of cardiac dysfunction
5) Cardiac transplantation for severe dilated cardiomyopathy
Management of cardiac involvement in carriers of BMD
Over 16 years of age, ECG every 5 years
Medical therapy of DMD
1)
2)
3)
1) Drug therapy
2) Nutrition and dietary supplements
3) Endocrine treatment of delayed puberty
Mechanism of action of steroids in DMD
Unknown
Theorised mechanism of action of steroids in treating DMD 1) 2) 3) 4) 5)
1) Positive effect on myogenesis
2) Stabilisation of muscle fibre membranes
3) Attenuation of muscle necrosis (controversial)
4) Effect on intracellular Ca2+ concentrations
5) Immunosuppressive effect, particularly CD8+
Only drug treatment shown to be effective in DMD
Corticosteroid treatment
When are steroids prescribed in DMD?
4-6 years
At a time of decline, when falls are frequent
Would be offered earlier, but side effects are too great an issue
When are effects of steroid treatment apparent?
First apparent after 10 days, peak effectiveness after 3 months
Positive effects of steroid treatment 1) 2) 3) 4) 5)
1) Slows disease progression
2) Prolong independent ambulation by 2-3 years
3) Preserve respiratory muscle function
4) Delay onset of cardiomyopathy, scoliosis
5) Prolong survival
How long are boys on steroid therapy?
At least until they are no longer ambulatory
Side effects of corticosteroids 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12)
1) Cushingoid features
2) Growth failure (short boys)
3) Weight gain
4) Avascular necrosis, osteoporosis of bone
5) Myopathy
6) Diabetes
7) Acne
8) Hypertension
9) Mood disturbances
10) Cataracts, glaucoma
11) Infections
12) Adrenal suppression
Are side effects of steroids linked to duration and dose of therapy?
Yes
Energy requirements for young boys with DMD
Unknown
Weights at different stages of DMD
1)
2)
1) Mid stage - Obesity is common(decreased energy expenditure, decreased activity, corticosteroid side effects)
2) Late-stage - Weight loss (swallowing difficulties, poor oral intake)
Common GIT problems in late-stage DMD patients after surgery
Constipation, gastro-intestinal reflux
Why are micronutrients needed in DMD?
Corticosteroids lead to osteoporosis (decreased bone formation, increased bone resorption)
Dietary vitamin D and calcium needed
Factors contributing to poor bone health in DMD
1)
2)
3)
1) Decreased mobility
2) Muscle weakness
3) Steroid therapy
Complications of poor bone health in DMD 1) 2) 3) 4)
1) Fractures (Long bone, vertebral)
2) Osteoporosis, osteopenia
3) Scoliosis
4) Bone pain
How can bone health be assessed?
1) Blood tests
2) Bone density scans
3) Bone X ray
Blood tests for bone health 1) 2) 3) 4)
1) Calcium
2) Phosphate
3) Alkaline phosphatase
4) Vitamin D
Number of DMD patients who fracture a bone
20-45%
Effect of a long bone fracture in DMD
Might lose ambulation
Number of DMD patients who fracture a vertebrae
30% (often asymptomatic, could predispose to scoliosis)
Adult DMD issues 1) 2) 3) 4) 5)
1) Delayed puberty
2) Depression
3) Sexuality
4) Employment
5) Cognitive issues
