lecture 35 Flashcards
1
Q
What are the principles of managing DMD?
A
Multidisciplinary team
- genetic counselling
- maintaining ambulation
- prevention and treatment of contractures
- anticipatory monitoring for DMD complications
- medical therapy of DMD
- pallative care
- resp. doctor
- speech pathologist
- neurologist
- physio
- occupational
- social worker
- orthopaedic surgeon → orthopaedic managent
- cardiologist
- psychosocial management
- corticosterods
- sees up to all of these people in one visit
2
Q
What is genetic counselling?
A
- commences at time of diagnosis
- a lot of guilt –> inherited
- the aim is disease prevention
- allow those who are carriers to have normal boys
- allow those who are not carriers to stop worrying
- a deletion is demonstrated in about 2/3 of patients
- there are still issues with confirming carrier status in females
- if the proband (their son) has no demonstrable deletion
- germinal mosaicism
- up to 1/3 mutations are de novo
- antenatal diagnosis is most accurate with deletions
- ? role of newborn screening for DMD
- debate
- look for common deletions?
- ethical issues
- still some difficulties
3
Q
how is ambulation maintained? why do we maintain it?
A
- as long as the child with DMD is ambulant, he can live a reasonably independent existence and cope with most daily activities
- when ambulant, there is less tendency to develop contractures and scoliosis
- once the child loses ambulation he loses much of his independence and is prone to increasing complications such as contractures and deformites
- wheelchair = big deal
- weight control, diet, exercise: want to avoid obesity
- prevent contractures
- physiotherapy
- corticosteroids
4
Q
What are joint contractures in DMD?
A
- toe-walking is common in early DMD
- achilles tendon contractures
- progressive contractures: hips, knees, elbows, wrists
- more problematic after wheelchair bound
arise because of:
- static positioning in a position of flexion
- muscle imblance around joint
- fibrotic chagnes in muscle tissue
5
Q
How do we prevent/minimise contractures?
A
- maintain ambulation
- passive stretching, physiotherapy
- active, active-assisted and passive stretching
- need to do it everyday
- night-time splints and braces
- try to make exciting e.g. space boots
- surfical release of contractures
- tendo achilles releases
- anterior hip releases
6
Q
What is the surgical approach?
A
- individual approach in all
- surgical approaches vary
- surgery for lower extremity contractures may prolong ambulation by 1-3 years
- bracing is required post-operatively
- important to mobilise boys immediately post-operatively
7
Q
How much exercise in DMD?
A
- concerns regarding contraction-induced muscle fibre injury
- sub-maximal aerobic exercise has a number of positives
- CV health
- maintenance of muscle strength and range of motion, avoidance of disuse atrophy
- weight control
- quality of life
- avoid overwork and over-exertion
- avoid eccentric/high-resistance strength training
- swimming: aerobic, uses respiratory muscles, can be continued by the non-ambulant
- kids are good at regulating own level of activity
8
Q
What is anticipatory monitoring?
A
for expected or common cpmplications of DMD
- learning problems
- scoliosis
- respiratory muscle weakness
- cardiomyopathy
9
Q
How are learning disabilites managed?
A
- early intervention strategies
- speech therapy, physiotherapy (maybe in school setting), 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
10
Q
What is scoliosis in DMD?
A
- boys not treated with steroids:
- -90% chance of developing scoliosis
- small chance of vertebral compression fractures from osteoporisis
- boys treated with steroids:
- less risk of scolios
- greater risk of vertebral fractures
11
Q
How do we monitor the spine in DMD?
A
- clinical observation through the ambulatory phase
- once not walking:assessed at each visit
- annual x-rays
- guidelines for surgery
- spinal curve > 25 degrees
- vital capacity ? 30% of predicted
- no active infection
- no significant cardiomyopathy
- important to only do when necessary, it is a big surgery, big operative risks, hard to recover from etc etc
12
Q
What is the cobb angle?
A
- 25ºangle of the spine
13
Q
What is spinal fusion?
A
purposes
- straightens the spine, improves seaated posture and comfort
- prevents further worsening of deformity
- eliminates pain due to vertebral fracture with osteoporisis
- slows the rate of respiratory decline
- doesn’t restore lost pulmonary function
- average afe at surgery is about 14 years
- in experienced centres mortality and morbidity are low
- spinal bracing improves posture and comfort in those unfit for surfery, but will not stop scoliosis progression
14
Q
What are potential complications?
A
complications of anesthesia
- malignant hyperthermia (at higher risk than normal population)
- respiratory problems
- cardiac arrhythmias
post-operative pain
loss of muscle conditioning
- rapid loss of strength with immoblisation
- deconditioning
loss of arm use
- decreased spinal mobility
15
Q
What are anaesthetic risks in DMD?
A
- malignant hyperthermia
- a pharmacogenetic predisposition to high fever and muscle breakdown after exposure to some anaesthetic agents
- acute hyperkalemia (cardiac arrhythmias) without kyperthermia
- profound hyperCKaemia with induction anaesthesia
need to avoid ‘triggering’ anaesthetics: halothane, succinylcholine
disease-related risks
- acute cardiac and respiratory decompensation
16
Q
What is respiratory function in DMD?
A
- restrictive deficit from weak intercostal muscles
- vital capacity in the early years increases with age and growth
- in the early teens, vital cpaacity plateaus then devlines by 5-10%/year
- respiratory failure occurs in the late teens or early 20s
- progression from SDB to nocturnal hypoventilation, to daytime hypoventilation
- nocturnal assisted ventilation
- relieves symptoms
- reduced hospitalisations
- better quality of life?
- ? prolongs life
17
Q
How is respiratory function monitored in DMD?
A
- annual measurement of pulmonary function tests
- PFTs best predictor of survival in DMD
- vital capacity < 40% predicted: risk of SDB
- VC < 3 years if not ventilated
- annual sleep study:
- desaturations, hypercapnia indicate decreased respiratory reserve
- check peak cough flow yearly if possible
- low PCF: risk respiratory infections/failure
18
Q
What is non-invasive ventilation?
A
- CPAP, BIPAP
- looks terrible
- sleep better so will be compliant
- strapped on to provide pressur e
19
Q
Mechanism of action of NIV?
A
- ventilator provides air at positive pressure via mask
- improves lung expansion
- improves alveolar ventilation
- reduces work of breathing and respiratory fatigue
20
Q
What is cardiac involvement in DMD?
A
- involvement of the heart may begin by 10, invariable by 18 years
- sinus tachycardia seen early in life
- enlargement of the heart (dilated cardiomyopathy) affects pump function
- sometimes preceded by localised hypertrophy, conduction defects
- insidious onset, symptoms masked by muscle weakness
- arrhythmias seen late in life
- cardiomyopathy also occurs in Becker MD
- progression slowed by use of
- ACE inhibitors
- Beta blockers
21
Q
How is cardiac involvement managed?
A
- baseline assessment by 6 years
- regular ECG and echocardiography in all boys
- monitor for hypertension in boys on steroids
- treat signs and symptoms of cardiac dysfunction
BMD:
- similar monitoring regimen
- treat signs and symptoms of cardiac dysfunction
- cardiac transplantation for severe DCM
Carriers:
- >16 years: ECG and echo every 5 years
22
Q
What is medical therapy of DMD?
A
- drug therapy: corticosteroids
- nutrition and dietary supplements
- endocrine treatment of delayed puberty
- cushinoid
23
Q
What are corticosteroids?
A
- prednisilone
- the mechanism of action of steroids in DMD is unknown
- there are a number of theories:
- positive effect of steroids on myogenesis
- anabolic effect on muscle, resulting in increased muscle mass
- stabilisation of muscle fibre membranes
- attenuation of muscle necrosis (this is controversial)
- effect on intracellular calcium concentrations
- immunosuppressive effect with reduction of mononucleated cells, in particular cytotoxic CD8 cells
24
Q
What are effects of corticosteroids?
A
- the ONLY medical treatment shown to be effective in DMD
- steroids improve strength rapidly in DMD
→offered at time of decline and frequent falls (4-6years)
→ would be offered earlier if side-effects were less of an issue
→ effect measurable in 10 days, maximal at 3 months
→ slowed progression of muscle weakness
→ continued at least until ambulation is lost - prolong independent ambulation by 2-3 years
- preserve respiratory muscle function
- delay onset of cardiomyopathy and scoliosis
- prolong survival
25
What are the side effects?
- cushingoid features
- growth failure (childhood)
- - boys are short
- weight gain
- - boys get heavy (major problem)
- bone
- - avascular necrosis
- - osteoporosis
- myopathy
- diabetes
- skin: acne, striae
- hypertension
- psychosis, mood disturbance
- eye: cataracts, glaucoma
- infections (steroids are immunosuppresant)
- adrenal suppression
- incidence + severity ∞ dose and dration of therapy
26
What nutrition and diet is recommended in DMD?
- energy requirements for youngboys with DMD are unknown
- middle stage: obesity is common
- - decreased energy expenditure, reduced voluntary activity
- - steroid side-effects
- inconclusive data on energy requirement in older boys
- late stage: swallowing difficulties, poor oral intake, weight loss
- constipation and gastro-oesophageal reflux common in older patients and after surgery
27
What micronutrients are required for DMD?
- steroids suppress bone formation nad icnrease bone resorption, causing osteoporosis
- steroids + decreased mobility --> increased risk of fractures and poor bone health
- most boys need dietary calcium and vitamin D supplementation with steroid therapy
28
What is bone health in DMD?
factors contributing to poor bone health:
- decreased mobilit
- muscle weakiness
- steroind therapy
complications of poor bone health in DMD:
- fractures (long bone and vertebral)
- osteoporosis and osteopaenia
- scoliosis
- bone pain
29
How do we asses bone health in DMD?
- blood tests: calcium, phosphate, alkaline phosphatase, vitamin D
- bone density scans
- spine X-rays
30
What are fractures in DMD?
long bones
- fractures in 20-45% of boys with DMD
- peak in late childhood, often minimal or no trauma
- can cause significant pain and disability
- boys ambulant prior to fractures may lose ability to walk
- - rapid rehabilition important, minimise immobility
- - in the non-ambulant, splinting may be better than casting
vertebral fractures:
- seen in 30% (mostly on steroids), often asymptomatic
- may predispose to the development of scoliosis
31
What are adult issues?
- delayed puberty
- adult physicians often have limited experience with DMD
- life expectancy continues to extend
- psychiatric issues: social isolation, depression are common in young men with DMD
- independent lving
- sexuality
- employment/vocational training (IT common)
- cognitive issues may complicate transition to adult services
32
What is pallative and psychiatric care in DMD?
- in patients with end-stage DMD, death should be prepared for early rather than late
- not considering this side of things leaves young men insecure, frightened and isolated
- depression, anxietry and social withdrawal are common and should be antivipated and treated
- palliative care is aimed at:
- - maximising quality of life for as long as possible
- - minimising stress and fear for families
- - giving young men choices and control over their death
33
How has the mean age of death changed?
- shifting the goal posts
- increased
- now about 28
- 60s/70s death in teens
- scoliosis surgery + vent = 28
34
What are conclusions in DMD?
- DMD is a complex disorder affecting multiple systems
- best management includes involvement of a large team
- standards-of-care are available for most facets of DMD
- treatment is aimed at maximising strength and quality of life for as long as possible
- - improving life for patients and their families
- - paving the way for more effective therapies
