Lecture 34 - Clinical Management of DMD Flashcards Preview

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Flashcards in Lecture 34 - Clinical Management of DMD Deck (75):
1

Type of treatment for DMD

Multidisciplinary

2

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

3

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

4

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.

5

When does DMD genetic counselling begin?

At diagnosis

6

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

7

How often is a deletion present in DMD patients?

2/3 of the time

8

Proportion of DMD mutations that are de novo

1/3

9

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

10

Ways to maintain ambulation
1)
2)
3)
4)

1) Weight control (diet, exercise)
2) Prevent contractures
3) Physiotherapy
4) Corticosteroid therapy

11

Type of walking that is common in early DMD

Toe walking

12

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

13

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)

14

How long can surgery for contractures prolong ambulation for?

1-3 years

15

Important post-operative thing to do after surgery for contractures

Mobilise patient immediately after surgery

16

Exercise that is good for DMD patients

Sub-maximal aerobic exercise

17

Things to avoid in exercise for DMD patients
1)
2)

1) Over-exertion
2) Eccentric or high-resistance weight training

18

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

19

Complications monitored for in DMD
1)
2)
3)
4)

1) Learning problems
2) Scoliosis
3) Respiratory muscle weakness
4) Cardiomyopathy

20

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

21

Chance of boys with DMD not on steroids developing scoliosis

90%

22

Scoliosis in DMD
1)
2)

1) Reduced chance if treated with steroids
2) Steroids increase risk of vertebral fractures

23

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

24

Once not ambulatory, how often are X-rays performed on spine?

Once per year

25

Average age of spinal fusion surgery

14 years

26

What does spinal bracing not prevent?

Scoliosis progression

27

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

28

What doesn't spinal fusion surgery restore?

Lost respiratory function

29

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

30

Why can a patient lose the use of his arms after spinal fusion surgery?

Decreased spinal mobility restricts movement of the upper limbs

31

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

32

Malignant hyperthermia

Pharmaco-genetic predisposition to high fever, muscle breakdown after exposure to some anaesthetics

33

Triggering anaesthetics
1)
2)

1) Halothane
2) Succinylcholine

34

Respiratory issues in DMD

Restrictive deficit from weak intercostal muscles

35

When does respiratory failure often occur in DMD?

Late teens, early twenties

36

Progression of respiratory problems in DMD
1)
2)
3)

1) Sleep-disordered breathing
2) Nocturnal hypoventilation
3) Diurnal hypoventilation

37

Way to help with nocturnal hypoventilation

Nocturnal assisted ventilation
Helps with symptoms, reduces hospitalisations
Not clear if it extends life

38

Best predictor of lifespan in DMD

Pulmonary function tests

39

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

40

In an annual sleep study, what indicates decreased respiratory reserve?

Hypercapnia, desaturation

41

Why is peak cough flow checked annually?

Low peak cough flow increases infection risk

42

Recommended respiratory tests for an ambulant patient 6 years or older

Sitting FVC, at least annually

43

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

44

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

45

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

46

What can hyperkalaemia from triggering anaesthetics lead to?

Irregular heartbeat

47

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

48

Common heart problem in DMD

Dilated cardiomyopathy

49

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

50

What slows the progression of heart problems in DMD?
1)
2)

1) Angiotensin-converting enzyme
2) Beta blockers

51

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

52

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

53

Management of cardiac involvement in carriers of BMD

Over 16 years of age, ECG every 5 years

54

Medical therapy of DMD
1)
2)
3)

1) Drug therapy
2) Nutrition and dietary supplements
3) Endocrine treatment of delayed puberty

55

Mechanism of action of steroids in DMD

Unknown

56

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+

57

Only drug treatment shown to be effective in DMD

Corticosteroid treatment

58

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

59

When are effects of steroid treatment apparent?

First apparent after 10 days, peak effectiveness after 3 months

60

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

61

How long are boys on steroid therapy?

At least until they are no longer ambulatory

62

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

63

Are side effects of steroids linked to duration and dose of therapy?

Yes

64

Energy requirements for young boys with DMD

Unknown

65

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)

66

Common GIT problems in late-stage DMD patients after surgery

Constipation, gastro-intestinal reflux

67

Why are micronutrients needed in DMD?

Corticosteroids lead to osteoporosis (decreased bone formation, increased bone resorption)
Dietary vitamin D and calcium needed

68

Factors contributing to poor bone health in DMD
1)
2)
3)

1) Decreased mobility
2) Muscle weakness
3) Steroid therapy

69

Complications of poor bone health in DMD
1)
2)
3)
4)

1) Fractures (Long bone, vertebral)
2) Osteoporosis, osteopenia
3) Scoliosis
4) Bone pain

70

How can bone health be assessed?

1) Blood tests
2) Bone density scans
3) Bone X ray

71

Blood tests for bone health
1)
2)
3)
4)

1) Calcium
2) Phosphate
3) Alkaline phosphatase
4) Vitamin D

72

Number of DMD patients who fracture a bone

20-45%

73

Effect of a long bone fracture in DMD

Might lose ambulation

74

Number of DMD patients who fracture a vertebrae

30% (often asymptomatic, could predispose to scoliosis)

75

Adult DMD issues
1)
2)
3)
4)
5)

1) Delayed puberty
2) Depression
3) Sexuality
4) Employment
5) Cognitive issues