Lecture 33 - Muscular Dystrophies - Clinical Aspects Flashcards Preview

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Flashcards in Lecture 33 - Muscular Dystrophies - Clinical Aspects Deck (43):
1

List some dystrophinopathies

• Duchenne muscular dystrophy
• Becker muscular dystrophy

Be aware of these others:

• Familial cramps + myalgia syndrome

Others:
• X-linked dilated cardiomyopathy
• Isolated elevated CK
• Manifesting carrier females
• Isolated quadriceps myopathy

All due to mutation in dystrophin of some sort

2

Compare the following in DMD and BMD:
• Age of onset
• Incidence
• Age of diagnosis
• Wheelchair dependency

Age of onset:
• DMD: 5

Incidence
• DMD: 1/3500
• BMD: 1/35000

Age of diagnosis
• DMD: 2-4 years
• BMD: variable

Wheelchair dependency
• DMD: 12
• BMD: not before 16, if ever

3

To where does the Dystrophin gene map?

Xp21

4

List the clinical presentations of DMD

• Delayed motor milestones
- Mean age of walking is 18 months (normally t lift head when lying on the end of a bed

• Gait difficulties

• Fatigability, clumsiness

• Speech delay

5

When do children usually start to walk?

Before the age of 18 months

In DMD, the average age of walking is 18 months

6

In DMD, which muscles are seen to be hypertrophied?

Which muscles are spared?

Characterise the hypertrophy

• Calves
Also:
• Quads
• Gluteals
• Deltoid
• Even tongue

Not affected:
• Facial muscles
• Extra-ocular muscles

Early hypertrophy
Late pseudohypertrophy:
• Excess fat and connective tissue

7

Describe Gowers' sign

Of what is it indicative?

Boy lying on back on the ground

Asked to stand up

Child will:

1. Roll onto their stomach
2. Crouch on all fours, push up on arms
3. Hands walk up legs

This is not the normal way to stand up
An important neurological sign

Provides a mechanical advantage if there is proximal weakness around the pelvic girdle

Indication:
• Indicates proximal weakness in limb girdle (hip)
• Only considered pathological and indicative of proximal weakness after the age of four
• This is normal in children younger than three

• It is also seen in other muscle disorders

8

Describe the feature of muscle atrophy

Just important to remember that muscles can be thinned as well as hypertrophied

9

Describe the process of diagnosis of DMD

-- Screening --

1. Serum Creatine Kinase level
• Normal: 10 000 IU/L
• Degeneration of muscle, leakage of CK into the serum

2. Thyroid function tests
• Hypothyroidism can look like DMD
• Need to exclude this

-- Genetic testing --

3. MLPA
• True positive in 65-70% of cases (i.e. of boys with DMD)
• Deletions: 65%
• Duplications: 5%
• Point mutations: 10-15%

4. Muscle biopsy
• Genetic tests were negative, but there is great suspicion of DMD
• Gold standard
• Histological tests performed

10

In what proportion of cases is muscle biopsy required?

1/3rd

11

Describe the possible results of the serum CK test

There are lots of things that could cause abnormal (or normal) CK

Elevated CK does not mean that it is a muscle problem

1. Normal: less than 200 IU/L
• DM1

2. Mildly elevated: 200-1000

3. Elevated: more than 1000 IU/L
• DMD (>10 000)
• BMD
• LGMD
• FSH MD

12

Describe the natural history of DMD

3-6 years: Honeymoon phase
• Still ongoing gains in strength
• But not at the same rate as other healthy children
• Gower sign
• Calf pseudohypertrophy

8 years: marked functional difficulties
• Increasing muscle weakness and fatigability
• Increasingly prominent lumbar lordosis
• Progressive contractures

10-13 years:
• Loss of ambulation - transition to wheelchair
• Progessive scoliosis
• Progressive respiratory deficit

Late teens, early 20's: Death
• Due to respiratory or cardiac failure

13

What is the average age of death in DMD?

Death average approx. 25 years

14

What is death usually due to in DMD?

Respiratory failure (90%)

Cardiac failure (10%)
• Cardiomyopathy
• Arrhythmias

15

What are contractures?

Joint fixed in a position of flexion, unable to be extended

16

Describe the natural history of BMD

Can be quite variable

Clinical onset:
• Commonly 5-15
• Can be as late as 20-30

Progression
• Limb girdle weakness
• Cardiomyopathy
• Definitely no wheelchair before 15
• Calf pain and myalgias

Death
• After 30, generally
• Cardiomyopathy, respiratory failure

17

In which congenital MD is cardiomyopathy more common?

BMD

18

Describe the effect of DMD on the respiratory system

Restrictive deficit due to:
Weakness of intercostal muscles (and diaphragm, to a lesser extent)

Vital capacity
• Early years: increases with age and growth
• In early teens: plateaus and then declines steadily (5-10% / year)

Respiratory failure:
• Usually in the late teens or early 20s

19

If there are weak respiratory muscles, what is the first clinical sign?

Describe:
• Manifestation
• Cause
• Progression

1. Sleep-disordered breathing

Manifests as:
• Sleepiness
• Headache
• Fatigability
• Poor exercise tolerance
• Poor school performance

Due to:
• Hypercapnia (CO2 retention)
• Not hypoxia

Progression:
2. Nocturnal hypoventilation

3. Daytime hypoventilation

20

What sort of lung disease does muscle weakness cause?

Restrictive lung disease

21

Compare restrictive and obstructive lung disease

Restrictive:
• Reduced expansion of lung parenchyma
• Decreased total lung capacity
• Due to muscle weakness
• Also seen when there is fibrosis and restriction of lung movement
• FEV uncharged

Obstructive:
• Increased resistance in airway
• e.g. Asthma
• Decrease maximal airflow rates in lung function tests, i.e. decreased FEV1

22

What is Atelectasis?

What causes it?

Collapse of lung parenchyma

Caused by poor aeration of lungs

23

Describe what is seen in advanced DMD respiratory deficit

• Progression to nocturnal / daytime hypoventilation

Development of:
• Atelectasis
• Pneumonitis

Scoliosis compounds this

24

Describe scoliosis in DMD

What causes it?

Due to imbalance of paraspinal muscles

Curves depending on which side is weaker/stronger

25

Describe cardiac involvement in DMD and BMD

Which disorders are seen?
Describe them

What are the sequelae?

In order of prevalence:
1. Dilated cardiomyopathy
2. Hypertrophy
3. Conduction deficits

Cardiomyopathy:
• Decreased left ventricular contractility
• Occasional cardiac failure
• Doesn't pump properly
• Commonly asymptomatic / subclinical (because kids aren't really exercising)

Arrhythmias:
• Abnormal electrical activity of the heart
• Less common

Sequelae:
• Myocardial fibrosis
• Sinus tachycardia (Heart must beat faster to compensate)
• Ectopic rhythms

26

Compare the two types of cardiomyopathy

Which is more common in DMD?

Dilated:
• Cardiac muscle floppy and baggy
• More common in DMD

Hypertrophic:
• Muscle is thickened
• Less common in DMD, but still observed

27

Describe the orthopaedic involvement in DMD

1. Contractures
• Hips
• Knees
• Elbows
• Wrists
• Achilles and iliotibial band→ toe walking

2. Scoliosis
• Increases rapidly after non-ambulant
• Sitting, slumped to one side → scoliosis

3. Lumbar lordosis

28

Describe the CNS involvement in DMD

Is is static or progressive?

Which disorders are sometimes seen in DMD?

Static cognitive impairment

• Affects verbal (rather than performance) IQ
• Mean IQ curve shifted one standard deviation to the left

Verbal troubles:
• Following verbal instructions
• Comprehension of verbal information
• Memory storage of verbal information

Two major types:
• Reduced verbal IQ
• Reduced total IQ (<80)

Occasional:
• Autism
• Aspergers
• ADHD

29

How common is cognitive involvement in DMD?

Variable

About 1/3rd affected

30

Describe the cause of cognitive problems in DMD

Multifactorial:
1. Altered dystrophin expression in brain
• Static

2. Steroids
• Behavioural changes

3. Psychosocial effects
• Anxiety
• Depression
• Behavioural problems (steroids)

4. Effect on family
• Parental expectations
• Parental mood problems

5. Effect of chronic illness
• School absences
• Visits to hospital and doctors

31

Which muscles are spared in DMD?

• Extra-ocular muscles
• Facial muscles (usually)

32

Describe muscle disorder in DMD

Proximal weakness:
• Weak neck flexors
• Weak limb girdle (hip, shoulder)
• Weak trunk muscles

Pseudohypertrophy

Rubbery muscles

Hypotonia (floppy baby)

33

What is the difference between cardiac arrhythmias and cardiomyopathy?

Cardiomyopathy: structural problems

Arrhythmias: irregular electrical activity of the heart

34

When is ambulation usually lost in DMD?

Anywhere between 8-14 years

Definitely by 15

35

In all neuromuscular disorders, respiratory muscle function is worst during ...

Why?

... sleep

There is decreased muscle tone and central drive at this time

Leads to SDB

36

What is SDB?

Sleep disordered breathing

37

When is SDB the worst?

During REM sleep

38

What is the interaction between scoliosis and respiratory function?

Increased scoliosis → increased loss of respiratory reserve

39

When is cardiomyopathy seen in DMD and BMD?

Teenagers: 1/3rd

18 years: ½

>18 years: all

40

What percent of deaths does cardiac failure account for in DMD?

10%

41

What is sinus tachycardia?

Heart beats faster to compensate

42

When does scoliosis occur in DMD?

Increases rapidly once boy is non-ambulant

43

How can scoliosis be treated?

What are the outcomes of this?

Surgery to insert metal rod

• Corrects spine to some degree

• Stabilises lung function
• Does not improve lung function