Neuromuscular Disease

Question 1

What are the two potential causes for neuromuscular junction disease?

Answer 1

A failure of the NMJ to release sufficient ACh, or a failure of the muscle to respond to this ACh

Question 2

What is the consequence of failure to release or respond to ACh in neuromuscular junction disease?

Answer 2

Reduced/absent muscle contraction

Question 3

What are some ways to recognise muscle weakness caused by neuromuscular junction disease?

Answer 3

It is usually bilateral, and gets worse with repeated use

Question 4

What is the motor end plate?

Answer 4

The synapses formed between motor neurones and muscles

Question 5

What is curare? This is toxic if given how?

Answer 5

A plant like compound which occupies the same position as the ACh receptor but it does not open ion channels so there is no muscle contraction / IV or IM

Question 6

What is Botulism? Who is it often seen in?

Answer 6

An organism present in soil causing food and wounds to become infected / IVDU

Question 7

What are the two main pre-synaptic NMJ diseases?

Answer 7

Botulism and Lambert-Eaton syndrome

Question 8

What is the clinical presentation of Botulism?

Answer 8

Rapid onset weakness without sensory loss

Question 9

What is the pathophysiology behind Lambert-Eaton syndrome?

Answer 9

There are antibodies to pre-synaptic Ca++ channels which leads to less vesicle (containing ACh) release

Question 10

Lambert-Eaton syndrome is often a paraneoplastic syndrome. It has a strong association with what?

Answer 10

Small cell lung cancer

Question 11

How will patients with Lambert-Eaton syndrome present?

Answer 11

Proximal weakness, affecting the lower and then upper limbs

Question 12

How is Lambert-Eaton syndrome treated?

Answer 12

3,4-diaminopyridine

Question 13

What autoantibodies are seen in myasthenia gravis?

Answer 13

Postsynaptic ACh receptors

Question 14

What is the only postsynaptic NMJ disorder?

Answer 14

Myasthenia gravis

Question 15

Describe the two peak incidences of myasthenia gravis?

Answer 15

Young females in the 3rd decade of life, or males in the 6th/7th decades of life

Question 16

What happens to the incidence of antibody positive myasthenia gravis?

Answer 16

It increases with age and is more common in males

Question 17

ACh autoantibodies are found in what % of people with myasthenia gravis? If these are not found, what other autoantibody can you look for?

Answer 17

80-90% / Anti-musc

Question 18

What is a clinical feature which is closely associated with myasthenia gravis and may be the cause behind the pathology?

Answer 18

Thymus problems e.g. hyperplasia or thymoma

Question 19

What is the typical clinical feature of myasthenia gravis?

Answer 19

Typically fluctuating weakness which gets worse throughout the day

Question 20

What are some of the most common muscles/muscle groups that myasthenia gravis would present in?

Answer 20

Extraocular, facial and bulbar weakness

Question 21

Give some examples of how the muscle weakness in myasthenia gravis might present?

Answer 21

Eye shutting by the end of the day, speech that becomes slurred with talking, inability to finish a meal because of difficulty swallowing/chewing

Question 22

If limb weakness occurs in myasthenia gravis, is it typically distal or proximal?

Answer 22

Proximal

Question 23

Describe the acute treatment of myasthenia gravis?

Answer 23

ABCDE if required, ACh inhibitor (pyridostigmine), IV immunoglobulins and thymectomy

Question 24

What are some long term treatment options for myasthenia gravis?

Answer 24

Steroids (prednisolone) or steroid sparing agents (azathioprine)

Question 25

What are some emergency treatment options for myasthenia gravis?

Answer 25

Plasma exchange or immunoglobulin

Question 26

What is a myasthenic crisis? What are some things that can trigger one?

Answer 26

A severe, acute exacerbation of symptoms / infection, drugs (gentamicin/anti-arrhythmics), pregnancy and stress

Question 27

If myasthenia gravis was to cause death in a patient, what would be some potential causes for this?

Answer 27

Respiratory failure or aspiration pneumonia, side effects of immunosuppression in the elderly

Question 28

The smallest contractile unit is the muscle fibre, these are each surrounded by a thin layer of what?

Answer 28

Endomysium

Question 29

20-80 muscle fibres are grouped together to form a what? This is then surrounded by what?

Answer 29

Fascicle / perimysium

Question 30

A large number of fascicles are ensheathed by what?

Answer 30

Epimysium

Question 31

What are fasciculations? These are usually a sign of disease where?

Answer 31

Visible spontaneous switches of muscle / the motor neurone

Question 32

What is myotonia?

Answer 32

The failure of a muscle to relax after use

Question 33

What are some signs that might be seen in dermatomyositis?

Answer 33

Shawl sign, heliotrope rash, Gottron’s papules on knuckles and extensor surfaces

Question 34

What marker is raised in poly and dermatomyositis? What medication do they respond to?

Answer 34

CK / steroids

Question 35

In inclusion body myositis, there is characteristic sparing of what part of the body?

Answer 35

Thumb

Question 36

How is myotonic dystrophy inherited? How are most muscular dystrophies inherited?

Answer 36

Autosomal dominant / X linked recessive

Question 37

Duchenne and Becker muscular dystrophy are both associated with defects in what?

Answer 37

Dystrophin

Question 38

Which drugs are the most likely to cause problems with the muscles?

Answer 38

Steroids and statins

Question 39

What happens in rhabdomyolysis?

Answer 39

Damage to the skeletal muscle causes leakage of toxic intracellular contents into the plasma which can cause renal failure and DIC

Question 40

What is the triad of rhabdomyolysis?

Answer 40

Myalgia, muscle weakness and myoglobinuria