Myasthenia Gravis

Question 1

What is myasthenia gravis?

Answer 1

An autoimmune condition affect the NMJ.

Causes muscle weakness that progressively worsens with activity and improves with rest.

Question 2

What does myasthenia gravis have a strong link with?

Answer 2

Thymomas (thymus gland tumour)

Question 3

What happens at the NMJ?

Answer 3

Motor neurones communicate with muscles via the NMJ.

One one side of the synapse is the presynaptic membrane of the axon terminal of the motor neurone.

On the other side is the postsynaptic membrane of the motor end plate of the muscle cell.

The axons release acetylcholine (ACh) from the presynaptic membrane which travels across the synapse and attaches to receptors on the postsynaptic membrane, simulating muscle contraction.

Question 4

What antibodies are found in most patients with myasthenia gravis?

Answer 4

Acetylcholine receptor (AChR) antibodies

Question 5

Pathophysiology of myasthenia gravis?

Answer 5

AChR antibodies bind to the postsynaptic ACh receptors, blockign them and preventing stimulation by ACh.

The more the receptors are used during muscle activity, the more they become blocked.

With rest, the receptors are cleared, and the symptoms improve.

Question 6

What is the hallmark feature of myasthenia gravis?

Answer 6

Fluctuating muscle weakness that worsens with repetitive activity and improves with rest.

Symptoms are typically best in the morning and worst at the end of the day.

Question 7

What are 2 other antibodies that can cause myasthenia gravis?

Answer 7

1) Muscle-specific kinase (MuSK) antibodies

2) Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies

These are important proteins for the creation and organisation of the ACh receptor.

Question 8

When are symptoms typically worst in myasthenia gravis?

Answer 8

End of day

Question 9

Symptoms in myasthenia gravis?

Answer 9

Weakness typically affects the ocular, bulbar, and limb muscles.

• diplopia
• ptosis
• dysarthria (difficulty speaking)
• dysphagia
• proximal limb weakness e.g. difficulty climbing stairs, standing from a seat or raising their hands above their head

Question 10

Range of severity of symptoms in myasthenia gravis?

Answer 10

Can range from mild, isolated ocular symptoms to generalized weakness, including respiratory muscle involvement, which can be life-threatening (myasthenic crisis).

Question 11

What are some drugs that may exacerbate myasthenia?

Answer 11

• penicillamine
• quinidine, procainamide
• beta-blockers
• lithium
• phenytoin
• antibiotics: gentamicin, macrolides, quinolones, tetracyclines

Question 12

What are 3 ways to elicit fatiguability in the muscles in myasthenia gravis?

Answer 12

1) Repeated blinking will exacerbate ptosis

2) Prolonged upward gazing will exacerbate diplopia on further testing

3) Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides

Question 13

What should you examine for in MG?

Answer 13

Thymectomy scar (midline)

Question 14

What autoantibodies can be tested for myasthenia gravis? (3)

Answer 14

1) AChR antibodies

2) Anti MuSK

3) Anti LRP4

Question 15

What is the most sensitive test for MG?

Answer 15

Single-fiber electromyography (SFEMG)

Question 15

What 2 electrophysiological studies can help to confirm the diagnosis of MG?

Answer 15

These tests assess neuromuscular transmission:

1) Repetitive nerve stimulation (RNS)

2) Single-fiber electromyography (SFEMG)

Question 16

Repetitive nerve stimulation results in MG?

Answer 16

This test involves repetitive electrical stimulation of a peripheral nerve while recording the compound muscle action potentials (CMAPs) from a target muscle.

A decline in the amplitude of CMAPs after repetitive nerve stimulation, known as decrement, supports the diagnosis of MG.

Question 17

What imaging should be performed in MG? Why?

Answer 17

CT or MRI –> to assess for a thymoma or thymic hyperplasia

Question 18

The edrophonium test may be done in MG. What is this?

Answer 18

1) Patients are given IV edrophonium chloride (or neostigmine)

2) Normally, cholinesterase enzymes in the neuromuscular junction break down ACh

3) Edrophonium blocks these enzymes, reducing the breakdown of ACh

4) As a result, the level of ACh at the NMJ rises, temporarily relieving the weakness.

5) A positive result suggests a diagnosis of myasthenia gravis.

Question 19

Mechanism of neostigmine?

Answer 19

Acetylcholinesterase inhibitor –> results in more ACh being available in synapse –> more of it can bind to the fewer receptors present in MG

Question 20

Mx options in MG?

Answer 20

1) Pyridostigmine

2) Immunosuppression e.g. prednisolone or azathioprine)

3) Thymectomy

4) Rituximab (considered where other treatments fail)

5) Plasma exchange (PLEX) and IV immunoglobulin in myasthenic crisis.

Question 21

Role of pyridostigmine in MG?

Answer 21

It is a cholinesterase inhibitor –> prolongs the action of ACh and improves symtpoms.

Question 22

Role of immunosuppression in MG?

Answer 22

Supresses production of antibodies

Question 23

What is a myasthenic crisis?

Answer 23

A potentially life-threatening complication.

It causes an acute worsening of symptoms, often triggered by another illness, e.g. RTI.

Respiratory muscle weakness can lead to respiratory failure.

Question 24

Mx of a myasthenic crisis?

Answer 24

Patients may require non-invasive ventilation or mechanical ventilation.

Mx –> IV immunoglobulins & plasmapheresis