Myasthenia Gravis

Question 1

What is myasthenia gravis?

Answer 1

Chronic autoimmune disorder of the post-synaptic membrane at the NMJ in skeletal muscle.

• Circulating antibodies against nAChR & associated proteins impair neuromuscular transmission

–> causes muscle weakness

Question 2

What are the causes of myasthenia gravis?

Answer 2

• Impairment of neuromuscular junction transmission
• Most commonly due to autoantibodies against the nAchR
• Myasthenia gravis is associated with other autoimmune conditions (e.g. pernicious anaemia)

Question 3

What is Lambert-Eaton syndrome?

Answer 3

paraneoplastic subtype of myasthenia gravis caused by autoantibodies against pre-synaptic Ca2+ channels –> to impairment of ACh release

Question 4

Summarise the epidemiology of myasthenia gravis

Answer 4

• Prevalence: 8-9/100,000
• More common in FEMALES at younger ages
• Equal gender distribution in middle age

Question 5

What are the risk factors of myasthenia gravis?

Answer 5

• Family Hx of autoimmune disorders
• genetic markers
  
  • Specific HLA genes
  • SNPs in other genes involved in immune system
• cancer targeted therapy
  
  • ​checkpoint inhibitors

Question 6

What are the presenting symptoms of myasthenia gravis?

Answer 6

Muscle weakness

• worsens with repetitive use or towards the end of the day

Ocular symptoms

• Drooping eyelids
• Diplopia

Bulbar symptoms

• Facial weakness (myasthenic snarl)
• Disturbed hypernasal speech
• Difficulty smiling, chewing or swallowing

Question 7

What happens to muscle weakness in Lambert-Eaton syndrome with repeated use?

Answer 7

muscle weakness improves after repeated use

Question 8

What are the signs of myasthenia gravis O/E?

Answer 8

• May be generalised (affecting many muscle groups)
• May be bulbar (affecting the bulbar muscles i.e. those associated with cranial nerves 9, 10, 11 and 12)
• May be ocular

Eye Signs

• Ptosis
• Complex ophthalmoplegia
• Check for ocular fatigue
  
  • by asking the patient to sustain and upward gaze for 1 min and watch the progressive ptosis that develops
• ice on Eyes Test
  
  • Placing ice packs on closed eyelids for 2 mins can improve neuromuscular
  • transmission and reduce ptosis

Bulbar Signs

• Reading aloud may cause dysarthria or nasal speech

Limbs

• Test the power of a muscle before and after repeated use of the muscle

Question 9

What does bulbar mean?

Answer 9

bulbar = relating to the medulla oblongata (cranial nerves 9, 10, 11 and 12 have their nuclei in the medulla)

Question 10

What are the primary investigations for ?myasthenia gravis ?

Answer 10

• serum acetylcholine receptor (AChR) antibody analysis
• muscle-specific tyrosine kinase (MuSK) antibodies
• serial pulmonary function tests
  
  • Indicated if shortness of breath and suspected MG crisis.
  • MG crisis: low FVC and NIF

Question 11

What investigations should be considered for ?MS ?

Answer 11

• striational antibodies
  
  • ​not routinely done
• repetitive nerve stimulation
  
  • >10% decline in compound muscle action potential (CMAP) amplitude between the first and fourth potential in a train of 10 stimulations
• single fibre EMG
  • ​increase variability in motor latencies (jitter) or complete failure of neuromuscular transmission (block) in some muscle fibres
• CT chest
  
  • to detect thymoma