Myasthenia Gravis

Question 1

What is the pathophysiology behind myasthenia gravis?

Answer 1

• Auto-antibody to nicotinic ACh receptor (NAChR) at the neuromuscular junction.
  
  • B and T cell involvement.

Question 2

How common is myasthenia gravis? In whom does it commonly occur?

Answer 2

• 1/8000 prevalence.
  
  • 2 peaks: young females – associated with other autoimmune diseases (RA, SLE) and thymic hyperplasia – and old males – associated with thymic atrophy or thymoma (10%).

Question 3

Which signs and symptoms are seen in myasthenia gravis?

Answer 3

• Fatigable muscle weakness usually in following order:
  
  • Extraocular: ptosis, diplopia. Presenting complaint in 50%.
  • Bulbar: dysarthria/phonia/phagia.
  • Face: myasthenic snarl on smiling.
  • Neck
  • Limb girdle i.e. proximal weakness.
  • Trunk
  • Fatiguability: cannot hold eyes in upward gaze for more than a few seconds, voice becomes quiet on counting to 50.
  • Weak forced eye closure that is easily overcome.
  • Reflexes, bulk, tone, and sensation all normal.

Question 4

Which factors can worsen the symtpoms of MG?

Answer 4

• Intercurrent illness: infection, ↓K+.
  
  • Over-treatment.
  • Altered climate.
  • Physiological stress: pregnancy, emotion, exercise.
  • Drugs: gentamycin, tetracycline, opioids, quinine, β-blockers.

Question 5

Which differential diagnoses might you consider in a patient with MG type symptoms?

Answer 5

• Polymyositis
  
  • Multiple sclerosis.
  • Motor neuron disease.
  • Guillain Barré syndrome.
  • Lambert-Eaton myasthenic syndrome.
  • Botulism. Causes ↓ACh release at NMJ.

Question 6

Which investigations should be carried out in suspected MG?

Answer 6

• Anti-AChR Ab:
  
  • 90% sensitive, or 70% in ocular-only disease. May also be +ve in Lambert-Eaton, thymoma, or small cell lung cancer.
  • If -ve, check MuSK Ab (+ve in ⅓), and anti-SM Ab.
• Special tests:
  
  • EMG, which should include repetitive nerve stimulation and single-fibre EMG.
  • Ice test: ice pack applied to closed eyelid for 2-5 minutes → ptosis improves in MG.
  • Tensilon test: tests response to sequential doses of short-acting IV cholinesterase inhibitor edrophonium, which should cause transient ↑power. No longer routine practice, and if it is done there should be resus facilities and atropine to hand.
• CT thorax to look for thymus changes.

Question 7

How is MG managed?

Answer 7

• Long-term cholinesterase inhibitor e.g. pyridostigmine. Cholinergic side effects: salivation, lacrimation, sweats, miosis, diarrhoea and vomiting, colic.
  
  • Immunosuppression for relapses: prednisolone, azathioprine, methotrexate, methylprednisolone IV, or plasma exchange.
  • Thymectomy if thymoma present. Also beneficial in treatment-resistant MG even if thymoma absent.

Question 8

What is the prognosis for MG?

Answer 8

• Often follows a relapsing-remitting course.

* Normal life expectancy for most with treatment.