Myasthenia Gravis

Question 1

Definition of MG

Answer 1

• Autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest
• Affects women at 40 years and men at 60 years
• Strong link with thymomas

Question 2

Pathophysiology of MG

Answer 2

• Motor nerves communicate with muscles at the NMJ
• At the NMJ, axons of motor nerves are situated across a synapes from the post-synaptic membrane of the muscle cell
• Axons release a neurotransmitter from the pre-synaptic membrane called acetylcholine (ACh)
• ACh attaches to receptors on the post-synaptic membrane, stimulating them and causing muscle contraction
• In MG, ACh receptor antibodies are produced which bind to the post-synaptic NMJ receptors and lock the action of ACh
• These antibodies also activate the complement system within the NMJ causing damage to the post-synaptic membrane

Question 3

Presentation of MG

Answer 3

• Symptoms mostly affect proximal muscles and small muscles of the head and neck
• Extraocular muscle weakness causing diplopia
• Eyelid weakness causing ptosis
• Weakness of the facial movements
• Difficulty swallowing
• Fatigue in the jaw when chewing
• Slurred speech
• Progressive weakness with repetitive movements

Question 4

Diagnosis of MG

Answer 4

• On examination check for thymectomy scar, repeated blinking will exacerbate ptosis, check upward gaze for diplopia, repeat abduction of one arm 20 times (reduced movement) and check FVC on spirometry
• Acetylcholine receptor (ACh-R) antibodies
• Muscle-specific kinase (MuSK) antibodies
• LRP4 antibodies
• CT/MRI of the thymus for thymoma
• Edrophonium test (neostigmine) increases amount of ACh and temporarily releaves symptoms

Question 5

Management of MG

Answer 5

• Reversible acetylcholinesterase inhibitors (pyridostigmine or neostigmine) increases levels of ACh
• Immunosuppression (prednisolone or azathioprine) suppresses production of anitbodies
• Thymectomy
• Monoclonal antibodies (rituximab, eculizumab)

Question 6

Myasthenic crisis

Answer 6

• Causes an acute worsening of symptoms
• Often triggered by other illnesses such as RTIs
• Can lead to respiratory failure due to weakness of respiratory muscles
• May require NIV with BiPAP or intubation and ventilation
• Medical treatments include immunomodulatory therapies such as IVIG and plasma exchange