Myasthenia Gravis
Myasthenia Gravis is an autoimmune disease characterised by fatiguable muscle weakness. It has a strong association with Thymic hyperplasia (more common) and Thymoma.
Pathophysiology
Anti-AChR binds to the postsynaptic NMJ receptors, therefore preventing muscle stimulation. As the muscle is used more during activity, the receptors become more blocked up by these antibodies, therefore leading to the characteristic fatigable muscle weakness.
Anti-MuSK is also produced and has the same effect as anti-AChR, but is much less common
MuSK is an important protein for the production of AChR
N.B. Anti-MuSK is also known as anti muscle-specific tyrosine kinase.
Presentation
Fatiguable weakness – Typically minimal in the morning and worst at end of the day. Usually affects the proximal muscles first, and small muscles of the head and neck, leading to:
Ptosis, Diplopia – extraocular muscles
Difficulty smiling or chewing – Facial muscles
Slurred speech, Difficulty swallowing and chewing – Bulbar symptoms
Neck flexion weakness
Symptoms tend to be exacerbated by Infection, Pregnancy, and Hypokalaemia.
Signs seen O/E include:
Repeated blinking exacerbates ptosis
Prolonged upward gaze exacerbates diplopia
Repeated arm abduction results in unilateral weakness
Normal reflexes and sensation
Investigations
Anti-AChR – Raised in 90%
If -ve, do Anti-MuSK
EMG – Decrement of amplitude on repetitive stimulation
Imaging – CT/MRI of Thymus
Management
Acute relapse - Prednisolone
Dose decreased on remission, and bone protection is given
Long-term - Reversible AchE inhibitors e.g. Pyridostigmine or Neostigmine
SEs – Increased salivation, teary eyes, sweating, vomiting, diarrhoea
N.B. This drug class increases cholinergic activity, therefore its side-effects are the opposite of anti-cholingerics (can't see, can't pee, can't spit, can't s*it).
Consider Thymectomy. It's beneficial even in those w/o thymoma, i.e. younger patients.
Myasthenic Crisis
This is an acute, life-threatening worsening of symptoms that's usually triggered by infection. It often presents with respiratory involvement, therefore leading to respiratory failure and requiring NIV w/BiPAP, or Intubation. The severity is assessed by monitoring FVC.
Management - IVIG or PLEX (aim is to remove the auto-antibodies)