- Ptosis, Diplopia (extraoccular muscle weaknss), dysphagia & facial weakness, respiratory failure
- In some patients: no ocular or facial weakness occurs
- Fatigable weakness, worse after exertion
- Fixed proximal myopathy in end stage disease
Findings on Investigations:
Neurotransmitter related tests:
Edraphonium test (Tensilon):
- 10 mg I.V. (2mg initially & 8mg after 30 seconds)
- or Neostigmine test 1.5mg I.M.
- Keep atropine ready
- Use saline control first
- Anti-AChR: positive in ~80 % of generalised & 50% of ocular myasthenia gravis: Subtypes: blocking, binding, modulating
- Anti-MUSK (muscle-specific tyrosine kinase): Positive in 7%
- Anti Lrp4 antibodies in myasthenia gravis, this inhibits binding with aggrin
Nerve Conduction Studies/Electromyography NCS/EMG:
Repetitive nerve stimulation test (RNST) of a weak muscle at 3 Hz i.e. Low frequency:
- Decreased amplitude, decremental response.
- CT thorax: thymoma or thymic hyperplasia
- TFTs: high association with thyroid disease
- Rarely needed for diagnosis
- Lymphocytitic infiltrates rarely. Type 2 fibre atrophy (non-specific)
- Electron microscopy: simplification of post synaptic membrane. Flattening & atrophy of post synaptic folds. Reduced density of acetylcholine receptors.
- Avoid exacerbating drugs
Supportive therapy during crisis:
- Dysphagia: Consider NG tube for feeding
- Monitor Foced Vital Capacity (FVC) and negative inspiratory force (NIF), intubation if necessary
- 20/30/40 rule for imminent respiratory failure:
- Vital capacity <20mL/Kg
- Maximum inspiratory force MIF <30
- Maximum expiratory pressure <40
- If intubating: Avoid succinylcholine (risk of hyperkalemia)
- Pyridostigmine +/-atropine for side effects
- Consider prednisolone high dose (1-1.5mg Kg/day) then taper & low maintenance dose on alternate days
- May get worse before they get better if generalised
- Steroid sparing agents:
- Azathioprine orally
- Mycophenolate mofetil oral BID, controversial. [Pilot] . No effect in short term in steroid responsive patients. [RCT]
In Myasthenic crisis:
- Consider mechanical ventilation
- Intravenous immunoglobulin IVIg 2g per kg
- Deymeer, F., et al., Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis. Neurology, 2007. 68(8): p. 609-11.
- Ciafaloni, E., et al., Mycophenolate mofetil for myasthenia gravis: an open-label pilot study. Neurology, 2001. 56(1): p. 97-9.
- Sanders, D.B., et al., An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology, 2008. 71(6): p. 400-6.
- A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology, 2008. 71(6): p. 394-9.