Myasthenia Gravis

Diseases, ,

Clinical features:

  • 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
Antibodies:
  • 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.
Other tests:
  • CT thorax: thymoma or thymic hyperplasia
  • TFTs: high association with thyroid disease

Muscle biopsy:

  • 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.

Treatment options:

  • 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)

Symptomatic:

  • Pyridostigmine +/-atropine for side effects

Consider thymectomy
Long-term Immunosuppression:

  • 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
  • Plasmaphoresis

Related articles:

References:

  • 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.