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Myasthenia Gravis

From Mediwikis

Features

  • Muscular fatigue
  • Ptosis
  • Diplopia
  • Dysphagia
  • Dysarthria
  • Facial paresis
  • Proximal limb weakness

Risk Factors

  • Unknown

Pathophysiology

MG is a chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction in skeletal muscle.

An autoimmune attack against acetylcholine (ACh) nicotinic receptors results in the destruction of the post-synaptic membrane and a loss of available receptors. This leads to a reduction in the levels of ACh released during nerve impulses, which combined with the normal physiological pre-synaptic rundown results in the characteristic fatigability seen in patients.

The autoimmune attack is usually facilitated by anti-AChR antibodies (80-90% of patients), which block the receptors causing complement mediated damage to the membrane. The loss of immunological tolerance to the self antigen AChR is not yet fully understood.

Patients who do not have anti-AChR antibodies are considered seronegative MG but many have antibodies against muscle specific tyrosine kinase, which plays a role in anchoring acetylcholine receptor at the tips of polysynaptic folds.[1]

Typically extra-ocular muscles are the first to be affected and as a result ophthalmic presentations are usually the first to be observed.

75% of patients experience thymus abnormalities, such as hyperplasia or thymoma. This may be due to epithelial myoid cells expressing AChRs on their surface membranes and so experience an autoimmune response due to molecular mircry.

Smooth and cardiac muscle is typically unaffected due to the cholinergic receptors at these tissues having different antigenicity.

Investigations

  • Serology
    • Anti-AChR antibodies increased
    • Anti-MuSK antibodies increased
  • Serial Pulmonary Function Tests
    • Reduced FVC

Management Options

  • Pyridostigmine 30-60mg O immediate release BD initially
  • Prednisolone 15-20mg O OD initially
  • Thymectomy
  • Plasma exchange
  • IV Immunoglobulin 400mg/Kg/IV (5 day duration)
  • Immunosuppressive therapy eg Ciclosporin 2.5mg/Kg O BD

See also: Myasthenic Crisis

References

  1. http://emedicine.medscape.com/article/1171206-overview#a4