Myasthenia gravis (MG) is an autoimmune disease that results in the failure of neuromuscular transmission.

Epidemiology

• Incidence - 3-4/1,000,000
• Sex - bimodal distribution for age of onset
  • Women - 20-30 years
  • Men - 55-60 years

Pathophysiology

• Autoimmune disorder
• AChR antibodies are formed which induce:
  • Binding and activation of  complement at the neuromuscular junction
  • Accelerated degradation of AChR molecules crosslinked by antibody  
  • Functional AChR block
• Postsynaptic membrane is destroyed decreasing available binding sites for acetylcholine which leads to muscle weakness

Clinical Presentation

• Characteristic muscle weakness that worsens after use of affected muscles
• Swallowing difficulties
• Extraocular muscle (EOM) weakness - diplopia
  • Symptoms are present in 2/3 of patients
  • If symptoms remain limited to EOM (10% of patients) then MG is ocular MG
• Death in severe cases
• Commonly associated with thymoma

Treatment

• Anticholinesterase drugs, thymectomy, immunosuppression and plasmapheresis

Diagnosis

• Indications for ordering
  • Initiate testing based on classic symptoms of weakness and muscle fatigability
• Laboratory testing
  • Confirms clinical history
  • Serum antibody testing - positive test is diagnostic of MG
    • Anti-AChR measurement
      • Positive in 85% of patients
      • However, negative AChR does not exclude disease
      • Approximately 50% of ocular myasthenia patients are negative
    • Anti-MuSK
      • Detectable in 30-40% of anti-AChR negative patients
      • Do not order if patient clinically has isolated ocular myasthenia
    • Anti-striational protein
      • Detectable in 80% of thymomatous MG and 30% of nonthymomatous MG patients
      • Rare in ocular MG
• Other testing
  • Consider anticholinesterase testing (Tensilon test using Edrophonium) in AChR-negative patients - improvement in strength is diagnostic of MG
  • Consider repetitive stimulation or single fiber electromyogram (EMG)
    • Positive in 90% of MG patients - demonstrates a primary postsynaptic neuromuscular junctional disorder

Differential Diagnosis

• Guillain-Barré
• Amyotrophic lateral sclerosis (ALS) - Lou Gehrig disease
• Eaton Lambert syndrome
• Botulism
• Brainstem injury
• Poliomyelitis
• Polymyositis
• Acute intermittent porphyria