Myasthenia Gravis Lecture Notes

Definition and Overview

• Myasthenia Gravis
  • Latin for "grave muscle weakness"
  • Autoimmune disease affecting skeletal muscles
  • Progressive weakness throughout the day
  • Weaker with repetitive movements

Symptoms

• Affects extraocular muscles leading to:
  • Diplopia (double vision)
  • Ptosis (drooping eyelids)
• Bimodal distribution in age:
  • Young women (20s and 30s)
  • Older men (60s and 70s)

Normal Muscle Contraction

• Motor neurons release acetylcholine at neuromuscular junction
• Acetylcholine binds to nicotinic acetylcholine receptors on muscle cell membranes
• Binding triggers muscle contraction

Pathophysiology of Myasthenia Gravis

• Autoimmune Disease
  • Type II hypersensitivity
  • Cytotoxic injury mediated by autoantibodies
• Antibodies in Myasthenia Gravis
  • Target nicotinic acetylcholine receptors
  • Prevent acetylcholine from binding
  • Activate the complement system causing muscle cell destruction
• Minority produce muscle-specific receptor tyrosine kinase antibodies
  • Attack proteins inside muscle cells
  • Lead to cell destruction
• Paraneoplastic Syndrome
  • Occurs due to underlying cancers like bronchogenic carcinoma or thymoma

Myasthenic Crisis

• Life-threatening manifestation
• Can affect breathing muscles

Treatment

• Medications
  • Acetylcholinesterase inhibitors (e.g., neostigmine, pyridostigmine)
    • Increase acetylcholine concentration
  • Immunosuppressive drugs (e.g., prednisone)
    • Reduce harmful antibodies
• Surgical Treatment
  • Thymectomy
    • Reduces muscle weakness symptoms
    • Possibly affects helper T-cells

Summary

• Myasthenia Gravis: Type II hypersensitivity
• Antibodies block nicotinic acetylcholine receptors
• Affects young women/older men
• Commonly impacts extraocular muscles

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