4.08 Myasthenia Gravis and Lambert Eaton Syndrome

MSK/Rheumatology review for the USMLE Step 1 Exam

• Introduction:
  • Review of neuromuscular junction and its components: presynaptic part, postsynaptic part, synaptic cleft.
  • Cascade of events leading to the release of acetylcholine into the synaptic cleft.
• Myasthenia Gravis:
  • Autoimmune neuromuscular junction disease.
  • Fluctuating muscle weakness, especially ocular and eyelid weakness, distal limb weakness.
  • Antibodies target nicotinic acetylcholine receptors (n-AChR's).
  • Association with thymic hyperplasia and enlarged thymus.
  • Treatment: Acetylcholinesterase inhibitors (AChE inhibitors), immunosuppressants.
• Lambert Eaton Syndrome:
  • Autoimmune neuromuscular junction disease associated with cancer.
  • Fluctuating muscle weakness, autonomic dysfunction, decreased reflexes.
  • Antibodies target presynaptic calcium channels on nerve terminals.
  • Autonomic manifestations due to calcium channels also present in smooth muscle.
  • Around 50% of cases associated with an underlying malignancy.
  • Treatment: Immunosuppression, addressing underlying malignancy if present.