A 45-year-old presents with ptosis, ophthalmoplegia, and proximal muscle weakness that worsens with repetitive use. EMG shows decremental response at 3 Hz stimulation. Which physiological mechanism explains the EMG finding?
- A Reduced acetylcholine synthesis in presynaptic terminals depleted by repetitive activity
- B Antibody-mediated destruction of postsynaptic acetylcholine receptors reducing endplate potential amplitude below threshold with repetitive stimulation ✓
- C Presynaptic calcium channel blockade preventing vesicle fusion with increased stimulation
- D Impaired acetylcholinesterase activity causing receptor desensitization from excess ACh
Explanation
This is myasthenia gravis (MG). In MG, anti-AChR antibodies reduce functional postsynaptic nicotinic receptor density. At rest, endplate potentials (EPPs) are above threshold. With repetitive stimulation, normal quantal ACh release decreases slightly (physiological reduction); in healthy NMJ this is trivial. In MG, the reduced receptor reserve means that even small decrements in released quanta push EPPs below threshold, failing to trigger action potentials in some fibers — producing the characteristic decremental EMG response. Option A may contribute minimally; option C describes Lambert-Eaton syndrome (incremental response); option D is incorrect as AChE is normal in MG.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.