What is the mechanism most consistent with fatigable weakness in myasthenia gravis?

• A. Demyelination of peripheral nerves
• B. Deficiency of dystrophin
• C. Autoantibody binding to acetylcholine receptors
• D. T-cell mediated destruction of myelin

Answer: (C)

Fatigable weakness in myasthenia gravis comes from impaired transmission at the neuromuscular junction due to antibodies targeting acetylcholine receptors on the postsynaptic membrane. These autoantibodies bind to the receptors, cause cross-linking and internalization of receptors, and activate complement to damage the postsynaptic folds. With repeated use, there are fewer functional receptors available to respond to acetylcholine, so the end-plate potential often fails to trigger a muscle action potential, leading to weakness that worsens with activity and improves with rest or acetylcholinesterase inhibitors. This pattern and mechanism specifically explain the fluctuating weakness seen in MG. Other choices describe mechanisms seen in different diseases, such as demyelination or dystrophin deficiency, which do not produce the characteristic fatigable, neuromuscular-junction–based weakness.