Which disease involves fatigable weakness that improves with rest and is associated with antibodies against the acetylcholine receptor?

• A. Lambert-Eaton syndrome
• B. Guillain-Barré syndrome
• C. Multiple Sclerosis
• D. Myasthenia gravis

Answer: (D)

Fatigable weakness that improves with rest points to a disorder of neuromuscular transmission. In myasthenia gravis, autoantibodies target postsynaptic acetylcholine receptors at the neuromuscular junction. This reduces both the number and effectiveness of receptors, so each nerve impulse produces a smaller end-plate potential. With repeated use, the already marginiled transmission deteriorates, and muscles become progressively weaker. Rest temporarily allows more acetylcholine to activate the remaining receptors, improving contraction strength, which is why the weakness improves after a break. The presence of antibodies against the acetylcholine receptor is a hallmark feature of this disease.

Clinically, you often see ocular involvement like ptosis and diplopia early on, with weakness that worsens with activity and can involve bulbar or generalized muscles. Diagnostic tests that demonstrate improvement with acetylcholinesterase inhibitors or a positive edrophonium response support this mechanism. This pattern helps distinguish it from other conditions: Lambert-Eaton syndrome involves antibodies to presynaptic calcium channels and usually shows improvement with activity rather than rest, while Guillain-Barré syndrome and multiple sclerosis are broader nervous system disorders with different typical presentations and pathophysiology.