A 58-year-old heavy smoker reports progressive difficulty climbing stairs and rising from a chair over three months. On examination, proximal lower limb weakness is present, deep tendon reflexes are reduced, and strength clearly improves after a few minutes of sustained voluntary contraction. Which finding best explains this syndrome?

• A Antibodies against postsynaptic acetylcholine receptors at the neuromuscular junction
• B Antibodies against presynaptic voltage-gated calcium channels reducing acetylcholine release ✓
• C Autoimmune destruction of muscle fibers mediated by complement deposition on sarcolemma
• D Paraneoplastic cerebellar degeneration due to anti-Yo antibodies

Explanation

Facilitation with repeated use is characteristic of Lambert-Eaton myasthenic syndrome, caused by autoantibodies against presynaptic voltage-gated calcium channels that impair acetylcholine release; it is strongly associated with small cell lung carcinoma. Myasthenia gravis involves postsynaptic acetylcholine receptor antibodies and characteristically fatigues with use, the opposite pattern, which kills option A. Options C and D describe polymyositis and paraneoplastic cerebellar degeneration respectively.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.