A 62-year-old man with squamous cell carcinoma of the lung presents with muscle weakness, proximal more than distal, and autonomic dysfunction. Electromyography shows facilitation of muscle action potentials with repetitive stimulation. The paraneoplastic syndrome is caused by antibodies directed against which target?

• A Acetylcholine receptors at the neuromuscular junction
• B Voltage-gated potassium channels
• C Anti-Hu (ANNA-1) nuclear RNA-binding proteins
• D Voltage-gated calcium channels (P/Q-type) ✓

Explanation

The clinical picture describes Lambert-Eaton myasthenic syndrome (LEMS), a paraneoplastic syndrome most commonly associated with small cell lung cancer (though also seen with other lung tumors). Antibodies against presynaptic voltage-gated calcium channels (P/Q-type) impair acetylcholine release, causing proximal weakness and autonomic dysfunction; crucially, EMG shows increment (facilitation) with repetitive stimulation, distinguishing it from myasthenia gravis. Anti-Hu antibodies cause paraneoplastic sensory neuropathy/encephalomyelitis, not LEMS.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.