Lambert-Eaton myasthenic syndrome

LEMS is caused by autoantibodies against P/Q-type voltage-gated calcium channels (VGCC) located on presynaptic terminals of neuromuscular junctions. Unlike myasthenia gravis, which affects postsynaptic acetylcholine receptors, LEMS impairs calcium-dependent acetylcholine release from motor nerve terminals. This results in characteristic proximal muscle weakness that paradoxically improves with repetitive muscle contraction (post-exercise facilitation) due to calcium accumulation. The syndrome presents with proximal lower extremity weakness, reduced deep tendon reflexes that increase after exercise, and autonomic symptoms including dry mouth, constipation, and erectile dysfunction. Electromyography shows low-amplitude compound muscle action potentials (CMAPs) that increase >100% after high-frequency repetitive nerve stimulation or brief maximal exercise. LEMS is paraneoplastic in ~60% of cases, most commonly associated with small cell lung cancer (SCLC), as these tumors express similar VGCC that trigger cross-reactive autoantibodies. Non-paraneoplastic cases are often associated with other autoimmune conditions. Treatment includes immunosuppression, plasma exchange, and 3,4-diaminopyridine (which blocks potassium channels, prolonging depolarization and increasing calcium influx).