Snapshot A 61-year-old man presents to his neurologist for weakness. He reports that he has weakness with getting up from a chair or climbing the stairs. He also says that he has been having a lot of dry mouth lately, requiring him to frequently drink water. He smokes 1 pack of cigarettes daily for the past 35 years. Physical examination is notable for proximal upper and lower extremity weakness. There is also recovery of his patellar reflexes with brief and vigorous muscle contraction. Serum studies are notable for autoantibodies against voltage-gated calcium channels. Introduction Definition neuromuscular junction disease characterized by progressive muscle weakness Associated conditions small cell lung cancer Etiology Paraneoplastic or nonparaneoplastic phenomenon Pathogenesis Autoantibodies directed against presynaptic voltage-gated calcium channels leads to decreased release of acetylcholine into the neuromuscular junction reduced acetylcholine dereases muscle contraction and results in subsequent weakness Presentation Symptoms/physical exam proximal muscle weakness initially involving the lower extremities autonomic instability dry mouth (most common) orthostatic hypotension improvement in muscle strength (and recovery of deep tendon reflexes) with vigorous and brief muscle contraction Studies Making the diagnosis this is a clinical diagnosis Electromyography confirms the diagnosis findings improved post-exercise increase in compound muscle action potential on repetitive nerve stimulation Serum presence of autoantibodies against voltage-gated calcium channels present in about 85-95% of patients with Lambert-Eaton syndrome Differential Myasthenia gravis differentiating factor fatigable muscle weakness Treatment If Lambert-Eaton syndrome is secondary to small cell lung cancer, then addressing the malignancy will improve symptoms Medical amifampridine indication in patients with function-limiting muscular weakness Prognosis Addressing the underlying cancer will typically improve symptoms