Lambert-Eaton myasthenic syndrome (LEMS) is a slowly progressive autoimmune disease characterized by muscle weakness, muscle fatigue, and autonomic symptoms. Muscles of the shoulder / pelvic girdle, trunk, and lower extremities may be affected first. Difficulty standing from a seated position is common, and extraocular muscles are often spared. LEMS may be associated with autonomic symptoms like constipation, mouth dryness, micturition difficulty, and impotence. Males are more commonly affected than females (5:1 ratio), and the disease often presents in middle age.

This is a disorder of the neuromuscular junction that is characterized by autoantibodies to voltage-gated calcium channels at the presynaptic motor terminal. Ninety percent of patients have antibodies to P/Q-type voltage-gated calcium channels in motor and autonomic nerve terminals. Interference in the presynaptic nerve terminal causes a reduction in ACh quanta release with each action potential. The mechanism is similar to that of botulism, in which neuromuscular acetylcholine release is inhibited.

LEMS is considered a paraneoplastic syndrome when associated with malignancy, and small cell lung cancer (SCLC) is associated with 60% of cases. Calcium channel antibodies also bind to the protein synaptotagmin in SCLC cells. Less frequently, LEMS may be associated with Hodgkin lymphoma, leukemia, prostate cancer, laryngeal carcinoma, breast carcinoma, Merkel cell carcinoma, and malignant thymoma.

If cancer is found, mortality is significant. The cause is unknown in about 40% of cases.