Lambert-Eaton myasthenic syndrome (LEMS) is an
autoimmune disease of the neuromuscular junction, and approximately 60% of patients with LEMS have a
tumor, mostly
small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical data of Japanese patients in the present study are as follows: the ratio of men to women is 3: 1 (mean age, 62 years; age range, 17-80 years). Of the patients with LEMS, 61% have SCLC, whereas the others do not have
cancer. Clinical symptoms are usually characterized by proximal
muscle weakness and
dysautonomia. In less than 10% of the patients, there are signs of
cerebellar dysfunctions (
paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS), and these are usually associated with SCLC. The diagnosis can be confirmed by detecting a specific antibody in a radioimmunoprecipitation assay and finding reduced amplitude of compound muscle action potential that increases by over 100% after maximum voluntary activation or 50Hz of nerve stimulation. The pathomechanism of LEMS is characterized by impaired transmission across the neuromuscular junction because of
autoantibodies directed against the presynaptic P/Q-type voltage-gated
calcium channels (P/Q-VGCCs). Histopathologic evaluation of the cerebellum in patients with PCD-LEMS showed a reduced number of P/Q-type VGCCs in the molecular layer. Therefore, it was hypothesized that P/Q-VGCC
antibodies may induce
cerebellar dysfunction after entering the CNS in patients with PCD-LEMS. Specific
tumor therapy in patients with LEMS as well as
cancer often improves the
neurologic deficit.
Tumor removal is the primary treatment for LEMS. If the result of the primary screening is negative, screening should be repeated after 3-6 months and thereafter every 6 months for up to 2 years. Most patients benefit from 3, 4-diaminopyridine administered with
pyridostigmine. In those with severe weakness, intravenous
gamma globulin (
IVIg) or
plasmapheresis confers short-term benefits.
Prednisone when administered alone or in combination with immunosuppressive drugs can achieve long-term control of the disorder.