title: [Autoantibody against the presynaptic P/Q-type voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome].
abstract: Antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis in the 1970s'. Since then, other neurological disorders associated with autoantibodies have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs) are detected in patients with Lambert-Eaton myasthenic syndrome (LEMS). These antibodies interfere with the calcium-dependent release of acetylcholine from the presynaptic membrane. LEMS is an autoimmune disorder affecting the neuromuscular junction, and is characterized by proximal muscle weakness, reduction of tendon reflex, and autonomic dysfunction. Electrophysiological examinations show small-amplitude compound muscle action potentials and increments on rapid repetitive nerve stimulation. Fifty to sixty percent of LEMS patients present with tumors, mostly small cell lung carcinoma (SCLC), as a paraneoplastic syndrome. SCLC is a neuroendocrine tumor, which expresses neuronal VGCCs. Some patients present cerebellar ataxia, which is always accompanied by SCLC. These patients tend to show higher titers of VGCC antibodies than that by LEMS patients with no ataxia. The diagnosis can be confirmed by finding reduced compound muscle action potential amplitudes at rest that shows increments greater than 100% with repetitive nerve stimulation and antibody detection by using radioimmunoprecipitation assays. The treatment options are generally categorized as anti-tumor, immunomodulating, immunosuppressing, and symptomatic treatments. In cases with SCLC, effective treatment against the tumor can improve LEMS. Plasmapheresis and intravenous administration of high-dose immunoglobulins have a short effect. Prednisone, alone or in combination with immunosuppressants can achieve long-term control of the disorder.
authors.affiliation: Department of Neurology, National Hospital Organization Nagasaki-Kawatana Medical Center, Japan.
authors.forename: Waka
authors.initials: W
authors.lastname: Sakai
authors.forename: Shunya
authors.initials: S
authors.lastname: Nakane
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuo
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D020865:Calcium Channels, P-Type / Q000276:immunology*; D020907:Calcium Channels, Q-Type / Q000276:immunology*; D003937:Diagnosis, Differential; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000276:immunology; D055752:Small Cell Lung Carcinoma / Q000150:complications / Q000276:immunology
chemical_list: D001323:Autoantibodies; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type