[P/Q-type Calcium Channel Antibodies in Lambert-Eaton Myasthenic Syndrome].

Abstract

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. Approximately 50-60% of patients with LEMS have a tumor, most often small cell lung cancer (SCLC), making LEMS a paraneoplastic neurological syndrome. In Japan, the clinical picture is a male: female ratio of 3:1; mean age, 62 years (17-80 years); and 61% of LEMS patients have SCLC (SCLC-LEMS), with the remainder of patients having no cancer. Patients with LEMS develop a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes with post-tetanic potentiation, and autonomic symptoms. Interestingly, less than 10% of patients with LEMS have cerebellar ataxia (LEMS with paraneoplastic cerebellar degeneration). Considering its pathomechanisms, LEMS is a presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired by autoantibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) at active zones reducing quantal release of acetylcholine, although an animal model using immunization with purified P/Q-VGCCs has not yet been established. The diagnosis can be confirmed by finding a reduced compound muscle action potential amplitude that increases by over 60% following maximum voluntary activation or 50 Hz nerve stimulation. Approximately 90% of patients who satisfy the above electrophysiological diagnostic criteria are positive for P/Q-VGCC antibodies have their diagnosis confirmed. Specific tumor therapy in SCLC-LEMS will often improve the neurologic deficit. Tumor removal is the primary treatment for LEMS. If primary tumor screening is negative, screening should be repeated after 3-6 months, followed by screening every 6 months until 2 years post diagnosis. Most patients benefit from 3,4-diaminopyridine being administered with pyridostigmine. In those with severe weakness, high-dose intravenous gamma-globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone, alone or combined with immunosuppressive drugs, can achieve long-term control of the disorder. The results of a prospective cohort study showed that the presence of LEMS with SCLC had a significant survival advantage independent of other prognostic factors including disease extent, age, sex, performance status, and serum sodium values.

• Authors: Hiroko Kitanosono, Hirokazu Shiraishi, Masakatsu Motomura
• Journal: Brain and nerve = Shinkei kenkyu no shinpo (Brain Nerve) Vol. 70 Issue 4 Pg. 341-355 (Apr 2018) ISSN: 1881-6096 [Print] Japan
• PMID: 29632282 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Calcium Channels, Q-Type

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Animals
• Autoantibodies (immunology)
• Calcium Channels, Q-Type (immunology)
• Child
• Female
• Humans
• Japan
• Lambert-Eaton Myasthenic Syndrome (diagnosis, immunology, therapy)
• Lung Neoplasms (complications)
• Male
• Middle Aged
• Prospective Studies
• Small Cell Lung Carcinoma (complications)
• Young Adult