Rinsho Shinkeigaku (Clinical Neurology)

Educational Lecture 15

The pathophysiology and treatment of autoimmune neuromuscular junction diseases

Masakatsu Motomura, M.D.

Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University

The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibodymediated disorders. Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies against acetylcholine receptors (AChR) and muscle-specific receptor tyrosine kinase (MuSK)/LDLreceptor related protein 4 which are AChR-associated transmembrane post-synaptic proteins involved in AChR aggregation. The seropositivity rates for AChR positive and MuSK positive MG in Japan are 80-85% and 5-10%/less than 1%,respectively. The incidence of late-onset MG, defined as onset after age 50 years, has been increasing worldwide. A nationwide epidemiological survey in Japan also revealed that the rates of late-onset MG had increased from 20% in 1987 to 42% in 2006. In 2010, a guideline for standard treatments of late-onset MG was published by the Japanese Society of Neurological Therapeutics. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction and approximately 60% of LEMS patients have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical pictures of Japanese LEMS patients are as follows; male dominant sex ratio (3 : 1), mean age 62 years (17-80 years), 61% of LEMS have SCLC, and the remaining are without cancer. In less than 10% of cases there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS) as well, often associated with SCLC. Most patients benefit from 3, 4-diaminopyridine plus pyridostigmine. In paraneoplastic LEMS, treatment of the tumor often results in neurological improvement. In non-paraneoplastic LEMS, prednisone alone or combined with immunosuppressants are treatment options. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.
Full Text of this Article in Japanese PDF (344K)

(CLINICA NEUROL, 51: 872|876, 2011)
key words: antibody-mediated disorders, myasthenia garvis: MG, Lambert-Eaton myasthenic syndrome: LEMS, musclespecific receptor tyrosine kinase: MuSK, LDL-receptor related protein 4: Lrp4

(Received: 20-May-11)