27 May 2004
Lambert Eaton myasthenic syndrome is an autoimmune disorder of the neuromuscular junction, clinically characterised by proximal muscle weakness and autonomic dysfunction. In half of the patients a small cell lung carcinoma is found.
M.J. Titulaer, M.D.
J.J.G.M. Verschuuren, M.D., Ph.D.
P.W. Wirtz, M.D., Ph.D.
Lambert Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction. The disease is characterized by muscle weakness and autonomic dysfunction. In more than 90% of the patients the muscle weakness starts proximally in the legs. Weakness can spread to other skeletal muscles in a caudo-cranial order. In some patients this might lead to a need for artificial respiration. Ptosis and diplopia can be present, but tend to be milder than in autoimmune myasthenia gravis. Autonomic dysfunction in this disorder is characterized by the presence of a dry mouth, dryness of the eyes, blurred vision, impotence and obstipation, and is mostly mild to moderate. In half of the LEMS patients a small cell lung cancer (SCLC) will be found, mostly within 1 year after the diagnosis of LEMS. In rare cases patients with LEMS and a SCLC develop a paraneoplastic cerebellar degeneration.
Natural course and prognosis
In patients with SCLC, LEMS generally develops more progressively than in patients without SCLC. Survival in LEMS patients with SCLC is poor, due to the aggressiveness of the tumour, but is higher than is SCLC patients without LEMS.
In the Netherlands, the prevalence rate is 2.5 x 10-6, the annual incidence 0.4 x 10-6
The diagnosis is based on a typical history with in addition at least one of the following:1) low compound muscle action potential after nerve stimulation with decrement at low frequency stimulation (3 Hz) of more than 10%, and increment after high frequency stimulation (more than 20 Hz or preferably maximal voluntary contraction) of more than 100%. 2) presence of anti-P/Q-type voltage-gated calcium channel antibodies in the serum. Anti-P/Q-type VGCC antibodies are present in the serum of at least 85% of the patients (5).
In patients with LEMS (without SCLC) an increased (familial) frequency of additional autoimmune disorders is found, as well as high association with the HLA-B8DR3DQ2 haplotype, that associates with several other autoimmune disorders.
3,4-diaminopyridine is an effective drug in the treatment of LEMS. The additional effect of pyridostigmine is uncertain. Immunosuppressive therapy consists of prednisone and azathioprine. Immunoglobulins are also proven to be effective in LEMS. In patient with SCLC, LEMS generally remits with chemotherapy.
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