Authors

M.J. Titulaer, M.D.
J.J.G.M. Verschuuren, M.D., Ph.D.
P.W. Wirtz, M.D., Ph.D.

Clinical features
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.

Epidemiology

In the Netherlands, the prevalence rate is 2.5 x 10^-6, the annual incidence 0.4 x 10^-6

Differential diagnosis

Myasthenia gravis

Ancillary investigations
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).

Genetics
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.

Therapy
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.

References

1. O'Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 1988;111:577-96.
2. Wirtz PW, Sotodeh M, Nijnuis M, Van Doorn PA, Van Engelen BG, Hintzen, RQ, De Kort PL, Kuks JB, Twijnstra A, De Visser M, Visser LH, Wokke JH, Wintzen AR, Verschuuren JJ. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome.
   J Neurol Neurosurg Psychiatry. 2002;73:766-8.
3. O'Suilleabhain P, Low PA, Lennon VA. Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates. Neurology 1998;50:88-93.
4. Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Valldeoriola F, Antoine JC, Rosenblum MK, Rosenfeld MR, Newsom-Davis J, Posner JB, Dalmau J. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain. 1997;120:1279-300.
5. Motomura M, Johnston I, Lang B, Vincent A, Newsom-Davis J. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.
   J Neurol Neurosurg Psychiatry. 1995;58:85-7.
6. Maddison P, Newsom-Davis J, Mills KR, Souhami RL. Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma.
   Lancet. 1999;353:117-8.