Lambert Eaton myasthenic syndrome

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 proximal 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 ophthalmoplegia 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, constipation, impaired sweating, or orthostatic hypotension. The autonomic dysfunction is mostly mild to moderate, in contrast to the severe disabling autonomic dysfunction in the anti-Hu syndrome. In half of the LEMS patients a small cell lung cancer (SCLC) will be found, mostly within 2 years after the diagnosis of LEMS.

 

Figure: Tumour detection in relation to the time of diagnosis of LEMS in 133 patients. (adapted from Wirtz et al. Clin Neurol Neurosurg. 2002;104:359-63).

In rare cases patients with LEMS and a SCLC develop a paraneoplastic cerebellar degeneration. In some patients cerebellar degeneration is present together with anti-voltage gated calcium channel (VGCC) antibodies, but without clinical signs or symptoms of myasthenic muscle weakness.

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.

Associated antibodies

Anti-P/Q-type VGCC antibodies are present in the serum of at least 85% of the patients. These antibodies are found in both forms of LEMS, with or without SCLC.
Antibodies to N-type VGCC have also been found in the serum. Their contribution to the muscle weakness or autonomic dysfunction is not completely understood, but is probably small. They are not used for diagnostic purposes.

Treatment

In contrast to most of the paraneoplastic neurological syndromes of the central nervous system LEMS responds very well to treatment. Symptomatic treatment consists of 3,4-diaminopyridine (3,4-DAP). Addition of pyridostigmin can also be tried; this drug is less effective as monotherapy than 3,4-DAP. More severe LEMS responds favourably to immunosuppressive treatment, like prednison and azathioprine. Plasma-exchange or intravenous immunoglobulins can be used in severe cases. Tumour treatment in SCLC-associated LEMS often results in remission of the muscle weakness and autonomic dysfunction. The presence of paraneoplastic LEMS in patients with SCLC results in longer survival compared to patients without LEMS.

 

Selected 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.