Abstract
Introduction:
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction. Antibody-mediated functional loss of voltage-gated calcium channels (VGCCs) on the presynaptic surface results in reduced neurotransmitter release. Muscle weakness starts in the proximal limbs and is accompanied by autonomic failure and areflexia. About 50-60% of the patients have small-cell lung cancer (SCLC), with antibodies produced in reaction to VGCC on tumor cells. In non-tumor LEMS, an autoimmune reaction causes antibody production. Knowledge of the pathophysiology of antibody production in SCLC-LEMS and non-tumor LEMS and a detailed understanding of the neuromuscular junction and its dysfunction in LEMS is needed for drug development.
Areas covered:
This review gives an overview of the clinical symptoms, diagnosis and pathophysiology of LEMS. Current treatment options and results of recent research on newly developed symptomatic treatment are described.
Expert opinion:
Extensive search for SCLC is needed in LEMS patients. Appropriate tumor treatment should be started in SCLC-LEMS. In both SCLC-LEMS and non-tumor LEMS, symptomatic treatment consists of 3,4-diaminopyridine. If insufficient, pyridostigmine can be added, although a small trial failed to prove its benefit in LEMS and it is probably only efficient in a subset of patients. In moderate-to-severe disease, immunosuppressive treatment with prednisolone and azathioprine should be started. Research on drugs in LEMS is complicated by the infrequency of the disorder. Future developments are mainly expected in the field of symptomatic treatment. Possibly, further studies on immunosuppression in myasthenia gravis will be meaningful for the therapeutic strategy in LEMS as well.
| Original language | English |
|---|---|
| Pages (from-to) | 159-167 |
| Number of pages | 9 |
| Journal | Expert Opinion on Orphan Drugs |
| Volume | 2 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2014 |
Bibliographical note
Funding Information:is supported by a grant from the Prinses Beatrix Spierfonds. JJGM Verschuuren is involved in the thymectomy trial that is sponsored by the NIH, and in a FP7 European grant on testing a vaccine to treat AChR MG with the company Curavac. The neurology department of the LUMC has received fees from BioMarin Ltd in 2009 --2010, because of consultancies by JJGM Verschuuren in the field of LEMS. JJGM Verschuuren did not receive any personal payments. A van Sonderen and PW Wirtz do not report any disclosures.
Funding Information:
MJ Titulaer is supported by grants from the Netherlands Organisation for Scientific Research (NOW, Veni-incentive), the Dutch Epilepsy Foundations (NEF, project 14-19), an ErasmusMC fellowship and a clinical research fellowship by the Dutch Cancer Society (KWF, number 2009-4451). MJ Titulaer received a travel grant for lecturing in India from Sun Pharma, India. MJ Titulaer was involved in the thymectomy trial sponsored by the NIH.
