Lambert-Eaton Myasthenic Syndrome (LEMS) Medication

Medical therapy is tailored for each patient and might include various combinations of the drugs listed below. Therapy is best coordinated with the primary care physician and appropriate consultants.

The initial pharmacotherapy for Lambert-Eaton myasthenic syndrome (LEMS) is with agents that increase the transmission of acetylcholine (ACh) across the neuromuscular junction, either by increasing the release of ACh or by decreasing the action of acetylcholinesterase. Treatment of the associated cancer may also decrease the weakness and other symptoms.

If these treatments are not effective and the patient has relatively mild weakness, aggressive immunotherapy may be warranted. In such cases, plasma exchange (PEX) or high-dose intravenous immunoglobulin (IVIg) may be used initially to induce rapid, albeit transitory, improvement.

Immunosuppressants should be added for more sustained improvement. Prednisone and azathioprine, the most frequently used immunosuppressants, can be used alone or in combination. Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot take or do not respond well to azathioprine.

IVIg, given in a course of 2 g/kg over 2-5 days, also induces clinically significant temporary improvement in many patients. The frequency of improvement in response to repeated courses of treatment has not been determined.

Class Summary

Neuromuscular agents produce symptomatic improvement in strength, autonomic symptoms, or both in some patients with LEMS. They act by inhibiting the breakdown of ACh, which is intended to help compensate for the relative lack of ACh quanta release in LEMS. They usually do not provide a significant improvement; however, a few patients with mild disease may note some difference.

Aminopyridines block potassium channels in membranes and facilitate chemical synaptic transmission at autonomic, neuromuscular, and central synapses. Both 4-aminopyridine and 3,4-diaminopyridine (DAP) have been used, but 4-aminopyridine is thought to be less effective and is almost twice as toxic, with many neurologic effects reported.

Acetylcholinesterase inhibitors do not usually produce dramatic improvement in LEMS, but they may provide relief from weakness or dry mouth in some patients. Pyridostigmine is the preferred agent and should be administered for several days before assessing response.

Pyridostigmine bromide (Mestinon, Regonol)

Pyridostigmine blocks ACh hydrolysis by cholinesterase, resulting in ACh accumulation at synapses and increasing stimulation of cholinergic receptors at myoneural junction.

In most of the literature, the consensus seems to be that monotherapy with a cholinesterase inhibitor is ineffective. It is in combination with drugs such as 3,4-diaminopyridine that cholinesterase inhibitors may have some slight benefit.

3,4-Diaminopyridine (DAP)

For more than 20 years, DAP has been used to improve strength and autonomic function in patients with LEMS. Effect begins about 20 minutes after an oral dose. Each dose lasts about 4 hours, and maximum effect of a given dosage may not be observed for 2-3 days. Patients with or without underlying cancer benefit from DAP. In the authors' experience, >80% of patients with LEMS have significant clinical benefit; in over half of these, improvement is marked.

This agent is not approved for clinical use in the United States, but it is available on a compassionate-use basis for individual patients. In most patients, pyridostigmine enhances and prolongs DAP's duration of action, permitting lower doses.

Obtain application process information from Jacobus Pharmaceutical Co., Inc., Princeton, NJ, 609-799-1176 (fax).

Guanidine HCl

Guanidine is thought to act by increasing free intracellular calcium concentrations through inhibition of mitochondrial respiration. It inhibits respiration by blocking potassium channels and thus prolonging the nerve terminal action potential. This increases release of ACh after nerve impulses and may decrease rates of repolarization and depolarization of muscle cell membranes. It temporarily improves strength in many patients with LEMS. Maximal effect may take 2-3 days. This agent is primarily cited in case reports and has not been studied in randomized trials.

Class Summary

If the therapies already described are ineffective, more aggressive immunotherapy may be indicated. Therapy can take the form of plasma exchange or high-dose IVIg, with the potential for more long-term immunosuppression, usually with prednisone or azathioprine.

Prednisone

Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders. The combination of corticosteroid therapy with azathioprine may be more effective than steroid monotherapy.

Azathioprine (Imuran, Azasan)

Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins. These effects may inhibit formation of immune cells, possibly reducing activity of immune system.

Class Summary

Agents in this category may be used to improve clinical and immunologic aspects of LEMS. They may decrease autoantibody production and increase solubilization and removal of immune complexes. IVIg can be an effective treatment for LEMS.

Intravenous immunoglobulin (IVIg) (Gamunex, Gammagard, Carimune NF)

Features of IVIg that may be relevant to efficacy include neutralization of circulating antibodies through anti-idiotypic antibodies; downregulation of proinflammatory cytokines, including interferon gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of suppressor T cells; blockade of the complement cascade; promotion of remyelination; and a possible increase in cerebrospinal fluid (CSF) immunoglobulin (IgG).