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Lambert-Eaton Myasthenic Syndrome (LEMS) Medication

  • Author: David E Stickler, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
 
Updated: May 06, 2016
 

Medication Summary

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.

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Neuromuscular agents

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.

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Immunosuppressants

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 (Rayos)

 

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.

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Blood products

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-C, Gammagard, Carimune NF, Octagam, Privigen)

 

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).

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Contributor Information and Disclosures
Author

David E Stickler, MD Assistant Professor, Department of Neurosciences, Director of Electromyography Laboratory, Director of MDA Clinic, Director of Neuromuscular Service, Director of ALS Clinic, Medical University of South Carolina

David E Stickler, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Acknowledgements

Paul E Barkhaus, MD Professor, Department of Neurology, Medical College of Wisconsin; Director of Neuromuscular Diseases, Milwaukee Veterans Affairs Medical Center

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association

Disclosure: Nothing to disclose.

Neil A Busis, MD Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Pamela L Dyne, MD Professor of Clinical Medicine/Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center

Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Paul Kleinschmidt, MD Consulting Staff, Department of Emergency Medicine, Womack Army Medical Center

Paul Kleinschmidt, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: ScrubCast, INC Ownership interest Other

Donald B Sanders, MD EMG Laboratory Director, Professor of Medicine (Neurology), Division of Neurology, Duke University Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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  3. Wirtz PW, Sotodeh M, Nijnuis M, Van Doorn PA, Van Engelen BG, Hintzen RQ, et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 2002 Dec. 73(6):766-8. [Medline]. [Full Text].

  4. Sabater L, Titulaer M, Saiz A, Verschuuren J, Güre AO, Graus F. SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology. 2008 Mar 18. 70(12):924-8. [Medline].

  5. Titulaer MJ, Wirtz PW, Willems LN, van Kralingen KW, Smitt PA, Verschuuren JJ. Screening for small-cell lung cancer: a follow-up study of patients with Lambert-Eaton myasthenic syndrome. J Clin Oncol. 2008 Sep 10. 26(26):4276-81. [Medline].

  6. Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2011 Feb 16. 2:CD003279. [Medline].

  7. Tarr TB, Lacomis D, Reddel SW, Liang M, Valdomir G, Frasso M, et al. Complete reversal of Lambert-Eaton myasthenic syndrome synaptic impairment by the combined use of a K+ channel blocker and a Ca2+ channel agonist. J Physiol. 2014 Aug 15. 592:3687-96. [Medline].

  8. Maddison P, Newsom-Davis J. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2005 Apr 18. CD003279. [Medline].

  9. Illa I. IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current status. J Neurol. 2005 May. 252 Suppl 1:I14-8. [Medline].

 
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Characteristic responses to repetitive nerve stimulation in patient with Lambert-Eaton myasthenic syndrome. (A) Responses elicited from hand muscle by stimulation of nerve at 3 Hz. Amplitude of initial response is less than normal, and response is decremental. (B) Responses as in A, immediately after voluntary activation of muscle for 10 seconds. Amplitude has increased. (C) Responses in hand muscle elicited by 20-Hz stimulation of nerve for 10 seconds. Response amplitude is less than normal initially, falls further during first few stimuli, then increases and ultimately becomes more than twice initial value.
Compound muscle action potentials elicited from hand muscle before and immediately after maximal voluntary activation of muscle for 10 seconds. Amplitude is small initially, increasing almost 10 times after activation.
 
 
 
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