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Lambert-Eaton Myasthenic Syndrome (LEMS) Workup

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

Approach Considerations

In the emergency setting, very few tests are of importance in regard to Lambert-Eaton myasthenic syndrome (LEMS), because the diagnosis is not made in the emergency department (ED). It would be reasonable, however, to consider basic tests in any patient with cancer who reports weakness and dry mouth. These basic tests would include the following:

  • Complete blood count
  • Basic chemistry
  • Pulse oximetry

Other, more specific tests are ordered as indicated (see below).

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Antibody Assays

Voltage-gated calcium channel antibodies

Antibodies to voltage-gated calcium channels (VGCCs) have been reported in 75-100% of LEMS patients who have small cell lung cancer (SCLC) and in 50-90% of LEMS patients who do not have underlying cancer.

They are also found in fewer than 5% of patients with myasthenia gravis (MG), in up to 25% of patients with lung cancer without LEMS, and in some patients who do not have LEMS but have high levels of circulating immunoglobulins (eg, those with systemic lupus erythematosus or rheumatoid arthritis).

The sensitivity and specificity of the VGCC antibody assay are affected by the source of the antigen and the specific laboratory measuring the antibody.

Reports suggest that SOX1, an immunogenic tumor antigen in SCLC, may play a role in identifying LEMS patients with lung cancer.[4]

Acetylcholine receptor antibodies

ACh receptor (AChR) antibodies are most commonly associated with myasthenia gravis (MG) and are occasionally found in low titers in LEMS. The only true methods of differentiating MG from LEMS are the detection of AChR antibodies and the presence of underlying malignancy.

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Imaging Studies and Bronchoscopy

SCLC is the malignancy most frequently associated with LEMS. In all adult patients with LEMS, diagnostic imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest for cancer detection should be performed. Screening strategies may help to detect SCLC in patients with newly diagnosed LEMS and therefore offer a better approach to treatment.

If imaging findings are negative in a patient with a substantial risk of having lung cancer, bronchoscopy should be performed. If both imaging and bronchoscopy results are initially negative and risk factors for lung cancer are present, positron emission tomography (PET) scanning should be considered. If all imaging study results are negative in such patients, periodic reassessment thereafter is indicated.

In a large cohort study, Titulaer et al screened for tumors using various methods (CT, radiography,18 F-fluorodeoxyglucose PET (FDG-PET), bronchoscopy, or mediastinoscopy) and found that CT of the thorax detected 93% of the tumors.[5]

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Repetitive Nerve Stimulation Studies

Repetitive nerve stimulation (RNS) studies confirm the diagnosis of LEMS by demonstrating characteristic findings (see the image below). Compound muscle action potentials (CMAPs) recorded with surface electrodes are usually small, often less than 10% of normal, and fall during 1- to 5-Hz RNS.

Characteristic responses to repetitive nerve stimu 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.

During stimulation at 20-50 Hz, the CMAP increases in size (ie, facilitation) and characteristically becomes at least twice the size of the initial response. A similar increase in CMAP size is seen immediately after the patient voluntarily contracts the muscle maximally for several seconds (see the image below).

Compound muscle action potentials elicited from ha 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.

In virtually all patients with LEMS, a decremental response to low-frequency nerve stimulation is observed in the hand muscles. This finding is not specific to LEMS and can be seen in MG and other neuromuscular diseases.

In LEMS, the CMAP amplitude is low in most muscles tested. This finding is also nonspecific and is commonly observed in other neuromuscular diseases.

Facilitation greater than 100% is seen in some but not all muscles (or in all patients) with LEMS. Facilitation greater than 50% in any muscle suggests LEMS. However, these findings might also be observed in MG. If facilitation is greater than 100% in most muscles tested or greater than 400% in any muscle, the patient almost certainly has LEMS. If facilitation is less than 50% in all muscles tested, the patient still may have LEMS, especially if weakness has been present for only a short time or the patient has been partially treated.

When LEMS is mild, the electromyography (EMG) findings may resemble those of MG, including normal CMAP amplitudes, decremental response to RNS at low rates, and little facilitation. One helpful feature is that in LEMS, the EMG findings are usually more severe than the clinical findings would suggest. The opposite is frequently true in MG.

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Electromyography

Needle electromyography

Conventional needle EMG in LEMS demonstrates markedly unstable motor unit action potentials, which vary in shape during voluntary activation.

Single-fiber electromyography

The jitter and blocking measured by single-fiber EMG is increased markedly in LEMS, frequently out of proportion to the severity of weakness. In many endplates, jitter and blocking decrease as the firing rate increases. This pattern is not seen in all endplates or in all patients with LEMS.

Because jitter and blocking may also decrease at higher firing rates in some endplates of patients with MG, this pattern does not confirm an LEMS diagnosis unless it is dramatic and seen in most muscles.

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Edrophonium (Tensilon) Test

Testing with edrophonium (Tensilon) may be performed to help differentiate LEMS from MG. However, such testing is highly subjective, and it is of little value in the diagnosis of LEMS in the ED.

The test may produce an improvement in strength, but rarely is the response in patients with LEMS as noticeable as the typical response in patients with MG.

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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
  1. Tarr TB, Wipf P, Meriney SD. Synaptic Pathophysiology and Treatment of Lambert-Eaton Myasthenic Syndrome. Mol Neurobiol. 2014 Sep 9. [Medline].

  2. Young JD, Leavitt JA. Lambert-Eaton Myasthenic Syndrome: Ocular Signs and Symptoms. J Neuroophthalmol. 2016 Mar. 36 (1):20-2. [Medline].

  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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