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Lambert-Eaton Myasthenic Syndrome: Differential Diagnoses & Workup

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
Coauthor(s): Donald B Sanders, MD, EMG Laboratory Director, Professor of Medicine (Neurology), Division of Neurology, Duke University Medical Center
Contributor Information and Disclosures

Updated: Jan 29, 2009

Differential Diagnoses

Acute Inflammatory Demyelinating Polyradiculoneuropathy
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Dermatomyositis/Polymyositis
Inclusion Body Myositis
Myasthenia Gravis
Spinal Muscular Atrophy

Other Problems to Be Considered

Cachexia
Paraneoplastic neuropathy

Workup

Laboratory Studies

  • Voltage-gated calcium channel antibodies
    • VGCC antibodies have been reported in 75-100% of patients with Lambert-Eaton myasthenic syndrome (LEMS) who have SCLC and in 50-90% of patients with LEMS without underlying cancer.
    • They are also found in fewer than 5% of patients with 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, systemic lupus erythematosus, rheumatoid arthritis).
    • Sensitivity and specificity of the VGCC assay are affected by the source of antigen and the specific laboratory measuring the antibody.
    • Reports suggest that SOX1, an immunogenic tumor antigen in small cell lung cancer, may play a role in identifying LEMS patients with lung cancer.1

Imaging Studies

  • CT scanning or MRI of chest
    • SCLC is the malignancy most frequently associated with LEMS.
    • In all adult patients with LEMS, imaging studies of the chest for cancer detection should be performed. 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.

Other Tests

  • Acetylcholine receptor antibodies
    • ACh receptor (AChR) antibodies are most commonly associated with MG.
    • AChR antibodies are occasionally found in low titers in LEMS.

Procedures

  • Repetitive nerve stimulation studies
    • These studies confirm the LEMS diagnosis by demonstrating characteristic findings on electrodiagnostic studies (see Media file 1). 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 repetitive nerve stimulation (RNS).
    • 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 Media file 2).
    • 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.
  • 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.
  • Bronchoscopy: If risk of lung cancer is substantial and findings on imaging studies are normal, perform bronchoscopy to detect SCLC. If these findings are also normal, consider PET scanning.

More on Lambert-Eaton Myasthenic Syndrome

Overview: Lambert-Eaton Myasthenic Syndrome
Differential Diagnoses & Workup: Lambert-Eaton Myasthenic Syndrome
Treatment & Medication: Lambert-Eaton Myasthenic Syndrome
Follow-up: Lambert-Eaton Myasthenic Syndrome
Multimedia: Lambert-Eaton Myasthenic Syndrome
References
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References

  1. Sabater L, Titulaer M, Saiz A, Verschuuren J, Güre AO, Graus F. SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology. March 2008;70:924-928. [Medline].

  2. Chalk CH, Murray NM, Newsom-Davis J, et al. Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. Neurology. Oct 1990;40(10):1552-6. [Medline].

  3. Elmqvist D, Lambert EH. Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin Proc. Oct 1968;43(10):689-713. [Medline].

  4. Lambert EH, Eaton LM, Rooke ED. Defect of neuromuscular conduction associated with malignant neoplasms. Am J Physiol. 1956;187:612-613. [Medline].

  5. Lennon VA. Serological profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology. 1997;48 (Suppl 5):S23-S27. [Medline].

  6. Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. Jun 1 1995;332(22):1467-74. [Medline].

  7. Lundh H, Nilsson O, Rosen I. Novel drug of choice in Eaton-Lambert syndrome. J Neurol Neurosurg Psychiatry. Jul 1983;46(7):684-5. [Medline].

  8. Lundh H, Nilsson O, Rosen I, Johansson S. Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome. Acta Neurol Scand. Aug 1993;88(2):136-40. [Medline].

  9. McEvoy KM, Windebank AJ, Daube JR, Low PA. 3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med. Dec 7 1989;321(23):1567-71. [Medline].

  10. O'Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain. Jun 1988;111 ( Pt 3):577-96. [Medline].

  11. Pellkofer HL, Armbruster L, Krumbholz M, Titulaer MJ, Verschuuren JJ, Schumm F, et al. Lambert-Eaton myasthenic syndrome differential reactivity of tumor versus non-tumor patients to subunits of the voltage-gated calcium channel. Journal of Neuroimmunology. 2008;epub ahead of print:[Medline].

  12. Sanders DB. Lambert-Eaton myasthenic syndrome: clinical diagnosis, immune-mediated mechanisms, and update on therapies. Ann Neurol. May 1995;37 Suppl 1:S63-73. [Medline].

  13. Sanders DB, Massey JM, Sanders LL, Edwards LJ. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology. Feb 8 2000;54(3):603-7. [Medline].

  14. Tim RW, Massey JM, Sanders DB. Lambert-Eaton myasthenic syndrome (LEMS). Clinical and electrodiagnostic features and response to therapy in 59 patients. Ann N Y Acad Sci. May 13 1998;841:823-6. [Medline].

  15. Tim RW, Sanders DB. Repetitive nerve stimulation studies in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. Sep 1994;17(9):995-1001. [Medline].

  16. Wirtz PW, Bradshaw J, Wintzen AR, Verschuuren JJ. Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families. J Neurol. Oct 2004;251(10):1255-9. [Medline].

  17. Wirtz PW, Wintzen AR, Verschuuren JJ. Lambert-Eaton myasthenic syndrome has a more progressive course in patients with lung cancer. Muscle Nerve. Aug 2005;32(2):226-9. [Medline].

  18. Zambelis T, Foutsitzi A, Giannakopoulou A, et al. Lambert-Eaton myasthenic syndrome. Clinical and electrophysiological findings in seven cases. Electromyogr Clin Neurophysiol. Jul-Aug 2004;44(5):289-92. [Medline].

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Further Reading

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Keywords

Lambert-Eaton myasthenic syndrome, LEMS, acetylcholine release, ACh release, neuromuscular transmission, small cell lung cancer, SCLC, non-SCLC lung cancer, non–small cell lung cancer, lymphosarcoma, malignant thymoma, carcinoma of the breast, carcinoma of the stomach, carcinoma of the colon, carcinoma of the prostate, carcinoma of the bladder, carcinoma of the kidney, carcinoma of the gallbladder

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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 and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Donald B Sanders, MD, EMG Laboratory Director, Professor of Medicine (Neurology), Division of Neurology, Duke University Medical Center
Donald B Sanders, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

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

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

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