UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Lambert-Eaton myasthenic syndrome: Treatment and prognosis

Author
David H Weinberg, MD
Section Editors
Jeremy M Shefner, MD, PhD
Lisa M DeAngelis, MD, FAAN, FANA
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION

Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular junction transmission with the primary clinical manifestation of muscle weakness. Knowledge of subtle clinical features and laboratory abnormalities that accompany LEMS permits the early identification of the disorder. Early recognition of LEMS is particularly important because of its strong association with small cell lung cancer (SCLC). Although LEMS can occur at any point in the course of SCLC, it may serve as a marker for early disease, and thus allow more effective treatment of this malignancy.

This topic will review treatment for LEMS. The clinical features and diagnosis of this disorder are discussed separately. (See "Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis".)

EVALUATION FOR MALIGNANCY

The first priority in the management of LEMS is to evaluate for a primary underlying malignancy. Treatment of the underlying malignancy may be the only intervention necessary to produce improvement in neurologic symptoms.

Small cell lung cancer — Small cell lung cancer (SCLC) is the most common associated tumor in patients with LEMS. Suspicion for lung cancer is particularly high among patients with a history of smoking who are ≥50 years of age [1]. Population studies have consistently shown that approximately one-half of LEMS cases are associated with a malignancy, which is usually SCLC. In a clinical series that included 50 patients with LEMS, SCLC was present in 21 of 25 patients (84 percent) with cancer [2]. From the perspective of patients who have SCLC, the incidence and prevalence of LEMS are estimated to be approximately 3 percent each [3-5]. (See "Pathobiology and staging of small cell carcinoma of the lung".)

Other malignancies — The other malignancies most convincingly associated with LEMS are lymphoproliferative disorders, including Hodgkin lymphoma [6-8]. LEMS has been rarely associated with atypical carcinoid [9], Merkel cell carcinoma [10], thymic neuroendocrine carcinoma [11], malignant thymoma [12] and neuroblastoma [8].

                     
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 11, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Sanders DB, Guptill JT. Myasthenia gravis and Lambert-Eaton myasthenic syndrome. Continuum (Minneap Minn) 2014; 20:1413.
  2. O'Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 1988; 111 ( Pt 3):577.
  3. Wirtz PW, Lang B, Graus F, et al. P/Q-type calcium channel antibodies, Lambert-Eaton myasthenic syndrome and survival in small cell lung cancer. J Neuroimmunol 2005; 164:161.
  4. Elrington GM, Murray NM, Spiro SG, Newsom-Davis J. Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients. J Neurol Neurosurg Psychiatry 1991; 54:764.
  5. Payne M, Bradbury P, Lang B, et al. Prospective study into the incidence of Lambert Eaton myasthenic syndrome in small cell lung cancer. J Thorac Oncol 2010; 5:34.
  6. Argov Z, Shapira Y, Averbuch-Heller L, Wirguin I. Lambert-Eaton myasthenic syndrome (LEMS) in association with lymphoproliferative disorders. Muscle Nerve 1995; 18:715.
  7. Lemal R, Chaleteix C, Minard P, et al. Large granular lymphocytic leukemia associated with Lambert-Eaton Myasthenic Syndrome: A case report. Leuk Res Rep 2013; 2:32.
  8. Hajjar M, Markowitz J, Darras BT, et al. Lambert-Eaton syndrome, an unrecognized treatable pediatric neuromuscular disorder: three patients and literature review. Pediatr Neurol 2014; 50:11.
  9. Gutmann L, Phillips LH 2nd, Gutmann L. Trends in the association of Lambert-Eaton myasthenic syndrome with carcinoma. Neurology 1992; 42:848.
  10. Siau RT, Morris A, Karoo RO. Surgery results in complete cure of Lambert-Eaton myasthenic syndrome in a patient with metastatic Merkel cell carcinoma. J Plast Reconstr Aesthet Surg 2014; 67:e162.
  11. Nalbantoglu M, Kose L, Uzun N, et al. Lambert-Eaton myasthenic syndrome associated with thymic neuroendocrine carcinoma. Muscle Nerve 2015; 51:936.
  12. Lauritzen M, Smith T, Fischer-Hansen B, et al. Eaton-Lambert syndrome and malignant thymoma. Neurology 1980; 30:634.
  13. Titulaer MJ, Wirtz PW, Willems LN, et al. Screening for small-cell lung cancer: a follow-up study of patients with Lambert-Eaton myasthenic syndrome. J Clin Oncol 2008; 26:4276.
  14. Titulaer MJ, Soffietti R, Dalmau J, et al. Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 2011; 18:19.
  15. Titulaer MJ, Klooster R, Potman M, et al. SOX antibodies in small-cell lung cancer and Lambert-Eaton myasthenic syndrome: frequency and relation with survival. J Clin Oncol 2009; 27:4260.
  16. Titulaer MJ, Maddison P, Sont JK, et al. Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMS. J Clin Oncol 2011; 29:902.
  17. Wirtz PW, Verschuuren JJ, van Dijk JG, et al. Efficacy of 3,4-diaminopyridine and pyridostigmine in the treatment of Lambert-Eaton myasthenic syndrome: a randomized, double-blind, placebo-controlled, crossover study. Clin Pharmacol Ther 2009; 86:44.
  18. Oh SJ, Kim DS, Head TC, Claussen GC. Low-dose guanidine and pyridostigmine: relatively safe and effective long-term symptomatic therapy in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1997; 20:1146.
  19. Sanders DB, Massey JM, Sanders LL, Edwards LJ. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000; 54:603.
  20. McEvoy KM, Windebank AJ, Daube JR, Low PA. 3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med 1989; 321:1567.
  21. Oh SJ, Claussen GG, Hatanaka Y, Morgan MB. 3,4-Diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS. Muscle Nerve 2009; 40:795.
  22. Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev 2011; :CD003279.
  23. Oh SJ, Shcherbakova N, Kostera-Pruszczyk A, et al. Amifampridine phosphate (Firdapse(®)) is effective and safe in a phase 3 clinical trial in LEMS. Muscle Nerve 2016; 53:717.
  24. Wirtz PW, Titulaer MJ, Gerven JM, Verschuuren JJ. 3,4-diaminopyridine for the treatment of Lambert-Eaton myasthenic syndrome. Expert Rev Clin Immunol 2010; 6:867.
  25. Catalyst Pharmaceuticals provides update on the status of its Firdapse development activities. https://globenewswire.com/news-release/2017/08/30/1104204/0/en/Catalyst-Pharmaceuticals-Provides-Update-on-the-Status-of-its-Firdapse-Development-Activities.html (Accessed on October 03, 2017).
  26. Blumhardt LD, Joekes AM, Marshall J, Philalithis PE. Guanidine treatment and impaired renal function in the Eaton-Lambert syndrome. Br Med J 1977; 1:946.
  27. Kamenskaya MA, Elmqvist D, Thesleff S. Guanidine and neuromuscular transmission. I. Effect on transmitter release occurring spontaneously and in response to single nerve stimuli. Arch Neurol 1975; 32:505.
  28. O SJ, Kim KW. Guanidine hydrochloride in the Eaton-Lambert syndrome. Electrophysiologic improvement. Neurology 1973; 23:1084.
  29. Sanders DB. Lambert-eaton myasthenic syndrome: diagnosis and treatment. Ann N Y Acad Sci 2003; 998:500.
  30. Maddison P, Lang B, Mills K, Newsom-Davis J. Long term outcome in Lambert-Eaton myasthenic syndrome without lung cancer. J Neurol Neurosurg Psychiatry 2001; 70:212.
  31. Bain PG, Motomura M, Newsom-Davis J, et al. Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Neurology 1996; 47:678.
  32. Muchnik S, Losavio AS, Vidal A, et al. Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin. Muscle Nerve 1997; 20:674.
  33. Rich MM, Teener JW, Bird SJ. Treatment of Lambert-Eaton syndrome with intravenous immunoglobulin. Muscle Nerve 1997; 20:614.
  34. Takano H, Tanaka M, Koike R, et al. Effect of intravenous immunoglobulin in Lambert-Eaton myasthenic syndrome with small-cell lung cancer: correlation with the titer of anti-voltage-gated calcium channel antibody. Muscle Nerve 1994; 17:1073.
  35. Bird SJ. Clinical and electrophysiologic improvement in Lambert-Eaton syndrome with intravenous immunoglobulin therapy. Neurology 1992; 42:1422.
  36. Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012; 78:1009.
  37. Wittstock M, Benecke R, Zettl UK. Therapy with intravenous immunoglobulins: complications and side-effects. Eur Neurol 2003; 50:172.
  38. Streib EW, Rothner AD. Eaton-Lambert myasthenic syndrome: long-term treatment of three patients with prednisone. Ann Neurol 1981; 10:448.
  39. Lang B, Newsom-Davis J, Wray D, et al. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet 1981; 2:224.
  40. Dau PC, Denys EH. Plasmapheresis and immunosuppressive drug therapy in the Eaton-Lambert syndrome. Ann Neurol 1982; 11:570.
  41. Newsom-Davis J, Murray NM. Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology 1984; 34:480.
  42. Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol 2003; 23:191.
  43. Maddison P, McConville J, Farrugia ME, et al. The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2011; 82:671.
  44. Boutin E, Rey C, Romeu M, et al. [Favourable outcome after treatment with rituximab in a case of seronegative non-paraneoplastic Lambert-Eaton myasthenic syndrome]. Rev Med Interne 2013; 34:493.
  45. Motomura M, Hamasaki S, Nakane S, et al. Apheresis treatment in Lambert-Eaton myasthenic syndrome. Ther Apher 2000; 4:287.
  46. Maddison P, Newsom-Davis J, Mills KR, Souhami RL. Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma. Lancet 1999; 353:117.
  47. Maddison P, Gozzard P, Grainge MJ, Lang B. Long-term survival in paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology 2017; 88:1334.
  48. Titulaer MJ, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: tumor versus nontumor forms. Ann N Y Acad Sci 2008; 1132:129.
  49. Berglund S, Eriksson M, von Eyben FE, et al. Remission by chemotherapy of the Eaton-Lambert myasthenic syndrome in a patient with small cell bronchogenic carcinoma. Acta Med Scand 1982; 212:429.
  50. Jenkyn LR, Brooks PL, Forcier RJ, et al. Remission of the Lambert-Eaton syndrome and small cell anaplastic carcinoma of the lung induced by chemotherapy and radiotherapy. Cancer 1980; 46:1123.
  51. 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 1990; 40:1552.
  52. Oh SJ. SFEMG improvement with remission in the cancer-associated Lambert-Eaton myasthenic syndrome. Muscle Nerve 1989; 12:844.