Treatment of Lambert-Eaton myasthenic syndrome
- David H Weinberg, MD
David H Weinberg, MD
- Associate Professor of Neurology
- Tufts University School of Medicine
- Section Editors
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Jerome B Posner, MD
Jerome B Posner, MD
- Editor-in-Chief — Neurology
- Section Editor — Neurooncology
- Evelyn Frew American Cancer Society Clinical Research Professor
- Memorial Sloan-Kettering Cancer Center
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 "Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome".)
EVALUATION FOR MALIGNANCY
The aggressive search for a primary underlying malignancy in patients with any risk factors for small cell lung is central to the management of patients with Lambert-Eaton myasthenic syndrome (LEMS). (See "Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome".)
Small cell lung cancer (SCLC) is the most common associated tumor in patients with LEMS. Although available evidence suggests that early diagnosis does not confer longer survival in SCLC, there is some evidence that the presence of LEMS does imply a better prognosis [1,2].
The role of evaluating patients for occult SCLC was illustrated by a series of 100 patients with LEMS seen in a neurology clinic between 1998 and 2006 . With a minimum follow-up of three years, 54 patients had been diagnosed with SCLC. Overall, 92 percent of those with SCLC were diagnosed within three months and 96 percent within one year of their evaluation for LEMS. The most useful screening procedure was computed tomography (CT) of the thorax, which was more sensitive than routine chest x-ray (sensitivity 93 versus 51 percent) . Positron emission tomography (PET) was useful in selected cases and should be considered for any patient at the initial workup in whom the chest CT is nondiagnostic. (See "Computed tomographic and positron emission tomographic scanning of pulmonary nodules" and "Pathobiology and staging of small cell carcinoma of the lung".)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Oh SJ. SFEMG improvement with remission in the cancer-associated Lambert-Eaton myasthenic syndrome. Muscle Nerve 1989; 12:844.
- 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.
- Kalia J, Swartz KJ. Elucidating the molecular basis of action of a classic drug: guanidine compounds as inhibitors of voltage-gated potassium channels. Mol Pharmacol 2011; 80:1085.
- 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.
- 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.
- Oh SJ, Kim KW. Guanidine hydrochloride in the Eaton-Lambert syndrome. Electrophysiologic improvement. Neurology 1973; 23:1084.
- Sanders DB. Lambert-eaton myasthenic syndrome: diagnosis and treatment. Ann N Y Acad Sci 2003; 998:500.
- 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.
- Murray NM, Newsom-Davis J. Treatment with oral 4-aminopyridine in disorders of neuromuscular transmission. Neurology 1981; 31:265.
- Sanders DB, Massey JM, Sanders LL, Edwards LJ. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000; 54:603.
- 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.
- 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.
- 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.
- Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev 2011; :CD003279.
- 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.
- 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.
- Rich MM, Teener JW, Bird SJ. Treatment of Lambert-Eaton syndrome with intravenous immunoglobulin. Muscle Nerve 1997; 20:614.
- 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.
- Bird SJ. Clinical and electrophysiologic improvement in Lambert-Eaton syndrome with intravenous immunoglobulin therapy. Neurology 1992; 42:1422.
- 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.
- Wittstock M, Benecke R, Zettl UK. Therapy with intravenous immunoglobulins: complications and side-effects. Eur Neurol 2003; 50:172.
- Streib EW, Rothner AD. Eaton-Lambert myasthenic syndrome: long-term treatment of three patients with prednisone. Ann Neurol 1981; 10:448.
- Lang B, Newsom-Davis J, Wray D, et al. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet 1981; 2:224.
- Dau PC, Denys EH. Plasmapheresis and immunosuppressive drug therapy in the Eaton-Lambert syndrome. Ann Neurol 1982; 11:570.
- Newsom-Davis J, Murray NM. Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology 1984; 34:480.
- Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol 2003; 23:191.
- 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.
- Motomura M, Hamasaki S, Nakane S, et al. Apheresis treatment in Lambert-Eaton myasthenic syndrome. Ther Apher 2000; 4:287.
- 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.