Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis
- David H Weinberg, MD
David H Weinberg, MD
- Associate Professor of Neurology
- Tufts University School of Medicine
- Section Editors
- Lisa M DeAngelis, MD, FAAN, FANA
Lisa M DeAngelis, MD, FAAN, FANA
- Section Editor — Neurooncology
- Chair, Department of Neurology
- Lillian Rojtman Berkman Chair in Honor of Jerome B. Posner
- Memorial Sloan Kettering Cancer Center
- 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
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 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.
This topic will review the pathophysiology, clinical features, and diagnosis of LEMS. Treatment and prognosis of LEMS is discussed separately. (See "Lambert-Eaton myasthenic syndrome: Treatment and prognosis".)
LEMS is a disorder of reduced acetylcholine (Ach) release from the presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration, and normal postsynaptic acetylcholine receptors. Lambert and Elmqvist, through a series of elegant intracellular muscle recordings, found that patients with what is now called LEMS had the following unique features [1,2]:
●Normal miniature endplate potential amplitude, demonstrating normal postsynaptic sensitivity to acetylcholine (ACh)
●Markedly reduced evoked endplate potential amplitude, suggesting a significant reduction in ACh releaseTo 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:
- Lambert EH, Elmqvist D. Quantal components of end-plate potentials in the myasthenic syndrome. Ann N Y Acad Sci 1971; 183:183.
- Elmqvist D, Lambert EH. Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin Proc 1968; 43:689.
- Molenaar PC, Newsom-Davis J, Polak RL, Vincent A. Eaton-Lambert syndrome: acetylcholine and choline acetyltransferase in skeletal muscle. Neurology 1982; 32:1061.
- Lang B, Newsom-Davis J, Wray D, et al. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet 1981; 2:224.
- Kim YI. Passive transfer of the Lambert-Eaton myasthenic syndrome: neuromuscular transmission in mice injected with plasma. Muscle Nerve 1985; 8:162.
- Kim YI. Passively transferred Lambert-Eaton syndrome in mice receiving purified IgG. Muscle Nerve 1986; 9:523.
- Kim YI, Sanders DB, Johns TR, et al. Lambert-Eaton myasthenic syndrome: the lack of short-term in vitro effects of serum factors on neuromuscular transmission. J Neurol Sci 1988; 87:1.
- 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.
- Motomura M, Hamasaki S, Nakane S, et al. Apheresis treatment in Lambert-Eaton myasthenic syndrome. Ther Apher 2000; 4:287.
- Motomura M, Johnston I, Lang B, et al. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1995; 58:85.
- Lang B, Pinto A, Giovannini F, et al. Pathogenic autoantibodies in the lambert-eaton myasthenic syndrome. Ann N Y Acad Sci 2003; 998:187.
- Pinto A, Gillard S, Moss F, et al. Human autoantibodies specific for the alpha1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons. Proc Natl Acad Sci U S A 1998; 95:8328.
- Benatar M, Blaes F, Johnston I, et al. Presynaptic neuronal antigens expressed by a small cell lung carcinoma cell line. J Neuroimmunol 2001; 113:153.
- Lang B, Vincent A, Murray NM, Newsom-Davis J. Lambert-Eaton myasthenic syndrome: immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity. Ann Neurol 1989; 25:265.
- Schoser B, Eymard B, Datt J, Mantegazza R. Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer. J Neurol 2017; 264:1854.
- Wirtz PW, Bradshaw J, Wintzen AR, Verschuuren JJ. Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families. J Neurol 2004; 251:1255.
- Wirtz PW, Smallegange TM, Wintzen AR, Verschuuren JJ. Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases. Clin Neurol Neurosurg 2002; 104:359.
- Lennon VA, Lambert EH, Whittingham S, Fairbanks V. Autoimmunity in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1982; 5:S21.
- Wirtz PW, Nijnuis MG, Sotodeh M, et al. The epidemiology of myasthenia gravis, Lambert-Eaton myasthenic syndrome and their associated tumours in the northern part of the province of South Holland. J Neurol 2003; 250:698.
- Abenroth DC, Smith AG, Greenlee JE, et al. Lambert-Eaton myasthenic syndrome: Epidemiology and therapeutic response in the national veterans affairs population. Muscle Nerve 2017; 56:421.
- 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.
- Wirtz PW, Wintzen AR, Verschuuren JJ. Lambert-Eaton myasthenic syndrome has a more progressive course in patients with lung cancer. Muscle Nerve 2005; 32:226.
- 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.
- 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.
- O'Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 1988; 111 ( Pt 3):577.
- EATON LM, LAMBERT EH. Electromyography and electric stimulation of nerves in diseases of motor unit; observations on myasthenic syndrome associated with malignant tumors. J Am Med Assoc 1957; 163:1117.
- Titulaer MJ, Wirtz PW, Kuks JB, et al. The Lambert-Eaton myasthenic syndrome 1988-2008: a clinical picture in 97 patients. J Neuroimmunol 2008; 201-202:153.
- Mason WP, Graus F, Lang B, et al. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain 1997; 120 ( Pt 8):1279.
- Nakao YK, Motomura M, Fukudome T, et al. Seronegative Lambert-Eaton myasthenic syndrome: study of 110 Japanese patients. Neurology 2002; 59:1773.
- Payne S, Wilkins D, Howard R. An unusual cause of dysphagia. J Neurol Neurosurg Psychiatry 2005; 76:146.
- Guruprakash GH, Ahmed I, Shadchehr A. Prostatic carcinoma. Report of a case presenting with dysphagia due to Eaton-Lambert syndrome. J Kans Med Soc 1982; 83:617.
- Jiang JR, Shih JY, Wang HC, et al. Small-cell lung cancer presenting with Lambert-Eaton myasthenic syndrome and respiratory failure. J Formos Med Assoc 2002; 101:871.
- Clark CV, Newsom-Davis J, Sanders MD. Ocular autonomic nerve function in Lambert-Eaton myasthenic syndrome. Eye (Lond) 1990; 4 ( Pt 3):473.
- O'Suilleabhain P, Low PA, Lennon VA. Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates. Neurology 1998; 50:88.
- Young JD, Leavitt JA. Lambert-Eaton Myasthenic Syndrome: Ocular Signs and Symptoms. J Neuroophthalmol 2016; 36:20.
- Wirtz PW, Sotodeh M, Nijnuis M, et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2002; 73:766.
- Breen LA, Gutmann L, Brick JF, Riggs JR. Paradoxical lid elevation with sustained upgaze: a sign of Lambert-Eaton syndrome. Muscle Nerve 1991; 14:863.
- Burns TM, Russell JA, LaChance DH, Jones HR. Oculobulbar involvement is typical with Lambert-Eaton myasthenic syndrome. Ann Neurol 2003; 53:270.
- Rudnicki SA. Lambert-Eaton myasthenic syndrome with pure ocular weakness. Neurology 2007; 68:1863.
- Laroche CM, Mier AK, Spiro SG, et al. Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. Thorax 1989; 44:913.
- Barr CW, Claussen G, Thomas D, et al. Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1993; 16:712.
- Nicolle MW, Stewart DJ, Remtulla H, et al. Lambert-Eaton myasthenic syndrome presenting with severe respiratory failure. Muscle Nerve 1996; 19:1328.
- Beydoun SR. Delayed diagnosis of Lambert-Eaton myasthenic syndrome in a patient presenting with recurrent refractory respiratory failure. Muscle Nerve 1994; 17:689.
- Preston DC, Shapiro BE. Neuromuscular junction disorders. In: Electromyography and neuromuscular disorders: Clinical-electrophysiologic correlations, 3rd ed, Elsevier, 2013. p.529.
- Oh SJ, Kim DE, Kuruoglu R, et al. Electrophysiological and clinical correlations in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1996; 19:903.
- AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: summary statement. Muscle Nerve 2001; 24:1236.
- AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome. Muscle Nerve 2001; 24:1239.
- Tim RW, Massey JM, Sanders DB. Lambert-Eaton myasthenic syndrome: electrodiagnostic findings and response to treatment. Neurology 2000; 54:2176.
- Oh SJ. Diverse electrophysiological spectrum of the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1989; 12:464.
- Oh SJ, Kurokawa K, Claussen GC, Ryan HF Jr. Electrophysiological diagnostic criteria of Lambert-Eaton myasthenic syndrome. Muscle Nerve 2005; 32:515.
- Bady B, Truffert A, Brechard M, et al. [Electrophysiologic data on myasthenic syndromes of the Lambert-Eaton type. A series of 23 cases]. Neurophysiol Clin 1992; 22:27.
- Tim RW, Sanders DB. Repetitive nerve stimulation studies in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1994; 17:995.
- Hatanaka Y, Oh SJ. Ten-second exercise is superior to 30-second exercise for post-exercise facilitation in diagnosing Lambert-Eaton myasthenic syndrome. Muscle Nerve 2008; 37:572.
- Crone C, Christiansen I, Vissing J. Myopathic EMG findings and type II muscle fiber atrophy in patients with Lambert-Eaton myasthenic syndrome. Clin Neurophysiol 2013; 124:1889.
- Trontelj JV, Stålberg E. Single motor end-plates in myasthenia gravis and LEMS at different firing rates. Muscle Nerve 1991; 14:226.
- Chaudhry V, Watson DF, Bird SJ, Cornblath DR. Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1991; 14:1227.
- Oh SJ, Ohira M. Single-fiber EMG and clinical correlation in Lambert-Eaton myasthenic syndrome. Muscle Nerve 2013; 47:664.
- Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995; 332:1467.
- Pellkofer HL, Armbruster L, Krumbholz M, et al. Lambert-eaton myasthenic syndrome differential reactivity of tumor versus non-tumor patients to subunits of the voltage-gated calcium channel. J Neuroimmunol 2008; 204:136.
- Kim YI. Lambert-Eaton myasthenic syndrome: evidence for calcium channel blockade. Ann N Y Acad Sci 1987; 505:377.
- Sanders DB, Guptill JT. Myasthenia gravis and Lambert-Eaton myasthenic syndrome. Continuum (Minneap Minn) 2014; 20:1413.
- Newsom-Davis J, Leys K, Vincent A, et al. Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. J Neurol Neurosurg Psychiatry 1991; 54:452.
- Oh SJ. Myasthenia gravis Lambert-Eaton overlap syndrome. Muscle Nerve 2016; 53:20.
- Voltage-gated calcium channel
- Paraneoplastic LEMS
- Non-paraneoplastic LEMS
- CLINICAL FEATURES
- Muscle weakness
- Postexercise facilitation
- Autonomic dysfunction
- Ptosis and cranial nerve involvement
- Respiratory failure
- EVALUATION AND DIAGNOSIS
- Confirming the diagnosis
- Electrodiagnostic studies
- - Motor and sensory nerve conduction studies
- - Repetitive nerve stimulation and exercise testing
- - Needle electromyography
- - Single fiber electromyography
- VGCC antibody testing
- Evaluation for malignancy
- DIFFERENTIAL DIAGNOSIS
- Progressive muscle weakness
- Myasthenia gravis
- SUMMARY AND RECOMMENDATIONS