Immunological Mechanisms in the Lambert-Eaton Myasthenic Syndrome

  • A. Evoli
  • P. A. Tonali
Part of the Topics in Neuroscience book series (TOPNEURO)


The Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of neuromuscular and autonomic synaptic transmission. It is paraneoplastic in about 50% of cases, generally being associated with small-cell lung carcinoma (SCLC). In non-cancer cases, it can be associated with other autoimmune diseases [1].


Maximal Voluntary Contraction Immunological Mechanism Muscle Nerve Synaptic Vesicle Protein Repetitive Nerve Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    O’Neill JH, Murray NMF, Newsom-Davis J (1988) The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 111:577–596PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson HJ, Churchill-Davidson HC, Richardson AT (1953) Bronchial neoplasm with myasthenia: prolonged apnoea after administration of succinylcholine. Lancet ii:1291–1293CrossRefGoogle Scholar
  3. 3.
    Eaton LM, Lambert EH (1957) Electromyography and electrical stimulation in diseases of the motor unit: observations on a myasthenic syndrome associated with malignant tumors. JAMA 163:1117–1124CrossRefGoogle Scholar
  4. 4.
    Lambert EH, Rooke ED, Eaton LM, Hodgson CH (1962) Myasthenic syndrome occasionally associated with bronchial neoplasm: neurophysiologic studies. In: Viets HR (ed) Myasthenia gravis. Thomas, Springfield, Ill, pp 362–410Google Scholar
  5. 5.
    Lambert EH, Elmquist D (1971) Quantal components of end-plate potentials in the myasthenic syndrome. Ann N Y Acad Sci 183:183–199PubMedCrossRefGoogle Scholar
  6. 6.
    Fukunaga H, Engel AG, Osame M, Lambert EH (1982) Paucity and disorganization of presynaptic membrane active zones in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 5:686–697CrossRefGoogle Scholar
  7. 7.
    Lang B, Newsom-Davis J, Wray D et al (1981) Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet ii:224–226CrossRefGoogle Scholar
  8. 8.
    Fukunaga H, Engel AG, Lang B et al (1983) Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci USA 80:7636–7640PubMedCrossRefGoogle Scholar
  9. 9.
    Fukuoka T, Engel AG, Lang B et al (1987) Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones. Ann Neurol 22:193–199PubMedCrossRefGoogle Scholar
  10. 10.
    Lang B, Newsom-Davis J, Peers C et al (1987) The effects of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. J Physiol 390:257–270PubMedGoogle Scholar
  11. 11.
    Nagel A, Engel AG, Lang B et al (1988) Lambert-Eaton myasthenic syndrome IgG depletes presynaptic membrane active zones particles by antigenic modulation. Ann Neurol 24:552–558PubMedCrossRefGoogle Scholar
  12. 12.
    Roberts A, Perera S, Lang B et al (1985) Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature 317:737–739PubMedCrossRefGoogle Scholar
  13. 13.
    Greenberg DA (1999) Neuromuscular disease and calcium channels. Muscle Nerve 22:1341–1349PubMedCrossRefGoogle Scholar
  14. 14.
    Catterall WA (1998) Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. Cell Calcium 24:307–324PubMedCrossRefGoogle Scholar
  15. 15.
    Walker D, De Waard M (1998) Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function. Trends Neurosci 21:148–154PubMedCrossRefGoogle Scholar
  16. 16.
    Birnbaumer L, Campbell KP, Catterall WA et al (1994) The naming of voltage-gated calcium channels. Neuron 13:505–506PubMedCrossRefGoogle Scholar
  17. 17.
    Protti DA, Reisin R, Mackhnley TA, Uchitel OD (1996) Calcium channel blockers and transmitter release at the normal human neuromuscular junction. Neurology 46:1391–1396PubMedCrossRefGoogle Scholar
  18. 18.
    Day NC, Wood SJ, Ince PG et al (1997) Different localization of voltage-dependent calcium channel α1 subunits at the human and rat neuromuscular junction. J Neurosci 17:6226–6235PubMedGoogle Scholar
  19. 19.
    Liu H, De Waard M, Scott VES et al (1996) Identification of three subunits of the high affinity ω-conotoxin MVIIC-sensitive Ca2+ channel. J Biol Chem 271:13801–13810Google Scholar
  20. 20.
    Stanley EF (1997) The calcium channel and the organization of the presynaptic transmitter release face. Trends Neurosci 20:404–409PubMedCrossRefGoogle Scholar
  21. 21.
    Turner KM, Burgoyne RD, Morgan A (1999) Protein phosphorylation and the regulation of synaptic membrane traffic. Trends Neurosci 22:459–464PubMedCrossRefGoogle Scholar
  22. 22.
    Chen YA, Scales SL Patel SM et al (1999) SNARE complex formation is triggered by Ca2+ and drives membrane fusion. Cell 97:165–174PubMedCrossRefGoogle Scholar
  23. 23.
    Sher E, Gotti C, Canal N et al (1989) Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic sindrome. Lancet ii:640–643CrossRefGoogle Scholar
  24. 24.
    Lennon VA, Kryzen TJ, Griesman GE et al (1995) Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 332:1467–1474PubMedCrossRefGoogle Scholar
  25. 25.
    Motomura M, Johnston I, Lang B et al (1995) An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 58:85–87PubMedCrossRefGoogle Scholar
  26. 26.
    Satoh Y, Hirashima N, Tokumaru H et al (1998) Lambert-Eaton syndrome antibodies inhibit acetylcholine release and P/Q-type Ca2+ channels in electric ray nerve endings. J Physiol 508:427–438PubMedCrossRefGoogle Scholar
  27. 27.
    Waterman SA (1996) Multiple subtypes of voltage-gated calcium channel mediate transmitter release from parasympathetic neurons in the mouse bladder. J Neurosci 16:4155–4161PubMedGoogle Scholar
  28. 28.
    Waterman SA (1997) Role of N-, P-, and Q-type voltage-gated calcium channels in transmitter release from sympathetic neurons in the mouse vas deferens. Br J Pharmacol 120:393–398PubMedCrossRefGoogle Scholar
  29. 29.
    O’Sulleabhain P, Low PA, Lennon VA (1998) Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome. Serologic and clinical correlates. Neurology 50:80–93Google Scholar
  30. 30.
    Waterman S, Lang B, Newsom-Davis J (1997) Effect of Lambert-Eaton myasthenic syndrome antibodies on autonomic neurons in the mouse. Ann Neurol 42:147–156PubMedCrossRefGoogle Scholar
  31. 31.
    Lang B, Waterman S, Pinto A et al (1998) The role of autoantibodies in Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 841:596–605PubMedCrossRefGoogle Scholar
  32. 32.
    Houzen H, Hattori Y, Kanno M et al (1998) Functional evaluation of inhibition of autonomic transmitter release by autoantibody from Lambert-Eaton myasthenic syndrome. Ann Neurol 43:677–680PubMedCrossRefGoogle Scholar
  33. 33.
    Mason WP, Graus F, Lang B et al (1997) Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain 120:1279–1300PubMedCrossRefGoogle Scholar
  34. 34.
    Pinto A, Gillard S, Moss F et al (1998) Human antibodies specific for the α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons. Proc Natl Acad Sci USA 95:8328–8333PubMedCrossRefGoogle Scholar
  35. 35.
    Takamori M, Iwasa K, Komai K (1998) Antigenic sites of the vohage-gated calcium channels in the Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 841:625–635PubMedCrossRefGoogle Scholar
  36. 36.
    Iwasa K, Takamori M, Komai K, Mori Y (2000) Recombinant calcium channel is recognized by Lambert-Eaton myasthenic syndrome antibodies. Neurology 54:757–759PubMedCrossRefGoogle Scholar
  37. 37.
    Komai K, Iwasa K, Takamori M (1999) Calcium channel peptide can cause an autoimmune-mediated model of Lambert-Eaton myasthenic syndrome in rats. J Neurol Sci 166:126–130PubMedCrossRefGoogle Scholar
  38. 38.
    Verschnüren JJ, Dalmau J, Tunnel R et al (1998) Antibodies against the calcium channel β-subunit in the Lambert-Eaton myasthenic syndrome. Neurology 50:475–479CrossRefGoogle Scholar
  39. 39.
    Hajela RK, Atchison WD (1995) The proteins synaptotagmin and syntaxin are not general targets of Lambert-Eaton myasthenic syndrome autoantibodies. J Neurochem 64:1245–1251PubMedCrossRefGoogle Scholar
  40. 40.
    Takamori M, Maruta T, Komai K (2000) Lambert-Eaton myasthenic syndrome as an autoimmune calcium-channelopathy. Neurosci Res 36:183–191PubMedCrossRefGoogle Scholar
  41. 41.
    Vernino S, Adamski J, Kryzer TJ et al (1998) Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer related syndromes. Neurology 50:1806–1813PubMedCrossRefGoogle Scholar
  42. 42.
    Sanders DB (1995) Lambert-Eaton myasthenic syndrome: clinical diagnosis, immunemediated mechanisms, and update on therapies. Ann Neurol 37 (S1):S63–S73PubMedCrossRefGoogle Scholar
  43. 43.
    Lennon VA, Lambert EH, Whittingham S, Fairbanks V (1982) Autoimmunity in the Lambert-Eaton syndrome. Muscle Nerve 5:S21–S25PubMedGoogle Scholar
  44. 44.
    Maddison P, Newsom-Davis J, Mills KR (1998) Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 65:213–217PubMedCrossRefGoogle Scholar
  45. 45.
    Oh SJ (1988) Electromyography. Neuromuscular transmission studies. Williams and Wilkins, BaltimoreGoogle Scholar
  46. 46.
    Oh SJ, Kim DE, Kuruoglu R et al (1996) Electrophysiological and clinical correlations in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 19:903–906PubMedCrossRefGoogle Scholar
  47. 47.
    Oh SJ (1989) Diverse electrophysiological spectrum of the Lambert-Eaton myasthenic syndrome. Muscle Nerve 12:464–469PubMedCrossRefGoogle Scholar
  48. 48.
    Lo Monaco M, Milone M, Padua L, Tonali P (1997) Combined low-rate nerve stimulation and maximal voluntary contraction in the detection of compound muscle action potential facilitation in Lambert-Eaton myasthenic syndrome. Muscle Nerve 20:1207–1208CrossRefGoogle Scholar
  49. 49.
    Motomura M, Lang B, Johnston I et al (1997) Incidence of serum anti-P/Q type and N-type antibodies in the Lambert-Eaton myasthenic syndrome. J Neurol Sci 147:35–42PubMedCrossRefGoogle Scholar
  50. 50.
    Nakao YN, Motomura M, Suenaga A et al (1999) Specificity of ω-conotoxin MVIIC-binding and blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome. J Neurol 246:38–44PubMedCrossRefGoogle Scholar
  51. 51.
    Voltz, Carpentier AF, Rosenfeld MR et al (1999) P/Q type voltage-gated calcium channel antibodies in paraneoplastic disorders of the central nervous system. Muscle Nerve 22:119–122PubMedCrossRefGoogle Scholar
  52. 52.
    Vernino S, Lennon VA (2000) New Purkinje cell -voltage-gatedbody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 47:297–305PubMedCrossRefGoogle Scholar
  53. 53.
    Chalk CH, Murray NMF, Newsom-Davis J et al (1990) Response of the Lambert-Eaton myasthenic syndrome to the treatment of the associated small-cell lung carcinoma. Neurology 40:1552–1556PubMedCrossRefGoogle Scholar
  54. 54.
    Sanders DB, Massey JM, Sanders LL, Edwards LJ (2000) A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 54:603–607PubMedCrossRefGoogle Scholar
  55. 55.
    Thomsen RH, Wilson DF (1983) Effects of 4-aminopyridine and 3,4-diaminopyridine on transmitter release at the neuromuscular junction. J Pharmacol Exp Ther 227:260–265PubMedGoogle Scholar
  56. 56.
    Newsom-Davis J (1998) A treatment algorithm for Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 841:817–822PubMedCrossRefGoogle Scholar
  57. 57.
    Oh SJ, Kim DS, Kwon KH et al (1998) Wide spectrum of symptomatic treatment in Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 841:827–831PubMedCrossRefGoogle Scholar
  58. 58.
    Newsom-Davis J, Murray JNM (1984) Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology 34:480–485PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2002

Authors and Affiliations

  • A. Evoli
    • 1
  • P. A. Tonali
    • 1
  1. 1.Institute of NeurologyCatholic UniversityRomeItaly

Personalised recommendations