A myasthenic syndrome associated with small-cell tumours of the bronchus and with autoimmune diseases (Eaton-Lambert syndrome) has been attributed to diminished probability that a nerve action potential will release acetylcholine (ACh) from terminals of cholinergic nerves (somatic motor and autonomic) This model derives from evidence for reduced quantal content of the transmitter released by a nerve impulse The test procedure implies certain constancies of postsynaptic response Abnormal responses to ACh-agonists indicate that receptor response is not normal It is suggested that all previously described neuromuscular responses are compatible with a new model: the subsynaptic apparatus produces excess acetylcholinesterase (AChE) which limits the endplate conductance changes produced by normal output of ACh This model is supported by earlier ultramicroscopic studies which cannot be accounted for by the contemporary model.
It is proposed that enzyme induction by peptide or immunoglobulin may also be responsible for other paraneoplastic syndromes.
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References
1.
EatonLMLambertEH. Electromyography and electric stimulation of nerves in diseases of motor unit. Observations on myasthenic syndrome associated with malignant tumors. JAMA1957; 163:1117–1124.
2.
SimpsonJALenmanJAR. The effect of frequency of stimulation in neuromuscular disease. Electroenceph Clin Neurophysiol1959; 11:604–605.
3.
ElmqvistDLambertEH. Detailed analysis of neuromuscular transmission in a patient with myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin Proc1968; 43:689–713.
4.
LambertEHElmqvistD. Quantal components of endplate potentials in the myasthenic syndrome. Ann NY Acad Sci1971; 183:183–199.
5.
StalbergETronteljJ. Single Fibre Electromyography. Surrey: Mirvalle Press, 1979:131.
6.
HubbardJI. The effect of calcium and magnesium on the spontaneous release of transmitter from mammalian motor nerve endings. J Physiol (Lond)1961; 159:507–517.
7.
ElmqvistD. Potassium induced release of transmitter at the human neuromuscular junction. Acta Physiol Scand1965; 63:340–344.
8.
SimpsonJA. The defect in myasthenia gravis. In BittarEEBittarN. (eds). The Biological Basis of Medicine. London and New York: Academic Press1969; 3:345–387.
9.
SimpsonJA. A morphological explanation of the transmission defect in myasthenia gravis. Ann NY Acad Sci1971; 183:241–247.
10.
SimpsonJA. Myasthenia gravis: A new hypothesis. Scott Med J.1960; 5:419–436.
11.
EngelAGLambertEHHowardFM. Immune complexes (IgG and C3) at the motor endplate in myasthenia gravis: Ultrastructural and light microscopic localization and electrophysiological correlations. Mayo Clin Proc1977; 52:267–280.
12.
Cull-CandySGMilediRTrautmannAUchitelOD. On the release of the transmitter at normal, myasthenia gravis and myasthenic syndrome affected human endplates. J Physiol (Lond)1980; 299:621–638.
13.
HubbardJILlinasRQuastelDMJ. Electrophysiological Analysis of Synaptic Transmission. London: Edward Arnold (Publishers) Ltd, 1969.
14.
LambertEH. Defects of neuromuscular transmission in syndromes other than myasthenia gravis. Ann NY Acad Sci1966; 135:367–384.
15.
LundhHNilssonORosenI. 4-Aminopyridine–a new drug tested in the treatment of Eaton-Lambert syndrome. J Neurol Neurosurg Psychiat1977; 40:1109–1112.
16.
LambertEHRookeED. Myasthenic state and lung cancer. In BrainLordNorrisFH. (eds). The Remote Effects of Cancer on the Nervous System. New York: Grune and Stratton, 1965;67–80.
17.
KrnjevicKMilediR. Some effects produced by adrenaline upon neuromuscular propagation in rats. J. Physiol (Lond)1958; 141:291–304.
18.
LambertEHEatonLMRookeED. Defect of neuromuscular conduction associated with malignant neoplasms. Amer J Physiol1956; 187:612.
19.
AndersonHJChurchill-DavidsonHCRichardsonAT. Bronchial neoplasm with myasthenia. Prolonged apnoea after administration of succinylcholine. Lancet1953; 2:1291–1293.
20.
WiseRP. A myasthenic syndrome complicating bronchial carcinoma. Anaesthesia1962; 17:488–504.
21.
WiseRPMacDermotV. A myasthenic syndrome associated with bronchial carcinoma. J Neurol Neurosurg Psychiat1962; 25:31–39.
22.
LambertEHRookeEDEatonLMHodgsonCH. Myasthenic syndrome occasionally associated with bronchial neoplasm: Neurophysiological studies. In VietsHR. (ed). Myasthenia Gravis: The Second International Symposium Proceedings. Springfield Illinois: Charles C. Thomas. 1961;362–410.
23.
LindstromJMLambertEH. Content of acetylcholine receptor and antibodies bound to receptor in myasthenia gravis, experimental autoimmune myasthenia gravis and Eaton-Lambert syndrome. Neurology (Minneap)1978; 28:130–138.
24.
BensonWMMeekWJ. Hydrolysis of choline esters in the presence of adrenalin. Amer J Physiol1949; 158:327–331.
25.
EngelAGSantaT. Histometric analysis of the ultrastructure of the neuromuscular junction in myasthenia gravis and in the myasthenic syndrome. Ann NY Acad Sci1971; 183:46–63.
26.
PorterOWBarnardEA. Ultrastructural studies on the acetylcholine receptor at motor endplates of normal and pathologic muscles. Ann NY Acad Sci1976; 274:85–107.
27.
HartzellHCKufflerSWYoshikamiD. Postsynaptic potentiation: Interaction between quanta of acetylcholine at the skeletal neuromuscular synapse”. J Physiol (Lond)1975; 251:427–463.
28.
KordasM. On the role of junctional cholinesterase in determining the time course of the end-plate current. J Physiol (Lond)1977: 270:133–150.
29.
WakeK. Formation of myoneural and myotendinous junctions in the chick embryo. Cell Tissue Res1976; 173:383–400.
30.
ButlerIJDrachmanDBGoldbergAM. The effect of disease on cholinergic enzymes. J Physiol (Lond)1978; 274:593–600.
31.
DrachmanDB. Neutrotrophic regulation of muscle cholinesterase: Effects of botulinum toxin and denervation. J Physiol (Lond)1972; 226:619–627.
32.
FestoffBWFernandezHL. Plasma and red blood cell acetylcholinesterase in amyotrophic lateral sclerosis. Muscle Nerve.1981; 4:41–47.
33.
EngelAGLambertEHGomezMR. A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. Ann Neurol1977: 1:315–330.
34.
RathboneMBeresfordBYacoobC. Characterisation of a factor from nerve tissue that prevents post-denervation loss of the cholinesterase in cultured muscle. In BradleyWGGardner-MedwinDWaltonJN. (eds). Recent Advances in Myology. Amsterdam: Excerpta Medica and New York: American Elsevier, 1975;6–15.
35.
RaffMC. Histamine release from mast cells: An unusually accessible model of a ligand-induced cell response. In TalwarGP. (ed). Regulation of Growth and Differentiated Function in Eukaryote Cells. New York: Raven Press, 1975:177–184.
36.
HavemannKGroppCScheuerAScherfeTGramseM. ACTH-like activity in immune complexes of patients with oat-cell carcinoma of lung. Brit J Cancer1979; 39:43–50.
37.
LangBNewsom-DavisJWrayDVincentA. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet1981; 2:224–226.
