Summary
The axonal patterns of Guillain-Barré syndrome, associated in many cases with antecedentCampylobacter jejuni infection, are now recognized as frequent causes of acute flaccid paralysis in some regions of the world. This study examined ultrastructurally the PNS of seven cases of the acute motor axonal neuropathy form of Guillain-Barré syndrome. In this disorder previous studies of advanced cases have found Wallerian-like degeneration of motor fibres in the spinal roots and peripheral nerves, with little lymphocytic inflammation or demyelination. The present study was focused on identifying early changes and establishing the sequence of changes. By electron microscopy the earliest and mildest changes consisted of lengthening of the node of Ranvier with distortion of the paranodal myelin, and in some instances with breakdown of the outermost myelin terminal loops. At this stage many nodes had overlying macrophages which extended their processes through the Schwann cell basal lamina covering the node and apposed the axolemma. Macrophage processes then extended beneath the myelin terminal loops, and the whole macrophage entered the periaxonal space at the paranode. Macrophage processes dissected the axon from the adaxonal Schwann cell plasmalemma and the macrophages advanced into the internodal periaxonal space, where they typically surrounded a condensed-appearing axon. At this stage the adaxonal Schwann cell cytoplasm regularly degenerated and disappeared, so that the periaxonal space was bounded by the innermost myelin lamella, and the axolemma of many fibres could not be seen. The internodal myelin sheath and the abaxonal Schwann cell cytoplasm remained normal. This arrangement appeared to be stable for some time, but in many fibres the axon subsequently underwent Wallerian-like degeneration. By interfering with impulse conduction, these nodal and periaxonal changes may explain paralysis in some pathologically mild cases. In addition, at early stages, these changes may be reversible, thus explaining the rapid recovery of some patients who become paralysed with acute motor axonal neuropathy. These observations, taken together with previous studies, suggest that acute motor axonal neuropathy is an antibody- and complement-mediated disorder in which the relevant epitopes are present on the nodal and internodal axolemma.
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References
Aguayo, A. J., Attiwell, M., Trecarten, J., Perkins, S &Bray, G. M. (1977a) Abnormal myelination in transplanted trembler mouse Schwann cells.Nature 265, 73–5.
Aguayo, A. J., Kasarjian, J., Samene, E., Kongshaun, P. &Bray, G. M. (1977b) Myelination of mouse axons by Schwann cells transplanted from normal and abnormal human nerves.Nature 268, 753–5.
Asbury, A. K., Arnason, B. G. &Adams, R. D. (1969) The inflammatory lesion in idiopathic polyneuritis.Medicine 48, 173–215.
Berciano, J., Coria, F., Monton, F., Calleja, J., Figols, J. &Lafarga, M. (1993) Axonal form of Guillain-Barré syndrome: evidence for macrophage-associated demyelination.Muscle and Nerve 16, 744–51.
Cole, J. S., Messing, A., Trojanowski, J. Q. &Lee, V. M.-Y. (1994) Modulation of axon diameter and neurofilaments by hypomyelinating Schwann cells in transgenic mice.Journal of Neuroscience 14, 6956–66.
Corbo, M., Quattrini, A., Latov, N., &Hays, A. P. (1993) Localization of GM1 and Gal(beta 1–3)GalNAc antigenic determinants in peripheral nerve.Neurology 43, 809–14.
Dewaegh, S. M., Lee, V. M.-Y. &Brady, S. T. (1992) Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells.Cell 68, 451–63.
Dyck, P. J. (1993) Is there an axonal variety of GBS?Neurology 43, 1277–80.
Enders, U., Karch, H., Toyka, K. V., Michels, M., Zielasek, J., Pette, M., Heesemann, J. &Hartung, H.-P. (1993) The spectrum of immune responses toCampylobacter jejuni and glycoconjugates in Guillain-Barré syndrome and in other neuroimmunological disorders.Annals of Neurology 34, 136–44.
Feasby, T. E., Gilbert, J. J., Brown, W. F., Bolton, C. F., Hahn, A. F., Koopman, W. F. &Zochodne, D. W. (1986) An acute axonal form of Guillain-Barré polyneuropathy.Brain 109, 1115–26.
Feasby, T. E., Hahn, A. F., Brown, W. F., Bolton, C. F., Gilbert, J. J. &Koopman, W. J. (1993) Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms?Journal of the Neurological Sciences 116, 185–92.
Fujimoto, S., Yuki, N., Itoh, T. &Amako, K. (1992) Specific serotype ofCampylobacter jejuni associated with Guillain-Barré syndrome.Journal of Infectious Disease 165, 183.
Fuller, G. N., Jacobs, J. M., Lewis, P. D. &Lane, R. J. M. (1992) Pseudoaxonal Guillain-Barré syndrome: severe demyelination mimicking axonopathy. A case with pupillary involvement.Journal of Neurology, Neurosurgery, and Psychiatry 55, 1079–83.
Ganser, A. L., Kirschner, D. A. &Willinger, M. (1983) Ganglioside localization on myelinated nerve fibres by cholera toxin binding.Journal of Neurocytology 12, 921–38.
Ganser, A. L. &Kirschner, D. A. (1984) Differential expression of gangliosides on the surfaces of myelinated nerve fibres.Journal of Neuroscience Research 12, 245–55.
Glass, J. D., Brushart, T. M., George, E. B. &Griffin, J. W. (1993) Prolonged survival of transected nerve fibres in C57BL/Ola mice is an intrinsic characteristic of the axon.Journal of Neurocytology 22, 311–21.
Glass, J. D., Schryer, B. L. &Griffin, J. W. (1994) Calcium-mediated degeneration of the axonal cytoskeleton in the Ola mouse.Journal of Neurochemistry,62, 2472–5.
Goldstein, J. M., Azizi, S. A., Booss, J. &Vollmer, T. L. (1993) Human immunodeficiency virus-associated motor axonal polyradiculoneuropathy.Archives of Neurology 50, 1316–19.
Gregson, N. A., Jones, D., Thomas, P. K. &Willison, H. J. (1991) Acute motor neuropathy with antibodies to GM1 ganglioside.Journal of Neurology 238, 447–51.
Griffin, J. W. &Price, D. L. (1981a) Demyelination in experimental IDPN and hexacarbon neuropathies: evidence for an axonal influence.Laboratory Investigation 45, 130–41.
Griffin, J. W. &Price, D. L. (1981b) Schwann cell and glial responses in 3,3′-iminodipropionitrile intoxication. I. Schwann cell and oligodendrocyte ingrowths.Journal of Neurocytology 10, 955–1007.
Griffin, J. W., Price, D. L., Drachman, D. B. &Morris, J. (1981) Incorporation of axonally transported glyco-proteins into axolemma during nerve regeneration.Journal of Cell Biology 88, 205–14.
Griffin, J. W., Drucker, N., Gold, B. G., Rosenfeld, J., Benzaquen, M., Charnes, L. R., Fahnestock, K. E. &Stocks, E. A. (1987) Schwann cell proliferation and migration during paranodal demyelination.Journal of Neuroscience 7, 682–99.
Griffin, J. W., Li, C. Y., Ho, T. W., Tian, M., Gao, C. Y., Xue, P., Mishu, B., Cornblath, D. R., Macko, C., McKhann, G. M. &Asbury, A. K. (1995a) Pathology of the motor-sensory axonal Guillain-Barré syndrome.Annals of Neurology, in press.
Griffin, J. W., Li, C. Y., Ho, T. W., Xue, P., Macko, C., Cornblath, D. R., Gao, C. Y., Yang, C., Tian, M., Mishu, B., McKhann, G. M. &Asbury, A. K. (1995b) Guillain-Barré syndrome in northern China: the spectrum of neuropathological changes in clinically defined cases.Brain 118, 577–95.
Hall, S. M., Hughes, R. A., Atkinson, P. F., McColl, I. &Gale, A. (1992) Motor nerve biopsy in severe Guillain-Barré syndrome.Annals of Neurology 31, 441–4.
Hirano, A. (1983) Reaction of the periaxonal space to some pathological process. InProgress in Neuropathology, Vol. 5 (edited byZimmerman, H. M.) pp. 99–112. New York: Raven Press.
Ho, T. W., Mishu, B., Li, C. Y., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J. &McKhann, G. M. (1995) Guillain-Barré syndrome in northern China: relationship toCampylobacter jejuni infection and anti-glycolipid antibodies.Brain 118, 597–605.
Honavar, M., Tharakan, J. K. J., Hughes, R. A. C., Leibowitz, S. &Winer, J. B. (1991) A clinicopathological study of the Guillain-Barré syndrome.Brain 114, 1245–69.
Hsieh, S.-T., Kidd, G. J., Crawford, T. O., Xu, Z., Lin, W.-M., Trapp, B. D., Cleveland, D. W. &Griffin, J. W. (1994) Regional modulation of neurofilament organization by myelination in normal axons.Journal of Neuroscience 14, 6392–401.
Inuzuka, T., Quarles, R. H., Heath, J. &Trapp, B. D. (1985) Myelin-associated glycoprotein and other proteins in Trembler mice.Journal of Neurochemistry 44, 793–7.
Jackson, C. E., Barohn, R. J. &Mendell, J. R. (1993) Acute paralytic syndrome in three American men. Comparison with Chinese cases.Archives of Neurology 50, 732–5.
Jones, H. B. &Cavanagh, J. B. (1983) Distortions of the nodes of Ranvier from axonal distention by filamentous masses in hexacarbon intoxication.Journal of Neurocytology 12, 439–58.
Koblar, S. A., Gregson, N. A., Hughes, R. A. C., Doherty, P. &Walsh, F. S. (1991)Campylobacter neuropathy.Neurology 41, 1327–8.
Kornberg, A. J., Pestronk A., Bieser, K., Ho, T. W., McKhann, G. M., Wu, H. S. &Jiang, Z. (1994) The clinical correlates of high-titer IgG anti-GM1 antibodies.Annals of Neurology 35, 234–7.
Korobkin, R., Asbury, A. K., Sumner, A. J. &Nielsen, S. L. (1975) Glue-sniffing neuropathy.Archives of Neurology 32, 158–62.
Kusunoki, S., Chiba, A., Kon, K., Ando, S., Arisawa, K., Tate, A. &Kanazawa, I. (1994) N-acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain-Barré syndrome.Annals of Neurology 35, 570–6.
Latov, N., Hays, A. P., Donofrio, P. D., Lio, J., Ho, H., McGinnis, S., Manaussos, K., Freddo, L., Shy, M., Sherman, W. H., Chang, H. W., Greenberg, H. S., Albers, J. W., Allessi, A. G., Keren, D., Yu, R. K., Rowland, L. P. &Kabat, E. A. (1988) Monoclonal IgM with unique binding to ganglioside GM1 and GD1b and to lact-N-tetraose associated with human motor neuron disease.Neurology 38, 763–8.
McKhann, G. M., Cornblath, D. R., Griffin, J. W., Ho, T. W., Li, C. Y., Jiang, Z., Wu, H. S., Zhaori, G., Liu, Y., Jou, L. P., Liu, T. C., Gao, C. Y., Mao, J. Y., Blaser, M. J., Mishu, B. &Asbury, A. K. (1993) Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China.Annals of Neurology 33, 333–42.
Oomes, P. G., Van der Meche, F. G., Markus-Silvis, L., Meulstee, J. &Kleyweg, R. P. (1991)In vivo effects of sera from Guillain-Barré subgroups: an electrophysiological and histological study on rat nerves.Muscle and Nerve 14, 1013–20.
Peters, A., Palay, S. L. &Webster, H. Def. (1991).The Fine Structure of the Nervous System: Neurons and their Supporting Cells, 3rd ed. New York: Oxford University Press.
Prineas, J. W. (1972) Acute idiopathic polyneuritis. An electron microscope study.Laboratory Investigation 26, 133–47.
Prineas, J. W. (1981) Pathology of the Guillain-Barré syndrome.Annals of Neurology 9(Suppl), 6–19.
Raine, C. S., Wisniewski, H. &Prineas, J. (1969) An ultrastructural study of experimental demyelination and remyelination.Laboratory Investigation 21, 316–27.
Ramos-Alvarez, M., Bessudo, L. &Sabin, A. (1969) Paralytic syndromes associated with noninflammatory cytoplasmic or nuclear neuronopathy: acute paralytic disease in Mexican children, neuropathologically distinguishable from Landry-Guillain-Barré syndrome.Journal of the American Medical Association 207, 1481–92.
Schlaepfer, W. W. &Bunge, R. P. (1973) Effects of calcium ion concentration on the degradation of amputated axons in tissue culture.Journal of Cell Biology 59, 456–70.
Schlaepfer, W. W. &Hasler, M. B. (1979) Characterization of the calcium-induced disruption of neurofilaments in rat peripheral nerves.Brain Research 168, 299–309.
Spencer, P. S. &Schaumburg, H. H. (1977) Ultrastructural studies of the dying back process. III. The evolution of experimental peripheral giant axonal degeneration.Journal of Neuropathology and Experimental Neurology 36, 276–99.
Spencer, P. S. &Thomas, P. K. (1974) Ultrastructural studies of the dying back process. II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axons.Journal of Neurocytology 3, 763–83.
Stanley, E., Griffin, J. W. &Fahnestock, K. E. (1985) Effect of IDPN-induced axonal swellings and paranodal demyelination on conduction in motor nerve fibres.Journal of the Neurological Sciences 69, 183–200.
Tessler, A., Autilio-Gambetti, A. &Gambetti, P. (1980) Axonal growth during regeneration: a quantitative autoradiographic study.Journal of Cell Biology 87, 197–203.
Thomas, F. P., Adapon, H. P., Goldberg, G. P., Latov, N. &Hays, A. P. (1989a) Localization of neural epitopes that bind to IgM monoclonal autoantibodies (M-proteins) from two patients with motor neuron disease.Journal of Neuroimmunology 21, 31–9.
Thomas, F. P., Lee, A. M., Romas, S. &Latov, N. (1989b) Monoclonal IgMs with anti-Gai (beta-3)Ga1NAc activity in lower motor neuron disease: identification of glyco-protein antigens in neural tissue and cross-reactivity with serum immunoglobulins.Journal of Neuroimmunology 23, 167–74.
Trapp, B. D. (1988) Distribution of the myelin-associated glycoprotein and P0 protein during myelin compaction in Quaking mouse peripheral nerve.Journal of Cell Biology 107, 675–85.
Trapp, B. D., Quarles, R. H. &Griffin, J. W. (1984a) Myelin-associated glycoprotein and myelinating Schwann cell-axon interaction in chronic beta, beta-iminodipropionitrile neuropathy.Journal of Cell Biology 98, 1272–8.
Trapp, B. D., Quarles, R. H. &Suzuki, K. (1984b) Immunocytochemical studies of quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the periaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells.Journal of Cell Biology 99, 594–606.
Triggs, W. J. &Cros, D. (1993) Axonal Guillain-Barré syndrome.Neurology 43, 1443.
Triggs, W. J., Cross, D., Gominak, S. C., Zuniga, G., Beric, A. I., Shahani, B. T., Ropper, A. H. &Roongta, S. M. (1992) Motor nerve inexcitability in Guillain-Barré syndrome.Brain 115, 1291–302.
Uncini, A., Santoro, M., Corbo, M., Lugaresi, A. &Latov, N. (1993) Conduction abnormalities induced by sera of patients with multifocal motor neuropathy and anti-GM1 antibodies.Muscle and Nerve 16, 610–15.
Vriesendorp, F. J., Mishu, B., Blaser, M. &Koski, C. L. (1993) Serum antibodies to GM1, peripheral nerve myelin, andCampylobacter jejuni in patients with Guillain-Barré syndrome and controls: correlation and prognosis.Annals of Neurology 34, 130–5.
Walsh, F. S., Cronin, M., Koblar, S., Doherty, P., Winer, J., Leon, A. &Hughes, R. A. C. (1991) Association between glycoconjugate antibodies andCampylobacter injection in patients with Guillain-Barré syndrome.Journal of Neuroimmunology 34, 43–51.
Willison, H. J., Paterson, G., Kennedy, P. G. &Veitch, J. (1994) Cloning of human anti-GM1 antibodies from motor neuropathy patients.Annals of Neurology 35, 471–8.
Willison, H. J. &Kennedy, P. G. (1993) Gangliosides and bacterial toxins in Guillain-Barré syndrome.Journal of Neuroimmunology 46, 105–12.
Winer, J. B., Hughes, R. A. C. &Osmond, C. (1988) A prospective study of acute idiopathic neuropathy. 2. Antecedent events.Journal of Neurology, Neurosurgery and Psychiatry,51, 613–18.
Yuki, N., Yoshino, H., Sato, S. &Miyatake, T. (1990) Acute axonal polyneuropathy associated with anti-GM1 antibodies followingCampylobacter jejuni enteritis.Neurology 40, 1900–2.
Yuki, N., Sato, S., Itoh, T. &Miyatake, T. (1991) HLA-B35 and acute axonal polyneuropathy followingCampylobacter jejuni infection.Neurology 41, 1561–3.
Yuki, N., Handa, S., Taki, T., Kasama, T., Takahashi, M. &Saito, K. (1992a) Cross-reactive antigen between nervous tissue and a bacterium elicits Guillain-Barré syndrome: molecular mimicry between gangliocide GM1 and lipopolysaccharide from Penner's serotype 19 ofCampylobacter jejuni.Biomedical Research 13, 451–3.
Yuki, N., Yoshino, H., Sato, S., Shinozawa, K. &Miyatake, T. (1992b) Severe acute axonal form of Guillain-Barré syndrome associated with IgG and anti-GD1a antibodies.Muscle and Nerve 15, 899–903.
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Griffin, J.W., Li, C.Y., Macko, C. et al. Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barré syndrome. J Neurocytol 25, 33–51 (1996). https://doi.org/10.1007/BF02284784
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DOI: https://doi.org/10.1007/BF02284784