Skip to main content
SpringerLink
Log in

Neuroimmunologic Mechanisms in the Etiology of Multiple Sclerosis

  • Chapter
Neuroinflammation

Part of the book series: Contemporary Neuroscience ((CNEURO))

  • 235 Accesses

Abstract

Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disorder of the central nervous system (CNS) (1,2) that is heterogeneous with respect to its clinical course, response to therapy, radiology, structural pathology, and immunopathogenesis. The factors that contribute to this heterogeneity are largely unknown, although it is likely a complex trait with genetic and environmental components. MS is a disease of young people with a median age of onset of 28 yr, and affects approx 0.1% of the population in temperate climates. The disorder is the most common cause of nontraumatic disability in young adults, with 50% of patients requiring a cane to walk 15 yr after disease onset (3).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Noseworthy, J. H. (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399 (Suppl.), A40 - A47.

    PubMed  CAS  Google Scholar 

  2. Noseworthy, J. H., Lucchinetti, C. F., Rodriguez, M., and Weinshekner, B. G. (2000) Medical progress: multiple sclerosis. N. Engl. J.Med. 343, 938–952.

    Article  PubMed  CAS  Google Scholar 

  3. Weinshenker, B. G., Bass, B., Rice, G. P., Noseworthy, J., Carriere, W., Baskerville, J., et al. (1989) The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain 112, 133–146.

    Article  PubMed  Google Scholar 

  4. Schumacher, G. A., Beebe, G., Kilber, R. F., et al. (1965) Problems of experimental trials of therapy in MS: report of the panel on evaluation of experimental trials in MS. Ann. NY Acad. Sci. 122, 552–568.

    Article  Google Scholar 

  5. Prineas, J. W. (1985) The neuropathology of multiple sclerosis, in Handbook of Clinical Neurology Volume 47: Demyelinating Diseases ( Koetsier, J. C., ed.), Elsevier Science, Amsterdam, pp. 337–395.

    Google Scholar 

  6. Lassmann, H. (1998) Pathology of multiple sclerosis, in McAlpine’s Multiple Sclerosis ( Compston, A., Ebers, G., Lassmann, H., McDonald, I., Matthews, B., and Wekerle, H., eds.), Churchill Livingstone, London, pp. 323–358.

    Google Scholar 

  7. Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., and Lassmann, H. (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis lesions: a study of 113 cases. Brain 122, 2279–2295.

    Article  PubMed  Google Scholar 

  8. Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., and Lassmann, H. (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707–717.

    Article  PubMed  CAS  Google Scholar 

  9. Lassmann, H., Brück, W., and Lucchinetti, C. (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol. Med. 7, 115–121.

    Article  PubMed  CAS  Google Scholar 

  10. Marburg, O. (1906) Die sogenannte “akute multiple sklerose.” Jahrb. Psychiatrie 27, 211–312.

    Google Scholar 

  11. Wood, D. D., Bilbao, J. M., O’Connors, P., and Moscarello, M. A. (1996) Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein. Ann. Neurol. 40, 18–24.

    Article  PubMed  CAS  Google Scholar 

  12. Storch, M. K., Piddlesden, S., Haltia, M., Iivanainen, M., Morgan, P., and Lassmann. H. (1998) Multiple sclerosis: in situ evidence for antibody and complement mediated demyelination. Ann. Neurol. 43, 465–471.

    Article  PubMed  CAS  Google Scholar 

  13. Genain, C. P., Cannella, B., Hauser, S. L., and Genain, C. P. (1999) Identification of auto-antibodies associated with myelin damage in multiple sclerosis. Nat. Med. 5, 170–175.

    Article  PubMed  CAS  Google Scholar 

  14. Hart, M. and Earle, K. (1975) Haemorrhagic and perivenous encephalitis: a clinical-pathoological review of 38 cases. J. Neurol. Neurosurg. Psych. 38, 585–591.

    Article  CAS  Google Scholar 

  15. Kesselring, J., Miller, D. H., Robb, S. A., Kendall, B. E., Moseley, I. F., Kingsley, D., et al. (1990) Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 113, 291–302.

    Article  PubMed  Google Scholar 

  16. Devic. C. (1894) Myelite subaigue complique de nevrite optique. Bull Med. 5, 18–30.

    Google Scholar 

  17. Wingerchuk, D. M., Hogancamp, W. E., O’Brien, P. C., and Weinshenker, B. G. (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53, 1107–1114.

    Article  PubMed  CAS  Google Scholar 

  18. Lucchinetti, C. F., Mandler, R., McGavern, D., Bruck, W., Gleich, G., Ransohoff, R., et al. (2002) A role for humoral mechanisms in the pathogenesis of Devic’ s neuromyelitis optica. Brain 125, 1450–1461.

    Article  PubMed  Google Scholar 

  19. Brück, W., Porada, P., Poser, S., et al. (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann. Neurol. 38, 788–796.

    Article  PubMed  Google Scholar 

  20. Brück, W., Sommermeier, N., Bergmann, M., Zettl, U., Goebel, H. H., Kretzschmar, H. A., et al. (1996) Macrophages in multiple sclerosis. Immunobiology 195, 588–600.

    Article  PubMed  Google Scholar 

  21. Lassmann, H., Raine, C. S., Antel, J., and Prineas, J. W. (1998) Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J. Neuroimmunol. 86, 213–217.

    Article  PubMed  CAS  Google Scholar 

  22. Prineas, J. W. and Wright, R. G. (1978) Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab. Invest. 38, 409–421.

    PubMed  CAS  Google Scholar 

  23. Lassmann, H. (1983) Comparative Neuropathology of Chronic Experimental Allergic Encephalomyelitis and Multiple Sclerosis. Springer-Verlag, Heidelberg.

    Book  Google Scholar 

  24. Sorensen, T. L., Tani, M., Jensen, J., Pierce, V., Lucchinetti, C., Folcik, V. A., et al. (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J. Clin. Invest. 103, 807–815.

    Article  PubMed  CAS  Google Scholar 

  25. Simpson, J. E., Newcombe, J., Cuzner, M. L., and Woodroofe, M. N. (2000) Expression of the interferon-y-inducible chemokines IP-10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions. Neuropathol. Appl. Neurobiol. 26, 133–142.

    Article  PubMed  CAS  Google Scholar 

  26. Simpson, J., Rezaie, P., Newcombe, J., Cuzner, M. L., Male, D., and Woodroofe, M. N. (2000) Expression of (3-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous systen tissue. J. Neuroimmunol. 108, 192–200.

    Article  PubMed  CAS  Google Scholar 

  27. Scotet, E., Peyrat, M.-A., Saulquin, X., Retiere, C., Couedel, C., Davodeau, F., et al. (1999) Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes. Eur. J. Immunol. 29, 973–985.

    Article  PubMed  CAS  Google Scholar 

  28. Babbe, H., Roers, A., Waisman, A., Lassmann, H., Goebels, N., Hohlfeld, R., et al. (2000) Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J. Exp. Med. 192, 393–404.

    Article  PubMed  CAS  Google Scholar 

  29. Bitsch, A., Schuchardt, J., Bunkowski, S., Kuhlmann, T., and Bruck, W. (2000) Acute axonal injury in multiple sclerosis: correlation with demyelination and inflammation. Brain 123, 1174–1183.

    Article  PubMed  Google Scholar 

  30. Reindl, M., Linington, C., Brehm, U., Egg, R., Dilitz, E., Deisenhammer, F., et al. (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122, 2047–2056.

    Article  PubMed  Google Scholar 

  31. Lindert, R.-B., Haase, C. G., Brehm, U., Linington, C., Wekerle, H., Hohlfeld, R. (1999) Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein. Brain 122, 2089–2099.

    Article  PubMed  Google Scholar 

  32. Guseo, A. and Jellinger, K. (1975) The significance of perivascular infiltrates in multiple sclerosis. J. Neurol. 211, 51–60.

    Article  PubMed  CAS  Google Scholar 

  33. Kerschensteiner, M., Gallmeier, E., Behrens, L., et al. (1999) Activated human T cells, B cells and monocytes produce brain-derived neurotrophic factor (BDNF) in vitro and in brain lesions: a neuroprotective role for inflammation? J. Exp. Med. 189, 865–870.

    Article  PubMed  CAS  Google Scholar 

  34. Giovannoni, G., Lai, M., Thorpe, J., Kidd, D., Chamoun, V., Thompson, A. J., et al. (1997) Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium-enhanced magnetic resonance imaging. Neurology 48, 1557–1565.

    Article  PubMed  CAS  Google Scholar 

  35. Yong, V. W., Krekoski, C. A., Forsyth, P. A., Bell, R., and Edwards, D. R. (1998) Matrix metalloproteinases and diseases of the CNS. Trends Neurosci. 21, 75–80.

    Article  PubMed  CAS  Google Scholar 

  36. Chandler, S., Miller, K. M., Clements, J. M., Lury, J., Corkill, D., Anthony, D. C., et al. (1997) Matrix metalloproteinases, tumour necrosis factor and multiple sclerosis: an overview. J. Neuroimmunol. 72, 155–161.

    Article  PubMed  CAS  Google Scholar 

  37. Cuzner, M. L., Gveric, D., Strand, C., Loughlin, A. J., Paeman, L., Opdenakker, G., et al. (1996) The expression of tissue-type plasminogen activator, matrix metalloproteinases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J. Neuropathol. Exp. Neurol. 55, 1194–1204.

    Article  PubMed  CAS  Google Scholar 

  38. Maeda, A. and Sobel, R. A. (1996) Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 55, 300–309.

    Article  PubMed  CAS  Google Scholar 

  39. Lee, M. A., Palace, J., Stabler, G., Ford, J., Gearing, A., and Miller, K. (1999) Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain 122, 191–197.

    Article  PubMed  Google Scholar 

  40. Uhm, J. H., Dooley, N. P., Stuve, O., Francis, G. S., Duquette, P., Antel, J. P., et al. (1999) Migratory behavior of lymphocytes isolated from multiple sclerosis patients: effects of interferon beta-lb therapy. Ann. Neurol. 46, 319–324.

    Article  PubMed  CAS  Google Scholar 

  41. Yong, V. W., Chabot, S., Stuve, O., and Williams, G. (1998) Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 51, 682–689.

    Article  PubMed  CAS  Google Scholar 

  42. Bonecchi, R., Bianchi, G., Bordignon, P. P., D’ Ambrosio, D., Lang, R., Borsatti, A., et al. (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th 1 s) and Th2s. J. Exp. Med. 187, 129–134.

    Article  PubMed  CAS  Google Scholar 

  43. Zhang, G. X., Baker, C. M., Kolson, D. L., and Rostomi, A. M. (2000) Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis. Multiple Sclerosis 6, 3–13.

    PubMed  CAS  Google Scholar 

  44. Lucchinetti, C. F., Bruck, W., Rodriguez, M., and Lassmann, H. (1998) Multiple sclerosis: lessons learned from neuropathology. Semin. Neurol. 18, 337–349.

    Article  PubMed  CAS  Google Scholar 

  45. Lovas, G., Szilâgyi, N., Majtényi, K., Palkovits, M., and Kolomy, S. (2000) Axonal changes in chronic demyleinated cervical spinal cord plaques. Brain 123, 308–317.

    Article  PubMed  Google Scholar 

  46. Prineas, J. W. and Graham, J. S. (1981) Multiple sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann. Neurol. 10, 149–158.

    Article  PubMed  CAS  Google Scholar 

  47. Prineas, J. W., Kwon, E. E., Cho, E. S., and Sharer, L. R. (1984) Continual breakdown and regeneration of myelin in progressive multiple sclerosis. Ann. NYAcad. Sci. 436, 11–32.

    Article  CAS  Google Scholar 

  48. Linington, C., Bradl, M., Lassmann, H., Brunner, C., and Vass, K. (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am. J. Pathol. 130, 443–454.

    PubMed  CAS  Google Scholar 

  49. Zajicek, J. P., Wing, M., Scolding, N. J., and Compston, D. A. (1992). Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing. Brain 115, 1611–1631.

    PubMed  Google Scholar 

  50. Raine, C. S., Cannella, B., Hauser, S. L., and Genain, C. P. (1999) Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen-specific antibody mediation. Ann. Neurol. 46, 144–160.

    Article  PubMed  CAS  Google Scholar 

  51. Weinshenker, B. G., O’Brien, P. C., Petterson, T. M., et al. (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann. Neurol. 46, 878–886.

    Article  PubMed  CAS  Google Scholar 

  52. Canella, B. and Raine, C. S. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann. Neurol. 37, 424–435.

    Article  Google Scholar 

  53. Link, H. (1998) The cytokine storm in multiple sclerosis. Multiple Sclerosis 4, 12–15.

    Article  PubMed  CAS  Google Scholar 

  54. Murray, P. D., Pavelko, K. D., Leibowitz, J., Lin, X., and Rodriguez, M. (1998) CD4+ and CD8+ T-cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis. J. Virol. 72, 7320–7329.

    PubMed  CAS  Google Scholar 

  55. D’Souza, S.D., Bonetti, B., Balasingam, V., Cashman, N. R., Barker, P. A., Troutt, A. B., et al. (1996) Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J. Exp. Med. 184, 2361–2370.

    Article  PubMed  Google Scholar 

  56. Probert, L., Akassoglou, K., Pasparakis, M., Kontogeorgos, G., and Kollias, G. (1995) Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor a. Proc. Natl. Acad. Sci. USA 92, 11294–11298.

    Article  PubMed  CAS  Google Scholar 

  57. Chiang, C.-S., Powell, H. C., Gold, L. H., Samimi, A., and Campbell, I. L. (1996) Macrophage/microglial-mediated primary demyelination and motor disease induced by the central nervous system production of interleukin-3 in transgenic mice. J. Clin. Invest. 97, 1512–1524.

    Article  PubMed  CAS  Google Scholar 

  58. Grenier, Y., Ruijs, T. C., Robitaille, Y., Olivier, A., and Antel, J. P. (1989) Immunohistochemical studies of adult human glial cells. J. Neuroimmunol. 21, 103–115.

    Article  PubMed  CAS  Google Scholar 

  59. Tsuchida, T., Parker, K. C., Turner, R. V., McFarland, H. F., Coligan, J. E., and Biddison, W. E. (1994) Autoreactive CD8+ T cell responses to human myelin protein-derived peptides. Proc. Natl. Acad. Sci. USA 91, 10859–10863.

    Article  PubMed  CAS  Google Scholar 

  60. Jiang, H., Zhang, S. L., and Pernis, B. (1992) Role of CD8+T cells in murine experimental allergic encephalomyelitis. Science 256, 1213–1215.

    Article  PubMed  CAS  Google Scholar 

  61. Koh, D. R., Fung-Leung, W. P., Ho, A., et al. (1992) Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice. Science 256, 1210–1213.

    Article  PubMed  CAS  Google Scholar 

  62. Sun, D., Qin, Y., Chluba, J., Epplen, J. T., and Wekerle, H. (1988) Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T-T-cell interactions. Nature 332, 843–845.

    Article  PubMed  CAS  Google Scholar 

  63. Huseby, E. S., Liggitt, D., Brabb, T., et al. (2001) A pathogenic role for myelin-specific CD8 (+) T-cells in a model for multiple sclerosis. J. Exp. Med. 194, 669–676.

    Article  PubMed  CAS  Google Scholar 

  64. Sun, D., Whitaker, J. N., Huang, Z., et al. (2001) Myelin antigen specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J. Immunol. 166, 7579–7587.

    PubMed  CAS  Google Scholar 

  65. D’Souza, S., Alinauskas, K., McCrea, E., Goodyer, C., and Antel, J. P. (1995) Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury. J. Neurosci. 15, 7293–7300.

    PubMed  Google Scholar 

  66. Scolding, N., Jones, J., Compston, D. A., and Morgan, B. P. (1990) Oligodendrocyte susceptibility to injury by T-cell perforin. Immunology 70, 6–10.

    PubMed  CAS  Google Scholar 

  67. Fazakerley, J. K. and Buchmeier, M. J. (1993) Pathogenesis of virus-induced demyelination. Adv. Virus Res. 42, 249–324.

    Article  PubMed  CAS  Google Scholar 

  68. Carrigan, D. R., Harrington, D., and Knox, K. K. (1996) Subacute leukoencephalitis caused by CNS infection with human herpesvirus-6 manifesting as acute multiple sclerosis. Neurology 47, 145–148.

    Article  PubMed  CAS  Google Scholar 

  69. Sanders, V. J., Waddell, A. E., Felisan, S. L., Li, X., and Conrad, A. J. (1996) Herpes simplex virus in postmortem multiple sclerosis brain tissue. Arch. Neurol. 53, 123–124.

    Article  Google Scholar 

  70. Challoner, P. B., Smith, K. T., Parker, J. D., MacLeod, D. L., Coulter, S. N., Rose, T. M., et al. (1995) Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc. Natl. Acad. Sci. USA 92, 7440–7444.

    Article  PubMed  CAS  Google Scholar 

  71. Johnson, A. W., Land, J. M., Thompson, E. J., et al. (1995) Evidence for increased nitric oxide production in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 58, 107.

    Article  PubMed  CAS  Google Scholar 

  72. Bo, L., Dawson, T. M., Wesselingh, S., Mork, S., Choi, K., Kong, P. A., et al. (1994) Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann. Neurol. 35, 778–786.

    Article  Google Scholar 

  73. Pitt, D., Werner, P., and Raine, C. (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med. 6, 67–69.

    Article  PubMed  CAS  Google Scholar 

  74. Ozawa, K., Suchanek, G., Breitschopf, H., Brück, W., Budka, H., Jellinger, K., et al. (1994) Patterns of oligodendroglia pathology in multiple sclerosis. Brain 117, 1311–1322.

    Article  PubMed  Google Scholar 

  75. Freedman, M. S., Ruijs, T. C., Selin, L. K., and Antel, J. P. (1991) Peripheral blood gamma/delta T cells lyse fresh human brain derived oligodendrocytes. Ann. Neurol. 30, 794–780.

    Article  PubMed  CAS  Google Scholar 

  76. Griot, C., Vandevelde, M., Richard, A., Peterhans, E., and Stocker, R. (1993) Selective degeneration of oligodendrocytes mediated by reactive oxygen species. Free Radical Res. Commun. 11, 181–193.

    Article  Google Scholar 

  77. Mitrovic, B., Ignarro, L. J., Montestruque, S., et al. (1994) Nitric oxide as a potential pathological mechanism in demyelination: its differential effects on primary glial cells in vitro. Neuroscience 61, 575–585.

    Article  PubMed  CAS  Google Scholar 

  78. Louis, J. C., Magal, E., Takayama, S., and Varon, S. (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259, 689–692.

    Article  PubMed  CAS  Google Scholar 

  79. Ludwin, S. K. and Johnson, E. S. (1981) Evidence of a “dying-back” gliopathy in demyelinating disease. Ann. Neurol. 9, 301–305.

    Article  PubMed  CAS  Google Scholar 

  80. Rodriguez, M. and Scheithauer, B. W. (1994) Ultrastructure of multiple sclerosis. Ultrastruct. Pathol. 18, 3–13.

    Article  PubMed  CAS  Google Scholar 

  81. Rodriguez, M. (1985) Virus-induced demyelination in mice: “dying-back” of oligodendrocytes. Mayo Clin. Proc. 3, 433–438.

    Google Scholar 

  82. Wolswijk, G. (1998) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci. 18, 601–609.

    PubMed  CAS  Google Scholar 

  83. Lassmann, H., Brück, W., Lucchinetti, C., and Rodriguez, M. (1997) Remyelination in multiple sclerosis. Multiple Sclerosis 3, 133–136.

    Article  PubMed  CAS  Google Scholar 

  84. Prineas, J. W., Barnard, R. O., Kwon, E. E., Sharer, L. R., and Cho, E. S. (1993) Multiple sclerosis: remyelination of nascent lesions. Ann. Neurol. 33, 137–151.

    Article  PubMed  CAS  Google Scholar 

  85. Prineas, J. W., Barnard, R. O., Revesz, T., Kwon, E. E., Sharer, L., and Cho, E. (1993) Multiple sclerosis: pathology of recurrent lesions. Brain 116, 681–693.

    Article  PubMed  Google Scholar 

  86. Raine, C. S., Scheinberg, L., and Waltz, J. M. (1981) Multiple sclerosis: oligodendrocyte survival and proliferation in an active established lesion. Lab. Invest. 45, 534–546.

    PubMed  CAS  Google Scholar 

  87. Brück, W., Schmied, M., Suchanek, G., Brück, Y., Breitschopf, H., Poser, S., et al. (1994) Oligodendrocytes in the early course of multiple sclerosis. Ann. Neurol. 35, 65–73.

    Article  PubMed  Google Scholar 

  88. Chang, A., Tourtellotte, W. W., Rudick, R., and Trapp, B. D. (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346, 165–173.

    Article  PubMed  Google Scholar 

  89. Kornek, B. and Lassmann, H. (1999) Axonal pathology in multiple sclerosis: a historical note. Brain Pathol. 9, 651–656.

    Article  PubMed  CAS  Google Scholar 

  90. Li, G. L., Farooque, M., Holtz, A., and Olsson, Y. (1995) Changes of 13-amyloid precursor protein after compression trauma to the spinal cord: an experimental study in the rat using immunohistochemistry. J. Neurotrauma 12, 269–277.

    Article  PubMed  CAS  Google Scholar 

  91. Pelletier, J., Suchet, L., Witjas, T., Habib, M., Guttmann, C. R. G., Salamon, G., et al. (2001) A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis. Arch. Neurol. 58, 105–111.

    Article  PubMed  CAS  Google Scholar 

  92. Bramlett, H. M., Kraydieh, S., Green, E. J., and Dietrich, W. D. (1997) Temporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats. J. Neuropathol. Exp. Neurol. 56, 1132–1141.

    Article  PubMed  CAS  Google Scholar 

  93. Yam, P. S., Takasago, T., Dewar, D., Graham, D. I., and McCulloch, J. (1997) Amyloid precursor protein accumulates in white matter at the matgin of a focal ischaemic lesion. Brain Res. 760, 150–157.

    Article  PubMed  CAS  Google Scholar 

  94. Ferguson, B., Matyszak, M. K., Esiri, M., and Perry, V. H. (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120, 393–399.

    Article  PubMed  Google Scholar 

  95. Kornek, B., Storch, M., Weissert, R., Wallstroem, E., Stefferl, A., Olsson, T., et al. (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive and remyelinated lesions. Am. J. Pathol. 157, 267–276.

    Article  PubMed  CAS  Google Scholar 

  96. Trapp, B. D., Peterson, J., Ransahoff, R. M., Rudick, R., Sverre, M., and Bo, L. (1998) Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338, 278–285.

    Article  PubMed  CAS  Google Scholar 

  97. Matthews, P. M., De Stefano, N., Narayanan, S., Francis, G. S., Wolinsky, J. S., Antel, J. P., et al. (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin. Neurol. 18, 327–336.

    Article  PubMed  CAS  Google Scholar 

  98. Birken, D. L. and Oldendorf, W. H. (1989) N-Acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci. Behay. Rev. 13, 23–31.

    Article  CAS  Google Scholar 

  99. Fisher, E., Rudick, R. A., Cutter, G., Baier, M., Miller, D., Weinstock-Guttman, B., et al. (2000) Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Multiple Sclerosis 6, 373–377.

    PubMed  CAS  Google Scholar 

  100. Pesini, P., Kopp, J., Wong, H., Walsh, J. H., Grant, G., and Hökfelt, T. (1999) An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system. Brain Res. 828, 41–59.

    Article  PubMed  CAS  Google Scholar 

  101. Grimaud, J., Barker, G. J., Wang, L., Lai, M., MacManus, D. G., Webb, S. L., et al. (1999) Correlation of magnetic resonance imaging parameters with clinical disability in multiple sclerosis: a preliminary study. J. Neurol. 246, 961–967.

    Article  PubMed  CAS  Google Scholar 

  102. Paolillo, A., Pozzilli, C., Gasperini, C., Giugni, E., Mainero, C., Giuliani, S., et al. (2000) Brain atrophy in relapsing-remitting multiple sclerosis: relationship with “black holes,” disease duration and clinical disability. J. Neurol. Sci. 174, 85–91.

    Article  PubMed  CAS  Google Scholar 

  103. Lovas, G., Szilagyi, N., Majtenyi, K., et al. (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123, 308–317.

    Article  PubMed  Google Scholar 

  104. Mews, I., Bergmann, M., Bunkowski, S., Gullotta, F., and Bruck, W. (1998) Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Multiple Sclerosis 4, 55–62.

    PubMed  CAS  Google Scholar 

  105. Evangelou, N., Esiri, M. M., Smith, S., Palace, J., and Matthews, P. M. (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann. Neurol. 47, 391–395.

    Article  PubMed  CAS  Google Scholar 

  106. Bjartmar, C., Kinkel, P. R., Kidd, G., Rudick, R. A., and Trapp, B. D. (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57, 1248–1252.

    Article  PubMed  CAS  Google Scholar 

  107. Rivera-Quinones, C., McGavern, D., Schmelzer, J. D., Hunter, S. F., Low, P. A., and Rodriguez, M. (1998) Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nat. Med. 4, 187–193.

    Article  PubMed  CAS  Google Scholar 

  108. Smith, K. J., Kapoor, R., and Felts, P. A. (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 9, 69–92.

    Article  PubMed  CAS  Google Scholar 

  109. Gimsa, U., Peter, S. V. A., Lehmann, K., Bechmann, I., and Nitsch, R. (2000) Axonal damage induced by invading T cells in organotypic central nervous system tissue in vitro: involvement of microglial cells. Brain Pathol. 10, 365–377.

    Article  PubMed  CAS  Google Scholar 

  110. Rawes, J. A., Calabrese, V. P., Khan, O. A., and DeVries, G. H. (1998) Antibodies to the axolemma-enriched fraction in the cerebrospinal fluid and serum of patients with multiple sclerosis and other neurological diseases. Multiple Sclerosis 3, 363–369.

    Article  Google Scholar 

  111. Sadatipour, B. T., Greer, J. M., and Pender, M. P. (1998) Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann. Neurol. 44, 980–983.

    Article  PubMed  CAS  Google Scholar 

  112. Perry, V. H., Brown, M. C., and Lunn, E. R. (1991) Very slow retrograde and Wallerian degeneration in the CNS of C57BL/Ola mice. Eur. J. Neurosci. 3, 102–105.

    Article  PubMed  CAS  Google Scholar 

  113. Lyon, M. F., Ogunkolade, B. W., Brown, M. C., Atherton, D. J., and Perry, V. H. (1993) A gene affecting Wallerian nerve degeneration maps distally on chromosome 4. Proc. Natl. Acad. Sci. USA 90, 9717–9720.

    Article  PubMed  CAS  Google Scholar 

  114. Bruck, W., Bruck, Y., Maruschak, B., and Friede, R. L. (1995) Mechanisms of macrophage recruitment in Wallerian degeneration. Acta Neuropathol. 89, 363–367.

    Article  PubMed  CAS  Google Scholar 

  115. Coleman, M. P., Confort, L., Buckmaster, E. A., Tarlton, A., Ewing, R. E., Browns, M. C., et al. (1998) An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse. Proc. Natl. Acad. Sci. USA 95, 9985–9990.

    Article  PubMed  CAS  Google Scholar 

  116. Conforti, L., Tarlton, A., Mack, T. G. A., Mi, W., Buckmaster, E. A., Wagner, D., et al. (2000) A Ufd2/D4Colele chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (W1ds) mouse. Proc. Natl. Acad. Sci. USA 97, 11377–11382.

    Article  PubMed  CAS  Google Scholar 

  117. Castelijns, J. A. and Barkhof, F. (1999) Magnetic resonance (MR) imaging as a marker for multiple sclerosis. Biomed. Pharmacother. 53, 351–357.

    Article  PubMed  CAS  Google Scholar 

  118. McFarland, H. F. (1999) Correlation between MR and clinical findings of disease activity in multiple sclerosis. AJNR 20, 1777–1778.

    PubMed  CAS  Google Scholar 

  119. Rovaris, M. and Filippi, M. (1999) Magnetic resonance techniques to monitor disease evolution and treatment trial outcomes in multiple sclerosis. Curr. Opin. Neurol. 12, 337–344.

    Article  PubMed  CAS  Google Scholar 

  120. Werring, D. J., Brassat, D., Droogan, A. G., Clark, C. A., Symms, M. R., Barker, G. J., et al. (2000) The pathogenesis of lesions and normal appearing white matter changes in multiple sclerosis. A serial diffusion MRI study. Brain 123, 1667–1676.

    Article  PubMed  Google Scholar 

  121. Truyen, L., van Waesberghe, J. H. T. M., van Walderveen, M. A. A., van Oosten, B. W., Polman, C. H., Hommes, O. R., et al. (1996) Accumulation of hypointense lesions (“black holes”) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 47, 1469–1476.

    Article  PubMed  CAS  Google Scholar 

  122. van Waesberghe, J. H. T. M., Kamphorst, W., De Groot, C. J. A., van Walderveen, M. A. A., Castelijns, J. A., Ravid, R., et al. (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann. Neurol. 46, 747–754.

    Article  PubMed  Google Scholar 

  123. Brex, P. A., Parker, G. J. M., Leary, S. M., Molyneux, P. D., Barker, G. J., Davie, C. A., et al. (2000) Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations. J. Neurol. Neurosurg. Psychiatry 68, 627–632.

    Article  PubMed  CAS  Google Scholar 

  124. De Stefano, N., Narayanan, S., Matthews, P. M., Mortilla, M., Dotti, M. T., Federico, A., et al. (2000) Proton MR spectroscopy to assess axonal damage in multiple sclerosis and other white matter diseases. J. Neurovirol. 6 (Suppl. 2), S121 - S129.

    Article  PubMed  Google Scholar 

  125. Jagust, W. J. and Noseworthy, J. H. (2000) Brain atrophy as a surrogate marker in MS. Faster, simpler, better? Neurology 54, 782–783.

    Article  PubMed  CAS  Google Scholar 

  126. Deloire-Grassin, M. S. A., Brochet, B., Quesson, B., Delalande, C., Dousset, V., Canioni, P., et al. (2000) In vivo evaluation of remyelination in rat brain by magnetization transfer imaging. J. Neurol. Sci. 178, 10–16.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Claudia F. Lucchinetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Brück
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Lassmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Oxon Medica, South San Francisco, CA, USA

    Paul L. Wood

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Lucchinetti, C.F., Brück, W., Lassmann, H. (2003). Neuroimmunologic Mechanisms in the Etiology of Multiple Sclerosis. In: Wood, P.L. (eds) Neuroinflammation. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-297-5_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-297-5_19

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9720-5

  • Online ISBN: 978-1-59259-297-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation