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Pathology of the Normal-Appearing White Matter in Multiple Sclerosis

  • W. Brück
  • C. Stadelmann
Chapter
Part of the Topics in Neuroscience book series (TOPNEURO)

Abstract

Multiple sclerosis (MS) is regarded a chronic inflammatory disease of the central nervous system (CNS) leading to multifocal demyelinated plaques. The pathological hallmarks of the lesions are (1) inflammation with a cellular infiltrate consisting of T cells, a few B cells and macrophages/microglia; (2) demyelination with loss of oligodendrocytes in the chronic disease stage and a variable degree of remyelination especially in the early disease course; (3) axonal damage with significant axonal loss in chronic MS plaques; and (4) gliosis with astrocyte proliferation and intensive glial fibre production [1, 2]. The majority of MS patients start with a relapsing-remitting course, in which the inflammatory-demyelinating component of the disease predominates. In the progressive disease stage, which may be either primary or secondary, an additional neurodegenerative component appears to be involved [3], leading to extensive neuroaxonal damage in the chronic MS brain [4]. Loss of axons seems to be the major determinant of the persistent neurological deficit in the progressive disease stage of MS patients [5].

Keywords

Multiple Sclerosis Multiple Sclerosis Patient Multiple Sclerosis Lesion Axonal Loss Primary Progressive Multiple Sclerosis 
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.

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References

  1. 1.
    Lassmann H (1998) Pathology of multiple sclerosis. In: Compston A, Ebers G, Lassmann H et al (eds) McAlpine’s multiple sclerosis. Churchill Livingstone, London, pp 323–358Google Scholar
  2. 2.
    Prineas JW (1985) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Demyelinating diseases. Elsevier Science, Amsterdam, pp 213–257Google Scholar
  3. 3.
    Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 46:907–911PubMedCrossRefGoogle Scholar
  4. 4.
    Lassmann H (2003) Axonal injury in multiple sclerosis. J Neurol Neurosurg Psychiatry 74:695–697PubMedCrossRefGoogle Scholar
  5. 5.
    Trapp BD, Ransohoff R, Rudick R (1999) Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 12:295–302PubMedCrossRefGoogle Scholar
  6. 6.
    Brück W, Kuhlmann T, Stadelmann C (2003) Remyelination in multiple sclerosis. J Neurol Sci 206:181–185PubMedCrossRefGoogle Scholar
  7. 7.
    Barkhof F, Brück W, De Groot CJ et al (2003) Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol 60:1073–1081PubMedCrossRefGoogle Scholar
  8. 8.
    Brück W, Lucchinetti C, Lassmann H (2002) The pathology of primary progressive multiple sclerosis. Mult Scler 8:93–97PubMedCrossRefGoogle Scholar
  9. 9.
    Lassmann H, Brück W, Lucchinetti C (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 7:115–121PubMedCrossRefGoogle Scholar
  10. 10.
    Lucchinetti C, Brück W, Parisi J et al (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717PubMedCrossRefGoogle Scholar
  11. 11.
    Bitsch A, Brück W (2002) Differentiation of multiple sclerosis subtypes: implications for treatment. CNS Drugs 16:405–418PubMedCrossRefGoogle Scholar
  12. 12.
    Lucchinetti C, Brück W, Parisi J et al (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 122:2279–2295Google Scholar
  13. 13.
    Bitsch A, Kuhlmann T, da Costa C et al (2000) Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating activity and oligodendrocyte pathology. Glia 29:366–375PubMedCrossRefGoogle Scholar
  14. 14.
    Pitt D, Nagelmeier IE, Wilson HC, Raine CS (2003) Glutamate uptake by oligodendrocytes: implications for excitotoxicity in multiple sclerosis. Neurology 61:1113–1120PubMedCrossRefGoogle Scholar
  15. 15.
    Selmaj K, Cross AH, Farooq M et al (1991) Non-specific oligodendrocyte cytotoxicity mediated by soluble products of activated T cell lines. J Neuroimmunol 35:261–271PubMedCrossRefGoogle Scholar
  16. 16.
    D’Souza SD, Bonetti B, Balasingam V et al (1996) Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J Exp Med 184:2361–2370PubMedCrossRefGoogle Scholar
  17. 17.
    Matysiak M, Jurewicz A, Jaskolski D, Selmaj K (2002) TRAIL induces death of human oligodendrocytes isolated from adult brain. Brain 125:2469–2480PubMedCrossRefGoogle Scholar
  18. 18.
    Jurewicz A, Biddison WE, Antel JP (1998) MHC-class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. J Immunol 160:3056–3059PubMedGoogle Scholar
  19. 19.
    Merrill JE, Scolding NJ (1999) Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease. Neuropathol Appl Neurobiol 25:435–458PubMedCrossRefGoogle Scholar
  20. 20.
    Lassmann H, Brück W, Lucchinetti C, Rodriguez M (1997) Remyelination in multiple sclerosis. Mult Scler 3:133–136PubMedCrossRefGoogle Scholar
  21. 21.
    Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5:22–31PubMedCrossRefGoogle Scholar
  22. 22.
    Brück W, Schmied M, Suchanek G et al (1994) Oligodendrocytes in the early course of multiple sclerosis. Ann Neurol 35:65–73PubMedCrossRefGoogle Scholar
  23. 23.
    Prineas JW, Barnard RO, Kwon EE et al (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137–151PubMedCrossRefGoogle Scholar
  24. 24.
    Raine CS, Scheinberg L, Waltz JM (1981) Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion. Lab Invest 45:534–546Google Scholar
  25. 25.
    Lucchinetti CF, Brück W, Rodriguez M, Lassmann H (1996) Distinct patterns of multiple sclerosis pathology indicates heterogeneity in pathogenesis. Brain Pathol 6:259–274PubMedCrossRefGoogle Scholar
  26. 26.
    Kornek B, Lassmann H (1999) Axonal pathology in multiple sclerosis. A historical note. Brain Pathol 9:651–656CrossRefGoogle Scholar
  27. 27.
    Mews I, Bergmann M, Bunkowski S et al (1998) Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Mult Scler 4:5–62CrossRefGoogle Scholar
  28. 28.
    Lovas G, Szilágyi N, Komoly S et al (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123:308–317PubMedCrossRefGoogle Scholar
  29. 29.
    Kuhlmann T, Lingfeld G, Bitsch A et al (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212PubMedCrossRefGoogle Scholar
  30. 30.
    Allen IV, McKeown SR (1979) A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 41:81–91PubMedCrossRefGoogle Scholar
  31. 31.
    Tartaglia MC, Narayanan S, De Stefano N et al (2002) Choline is increased in prelesional normal appearing white matter in multiple sclerosis. J Neurol 249:1382–1390PubMedCrossRefGoogle Scholar
  32. 32.
    Allen IV, McQuaid S, Mirakhur M, Nevin G (2001) Pathological abnormalities in the normal-appearing white matter in multiple sclerosis. Neurol Sci 22:141–144PubMedCrossRefGoogle Scholar
  33. 33.
    Gobin SJ, Montagne L, van Zutphen M et al (2001) Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions. Glia 36:68–77PubMedCrossRefGoogle Scholar
  34. 34.
    Gveric D, Hanemaaijer R, Newcombe J et al (2001) Plasminogen activators in multiple sclerosis lesions. Implications for the inflammatory response and axonal damage. Brain 124:1978–1988PubMedCrossRefGoogle Scholar
  35. 35.
    Lindberg RLP, De Groot CJA, Montagne L et al (2001) The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 124:1743–1753PubMedCrossRefGoogle Scholar
  36. 36.
    Plumb J, McQuaid S, Mirakhur M, Kirk J (2002) Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol 12:154–169PubMedCrossRefGoogle Scholar
  37. 37.
    Kirk J, Plumb J, Mirakhur M, McQuaid S (2003) Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination. J Pathol 201:319–327PubMedCrossRefGoogle Scholar
  38. 38.
    Trapp BD, Peterson J, Ransohoff RM et al (1998) Axonal transection in the lesions of multiple sclerosis. New Engl J Med 338:278–285PubMedCrossRefGoogle Scholar
  39. 39.
    Bitsch A, Schuchardt J, Bunkowski S et al (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123:1174–1183PubMedCrossRefGoogle Scholar
  40. 40.
    Waller A (1850) Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibers. Phil Trans R Soc Lond (Biol) 140:423–429CrossRefGoogle Scholar
  41. 41.
    Brück W (1997) The role of macrophages in Wallerian degeneration. Brain Pathol 7:741–752PubMedCrossRefGoogle Scholar
  42. 42.
    Bjartmar C, Kinkel PR, Kidd G et al (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248–1252PubMedCrossRefGoogle Scholar
  43. 43.
    Evangelou N, Esiri MM, Smith S et al (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391–395PubMedCrossRefGoogle Scholar
  44. 44.
    Evangelou N, Konz D, Esiri MM et al (2000) Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. Brain 123:845–1849CrossRefGoogle Scholar
  45. 45.
    Ganter P, Prince C, Esiri MM (1999) Spinal cord axonal loss in multiple sclerosis: a post-mortem study. Neuropathol Appl Neurobiol 25:459–467PubMedCrossRefGoogle Scholar
  46. 46.
    Giordana MT, Richiardi P, Trevisan E, Boghi A, Palmucci L (2002) Abnormal ubiquitination of axons in normally myelinated white matter in multiple sclerosis brain. Neuropathol Appl Neurobiol 28:35–41PubMedCrossRefGoogle Scholar
  47. 47.
    Fu L, Matthews PM, De Stefano N et al (1998) Imaging axonal damage of normal appearing white matter in multiple sclerosis. Brain 121:103–113PubMedCrossRefGoogle Scholar
  48. 48.
    Casanova B, Martinez-Bisbal MC, Valero C et al (2003) Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis. A 1HMRS study. J Neurol 250:22–28Google Scholar
  49. 49.
    Itoyama Y, Sternberger NH, Webster HD (1980) Immunocytochemical observations on the distribution of myelin associated glycoprotein and myelin basic protein in multiple sclerosis lesions. Ann Neurol 7:167–177PubMedCrossRefGoogle Scholar
  50. 50.
    Wilczak N, De Keyser J (1997) Insulin-like growth factor-I receptors in normal appearing white matter and chronic plaques in multiple sclerosis. Brain Res 772:243–246PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2004

Authors and Affiliations

  • W. Brück
  • C. Stadelmann

There are no affiliations available

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