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Evidence for an Early Treatment of Multiple Sclerosis

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Early Indicators Early Treatments Neuroprotection in Multiple Sclerosis

Part of the book series: Topics in Neuroscience ((TOPNEURO))

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Abstract

Multiple sclerosis (MS) is a disease leading to a significant disability in the vast majority of patients [1, 2]. The available immunomodulatory treatments are not a cure for MS, but there is clear evidence from class I clinical trials that they significantly reduce the disease activity and delay the increase of disability in relapsing-remitting patients [3-10]. However, the positive effects are less clear in secondary progressive patients [11, 12]. The different effects of immunomodulatory treatments according to the disease course is probably explained by the complex pathogenesis of MS. Indications on the use of available therapies for MS have substantially changed in a few years, passing from a conservative [13, 14] to a more-aggressive attitude [15]. It is interesting to note that the consensus statement of the Canadian MS Clinic Network, recently published [15], on the use of disease modifying agents in MS, requires evidence of ongoing disease activity, which can be based on clinical or magnetic resonance imaging (MRI) data. The previous consensus of treatment [13, 14, 16, 17] required two or more relapses in the last 2 years in order to start treatment. These changes are probably explained by the results of the new trials testing the efficacy and safety of inter-ferons and glatiramer acetate [5-7, 10], by the experience acquired during these years, and by the recent knowledge of the pathophysiology of the disease. The demonstration of early irreversible axonal damage is a strong argument in favor of early treatment, an option that is beginning to be favored by many neurologists [18, 19].

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References

  1. Confavreux C, Aimard G, Devic M (1980) Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 103:281–300

    Article  PubMed  CAS  Google Scholar 

  2. Weinshenker BG, Bass B, Rice GPA, Noseworthy J, Carriere W, Baskerville J, Ebers GC (1989) The natural history of multiple sclerosis: a geographically based study. Clinical course and disability. Brain 112:133–146

    Article  PubMed  Google Scholar 

  3. The IFNB MS Study Group (A) (1993) Interferon Beta-lb is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:655–661

    Article  Google Scholar 

  4. Jacobs LD, Cookfair DL, Rudick RA et al (1996) Intramuscular interferon beta-la for disease progression in relapsing multiple sclerosis. Ann Neurol 39:285–294

    Article  PubMed  CAS  Google Scholar 

  5. Rudick RA, Goodkin D, Jacobs L et al (1997) Impact of interferon beta-la on neurologic disability in relapsing multiple sclerosis. Neurology 49:358–363

    Article  PubMed  CAS  Google Scholar 

  6. PRISMS (Prevention of Relapses and Disability by Interferon B-la Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon β-la in relapsing/remitting multiple sclerosis. Lancet 352:1498–1504

    Article  Google Scholar 

  7. The OWIMS Study. The Once Weekly Interferon for MS study Group (OWIMS) (1999) Evidence of interferon (3-la dose response in relapsing-remitting MS. Neurology 53:679–686

    Article  Google Scholar 

  8. Johnson KP, Brooks RB, Cohen JA, The Copolymer 1 Multiple Sclerosis Research Group (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of the phase III multicenter, double-blind, placebo-controlled trial. Neurology 45:1268–1276

    Article  Google Scholar 

  9. Johnson KP, Brooks RB, Cohen JA, The Copolymer 1 Multiple Sclerosis Research Group (1998) Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology 50:701–708

    Article  Google Scholar 

  10. Comi G, Filippi M, Copaxone MRI Study Group (1999) The effect of glatiramer acetate (Copaxone) on disease activity as measured by cerebral MRI in patients with relapsing-remitting multiple sclerosis (RRMS) Neurology 52:A289

    Google Scholar 

  11. European Study Group on Interferon β- lb in Secondary Progressive MS (1998) Placebo multicentre randomised trial of interferon β-lb in treatment of secondary progressive multiple sclerosis. Lancet 352:1491–1497

    Article  Google Scholar 

  12. Paty DW on behalf of the SPECTRIMS Study Group (1999) Results of the 3-year, double blind, placebo controlled study of interferon beta-la (Rebif) in secondary progressive MS. J Neurol 246 [suppl 11:I15

    Google Scholar 

  13. Report of the Quality Standards Subcommittee of the American Academy of Neurology (1994) Practice advisory on selection of patients with multiple sclerosis for treatment with Betaseron. Neurology 44:1537–1540

    Article  Google Scholar 

  14. Lublin FD, Whitaker JN, Eidelman BH, Miller AE, Arnason BGW, Burks JS (1996) Management of patients receiving interferon beta-lb for multiple sclerosis. Neurology 46:12–18

    Article  PubMed  CAS  Google Scholar 

  15. Oger J, Freedman M (1999) Consensus Statement of the Canadian MS Clinical Network on: The Use of Disease Modyfing Agents in Multiple Sclerosis. Can J Neurol Sci 26:274–275

    PubMed  CAS  Google Scholar 

  16. Polman CH, Miller DH, Mcdonald WI, Thompson AJ (1999) Treatment recommendations for interferon 13 in multiple sclerosis. J Neurol Neurosurg Psychiatry 67:561–566

    Article  PubMed  CAS  Google Scholar 

  17. Rieckman P, Toyka KV, and the Austrian-German-Swiss Multiple Sclerosis Therapy Consensus Group (MSTCG) (1999) Escalating immunotherapy of multiple sclerosis. Eur Neurol 42:121–127

    Article  Google Scholar 

  18. Comi G, Martinelli V, Martino G (1998) Early treatment of multiple sclerosis. Eur J Neurol 5 [suppl 2J:S19–S21

    Google Scholar 

  19. Rudick AR (1999) Disease-modifying drugs for relapsing remitting multiple sclerosis and future directions for multiple sclerosis therapeutics. Arch Neurol 56:1079–1084

    Article  PubMed  CAS  Google Scholar 

  20. Filippi M, Horsfield MA, Morissey SP, MacManus DG, Rudge P, McDonald WI, Miller DH (1994) Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis. Neurology 44:635–641

    Article  PubMed  CAS  Google Scholar 

  21. O’Riordan JI, Thompson AJ, Kingsley PE, MacManus DG, Kendall BE, Rudge P, McDonald WI, Miller DH (1998) The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain 121:495–503

    Article  PubMed  Google Scholar 

  22. Brex PA, O’Riordan JI, Miszkiel KA, Moseley IF, Thompson AJ, Plant GT, Miller DH (1999) Multisequence MRI in clinically isolated syndromes and the early development of MS. Neurology 53:1184–1190

    Article  PubMed  CAS  Google Scholar 

  23. Comi G, Filippi M, Barkhof F and the ETOMS Study Group (2001) Effects of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576–1582

    Article  Google Scholar 

  24. Lucchinetti C et al (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717

    Article  PubMed  CAS  Google Scholar 

  25. Soldestrom M, Jin Ya-Ping, Hillert J, Link H (1998) Optic neuritis: prognosis for multiple sclerosis from MRI, CSF, and HLA findings. Neurology 50:708–714

    Article  Google Scholar 

  26. Sciacca FL, Ferri C, Vandenbroeck K, Veglia F, Gobbi C, Martinelli F, Franciotta D, Zaffaroni M, Marrosu M, Martino G, Martinelli V, Comi G, Canal N, Grimaldi LMG (1999) Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS. Neurology 52:1896–1898

    Article  PubMed  CAS  Google Scholar 

  27. Weinshenker BG (1994) Natural history of multiple sclerosis. Ann Neurol 36 [Suppl]: 56–511

    Google Scholar 

  28. Runmarker B, Andersen O (1993) Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 116:117–134

    Article  PubMed  Google Scholar 

  29. Yu BM, Johnson MJ, Tuohy VK (1996) A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. J Exp Med 183:1777–1788

    Article  PubMed  CAS  Google Scholar 

  30. Thuoy VK, Weinstock-Guttman B, Kinkel RP (1997) Diversity and plasticity of self recognition during the development of multiple sclerosis. J Clin Invest 99:1682–1690

    Article  Google Scholar 

  31. Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL (1997) Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci U S A 94:599–603

    Article  PubMed  CAS  Google Scholar 

  32. Nicoletti F et al (1996) Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis. Neuroimmunology 70:87–90

    Article  CAS  Google Scholar 

  33. Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H (1996) Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 6:259–274

    Article  PubMed  CAS  Google Scholar 

  34. Lassmann H (1998) Neuropathology in multiple sclerosis: new concepts. Mult Scler 4:93–98

    PubMed  CAS  Google Scholar 

  35. Bo L et al (1994) Induction of nitricoxide synthase in demyeinating regions of multiple sclerosis brains. Ann Neurol 36:778–786

    Article  PubMed  CAS  Google Scholar 

  36. Charcot JM (1868) Histologie de la sclerose en plaques. Gaz Hop (Paris) 141:554–558

    Google Scholar 

  37. Putnam TJ (1936) Studies in multiple sclerosis. Arch Neurol Psychol 35:1289–1308

    Article  Google Scholar 

  38. Greenfield J, King L (1936) Observations on the histopathology of the cerebral lesions in disseminated sclerosis. Brain 59:445–458

    Article  Google Scholar 

  39. Prineas WJ, Barnard RO, Revesz T, Kwon EE, Sharer L, Cho ES (1993) Multiple sclerosis. Pathology of recurrent lesions. Brain 116:681–693

    Article  PubMed  Google Scholar 

  40. Rodriguez et al (1992) Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease. J Neuroimmunol 40:255–263

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  42. Ozawa K, Suchanek G, Breitschopf H, Bruck W, Budka H, Jellinger K, Lassmann H (1994) Patterns of oligodendroglia pathology in multiple sclerosis. Brain 117:1311–1322

    Article  PubMed  Google Scholar 

  43. Linington C, Engelhardt B, Kapocs G, Lassmann H (1992) Induction of persistenly demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demylinating antibody. J Neuroimmunol 40:219–224

    Article  PubMed  CAS  Google Scholar 

  44. Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393–399

    Article  PubMed  Google Scholar 

  45. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. New Engl J Med 338:278–285

    Article  PubMed  CAS  Google Scholar 

  46. Raine C, Cannella B, Hauser S, Genain C (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 

  47. Lovas G, Szilagyi N, Majtenyi K, Palkovits M, Komoly S (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123:308–317

    Article  PubMed  Google Scholar 

  48. Filippi M, Campi A, Colombo B, Pereira C, Martinelli V, Baratti C, Comi G (1996) A spinal cord MRI study of benign and secondary progressive multiple sclerosis. J Neurol 243(7):502–505

    Article  PubMed  CAS  Google Scholar 

  49. Losseff NA, Webb SL, O’Riordan JI, Page R, Wang L, Barker GJ, Tofts PS, McDonald WI, Miller DH, Thompson AJ (1996) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119:701–708

    Article  PubMed  Google Scholar 

  50. Narayana PA, Doyle TJ, Lai D, Wolinsky JSM (1998) Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 43:56–71

    Article  PubMed  CAS  Google Scholar 

  51. Tourbah A, Stievenart JL, Gout O, Fontaine B, Liblau R, Lubetzki C, Cabanis EA, Lyon-Caen O (1999) Localized proton magnetic resonance spectroscopy in relapsing remitting versus secondary progressive multiple sclerosis. Neurology 53:1091–1097

    Article  PubMed  CAS  Google Scholar 

  52. Sarchielli P, Presciutti O, Pelliccioli GP, Tarducci R, Gobbi G, Chiarini P, Alberti A, Vicinanza F, Gallai V (1999) Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients. Brain 122:513–521

    Article  PubMed  Google Scholar 

  53. Matthews PM, De Stefano N, Narayanan S, Francis GS, Wolinsky JS, Antel JP, Arnold DL (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 

  54. Falini A, Calabrese G, Filippi M, Origgi D, Lipari S, Colombo B, Comi G, Scotti G (1998) Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability. Am J Neuroradiol 19:223–229

    PubMed  CAS  Google Scholar 

  55. Rocca MA, Mastronardo G, Rodegher M, Comi G, Filippi M (1999) Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. Am J Neuroradiol 20:821–827

    PubMed  CAS  Google Scholar 

  56. Davie CA, Silver NC, Barker GJ, Tofts PS, Thompson AJ, McDonald WI, Miller DH (1999) Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup? J Neurol Neurosurg Psychiatry 67:710–715

    Article  PubMed  CAS  Google Scholar 

  57. Filippi M, Rocca MA, Minicucci L, Martinelli V, Ghezzi A, Bergamaschi R, Comi G (1999) Magnetization transfer imaging of patients with definite MS and negative conventional MRI. Neurology 52:845–848

    Article  PubMed  CAS  Google Scholar 

  58. Brochet B, Dousset V (1999) Pathological correlates of magnetization transfer imaging abnormalities in animal models and humans with multiple sclerosis. Neurology 53 [Suppl3]:S127

    Google Scholar 

  59. Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704

    Article  PubMed  CAS  Google Scholar 

  60. Dastidar P, Heinonen T, Lehtimaki T, Ukkonen M, Peltola J, Erila T, Laasonen E, Elovaara I (1999) Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis. J Neurol Sci 165:36–42

    Article  PubMed  CAS  Google Scholar 

  61. van Waesberghe JH, Kampphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama à Nijeholt G, van der Valk P, Polman C, Thompson AJ, Barkhof F (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46:747–754

    Article  PubMed  Google Scholar 

  62. Gass A et al (1994) Correlation of magnetization transfer ratio with disability in multiple sclerosis. Ann Neurol 36:62–67

    Article  PubMed  CAS  Google Scholar 

  63. Filippi M et al (1999) Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI. Neurology 52:588–594

    Article  PubMed  CAS  Google Scholar 

  64. Filippi M et al (1995) A magnetization transfer imaging study of normal appearing white matter in multiple sclerosis. Neurology 45:478–482

    Article  PubMed  CAS  Google Scholar 

  65. Iannucci G, Tortorella C, Rovaris M, Sormani MP, Comi G, Filippi M (2000) Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. Am J Neuroradiol 21:1034–1038

    PubMed  CAS  Google Scholar 

  66. Brex PA et al (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691

    Article  PubMed  CAS  Google Scholar 

  67. Rudick RA et al (1999) Use of the brain parenchimal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 10:1698–1704

    Article  Google Scholar 

  68. Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fisher JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer III FE, Brownscheidle and The Multiple Sclerosis Collaborative Research (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. Neurology 53:139–148

    CAS  Google Scholar 

  69. Beck RW, Cleary PA, Trobe JD et al (1993) The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. N Engl J Med 329:1764–1769

    Article  PubMed  CAS  Google Scholar 

  70. Optic Neuritis Study Group (1997) The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial. Neurology 49:1404–1413

    Article  Google Scholar 

  71. Jacobs LD, Beck RW, Simon JH and the CHAMPS Study Group (2000) Intramuscular interferon b-la therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 343:898–904

    Article  Google Scholar 

  72. McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. G. Comi
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  2. L. Moiola
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Editors and Affiliations

  1. European Charcot Foundation, Nijmegen, The Netherlands

    Otto R. Hommes

  2. Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

    Giancarlo Comi

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Comi, G., Moiola, L. (2004). Evidence for an Early Treatment of Multiple Sclerosis. In: Hommes, O.R., Comi, G. (eds) Early Indicators Early Treatments Neuroprotection in Multiple Sclerosis. Topics in Neuroscience. Springer, Milano. https://doi.org/10.1007/978-88-470-2117-4_1

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  • DOI: https://doi.org/10.1007/978-88-470-2117-4_1

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2171-6

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