Benign Multiple Sclerosis: A Distinct Clinical Entity with Therapeutic Implications

  • S. J. Pittock
  • M. Rodriguez
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 318)

This chapter describes the natural history of multiple sclerosis and, in particular, reviews the controversy regarding the entity of benign multiple sclerosis. Based on the Olmsted County population prevalence cohort study performed at the Mayo Clinic, MS patients with EDSS scores of 2 or lower followed for a period of 5–10 years have a very small risk of developing disability over the next 10–20 years. Based on these findings, this chapter reviews the indications, efficacy, mode of action, and side effect profiles of the currently approved and available diseasemodifying agents for the treatment of multiple sclerosis. The efficacy of these agents is discussed based on the concepts of evidence-based medicine and the natural history of the disease. We review the arguments for and against treating all patients with MS. The authors propose an individualized approach to the use of these agents in the MS population.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    The IFBN multiple sclerosis study group (1993) Interferon beta-1b is effective in relapsingremitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:655-661Google Scholar
  2. 2.
    European study group in interferon beta-1b in secondary progressive MS (1998) placebocontrolled multicentre randomised trail of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 352:1491-1497CrossRefGoogle Scholar
  3. 3.
    Amato M, Ponziani G (2000) A prospective study on the prognosis of multiple sclerosis. Neurol Sci 21:831-838CrossRefGoogle Scholar
  4. 4.
    Bauer H, Firnhaber W, Winkler W (1965) Prognostic criteria in multiple sclerosis. Ann N Y Acad Sci 122:542-551PubMedCrossRefGoogle Scholar
  5. 5.
    Brass S, Narayanan S, Antel J, Lapierre Y, Collins L, Arnold D (2004) Axonal damage in multiple sclerosis patients with high versus low expanded disability status scale score. Can J Neurol Sci 31:225-228PubMedGoogle Scholar
  6. 6.
    Charcot J (1872) Leçons sur les maladies du système nerveux faites à La Salpetière. In: Delahaye A, Lecrosnier E (eds) Progres Medicale, ParisGoogle Scholar
  7. 7.
    Cohen J, Cutter G, Fischer J, Goodman A, Heidenreich F, Kooijmans M, Sandrock A, Rudick R, Simon J, Simonian N, Tsao E, Whitaker J, IMPACT Investigators. (2002) Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 59:679-686PubMedGoogle Scholar
  8. 8.
    Confavreux C, Aimard D, Devic M (1980) Course and prognosis of multiple sclerosis assessed by the computerised data processing of 349 patients. Brain 103:281-300CrossRefPubMedGoogle Scholar
  9. 9.
    Confavreux C, Compston A (2005) The natural history of multiple sclerosis. In: Compston A, Confavreaux C, Lassmann H, McDonald I, Miller D, Noseworthy J et al., (eds) Mcalpine’s multiple sclerosis, 4th edn. Churchill Livingston, Philadelphia, pp 183-272Google Scholar
  10. 10.
    Confavreux C, Vukusic S, Adeleine P (2003) Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process. Brain 126:770-782CrossRefPubMedGoogle Scholar
  11. 11.
    Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430-1438CrossRefPubMedGoogle Scholar
  12. 12.
    Davie C, Silver N, Barker G, Tofts P, Thompson AJ, McDonald W, Miller D (1999) Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup? J Neurol Neurosurg Psychiatry 67:710-715CrossRefPubMedGoogle Scholar
  13. 13.
    De Stefano N, Battaglini M, Stromillo ML, Zipoli V, Bartolozzi ML, Guidi L, Siracusa G, Portaccio E, Giorgio A, Sorbi S, Federico A, Amato MP (2006) Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis. Brain 129:2008-2016CrossRefPubMedGoogle Scholar
  14. 14.
    Eriksson M, Andersen O, Runmarker B (2003) Long-term follow-up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler 9:260-274CrossRefPubMedGoogle Scholar
  15. 15.
    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. ANJR Am J Neuroradiol 19:223-229Google Scholar
  16. 16.
    Filippi M, Campi A, Mammi S, Martinelli V, Locatelli T, Scotti G, Amadio S, Canal N, Comi G (1995) Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 58:31-37CrossRefPubMedGoogle Scholar
  17. 17.
    Filippi M, Campi A, Mammi S, Sacares P, MacManus D, Thompson A, Tofts P, McDonald W, Miller D (1994) Benign and secondary progressive multiple sclerosis: A preliminary quantitative MRI study. J Neurol 241:246-251CrossRefPubMedGoogle Scholar
  18. 18.
    Filippi M, Inglese M, Rovaris M, Sormani M, Horsfield M, Iannucci P, Colombo B, Comi G (2000) Magnetization transfer imaging to monitor the evolution of MS: A 1-year follow-up study. Neurology 55:940-946PubMedGoogle Scholar
  19. 19.
    Fog T, Linnemann F (1970) The course of multiple sclerosis in 73 cases with computerdesigned curves. Acta Neurol Scand 46:1-175CrossRefGoogle Scholar
  20. 20.
    Francis G (2004) Importance of benefit-to-risk assessment for disease-modifying drugs used to treat MS. J Neurol 251:V42-V49CrossRefPubMedGoogle Scholar
  21. 21.
    Frohman E, Havrdova E, Lublin F, Barkhof F, Achiron A, Sharief M, Stuve O, Racke M, Steinman L, Weiner H, Olek M, Zivadinov R, Corboy J, Raine C, Cutter G, Richert J, Filippi M (2006) Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis. Arch Neurol 63:614-619CrossRefPubMedGoogle Scholar
  22. 22.
    Goodkin D, Hertsgaard D (2000) Seasonal variation of multiple sclerosis exacerbations in North Dakota. Arch Neurol 46:1015-1018Google Scholar
  23. 23.
    Hartung H, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey S, Krapf H, Zwingers T (2002) Mitoxantrone in progressive multiple sclerosis: A placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360(9350):2018-2025CrossRefPubMedGoogle Scholar
  24. 24.
    Hawkins S, McDonnella G (1999) Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 67:148-152CrossRefPubMedGoogle Scholar
  25. 25.
    Horsfield M, Lai M, Webb S, Barker G, Tofts P, Turner R, Rudge P, Miller D (1996) Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance. Magn Reson Med 36:393-400CrossRefPubMedGoogle Scholar
  26. 26.
    Johnson K, Brooks B, Cohen J, Ford C, Goldstein J, Lisak R, Myers L, Panitch H, Rose J, Schiffer R, Vollmer T, Weiner L, Wolinsky J (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 45:1268-1276PubMedGoogle Scholar
  27. 27.
    Johnson K, Brooks B, Ford C, Goodman A, Guarnaccia J, Lisak R, Myers L, Panitch H, Pruitt A, Rose J, Kachuck N, Wolinsky J (2000) Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 multiple sclerosis study group. Mult Scler 6:255-266PubMedGoogle Scholar
  28. 28.
    Kantarci O, De Andrade M, Weinshenker B (2002) Identifying disease modifying genes in multiple sclerosis. J Neuroimmunol 123:144-159CrossRefPubMedGoogle Scholar
  29. 29.
    Kantarci O, Siva A, Eraksoy M, Karabudak R, Sutlas N, Agaoglu J, Turan F, Ozmenoglu M, Togrul E, Demirkiran M (1998) Survival and predictors of disability in Turkish MS patients. Turkish Multiple Sclerosis Study Group (TUMSSG). Neurology 51:765-772PubMedGoogle Scholar
  30. 30.
    Kappos L, Clanet M, Sandberg-Wollheim M, Radue E, Hartung H, Hohlfeld R, Xu J, Bennett D, Sandrock A, Goelz S (2005) Neutralizing antibodies and efficacy of interferon beta-1a: A 4-year controlled study. Neurology 65:40-47CrossRefPubMedGoogle Scholar
  31. 31.
    Kermode AG, Tofts PS, Thompson AJ, MacManus DG, Rudge P, Kendall BE, Kingsley DP, Moseley IF, du Boulay EP, McDonald WI (1990) Heterogeneity of blood-brain barrier changes in multiple sclerosis: An MRI study with gadolinium-DTPA enhancement. Neurology 40:229-235PubMedGoogle Scholar
  32. 32.
    Kinkel R (2006) Im interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 66:678-684CrossRefPubMedGoogle Scholar
  33. 33.
    Koopman R, Li D, Grochowsky E, Cutler P, Paty D (1989) Benign versus chronic progressive multiple sclerosis: Magnetic resonance imaging features. Ann Neurol 25:74-81CrossRefGoogle Scholar
  34. 34.
    Kurtzke J (1977) Geography in multiple sclerosis. J Neurol 215:1-26CrossRefPubMedGoogle Scholar
  35. 35.
    Kurtzke J (1983) Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 33:1444-1452PubMedGoogle Scholar
  36. 36.
    Kurtzke J, Beebe G, Nagler B, Auth T, Kurland L, Nefzger M (1968) Studies on natural history of multiple sclerosis. 4: Clinical features of the onset bout. Acta Neurol Scand 44:467-499CrossRefPubMedGoogle Scholar
  37. 37.
    Kurtzke J, Beebe G, Nagler B, Nefzger M, Auth T, Kurland L (1970) Studies on the natural history of multiple sclerosis 5: Long-term survival in young men. Arch Neurol 22:215-225PubMedGoogle Scholar
  38. 38.
    Langer-Gould A, Popat R, Huang S, Cobb K, Fontoura P, Gould M (2006) Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. Arch Neurol 63:1686-1691CrossRefPubMedGoogle Scholar
  39. 39.
    Leibowitz U, Alter M (1970) Clinical factors associated with increased disability in multiple sclerosis. Acta Neurol Scand 46:53-70CrossRefPubMedGoogle Scholar
  40. 40.
    Leibowitz U, Alter M (1973) Multiple sclerosis: Clues to its cause. Amsterdam: North HollandGoogle Scholar
  41. 41.
    Li D, Zhao G, Paty D, University of British Columbia MS/MRI Analysis Research Group, SPECTRIMS Study Group (2001) Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology 56:1505-1513Google Scholar
  42. 42.
    Lublin F, Reingold S (1996) The national multiple sclerosis society USA advisory committee on clinical trails of new agents in multiple sclerosis. Defining the clinical course of multiple sclerosis: Results of an international survey. Neurology 46:907-911PubMedGoogle Scholar
  43. 43.
    McAlpine D (1964) The benign form of multiple sclerosis: Results of a long-term study. BMJ 2:1029-1032CrossRefPubMedGoogle Scholar
  44. 44.
    McAlpine D, Compston N (1952) Some aspects of the natural history of disseminated sclerosis. Q J Med 21:135-167PubMedGoogle Scholar
  45. 45.
    Minneboo A, Uitdehaag B, Ader H, Barkhof F, Polman C, Castelijins J (2005) Patterns of enhancing lesion evolution in multiple sclerosis are uniform within patients. Neurology 65:56-61CrossRefPubMedGoogle Scholar
  46. 46.
    Myhr K, Riise T, Vedeler C, Nortvedt MW, Gronning R, Midgard R, Nyland HI (2001) Disability and prognosis in multiple sclerosis: demographic and clinical variables important for the ability to walk and awarding of disability pension. Mult Scler 7:59-65PubMedGoogle Scholar
  47. 47.
    Noseworthy J, Miller D, Compston A (2005) Disease-modifying treatments in multiple sclerosis. Churchill Livingston, London, pp 729-802Google Scholar
  48. 48.
    Patzold U, Pocklington P (1982) Course of multiple sclerosis: Results of a prospective study carried out of 102 MS patients from 1976-1980. Acta Neurol Scand 65:248-266CrossRefPubMedGoogle Scholar
  49. 49.
    Pittock S (2007) Does benign MS today imply benign MS tomorrow? Implications for treatment. Neurology 68:480-481CrossRefPubMedGoogle Scholar
  50. 50.
    Pittock S, Mayr W, McClelland R, Jorgensen N, Weigand S, Noseworthy J, Rodriguez M (2004) Disability profile of MS did not change over 10 years in a population-based prevalence cohort. Neurology 62:601-606PubMedGoogle Scholar
  51. 51.
    Pittock S, Mayr W, McClelland R, Jorgensen N, Weigand S, Noseworthy J, Weinshenker B, Rodriguez M (2004) Change in MS-related disability in a population-based cohort: A 10-year follow-up study. Neurology 62:51-59PubMedGoogle Scholar
  52. 52.
    Pittock S, McClelland R, Mayr W, Jorgensen N, Weinshenker B, Noseworthy J, Rodriguez M (2004) Clinical implications of benign multiple sclerosis: A 20-year population-based followup study. Ann Neurol 56:303-306CrossRefPubMedGoogle Scholar
  53. 53.
    Pittock S, Noseworthy J, Rodriguez M (2007) MRI findings in benign multiple sclerosis are variable. J Neurol 254:539-541CrossRefPubMedGoogle Scholar
  54. 54.
    Pittock S, Weinshenker B, Noseworthy J, Lucchinetti C, Keegan M, Wingerchuk D, Carter J, Shuster E, Rodriguez M (2006) Not every patient with multiple sclerosis should be treated at time of diagnosis. Arch Neurol 63:611-614CrossRefPubMedGoogle Scholar
  55. 55.
    Polman C, O’Connor P, Havrdova E, Hutchinson M, Kappos L, Miller D, Phillips J, Lublin F, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara M, Sandrock A (2006) A randomized, placebocontrolled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899-910CrossRefPubMedGoogle Scholar
  56. 56.
    Ramsaransing G, De Keyser J (2006) Benign course in multiple sclerosis: A review. Acta Neurol Scand 113:359-369CrossRefPubMedGoogle Scholar
  57. 57.
    Rodriguez M, Siva A, Cross S, Stolp-Smith K, O’Brien P, Kurland L (1994) Impairment, disability, and handicap in multiple sclerosis: A population-based study in Olmsted county, Minnesota. Neurology 44:28-33Google Scholar
  58. 58.
    Runmarker B, Andersen O (1993) Prognostic factors in multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 116:117-134CrossRefPubMedGoogle Scholar
  59. 59.
    Sayao A, Devonshire V, Tremlett H (2007) Longitudinal follow-up of ‘benign’ multiple sclerosis at 20 years. Neurology 68:480-481CrossRefGoogle Scholar
  60. 60.
    SPECTRIMS Study Group HR (2001) Randomized controlled trial of interferon-beta-1a in secondary progressive ms: Clinical results. Neurology 56:1496-1504Google Scholar
  61. 61.
    Thompson A (1999) Benign multiple sclerosis. J Neurol Neurosurg Psychiatry 67:138CrossRefPubMedGoogle Scholar
  62. 62.
    Thompson A, Kermode A, MacManus D, Kendall BE, Kingsley DP, Moseley IF, McDonald WI (1990) Patterns of disease activity in multiple sclerosis: Clinical and magnetic resonance imaging study. BMJ 300:631-634CrossRefPubMedGoogle Scholar
  63. 63.
    Thompson AJ, Miller D, Youl B, MacManus D, Moore S, Kingsley D, Kendall B, Feinstein A, Mcdonald WI (1992) Serial gadolinium-enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. Neurology 42:60-62PubMedGoogle Scholar
  64. 64.
    Traboulsee A, Dehmeshki J, Peters K, Griffin C, Brex P, Silver N, Ciccarrelli O, Chard D, Barker G, Thompson A, Miller D (2003) Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities. Mult Scler 9:566-573CrossRefPubMedGoogle Scholar
  65. 65.
    Tremlett H, Paty D, Devonshire V (2005) Disability progression in multiple sclerosis is slower than previously reported. Neurology 66:172-177CrossRefGoogle Scholar
  66. 66.
    van Waesberghe J, Walderveen M, Castelijins J, Scheltens P, Nijeholt G, Polman C, Barkof F (1998) Patterns of lesion development in multiple sclerosis: Longitudinal observations with t1-weighted spin-echo and magnetization transfer MR. AJNR Am J Neuroradiol 19:675-683PubMedGoogle Scholar
  67. 67.
    Weinshenker B, Bass B, Rice G (1989a) The natural history of multiple sclerosis: A geographically based study. 1. Clinical course and disability. Brain 112:133-146CrossRefGoogle Scholar
  68. 68.
    Weinshenker B, Bass B, Rice G, Noseworthy J, Carriere W, Baskerville J, Ebers G (1989b) The natural history of multiple sclerosis: A geographically based study. 2. Predictive value of the early clinical course. Brain 112:133-146CrossRefGoogle Scholar
  69. 69.
    Weinshenker B, Rice G, Noseworthy J, Carriere W, Baskerville J, Ebers G (1991) The natural history of multiple sclerosis: A geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain 114:1045-1056CrossRefPubMedGoogle Scholar
  70. 70.
    Wingerchuk D (2006) Multiple sclerosis disease-modifying therapies: Adverse effect surveillance and management. Expert Rev Neurotherapeutics 6:333-346CrossRefGoogle Scholar
  71. 71.
    Yousry T, Major E, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue E, Jager H, Clifford D (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354:924-933CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • S. J. Pittock
    • 1
  • M. Rodriguez
    • 2
  1. 1.Department of Neurology, Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Departments of Neurology and ImmunologyMayo Clinic, College of MedicineRochesterUSA

Personalised recommendations