Skip to main content
SpringerLink
Log in

Prognostic factors for multiple sclerosis: the importance of natural history studies

  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Detailed studies of the natural history of untreated multiple sclerosis (MS) have been carried out in London, Ontario, Canada, over the past generation. There are now some 25,000 patient-years of follow-up in a cohort of slightly more than 1000 individuals. From the data, it is clear that a number of factors are associated with long-term outcome of the disease.

The Ontario database reveals several prognostic variables that are clinical in nature, which can be used to evaluate prognosis in any clinical subtype. The most important factors include the development of a progressive deficit and time to onset of progressive deficit. In addition, and independently, a high number of relapses in the first and second year is associated with poor long-term outcome, as is the development of early unremitting disability. An important question is whether or not primary-progressive (PP) MS represents an independent entity separate from secondary-progressive (SP) MS. No specific category of PP disease is distinguishable from SP disease using available clinical measures. There is reason to believe that magnetic resonance imaging (MRI) activity (when appropriately controlled for other unequally distributed factors, such as age) will be found to be very similar.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

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

    PubMed  Google Scholar 

  2. Cottrell DA, Kremenchutzky M, Rice GPA, Hader W, Baskerville J, Ebers GC (1999) The natural history of multiple sclerosis: a geographically based study. 6.Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis. Brain 122:641–647

    Article  PubMed  Google Scholar 

  3. Cottrell DA, Kremenchutzky M, Rice GP, Koopman WJ, Hader W, Baskerville J, Ebers GC (1999) The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain 122:625–639

    Article  PubMed  Google Scholar 

  4. Ebers GC, Koopman WJ, Hader W, Sadovnick AD, Kremenchutzky M, Mandalfino P, Wingerchuk DM, Baskerville J, Rice GP (2000) The natural history of multiple sclerosis: a geographically based study: 8. Familial multiple sclerosis. Brain 123:641–649

    Article  PubMed  Google Scholar 

  5. Ebers GC, Sadovnick AD, Risch NJ (1995) A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 377:150–151

    Article  PubMed  Google Scholar 

  6. Fazekas F, Offenbacher H, Fuchs S, Schmidt R, Niederkorn K, Horner S, Lechner H (1988) Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 38:1822–1825

    PubMed  Google Scholar 

  7. Kidd D, Thorpe JW, Kendall BE, Barker GJ, Miller DH, McDonald WI, Thompson AJ (1996) MRI dynamics of brain and spinal cord in progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 60:15–19

    PubMed  Google Scholar 

  8. Kremenchutzky M, Cottrell D, Rice G, Hader W, Baskerville J,Koopman W, Ebers GC (1999) The natural history of multiple sclerosis: a geographically based study. 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation. Brain 122:1941–1950

    Article  PubMed  Google Scholar 

  9. Kremenchutzky M, Lee D, Rice GP, Ebers GC (2000) Diagnostic brain MRI findings in primary progressive multiple sclerosis. Mult Scler 6:81–85

    Article  PubMed  Google Scholar 

  10. Kurtzke JF (1993) Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev 6:382–427

    PubMed  Google Scholar 

  11. Leibowitz U, Alter M, Halpern L (1964) Clinical course of multiple sclerosis in Israel. III. Clinical course and prognosis related to age at onset. Neurology 14:926–932

    PubMed  Google Scholar 

  12. Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey.National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911

    PubMed  Google Scholar 

  13. Masterman T, Ligers A, Olsson T, Andersson M, Olerup O, Hillert J (2000) HLA-DR15 is associated with lower age at onset in multiple sclerosis. Ann Neurol 48:211–219

    Article  PubMed  Google Scholar 

  14. Masterman T, Hillert J (2002) HLADR15 and age at onset in multiple sclerosis. Eur J Neurol 9:179–180

    Article  PubMed  Google Scholar 

  15. Paty DW, Oger JJ, Kastrukoff LF, Hashimoto SA, Hooge JP, Eisen AA, Eisen KA, Purves SJ, Low MD, Brandejs V, et al. (1988) MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evolked potentials, oligoclonal banding, and CT. Neurology 38:180–185

    PubMed  Google Scholar 

  16. Revesz T, Kidd D, Thompson AJ, Barnard RO, McDonald WI (1994) A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain 117:759–765

    PubMed  Google Scholar 

  17. Shepherd DI, Downie AW (1980) A further prevalence study of multiple sclerosis in north-east Scotland. J Neurol Neurosurg Psychiatry 43:310–315

    PubMed  Google Scholar 

  18. Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B, Dousset V, Filippi M, Hintzen R, Montalban X, Polman CH, Rovira A, de Sa J, Thompson AJ (2000) One year follow up study of primary and transitional progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 68:713–718

    Article  PubMed  Google Scholar 

  19. Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DP, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62

    Article  PubMed  Google Scholar 

  20. Thompson AJ, Polman CH, Miller DH, McDonald WI, Brochet B, Filippi M Montalban X, De Sa J (1997) Primary progressive multiple sclerosis. Brain 120:1085–1096

    Article  PubMed  Google Scholar 

  21. Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH, Polman CH, Stevenson VL, McDonald WI (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47:831–835

    Article  PubMed  Google Scholar 

  22. Thompson AJ, Hutchinson M, Brazil J, Feighery C, Martin EA (1986) A clinical and laboratory study of benign multiple sclerosis. Q J Med 58:69–80

    PubMed  Google Scholar 

  23. Van Lambalgen R, Sanders EA, D’Amaro J (1986) Sex distribution, age of onset and HLA profiles in two types of multiple sclerosis. A role for sex hormones and microbial infections in the development of autoimmunity? J Neurol Sci 76:13–21

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  25. Weinshenker BG, Bass, B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC (1989) The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain 112:1419–1428

    PubMed  Google Scholar 

  26. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC (1991) The natural history of multiple sclerosis: a geographically based study. 3.Multivariate analysis of predictive factors and models of outcome. Brain 114:1045–1056

    PubMed  Google Scholar 

  27. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC (1991) The natural history of multiple sclerosis: a geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials. Brain 114:1057–1067

    PubMed  Google Scholar 

  28. Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC; Canadian Collaborative Study Group (2003) Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci USA 100:12877–12882

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Neurology, Radcliffe Infirmary University of Oxford, Woodstock Road, Oxford, OX2 6HE, UK

    George C. Ebers

Authors
  1. George C. Ebers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George C. Ebers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ebers, G.C. Prognostic factors for multiple sclerosis: the importance of natural history studies. J Neurol 252 (Suppl 3), iii15–iii20 (2005). https://doi.org/10.1007/s00415-005-2012-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-2012-4

Key words

Search

Navigation