Journal of Neurology

, Volume 264, Issue 6, pp 1068–1075 | Cite as

Can we predict benign multiple sclerosis? Results of a 20-year long-term follow-up study

  • Arianna SartoriEmail author
  • Mohammad Abdoli
  • Mark S. Freedman
Original Communication


Benign multiple sclerosis (MS) is a discussed clinical entity, with variable reported prevalence (6–64%) requiring at least 5–10 years of clinical observation. Moreover, many benign patients progress with time becoming no longer benign (NLB). The objective of this study is to compare benign MS patients (EDSS ≤3, 10 years from disease onset) who still fulfilled the definition at 20 years to those NLB. In our retrospective study based on Ottawa Hospital MS Clinic database, 175 benign patients fulfilled the inclusion criteria (clinically definite MS, EDSS ≤3 at 10 years, disease onset from 1983 to 1993, and clinical assessments performed at 10 ± 1 and 20 ± 1 years from onset). Out of the identified patients, 66.3% remained benign at 20 years; however, by changing the definition for benign to EDSS ≤2 or ≤1 at 10 years, they increased to 71.9 and 81.6%, respectively. Female sex, EDSS ≤1 at 10 years, and a pure sensory onset were associated with a benign course, while a pure motor onset with an NLB condition. According to multivariate analysis, an EDSS ≤2 at 10 years predicted a long-term benign course. Our study questions the current definition of “benign” MS, suggesting a more stringent EDSS cutoff at 10 years to predict long-term benign prognosis.


Multiple sclerosis Benign course Prognosis Long-term follow-up Natural history Disease modifying drugs 


Compliance with ethical standards 

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

This study has been performed in accordance with the Declaration of Helsinki and with the ethical standards of the institution.


  1. 1.
    McAlpine D (1961) The benign form of multiple sclerosis. A study based on 241 cases seen within 3 years of onset and followed up until the tenth year or more of the disease. Brain 84:186–203CrossRefPubMedGoogle Scholar
  2. 2.
    Kurtzke JF, Beebe GW, Nagler B et al (1977) Studies on the natural history of multiple sclerosis VIII. Early prognostic features of the later course of the illness. J Chron Dis 30:819–830CrossRefPubMedGoogle Scholar
  3. 3.
    Poser S, Wikström J, Bauer HJ (1979) Clinical data and the identification of special forms of multiple sclerosis in 1271 cases studied with a standardized documentation system. J Neurol Sci 40:159–168CrossRefPubMedGoogle Scholar
  4. 4.
    Thompson AJ, Hutchinson M, Brazil J et al (1986) A clinical and laboratory study of benign multiple sclerosis. QJM 225:69–80Google Scholar
  5. 5.
    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 46:907–911CrossRefPubMedGoogle Scholar
  6. 6.
    Ramsaransing GS, De Keyser J (2006) Benign course in multiple sclerosis: a review. Acta Neurol Scand 113:359–369CrossRefPubMedGoogle Scholar
  7. 7.
    Ramsaransing GSM, De Keyser J (2007) Predictive value of clinical characteristics for benign multiple sclerosis. Eur J Neurol 14:885–889CrossRefPubMedGoogle Scholar
  8. 8.
    Sayao AL, Devonshire V, Tremlett H (2007) Longitudinal follow-up of “benign” multiple sclerosis at 20 years. Neurology 68:496–500CrossRefPubMedGoogle Scholar
  9. 9.
    Costelloe L, Thompson A, Walsh C et al (2008) Long-term clinical relevance of criteria designating multiple sclerosis as benign after 10 years of disease. J Neurol Neurosurg Psychiatry 79:1245–1248CrossRefPubMedGoogle Scholar
  10. 10.
    Glad SB, Nyland HI, Aarseth JH et al (2009) Long-term follow-up of benign multiple sclerosis in Hordaland County, Western Norway. Mult Scler 15:942–950CrossRefPubMedGoogle Scholar
  11. 11.
    Leray E, Coustans M, Le Page E et al (2013) ‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study. Mult Scler 19:458–465CrossRefPubMedGoogle Scholar
  12. 12.
    Pittock SJ, McClelland RL, Mayr WT et al (2004) Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study. Ann Neurol 56:303–306CrossRefPubMedGoogle Scholar
  13. 13.
    Hirst C, Ingram G, Swingler R et al (2008) Change in disability in patients with multiple sclerosis: a 20-year prospective population-based analysis. J Neurol Neurosurg Psychiatry 79:1137–1143CrossRefPubMedGoogle Scholar
  14. 14.
    Jacobs LD, Beck RW, Simon JH et al (2000) Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343:898–904CrossRefPubMedGoogle Scholar
  15. 15.
    Comi G, Filippi M, Barkhof F et al (2001) Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomized study. Lancet 357:1576–1582CrossRefPubMedGoogle Scholar
  16. 16.
    Kappos L, Polman CH, Freedman MS et al (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndrome. Neurology 67:1242–1249CrossRefPubMedGoogle Scholar
  17. 17.
    Comi G, Martinelli V, Rodegher M et al (2009) Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 374:1503–1511CrossRefPubMedGoogle Scholar
  18. 18.
    Freedman MS, Comi G, De Stefano N et al (2014) Moving toward earlier treatment of multiple sclerosis: findings from a decade of clinical trials and implications for clinical practice. Mult Scler Relat Disord 3:147–155CrossRefPubMedGoogle Scholar
  19. 19.
    Freedman MS (2013) Present and Emerging Therapies for Multiple Sclerosis. Continuum (Minneap Minn) 19:968–991Google Scholar
  20. 20.
    Oh J, O’Connor PW (2015) Novel and imminently emerging treatments in relapsing-remitting multiple sclerosis. Curr Opin Neurol 28:230–236CrossRefPubMedGoogle Scholar
  21. 21.
    Poser CM, Paty DW, Scheinberg L et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231CrossRefPubMedGoogle Scholar
  22. 22.
    Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMedGoogle Scholar
  23. 23.
    Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Joseph FG, Hirst CL, Pickersgill TP et al (2009) CSF oligoclonal band status informs prognosis in multiple sclerosis: a case control study of 100 patients. J Neurol Neurosurg Psychiatry 80:292–296CrossRefPubMedGoogle Scholar
  25. 25.
    Portaccio E, Stromillo ML, Goretti B et al (2009) Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis. Neurology 73:498–503CrossRefPubMedGoogle Scholar
  26. 26.
    Perini P, Tagliaferri C, Belloni M et al (2001) The HLA-DR13 haplotype is associated with benign multiple sclerosis in northeast Italy. Neurology 57:158–159CrossRefPubMedGoogle Scholar
  27. 27.
    Amato MP, Zipoli V, Goretti B et al (2006) Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 253:1054–1059CrossRefPubMedGoogle Scholar
  28. 28.
    Calabrese M, Favaretto A, Poretto V et al (2013) Low degree of cortical pathology is associated with benign course of multiple sclerosis. Mult Scler 19:904–911CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Neurology Unit, Department of Medical, Surgical, and Health SciencesUniversity of Trieste, ASUITs, Cattinara HospitalTriesteItaly
  2. 2.Multiple Sclerosis Research Clinic, Division of Neurology, Department of Medicine, Ottawa Hospital Research InstituteUniversity of Ottawa, Ottawa Hospital MS ClinicOttawaCanada

Personalised recommendations