Clinical prognostic factors in multiple sclerosis: a natural history review

Nat Rev Neurol. 2009 Dec;5(12):672-82. doi: 10.1038/nrneurol.2009.178.


This Review summarizes the natural history studies on multiple sclerosis (MS) that have evaluated prognostic factors. Reassessment of prognostic factors is warranted, as our ability to offer patients a reliable prognosis is limited, yet we rely on this knowledge to appropriately design clinical trials and interpret their results. The selection criteria for studies to review included a geographical referral base, duration of at least 9 years, prospective design, and populations of at least 100 patients with MS. For all forms of MS combined, negative prognostic factors included progressive disease, and disability at 2 and 5 years. In relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) combined, negative prognostic factors were the onset of progression, a higher relapse rate, greater disability in the first 5 years, a shorter interval to the second relapse, and the involvement of more systems. Additional negative factors include a shorter time to progression in SPMS and a faster rate of disability in the first 2 and 5 years in primary progressive MS (PPMS). Onset of progression, relapse rate and disability in the initial 5 years could be fruitful therapeutic targets; however, longer-term clinical trials will be required to justify these end points.

Publication types

  • Review

MeSH terms

  • Databases, Factual / statistics & numerical data
  • Disability Evaluation*
  • Disease Progression*
  • Humans
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / physiopathology*
  • Prognosis