Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes

Neurology. 2010 Jun 8;74(23):1868-76. doi: 10.1212/WNL.0b013e3181e24136.


Objective: To assess the time course of brain atrophy and the difference across clinical subtypes in multiple sclerosis (MS).

Methods: The percent brain volume change (PBVC) was computed on existing longitudinal (2 time points) T1-weighted MRI from untreated (trial and nontrial) patients with MS. Patients (n = 963) were classified as clinically isolated syndromes suggestive of MS (CIS, 16%), relapsing-remitting (RR, 60%), secondary progressive (SP, 15%), and primary progressive (9%) MS. The median length of follow-up was 14 months (range 12-68).

Results: There was marked heterogeneity of the annualized PBVC (PBVC/y) across MS subtypes (p = 0.003), with higher PBVC/y in SP than in CIS (p = 0.003). However, this heterogeneity disappeared when data were corrected for the baseline normalized brain volume. When the MS population was divided into trial and nontrial subjects, the heterogeneity of PBVC/y across MS subtypes was present only in the second group, due to the higher PBVC/y values found in trial data in CIS (p = 0.01) and RR (p < 0.001). The estimation of the sample sizes required for demonstrating a reduction of brain atrophy in patients in a placebo-controlled trial showed that this was larger in patients with early MS than in those with the progressive forms of the disease.

Conclusions: This first large study in untreated patients with multiple sclerosis (MS) with different disease subtypes shows that brain atrophy proceeds relentlessly throughout the course of MS, with a rate that seems largely independent of the MS subtype, when adjusting for baseline brain volume.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Atrophy / etiology
  • Atrophy / pathology
  • Brain / pathology*
  • Community Health Planning
  • Disability Evaluation
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / classification*
  • Multiple Sclerosis / complications*
  • Retrospective Studies
  • Statistics as Topic