Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis

J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):93-9. doi: 10.1136/jnnp-2014-309903. Epub 2015 Apr 22.


Objective: To assess whether it is feasible to establish specific cut-off values able to discriminate 'physiological' or 'pathological' brain volume rates in patients with multiple sclerosis (MS).

Methods: The study was based on the analysis of longitudinal MRI data sets of patients with MS (n=206, 87% relapsing-remitting, 7% secondary progressive and 6% primary progressive) and healthy controls (HC; n=35). Brain atrophy rates were computed over a mean follow-up of 7.5 years (range 1-12) for patients with MS and 6.3 years (range 1-12.5) for HC with the SIENA software and expressed as annualised per cent brain volume change (PBVC/y). A weighted (on the follow-up length) receiver operating characteristic analysis and the area under the curve (AUC) were used for statistics.

Results: The weighted PBVC/y was -0.51±0.27% in patients with MS and -0.27±0.15% in HC (p<0.0001). There was a significant age-related difference in PBVC/y between HC older and younger than 35 years of age (p=0.02), but not in patients with MS (p=0.8). The cut-off of PBVC/y, as measured by SIENA that could maximise the accuracy in discriminating patients with MS from HC, was -0.37%, with 67% sensitivity and 80% specificity. According to the observed distribution, values of PBVC/y as measured by SIENA that could define a pathological range were above -0.52% with 95% specificity, above -0.46% with 90% specificity and above -0.40% with 80% specificity.

Conclusions: Our evidence-based criteria provide values able to discriminate the presence or absence of 'pathological' brain volume loss in MS with high specificity. Such results could be of great value in a clinical setting, particularly in assessing treatment efficacy in MS.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Area Under Curve
  • Atrophy
  • Brain / pathology*
  • Disease Progression
  • Evidence-Based Medicine
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / therapy
  • ROC Curve
  • Reference Standards
  • Reproducibility of Results
  • Young Adult