The changing clinical course of multiple sclerosis: a matter of gray matter

Ann Neurol. 2013 Jul;74(1):76-83. doi: 10.1002/ana.23882. Epub 2013 Aug 6.


Objective: Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing-remitting to secondary progressive have not been clarified yet. We specifically designed a prospective 5-year longitudinal study aimed at assessing demographic, clinical, and magnetic resonance imaging (MRI) parameters that could predict the changing clinical course of MS.

Methods: At study entry and after 5 years, clinical and MRI (ie, gray matter and white matter lesions, including spinal cord lesions, and global and regional cortical thinning) parameters were assessed in a training set of 334 consecutive relapsing-remitting MS patients and in an independent validation set of 84 relapsing-remitting MS patients.

Results: Sixty-six (19.7%) relapsing-remitting MS patients changed their clinical course during the study and entered into the secondary progressive phase. Age (p = 0.001, odds ratio [OR] = 1.2), cortical lesion volume (p < 0.001, OR = 1.7), and cerebellar cortical volume (p < 0.001, OR = 0.2) at study entry were found to predict the changing clinical course. The model including only these 3 variables correctly identified 252 of 268 (94.0%) patients who maintained the relapsing-remitting course and 58 of 66 (87.8%) patients who became secondary progressive (cross-validated error rate = 7.2%). When applied on the validation set, the model obtained a similar error rate (8.4%).

Interpretation: A prediction model based on age, cortical lesion load, and cerebellar cortical volume suitably explains the probability of relapsing-remitting MS patients evolving into the progressive phase. Gray matter damage appears to play a pivotal role in determining the changing clinical course of MS.

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology*
  • Cluster Analysis
  • Disability Evaluation
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Multivariate Analysis
  • Spinal Cord / pathology*
  • Young Adult