title: The changing clinical course of multiple sclerosis: a matter of gray matter.
abstract: 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: First Neurological Clinic, Department of Neurosciences, University Hospital of Padua, Padua, Italy; Neuroimaging Unit, Euganea Medica, Padua, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Calabrese
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
authors.forename: Valentina
authors.initials: V
authors.lastname: Poretto
authors.forename: Alice
authors.initials: A
authors.lastname: Favaretto
authors.forename: Aldo
authors.initials: A
authors.lastname: Morra
authors.forename: Francesca
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Perini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D016000:Cluster Analysis; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D015999:Multivariate Analysis; D013116:Spinal Cord / Q000473:pathology*; D055815:Young Adult