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


Address correspondence to Dr Calabrese, First Neurology Clinic, Dept. of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padua, Italy. E-mail:



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.


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.


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%).


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. Ann Neurol 2013;74:76–83