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

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

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First Neurological Clinic, Department of Neurosciences, University Hospital of Padua, Padua, Italy; Neuroimaging Unit, Euganea Medica, Padua, Italy.



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.

[Indexed for MEDLINE]

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