Background: Evidence is accumulating that indicates that a selected assessment of gray matter (GM) damage is able to provide strong paraclinical correlates of multiple sclerosis (MS) severity. Objective: To investigate the pattern of regional GM atrophy in patients with benign MS (BMS) vs those with secondary progressive MS (SPMS) to better elucidate the factors associated with a favorable status in patients with MS. Design: Cross-sectional survey from January 2006 to August 2007. Setting: Referral, hospital-based MS clinics. Patients: Sixty patients with BMS, 35 patients with SPMS, and 21 healthy volunteers. Main Outcome Measures: Neuropsychological tests exploring memory, attention, and frontal lobe cognitive domains were administered to BMS patients. A voxel-based morphometry analysis of GM concentration was performed using statistical parametric mapping and a threshold of 0.05, corrected for multiple comparisons. Results: Twelve BMS patients (20%) had an abnormal performance on 3 or more neuropsychological tests. Compared with healthy individuals, BMS patients had a reduced GM volume in the subcortical and frontoparietal regions. Compared with BMS patients, those with SPMS had a significant GM loss in the cerebellum. No differences between BMS and SPMS patients were found when only BMS patients with cognitive impairment or those with shorter disease duration (15-19 years) and higher Expanded Disability Status Scale scores (>2.0) were considered. Conclusions: Cerebellar GM atrophy seems to be a major determinant of irreversible locomotor disability in MS. The absence of cognitive impairment and a longer disease duration or lower Expanded Disability Status Scale score may identify those BMS patients with the potential for a favorable disease evolution.
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