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Sarlota Mesaros, MD; Marco Rovaris, MD; Elisabetta Pagani, PhD; Annalisa Pulizzi, MD; Domenico Caputo, MD; Angelo Ghezzi, MD; Antonio Bertolotto, MD; Ruggero Capra, MD; Monica Falautano, PhD; Vittorio Martinelli, MD; Giancarlo Comi, MD; Massimo Filippi, MD

Arch Neurol. 2008;65(9):1223-1230.

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.

Author Affiliations: Neuroimaging Research Unit (Drs Mesaros, Rovaris, Pagani, and Filippi) and Department of Neurology (Drs Rovaris, Pulizzi, Falautano, Martinelli, Comi, and Filippi), Scientific Institute and University Ospedale San Raffaele, and Department of Neurology, Scientific Institute Don Gnocchi (Dr Caputo), Milan, Italy; and Multiple Sclerosis Centers, Ospedale di Gallarate, Gallarate (Dr Ghezzi), Ospedale di Orbassano, Orbassano (Dr Bertolotto), and Ospedale Richiedei, Gussago (Dr Capra), Italy.

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