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Published online before print September 24, 2008, doi:10.1212/01.wnl.0000319694.14251.95)
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NEUROLOGY 2008;71:1521-1526
© 2008 American Academy of Neurology

Cognitive impairment and structural brain damage in benign multiple sclerosis

M. Rovaris, MD, G. Riccitelli, PhD, E. Judica, MD, F. Possa, PhD, D. Caputo, MD, A. Ghezzi, MD, A. Bertolotto, MD, R. Capra, MD, M. Falautano, PhD, F. Mattioli, MD, V. Martinelli, MD, G. Comi, MD and M. Filippi, MD

From the Neuroimaging Research Unit (M.R., G.R., M. Filippi) and Department of Neurology (M.R., E.J., F.P., M. Falautano, V.M., G.C., M. Filippi), Scientific Institute and University Ospedale San Raffaele, Milan; Department of Neurology (D.C.), Scientific Institute Don Gnocchi, Milan; Multiple Sclerosis Center (A.G.), Ospedale di Gallarate, Gallarate; Multiple Sclerosis Center (A.B.), Ospedale di Orbassano, Orbassano; and Multiple Sclerosis Center (R.C., F.M.), Spedali Civili, Brescia, Italy.

Address correspondence and reprint requests to Dr. Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, via Olgettina 60, 20132 Milan, Italy

Objective: Although in benign multiple sclerosis (BMS) locomotor disability is absent or only minimal, subclinical cognitive impairment seems to occur in many cases. Diffusion tensor (DT) MRI enables us to quantify the extent of "actual" tissue damage, which goes undetected when using conventional MRI. Against this background, we investigated the extent of structural brain damage underlying cognitive dysfunction in BMS, with the ultimate aim to move a first step toward a more reliable definition of this disease phenotype.

Methods: Conventional and DT MRI scans of the brain were acquired from 62 BMS patients. Thirty-six secondary progressive multiple sclerosis (SPMS) patients and 19 healthy subjects served as controls. In BMS patients, neuropsychological tests exploring memory, attention, and frontal lobe functions were administered. Normalized brain volume (NBV), mean diffusivity (MD), and fractional anisotropy (FA) of the normal-appearing white matter (NAWM) and MD of the gray matter (GM) were computed.

Results: Twelve BMS patients (19%) fulfilled predefined criteria for cognitive impairment. BMS patients had abnormal MD and FA values from both NAWM and GM. Whereas BMS patients without cognitive impairment had lower T2 LV (p = 0.03), higher NBV (p = 0.006), and lower average GM MD (p = 0.03) than SPMS patients, BMS patients with cognitive impairment did not significantly differ from SPMS patients for any MRI-derived metric.

Conclusions: In benign multiple sclerosis (BMS), cognitive dysfunction is associated with severe structural brain damage, which resembles that of patients with a much more disabling disease course. A reliable definition of BMS should, therefore, include the preservation of cognitive functioning as an additional requisite.

GLOSSARY: BMS = benign multiple sclerosis; DT = diffusion tensor; EDSS = Expanded Disability Status Scale; FA = fractional anisotropy; FDR = false discovery rate; FOV = field of view; GM = gray matter; LV = lesion volume; MD = mean diffusivity; MP-RAGE = magnetization-prepared rapid-acquisition gradient echo; MS = multiple sclerosis; NAWM = normal-appearing white matter; NBV = normalized volume; PASAT = Paced Auditory Serial Attention Test–3" Version; PGSE = pulsed-gradient echo-planar; ROCF = Rey–Osterrieth Complex Figure; SPMS = secondary progressive multiple sclerosis; TE = echo time; TR = repetition time; WM = white matter.

filippi.massimo{at}hsr.it

e-Pub ahead of print on September 24, 2008, at www.neurology.org.

Supported by a grant from the Fondazione Italiana Sclerosi Multipla (FISM; contract no. 2005/R/18).

Disclosure: The authors report no disclosures.

Received December 17, 2007. Accepted in final form April 2, 2008.






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