Cognitive impairment and structural brain damage in benign multiple sclerosis

Abstract

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.