Background

The definition of benign multiple sclerosis (BMS) is based on the long disease duration and low level of disability of subjects, without taking into consideration other features, such as cognitive deficits. Purpose. To apply voxel-wise methods to investigate whether cognitive dysfunction in BMS patients is associated with specific patterns of regional damage in the brain gray matter (GM) and white matter (WM).

Methods

Using a 3.0 Tesla scanner, high-resolution 3D T1-weighted, diffusion tensor (DT) and dual-echo images were acquired from 38 BMS patients (Expanded Disability Status Scale score < 3.0 and disease duration >15 years) and 50 matched healthy subjects (HC). All patients underwent neuropsychological assessment through the Rao Brief Repeatable battery. Patients with abnormal scores (z-score>2) in at least 2 tests were considered as cognitively impaired (CI). Regional GM atrophy was estimated using a voxel-based morphometry analysis (1), while WM microstructural abnormalities were investigated with Tract Based Spatial Statistics (TBSS) analysis (2).

Results

Sixteen (42%) BMS were classified as CI. Compared to HC, cognitive preserved (CP) BMS patients had significant GM atrophy of the thalami, left precuneus and left middle cingulate gyrus. Additional areas of GM atrophy in CI patients were found in the anterior and posterior cingulate gyrus, left caudate nucleus, and right precentral gyrus (Figure 1). Compared to HC, CP and CI BMS patients had decreased fractional anisotropy (FA) of supratentorial and infratentorial WM tracts and increased mean (MD), axial (AD) and radial (RD) diffusivity of the main supratentorial WM tracts. CI patients had additional increased MD and RD of several infratentorial regions located in the cerebellum and brainstem (Figure 2). No area was more affected in CP vs CI BMS patients.

Conclusions

Distinct regional patterns of GM atrophy and WM microstructural abnormalities, functionally relevant for cognitive processing, are associated with CI in MS patients with a benign course. These findings support the need for a new clinical definition of BMS, including cognitive features.

Acknowledgements

Partially supported by Fondazione Italiana Sclerosi Multiple (FISM2013/S/1).

References

1) Ashburner J. Computational anatomy with the SPM software. Magn Reson Imaging. 2009;27(8):1163-74. 2) Smith SM, Jenkinson M, Johansen-Berg H, et al. Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. NeuroImage, 2006;31:1487-1505.