Regional White Matter Abnormalities and Cognitive Impairment in MS: A Multicenter TBSS Study (P6.135)

Objectives. To apply TBSS in a multi-center setting to assess the spatial distribution of white matter (WM) damage in multiple sclerosis (MS) and its relationship with global cognitive impairment as well as deficits in selected cognitive domains. Background. Single center studies have shown an association between disrupted WM architectural integrity and clinical manifestations in MS. Methods. This study was conducted at six European sites using 3.0 Tesla scanners. Fifty-one MS patients and 57 sex-matched healthy controls (HC) underwent MRI, including diffusion tensor imaging (DTI). Patients with at least two abnormal tests at neuropsychological evaluation were considered as cognitively impaired (CI). TBSS was applied for voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) maps. T2 lesion probability maps (LPM) were also derived. Between-group differences and correlations with cognitive tests were reported at a threshold of 0.01 (adjusted for age and scanner). Results. Twenty-two MS patients were CI. Compared to cognitively preserved, CI patients showed FA/MD abnormalities of the corpus callosum, forceps major and minor, superior and inferior longitudinal fasciculi, corona radiata, inferior fronto-occipital fasciculi, uncinate fasciculi, anterior thalamic radiation, fornix, thalamus, left cingulum. Only a minimal overlap was found between regional DT MRI abnormalities and T2 LPMs. Significant correlations were found between: 1) global cognitive, attention and spatial memory Z score vs FA/MD of the majority of the damaged areas; 2) verbal fluency Z score vs FA/MD of corona radiata, corpus callosum, inferior fronto-occipital fascicului, left uncinate fasciculus; 3) WCST scores vs MD of the thalamus and fornix. Conclusions. The application of TBSS to define the regional distribution of WM damage in a multi-center setting in MS patients is feasible and contributes to better characterize disease cognitive manifestations. Study Supported by: The ECTRIMS-MAGNIMS Fellowship in MRI.