Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis

Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden

MRI example of white matter lesions and the segmented deep grey matter structures.

<p>Lesions and anatomical regions of interest are illustrated on a set of MR images from a 53 year-old male MS patient. Left – axial FLAIR; right – axial diffusivity map. The output of computer-assisted segmentation of the lesions is shown on FLAIR. The 3D models of the manually outlined caudate (green), putamen (blue) and thalamus (red) are overlaid on the fractional anisotropy map of a single section containing these structures.</p

Scatterplots showing the observed significant correlations between fractional anisotropy (FA) of the three deep grey matter structures of interest and other variables of clinical relevance.

<p>Caudate FA showed a positive correlation with the Expanded Disability Status Scale (EDSS), Ambulation Index and depressive symptomatology as measured by the Center for Epidemiologic Studies Depression scale (CES-D). Putamen FA showed a positive correlation with White Matter (WM) Lesion Volume, as well as an inverse correlation with the Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall and Delayed Free Recall scores. Thalamus FA showed an inverse correlation with the Symbol Digit Modalities Test (SDMT) and the California Verbal Learning Test-II (CVLT-II) Total Learning scores, as well as a positive correlation with the CES-D score.</p

Spearman's correlations between fractional anisotropy of the deep grey matter nuclei and neuropsychological status in the cognitively tested MS subgroup (n = 16).

<p>All values shown are not corrected for age and gender with statistical significance (p≤0.05) indicated in bold. Values shown in italics are those that remained significant after correction for age, gender and educational status.</p

Demographic, clinical and MRI characteristics.

a<p>Mann-Whitney test;</p>b<p>Chi-squared test.</p

The Minimal Assessment of Cognitive Function in MS battery: cognitive domains, neuropsychological tests and component scores.

<p>The Minimal Assessment of Cognitive Function in MS battery: cognitive domains, neuropsychological tests and component scores.</p

Boxplots showing the distributions of fractional anisotropy and mean diffusivity values in the caudate, putamen and thalamus in patients with multiple sclerosis (MS) and controls.

<p>The significant p-values for fractional anisotropy difference between the two groups are reported (general linear model, controlling for age and gender). Thick lines inside the boxes indicate the median value. The whiskers indicate the top and bottom quartiles. Circles are outliers. Fractional anisotropy is a scalar value between 0 and 1; Mean diffusivity is expressed in µm²/s.</p