White-matter lesions drive deep gray-matter atrophy in early multiple sclerosis: support from structural MRI

Muehlau, Mark; Buck, Dorothea; Foerschler, Annette; Boucard, Christine C.; Arsic, Milan; Schmidt, Paul; Gaser, Christian; Berthele, Achim; Hoshi, Muna; Jochim, Angela; Kronsbein, Helena; Zimmer, Claus; Hemmer, Bernhard; Ilg, Rüdiger (October 2013): White-matter lesions drive deep gray-matter atrophy in early multiple sclerosis: support from structural MRI. In: Multiple Sclerosis Journal, Vol. 19, No. 11: pp. 1485-1492

Abstract

Background: In MS, the relationship between lesions within cerebral white matter (WM) and atrophy within deep gray matter (GM) is unclear. Objective: To investigate the spatial relationship between WM lesions and deep GM atrophy. Methods: We performed a cross-sectional structural magnetic resonance imaging (MRI) study (3 Tesla) in 249 patients with clinically-isolated syndrome or relapsing-remitting MS (Expanded Disability Status Scale score: median, 1.0; range, 0-4) and in 49 healthy controls. Preprocessing of T1-weighted and fluid-attenuated T2-weighted images resulted in normalized GM images and WM lesion probability maps. We performed two voxel-wise analyses: 1. We localized GM atrophy and confirmed that it is most pronounced within deep GM; 2. We searched for a spatial relationship between WM lesions and deep GM atrophy; to this end we analyzed WM lesion probability maps by voxel-wise multiple regression, including four variables derived from maxima of regional deep GM atrophy (caudate and pulvinar, each left and right). Results: Atrophy of each deep GM region was explained by ipsilateral WM lesion probability, in the area most densely connected to the respective deep GM region. Conclusion: We demonstrated that WM lesions and deep GM atrophy are spatially related. Our results are best compatible with the hypothesis that WM lesions contribute to deep GM atrophy through axonal pathology.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Keywords: Multiple sclerosis; relapsing-remitting multiple sclerosis; clinically-isolated syndrome; magnetic resonance imaging; voxel-based morphometry; gray-matter atrophy; white-matter lesions; brain damage
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1352-4585
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English