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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




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.