Early silent microstructural degeneration and atrophy of the thalamocortical network in multiple sclerosis

Recent studies on patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) demonstrated thalamic atrophy. Here we addressed the following question: Is early thalamic atrophy in patients with CIS and relapsing-remitting MS (RRMS) mainly a direct consequence of white matter (WM) lesions-as frequently claimed-or is the atrophy stronger correlated to "silent" (nonlesional) microstructural thalamic alterations? One-hundred and ten patients with RRMS, 12 with CIS, and 30 healthy controls were admitted to 3 T magnetic resonance imaging. Fractional anisotropy (FA) was computed from diffusion tensor imaging (DTI) to assess thalamic and WM microstructure. The relative thalamic volume (RTV) and thalamic FA were significantly reduced in patients with CIS and RRMS relative to healthy controls. Both measures were also correlated. The age, gender, WM lesion load, thalamic FA, and gray matter volume-corrected RTV were reduced even in the absence of thalamic and extensive white matter lesions-also in patients with short disease duration (≤24 months). A voxel-based correlation analysis revealed that the RTV reduction had a significant effect on local WM FA-in areas next to the thalamus and basal ganglia. These WM alterations could not be explained by WM lesions, which had a differing spatial distribution. Early thalamic atrophy is mainly driven by silent microstructural thalamic alterations. Lesions do not disclose the early damage of thalamocortical circuits, which seem to be much more affected in CIS and RRMS than expected. Thalamocortical damage can be detected by DTI in normal appearing brain tissue. Hum Brain Mapp 37:1866-1879, 2016. © 2016 Wiley Periodicals, Inc.