Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome

Abstract

Study Objectives Integrated information on brain microstructural integrity and iron storage and its impact on the morphometric profile is not available in restless legs syndrome (RLS). We applied multimodal magnetic resonance imaging (MRI) including diffusion tensor imaging, the transverse relaxation rate (R2*), a marker for iron storage, as well as gray and white matter volume measures to characterize RLS-related MRI signal distribution patterns and to analyze their associations with clinical parameters. Methods Eighty-seven patients with RLS (mean age 51, range 20–72 years; disease duration, mean 13 years, range 1–46 years, of those untreated n = 30) and 87 healthy control subjects, individually matched for age and gender, were investigated with multimodal 3T MRI. Results Volume of the white matter compartment adjacent to the post- and precentral cortex and fractional anisotropy (FA) of the frontopontine tract were both significantly reduced in RLS compared to healthy controls, and these alterations were associated with disease duration (r = 0.25, p = 0.025 and r = 0.23, p = 0.037, respectively). Corresponding gray matter volume increases of the right primary motor cortex in RLS (p < 0.001) were negatively correlated with the right FA signal of the frontopontine tract (r = −0.22; p < 0.05). Iron content evaluated with R2* was reduced in the putamen as well as in temporal and occipital compartments of the RLS cohort compared to the control group (p < 0.01). Conclusions Multimodal MRI identified progressing white matter decline of key somatosensory circuits that may underlie the perception of sensory leg discomfort. Increases of gray matter volume of the premotor cortex are likely to be a consequence of functional neuronal reorganization.

White matter tract-specific alterations in patients with primary restless legs syndrome

“…Several DTI studies of RLS reported alterations of motor and somatosensory systems, but the details of the results have been different among studies. Some studies reported decreased FA values in variable supratentorial WM tracts including WM close to the motor and somatosensory cortices, CG, putamen, genu of the corpus callosum, and internal capsule 6 , 8 , 12 . Two studies reported involvement of infratentorial structures such as brain stem, cerebellum, and upper cervical cords in RLS patients 9 , 10 .…”

“…The discrepancies between results might be explained by differences in post-processing methodologies between studies and the technical limitations of these previous methods. These studies used voxel-based approaches 6 , 8 – 10 , 12 or the TBSS method 7 , 11 , which resulted in mixed values for multiple fiber tracts with different orientations. Differences in sample size, magnetic field strength, and rate of possible comorbid sleep disorders also might have contributed to the discrepancies between results.…”

“…Several DTI studies have assessed WM changes in patients with RLS, but the extent and features of WM abnormalities were inconsistent. Some DTI studies have observed disruptions to WM integrity close to the somatosensory cortex or prefrontal cortices, corpus callosum, internal capsule, basal ganglia, brain stem, spinal cord, and cerebellum 6 , 8 – 10 , 12 , while others did not find any differences in the WM of RLS patients compared with that of normal controls 7 , 11 .…”

“…Previous DTI studies of RLS have used the voxel-wise approach 6 , 8 , 10 , 12 and tract-based spatial statistics (TBSS) method 7 , 9 , 17 . The voxel-wise approach can not specify anatomically which WM tracts are impaired, which is essential for identifying possible disruptions in connectivity between two specific brain regions.…”

Birds of a Feather Flock Together: Disadvantageous Decision Making in Augmented Restless Legs Syndrome Patients with and without Impulse Control Disorders

“…It is likely that impulsive choices, as demonstrated by the beads task, are due to neuroplastic changes caused by long-term dopaminergic medication similar to what has been described in patients with Parkinson’s disease and ICDs [ 14 , 21 ]. One study on multimodal MR imaging in RLS identified higher connectivity within the left executive network, associated with attention, working memory, and decision making [ 22 ]. Interestingly, in our study additional presence of an ICD symptom did not worsen performance on the beads task.…”