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

Hea Ree Park,Seunghwan Oh,Hye Ryun Kim,Eun Yeon Joo,Joon-Kyung Seong

doi:10.1038/s41598-021-95238-6

Abstract

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.

Highlights

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent
In the past few years, novel MRI modalities such as diffusion tensor imaging (DTI) and functional MRI have been used to identify structural or functional changes in the central nervous system of RLS patients that are undetectable by conventional MRI6–15
Patients with PLMs during sleep as seen during PSG (n = 12) had negative correlations between Fractional anisotropy (FA) values in the subcortical part of the left corticospinal tract (CST) and number of PLMs (p = 0.044, Fig. 3D) and MAI (p = 0.045, Fig. 3E). In this cross-sectional, case–control study, the tract-specific statistical analysis (TSSA) method revealed that patients with RLS had altered FA values in multiple major WM tracts, correlated with neuropsychological and polysomnographic parameters

Summary

Introduction

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. The tract-based spatial statistics (TBSS) method, a widely used DTI technique, can facilitate investigations of local microstructural alterations through nonlinear registration followed by projection of diffusion parameters onto a WM skeleton[19]. This projection onto a group mean skeleton adopted in TBSS might mix differently oriented, multiple adjacent fibers given that TBSS discards fiber orientation[20]. This system uses the results of subject-specific tractography and a tract classification method that acquires the fiber directions in subject-specific tractography maps

Methods

Results

Conclusion