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Purpose: This study aims to investigate the effect of electronic stimulation (ES) as a non-pharmacological treatment in restless legs syndrome (RLS)., Methods: This is a randomized, single-blind study. A total of 46 patients were included, consisting of an active group and a sham group with 22 and 24 members, respectively. The stimulation was administered to bilateral lower legs using the tapping mode (3 Hz) on a handheld ES device, and symptom changes were measured in both groups. The effects of the stimuli were analyzed with repeated measures ANOVA., Results: The symptom severity was significantly reduced in the active group, and showed significant interaction effects in the time * group ( F  = 4.441, p  = 0.031). Although both the active and sham groups reported improved symptoms upon receiving longer periods of treatment, the effect of the ES was greater in the active group., Conclusions: ES treatment resulted in symptom improvement when using ideal levels of stimulation intensity. ES can be considered as a non-pharmacological treatment option for RLS.

Background and Purpose: Restless legs syndrome (RLS) is a neurological disorder which is most commonly identified by an urge to move the legs. It often shows alterations in sensory processing which implies the salience network (SN) is experiencing changes. This study investigates the functional connectivity (FC) between the SN and other areas of the brain in RLS patients during the resting state period., Methods: Thirty patients with drug naïve idiopathic RLS and 30 healthy age and gender matched controls were included in this study. Resting state fMRIs were performed in the morning during the asymptomatic period. The SN comparisons were conducted between the two groups., Results: The RLS group showed a reduction in SN FC in the right pyramis, and an increase in SN FC in the bilateral orbitofrontal gyri and right postcentral gyrus., Conclusions: The results of this study give reason to believe that SN FC in RLS patients is altered during asymptomatic periods. This could have an influence on the processing of the saliency of information, particularly sensory information processing and inhibition mechanisms.

Objectives: Resting-state brain connectivity has been shown to differ for Restless Legs Syndrome (RLS) compared to healthy control (CON) groups. This study evaluates the degree these RLS-CON differences are changed by concurrent treatment., Methods: Resting-state functional MRIs were obtained from 32 idiopathic RLS patients during the morning asymptomatic period and 16 age and gender-matched CON subjects. Of the 32 RLS patients, 16 were drug-naïve (DN-RLS), and 16 were regularly drug-treated using a dopamine agonist (DT-RLS). Various assessments of disease characteristics were also performed. The primary purpose was to assess the replicability of prior results and the effects of treatment on these differences between controls and untreated RLS patients. Resting-state connectivity was analyzed by a seed-based method using the bilateral ventral-posterolateral nuclei (VPLN) in the thalamus., Results: In the DN-RLS group, compared to the CON group, three areas (the bilateral lingual gyri and right middle temporal gyrus) were replicated. The three replicated areas did not significantly differ for DT-RLS compared to DN-RLS. DT-RLS compared to DN-RLS had significantly higher thalamic connectivity for the left uvula, right tuber, left anterior insula, and right declive., Conclusions: Thalamic connectivity to the bilateral lingual gyri and right middle temporal gyrus is a replicable finding in DN-RLS that was not affected by dopamine agonist treatments. Other changes in thalamic connectivity were altered by dopamine agonist treatment. These treatment effects may be pertinent to the known treatment benefits of a dopamine agonist on RLS symptoms., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Restless legs syndrome (RLS) patients compared to controls have been found to have abnormal patterns in the default mode network (DMN) in the morning when symptom threshold is the highest and symptoms are least likely to occur. If these morning abnormalities in DMN are pertinent to disease expression, then similar or further detectable differences may be expected on a nighttime assessment when RLS symptom threshold is at its lowest. The purpose of this study was to elucidate the potential neural mechanisms underlying the circadian aspect of RLS symptom expression by assessing diurnal changes in DMN., Methods: Fifteen drug-naïve subjects with idiopathic RLS and 15 age- and gender-matched healthy subjects had fMRI scans in the morning and evening. The DMN patterns were compared both for differences between morning and evening and between RLS and controls., Results: RLS patients compared to the healthy controls showed significant differences in morning and evening DMN. In particular, RLS patients showed consistent increased connectivity in the parietal lobule in both the morning and evening. In contrast, connectivity in the thalamus was increased in the morning and reduced in the evening. In addition, there were negative correlations between thalamic connectivity and the Korean versions of the international RLS scale and the quality-of-life subscore., Conclusions: The results indicated diurnal disturbances of the DMN in RLS subjects are consistent with both the circadian rhythm and severity of RLS. The circadian expression of RLS may relate to changes in arousal cortical-activation thresholds occurring with diurnal changes in the thalamic circuits of the DMN., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Previous studies have suggested that early-onset RLS (EOR) and late-onset RLS (LOR) might have different etiopathophysiologies. Few previous studies have examined accumulation of cerebrovascular ischemic changes as a potential cause of LOR., Methods: We recruited 39 RLS subjects (LOR: defined as age of RLS onset ≥45, n = 18 and EOR: age of onset <45; n = 21); and 39 healthy control subjects matched on age and sex. Structural magnetic resonance imaging (MRI) of the brain was performed for each subject, and images were graded for severity of periventricular white matter hyperintensities (PVH) and deep white matter hyperintensities (DWMH) independently by trained raters according to standardized methods., Results: Interrater reliabilities were 0.861 (p <0.001) for PVH and 0.900 (p <0.001) for DWMH. LOR subjects had a significantly higher grade of DWMH than the EOR subjects (p = 0.043) and age- and sex-matched controls (p = 0.015). In contrast, there was no difference in DWMH severity rating between the EOR group and the EC group or in PVH severity between the LOR or EOR groups and their age-matched controls., Conclusion: Our findings suggest that the presence and severity of DWMH is associated with LOR, but not with EOR. Further examination of the contribution of cerebrovascular disease to the etiopathogenesis of LOR is warranted., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The unusual sensations of restless legs syndrome/Willis-Ekbom disease (RLS/WED) are induced by rest or a low arousal state with a circadian variation in the threshold for induction. It has been suggested that the emergence of RLS/WED symptoms relates to abnormal brain functions dealing with internally generated stimuli. The purpose of this study was to investigate the changes in the default mode network (DMN) in RLS/WED subjects., Methods: Sixteen drug-naïve, idiopathic, RLS/WED subjects, and 16 age-matched and gender-matched healthy subjects were scanned in an asymptomatic resting state. A comparison of the DMN was conducted between the two groups. Resting state functional magnetic resonance imaging (MRI), Korean versions of the International RLS scale, and other sleep questionnaires were used., Results: The results showed reductions in the DMN connectivity in the left posterior cingulate cortex, the right orbito-frontal gyrus, the left precuneus, and the right subcallosal gyrus of the RLS/WED subjects. The DMN connectivity was increased in sensory-motor-associated circuits, which included the right superior parietal lobule, the right supplementary motor area, and the left thalamus. In addition, the connectivity between the DMN and thalamus was negatively correlated with that in the orbito-frontal gyrus and the subcallosal gyrus in the subjects., Conclusions: The results showed disturbances of the DMN in RLS/WED subjects that influence the thalamic relay sensory-motor-associated circuit. These findings may underscore the fact that RLS/WED subjects have disturbances in default mode network functions involving internal stimuli in the resting state. This may be related to compensatory changes to maintain resting., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The purpose of this study was to demonstrate whether or not restless legs syndrome (RLS) is associated with any morphological change in gray matter. Forty-six RLS subjects and 46 controls were enrolled. We performed voxel-based morphometry analysis and compared the results of the two groups. The RLS subjects showed significant regional decreases of gray matter volume in the left hippocampal gyrus, both parietal lobes, medial frontal areas and cerebellum (uncorrected, P<.001). We found that RLS patients showed structural alteration in the brain and alterations in certain parts of the brain in RLS patients are relevant to RLS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Restless legs syndrome (RLS) is a primary sensory disorder with a secondary motor component (e.g., urge to move), and the thalamus is known to play a central role in RLS. The purpose of our study was to explore the intrinsic changes in the thalamocortical circuit in RLS patients using a resting-state functional magnetic resonance imaging (fMRI) paradigm., Methods: Resting-state fMRIs were obtained in the morning from 25 idiopathic RLS patients who were not using RLS medications and 25 controls. Resting-state connectivity was analyzed by a seed-based method using Analysis of Functional NeuroImages (AFNI) software with the bilateral thalami (ventroposterolateral nucleus [VPLN]). The connectivity characteristics of RLS patients were compared to those of the controls., Results: We found that RLS patients showed reduced thalamic connectivity with the right parahippocampal gyrus, right precuneus, right precentral gyrus, and bilateral lingual gyri; however, the right superior temporal gyrus, bilateral middle temporal gyrus, and right medial frontal gyrus showed enhanced connectivity with the thalamus. RLS severity was negatively correlated with connectivity between the thalamus and right parahippocampal gyrus (r = -0.414; P = .040)., Conclusions: Our results suggest that the characteristics of the connectivity changes may reflect the pathways involved in producing RLS symptoms and indicate that RLS patients may have deficits in controlling and managing sensory information, which supports the act of viewing RLS as a disorder disrupting somatosensory processing., (Copyright © 2014 Elsevier B.V. All rights reserved.)