RLS Patients Research Articles

Time evolution of restless legs syndrome in haemodialysis patients.

BackgroundRestless legs syndrome (RLS) is characterized by an urge to move the extremities, accompanied by paraesthesiae, in the evening and at night. Uraemic RLS, a type of secondary RLS, occurs commonly in chronic kidney disease and end-stage renal disease. Progression of uraemic RLS over time is unclear. Therefore we investigated the prevalence, progression over time, risk factors and impact on survival of uraemic RLS in a cohort of dialysis patients. MethodsWe reviewed at the 7-year follow-up a cohort of haemodialysis (HD) patients we had previously investigated for RLS, through interviews, validated questionnaires and analysis of demographic and clinical data.ResultsAt the 7-year follow-up, RLS was present in 16% of patients, with a persistence rate of 33%. A correlation was obtained between RLS and older age, diabetes, low albumin and low body mass index. RLS was associated with reduced overall survival (median survival of 3.3 versus 3.7 years), particularly with the continuous form of RLS (1.61 years). There was a higher incidence of myocardial infarction and peripheral vascular disease, although not reaching statistical significance. RLS patients had absolute higher scores in all quality of life domains. A large majority of study patients (96%) reported being symptom-free within a few days or weeks following kidney transplantation.ConclusionsThe development of RLS, especially the continuous form, in patients undergoing HD has important consequences associated with decreased survival. Our results indicated an association between uraemic RLS and ageing, diabetes and malnutrition. Considerable efforts should be focused on the treatment of RLS, since it significantly and persistently impacts the quality of life of HD patients. Kidney transplantation could represent an effective treatment option for that RLS impacts on dialysis patients' quality of life, thus confirming the secondary nature of RLS in most HD patients.

Mineral absorption is an enriched pathway in a brain region of restless legs syndrome patients with reduced MEIS1 expression.

Restless legs syndrome is a common complex disorder with different genetic and environmental risk factors. Here we used human cell lines to conduct an RNA-Seq study and observed how the gene showing the most significant association with RLS, MEIS1, acts as a regulator of the expression of many other genes. Some of the genes affected by its expression level are linked to pathways previously reported to be associated with RLS. We found that in cells where MEIS1 expression was either increased or prevented, mineral absorption is the principal dysregulated pathway. The mineral absorption pathway genes, HMOX1 and VDR are involved in iron metabolism and response to vitamin D, respectively. This shows a strong functional link to the known RLS pathways. We observed the same enrichment of the mineral absorption pathway in postmortem brain tissues of RLS patients showing a reduced expression of MEIS1. The expression of genes encoding metallothioneins (MTs) was observed to be dysregulated across the RNA-Seq datasets generated from both human cells and tissues. MTs are highly relevant to RLS as they bind intracellular metals, protect against oxidative stress and interact with ferritins which manage iron level in the central nervous system. Overall, our study suggests that in a subset of RLS patients, the contribution of MEIS1 appears to be associated to its downstream regulation of genes that are more directly involved in pathways that are relevant to RLS. While MTs have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson’s diseases, this is a first report to propose that they have a role in RLS.

Moderate to severe but not mild RLS is associated with greater sleep-related sympathetic autonomic activation than healthy adults without RLS

IntroductionRestless legs syndrome (RLS) patients have been found to have high rates of transitory increases in the activity of the sympathetic autonomic nervous system with increases in heart rate and blood pressure. These were identified by evaluating heart rate or blood pressure changes independent of any leg movement analyses. There has been an implicit assumption this high rate of sympathetic activations is abnormal, but there has been no direct comparison for similar measures with a healthy population free of RLS. Thus, it is not known if during sleep the rates of sympathetic nervous system activation are greater for RLS than for a healthy population. The objectives of this study were to determine if: (1) RLS patients compared to healthy controls have a greater frequency of sympathetic nervous system activation (significant heart rate increases) with a higher percentage of leg movements associated with these activations; (2) the sympathetic activation frequency and its relation to leg movements correlate significantly with RLS severity in RLS patients; and (3) there is some minimum threshold for RLS severity defining an RLS population where most (eg 85%) have abnormally high rates of sympathetic activation. MethodsSleep data on 32 RLS patients and 21 matched healthy controls were obtained from a prior study. All leg movements during sleep (LMS) and periodic leg movements in sleep (PLMS) were identified following the new WASM criteria; LMS that were not PLMS were considered isolated leg movements in sleep (ILMS). All episodes with significant heart rate increases were identified following procedures established by Cassel et al., (2016, see further on for citation) ie a slope of linear regression ≥2.5 beats per minute over five consecutive heartbeats. Severity of RLS was evaluated using the International Restless Legs Study Group Scale (IRLS). ResultsRLS patients had significantly more heart rate increases than controls (67.88/hr vs. 9.87/hr). RLS patients had a significantly greater percentage of both LMS and PLMS occurring with heart rate increases than controls (44% vs. 30%; 48% vs. 18%, respectively). These measures correlated significantly with IRLS and also PLMS/hr. 85% of the RLS patients with IRLS scores >22 or PLMS >50/hr had rates of sympathetic activation that were >90th percentile for the healthy controls. ConclusionThis is the first paper documenting that RLS patients showed clearly increased sympathetic activation when identified independent of PLMS. This, however, occurs for more severe RLS and not milder RLS. It has been proposed that the abnormally high rate of sympathetic activation for RLS patients relates to development of adverse cardiovascular health consequences observed in some studies. Thus, these data may provide a basic standard for possible use in epidemiological studies to identify the level of RLS severity more likely to have adverse health consequences (eg, cardiovascular disease). Since two-thirds of RLS patients have mild to even intermittent disease, including all RLS is likely to miss the potential health consequences of RLS.

Seasonality of restless legs syndrome: symptom variability in winter and summer times

IntroductionRestless legs syndrome (RLS) is a common sensorimotor neurological disorder, with symptoms that might cause sleep fragmentation leading to excessive daytime sleepiness. A seasonality of RLS symptoms has been suggested; however, to date, no study focused on this aspect. In order to detect a possible seasonality of RLS manifestations, we evaluated RLS symptom severity and excessive daytime sleepiness in winter and summer in RLS patients. MethodsRLS patients who performed two follow-up visits in summer and winter were included in this retrospective bicentric analysis. RLS severity, measured with the International RLS Study Group rating scale (IRLS), and daytime sleepiness, measured with the Epworth Sleepiness Scale (ESS), were recorded in both seasons in Innsbruck and Rome Sleep Medicine Centers. ResultsIn sum, 64 RLS patients were included. In the overall sample, IRLS in summer was higher than in winter (p = 0.008). After gender stratification, this held true only in men (p = 0.008). When stratifying for centers, the seasonal variation in RLS severity was present exclusively in Rome (p < 0.001). Moreover, 20 RLS patients completed ESS in both seasonal periods, and scores in summer were higher than in winter (p < 0.001). ConclusionThis retrospective observational study showed an increase of RLS severity during summer compared to winter, supporting the hypothesis that RLS symptoms are more troublesome when temperatures are higher. Changes in microvascular regulation, sweating, and serum iron level changes may support this difference in RLS symptoms across the year. The documented seasonal variation in RLS severity with worsening in the warmer months needs to be investigated further in prospective studies.

TOX3 gene variant could be associated with painful restless legs

Background/ObjectiveRestless legs syndrome (RLS) is a neurological disorder with a strong genetic susceptibility. A painful RLS sub-phenotype has been described previously but the neurobiological basis for this phenotypic variant remains unknown. This study investigated whether any of the six initially discovered genomic loci associating with RLS (BTBD9, MEIS1, PTPRD, MAP2K5/SKOR1, TOX3, and an intergenic region on chromosome 2), were more strongly associated with complaints of painful versus non-painful RLS. MethodsRLS patients (N = 199; Age = 53.1 ± 16.8; 100% Caucasians; 57% women) diagnosed clinically were genotyped for known variants associating with RLS. Definition of painful RLS required that subjects selected “painful” from a list of 14 adjectives to describe their RLS sensory experience and answered positively to a separate question that queried specifically as to whether they perceived their RLS sensations as painful. Genotype association tests employed logistic regression analyses with assumption of an additive genetic model. Analyses were performed using PLINK software v1.07. ResultsWe identified two RLS patient subgroups: a painful (n = 41) and non-painful (n = 158). Among 10 tested SNPs, only rs3104767 (related to the TOX3 gene locus) was more associated with painful RLS. The minor allele T of SNP rs3104767 was associated with an increased risk of RLS being perceived as painful with an OR of 1.67 [CI = (1.01–2.74); p = 0.049]. Notably, this minor T allele associated with pain sensation in RLS patients in this study was the non-risk allele for RLS in the original RLS genome wide association study, but a similar trend was observed in a recent Parkinson disease sample study. ConclusionThis study might suggest the TOX3 gene variant as a potential genetic substrate for the painful RLS sub-phenotype. This was an exploratory small study and correction for multiple comparisons would have rendered the results not significant. Therefore, the above findings require replication in larger clinical as well as population-based samples of RLS subjects.

0667 Sleep Bruxism Associated With Restless Limbs Syndrome (RLS): A Dopamine Responsive Parasomnia.

Sleep Bruxism (SB) is a common parasomnia and movement disorder, of unknown etiology, affecting approximately 10% of the population. SB is known to cause insomnia, TMJ and dental and periodontal morbidity. Treatment with Occlusal devices does not stop SB or reduce all dental complications. No pharmacological treatments are currently available. Others have suggested an association of RLS and SB in population studies. Both SB and Periodic Limb Movements of Sleep (PLMS), seen in 80% of patients with RLS, occur in light, non-REM sleep. To our knowledge, there has not been a study of RLS patients to determine if SB is associated and, if so, if it responds to therapies for RLS. Patients meeting the IRLSSG criteria for RLS completed a 35 question survey investigating demographics, symptoms, comorbidities, family history and response to therapy. Charts were reviewed and interviews conducted to complete and clarify the data. The SB patients presented here are a subgroup of an ongoing study of RLS and associated conditions. 676 patients completed the survey at the time of this analysis. 241 (35.7%) had SB. 105 of 241 (43.6%) noted improvement of SB with dopamine agonists (DA). Excluding incomplete respondents (ie: patients who did not receive treatment or could not recall the response) 105 of 139 (75.5%) with RLS and SB had improvement of SB with DA therapy. These data support a strong association between RLS and SB, both movement disorders and parasomnias, and suggest that SB, in this population, may respond to treatment with DA. Although retrospective, non-controlled and unblinded, this study should encourage a blinded and placebo controlled trial of DA for SB associated with RLS. Finally, the data suggests that SB may be a manifestation of RLS and, as such, is a dopamine-responsive parasomnia with possible pharmacotherapy in the future. No support

Characterization of painful Restless Legs Syndrome sensations in an English-speaking South African population.

Background and aims Restless Legs Syndrome (RLS) is characterised by unusual sensations in the legs which can be described as painful in up to 60% of RLS patients. The purpose of this study was to characterise and examine whether the presence of pain influenced the words used to describe the sensations of RLS in an English speaking population. Methods RLS participants (n=55) were divided according to whether or not painful RLS sensations were reported upon questioning. They completed the McGill Pain Questionnaire (MPQ), the International Restless Legs Syndrome Severity Scale (IRLS) and selected descriptors from a list of previously published RLS terms. Results Thirty-five percent of the RLS patients had painful sensations. The participants with painful RLS had higher Pain Rating Index (PRI) scores [median (interquartile range) 21 (17-28) vs. 14 (7.5-21) p=0.0008] and IRLS scores [23 (17-28) vs. 18 (11.5-22.5) p=0.0175] than the participants with non-painful RLS. Patients with painful RLS symptoms selected more pain-related literature terms, chose significantly different words in eight of the MPQ subclasses (both sensory and affective) and selected more intense descriptors from certain MPQ subclasses than the non-painful RLS group. The terms that characterised painful RLS were "aching", "painful", "cramping" and "unbearable". Conclusions Descriptors of RLS sensations are changed by the presence of pain, which may indicate an aetiological difference in the patients who have painful RLS. Clinically, patients complaining of cramping and painful sensations may be diagnosed with a condition that mimics RLS. Thus, it is important that the most accurate set of descriptors for RLS are used to enable recognition of RLS and optimised treatment according to the RLS phenotype. Implications The diagnosis of RLS may be improved by overcoming language and cultural barriers and obtaining differential diagnostic terms for painful conditions mimicking RLS.

Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies

ObjectiveRestless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. MethodThe databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. ResultsThis analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21–5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92–3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02–9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. ConclusionThe available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.

Depression is differently associated with sleep measurement in obstructive sleep apnea, restless leg syndrome and periodic limb movement disorder

Depression causes sleep disturbance and is associated with various sleep-related disorders. However, how depression affects the symptomatic presentation of different sleep-related disorders is unclear. In this study, we investigated the sleep parameters of different sleep-related disorders between depressive and non-depressive patients. A total of 785 patients underwent polysomnography in a mental hospital from Jan 2012 to Jun 2013. We first analyzed variables between the depressive and non-depressive groups. The patients were then divided into four groups: obstructive sleep apnea (OSA, n = 339), restless leg syndrome (RLS, n = 51), periodic limb movement disorder (PLMD, n = 58) and comorbid group (OSA and RLS, n = 46). We next compared sleep measures between the depressive and non-depressive subjects within each groups. The patients with OSA and depression were significantly associated with a higher periodic limb movement index. Significantly more patients with RLS patients and depression had initial insomnia complaints. However, significantly more patients with PLMD and depression middle insomnia. Compared with non-depressive population, depressive patients had higher comorbidity with RLS and PLMD. Depression may have different association with the sleep parameters in different sleep-related disorders. Further investigations are needed to investigate how these findings may affect patients' awareness and clinicians' diagnosis and management of sleep-related disorders.

Reduced response to gabapentin enacarbil in restless legs syndrome following long-term dopaminergic treatment

ObjectivesTo determine whether long-term treatment with dopaminergic agents (DAs) might dampen the response to a non-dopaminergic agent, such as gabapentin enacarbil. MethodsWe performed a two-week randomized, double-blind, crossover, and placebo-controlled study in a single, referral center in dopamine treatment-naive patients and non-augmented patients continuously treated with dopaminergics for the last five consecutive years. Following washout from any previous CNS-active drugs, patients were randomized into one of two groups for two consecutive two-week treatment periods with gabapentin enacarbil (GBPen) and placebo. Treatment was administered at 7 PM at a fixed dose of 600 mg/day. RLS severity was measured weekly using the International RLS Scale (IRLS) and Clinical Global Improvement (CGI). An M-SIT was also performed between 6 pm and midnight at the end of each treatment condition. ResultsThere were no significant differences between groups in age, sex, duration of disease, ferritin levels, RLS severity at baseline, or existing concomitant conditions. Both groups improved more during treatment with GBPen than during placebo on the IRLS scale, CGI and mSIT. However, improvements were greater in the DA-naïve group than in long-term treatment with DAs group on the IRLS (p < 0.05), CGI (p < 0.01), and mSIT (p < 0.01). ConclusionsPrevious long-term treatment with DAs reduces future response to GBPen in RLS patients. Potential pathiophysiological explanations are discussed. Our finding has strong implications for the initial choice of treatment in RLS and supports the notion that initial treatment should not be started with DAs. Classification of evidenceThe study provides class II evidence supporting reduced effects of gabapentin enacarbil in RLS patients previously exposed to long-term treatment with dopamine agonists.

Validation of the self-administered version of the international Restless Legs Syndrome study group severity rating scale – The sIRLS

IntroductionThe International Restless Legs Study Group (IRLSSG) has developed the IRLS (International Restless Legs Syndrome Severity Scale) and validated it as a clinician/researcher administered scale to be used when both patient and examiner are present. The IRLSSG recognized the need for a self-completing scale that can be used economically in clinical practice and in large population-based studies. In this study the validity and the reliability of the IRLS as a self-administered scale (sIRLS) is assessed. MethodsEstablished RLS patients were recruited by eight centers in four countries and consented to participate in this study. The validity of the sIRLS was assessed by patients completing the sIRLS before a clinician administered the IRLS. The reliability of the sIRLS was assessed by patients completing the sIRLS again, two weeks after the first one, provided no change had occurred. ResultsOverall, 173 patients were recruited and 164 of them were included in the analyses. The sIRLS showed satisfactory scaling assumptions and no relevant floor or ceiling effect. One factor explained 61.3% of the variance. Cronbach's alpha was 0.93 and the item homogeneity index was 0.59. Intraclass correlation coefficient between the sIRLS and the IRLS was 0.94. The sIRLS standard error of measurement was 3.61 (½ SD at baseline = 4.11). The results mostly overlapped those of the IRLS analyzed in parallel. DiscussionThe sIRLS is a reliable, valid and precise instrument that showed tight association with the IRLS. These findings support the use of the sIRLS for self-evaluation of RLS severity. The responses obtained on the sIRLS and the IRLS scale varied slightly. Therefore, we recommend that either the sIRLS or the IRLS scale be used as the only scale for serial measures over time.

Do you have restless leg syndrome? I understood from your eyes.

According to many studies in the literature, there is a strong association between restless leg syndrome and dopaminergic dysfunction. Dopamine is also the major catecholamine in the retina and is also a possible transmitter of the amacrine and interplexiform cells. The aim of this study is to investigate the possible association between RLS and retinal thickness. In this study, we included 33 patients who were diagnosed with idiopathic RLS according to the "International RLS Study Group" criteria and 31 healthy subjects. All the patients and controls underwent routine ophthalmologic examination and had spectral-domain optical coherence tomography (OCT) performed. We compared the retinal thickness of the patients and control subjects. In the RLS group, foveal thickness was thinner then controls. Also, only inferior, superior, and temporal quadrant retina nerve fiber layer (RNFL) thickness were significantly thinner in the RLS group. The parafoveal ganglion cell complex (GCC) in the superior temporal, inferior temporal, inferior nasal quadrant, and perifoveal superior nasal thickness was also significantly thinner in the patient group. Pearson correlation analyses showed that there were statistically significant negative correlations between disease duration and macular GCC and RNFL thickness. Negative correlations were also detected between parafoveal superior, temporal, inferior and nasal macular thickness, parafoveal superior nasal, inferior temporal GCC thickness, and perifoveal superior nasal GCC thickness and disease duration. According to our results; most retinal layers are thinner in RLS patients, so it can be considered that OCT has a predictive value for progression of RLS.

Rate of augmentation and risk factors with long-term follow-up in Japanese patients with restless legs syndrome.

Preventing augmentation is the critical clinical issue for RLS treatment. As for augmentation in Asian RLS patients, there have been only four studies and the follow-up durations of these studies were not long. We investigated Japanese RLS patients with longer duration of treatment in a clinical setting. This study is a retrospective assessment of 42 RLS patients with follow-up durations of longer than 18months (78.4 ± 29.2, range 19-139) at two urban sleep centers in Osaka, Japan from May 2004 to April 2014. The mean age of first visit was 63.5 ± 14.1years old and the estimated age of RLS onset was 47.9 ± 16.5years old. Twenty-eight out of 42 patients were female. At initial evaluation, the mean International Restless Legs Scale score (IRLS score) was 22.0 ± 5.9. Thirty-one of 42 had already visited other clinics before coming to our sleep centers, and the number of clinics visited was 1.3 ± 0.6. Augmentation developed in two patients (4.8%), and the dosage of dopamine equivalent in patients with and without augmentation was 12.5 and 18.8mg vs. 15.8 ± 17.7mg. In the two RLS patients with augmentation, ferritin was 113.1 and 114.1ng/mL, respectively, and the number of clinics before coming to our sleep centers was both three. The augmentation rate of Japanese RLS patients from our study is low compared with previous Western and Asian studies. It might be attributable to racial difference, lower dosage of dopaminergic treatment, and the level of ferritin.

Use of cutaneous silent period parameters as a diagnostic indicator in patients with restless legs syndrome-a study in south Indian population

Objective: The objectives of this study were to investigate cutaneous-silent- period (CSP) parameters- CSP latency and CSP duration in patients with ‘Restless legs Syndrome’ and compare it with that of normal healthy controls. Methods: Thirty patients diagnosed with restless legs syndrome were included in this study. The cutaneous silent period was evoked by electrical stimulation of sural nerve whereby both CSP parameters CSP latency and CSP duration were recorded and analyzed. Results: The mean latencies of CSP among the thirty RLS patients were 101.95±12.12 while the control group showed 96.23± 9.16. There is a statistically significant high average latency in RLS patients (101.95± 12.12) than control group (96.23± 9.16) with p value=0.044. This study also showed the average CSP duration to be high in RLS patients (42.25± 11.12), when compared to the control group – 36.75± 8.35 (p value=0.035). Conclusion: While RLS is a common sensorimotor disorder, the diagnosis of RLS is purely clinical and there are no objective tests for the diagnosis. Unfortunately, the awareness is poor among the lay population, general practitioners and even specialists in the Indian subcontinent. The authors feel that the CSP test can be used as an objective method supporting the diagnosis of RLS. Furthermore, we believe that this paper will help create awareness in addition to encouraging more research in this arena from medical personnel in India.

Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in hemodialysis-associated restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a neurological disorder characterized by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on hemodialysis (HD) with RLS treated with rotigotine. Objectives(1) To establish the prevalence of RLS in our HD unit. (2) To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. Material and methodsA single-center, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analyzed: (1) Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. (2) Lower extremity symptoms questionnaire (QS). (3) RLS severity symptoms scale (SRLSS). (4) RLS quality of life: John Hopkins RLS-QoL (JH-QoL). (5) Sleep hygiene: SCOPA Scale. ResultsWe included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD and 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (>20%) and complete (>80%) remission, respectively, while 55.5% achieved “zero” symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. ConclusionsRLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on hemodialysis.

Efectos de la rotigotina sobre la sintomatología, calidad de vida e higiene de sueño en el síndrome de piernas inquietas en hemodiálisis

BackgroundRestless legs syndrome (RLS) is a neurological disorder characterised by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on haemodialysis (HD) with RLS treated with rotigotine. Objectives1.- To establish the prevalence of RLS in our HD unit. 2.- To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. Material and methodsA single-centre, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analysed: 1.- Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. 2.- Lower extremity symptoms questionnaire (QS). 3.- RLS severity symptoms scale (SRLSS). 4.- RLS Quality of life: John Hopkins RLS-QoL (JH-QoL). 5.- Sleep hygiene: SCOPA Scale. ResultsWe included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD. And 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (> 20%) and complete (> 80%) remission, respectively, while 55.5% achieved «zero» symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. ConclusionsRLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on haemodialysis.

Diurnal variation of default mode network in patients with restless legs syndrome

ObjectiveRestless 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. MethodsFifteen 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. ResultsRLS 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. ConclusionsThe 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.

Allocating provider resources to diagnose and treat restless legs syndrome: a cost-utility analysis

ObjectivesRestless legs syndrome (RLS) is a neurological disorder that is frequently misdiagnosed, resulting in delays in proper treatment. The objective of this study was to analyze the cost-utility of training primary care providers (PCP) in early and accurate diagnosis of RLS. MethodsWe used a Markov model to compare two strategies: one where PCPs received training to diagnose RLS (informed care) and one where PCPs did not receive training (standard care). This analysis was conducted from the US societal and health sector perspectives over one-year, five-year, and lifetime (50-year) horizons. Costs were adjusted to 2016 USD, utilities measured as quality-adjusted life-years (QALYs), and both measures were discounted annually at 3%. Cost, utilities, and probabilities for the model were obtained through a comprehensive review of literature. An incremental cost-effectiveness ratio (ICER) was calculated to interpret our findings at a willingness-to-pay threshold of $100,000/QALY. Univariate and multivariate analyses were conducted to test model uncertainty, in addition to calculating the expected value of perfect information. ResultsProviding training to PCPs to correctly diagnose RLS was cost-effective since it cost $2021 more and gained 0.44 QALYs per patient over the course of a lifetime, resulting in an ICER of $4593/QALY. The model was sensitive to the utility for treated and untreated RLS. The probabilistic sensitivity analysis revealed that at $100,000/QALY, informed care had a 65.5% probability of being cost-effective. ConclusionA program to train PCPs to better diagnose RLS appears to be a cost-effective strategy for improving outcomes for RLS patients.

Combined resting state functional magnetic resonance imaging and diffusion tensor imaging study in patients with idiopathic restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a common neurological disorder characterized by an urge to move the legs along with paraesthesia deep within them. In this study, we aimed to use diffusion tensor imaging (DTI) and regional homogeneity (ReHo) to investigate the changes in regional spontaneous brain activity change for RLS patients against age- and gender-matched normal control (NC) subjects. MethodsA total of 35 RLS patients and 27 age- and gender-matched NC subjects were recruited for group comparison research that used DTI and ReHo techniques. DTI was analysed by FSL and tract-based spatial statistics (TBSS) software to measure the values of fractional anisotropy (FA) or mean diffusivity (MD) in brain regions. Statistical Parametric Mapping 8 (SPM8) was used for data preprocessing and Data Processing Assistant for Resting-State fMRI (DPARSF) toolbox was used for ReHo calculation. For multiple comparison correction, the AlphaSim program implemented in AFNI was used to control the false-positive rate (corrected p < 0.05). ResultsThere was no significant difference between the iRLS and NC groups in age or gender. In the one-sample t-test, both the NC and RSL groups showed increased ReHo in the bilateral posterior cingulate/precuneus cortex compared to the groups' global means, indicating that the default mode network was at rest. The RLS group showed a smaller cluster size than the NC group. In the two-sample t-test, the RLS group showed increased ReHo in the bilateral middle frontal gyrus, anterior cingulate cortex, caudate nucleus, insula, thalamus, putamen and left posterior cingulate cortex compared to the NC group. The statistical analysis of DTI images did not show any difference between the two groups. TBSS group comparison did not reveal any difference in FA or mean diffusivity (MD) of any brain region. ConclusionRLS patients showed that greater ReHo within the striatum, thalamus and the limbic system, which implies that the emotional processing, motion control and cognition in the cortico-striatal-thalamic-cortical (CSTC) loop may be the site of dysfunction in RLS patients. This finding may provide imaging evidence to explore the pathophysiology of RLS. On the other hand, we did not see any change in the microstructure in the DTI analysis for RLS patients when compared to the NC group, which suggests a metabolic impairment.

Restless legs syndrome after high-risk TIA and minor stroke: association with reduced quality of life

BackgroundRestless legs syndrome (RLS) is a movement disorder that is associated with poor quality of life and depressive symptoms in the general population. Emerging evidence suggests that RLS is closely associated with cerebrovascular disease. We assessed the effect of RLS on quality of life after stroke and transient ischemic attack (TIA). MethodsIn this single-center prospective study, we recruited patients within 14 days of high-risk TIA or minor stroke. Patients were diagnosed with RLS using a questionnaire based on the 2003 International RLS Study Group criteria, and diagnoses were confirmed by a sleep neurologist. Follow-up assessments were conducted within 2–6 months of recruitment. The outcome of quality of life was measured using the Stroke-specific Quality of Life (SS-QoL). ResultsOf the 94 patients recruited into the study, 23 (24.4%) were diagnosed with RLS: 11 were newly diagnosed with RLS and 12 had RLS preceding the index stroke/TIA. There were no significant differences in baseline characteristics between those with or without RLS. Median SS-QoL in patients with RLS was lower at baseline (p = 0.008) and at follow-up (p = 0.002). RLS patients had more depressive symptoms at follow-up (p = 0.007). Ordinal logistic regression demonstrated that RLS was negatively associated with quality of life at baseline (OR = 0.28; p = 0.010) and at follow-up (OR = 0.14; p = 0.029), independent of functional outcome and depressive symptoms. ConclusionsRLS is common after stroke or TIA and negatively affects the quality of life. Screening for RLS after cerebrovascular events may be warranted, and future research should assess whether treatment of RLS can improve post-stroke quality of life.