Project description:BackgroundRestless legs syndrome (RLS) is frequent in dialysis patients and occurs predominantly in its most severe forms. The aim of the present study was to evaluate the effects of electroacupuncture (EA) in hemodialysis patients with RLS by heart rate variability (HRV) monitor.MethodsOne hundred twelve subjects who were hemodialysis patients with RLS will be divided into 2 groups: experimental and control. Each subject will receive the treatment relevant to their group 2 times a week for 4 weeks. After 4 weeks of treatment the subject will enter a 2-week washout period, after which the subjects will switch groups. Measurements will include HRV recordings, International Restless Legs Syndrome Rating Scale (IRLSRS) and Insomnia Severity Index (ISI).ResultThe results of this study will systematically evaluate the effectiveness and safety of electoracupuncture intervention for hemodialysis patients with RLS.DiscussionThis study is the first investigation to analyze the relationship between EA and the change of HRV by an objective monitor. If the findings of the current trial are positive, this study will also help support an effective, safe and cheap approach to clinical treatment of this challenging disorder, help foster improved understanding the relationship between autonomic nervous system and RLS, and ultimately contribute to elucidate the mechanisms of EA.Trial registrationClinicalTrials.gov Identifier: NCT04356794; registration date: April 22, 2020.
Project description:Study objectivesRecent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis. The study objectives were to evaluate whether the associations of RLS with all loci determined in previous GWAS for Caucasians can be replicated significantly for the Korean population and to elucidate whether an epistasis plays a role in the pathogenesis of RLS.Design setting and participantsDNA from 320 patients with RLS and 320 age- and sex-matched controls were genotyped for variants in the RLS loci.Measurements and resultsA significant association was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001, respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002), according to the model of inheritance. The OR for the interaction between rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the recessive model. There was no significant association between genotypes of all tested single nucleotide polymorphisms and the mean value of serum iron parameters.ConclusionsOur results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome.
Project description:IntroductionRestless legs syndrome (RLS) is a debilitating condition characterized by uncomfortable sensations in the legs, typically occurring during periods of rest or sleep. It is more prevalent during pregnancy and is linked to sleep disturbances, diminished quality of life, and pregnancy complications. However, previous studies yielded inconsistent findings among pregnant women in middle-income countries. Consequently, this systematic review and meta-analysis sought to determine the pooled prevalence of restless legs syndrome and its associated factors in these populations.MethodA systematic review and meta-analysis was conducted on published studies from middle-income countries until May 2023. The review strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant search terms were used to search for studies in PubMed, MEDLINE, EMBASE, and Google Scholar. Data extraction was performed using the Joanna Briggs Institute tool for prevalence studies. The meta-analysis was conducted using STATA 17 software, and heterogeneity was assessed using the I2 test, while publication bias was evaluated using Egger's test. Forest plots were also used to present the pooled prevalence and odds ratio (OR) with a 95% confidence interval (CI) using the random-effects model.ResultThis review included 22 studies from nine countries with a total of 17, 580 study participants. The overall pooled prevalence of RLS among pregnant women in middle-income countries was 13.82% (95% CI: 13.31, 14.32), and having low hemoglobin level (AOR: 1.68, 95% CI: 1.29, 2.18), history of RLS (AOR: 7.54, 95% CI: 3.02, 18.79), muscle cramps (AOR: 3.58, 95% CI: 1.21, 10.61), excessive day time sleepiness (AOR: 4.02, 95% CI: 1.34, 12.04), preeclampsia (AOR: 2.06, 95% CI: 1.28, 3.30), and taking prophylactic iron supplementation (AOR: 0.59, 95% CI: 0.50, 0.69) were the identified factors associated with it.ConclusionGenerally, nearly one in every eight pregnant women in middle-income countries develop restless legs syndrome during pregnancy. Having low hemoglobin level, a history of RLS, muscle cramps, excessive daytime sleepiness, preeclampsia, and taking prophylactic iron supplementation were the identified factors associated with it. These findings underscore the importance of addressing the identified factors associated with RLS in order to effectively mitigate its occurrence among pregnant women.
Project description:ObjectiveThis study investigated the proposed association between restless legs syndrome (RLS) and the prevalence of hypertension.MethodsA meta-analysis was conducted based on searches of the PUBMED, EMBASE, Cochrane Library, and Korean electronic databases. Cohort and cross-sectional studies reporting the incidence of hypertension in individuals with RLS were included. Dichotomous data were pooled to obtain an odds ratio (OR) and 95% confidence interval (CI) for the prevalence of hypertension in individuals with RLS. The main outcome measure of the study was prevalence of hypertension in patients with RLS compared with a control group.ResultsOne cohort study and eight cross-sectional studies were included in the meta-analysis. Individuals with RLS had an increased prevalence of hypertension (all studies: OR=1.13, 95% CI=1.04-1.23; cross-sectional studies: OR=1.12, 95% CI=1.01-1.24). However, in subgroup analyses controlling for cardiovascular risk factors, such as diabetes mellitus and dyslipidemia, the differences in the prevalence of hypertension between RLS and control patients were no longer significant.ConclusionPatients with RLS may have a higher prevalence of hypertension, according to a pooled analysis, but the results remain to be confirmed in well-designed prospective studies.
Project description:BackgroundRestless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis.MethodsWe conducted a cohort study of prevalent adult hemodialysis patients in Hamilton, Canada. The diagnosis of RLS was made using the 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria. All participants received three screening instruments: (i) a single screening question for RLS derived from a nondialysis population; (ii) a single question from the Edmonton Symptom Assessment System (ESAS); and (iii) the IRLSSG Rating Scale (IRLS). All instruments were compared with the reference standard using logistic regression from which receiver operating characteristics curves were generated. Cutoffs associated with maximum performance were identified.ResultsWe recruited 50 participants with a mean (SD) age of 64 (12.4) years, of whom 52% were male and 92% were on three times weekly hemodialysis. Using the reference standard, 14 (28%) had a diagnosis of RLS. The single screening question for RLS had an area under the receiver operating curve (AUROC) of 0.72 with a sensitivity of 85.7% and specificity of 58.3%. An ESAS cutoff of ≥1 had the highest AUROC at 0.65 with a sensitivity of 79% and specificity of 56%. An IRLS cutoff of ≥20 had the highest AUROC at 0.75 with a sensitivity of 71% and specificity of 81%.ConclusionIRLS had better specificity than the single question or ESAS for the diagnosis of RLS.
Project description:Restless legs syndrome (RLS) is a common sleep-related disorder for which the underlying biological pathways and genetic determinants are not well understood. The genetic factors so far identified explain less than 10% of the disease heritability. The first successful genome-wide association study (GWAS) of RLS was reported in 2007. This study identified multiple RLS associated risk variants including some within the non-coding regions of MEIS1. The MEIS1 GWAS signals are some of the strongest genetic associations reported for any common disease. MEIS1 belongs to the homeobox containing transcriptional regulatory network (HOX). Work in C. elegans showed a link between the MEIS1 ortholog and iron homeostasis, which is in line with the fact that central nervous system (CNS) iron insufficiency is thought to be a cause of RLS. Zebrafish and mice have been used to study the MEIS1 gene identifying an RLS-associated-SNP dependent enhancer activity from the highly conserved non-coding regions (HCNR) of MEIS1. Furthermore, this gene shows a lower expression of mRNA and protein in blood and thalamus of individuals with the MEIS1 RLS risk haplotype. Simulating this reduced MEIS1 expression in mouse models resulted in circadian hyperactivity, a phenotype compatible with RLS. While MEIS1 shows a strong association with RLS, the protein's function that is directly linked to an RLS biological pathway remains to be discovered. The links to iron and the enhancer activity of the HCNRs of MEIS1 suggest promising links to RLS pathways, however more in-depth studies on this gene's function are required. One important aspect of MEIS1's role in RLS is the fact that it encodes a homeobox containing transcription factor, which is essential during development. Future studies with more focus on the transcriptional regulatory role of MEIS1 may open novel venues for RLS research.
Project description:Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene-microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.
Project description:Restless legs syndrome (RLS) is a common sleep disorder that may be associated with pregnancy. Studies have found that the prevalence of RLS among pregnant women ranged from 10 to 34%. Typically, there is complete remission of symptoms soon after parturition; however, in some patients, they may continue postpartum. RLS has been shown to be associated with a number of complications in pregnancy including preeclampsia and increased incidence of Cesarean sections. Although multiple hypotheses have been proposed to explain this association, each individual hypothesis cannot completely explain the whole pathogenesis. Present understanding suggests that a strong family history, low serum iron and ferritin level, and high estrogen level during pregnancy might play important roles. Vitamin D deficiency and calcium metabolism may also play a role. Medical treatment of RLS during pregnancy is difficult and challenging considering the risks to mother and fetus. However, in some cases, the disease may be severe enough to require treatment.
Project description:Augmentation is a common complication of primary restless legs syndrome (RLS) during treatment; however, its incidence rate remains unclear.The aim of this study is investigate the rate of augmentation during RLS treatment.We searched 6 databases, including PubMed, OVID, Embase, Wiley citations, Web of Science research platform (including SciELO Citation Index, Medline, KCI Korean Journal Database, the Web of Science™ Core Collection), and the Cochrane library, and screened the reference lists of the included trials and recently published reviews.Randomized controlled trials and observational studies that reported augmentation events during RLS treatment.Primary RLS patients older than 18 years.No restrictions regarding intervention types were applied.Three investigators independently extracted and pooled the data to analyze the augmentation rate of the total sample and of patient subgroups with different interventions, treatment durations and drug regimens and different geographic origins. Fixed-effects or random-effects model was used for pooled analysis.A total of 60 studies involving 11,543 participants suggested an overall augmentation rate of 5.6% (95% confidence intervals (CI), 4.0-7.7). The augmentation incidence was 6.1% (95% CI, 4.1-9.1) for long-term treatment and 3.3% (95% CI, 1.4-7.3) for short-term treatment. In addition, 27.1% (95% CI, 12.3-49.5) of the levodopa-treated patients, 6.0% (95% CI, 4.1-8.8) of the patients treated with dopamine agonists, and 0.9% (95% CI, 0.2-3.3) of the patients taking pregabalin or gabapentin developed augmentation. Augmentation occurred in 7.2% (95% CI, 5.0-10.3) of the patients taking immediate-release drugs and in 1.7% (95% CI, 0.6-5.0) of the patients taking transdermal application.The main limitations are that the augmentation rates were not evaluated according to drug dosage, gender, and age and symptom severity.Approximately 5 to 6 in 100 RLS patients developed augmentation during treatment.