The Humanistic and Economic Burden of Restless Legs Syndrome

Objectives

To evaluate the humanistic and economic burden of a restless legs syndrome (RLS) diagnosis with regard to health-related quality of life, work productivity loss, healthcare resource use, and direct and indirect costs.

Study Design

Self-reported data came from the 2012 National Health and Wellness Survey (NHWS), a large, annual, nationally representative cross-sectional general health survey of US adults.

Methods

RLS patients (n = 2,392) were matched on demographic and health characteristics to Non-RLS respondents via propensity score matching differences between groups were tested with Bivariate and multivariable analyses.

Results

RLS patients had significantly lower health-related quality of life scores: Mental Component Summary (44.60 vs. 48.92, p<.001), Physical Component Summary (40.57 vs. 46.78, p<.001), Health Utilities (.63 vs. .71, p<.001) and higher levels of work productivity loss in the past seven days including absenteeism (8.1% vs. 9.3%, p<.001), presenteeism (26.5% vs. 15.8%, p<.001), and overall productivity loss (30.1% vs. 18.1%, p<.001) as well as general activity impairment (46.1% vs. 29.7%, p<.001). RLS patients had significantly higher healthcare resource use in the past 6 months than non-RLS patients: healthcare provider visits (7.46 vs. 4.42%, p<.001), ER visits (0.45 vs. 0.24, p<.001), and hospitalizations (0.24 vs. 0.15, p<.001). RLS patients also had higher estimated direct and indirect costs than non-RLS patients. Finally, it was found that across outcomes increasing severity is associated with increased economic and humanistic burden for RLS patients.

Conclusions

RLS patients suffer a greater humanistic and economic burden than those without RLS. Moreover as severity increases so does the burden of RLS.     

Restless Legs Syndrome in Chronic Pulmonary Disease

Eight consecutive patients referred for neurological opinion because of very severe “restless legs” all suffered from chronic pulmonary disease. It was considered that the restless legs syndrome was not a metabolic consequence of respiratory failure but a nervous manifestation of their invalidism.     

维持性血液透析患者合并不宁腿综合征的影响因素分析及有氧运动改善效果的临床研究

摘要 目的：分析维持性血液透析（MHD）患者合并不宁腿综合征（RLS）的影响因素,并探讨有氧运动对MHD合并RLS患者的改善效果。方法：选取2019年5月~2022年1月在首都医科大学附属北京朝阳医院进行MHD治疗的患者120例为研究对象。根据是否出现RLS将120例MHD患者分为合并RLS组（n=28）和未合并RLS组（n=92）。收集患者的临床资料,多因素Logistic回归分析MHD患者合并RLS的影响因素,并探讨有氧运动对MHD合并RLS患者的改善效果。结果：MHD合并RLS与性别、透析龄、高血压、饮酒史、收缩压、舒张压、血磷、维生素 B12（VitB12）、铁蛋白（SF）、同型半胱氨酸（Hcy）、血镁、β2微球蛋白（β2-MG）有关（P<0.05）。多因素Logistic回归分析结果显示：透析龄偏长、β2-MG偏高、VitB12偏高、Hcy偏高、饮酒史、SF偏低、血镁偏高、性别为女、血磷偏高是MHD合并RLS的危险因素（P<0.05）。干预12周后,MHD合并RLS患者的匹兹堡睡眠质量指数（PSQI）、焦虑自评量表（SAS）、抑郁自评量表（SDS）评分均较干预前下降（P<0.05）。结论：透析龄偏长、β2-MG偏高、VitB12偏高、Hcy偏高、饮酒史、SF偏低、血镁偏高、性别为女、血磷偏高均会增加MHD合并RLS的发生风险。有氧运动应用于MHD合并RLS患者,有助于改善患者的睡眠、抑郁和焦虑状况,效果较好。     

不宁腿综合征临床病例分析

目的:不宁腿综合征(restless legs syndrome,RLS)是神经系统常见的感觉运动障碍性疾病,在欧美是引起睡眠障碍较常见的原因之一,目前在我国对这一综合征的相关研究较少.本文目的旨在描述满足RLS最新诊断标准的RLS患者的临床特点及其对睡眠的影响.方法:实验对象选取2006年10月～2007年6月在哈医大二院门诊及住院的31例RLS患者,对患者的一般情况、临床特点及相关量表进行分析.结果:RLS临床表现谱与国外略有差异;RLS与睡眠障碍关系密切,特发性RLS对睡眠的影响更大.结论:RLS临床表现谱可能具有一定的人类种族差异;对RLS与睡眠障碍的关系有进一步进行深入研究的必要.     

家族性不宁腿综合征候选基因的连锁分析

不宁腿综合征（restless legs syndrome,RLS)是以下肢部出现蚁行样及酸、麻、胀等不适感而使肢体不得休息为特征的一组病症。由于症状常在晚间发作并导致运动不安,患者长期入睡困难,经受严重的继发性失眠。作为一种常见的神经系统疾病,RLS发病率高达5％,其中原发性RLS多呈阳性家族史,表现为单基因决定的常染色体显性遗传。现在,人们普遍认为RLS的发生很可能与神经系统内多巴胺能功能异常和脑内铁缺乏有关,并初步建立了脑铁－多巴胺能系统的致病模型。为了探求脑铁－多巴胺能系统在RLS中的作用,选择了与脑铁－多巴胺能系统相关的16个疾病侯选基因,在每个候选基因附近染色体区域内选取若干个微卫星多态标记,应用微卫星引物荧光标记－基因扫描技术,对一个汉族家族性不宁腿综合征家系进行了基因分型和常染色体显性遗传模式下的连锁分析,试图从分子遗传学层面上确认或排除一些可能与RLS相关的重要侯选基因。结果显示,当重组系数θ=0.00时,LOD值均小于－2.00,所选位点与家族性不宁腿综合征不连锁。由此得出结论,在本家系中,所有候选基因均与家族性不宁腿综合征的发病无关,家族性不宁腿综合征可能是由其他多巴胺传导和脑铁代谢相关基因所致,或是存在全新的致病机制参与RLS的发生。     

Restless Legs Syndrome and lateralized periodic movements due to a spinal schwannoma

We describe a case of Restless Legs Syndrome (RLS) associated to periodic limb movements (PLMs) in a woman with a cervical schwannoma. Neurological examination, laboratory tests, neurography and electromyography were unremarkable. Neuroimaging evidenced a schwannoma at C3 level that compressed the right ventral surface of the medulla. Somatosensory-evoked potentials showed absence of the N13 after right median nerve stimulation and reduction of amplitude of the same component after left nerve stimulation. A video-polysomnography documented PLMs with a marked prevalence of the right-sided movements. We believe that the cervical schwannoma played a role in the pathogenesis of RLS and of lateralized PLMs.

     

Restless Legs Syndrome,with Particular Reference to its Occurrence After Gastric Surgery

There is a higher incidence of restless legs syndrome (Ekbom''s syndrome) in patients after gastric surgery (11·3%) and with diabetes mellitus (17·0%) and uraemia (17·3%) than in patients who have been diagnosed as having a psychonoeurosis (4·0%) and in controls (2·0%). Three patients with malabsorption syndrome complained of restless legs, but these patients had abnormal neurological signs. The incidence after gastric surgery and in diabetes mellitus and uraemia remained high even when patients with any abnormal neurological signs were excluded.     

Sleep fragmentation and motor restlessness in a Drosophila model of Restless Legs Syndrome

Restless Legs Syndrome (RLS), first chronicled by Willis in 1672 and described in more detail by Ekbom in 1945, is a prevalent sensorimotor neurological disorder (5%-10% in the population) with a circadian predilection for the evening and night. Characteristic clinical features also include a compelling urge to move during periods of rest, relief with movement, involuntary movements in sleep (viz., periodic leg movements of sleep), and fragmented sleep. Although the pathophysiology of RLS is unknown, dopaminergic neurotransmission and deficits in iron availability modulate expressivity. Genome-wide association studies have identified a polymorphism in an intronic region of the BTBD9 gene on chromosome 6 that confers substantial risk for RLS. Here, we report that loss of the Drosophila homolog CG1826 (dBTBD9) appreciably disrupts sleep with concomitant increases in waking and motor activity. We further show that BTBD9 regulates brain dopamine levels in flies and controls iron homeostasis through the iron regulatory protein-2 in human cell lines. To our knowledge, this represents the first reverse genetic analysis of a "novel" or heretofore poorly understood gene implicated in an exceedingly common and complex sleep disorder and the development of an RLS animal model that closely recapitulates all disease phenotypes.     

Reduced Neural Synchrony in Patients with Restless Legs Syndrome during a Visual Oddball Task

Background

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an irresistible urge to move the legs. It has been reported that RLS patients show cognitive deficits, presumably due to hyperactivity causing loss of attention, or malfunctions in the frontal region resulting from sleep deprivation. However, the mechanism underlying cognitive deficits in RLS patients is mostly unknown. As an effort to clarifying this, we investigated the differences in neural activity and phase synchrony between healthy controls and RLS patients during cognitive task performances.

Methodology/Principal Findings

Seventeen female drug-naive RLS patients were enrolled in the study, and an age-matched group of thirteen healthy female volunteers served as controls. Multichannel event-related potentials (ERPs) were recorded from RLS patients and normal controls while performing a visual oddball task. In addition to conventional analyses of ERP waveforms and spectra, interregional gamma-band phase synchrony (GBPS) was investigated to observe the differences in interregional neural synchronies between normal and RLS patient groups. Strong GBPS was observed primarily between anterior and posterior regions along the midline for both groups. Along with significant reduction and delay of P300 ERP and induced gamma-band activity (GBA), the GBPS was considerably decreased in RLS patients compared to normal subjects, especially at frontal region.

Conclusions

Overall, our results support that cognitive dysfunction in RLS patients is associated with reduced interregional neural synchrony as well as alterations in local neural activity.     

Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q

Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction.05; P=6x10(-4); autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.     

Mouse Model for Protein Tyrosine Phosphatase D (PTPRD) Associations with Restless Leg Syndrome or Willis-Ekbom Disease and Addiction: Reduced Expression Alters Locomotion,Sleep Behaviors and Cocaine-Conditioned Place Preference

The receptor type protein tyrosine phosphatase D (PTPRD) gene encodes a cell adhesion molecule likely to influence development and connections of addiction-, locomotion- and sleep-related brain circuits in which it is expressed. The PTPRD gene harbors genome-wide association signals in studies of restless leg syndrome (Willis-Ekbom disease [WED]/restless leg syndrome [RLS]; p < 10⁻⁸) and addiction-related phenotypes (clusters of nearby single nucleotide polymorphisms [SNPs] with 10⁻² > p > 10⁻⁸ associations in several reports). We now report work that seeks (a) association between PTPRD genotypes and expression of its mRNA in postmortem human brains and (b) RLS-related, addiction-related and comparison behavioral phenotypes in hetero- and homozygous PTPRD knockout mice. We identify associations between PTPRD SNPs and levels of PTPRD mRNA in human brain samples that support validity of mouse models with altered PTPRD expression. Knockouts display less behaviorally defined sleep at the end of their active periods. Heterozygotes move more despite motor weakness/impersistence. Heterozygotes display shifted dose-response relationships for cocaine reward. They display greater preference for places paired with 5 mg/kg cocaine and less preference for places paired with 10 or 20 mg/kg. The combined data provide support for roles for common, level-of-expression PTPRD variation in locomotor, sleep and drug reward phenotypes relevant to RLS and addiction. Taken together, mouse and human results identify PTPRD as a novel therapeutic target for RLS and addiction phenotypes.     

Diseases in Patients Coming to a Sleep Center with Symptoms Related to Restless Legs Syndrome

Study Objective

To explore the profile of patients who visit a sleep center with symptoms that fulfill the four essential criteria for restless legs syndrome (RLS).

Design

A prospective study.

Setting

Outpatients from one sleep disorders clinic in Taiwan.

Participants

1,200 consecutive patients visit sleep disorders clinic with any sleep complaints.

Interventions

After completing a history and physical examination, all participants answered the RLS questionnaire. Subjects who fulfilled the four essential criteria for RLS were referred to a special clinic. A work-up including blood tests, polysomnography, and specialized neurological tests etc. was performed to make the final diagnosis.

Measurements and Results

A total of 1,185 participants were enrolled, and, of these, 131(11.1%) fulfilled the four essential criteria for RLS, and 121 completed the supplemental work-up. Their mean age was 47.6±13.3 and 52.9% were male. Insomnia and snoring were the most common chief complaints. Obstructive sleep apnea syndrome and other diseases were found in 103 patients. Only 18 (14.9%) patients had no comorbid condition and were diagnosed with primary RLS.

Conclusions

Symptoms of RLS are common in patients with sleep complaints. Even in a sleep clinic, using a questionnaire approach for identification of RLS has a low positive predictive value. Clinicians should pay attention to the limitations of the 4-item questionnaire in diagnosis of RLS and also the importance of a careful differential diagnosis to identify possible secondary causes of RLS.     

Restless legs syndrome

Being of the most frequent causes of insomnia, which in the end leads to chronic fatigue, inadequate performance of daily activities, and serious disruption of quality of living, restless legs syndrome (RLS) is nowadays not only a serious medical problem but a socio-economical one as well. Prevalence of the disorder in general population is estimated at 5 to 15%. Family history is positive in over 50% of idiopathic RLS patients which points to genetic basis of the disorder. The characteristics of the secondary or acquired form of RLS are symptoms that start later in life as well as a rapid progression of the disease. On the other hand, idiopathic RLS more often starts at a younger age and the prognoses are better. Over twenty disorders and conditions are brought in connection with secondary RLS. Although the cause of primary RLS is still unknown, there is a strong connection between central metabolism of iron as well as dopamine levels and RLS manifestation. A differential diagnosis of RLS includes a wide specter of motor and sensory disorders. Diagnosis is based on clinical features and the history of disease. To correctly diagnose idiopathic RLS one must first eliminate secondary causes of RLS and then also exclude any disorders with clinical features that mimic those of RLS. It has been estimated that some 20 to 25% of patients need pharmacological therapy. Best initial therapy is the application of nonergot dopamine agonists. Anticonvulsants, benzodiazepines and opioides can be given to patients who are refractory to dopaminergic therapy, those suffering from RLS with emphasized painful sensory component and those with RLS connected with insomnia.