Prevalence of restless legs syndrome in Parkinson's disease: a systematic review and meta-analysis of observational studies

ObjectiveRestless legs syndrome (RLS) and Parkinson's disease (PD) are common neurological disorders that respond to dopaminergic therapy. RLS prevalence among people with PD varies widely (0–38%) in the literature, complicating efforts to understand whether the two diseases might be associated.MethodThe databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for observational and case-control studies of RLS prevalence in PD. Eligible studies were meta-analyzed using Stata 12.0.ResultsPooled RLS prevalence in PD among various patient populations was 14%, and prevalence in Asia (12%) was slightly lower than outside Asia (16%). Prevalence was higher among patients who had previously received PD treatment (15%) than among drug-naïve patients (11%). Prevalence of RLS was higher in female PD patients (13%) than in male patients (11%). RLS prevalence was much higher among PD patients than among healthy controls (OR 2.86, 95% CI 2.10–3.90; p < 0.001).ConclusionThis meta-analysis may provide the first reliable pooled estimate of RLS prevalence in PD, and strong evidence that RLS risk is higher among PD patients than among healthy individuals.     

Bidirectional association between irritable bowel syndrome and restless legs syndrome: a systematic review and meta-analysis

BackgroundSeveral observational studies have shown that patients with irritable bowel syndrome (IBS) may have a high risk of restless legs syndrome (RLS). This systematic review and meta-analysis aimed to comprehensively investigate the bidirectional association between IBS and RLS.MethodsAll conservational studies on IBS and RLS were searched in MEDLINE (assessed by PubMed), Embase, Web of Science, CINAHL, the Cochrane Library database and Google Scholar from inception to June 14, 2020. The Newcastle–Ottawa Scale and Agency for Healthcare Research and Quality were used to assess the methodological quality of the cohort and cross-sectional studies, respectively. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using Reviewer Manager 5.3.ResultA total of five cross-sectional studies of moderate methodological quality and one cohort study of high methodological quality were included in our review. Four cross-sectional studies and one cohort study involving 86 438 individuals met the criteria of IBS predicating the onset of RLS. Patients with IBS had a nearly three-fold increased odds of RLS compared with controls (OR = 2.60, 95%CI: 2.17–3.12, P < 0.00001; I² = 48%, P = 0.11). Three sensitivity analyses confirmed the robustness of the pooled result. Two cross-sectional studies involving 3581 individuals met the criteria of RLS predicating the onset of IBS. RLS patients had a nearly four-fold increased odds of IBS compared with controls without RLS (OR = 3.87, 95%CI: 1.73–8.66, P = 0.0010; I² = 77%, P = 0.04).ConclusionIn this systematic review and meta-analysis, we found a substantial bidirectional association between IBS and RLS. More prospective, high-quality, population-based studies are warranted in the future.     

Clinical differences between menstrual migraine and nonmenstrual migraine: a systematic review and meta-analysis of observational studies

Journal of Neurology - Approximately 60% of female migraineurs experience menstrual migraine (MM). Whether MM is a distinct clinical entity with more severe migraine attacks and a worse prognosis...     

中国帕金森病患者不宁腿综合征患病率的meta分析

目的为了研究不宁腿综合征(RLS)在中国帕金森病(PD)患者中的患病率,以及其与一般人群中RLS患病率的比较。方法通过在万方医学网、中国知网(CNKI)、维普网、Pubmed和Web of Science数据库中检索关于中国PD患者RLS的患病率相关的横断面研究和病例﹣对照研究。经过筛选后的文献采用Stata 12.0来分析RLS在中国PD患者中的患病率。结果总共纳入了34项研究,其中按照诊断标准可分为IRLSSG组(n=7)、NMS问卷组(n=16)、PDSS组(n=4)以及自定标准的其他组(n=7)。meta分析结果提示,总的RLS患病率为33%;IRLSSG组RLS的患病率为23%;NMS问卷组的患病率为44%;PDSS组为13%;其他组为28%。RLS在PD组的患病率明显高于一般人群(OR=4.65,95%CI:2.39~9.03,P0.001)。结论 RLS在中国PD人群中的患病率为33%;依据不同的诊断标准得出的患病率有所差异。NMS问卷作为RLS的初筛具有一定作用,而对于PD中RLS患者的诊断则推荐采用IRLSSG。此外,中国PD人群中的RLS患病率要明显高于一般人群。     

Systematic review and meta-analysis of observational studies to understand the prevalence of restless legs syndrome in multiple sclerosis: an update

ObjectiveMultiple sclerosis (MS) is related to the demyelination of intracranial nerves at multiple sites, while restless legs syndrome (RLS) appears to be caused by dysfunction of the dopaminergic system. Since RLS prevalence is higher among MS patients than in the general population, we carried out an updated meta-analysis to understand whether the two diseases might be associated.MethodWeb of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were searched for observational and case-controlled studies of RLS prevalence in MS. Eligible studies were meta-analyzed using Stata 12.0.ResultsPooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case–control studies (23%). RLS prevalence was higher among female than male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (OR 3.96, 95%CI 3.29–4.77, p < 0.001).ConclusionOur meta-analysis updates the most recent meta-analysis in 2013 and provides perhaps the first reliable pooled estimate of RLS prevalence in MS. The available evidence strongly suggests that RLS risk is higher among MS patients than healthy controls.     

Association between restless legs syndrome and hypertension: a meta-analysis of nine population-based studies

Previous population-based studies evaluating the association between restless legs syndrome (RLS) and cardiovascular risk factors have showed inconsistent results, especially for the relationship between RLS and hypertension. We, therefore, aimed to meta-analyze to assess the association between RLS and hypertension. PubMed and Embase databases were systematically searched to identify eligible studies. Nine population-based cross-sectional studies were selected for inclusion, involving 102,408 individuals. Overall, the prevalence of hypertension in RLS subjects was higher than those without RLS (OR = 1.36, 95% CI, 1.18–1.57, P = 0.043). Our findings indicate that RLS is associated with increased blood pressure. More large-scale and prospective studies are warranted to further clarify the relationship and its potential mechanism.     

Prevalence of restless legs syndrome in a Japanese elderly population

ObjectiveTo estimate the prevalence of restless leg syndrome (RLS) in elderly Japanese people by means of a population-based survey of subjects aged ≥65 years.BackgroundStudies conducted worldwide have revealed large variations in the prevalence of RLS among different populations. However, few studies have been done in Japan.MethodsA population-based survey was carried out from 2003 to 2006 through a local healthcare project in the small town of Ajimu in a rural area of southern Japan. A Japanese translation of the questionnaire covering the four features of RLS as defined by the International RLS Study Group in 1995 was used to confirm the diagnosis of RLS. All participants aged ≥65 years were invited to fill out the questionnaire. Subjects with positive results underwent face-to-face interviews.ResultsA total of 1251 persons (men, 35%; mean age, 75.0 ± 6.1 years) answered the questionnaire. Of these 1251 participants, 70 (5.6%) (men, 20%; mean age, 75 ± 4.9 years) answered the questions on RLS positively. Face-to-face interviews and examination confirmed the diagnosis of RLS in 12 subjects. Therefore the overall prevalence of RLS in the elderly Japanese population was estimated at 0.96%, with a higher prevalence in women (1.23%) than in men (0.46%).ConclusionThe overall prevalence of RLS among inhabitants of Ajimu aged ≥65 years is 0.96%. Most of the subjects identified were women. The prevalence of RLS is lower in Japan than in studies conducted in European and North American populations.     

Prevalence of restless legs syndrome in blood donors

Iron deficiency anemia has been linked to restless legs syndrome (RLS) and regular blood donation may lead to iron deficiency. It has been reported that blood donations may be associated with RLS. A recent study from Sweden found that 25% of the women donors were affected by RLS. However, this type of study has not been replicated in the United States. We conducted a study in our blood donation unit between September and October 2008. To identify those with RLS, we used the RLS diagnostic index questionnaire by Benes et al. The proportion of blood donors with RLS was estimated and the number of blood donations and hemoglobin levels were compared according to RLS status. One hundred and fifty one patients were interviewed; 7 patients who donated only platelets were excluded, leaving 144 patients for analysis. There were 13 (9.0%, 95% confidence interval [CI]: 4.9–14.9%) patients with RLS. Of these, 7 (4.9%, 95% CI: 2.0–9.8%) had possible RLS and 6 (4.2%, 95% CI: 1.5–8.9%) had major or clinically relevant RLS. There was no dramatic association between RLS and number of blood donations or hemoglobin level (all P ≥ 0.21). In our sample of blood donors in the United States, the prevalence of major RLS was 4%. We could not demonstrate an association between RLS and the frequency of blood donation or hemoglobin level in our relatively small sample; a larger sample is needed to better identify any associations. © 2010 Movement Disorder Society     

Prevalence and correlates of restless legs syndrome in adolescents

Aim The aim of this study was to determine the prevalence and correlates of restless legs syndrome (RLS) in adolescents. Method A sleep questionnaire aimed at identifying ‘definite’ RLS criteria (also including the Strengths and Difficulties Questionnaire and the Epworth Sleepiness Scale) was completed by 3304 high school adolescents aged 15 to 18 years (49% male; 51% female) in Gaziantep, Turkey. The diagnosis of RLS was confirmed by face‐to‐face or phone interviewing. The χ² or Student’s t‐test and logistic regression tests were used for statistical evaluation. Results ‘Definite’ RLS was diagnosed in 3.6% of participants. RLS symptoms were reported to occur on more than one occasion per week (frequent RLS) in 2% of participants and to make it to difficult to fall asleep or stay asleep (RLS with sleeping difficulty) in 1.7%. The prevalence of the combination of frequent symptoms and sleeping difficulty was 0.8%. Logistic regression analysis revealed that RLS was independently associated with nocturnal bed‐wetting (4.2% vs 0.8%; p=0.004), sleeping difficulty (47% vs 32%; p=0.011), Epworth Sleepiness Scale score (4.9 vs 3.9; p=0.036), hyperactivity/inattention (25% vs 14%; p=0.049), awakening with discomfort in the legs (51% vs 30%; p<0.001), and parents with RLS‐implying symptoms (56% vs 38%; p=0.006). RLS with sleeping difficulty was associated with hyperactivity/inattention (p=0.007); frequent RLS was associated with arm restlessness (p=0.006). Interpretation ‘Definite’ RLS is not rare in adolescents; furthermore, it may be accompanied by several comorbid conditions that can impair quality of life in adolescents.     

Accompanying migrainous features in pediatric migraine patients with restless legs syndrome

Neurological Sciences - The present study aimed to examine the frequency of restless legs syndrome (RLS) in pediatric patients with migraine and tension-type headache (TTH) and to investigate...     

Prevalence of restless legs syndrome in a rural community in Japan

To assess the prevalence and clinical significance of restless legs syndrome (RLS) in a Japanese population, we carried out a community‐based survey in a rural area of Japan. We sent questionnaires requesting information on demographics, the Center for Epidemiological Studies Depression scale, the Short Form‐8, the Pittsburgh Sleep Quality Index, the National Institutes of Health/International RLS Study Group (IRLSSG) consensus questionnaire, and the IRLSSG severity scale for RLS (IRLS) to 5,528 eligible adult residents in the town of Daisen in the Tottori prefecture of Japan. Next, we performed telephone interviews to identify subjects with probable RLS. Of the 2,812 subjects (51.1%) who gave complete answers on the IRLSSG questionnaire, 50 (1.8%) were judged as RLS positive. The prevalence of RLS was significantly higher in women than in men, and significantly lower in individuals 60 years of age or older. Multiple logistic regression analysis revealed that the existence of RLS was significantly associated with depression, lowered mental quality of life, and sleep disturbances. The prevalence of RLS in adult Japanese populations may be lower than that reported in Caucasian populations. However, in a group of Japanese subjects, RLS had a significant impact on daytime functioning as well as subjective sleep quality. © 2008 Movement Disorder Society     

Functional neuroimaging studies in restless legs syndrome

Functional neuroimaging studies may contribute to elucidate pathophysiological mechanisms of the restless legs syndrome (RLS) which still remain unclear. Studies in patients with RLS have been performed using functional magnetic resonance imaging (fMRI), single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET). SPECT and PET studies revealed some controversial results of the pre- and postsynaptic dopaminergic neurotransmission system and cerebral metabolism in RLS probably reflecting a dysfunction of the central dopaminergic system. However, it still has to be determined whether these alterations affect the nigrostriatal and/or other central dopaminergic systems like the diencephalospinal or mesolimbic pathway and whether they are the primary mechanisms or only secondary phenomena within the manifestation of RLS symptoms. A subtle receptor dysfunction or a synaptic dopaminergic deficit may play a major role. fMRI investigations of RLS patients revealed an activation in the red nuclei and brainstem close to the reticular formation during the symptomatic period, suggesting that subcortical cerebral generators are involved in the pathogenesis of RLS. However, both techniques are not yet clinically relevant methods to differentiate RLS from other movement disorders during sleep. Further investigations, especially at night when RLS symptoms are most pronounced, will lead to a better understanding of the mechanisms underlying RLS.     

Restless legs syndrome and cognitive function among adults: a systematic review and meta-analysis

Journal of Neurology - Changes in the cognitive function of patients with restless legs syndrome is a growing area of research. Although several studies have been performed to investigate the...     

Management of augmentation of restless legs syndrome with rotigotine: a 1-year observational study

AimThe aim of this study is to assess the effect of switching to rotigotine transdermal patch on severity of restless legs syndrome (RLS) in patients who experienced acute augmentation with previous oral dopaminergics.MethodsIn this 13-month observational study, adults with moderate-to-severe RLS and augmentation were switched to rotigotine per the physician’s independent decision. Assessments included Clinical Global Impression severity score (CGI-1); (primary), treatment regimen for switching (secondary), RLS-6, International RLS Study Group Rating Scale (IRLS), and augmentation severity rating scale (ASRS).ResultsA total of 99 patients received rotigotine, of whom 46 completed observational period, and 43 were assessed for effectiveness. A total of 5 patients switched to rotigotine after a >1-day drug holiday, 23 switched overnight, 9 had an overlapping switch, and 6 received ongoing oral dopaminergics with rotigotine for ≥28 days. Of the 99 patients, 57 took concomitant RLS medications (excluding switching medications) on at least 1 day. At the final visit, median change in CGI-1 (Hodges–Lehman estimate [95% CI]) was −2.0 (–2.5, −1.50); 37 of the 43 patients improved by ≥1 CGI-1 category, and 16 of 43 were responders (≥50% improvement). RLS-6 and IRLS scores also improved. Patients had median ASRS of 0 at the final visit indicating “no worsening/occurrence of augmentation.” ASRS item 1 showed a shift in mean time of symptom onset (24-h clock) from 12:38 (baseline) to 18:25 (final visit). Most common reasons for withdrawal of rotigotine were adverse events (26 patients) and lack of efficacy (14 patients).ConclusionsSwitching from oral therapies to rotigotine was effective in improving RLS symptoms in 37 of the 43 patients (from the original population of 99 patients) who remained in the study over 13 months.Clinical trial registrationClinicalTrials.gov NCT01386944.     

共患不宁腿综合征对偏头痛患者情绪和睡眠的影响

目的探讨偏头痛患者的不宁腿综合征(RLS)的发病率及其对情绪和睡眠的影响。方法对200例偏头痛患者(偏头痛组)和100名正常成人(对照组)进行RLS发病率、严重程度、睡眠质量和焦虑及抑郁程度评分,比较偏头痛人群与对照组之间的差异。并对共患有RLS的偏头痛患者的情绪和睡眠情况进行分析。结果成人慢性偏头痛组的RLS发病率(16.25%)较对照组(5%)高,差异有统计学意义(P0.05);发作性偏头痛组的RLS发病率(12.5%)与对照组(5%)比较,差异无统计学意义(P0.05)。共患RLS的偏头痛患者较单纯偏头痛者的睡眠质量差、焦虑及抑郁评分高,差异有统计学意义(均P0.05)。头痛频率及RLS为抑郁、焦虑及睡眠障碍的影响因素(均P0.05)。偏头痛患者的汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分及匹茨堡睡眠质量量表(PSQI)评分与国际RLS评估量表(IRLS)的相关系数分别为rHAMD=0.397、rHAMA=0.434和rPSQI=0.500;RLS严重程度与抑郁、焦虑及睡眠障碍的严重程度呈正相关关系(均P0.05)。结论慢性偏头痛患者的RLS发病率更高,且RLS症状更严重。RLS的严重程度与抑郁、焦虑和睡眠障碍程度呈正相关关系。