继发性不宁腿综合征

本文回顾继发性不宁腿综合征的相关研究结果,介绍其常见病因。经研究显示,有多种因素可能与继发性不宁腿综合征的发生发展和严重程度相关,如肾衰竭、脊髓和周围神经病变、妊娠所致铁和叶酸缺乏及相应性激素变化;帕金森病多巴胺能系统功能紊乱;某些药物（抗抑郁药、抗精神病药、组胺受体阻断药）;吸烟、饮酒;咖啡因;偏头痛等。临床应详细询问病史,去除病因,提高患者生活质量。     

Predictors of clinical response in a double-blind placebo controlled crossover trial of gabapentin enacarbil for restless legs syndrome

ObjectivesRestless Legs Syndrome (RLS) is a sensory-motor disorder which produces sleep disturbance. Using data from a large clinical trial of gabapentin enacarbil (GEn) we sought to assess the ability of baseline, and changes from baseline, in clinical trial endpoints to predict treatment response.MethodsData were derived from a randomized, double-blind, placebo-controlled, crossover polysomnography study of gabapentin enacarbil 1200 mg (n = 121) or placebo (n = 123). Efficacy evaluations included: sleep measures from polysomnography, subjective sleep measures, Suggested Immobilization Test (SIT) measures, and International Restless Legs Severity Scale (IRLS) and Clinical Global Impression-Improvement (CGI-I). Correlations were evaluated using Spearman's rank correlation coefficients. Predictors of treatment response were separately assessed for GEn and placebo using categorical IRLS and CGI-I outcomes. Stepwise logistic regression models ascertained which combination of baseline and change from baseline variables predicted response.ResultsModerate to large correlations were observed between changes in the IRLS and changes in subjective sleep for both GEn and placebo, substantially larger for GEn than placebo. Small to moderate correlations were present between the change in IRLS and the change in SIT-discomfort for both GEn and placebo. In the stepwise regression, for both GEn and placebo, baseline and change from baseline SIT discomfort, as well as change in sleep quality, were strong predictors of response.ConclusionsChanges in sleep quality, and baseline and changes in SIT discomfort were prominent predictors of treatment response for GEn and placebo. Predictors of treatment response may allow for more targeted enrollment in future clinical trials and may provide insights into the efficacy of RLS treatments.     

不安腿综合征的诊治

目的 探讨不安腿综合征(RLS)的临床特征,为早期诊断和治疗提供参考.方法 结合相关文献,对16例确诊的不安腿综合征患者的临床表现、治疗、转归进行回顾性分析.结果 RLS是一种以双下肢感觉异常不适为主要症状的病因未明的疾病,可能与贫血、铁缺乏、糖尿病史、肾功能不全等有关.多巴胺受体激动剂为治疗该病的首选药,阿片类、抗惊厥药物、苯二氮类药物及铁剂治疗对部分患者有效.结论 RLS预后较好,及时的诊断和治疗可明显改善患者的生活质量.     

Olanzapine-induced restless legs syndrome

Only nine patients with olanzapine-induced restless legs syndrome (RLS) have been reported in the literature to our knowledge. We describe two patients with olanzapine-induced RLS treated at our hospital and review the nine reported patients. There were five women and six men aged between 28 and 62 years in the overall group. RLS symptoms emerged at olanzapine doses between 2.5 and 20 mg. The symptoms improved in all patients when the dose was reduced and immediately disappeared when the medication was stopped. International Restless Legs Scale (IRLS) scores ranged from 10 to 35. Three patients had a family history of idiopathic RLS. Supplemental drugs were administered to control RLS symptoms in five patients. Ropinirole was effective in one patient, while two patients did not respond to the drug. Propoxyphene effectively relieved symptoms in one patient who did not respond to ropinirole or clonazepam. RLS symptoms did not recur following substitution of other antipsychotic drugs for olanzapine. In conclusion, olanzapine can induce RLS, particularly in patients with a family history of idiopathic RLS. More than half of the patients experienced severe to very severe symptoms. A dose-dependent relationship was observed between olanzapine and RLS symptoms. A gradual increase in dose may prevent olanzapine-induced RLS. The optimal treatment for olanzapine-induced RLS is discontinuation of olanzapine.     

普拉克索治疗不宁腿综合征的Meta分析

目的 系统评价普拉克索治疗不宁腿综合征(restless legs syndrome,RLS)的疗效与安全性.方法 检索中国期刊全文数据库( CNKI)、美国国立医学生物信息中心PubMed数据库( PubMed)、荷兰医学文摘数据库(Embase)、Cochrane Library数据库关于普拉克索治疗RLS的随机、双盲、安慰剂对照研究.对符合条件的研究结果用RevMan 5.0软件进行Meta分析.以普拉克索组和安慰剂组在国际不宁腿研究组评分量表( International RLS Study Group rating scale,IRLS)评分变化方面的加权均数差(weighted mean difference,WMD)和普拉克索组相对于安慰剂组在临床疗效总评(clinical global impression-improvement,CGI-I)方面疗效显著率的相对危险度(relative risk,RR)为指标进行疗效评价,以其在不良事件方面的相对危险度为指标进行安全性评价.结果 共纳入5项研究,1776例患者被随机分配,其中普拉克索组945例,安慰剂组831例.Meta分析结果显示,普拉克索组相对于安慰剂组在IRLS评分变化方面的WMD=-6.34 (Z=12.76,P＜0.01),在CGI-I显著性评估方面的RR=1.65 (Z=10.39,P＜0.01);两组在不良事件方面的RR=1.14 (Z=1.87,P=0.06).结论 普拉克索是治疗RLS的有效且安全的药物.     

不宁腿综合征

不宁腿综合征为临床常见中枢神经系统感觉运动障碍性疾病,发病机制尚不明确,与遗传因素或多巴胺能系统功能失调有关。发病原因与缺铁性贫血、妊娠、免疫系统疾病、肾衰竭、糖尿病、周围神经病等有关。临床主要表现为感觉障碍、运动症状,并于休息时、傍晚或夜间出现或加重。以铁离子、多巴胺制剂、多巴胺受体激动药、抗癫痂药及阿片类药物为主要治疗药物,     

不宁腿综合征40例临床分析

目的 探讨不宁腿综合征(RLS)的临床表现,观察吡贝地尔对RLS的治疗效果.方法 对40例不宁腿综合征患者的临床特征和治疗结果 进行回顾性分析.结果 40例患者均有肢体不能忍受的不适感,迫切希望活动肢体,夜间症状加重,常伴失眠.根据国际不宁腿综合征研究组(IRLSSG)的诊断标准,平均得分24分.40例患者均给予吡贝地尔50mg睡前口服,治疗4周后,大多数患者主观症状明显改善,IRLSSG评分明显减少(平均得分11分).结论 不宁腿综合征常表现下肢不适,夜间加重,活动后减轻,常伴睡眠障碍,诊断主要依据临床表现,吡贝地尔治疗有一定效果.     

普拉克索治疗原发性不宁腿综合征的疗效和安全陛观察

目的 观察普拉克索对我国原发性不宁腿综合征(RLS)患者的治疗效果以及可能发生的不良反应. 方法 选择自2009年5月至11月在哈尔滨医科大学第二附属医院神经内科就诊的10例中到重度原发性RLS患者,给予普拉克索0.125～0.75mg/d,每日睡前2～3h顿服,持续治疗6周.利用国际RLS研究小组的RLS严重程度量表(mLS)、临床总体印象改善量表(CGI-I)、患者总体印象量表(PGI)和Epworth嗜睡量表(ESS)对患者治疗前后的RLS症状严重程度和嗜睡程度进行评估.并对结果进行统计学分析,同时记录不良反应.结果 (1)治疗后患者的IRLS评分较治疗前平均降低73.7%,比较差异有统计学意义(P<0.05),9例患者IRLS评分降低在50%以上;(2)治疗结束时,8例患者PGI评估选择很好或非常好,9例患者CGI-I评估为明显改善或非常明显改善;(3)患者ESS评分在治疗后较治疗前平均降低3.80±1.75,比较差异有统计学意义(P<0.05);(4)1例患者在治疗末期加量至0.5mg/d时出现轻度恶心,胃区不适,治疗结束停药2 d后症状自行消失;(5)1例患者首次用药后双下肢感觉异常和睡眠障碍即有明显改善.结论 为期6周的临床实验表明,在每日口服剂量为0.125～0.75 mg时,普拉克索对于我国原发性RLS的治疗是安全有效的.     

French consensus: Pharmacoresistant restless legs syndrome

Dopaminergic agonists, α2δ ligands and opioids are, as single-drug therapy, the first line treatment for restless legs syndrome (RLS/Willis-Ekbom disease). However, despite treatment efficacy, exacerbations of RLS may occur with overall worsening in symptoms severity, development of pain and symptoms spreading to other parts of the body, without meeting augmentation syndrome criteria. This development of “drug-resistant” RLS can cause pain, severe insomnia and psychiatric disorders that affect considerably patients’ quality of life. The lack of French recommendations for this form of RLS leave physicians with few options to help patients with physical and emotional distress. Our group of neurological experts and sleep specialists proposes a diagnostic and therapeutic strategy to provide better care and appropriate treatment through searching for the organic, psychiatric and/or iatrogenic causes of drug resistance. Once a drug-resistant RLS diagnosis has been confirmed, we recommend an obligatory work-up including: a video-polysomnogram, a biological evaluation including iron status, standard numeration and C-reactive protein level. Treatment will be comorbidity-dependent: dopaminergic agonist would be recommended in case of depression or associated periodic leg movements, α2δ ligand in case of insomnia, complaint of pain, or general anxiety, in association with low-dose opioids if necessary. Strong opioids should be preferred for multiresistant RLS.     

Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study

Background and PurposeRestless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement.Patients and MethodsThis was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period.ResultsBaseline International Restless Leg Scale (IRLS) scores for the treatment (24.8 ± 5.72) and placebo (23.0 ± 5.03) groups were similar. Baseline ferritin levels for the treatment (40.6 ± 15.3 ng/ml) and placebo (36.7 ± 20.8 ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3 ± 7.40) than in the placebo arm (1.14 ± 5.64), (p = 0.01). Ferritin levels increased more in the treatment arm (25.1 ± 20.3 ng/ml) than in the placebo arm (7.5 ± 13.7 ng/ml), (p = 0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p = 0.07).ConclusionsThis is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted.     

Seasonal trends in restless legs symptomatology: evidence from Internet search query data

ObjectivePatients with Willis-Ekbom disease (restless legs syndrome [RLS]) frequently report seasonal worsening of their symptoms; however, seasonal patterns in this disorder have not been systematically evaluated. The purpose of our investigation was to utilize Internet search query data to test the hypothesis that restless legs symptoms vary by season, with worsening in the summer months.MethodsInternet search query data were obtained from Google Trends. Monthly normalized search volume was determined for the term restless legs between January 2004 and December 2012. Using cosinor analysis, seasonal effects were tested for data from the United States, Australia, Germany, the United Kingdom, and Canada.ResultsCosinor analysis revealed statistically significant seasonal effects on search queries in the United States (P = .005), Australia (P = .00007), Germany (P = .00009), and the United Kingdom (P = .003), though a trend was present in the search data from Canada (P = .098). Search queries peaked in summer months in both northern (June and July) and southern (January) hemispheres. Search query volume increased by 24–40% during summer relative to winter months across all evaluated countries.ConclusionsEvidence from Internet search queries across a wide range of dates and geographic areas suggested a seasonality of restless legs symptomatology with a peak in summer months. Our novel finding in RLS epidemiology needs to be confirmed in additional samples, and underlying mechanisms must be elucidated.     

提高对不宁腿综合征规范诊断与治疗的认识

<正>不宁腿综合征(RLS)亦称Willis-Ekbom病(WED),是临床常见的神经系统运动感觉性疾病。流行病学调查显示,不同国家和地区成人不宁腿综合征患病率不同,欧美国家患病率明显高于亚洲国家,其中欧美国家成人患病率为5.0%～14.3%~([1-2])、亚洲国家为0.1%～1.9%~([3-4])。不宁腿综合征可发生于任何年龄阶段,且随着年龄的增长、患病率逐年增加,女性患病率高于男性。由于不宁腿综合征的诊断主要依靠临床症状,缺乏特异性,加之短期内不会造成明显损害,因此目前对该病的诊断率较低,治疗方法不甚规范。     

普拉克索治疗原发性不安腿综合征疗效观察

目的观察普拉克索治疗原发性不安腿综合征（RLS）的临床疗效及安全性。方法将66例原发性RLS患者随机分为普拉克索组与美多巴组,应用国际不安腿综合征评估量表（IRLS）和汉密尔顿抑郁量表（HAMD）分别于治疗前及治疗后6周进行病情评估,观察比较2组治疗前后各量表评分情况,并记录2组患者出现的药物不良反应。结果2组患者治疗后IRLS与HAMD评分较治疗前均明显下降（P〈0．05）,相比美多巴组,普拉克索组治疗后IRLS评分差异无统计学意义（P〉0．05）,但HAMD评分下降更为明显（P〈0．01）,2组药物不良反应发生率差异无统计学意义（P〉0．05）。结论普拉克索能有效缓解原发性RLS症状,且药物不良反应较小,相比美多巴其抗抑郁的优势更为明显。     

Relation of the International Restless Legs Syndrome Study Group rating scale with the Clinical Global Impression severity scale,the restless legs syndrome 6-item questionnaire,and the restless legs syndrome-quality of life questionnaire

BackgroundThe SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS. To provide clinical context for the IRLS and to guide the choice of assessment scales for RLS studies, our post hoc analysis of SP790 data evaluated associations between the IRLS and the CGI-1, IRLS and RLS-6, and the IRLS and RLS-QoL.MethodsScale associations were analyzed at baseline and at the end of maintenance (EoM) using data from the safety set (rotigotine and placebo groups combined [n = 458]). Changes from baseline to EoM in IRLS score vs comparator scale scores also were analyzed.ResultsThere was a trend towards increasing IRLS severity category with increasing CGI-1, RLS-6, and RLS-QoL score. Pearson product moment correlation coefficients showed correlations between IRLS and comparator scale scores at baseline and EoM as well as correlations for change from baseline to EoM.ConclusionCorrelations between the IRLS and comparator scales were substantial. These data indicate that the IRLS is clinically meaningful. The IRLS and CGI-1 are generally sufficient to evaluate the overall severity and impact of RLS symptoms in clinical trials.     

Acute post-stroke restless legs syndrome: the body of caudate nucleus considerations

ObjectivesTo investigate the relationship between the lesion location and post-stroke restless legs syndrome (RLS).MethodsA total of 376 patients with acute cerebral infarction were recruited from Tangshan Gongren Hospital, Department of Neurology between May 2016 and May 2017, all of whom were evaluated for RLS. Established RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in 2012. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS). The lesion location was evaluated with magnetic resonance imaging (MRI). The associations between the lesion location and post-stroke RLS were then analyzed by logistic regression.ResultsA total of 49 patients (13.03%) had RLS. The multivariate logistic regression model adjusting for post-stroke RLS risk factors including gender, age, history of hypertension, history of diabetes, history of stroke, smoking, drinking, body mass index (BMI), NIHSS, hemoglobin, platelet and homocysteine determined that body of caudate nucleus and pontine were significantly associated with post-stroke RLS with odds ratio (OR) of 26.26 (95% confidence interval (CI): 9.41–73.28,p < 0.001) and OR of 4.37 (95% CI: 1.24–15.34, p = 0.021). The stepwise logistic regression model with temporal lobe, parietal lobe, occipital lobe, frontal lobe, callosum, body of caudate nucleus, thalamus, lenticulo capsule, corona radiata, centrum semi-ovale and pontine as potential predictors yielded a predictor mode. The stepwise logistic regression predictor mode indicated that body of caudate nucleus and pontine predicted post-stroke RLS with similar OR to multivariate models of 23.61 (95% CI: 9.53–58.51, p < 0.001) and 4.46 (95% CI: 1.38–14.4, p = 0.012).ConclusionsThe ischemic infarcts located in body of caudate nucleus, pontine are significantly associated with post-stroke RLS. Body of caudate nucleus acute infarcts may play a role in the development of post-stroke RLS.     

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.     

Brain imaging and networks in restless legs syndrome

Several studies provide information useful to our understanding of restless legs syndrome (RLS), using various imaging techniques to investigate different aspects putatively involved in the pathophysiology of RLS, although there are discrepancies between these findings.The majority of magnetic resonance imaging (MRI) studies using iron-sensitive sequences supports the presence of a diffuse, but regionally variable low brain-iron content, mainly at the level of the substantia nigra, but there is increasing evidence of reduced iron levels in the thalamus. Positron emission tomography (PET) and single positron emission computed tomography (SPECT) findings mainly support dysfunction of dopaminergic pathways involving not only the nigrostriatal but also mesolimbic pathways. None or variable brain structural or microstructural abnormalities have been reported in RLS patients; reports are slightly more consistent concerning levels of white matter. Most of the reported changes were in regions belonging to sensorimotor and limbic/nociceptive networks. Functional MRI studies have demonstrated activation or connectivity changes in the same networks. The thalamus, which includes different sensorimotor and limbic/nociceptive networks, appears to have lower iron content, metabolic abnormalities, dopaminergic dysfunction, and changes in activation and functional connectivity. Summarizing these findings, the primary change could be the reduction of brain iron content, which leads to dysfunction of mesolimbic and nigrostriatal dopaminergic pathways, and in turn to a dysregulation of limbic and sensorimotor networks. Future studies in RLS should evaluate the actual causal relationship among these findings, better investigate the role of neurotransmitters other than dopamine, focus on brain networks by connectivity analysis, and test the reversibility of the different imaging findings following therapy.     

Clinical characteristics of Korean pediatric patients with restless legs syndrome

ObjectivesRestless legs syndrome (RLS) is a common neurological disorder but it is not sufficiently recognized in children and adolescents. It often overlaps with growing pains in children, and as a result the clinical characteristics of pediatric RLS are not well studied, especially in Asia. The purpose of this study is to investigate the clinical characteristics of pediatric RLS patients in Korea and compare it to those of adult RLS patients.MethodsWe retrospectively reviewed the medical records of all pediatric RLS patients (≤18 years) from January 2015 to December 2018 in a regional tertiary hospital sleep center. We randomly selected adult primary RLS patients without comorbid medical disorders from our sleep center's dataset as controls. The number of controls was determined to be twice the number of pediatric RLS patients according to sample size calculation. The clinical and polysomnographic (PSG) characteristics of both groups were compared. The independent t-test, chi-squared test, and Fisher's exact test were used for analyzing quantitative data between the two groups and p < 0.05 was considered statistically significant.ResultsTwenty-nine primary pediatric RLS patients and 57 adult RLS patients were enrolled. Pediatric RLS patients showed equal prevalence between sexes, as opposed to adults where there is female predominance. Ferritin level was significantly lower in pediatric patients, although it remained within the normal range. Also, pediatric RLS patients showed less severe RLS symptoms and had better sleep quality than adults did in both objective and subjective measures. In addition, PLMS was shown to be less common in pediatric RLS patients compared to adults.ConclusionsPediatric RLS patients showed relatively mild to moderate RLS symptoms and a smaller likelihood of experiencing PLMS than adult patients, which is comparable to similar western studies. Long-term evaluation of a patient's clinical course through multicenter clinical studies is strongly suggested for the future.     

Polysomnographic findings in restless legs syndrome (RLS) patients with severe augmentation

Background and objectivesAugmentation can occur frequently in restless legs syndrome (RLS) patients treated with dopaminergic agents. Video-polysomnographic (PSG) data from augmented RLS patients are scant. The aim of this study was to evaluate PSG findings in augmented RLS patients and compare them with those of non-augmented RLS patients.Patients and methodsValid PSG data were analyzed from 99 augmented and 84 non-augmented RLS inpatients who underwent one night PSG.ResultsBoth patient groups showed a high subjective burden of RLS symptoms. The mean scores on the International RLS Study Group Rating Scale (IRLS) were significantly higher in the group with augmentation than in the group without. The periodic leg movement index (PLMI) was increased in both groups, mostly on account of the PLM in wakefulness (PLMW). Both groups presented a reduced sleep efficiency and an increased sleep latency. The levodopa equivalent dose (LED) was significantly higher in the augmented group.ConclusionsOur study confirms that RLS patients with augmentation have disturbed sleep due to high amount of leg movements and fragmented sleep. Overall, however, polysomnographic characteristics were not different between insufficiently treated RLS and severely augmented RLS patients, implying that augmentation could represent a severe form of RLS and not a different phenomenon.