Prevalence of restless legs syndrome and periodic limb movement disorder in the general population

BACKGROUND: Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are two sleep disorders characterized by abnormal leg movements and are responsible for deterioration in sleep quality. However, the prevalence of these disorders is not well known in the general population. This study aims to document the prevalence of RLS and PLMD in the general population and to identify factors associated with these conditions. METHODS: Cross-sectional studies were performed in the UK, Germany, Italy, Portugal and Spain. Overall, 18,980 subjects aged 15 to 100 years old representative of the general population of these five European countries underwent telephone interviews with the Sleep-EVAL system. A section of the questionnaire assessed leg symptoms during sleep. The diagnoses of PLMD and RLS were based on the minimal criteria provided by the International Classification of Sleep Disorders. RESULTS: The prevalence of PLMD was 3.9% and RLS was 5.5%. RLS and PLMD were higher in women than in men. The prevalence of RLS significantly increased with age. In multivariate models, being a woman, the presence of musculoskeletal disease, heart disease, obstructive sleep apnea syndrome, cataplexy, doing physical activities close to bedtime and the presence of a mental disorder were significantly associated with both disorders. Factors specific to PLMD were: being a shift or night worker, snoring, daily coffee intake, use of hypnotics and stress. Factors solely associated with RLS were: advanced age, obesity, hypertension, loud snoring, drinking at least three alcoholic beverages per day, smoking more than 20 cigarettes per day and use of SSRI. CONCLUSIONS: PLMD and RLS are prevalent in the general population. Both conditions are associated with several physical and mental disorders and may negatively impact sleep. Greater recognition of these sleep disorders is needed.     

French Consensus: How to diagnose restless legs syndrome

Correct diagnosis of restless legs syndrome (RLS) is essential to patient care and treatment. Diagnosis is most often clinical and based on diagnostic criteria: the need to move the legs accompanied to varying degrees by unpleasant sensations, predominantly during the evening and improved by movement. In rare cases, clinical examination is insufficient and a polysomnography is necessary. Once a positive diagnosis has been made, a neurological examination and an assessment of iron status are required. The severity of the RLS must be evaluated to determine whether a specific treatment is necessary. Before treatment, it is essential to ensure that a definite diagnosis of RLS has been made and the phenotype characterised. This enables a personal treatment plan and limits the risk of augmentation syndrome.     

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment of pediatric restless legs syndrome and periodic limb movement disorder

BackgroundIron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD.MethodsThis was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed.ResultsThirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between “very much improved” and “much improved”. Ferritin increased from 14.6 μg/L ± 7.01 to 112.4 μg/L ± 65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild.ConclusionsChildren with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.     

Treatment of childhood-onset restless legs syndrome and periodic limb movement disorder using intravenous iron sucrose

Objective

An alternative treatment approach is needed for children who cannot tolerate oral iron preparations or when there is a need for rapid replenishment of iron stores. We report on the safety, adverse effects, and efficacy of intravenous iron sucrose in a retrospective sample of children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD).

Methods

Sixteen children with RLS/PLMD who received intravenous iron sucrose at our institution between 2005 and 2011 were identified. The diagnosis of RLS/PLMD was established after formal sleep consultation and nocturnal polysomnography (PSG). Serum ferritin was assayed in all 16 subjects prior to iron sucrose infusion and in 14 subjects after infusion. The medical records were reviewed for treatment-related details.

Results

The mean age of subjects was 6.6 years (range, 2–16 y; 5/16 girls). The mean periodic limb movement index (PLMI) was 18.2 ± 12.8. Fifteen of the 16 subjects (93.7%) had systemic or neurologic comorbidities. Fourteen of 16 (87.5%) subjects had received prior oral iron supplementation for sleep-related concerns, with the majority of the subjects either having gastrointestinal (GI) side effects or insufficient benefits. Intravenous iron sucrose therefore was provided to these 16 subjects through our outpatient pediatric infusion therapy center. The average dose of intravenous iron sucrose of 3.6 mg/kg was infused over 2 h. The baseline mean serum ferritin was 16.4 ± 6.6 ng/mL. After infusion with intravenous iron sucrose, the mean serum ferritin rose to 45.7 ± 22.4 ng/mL (n = 14; [95% confidence interval, 17.2–41.3]; P < .0001). Parental assessment of response to iron sucrose therapy was conducted on follow-up clinic visits or via telephone calls. There was improved sleep in 62.5% (n = 10) of subjects and no improvement in 12.5% (n = 2) of subjects. No follow-up information was available for 25% (n = 4) of subjects. Minor adverse events occurred in 25% (n = 4) of subjects—two subjects experienced difficulty with peripheral intravenous catheter placement, while two had transient GI symptoms, such as anorexia, nausea, and vomiting. None of the subjects had anaphylaxis.

Conclusions

Intravenous iron sucrose appears to be a relatively effective therapy for patients with childhood-onset RLS/PLMD and iron deficiency who do not tolerate or respond to oral iron supplements. Side effects were transient. The most common adverse events were difficulty with intravenous line placement and GI disturbance. There is a need for systematic prospective studies on the safety and efficacy of intravenous iron sucrose in RLS/PLMD in children.     

Pediatric restless legs syndrome and periodic limb movement disorder: Parent–child pairs

ObjectiveAlthough recent publications have reported the occurrence of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children and adolescents, the literature is relatively limited. The goals of this retrospective study were to (1) apply the recent International Classification of Sleep Disorders 2nd edition (ICSD-2) diagnostic criteria for RLS and PLMD in pediatric cases where periodic limb movements in sleep (PLMS) ?5 per hour were found; (2) review parental history of RLS; and (3) further define the clinical characteristics of RLS and PLMD in a pediatric subgroup where each child had a parent with clinically assessed RLS.MethodsThis was a retrospective analysis of consecutive polysomnograms (PSGs) with PLMS >5 per hour in patients ?19 years of age from a single pediatric sleep/neurology practice over 11 years. Excluded were cases with sleep apnea, narcolepsy, or medication that might induce or aggravate PLMS or RLS. ICSD-2 diagnostic criteria for definite RLS and PLMD were applied to the pediatric cases, and parental history for RLS was assessed. A subset of cases was included for detailed review if the child or adolescent had RLS or PLMD and a biological parent met RLS criteria and had a formal sleep evaluation.ResultsThere were 204 cases that met the initial inclusion criteria. A positive parental history of RLS was found in 53% of pediatric RLS cases and in 52% of pediatric PLMD cases. A subset of 37 children or adolescents and 36 biological parents, from 33 different families, met full inclusion criteria and are presented in detail. Of these 37, 10 had a diagnosis of RLS and 27 a diagnosis of PLMD. Over this same period of time, PLMS >5 per hour were found in 74% of pediatric definite RLS cases assessed by PSG.ConclusionsThis case series adds to the growing literature describing RLS and PLMD in children and adolescents using recently revised diagnostic criteria. The similar prevalence of parental RLS in both pediatric RLS and pediatric PLMD cases suggests a close association between PLMD and RLS in some cases. This supports the emerging view that PLMS may be a marker or endophenotype for a specific, common RLS genotype.     

The validity of the PAM-RL device for evaluating periodic limb movements in sleep and an investigation on night-to-night variability of periodic limb movements during sleep in patients with restless legs syndrome or periodic limb movement disorder using this system

BackgroundThe status of night-to-night variability for periodic limb movements in sleep (PLMS) has not been clarified. With this in mind, we investigated the validity of PLMS measurement by actigraphy with the PAM-RL device in Japanese patients with suspected restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) and the night-to-night variability of PLMS among the subjects.MethodsForty-one subjects (mean age, 52.1 ± 16.1 years) underwent polysomnography (PSG) and PAM-RL measurement simultaneously. Thereafter, subjects used the PAM-RL at home on four more consecutive nights.ResultsThe correlation between PLMS index on PSG (PLMSI-PSG) and PLM index on PAM-RL (PLMI-PAM) was 0.781 (P < .001). When the PLMSI cutoff value on PSG was set at 15 episodes per hour, the cutoff value for predicting this PLMSI level was 16.0 episodes per hour. When the condition was set to the level in which the mean interclass correlation coefficient reached ⩾0.9, the number of required nights for repeated measurements was 26 nights for subjects with PLMI of <15 episodes per hour and three nights for those with PLMI ⩾15 episodes per hour on PAM-RL.ConclusionsPAM-RL is thought to be valuable for assessing PLMS even in Japanese subjects. Recording of PAM-RL for three or more consecutive nights may be required to ensure the screening reliability of a patient with suspected pathologically frequent PLMS.     

EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep

In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short-term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.     

Restless legs syndrome and periodic limb movement disorder in the elderly

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the extremities, mostly the legs, caused or accompanied by unpleasant sensations in the affected limbs. Symptoms appear or increase in the evening or during the night and at rest. Sleep disturbances are the most frequent reason why patients seek medical aid. The diagnosis of periodic limb movement disorder (PLMD) requires polysomnographic confirmation and relies on the exclusion of other causes of sleep disturbances. The diagnosis of RLS is a clinical one and usually based on the patient's history. Diagnosis criteria should be applied in a modified form in the cognitively impaired elderly. The newly revised criteria emphasize behavioral indicators and supportive features in diagnosing RLS in this special population. Prevalence of both disorders increases strongly with age. Epidemiological studies revealed a 9% to 20% prevalence of RLS and an estimated 4% to 11% prevalence of PLMD in the elderly. Recent studies indicate RLS occurring approximately twice as often in older women than in older men. Treatment with dopaminergic drugs, opioids, anticonvulsants or hypnotics are usually well tolerated in the elderly. However, interaction with other medications and the possibility of severe sedation due to slower metabolism in the elderly should be considered.     

Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study Group

BackgroundSpecific diagnostic criteria for pediatric restless legs syndrome (RLS) were published in 2003 following a workshop at the National Institutes of Health. Due to substantial new research and revision of the adult RLS diagnostic criteria, a task force was chosen by the International Restless Legs Syndrome Study Group (IRLSSG) to consider updates to the pediatric diagnostic criteria.MethodsA committee of seven pediatric RLS experts developed a set of 15 consensus questions to review, conducted a comprehensive literature search, and extensively discussed potential revisions. The committee recommendations were approved by the IRLSSG executive committee and reviewed by the IRLSSG membership.ResultsThe pediatric RLS diagnostic criteria were simplified and integrated with the newly revised adult RLS criteria. Specific recommendations were developed for pediatric application of the criteria, including consideration of typical words used by children to describe their symptoms. Pediatric aspects of differential diagnosis, comorbidity, and clinical significance were then defined. In addition, the research criteria for probable and possible pediatric RLS were updated and criteria for a related condition, periodic limb movement disorder (PLMD), were clarified.ConclusionsRevised diagnostic criteria for pediatric RLS have been developed, which are intended to improve clinical practice and promote further research.     

Higher nocturnal systolic blood pressure in patients with restless legs syndrome compared with patients with insomnia

BackgroundThere is evidence linking restless legs syndrome (RLS) with increased blood pressure (BP), but the mechanism of this relation remains unclear. Is the BP increased due to some features of RLS or to deterioration of sleep caused by RLS? This study compared values of nocturnal BP in patients with RLS and patients with insomnia. If increased BP in RLS is a consequence of disordered sleep, then it should be similar to increased BP in insomnia.MethodsPolysomnographic recordings of patients admitted to a sleep center with RLS or insomnia were analyzed. Demographic and clinical data, objective sleep parameters, and nocturnal BP were compared.ResultsRecordings of 35 patients with RLS and 33 patients with insomnia were analyzed. The groups did not significantly differ in terms of demographic traits or prevalence of other comorbidities. Patients with RLS had significantly higher systolic BP during the night (122.4 ± 13.8 vs 116.3 ± 13.4; p = 0.03) and during sleep (121.4 ± 13.3 vs 115.7 ± 13.3; p = 0.04). The only significant difference in sleep architecture was an increased number of periodic limb movements in sleep (PLMS) and PLMS with arousal in the RLS group (25.5 ± 24.6 vs 13.9 ± 22.7; p = 0.02 and 4.7 ± 5.4 vs 2.1 ± 3.4; p = 0.01).ConclusionOur results suggest that patients with RLS have higher nocturnal BP than patients with insomnia, and that increased PLMS is related to the increase in BP.     

Autonomic complaints in patients with restless legs syndrome

BackgroundData regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS).MethodsWe compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 items in six domains scored from 0 to 3. The total score and domain scores were transformed to 0–100 points. Subjects with neurodegenerative disorders (i.e., dementia, Parkinsonism) were excluded.ResultsThe RLS group was younger (mean ± standard deviation, 77.9 ± 8.0 vs 80.5 ± 7.9 years; P = .03) and included more women (84% vs 69%; P = .04). The mean SCOPA-AUT total score was higher in the RLS group compared with the control group (20 ± 11 vs 16 ± 9; P = .005). Additionally the RLS group had abnormalities in gastrointestinal, cardiovascular, and pupillomotor domains. When comparing the percentage of subjects with any complaint on individual questions (score of ⩾1), the RLS group had a greater number of subjects with sialorrhea, constipation, early abdominal fullness, lightheadedness when standing, and heat intolerance.ConclusionsAutonomic complaints, especially gastrointestinal, cardiovascular, and oversensitivity to light, were significantly increased in subjects with RLS. Causes for autonomic dysfunction in RLS require further investigation.     

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。     

Restless legs syndrome and central nervous system gamma-aminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity

Background

Previous research has demonstrated abnormalities in glutamate and N-acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome (RLS) compared with healthy matched controls. However, levels of these transmitters in other RLS-related brain areas and levels of the most common inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been assessed.

Methods

This study examined GABA, glutamate, and NAA levels in the dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of proton magnetic resonance spectroscopy (¹H-MRS) at 4 tesla (4 T) and Megapress difference-editing in 18 subjects with RLS and a matched control group without RLS. Actigraphy was performed on the nights before scans to assess periodic limb movements of sleep (PLMS).

Results

Levels of GABA, glutamate, and NAA were no different between RLS and control subjects in any of the three voxels of interest. However, GABA levels were positively correlated with both PLM indices and RLS severity in the thalamus and negatively with both of these measures in the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in RLS than in controls.

Conclusion

Our preliminary data suggest that known cerebellar–thalamic interactions may modulate the intensity of RLS sensory and motor symptoms. In addition, anterior cingulate cortex may be associated with the affective components of the painful symptoms in this disorder.     

Outcomes of long-term iron supplementation in pediatric restless legs syndrome/periodic limb movement disorder (RLS/PLMD)

ObjectivesRestless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are thought to center around a genetically mediated sensitivity to iron insufficiency. Previous studies have shown the effectiveness of short-term iron therapy in children with low iron storage. Little is known, however, about long-term iron treatment in children with RLS and PLMD. Therefore, we performed this study to assess the long-term effect of iron therapy in children with RLS and PLMD.MethodsA retrospective chart review was performed for children who met the following criteria: A) diagnosed as having either RLS or PLMD, B) started on iron supplementation, C) followed up for >2 years in a sleep clinic. Baseline values for iron, ferritin, and periodic limb movement of sleep index (PLMS index) were defined in the three months leading up to the initiation of iron therapy. Values were also computed for follow-up periods of 3–6 months, 1–2 years, and >2 years. Serum iron and ferritin levels and PLMS index were compared between baseline and all subsequent follow-ups.ResultsIn total, 105 patients met inclusion criteria, of whom 64 were diagnosed with PLMD alone, seven with RLS alone, and 35 with both RLS and PLMD. The average age was 10.2 ± 5.3 years. Compared to the baseline (27.4 ± 12.1 ng/ml), the average ferritin values at 3–6 months (45.62 ± 21.2 ng/ml, p < 0.001, n = 34), 1–2 years (52.0 ± 48.3 ng/ml, p <0.001, n = 63), and >2 years (54.7 ± 40.5 ng/ml, p <0.001, n = 67) were all significantly increased. Inversely, compared to baseline (21 ± 27.0/h, n = 66), PLMS index values at 3–6 months (7.5 ± 9.5/h p < 0.05, n = 11), 1–2 years (6.9 ± 8.9/h, p <0.001, n = 29), and >2 years (10 ± 14.5/h, p <0.001, n = 31) were all significantly decreased. No significant change in serum iron levels was noted at any time point.ConclusionWhile retrospective in nature, this study demonstrates a sustained improvement in PLMS index and maintenance of adequate ferritin levels >2 years after iron therapy initiation in our RLS/PLMD cohort with a long-term follow-up. Iron therapy appears to lead to long-lasting improvements in children with RLS/PLMD.     

Pelvic movements as rhythmic motor manifestation associated with restless legs syndrome.

Video-polysomnographic monitoring of a patient with a 4-year history of an unpleasant restless sensation originating in his lower abdomen showed stereotyped, repetitive, rhythmic pelvic body movements resembling coital behaviour at the wake-sleep transition. We discuss the association between restless legs syndrome and rhythmic movement disorder as a particular manifestation of a spectrum of rhythmic sleep-related movement disorders.     

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.     

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.     

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.