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Background: Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children., Methods: A literature search was performed to identify papers appearing in MEDLINE from its inception to July 2016. The following inclusion criteria were used: human research on the treatment of RLS or periodic limb movements (PLM) with iron, sample size of at least five, and published in English. Two task force members independently evaluated each paper and classified the quality of evidence provided., Results: A total of 299 papers were identified, of these 31 papers met the inclusion criteria. Four studies in adults were given a Class I rating (one for IV iron sucrose, and three for IV ferric carboxymaltose); only Class IV studies have evaluated iron treatment in children. Ferric carboxymaltose (1000 mg) is effective for treating moderate to severe RLS in those with serum ferritin <300 μg/l and could be used as first-line treatment for RLS in adults. Oral iron (65 mg elemental iron) is possibly effective for treating RLS in those with serum ferritin ≤75 μg/l. There is insufficient evidence to make conclusions on the efficacy of oral iron or IV iron in children., Conclusions: Consensus recommendations based on clinical practice are presented, including when to use oral iron or IV iron, and recommendations on repeated iron treatments. New iron treatment algorithms, based on evidence and consensus opinion have been developed., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: At high altitude, prevalence of restless legs syndrome has been found to be greater than expected in small population-based studies, which did not use validated tools for identification of RLS. However, it is not known as to whether this increased prevalence is associated with altitude or increased risk factors for RLS in these populations or errors in identification of RLS., Method: This population based, door-to-door study was conducted at low altitude (400 m above sea level) and high altitudes (1900-2000 m and 3200 m above sea level) using random stratified sampling in Himalayan and sub-Himalayan region of India. Subjects between 18 and 84 years were screened for restless-legs-syndrome using the validated Cambridge-Hopkins RLS diagnostic questionnaire. Medical comorbidities were ascertained from their medical records. Their anthropometric measurements were obtained and wake resting oxygen saturation was monitored using finger pulse-oximeter. Physical activity during leisure time was evaluated by using the Goldin leisure time exercise questionnaire., Results: A total of 1689 subjects were included. Average age of the included subjects was 35.2 years; 55.2% were women. RLS was identified in 9.4% subjects with higher prevalence among women (13.6% women vs. 4.1% men; P < 0.001). RLS was significantly more prevalent at higher altitudes (12.2% at 1900-2000 m and 11.8% at 3200 m) compared to low altitude (2.5% at 400 m). The low altitude prevalence matched that reported in prior studies of RLS in India. Subjects with medical disorders sometimes related to RLS (eg, peripheral neuropathy, COPD, varicose veins and anemia) also had higher prevalence of RLS. Binary logistic regression controlling for female gender, number of pregnancies, peripheral neuropathy, varicose veins, anemia showed that high altitude independently significantly increased the likelihood of RLS (OR: 5.4, 95% CI: 2.8, 10.4)., Conclusion: RLS is about five times more prevalent at high than low altitudes even when controlling for effects of other medical conditions associated with increased risk of RLS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Patients with restless legs syndrome (RLS) have an elevated prevalence of mood disorders compared with the general population. We investigated the change of RLS-related mood impairment during treatment of RLS with pramipexole, a dopamine D(3)/D(2) agonist., Methods: Adults with moderate to very severe RLS were enrolled in a 12-week, double-blind, placebo-controlled Phase IV pramipexole trial. A moderate to very severe RLS-related mood disturbance at baseline (score ≥2 on Item 10 of the International RLS Study Group Rating Scale [IRLS]) was also required. Pramipexole (0.125 to 0.75 mg once daily) was flexibly titrated over the first 4 weeks., Results: The intent-to-treat population comprised 199 patients on placebo and 203 on pramipexole. At week 12, adjusted mean total-score changes on IRLS were -14.2±0.7 for pramipexole and -8.1±0.7 for placebo (p<0.0001), and on the Beck Depression Inventory version II, -7.3±0.4 for pramipexole and -5.8±0.5 for placebo (p=0.0199). For IRLS item 10, the 12-week responder rate (reduction to no or mild mood disturbance) was 75.9% for pramipexole and 57.3% for placebo (p<0.0001). Study withdrawal rates were higher for placebo (20.5%) than for pramipexole (12.8%)., Conclusions: In patients with RLS-related mood disturbance, pramipexole improved RLS while also improving RLS-related mood impairment. Tolerability of pramipexole was similar to that in previous studies., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Restless legs syndrome (RLS) is a neurological movement disorder, which often causes sleep problems. However, the comorbidity of this disorder is not well known. This study aimed to document the prevalence of RLS in the general population of Sweden and to identify factors associated with this condition., Methods: A cross-sectional study was performed in Sweden. One thousand subjects aged 18-90 years old underwent telephone interviews. The questionnaire assessed such factors as sleep variables, depressive mood, treatment of diabetes mellitus, and treatment with drugs for depression during the previous four-week period. RLS was diagnosed based on the minimal criteria provided by the International RLS Study Group., Results: The prevalence of RLS was 5% (5.7% in women, 3.5% in men). Severe or very severe RLS symptoms during the previous week were noted by 64% of the RLS subjects. Factors associated with RLS were insomnia, excessive daytime sleepiness, periodic limb movements in sleep, and depressed mood. Those affected by RLS were not more often consumers of drugs for depression than non-RLS subjects., Conclusions: RLS is prevalent in the general population in Sweden. RLS negatively influenced sleep and was associated with depressed mood. Antidepressive drug treatment was not associated with RLS.

Background and Purpose: To estimate prevalence and severity (using the International Restless Legs Syndrome Study Group Rating Scale (IRLS)) and to identify risk factors of restless legs syndrome (RLS)., Patients and Methods: Population-based cross-sectional study; 2005 randomly selected adults 18 years and above participated in a telephone interview in Norway and Denmark, employing the next-birthday technique., Results: Of the cross-section, 11.5% fulfilled the diagnostic criteria for RLS. Half of these reported the symptoms as moderate to very severe. Mean duration of the complaint was 10 years. Prevalence was higher in females than in males (13.4 vs 9.4%) and lowest in the youngest age group (18-29 years, 6.3%). From 30 years and above, no clear age-related difference was seen. Main predictors of RLS were insomnia (odds ratios: 1.71-3.16) and symptoms of periodic limb movements in sleep (3.20-7.85). The response rate was 47%, making the results less reliable., Conclusions: This study indicates that there is a high occurrence of RLS among adults. Main predictors are insomnia and periodic limb movements in sleep.

Background and Purpose: Restless legs syndrome (RLS) may be a cause of significant sleep disturbance. In a Swedish survey, the prevalence of RLS has been estimated to be 5.8% among men and 11.4% among women. Blood donation may result in iron deficiency, which is hypothesized to be one substantial cause of RLS., Patients and Methods: Nine hundred and forty-six (618 men, 328 women) consecutive blood donors aged 18-64 years, who attended a blood donation unit in mid-Sweden, answered a questionnaire that included questions about sleep habits. Frequency of blood donation was recorded and intake of iron tablets was assessed. Red blood cell distribution width (RDW) was also recorded. The value of RDW increases in relation to iron deficiency., Results: RLS affected 14.7% of male and 24.7% of female blood donors. The mean intake of iron among the blood donors after each blood donation was only 781 mg, although the recommended intake is 2000 mg. Among the women, 7.4% presented an RDW of >14.5%, which strongly indicates iron deficiency. In this group of women, 37.5% were affected by RLS. The female RLS-sufferers were more affected than the female non-RLS subjects by problems initiating sleep (P=0.006 maintaining sleep (P<0.0001) and were also less refreshed upon awakening (P<0.001)., Results: This study showed that RLS was common among female blood donors. Women with RLS were more iron-deficient than those without and were affected by impaired sleep.