Association of low serum ferritin levels with augmentation in patients with restless legs syndrome: A systematic review and meta-analysis.

BACKGROUND: Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation. METHODS: We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed. RESULTS: Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227). CONCLUSIONS: A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.

The effect of nonpharmacologic interventions for muscle cramps and restless-leg syndrome in hemodialysis patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: We performed a meta-analysis to evaluate the effect of the nonpharmacologic interventions on muscle related symptoms including cramping and restless leg syndrome in hemodialysis patients. METHODS: Articles published between 2002 and 2022 were searched in six databases. The standardized mean differences were determined by the upper and lower limits of 95% confidence intervals. Publication bias was assessed by conducting the Egger test and examined visually using a funnel plot. RESULTS: Fourteen studies were included in this meta-analysis. The types of interventions included exercise (n = 5), aromatherapy (n = 5), reflexology (n = 3), massage (n = 1), and acupressure (n = 1). The methodological quality assessment revealed 13 studies were strong quality, while only one study was moderate quality. The Egger test indicated no significant publication biases. CONCLUSION: Healthcare professionals can use non-pharmacological methods to manage muscle-related symptoms because of not only beneficial effects but also it is practical, well-tolerated, easy integrated into the treatment and care.

Phenotypical predictors of pregnancy-related restless legs syndrome and their association with basal ganglia and the limbic circuits.

Restless legs syndrome (RLS) in pregnancy is a common disorder with a multifactorial etiology. A neurological and obstetrical cohort of 308 postpartum women was screened for RLS within 1 to 6 days of childbirth and 12 weeks postpartum. Of the 308 young mothers, 57 (prevalence rate 19%) were identified as having been affected by RLS symptoms in the recently completed pregnancy. Structural and functional MRI was obtained from 25 of these 57 participants. A multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors of RLS. A decreased volume of the parietal, orbitofrontal and frontal areas shortly after delivery was found to be linked to persistent RLS symptoms up to 12 weeks postpartum, the symptoms' severity and intensity in the most recent pregnancy, and a history of RLS in previous pregnancies. The same negative relationship was observed between brain volume and not being married, not receiving any iron supplement and higher numbers of stressful life events. High cortisol levels, being married and receiving iron supplements, on the other hand, were found to be associated with increased volumes in the bilateral striatum. Investigating RLS symptoms in pregnancy within a brain-phenotype framework may help shed light on the heterogeneity of the condition.

The Effect of Parenteral or Oral Iron Supplementation on Fatigue, Sleep, Quality of Life and Restless Legs Syndrome in Iron-Deficient Blood Donors: A Secondary Analysis of the IronWoMan RCT.

Background: Besides anemia, iron deficiency may cause more subtle symptoms, including the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis of the IronWoMan randomized controlled trial (RCT) was to compare the frequency and severity of symptoms associated with iron deficiency before and after (intravenous or oral) iron supplementation in iron deficient blood donors. METHODS/DESIGN: Prospective, randomized, controlled, single-centre trial. (ClinicalTrials.gov: NCT01787526). SETTING: Tertiary care center in Graz, Austria. PARTICIPANTS: 176 (138 female and 38 male) whole-blood and platelet apheresis donors aged ≥ 18 and ≤ 65 years with iron deficiency (ferritin ≤ 30ng/mL at the time of blood donation). INTERVENTIONS: Intravenous iron (1 g ferric carboxymaltose, n = 86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n = 90). MEASUREMENTS: Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1), including questions about symptoms of restless legs syndrome (RLS), chronic fatigue syndrome (CFS), sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes in fingernails or hair. RESULTS: We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p < 0.001). Furthermore, a significant decrease in headaches, dyspnoea, dizziness and palpitations was reported (p < 0.05). There was no difference between the type of iron supplementation (intravenous versus oral) and clinical outcome data. CONCLUSION: Iron supplementation in iron-deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.

[Restless legs syndrome]. / Le syndrome des jambes sans repos.

Restless legs syndrome, also called Willis-Ekbom disease, is a frequent sensorimotor disease, more often encountered in women than men. It is characterized by an urge to move legs, during the evening or the beginning of the night, increased by rest and relieved by movement. Two forms are classically distinguished: primary restless legs syndrome occurring in young adults with family history and secondary forms occurring in older adults with comorbidities such as iron deficiency, chronic renal failure or neurological diseases (affecting central or peripheral nervous system). The clinical impact of the urge to move the legs may be major, including in particular sleep disorders which can profoundly alter the quality of life. Pathophysiology of restless legs syndrome still remains partially understood and probably relies on dopamine metabolism abnormality secondary to cerebral iron deficiency in genetically susceptible patients. That's why, besides nutritional and sleep hygiene advices, treatment of restless legs syndrome includes iron supplementation if there is an iron deficiency. Pharmacological treatment, for severe to very severe forms, includes use of dopamine agonists, antiepileptic drugs or opioids. These medications have numerous side effects and each prescription has to be individually customized for each patient.

Effects of glycerin oil and lavender oil massages on hemodialysis patients' restless legs syndrome.

OBJECTIVES: To determine the effects of glycerin oil and lavender oil massages on hemodialysis patients' restless legs syndrome (RLS). METHODS: Ninety hemodialysis patients with RLS were randomly allocated into two intervention groups and one control group, each consisting of 35 participants. The control group received routine care, and the intervention groups received effleurage massage with lavender and glycerin oil in addition to routine care for one month. RLS intensity was measured among the three groups using the Restless Legs Syndrome Rating Scale. RESULTS: At the beginning of the study, the results showed no significant difference among the three groups' scores. At the end of the study, the mean RLS scores were significantly lower in the intervention groups compared to the control group (F = 63.4, p ≤ 0.001). This difference was not significant between the two intervention groups; nonetheless, the differences between the control and lavender oil groups, as well as the control and glycerin oil groups, were significant (p < 0.05). CONCLUSION: The findings showed the effectiveness of the oils through the effleurage massage for reducing RLS in a sample of hemodialysis patients.

Does Improvement of Low Serum Ferritin Improve Symptoms of Restless Legs Syndrome in a Cohort of Pediatric Patients?

STUDY OBJECTIVES: To determine whether an oral iron supplement improves restless leg/restless sleep symptoms in a pediatric population. METHODS: In a cohort study, 47 patients (age 5-18 years) exhibiting restless legs/restless sleep symptoms and low serum ferritin levels (< 50 ng/mL) were given a daily oral iron supplement (ferrous sulfate + vitamin C) and re-evaluated 8 weeks later. A diagnosis of definite Restless Legs Syndrome (RLS) was determined based on criteria established by the International RLS Study Group. Using Wilcoxon signed-rank tests and Spearman rho, the change and association between the measures of Pediatric Restless Legs Syndrome Severity Scale and serum ferritin levels were also examined. RESULTS: Overall, the median change and distribution of ferritin was statistically significantly different after 8 weeks of treatment (40.0 versus 23.0 ng/mL, P < .0001). Median RLS score was also statistically significantly lower from baseline to follow-up (4.0 versus 6.0, P = .0283). Sixteen patients met criteria for definite RLS; however, the change in RLS score was not determined to be significant in our population (9.5 versus 7.0, P = .0558), despite significant change in ferritin (25.0 versus 42.5 ng/mL, P < .0001). In addition, no correlation was observed between change in RLS score and ferritin level (rho = -.39, P = .1362). CONCLUSIONS: In preliminary findings, we found a modest, yet nonsignificant improvement in children exhibiting restless sleep and RLS symptomatology, despite significant improvement in ferritin levels. Though not statistically significant, the findings can lend to the suggested benefit of iron supplementation in patients with RLS; however, clinical judgment and further research is necessary. CITATION: Rosen GM, Morrissette S, Larson A, Stading P, Barnes TL. Does improvement of low serum ferritin improve symptoms of restless legs syndrome in a cohort of pediatric patients? J Clin Sleep Med. 2019;15(8):1149-1154.

Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in haemodialysis-associated restless legs syndrome. / Efectos de la rotigotina sobre la sintomatología, calidad de vida e higiene de sueño en el síndrome de piernas inquietas en hemodiálisis.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterised by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on haemodialysis (HD) with RLS treated with rotigotine. OBJECTIVES: 1.- To establish the prevalence of RLS in our HD unit. 2.- To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. MATERIAL AND METHODS: A single-centre, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analysed: 1.- Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. 2.- Lower extremity symptoms questionnaire (QS). 3.- RLS severity symptoms scale (SRLSS). 4.- RLS Quality of life: John Hopkins RLS-QoL (JH-QoL). 5.- Sleep hygiene: SCOPA Scale. RESULTS: We included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD. And 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (> 20%) and complete (> 80%) remission, respectively, while 55.5% achieved «zero¼ symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. CONCLUSIONS: RLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on haemodialysis.

[Iron deficiency, Fatigue and Restless-Legs-Syndrome]. / Eisenmangel, Müdigkeit und Restless-Legs-Syndrom.

Iron deficiency without anaemia is a widespread health problem that often remains undetected. In this context, neurological and psychopathological problems like fatigue and poor concentration are a major issue, but also in Restless-Legs-Syndrome (RLS) iron deficiency is a key element.The exact pathogenesis is often unknown, however, it is known that iron is involved in several very important metabolic processes in the human body. In particular when it comes to fatigue and RLS, it's assumed that reduced activity of tyrosine hydroxylase - a central iron-dependent element of dopamine synthesis - can lead to deficiencies.As part of the therapy, oral iron supplementation is considered to be treatment of choice since it's most cost-effective and well tolerated. Intravenous iron treatment is indicated if primary attempts were not sufficient or not tolerated. To successfully replenish iron storages, about 500-1000 mg are needed. Doses of 200 mg can be administered (iron sucrose) or 1-2 single doses as for ferric carboxymaltose. A check of ferritin-levels not earlier than 8 weeks after last administration is recommended.

Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.

Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 µ/dL) than in the control subjects (256.92 ± 88.54 µ/dL; <0.001). Patients with zinc level <99 µ/dL had significantly more frequent mental manifestations (p < 0.001), cardiopulmonary symptoms (p = 0.004), restless leg syndrome (p = 0.016), and epithelial manifestations (p < 0.001) than patients with zinc level > 100 µ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.

Restless legs syndrome in pregnancy is connected with iron deficiency.

OBJECTIVE: Almost one-third of pregnant women develop symptoms of restless legs syndrome (RLS), which could have a negative impact on quality of life and the course of pregnancy and/or labor. The aim of our study was to determine possible risk factors for developing RLS in pregnant women. METHODS: A total of 300 random women in the third trimester of gravidity filled out a simple questionnaire based on the official diagnostic criteria for RLS. Respondents positive for RLS were interviewed to further characterize their symptoms. The parameters of iron metabolism were examined based on blood samples. All data were statistically analyzed. RESULTS: We detected significantly lower hemoglobin levels with signs of hypochromic anemia typical of iron deficiency in RLS-positive respondents, although oral iron supplementation was significantly higher in this group. The overall severity of symptoms correlated inversely with hemoglobin level. CONCLUSION: According to our results, it appears that serum iron level disturbances play a crucial role in the pathophysiology of secondary RLS in pregnant women.

Current trends in the management of uremic restless legs syndrome: a systematic review on aspects related to quality of life, cardiovascular mortality and survival.

Restless legs syndrome (RLS) affects almost one out of three end-stage renal disease patients. This review assesses the current treatment options for uremic RLS and the potential benefits of those treatments on quality of life parameters, cardiovascular mortality and survival. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. Fourteen studies met the inclusion criteria in which the international RLS study group criteria were used as the primary diagnostic tool. Both pharmacological and non-pharmacological approaches were found to reduce the severity of uremic RLS symptoms. Only four studies reported changes on aspects related to quality of life while those changes were also associated with health benefits that resulted in reduced cardiovascular risk. The severity of uremic RLS symptoms can be ameliorated by using dopamine agonists and gabapentin, intravenous iron, exercise or supplementation with vitamins C and E, although some of those treatment benefits may be transient. There is a lack of strong evidence regarding the effects of the pharmacological approaches on quality of life and cardiovascular survival and mortality. In contrast exercise has been proven beneficial in both reducing the RLS symptoms' severity score and improving the quality of life.

The effect of vitamin D supplements on the severity of restless legs syndrome.

PURPOSE: Clinical observation hinted improved symptoms of restless legs syndrome (RLS) after vitamin D supplements. Hence, the aim of this study is to evaluate the effect of vitamin D supplementation on the severity of RLS symptoms. METHODS: Twelve adult subjects diagnosed with primary RLS and vitamin D deficiency were recruited. Patients with secondary RLS were excluded from this study. The complete cell count; serum levels of ferritin, iron, glycated hemoglobin, and vitamin D3 (25 (OH) vitamin D); and renal and bone profiles of the patients were assayed. Patients with vitamin D deficiency (<50 nmol/l) were treated with vitamin D3 supplements (high oral dose or intramuscular injection). The severity scores of RLS were reassessed after the vitamin D3 level was corrected to >50 nmol/l and compared with those before the administration of the supplements. RESULTS: The median pretreatment vitamin D level was 21.7 nmol/l (13.45-57.4), which improved to 61.8 nmol/l (42.58-95.9) (P = 0.002) with the treatment. The median RLS severity score improved significantly from 26 (15-35) at baseline to 10 (0-27) after correction of the vitamin D levels (P = 0.002). CONCLUSION: This study indicates that vitamin D supplementation improves the severity of RLS symptoms and advocates that vitamin D deficiency is conceivably associated with RLS.

Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep.

OBJECTIVE: To evaluate possible abnormal increase in thalamic glutamate/glutamine levels for restless legs syndrome (RLS) indicating increased glutamatergic activity producing arousal that at night disrupts and shortens sleep. METHODS: (1)H MRS of the right thalamus was performed using a 1.5 T GE MRI scanner and the PROBE-P (PRESS) on 28 patients with RLS and 20 matched controls. The Glx signal (combination of mostly glutamate [Glu] and glutamine [Gln]) was assessed as a ratio to the total creatine (Cr). This study tested 2 primary hypotheses: 1) higher thalamic Glx/Cr for patients with RLS than controls; 2) thalamic Glx/Cr correlates with increased wake during the sleep period. RESULTS: The Glx/Cr was higher for patients with RLS than controls (mean ± SD 1.20 ± 0.73 vs 0.80 ± 0.39, t = 2.2, p = 0.016) and correlated significantly with the wake time during the sleep period (r = 0.61, p = 0.007) and all other RLS-related polysomnographic sleep variables (p < 0.05) except for periodic leg movements during sleep (PLMS)/hour. CONCLUSIONS: The primary findings introduce 2 new related dimensions to RLS: abnormalities in a major nondopaminergic neurologic system and the arousal disturbance of sleep. The strong relation of the arousal sleep disturbance to glutamate and the lack of relation to the PLMS motor features of RLS contrasts with the reverse for dopamine of a limited relation to arousal sleep disturbance but strong relation to PLMS. Understanding this dichotomy and the interaction of these 2 differing systems may be important for understanding RLS neurobiology and developing better treatments for RLS.

Risk factors and prevalence rate of restless legs syndrome among pregnant women in Taiwan.

BACKGROUND: The goal of this study was to assess the prevalence and clinical correlates of restless legs syndrome (RLS) among pregnant Taiwanese women. METHODS: We enrolled 461 pregnant women (18-45 years) admitted at Mackay Memorial Hospital for delivery from September 2010 to May 2011. The face-to-face questionnaire used to gather data included assessment of RLS diagnostic criteria, and questions related to RLS. RESULTS: The overall prevalence rate of RLS among the study participants was 10.4%; 2.8% were categorized as having chronic RLS. Participants without RLS reported higher folate and iron supplement consumption than those with RLS. Multivariate analysis revealed significant associations of RLS with anemia and peptic ulcer disease. Participants with transient RLS during pregnancy reported more regular coffee consumption before pregnancy, and better sleep latency, duration, and efficiency, than those with chronic RLS. Overall, 81.2% of RLS sufferers reported sleep disturbances. CONCLUSIONS: Our study revealed highly prevalent but poorly recognized RLS among Taiwanese pregnant women. The identification of predictors such as medical comorbidities, and protectors such as folate and iron supplements, is warranted for obstetric RLS. In most cases, symptoms began during the second or third trimester and resolved within a week after delivery. Restricted coffee consumption before pregnancy is encouraged, but further evidence is needed to support this recommendation.

Iron for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common neurologic syndrome and is associated with iron deficiency in many patients. It is unclear whether iron therapy is effective treatment for RLS. OBJECTIVES: The objective of this review was to assess the effects of iron supplementation (oral or intravenous) for patients with RLS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Jan 1995 to April 2011); EMBASE (Jan 1995 to April 2011); PsycINFO (Jan 1995 to April 2011); and CINAHL (Jan 1995 to April 2011). Corresponding authors of included trials and additional members of the International Restless Legs Syndrome Study Group were contacted to locate additional published or unpublished trials. SELECTION CRITERIA: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and at least two authors assessed trial quality. We contacted trial authors for missing data. MAIN RESULTS: Six studies (192 total subjects) were identified and included in this analysis. The quality of trials was variable. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the IRLS severity scale in four trials and another RLS symptom scale in a fifth trial. Combining data from the four trials using the IRLS severity scale, there was no clear benefit from iron therapy (mean difference in IRLS severity scores of -3.79, 95% CI: -7.68 to 0.10, p = 0.06). However, the fifth trial did find iron therapy to be beneficial (median decrease of 3 points in the iron group and no change in the placebo group on a 10 point scale of RLS symptoms, p = 0.01). Quality of life was improved in the iron group relative to placebo in some studies but not others. Changes in periodic limb movements were not different between groups (measured in two studies). Objective sleep quality, subjective sleep quality and daytime functioning were not different between treatment groups in the studies that assessed them. The single study of subjects with end stage renal disease did show a benefit of therapy. Most trials did not require subjects to have co-morbid iron deficiency and several excluded patients with severe anemia. The single study that was limited to iron deficient subjects did not show clear benefit of iron supplementation on RLS symptoms. There was no clear superiority of oral or intravenous delivery of iron. Iron therapy did not result in significantly more side effects than placebo (RR 1.39, 95% CI 0.85 to 2.27). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether iron therapy is beneficial for the treatment of RLS. Further research to determine whether some or all types of RLS patients may benefit from iron therapy, as well as the best route of iron administration, is needed.

Restless legs syndrome in children: a review and update on pharmacological options.

Restless legs syndrome (RLS), formally identified and described by Ekbom in the 1940s, is a common clinical disorder, characterized by an overwhelming urge to move the legs, often accompanied by uncomfortable and unpleasant sensations. This impulse can also be present in the upper limbs or other parts of the body. Well recognized in the adult population, the symptoms associated with this condition have commonly been reported to originate in childhood. However, identifying prospectively children suffering from RLS is still a challenging issue. Iron deficiency has been recognized as a feature frequently associated with RLS. Some authors also make a connection with the deficiency, RLS and other common problems encountered in children, such as attention deficit disorder with hyperactivity (ADHD). Linkage to different chromosomal loci has been achieved in recent genetic studies of large kindred, as well as identification of specific genes. Therapeutic considerations in children range from providing sound sleep hygiene to intervening pharmacologically. In that regard, use of iron supplements, dopaminergic stimulation, anticonvulsants, opiates, and benzodiazepines will be assessed along with newer options, such as rotigotine and gabapentin enacarbil. Considerations specific to childhood do apply, as no pharmacological therapy for restless legs syndrome have been approved by the Federal Drug Administration (FDA) in individuals of the pediatric age group.

Thomas de Quincey and his restless legs symptoms as depicted in "Confessions of an English Opium-Eater".

Thomas de Quincey, a British writer of 19th century, suffered insomnia from the age of 17 years. In his famous "Confessions of an English-Opium Eater" (1822), he described a symptomatology that could concord with restless legs syndrome long before he became addicted to opium. In this report, we analyze his clinical description and the circumstances leading to his opium addiction.

Lack of specific gray matter alterations in restless legs syndrome in elderly subjects.

Magnetic resonance imaging studies using voxel-based morphometry (VBM) have been inconsistent in demonstrating volumetric differences in patients with restless legs syndrome (RLS). Since treatment, age and selection of patients may introduce a methodological bias, we conducted optimized VBM analyses in unmedicated elderly subjects reporting RLS. Two hundred-four voluntaries, 65.9 +/- 0.6 year-old, free of any significant medical condition and without previous neurological or psychiatric medication, participated at the study. After exclusion of subjects having sleep-related breathing disorders and previous silent infarct, 71 subjects, 54 without RLS (RLS-) and 17 having RLS (RLS+) were analyzed. No structural change in gray matter density was found in RLS+ subjects compared to RLS- subjects. Subjects with RLS+ symptoms showed a small gray matter volume in the left occipital region without, however, statistical significance. VBM analysis did not show any significant change in subcortical and cortical gray matter in unmedicated elderly subjects with RLS symptoms. These results confirm the lack of specificity of thalamic and subcortical changes in restless legs syndrome.