The effect of vitamin D on restless legs syndrome: prospective self-controlled case study.

PURPOSE: To evaluate the effect of vitamin D on severity of restless legs syndrome in patients with idiopathic restless legs syndrome (RLS). METHODS: Patients with idiopathic RLS completed questionnaires including the International Restless Legs Severity Scale (IRLSS) and were evaluated for vitamin D deficiency. Patients with deficiency of vitamin D were treated with 50,000 units per week for 2 months. At the end of the 2 months, vitamin D levels were re-measured and disease severity was re-evaluated in patients who reached adequate vitamin D level. Subgroups of IRLSS questionnaire were also analyzed. RESULTS: Of 35 patients enrolled, 21 (60%) had vitamin D deficiency and received vitamin D therapy. In 2 patients, vitamin D levels did not rise to sufficient levels with supplementation and these 2 patients were excluded from analysis. The remaining 19 patients showed vitamin D levels increased from 13.2 ± 4.0 to 42.8 ± 9.6 ng/mL while IRLSS improved from 24.9 ± 5.1 to 21.1 ± 2.9 points (p <0.001). Selected subscores of the IRLSS were also improved including symptom severity (p <0.001), impact on sleep (p <0.001), symptom measures (p =0.002), and disease impact measures (p <0.001). There were trends toward improvement in subscores of frequency (p =0.11) and mood (p =0.051). CONCLUSIONS: The findings suggest that vitamin D levels should be evaluated in patients with RLS and if vitamin D deficiency is revealed, consideration should be given to replacement therapy.u.

Efficacy of the low-dose Saccharum iron treatment of idiopathic restless legs syndrome.

AIM: The aim of the study was to determine the efficacy of low-dose and high-dose Saccharum iron injected intravenously in patients with idiopathic restless legs syndrome (RLS) by detecting levels of serum ferritin (SF) and international RLS Severity Scale. METHODS: For this purpose, 38 patients with idiopathic RLS were randomly divided into the following two groups: low-dose group (18 cases) and high-dose group (20 cases). Low-dose group received Saccharum iron intravenously (200 mg/dose); once a week for 5 weeks with a total dose of 1000 mg. High-dose group received Saccharum iron intravenously (500 mg/dose); once every two weeks for 4 weeks with a total dose of 1000 mg. The pre- and post-treatment (at 2, 4, and 6 weeks) level of SF and RLS scores were determined and the differences were compared between two groups. RESULTS: Post-therapeutic SF levels increased significantly in both groups as compared with before treatment (P<0.05). At 6-week post-therapy, SF levels in low-dose group were significantly higher than those in high-dose group (P<0.05). The clinical symptoms were improved and RLS scores were lower than pretreatment ratings in both groups (P<0.05). After 6 weeks of treatment, RLS scores of low-dose group were lower than those of high-dose group (P<0.05). CONCLUSION: Both the low-dose and high-dose Saccharum iron treatments increased the SF levels and improved clinical symptoms in patients with idiopathic RLS; however, the low-dose iron treatment was found to be more effective and had fewer side effects.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

Early childhood-onset restless legs syndrome: symptoms and effect of oral iron treatment.

AIM: To describe symptoms of restless legs syndrome (RLS) in early childhood and the effect of oral iron treatment. METHODS: A study population comprising 22 children, 15 males and seven females referred for paediatric evaluation because of sleep disturbances. Presence of RLS was evaluated using the International RLS Study Group consensus criteria of RLS. In case of ferritin level below 50 ng/mL, oral iron treatment was initiated. Fourteen were examined by polysomnography as well, and periodic limb movement index during sleep (PLMSI) was calculated. Relief of symptoms was recorded by the parents and correlated with ferritin levels and PLMSI. RESULTS: Median age at onset of symptoms was 7.5 months (0-40 months). The most striking single symptom was awakening after 1-3 h of sleep followed by screaming, crying, kicking or hitting the legs. Oral iron supplementation had a positive ferritin-concentration-dependent clinical effect. A relation between high PLMSI and low ferritin levels was demonstrated. CONCLUSION: Symptoms of RLS may start as early as the first year of life, are accompanied by low ferritin levels and a high PLMSI and can be ameliorated by iron supplementation. An increased awareness and knowledge of RLS in early childhood are warranted.

Evaluation of oral iron treatment in pediatric restless legs syndrome (RLS).

OBJECTIVE: We conducted a retrospective chart review of children with restless legs syndrome (RLS) to evaluate the efficacy of oral iron treatment, which was administered open-label during the course of clinical care. In addition, we provided detailed clinical information about RLS in this pediatric cohort. PATIENTS AND METHODS: The study included 30 consecutive Japanese children with RLS who visited the Pediatric Sleep Clinic at Osaka University Hospital, and consisted of 17 boys and 13 girls, aged 2-14 years (mean ± SD, 6.5 ± 2.8). All-night polysomnography was performed in 18 patients and serum ferritin levels were measured in all the patients. After the diagnosis of RLS, iron was administered at doses between 1.6 and 7.8 mg/kg/day (3.2 ± 1.3). Serum ferritin was re-evaluated 3-6 months after iron treatment, or when RLS symptoms had disappeared. RESULTS: The patient age at onset of RLS symptoms ranged from six months to 13 years (4.3 ± 3.6). A positive family history was recognized in 19 children (63.3%). Serum ferritin levels before therapy were 9-62 ng/ml (26.6 ± 12.8) and oral iron supplementation was reported to be highly effective in 17 children, effective in 10, and ineffective in three. The serum ferritin level at follow-up was 23-182 ng/ml (83.5 ± 49.8). The onset of treatment effect was within approximately three months. CONCLUSIONS: Iron treatment could be effective in Japanese pediatric RLS.

High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron.

BACKGROUND AND OBJECTIVES: Iron depletion is common in regular blood donors. The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof, especially restless legs syndrome (RLS). METHOD: One hundred and twenty blood donors with at least five previous whole blood donations were randomized to receive either IV iron sucrose (Venofer(®), RenaPharma/Vifor, Uppsala, Sweden), 200 mg, or to 20×100 mg of oral iron sulphate (Duroferon(®), GlaxoSmithKline, Stockholm, Sweden), after each blood donation during 1 year. Iron status and RLS incidence and severity were investigated. RESULTS: Iron status was generally poor among regular blood donors, especially in women, with a high incidence of iron depletion (>20%) and RLS (18%). The IV iron group increased storage iron to a greater extent than the oral iron group after 12 months (P=0·0043). Female donors were more responsive to IV iron sucrose compared to oral iron sulphate, particularly female donors below 50 years of age. RLS severity scores were significantly lower in the IV iron group. The two treatments were safe. CONCLUSION: Iron status is poor in regular blood donors, restless legs syndrome is common, and the routine iron supplementation is insufficient. IV iron sucrose substitutes iron loss in blood donors more efficiently compared with oral iron sulphate, especially in women. Iron substitution to blood donors should be individualized and based on P-ferritin monitoring.

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

BACKGROUND AND PURPOSE: Restless 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 METHODS: This 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. RESULTS: Baseline 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+/-15.3ng/ml) and placebo (36.7+/-20.8ng/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+/-20.3ng/ml) than in the placebo arm (7.5+/-13.7ng/ml), (p=0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p=0.07). CONCLUSIONS: This 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.

Restless legs syndrome and pregnancy.

OBJECTIVE: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy and the puerperium. METHODS: A structured clinical interview, assessing symptoms since the beginning of pregnancy, was performed to a population of 642 pregnant women at the time of delivery and at follow-up evaluation (1, 3, and 6 months after delivery). Main hematologic tests were also evaluated. A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. RESULTS: Twenty-six percent of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and tended to disappear reaching the time of delivery. Affected women presented lower values of hemoglobin and mean corpuscular volume compared with healthy subjects (both groups received the same supplemental iron and folate therapy). CONCLUSIONS: Pregnancy is associated with transient restless legs syndrome.

A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disorder in patients with end-stage renal disease (ESRD) that causes motor agitation and insomnia. Because RLS has been associated with iron deficiency, we sought to investigate the effects of intravenous (IV) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial. METHODS: Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran, 1,000 mg, or normal saline IV in a blinded fashion. Patient demographic data were collected, and blood chemistry tests, liver function studies, serum iron levels, ferritin levels, and total iron-binding capacity were obtained at baseline and 1, 2, and 4 weeks postinfusion. Side effects or adverse events to interventions were monitored, and RLS symptoms were assessed by a rating scale at the same intervals. RESULTS: Eleven patients were randomly assigned to the administration of iron dextran, and 14 patients to the administration of saline. RLS severity scores were slightly higher in the placebo group at baseline, but hemoglobin levels, iron stores, and other biochemical parameters did not differ. Although no change in symptoms were seen in the placebo-treated group, significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion (-2; interquartile range [IQR], -6 to -1; P = 0.03, Wilcoxon's rank sums), but was greatest at 2 weeks (-3; IQR, -5 to -2 compared with -1 to 0; P = 0.01). Salutary effects of iron persisted at 4 weeks, but were no longer statistically significant. The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group. No differences in adverse events were noted between groups. CONCLUSION: High-dose iron dextran infusion is associated with a significant, but transient, reduction in symptoms of RLS in patients with ESRD.

Iron status and restless legs syndrome in the elderly.

The relationship between iron status and the restless legs syndrome (RLS) was examined in 18 elderly patients with RLS and in 18 matched control subjects. A rating scale with a maximum score of 10 was used to assess the severity of RLS symptoms. Serum ferritin levels were reduced in the RLS patients compared with control subjects (median 33 micrograms/l vs. 59 micrograms/l, p < 0.01, Wilcoxon signed rank test); serum iron, vitamin B12 and folate levels and haemoglobin levels did not differ between the two groups. Serum ferritin levels were inversely correlated with the severity of RLS symptoms (Spearman's rho -0.53, p < 0.05). Fifteen patients with RLS were treated with ferrous sulphate for 2 months. RLS severity score improved by a median value of 4 points in six patients with an initial ferritin < or = 18 micrograms/l, by 3 points in four patients with ferritin > 18 micrograms/l, < or = 45 micrograms/l and by 1 point in five patients with ferritin > 45 micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.