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Introduction: Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder characterized by an uncontrollable urge to move the legs, typically accompanied by discomfort. Low iron levels, pregnancy, and age are some identified risk factors. RLS is treated using various pharmacological options, including dopamine agonists, benzodiazepines, anticonvulsants, opioids, and bupropion. Iron supplementation, particularly with intravenous Ferric carboxymaltose (FCM), has gained attention due to the role of iron deficiency in RLS pathophysiology. This meta-analysis evaluates the efficacy and safety of FCM in treating RLS symptoms. Materials and methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines, using databases such as PubMed, Google Scholar, and Cochrane. Studies involving intravenous FCM in patients diagnosed with RLS were included. Statistical analysis was performed using Review Manager 5.4. Results: Seven studies involving 539 participants were analyzed. FCM significantly reduced IRLS scores (WMD = −5.77; 95% CI = [−8.85, −2.70]; p = 0.0002) and improved VAS and SF-36 scores compared to placebo. However, FCM did not significantly improve RLS quality of life scores. Adverse events were more common in the FCM group, particularly nausea, but no significant differences were found for severe adverse events. Conclusion: In conclusion, intravenous ferric carboxymaltose significantly reduces Restless Legs Syndrome symptoms, especially in patients with confirmed iron deficiency. The treatment appears generally well-tolerated, with adverse effects being manageable. However, further long-term studies are needed to fully assess the safety profile and confirm sustained symptom improvement in a broader population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42024585233. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs, worsened in the evening, occurring at rest, and relieved temporarily by movement. Although its pathophysiology remains incompletely understood, oxidative stress has been suggested. Uric acid (UA) is a marker associated with oxidative stress, and its reduced levels pose a risk for certain neurodegenerative diseases. In this study, we aimed to assess serum UA concentrations in RLS patients to gain insights into its role in the etiopathogenesis of the condition.: This study involved 200 individuals. Serum UA levels were compared with clinical parameters. Disease severity was assessed, categorizing patients into "mild," "moderate," "severe," and "very severe" subgroups. Comparative analysis of UA levels was conducted between these subgroups and the control group. Patients exhibited a statistically significant reduction in UA levels compared to controls (p = 0.001; p < 0.01). No significant disparities in UA levels were observed among patients based on RLS scores (p > 0.05). The generalized linear model in which UA serves as the dependent variable revealed statistically significant associations with the "moderate" and "severe" stages of RLS, as well as age (p < 0.05). Additionally, a ROC curve analysis was executed to evaluate the potential of UA as a biomarker. The ROC analysis, focusing on the patient-control classification, revealed a statistically significant area under the curve (AUC = 0.848, p < 0.001). Our study supports the hypothesis implicating serum UA levels in RLS pathogenesis. Further understanding of UA and its physiological effects will clarify on its role in RLS pathophysiology. [ABSTRACT FROM AUTHOR]

Restless legs syndrome/Willis–Ekbom disease (RLS/WED) causes a strong urge to move legs while resting. Restless legs syndrome/WED is an often-inherited disease occurring in 3% to 10% of adult populations, increasing with age. Severity varies from mild disturbance of sleep to painful restless legs and arms, loss of sleep, fatigue, and risk of suicide. Dopaminergic drugs relieve symptoms, but cause augmentation, ie, initially helpful but later increase the burden of symptoms. Oral gabapentinoids and opioids are often added, but opioid tolerance and adverse effects are common. With the high prevalence and incomplete help from oral drugs, significant unmet needs exist for effective therapy for severe RLS/WED. Ongoing spinal intrathecal infusion of low-dose morphine is effective, but not generally recognized, as only 12 cases have been published since 2002. We report 7 patients suffering from severe RLS/WED, who had no relief from oral dopaminergic, gabapentinoid, or opioid drugs; they all had excellent relief during ongoing spinal intrathecal infusion of morphine at only 1 to 5 μg/h, ongoing for 1 to 21 years without need of higher doses of morphine.. We suggest that morphine may be transported with the cerebrospinal fluid reaching and readjusting malfunctioning dopamine neuronal systems in the brain and spinal cord. The effects last only as long as the infusion continues. A patient with RLS/WED and persistent genital arousal disorder (PGAD) was relieved of both RLS/WED and PGAD symptoms. These case reports suggest that intrathecal infusion of low-dose morphine is an effective treatment of severe RLS. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) is a disease from the spectrum of movement disorders, the prevalence of which increases significantly during pregnancy and is associated with poor sleep, a drop in daytime energy, and the development of psychological disorders during pregnancy and the postpartum period. The IRLSS scale was used to determine the presence of RLS symptoms. The total test sample that included the tested and control groups was (n=390) subjects. The examined group consisted of pregnant women (n=260), and the control group consisted of female students (n=130). In total, 260 pregnant women were monitored 6 months after pregnancy. Three measurements were performed, first in the third trimester of pregnancy, second two months after delivery, third 6 months after delivery, while one cross-sectional measurement was performed for the control group. The prevalence of RLS in pregnancy is highest in the third trimester and amounts to 26.5 %. In the postpartum period, a significant decrease in the prevalence of RLS was observed, measured two months after delivery (18.1 %). Postpartum, over time, a decrease in the prevalence of RLS was noticed, and six months after delivery it was (7.3 %), when it practically approached the prevalence of the control group (standard population) which was (6.2 %). The prevalence of RLS is highest during the third trimester of pregnancy and decreases after delivery so that 6 months after delivery it approaches the prevalence of the standard population. [ABSTRACT FROM AUTHOR]

Introduction and Purpose of Research: Restless Leg Syndrome (RLS) or Willis-Ekbom disease, is a common neurological disorder significantly impacting one’s sleep and quality of life. It often coexists with various health issues, including diabetes and cardiovascular diseases. Aim of study: The primary purpose of this research is to explore diverse therapeutic options for RLS which are tailored to individual patient needs. In order to understand the complex pathophysiology of the discussed disease, recent advancements are taken into account. Material and Methods of Research: The review is grounded in findings from 36 recent studies sourced through a systematic search of open-access databases, including PubMed and Google Scholar, focusing on literature published between 2004 and 2024. Results: Adequate and effective management of RLS include non-pharmacological interventions, such as physical activity, acupuncture, yoga and near-infrared light therapy, which can complement pharmacotherapy or prevail as the primary treatment form. Iron therapy emerges as vital for many patients. The correlation between iron metabolism and RLS symptoms requires further analysis and research. Pharmacological strategies involve dopaminergic medications, low-potency opioids, and benzodiazepines, with a target on minimizing side effects and dependency. Conclusion: RLS affects approximately 5-10% of the population, severely disrupting sleep and daily functioning. The condition constrains individualized management, integrating non-pharmacological forms of treatment with pharmacological therapies to improve patient outcomes and reduce dependence on medication.

IntroductionRestless Legs Syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder characterized by an uncontrollable urge to move the legs, typically accompanied by discomfort. Low iron levels, pregnancy, and age are some identified risk factors. RLS is treated using various pharmacological options, including dopamine agonists, benzodiazepines, anticonvulsants, opioids, and bupropion. Iron supplementation, particularly with intravenous Ferric carboxymaltose (FCM), has gained attention due to the role of iron deficiency in RLS pathophysiology. This meta-analysis evaluates the efficacy and safety of FCM in treating RLS symptoms.Materials and methodsA systematic review and meta-analysis were conducted following the PRISMA guidelines, using databases such as PubMed, Google Scholar, and Cochrane. Studies involving intravenous FCM in patients diagnosed with RLS were included. Statistical analysis was performed using Review Manager 5.4.ResultsSeven studies involving 539 participants were analyzed. FCM significantly reduced IRLS scores (WMD = −5.77; 95% CI = [−8.85, −2.70]; p = 0.0002) and improved VAS and SF-36 scores compared to placebo. However, FCM did not significantly improve RLS quality of life scores. Adverse events were more common in the FCM group, particularly nausea, but no significant differences were found for severe adverse events.ConclusionIn conclusion, intravenous ferric carboxymaltose significantly reduces Restless Legs Syndrome symptoms, especially in patients with confirmed iron deficiency. The treatment appears generally well-tolerated, with adverse effects being manageable. However, further long-term studies are needed to fully assess the safety profile and confirm sustained symptom improvement in a broader population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024585233.

Purpose: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early‐onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. Methods: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log‐binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. Results: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person‐years; suicidality with self‐harm: 23.0 vs. 11.1 per 1000 person‐years; overdose‐ and suicide‐related events: 30.0 vs. 15.5 person‐years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86–1.88]); suicidality with self‐harm (adjusted RR, 1.30 [95% CI, 0.89–1.90]); or overdose‐ and suicide‐related events (adjusted RR, 1.30 [95% CI, 0.93–1.80]) was not significant with gabapentinoids. Conclusions: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome. [ABSTRACT FROM AUTHOR]

Background: Restless Leg Syndrome (RLS) is frequently associated with Chronic Kidney Disease (CKD), often under diagnosed and inadequately treated. Hence, this study aimed to ascertain the prevalence of CKD-induced RLS, exploring associated factors, pharmacotherapy and its impact on patients' quality of life. Materials and Methods: An observational prospective study conducted at Dhiraj General Hospital, Vadodara, from November 2022 to March 2023 included 246 CKD patients. Screening for RLS symptoms led to further evaluation and treatment in the Neurology department. Patients were re-evaluated after one month to assess treatment outcomes. Results: Analysis of 246 patients revealed a 6.91% prevalence of RLS in CKD. Factors contributing to RLS included anemia, advanced CKD stages and prolonged dialysis. Female gender emerged as a CKD risk factor. Pramipexole, Syndopa and Ropirinole effectively treated RLS in CKD patients. Conclusion: RLS substantially diminishes the quality of life in end-stage renal disease patients. Identification and management of contributing factors hold promise for improving outcomes and quality of life in CKD patients with RLS. [ABSTRACT FROM AUTHOR]

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Purpose: This study aimed to (1) evaluate in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) the presence of sleep disorders such as hypersomnia, fatigue, risk of apnea, and the presence of restless legs syndrome/Willis-Ekbom disease (RLS/WED); (2) evaluate quality of sleep in patients with MS and NMOSD; and (3) correlate them with clinical and imaging data. Methods: The study was cross-sectional and was carried out in the sector of demyelinating diseases of the neurology service of HUGV-UFAM, Manaus, Brazil, from January 2017 to December 2020. Results: Our sample consisted of 60 patients, 41 with MS and 19 with NMOSD. We found that patients with MS and NMOSD have poor sleep quality (65%) and hypersomnia (53% in MS; 47% in NMOSD), but low risk of apnea by STOP-BANG. The frequency of RLS/WE found was 14% in MS, and 5% in NMOSD. No correlation existed between sleep quality, number of relapses, and sleep quality for the Expanded Disability Status Scale (EDSS), i.e., fatigue/illness duration. Conclusion: Patients with MS and NMOSD have poor sleep quality, excessive sleepiness, and are at low risk for OSA, yet the frequency of RLS/WED is like that of the general population. There does not seem to be a significant difference between these sleep disorders in these demyelinating diseases of the CNS. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) has an increased estimated prevalence in patients with Parkinson's disease (PS). RLS frequently mimics symptoms intrinsic to PD, such as motor restlessness, contributing to making its diagnosis challenging in this population. We report the case of a patient with new-onset RLS following subthalamic deep-brain stimulation (DBS-STN). We assessed symptoms using suggested immobilization test (SIT) with both DBS-STN activated and switched off. A 59-year-old man with idiopathic PD developed disabling RLS following DBS-STN at age 58, with PD onset at 50 manifesting as left arm tremor. Despite improved motor symptoms during the month following surgery, the patient experienced left leg discomfort at rest, transiently alleviated by movements due to an irrepressible urge to move, and worsened at night. Symptoms had no temporal relationship with oral dopa-therapy and disappeared when DBS-STN was deactivated. A 1 h SIT assessed motor behavior with irrepressible urge to move, as well as sensory symptoms by visual analog scale. After 30 m DBS-STN was switched off followed by the appearance of tremor in the left arm while both motor and sensory symptoms of RLS disappeared in the left leg. The mechanisms of DBS-STN's impact on RLS remain controversial. We hypothesize the DBS-STN to induce in our patient a hyperdopaminergic tone. DBS-induced and DBS-ameliorated RLS represent interesting conditions to further understand the pathophysiology of RLS. Moreover, the present observation suggests that SIT can be a valuable tool to assess RLS in PD patients before and after DBS-STN in future prospective studies. • Deep brain stimulation may induce restless legs syndrome in Parkinson's patients. • Suggested immobilization test helps identify restless legs in Parkinson's patients. • Suggested immobilization test aids in distinguishing dyskinesia from restless legs. • A hyperdopaminergic tone may drive pathophysiology of restless legs syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background and objective Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. Methods A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients’ disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. Results The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). Conclusion Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality.

Background and objective: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. Methods: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients' disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. Results: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). Conclusion: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality. [ABSTRACT FROM AUTHOR]

Background and objective: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. Methods: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients' disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. Results: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). Conclusion: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality. [ABSTRACT FROM AUTHOR]

Introduction: This guideline establishes clinical practice recommendations for treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in adults and pediatric patients., Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the grading of recommendations assessment, development, and evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations., Good Practice Statement: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS., 1. In all patients with clinically significant RLS, clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity). Testing should ideally be administered in the morning avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw. Analysis of iron studies greatly influences the decision to use oral or intravenous (IV) iron treatment. Consensus guidelines, which have not been empirically tested, suggest that supplementation of iron in adults with RLS should be instituted with oral or IV iron if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20%, and only with IV iron if serum ferritin is between 75 and 100 ng/mL. In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations. These iron supplementation guidelines are different than for the general population., 2. The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, antidopaminergic medications, and untreated obstructive sleep apnea., 3. RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered., Recommendations: The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO (Patient, Intervention, Comparator, Outcome) question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation., Adults With Rls: 1. In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil (strong recommendation, moderate certainty of evidence)., 2. In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin (strong recommendation, moderate certainty of evidence)., 3. In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin (strong recommendation, moderate certainty of evidence)., 4. In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status (see good practice statement for iron parameters) (strong recommendation, moderate certainty of evidence)., 5. In adults with RLS, the AASM suggests the use of IV low molecular weight iron dextran over no IV low molecular weight iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., 6. In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., 7. In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, moderate certainty of evidence)., 8. In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole (conditional recommendation, low certainty of evidence)., 9. In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids (conditional recommendation, moderate certainty of evidence)., 10. In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation (conditional recommendation, moderate certainty of evidence)., 11. In adults with RLS, the AASM suggests against the standard use of levodopa (conditional recommendation, very low certainty of evidence)., Remarks: levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 12. In adults with RLS, the AASM suggests against the standard use of pramipexole (conditional recommendation, moderate certainty of evidence)., Remarks: pramipexole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 13. In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine (conditional recommendation, low certainty of evidence)., Remarks: transdermal rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 14. In adults with RLS, the AASM suggests against the standard use of ropinirole (conditional recommendation, moderate certainty of evidence)., Remarks: ropinirole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 15. In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS (conditional recommendation, moderate certainty of evidence)., 16. In adults with RLS, the AASM suggests against the use of carbamazepine (conditional recommendation, low certainty of evidence)., 17. In adults with RLS, the AASM suggests against the use of clonazepam (conditional recommendation, very low certainty of evidence)., 18. In adults with RLS, the AASM suggests against the use of valerian (conditional recommendation, very low certainty of evidence)., 19. In adults with RLS, the AASM suggests against the use of valproic acid (conditional recommendation, low certainty of evidence)., 20. In adults with RLS, the AASM recommends against the use of cabergoline (strong recommendation, moderate certainty of evidence)., Special Adult Populations With Rls: 21. In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin (conditional recommendation, very low certainty of evidence)., 22. In adults with RLS and ESRD, the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% (conditional recommendation, moderate certainty of evidence)., 23. In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C (conditional recommendation, low certainty of evidence)., 24. In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa (conditional recommendation, low certainty of evidence)., Remarks: levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 25. In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine (conditional recommendation, very low certainty of evidence)., Remarks: rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., Adults With Plmd: 26. In adults with PLMD, the AASM suggests against the use of triazolam (conditional recommendation, very low certainty of evidence)., 27. In adults with PLMD, the AASM suggests against the use of valproic acid (conditional recommendation, very low certainty of evidence)., Children With Rls: 28. In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence)., Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025;21(1):137-152., (© 2025 American Academy of Sleep Medicine.)

Introduction: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome and periodic limb movement disorder., Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat restless legs syndrome and periodic limb movement disorder in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations., Results: The literature search resulted in 3,631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations., Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med . 2025;21(1):153-199., (© 2025 American Academy of Sleep Medicine.)

Summary: Questionnaires for restless legs syndrome have rarely been validated against face‐to‐face interviews in the general population. We aimed to validate the modified Norwegian, seven‐item Cambridge‐Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face‐to‐face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen's kappa statistic (κ) of questionnaire‐ versus interview‐based diagnoses. We found acceptable validity of the seven‐item modified Cambridge‐Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23–0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35–0.58). We also found good validity through the combination of modified Cambridge‐Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single‐ and two‐item questionnaire‐based diagnoses overestimated interview‐based restless legs syndrome prevalence. The seven‐item modified Cambridge‐Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire‐based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire‐based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the relationship between Willis-Ekbom Disease/Restless Legs Syndrome and iron deficiency anemia in older people with dementia. Methods: A cross-sectional study was conducted with 70 older people diagnosed with dementia and restless leg syndrome in a Psychogeriatric outpatient clinic in a city in the interior of São Paulo, Brazil. The older people filled in instruments of sociodemographic characterization, measures to evaluate the Restless Legs Syndrome, neuropsychiatric symptoms, sleep quality, sleepiness and cognition. Blood data were also collected levels of creatinine, ferritin, red blood cells, hemoglobin and hematocrit, the latter collected in the patients' medical records. Results: The sample consists mostly of older people with mixed dementia (i.e., Alzheimer's disease + Vascular Dementia), with 39% of female patients and mean age of 77.80 years (9.36). This study identified a frequency of 15.7% of Restless Legs Syndrome. Patients with the syndrome present more frequency of neuropsychiatric symptoms, worse sleep quality, higher index of body mass and lower levels of ferritin (p <.05). Conclusions: A frequency of 15.7% was identified for restless leg syndrome among patients with dementia. In addition, patients with the syndrome have ferritin deficiency. [ABSTRACT FROM AUTHOR]

Objective/background: Restless legs syndrome (RLS) is a complex condition associated with circadian rhythm that disrupts sleep and can cause multisystemic consequences. This study assesses pharmacotherapy treatment initiation, estimates annual treatment prevalence, and assesses treatment patterns for early-onset idiopathic RLS.Methods: We used the MarketScan Commercial Claims Database from 2012 to 2019 to conduct a new user retrospective cohort study. Annual treatment prevalence was calculated from a cross-sectional sample. Newly diagnosed adults with early-onset (18-44 years) idiopathic RLS who initiated on and off-label gabapentinoids, dopamine agonists, or levodopa/carbidopa were included. Among monotherapy users who had one year of insurance enrollment, treatment patterns (single fill, continuous use of initiated therapy, switching, and add-on therapy) were examined and mean time on the initial treatment (as a measure of persistence) was calculated.Results: In total, 6, 828 patients were initiated on monotherapy treatment for early-onset idiopathic RLS in which 4,638 met all inclusion criteria. In 2019, annual prevalence of monotherapy treatment of diagnosed patients for ropinirole was 171.3/1,000 patients; 85.0/1,000 patients for pramipexole; and 132.1/1,000 patients for gabapentin. Overall, 22.3% (n = 1,033) of patients maintained their initiated pharmacotherapy for the entire year. Rotigotine had the longest persistence (mean 185.4 [161.4 SD] days) but this user group was the smallest (n = 29). Gabapentin enacarbil, pregabalin, and rotigotine use was low (2.8% total).Conclusion: Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined. [ABSTRACT FROM AUTHOR]

Background and purpose: Stroke‐related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally. Methods: Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18F‐FDG (2‐deoxy‐2‐[fluorine‐18]fluoro‐D‐glucose) positron emission tomography (PET) for glucose consumption, 123I‐FP‐CIT ([123]I‐2beta‐carbometoxy‐3beta‐[4‐iodophenyl]‐N‐[3‐fluoropropyl]nortropane) single‐photon emission computed tomography for dopamine reuptake and PET with 18F‐FDOPA ((3,4‐dihydroxy‐6‐[18]F‐fluoro‐l‐phenylalanine) for presynaptic dopaminergic synthesis. Results: Sixteen patients with sRLS, eight women and eight men, aged 41–81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico‐pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area. Conclusions: Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition. [ABSTRACT FROM AUTHOR]

Introduction: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated., Areas Covered: The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options., Expert Opinion: α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.

• Three-fourths of newly diagnosed RLS patients were initiated on a dopamine agonist. • Gabapentinoids are a first-line treatment alternative but were initiated less often. • Gabapentinoid initiators had more emergency department and inpatient encounters. • A significant risk of the primary outcome with gabapentinoids was not detected. • A significant risk of substance use disorders with gabapentinoids was detected. Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019. Adults with early-onset (18–44 years) idiopathic RLS initiating either gabapentinoids or DAs within 60 days of new diagnosis were followed up to two years. Incidence rates were calculated and a log-binomial regression model with propensity score weighting estimated relative risk of the outcome and of substance use disorders (SUDs) as a secondary analysis with gabapentinoids. Among a cohort of 6,672 patients, 4,986 (74.7%) initiated DAs and 1,686 (25.3%) gabapentinoids. Incidence of the primary outcome (49.8 [95% CI 40.8–69.3] per 1,000 person-years) and SUDs (49.5 [95% CI 40.6–59.9] per 1,000 person-years) were higher in the gabapentinoid group compared with the DA group. A statistically significant risk of mental health diagnoses with gabapentinoids was not detected, but SUD risk was significant after covariate adjustment. High-risk mental health comorbidities (i.e., SUDs) should be considered when initiating RLS treatments. [ABSTRACT FROM AUTHOR]

This systematic review aims to assess the association between attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for original articles that reported prevalence data on ADHD and RLS until January 24th, 2023. Two independent reviewers evaluated the quality of the articles using the National Institutes of Health assessment tool. Among the 208 articles identified between 1996 and 2022, 29 were included. In large general population studies, 2.6–15.3% of participants met the RLS criteria, of which 3.2–17.4% presented with ADHD. In the ADHD group, RLS symptoms ranged from 11 to 42.9% in children and 20–33.0% in adults. This suggests a strong co-occurrence between RLS and ADHD. A common characteristic of these conditions is sleep fragmentation, as discussed in the reviewed papers. Although large-scale studies with comparable diagnostic criteria across the lifespan are required, our findings may advocate a possible common physiological pathway, including sleep fragmentation and dopaminergic system impairment. [ABSTRACT FROM AUTHOR]

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Restless leg syndrome, also known as Willis-Ekbom disease, is a neurological sensorimotor disorder accompanied by an irresistible urge to move the legs with a fluctuating course of symptoms. It is a common disorder affecting all ages, with existing comorbidities and positive family history being associated with increased prevalence. Herein, we present a case of a 51-year-old female diagnosed with the bipolar affective disorder who developed restless leg syndrome following the use of olanzapine. Olanzapine is a second-generation antipsychotic which can cause restless leg syndrome due to its anti-dopaminergic action on the nervous system, particularly the spinal cord. Existing literature on olanzapine-induced restless leg syndrome has suggested managing this disorder by reducing the dose or replacing olanzapine with other drugs such as clonazepam, quetiapine, and aripiprazole. In our case, olanzapine was not replaced with other medications as the patient showed a significant improvement in bipolar affective disorder symptoms using olanzapine. Instead, clonazepam was added to the treatment regimen which was scheduled to be taken before olanzapine., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Restless legs syndrome or Willis-Ekbom disease (RLS/WED) is a sleep-related movement disorder characterized by an urge to move the legs. This impulse is usually accompanied by an uncomfortable and unpleasant sensation in the legs, which worsens at night and during periods of inactivity and is relieved by movement. Several studies in the literature reported the association between RLS and different antipsychotic medications. with Olanzapine, Quetiapine, and Clozapine identified as the most common causes. The literature suggests that the development of RLS in antipsychotic users may be attributed to the inhibition of dopaminergic neurotransmission or the impact of antipsychotics on iron metabolism. Diagnosing antipsychotic-induced RLS remains a substantial challenge in clinical practice, with challenges in the management of this condition also being widely reported in the current literature. In this article, we will review the evidence suggesting the association between RLS and the use of antipsychotic medications, differentiate between RLS and other movement disorders, and give a brief review of the pathophysiology, diagnosis, and management of RLS and its challenges among psychotic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Saber et al.)