Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study.

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

The Effect of Hot and Cold Water Applications on Restless Legs Syndrome Complaints and Sleep Quality of Pregnant Women: A Randomized Controlled Study.

Background: Pregnant women experience restless legs syndrome and intervention studies are needed to prevent this. This study evaluated the effect of hot and cold water applications on the severity of restless leg syndrome and sleep quality in pregnant women. Methods: It is a randomized controlled trial. The subjects comprised 80 (hot water group = 26, cold water group = 27, control group = 27) pregnant women. Pregnant women in intervention groups applied hot or cold water to their legs before going to bed for seven days. The control group did not do any application other than routine care. The data were collected with the Restless Legs Syndrome Diagnostic Form, Personal Information Form, Restless Leg Syndrome Severity Grading Scale, The Pittsburgh Sleep Quality Index, Application Satisfaction Form, and Post-Application Follow-up Chart. Results: While the Restless Legs Syndrome Severity Grading Scale and Pittsburgh Sleep Quality Index pre-test scores of the groups were similar (P > .05), the post-test scores were lower in the intervention groups than in the control group (P < .001). The effect of the applications started on the second day and the level of satisfaction with the application was similarly high in both groups (P < .05). During the follow-up, the syndrome severity scores of both the intervention groups were similar (P > .05), while the sleep quality of the cold group was better (P < .05) and most of the pregnant women did not need reapplication and they were satisfied with the application (P < .05). Conclusion: These safe interventions reduced the severity of restless legs syndrome in pregnant women and improved the quality of their sleep. Nurses can use these applications in pregnancy care, which begin to show effect in as little as two days.

Treatment of primary restless legs syndrome with Fu's subcutaneous needling: A case report.

RATIONALE: Fu's subcutaneous needling (FSN) is a novel acupuncture technique developed based on traditional needling principles that aims to alleviate diseases by improving local muscle conditions and blood supply. FSN have been widely used for the treatment of various diseases. Restless legs syndrome (RLS) is a common central nervous system disorder characterized by intense discomfort in the legs, particularly at night, leading to an urge to move the legs for relief. In this study, we report a case in which FSN was used to treat primary RLS. PATIENT CONCERNS: A 67-year-old patient complained of nocturnal discomfort in the right leg for over 4 months, the symptoms occurred 2-3 times, with uncontrollable movement impulses in the right leg during the onset, accompanied by a burning sensation, lasting about 2 h, accompanied by anxiety and insomnia. Imaging examinations revealed no spinal stenosis or history of kidney disease, rheumatic disease, diabetes, or Parkinson's disease. DIAGNOSES: The patient was diagnosed with primary RLS, and the International Restless Legs Syndrome Study Group rating scale (IRLS) score was 26. INTERVENTIONS: FSN was successfully performed three times per week on different days. No adverse and unanticipated events while the treatment. The total treatment course lasted for six weeks. OUTCOMES: After the treatment, the patient reported that the recent onset interval was approximately 10 days, each time lasting approximately 15 min. The patient's IRLS score was 5, After a follow-up of 2 months following the end of treatment, the patient reported that the incidence of RLS was approximately one episode within two weeks,each lasting approximately 10 min. LESSONS: FSN significantly improved leg discomfort and desire for leg movement in patients with RLS. FSN may exert its therapeutic effects by influencing connective and muscular tissues, thereby improving the condition of the central nervous system and the local blood supply in the legs. However, due to the limitation of a single clinical observation case, a randomized clinical trial with a sufficient follow-up time is needed.

Sex-specific patterns of discomfort in patients with restless legs syndrome.

STUDY OBJECTIVES: Sex differences in the prevalence of restless legs syndrome (RLS) have been reported, with a higher prevalence in women than in men. However, sex differences in clinical presentation remain unclear. We aimed to investigate the phenotypic differences in patients with RLS between sexes by comparing clinical presentations, iron status, polysomnographic parameters, and treatment. METHODS: We retrospectively evaluated 614 patients (225 men, 389 women) diagnosed with RLS. To enhance the robustness of the study, an age-matched control group of 179 men and 286 women without sleep disorders was also included. Information on demographics and sleep-related questionnaires were collected. Iron status was evaluated using blood samples, and polysomnography was performed to evaluate periodic leg movements and comorbid sleep disorders. RESULTS: Our analysis revealed no sex difference in the severity of RLS but a difference in the pattern of symptoms. Women had more frequent symptoms of pain and awakening during sleep, while men had more common motor symptoms (both self-reported symptoms and periodic leg movement on polysomnography). Women with RLS also had lower iron parameters and received more frequent iron supplementation therapy than men. In contrast to women with RLS, who presented higher sleep disturbances and depressive mood, men with RLS had a higher risk of comorbidities such as hypertension and cardiovascular disease. These sex differences were notably more pronounced than in the control group. CONCLUSIONS: This study suggests that sex differences exist in RLS phenotypes, and clinicians should consider these differences for treatment. CITATION: Kim J, Kim JR, Park HR, Joo EY. Sex-specific patterns of discomfort in patients with restless legs syndrome. J Clin Sleep Med. 2024;20(2):253-259.

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.

[Restless sleep disorder a new entity to considered in children]. / Trastorno de sueño inquieto: una nueva entidad clínica a considerar en niños.

Restless sleep disorder (RSD) is a condition recently described by a group of sleep experts who developed diagnostic and polysomnographic criteria after conducting a comprehensive review of the available literature where poor sleep or restless sleep is a symptom alone or that accompanies other disorders. This group defined RSD as a condition characterized by parental complaints of frequent jerking movements during sleep, position changes, and sleep disruption that cause significant impairment during the day. Diagnostic criteria include the presence of symptoms for at least 3 months, 3 times a week, and at least 5 movements per hour on polysomnography. Changes in behavior during the day, such as drowsiness, irritability, and hyperactivity that are not explained by a medical, pharmacological, or behavioral condition, should be considered. Its estimated prevalence is 7.7% of children referred for sleep problems. Children often have ferritin levels below 50 µg/l, a point in common with restless legs syndrome. Treatment consists of iron supplements, which have shown benefits in these children. To establish the diagnosis, secondary symptoms of medical origin or other sleep disorders such as restless legs syndrome or periodic limb movement disorder must be ruled out. The objective of this report is to review the current recommendations on this entity, describe the clinical, pathophysiological, and polysomnographic keys, in order to highlight the need to publicize this condition and expand studies in age groups other than those already defined and to generate treatment guidelines.

The Relationship between Serum Selenium Levels and Restless Leg Syndrome in Chronic Kidney Disease Patients.

Background and Objectives: Chronic kidney disease (CKD) is a global public health issue with rising incidence linked to substantial morbidity and mortality. Selenium, an antioxidant trace element, has been linked to low serum levels in end-stage renal disease. Restless Leg Syndrome (RLS), a sleep disorder, is prevalent in CKD patients and significantly impacts their quality of life. The objective of this study was to examine the correlation between serum selenium levels and the prevalence of restless leg syndrome in individuals with chronic kidney disease. Materials and Methods: Forty-six CKD patients undergoing serum selenium level assessments between 1 January 2020 and 28 February 2022, at the Hitit University Faculty of Medicine Department of Nephrology Outpatient Clinic or Hemodialysis Unit, were included. Patients over 18 years of age with no history of hematological or oncological diseases or acute or chronic inflammatory conditions were included in the study groups. Patients taking selenium supplements were excluded. Demographic data, comorbidities, and laboratory values were collected, and RLS presence and severity were evaluated. Statistical analyses include descriptive statistics, correlation analysis, the Mann-Whitney U test, Student's t test, and Chi-square test. Results: Among the 46 patients, 16 (34.78%) had RLS symptoms. The patient group included 34.78% predialysis, 34.78% peritoneal dialysis, and 30.44% hemodialysis patients, with a median age of 47.98 years. There was no difference in age, gender, and Charlson comorbidity between patients with or without RLS (p = 0.881, p = 0.702, p = 0.650). RLS prevalence varied across CKD subgroups, with hemodialysis patients having a higher prevalence (p = 0.036). Clinical parameters such as blood urea nitrogen, creatinine, calcium, phosphorus, platelet counts, and parathyroid hormone levels exhibited significant differences between patients with and without RLS (p < 0.05). Serum selenium levels were not significantly different between patients with and without RLS (p = 0.327). Conclusions: With an increased comorbidity burden, CKD poses a significant healthcare challenge. When accompanied by RLS, this burden can be debilitating. The difference in CKD stages between groups has shed light on a critical determinant of RLS in this population, emphasizing the role of the chronic kidney disease stage. In our study, serum selenium levels were not associated with the presence and severity of RLS. However, prospective studies with larger numbers of participants are needed to draw a definitive conclusion.

Hydrotherapy and acupressure in restless legs syndrome: A randomized, controlled, 3-armed, explorative clinical trial.

BACKGROUND: Restless legs syndrome (RLS) is a common neurological disease that has a significant impact on daily activities and quality of life, for which there is often no satisfactory therapy. Complementary medicine, such as acupressure and hydrotherapy, is used to treat patients with RLS; however, the clinical evidence is unclear. This study aims to investigate the effects and feasibility of self-administered hydrotherapy and acupressure in patients with RLS. METHODS: This is a randomized, controlled, open-label, exploratory, clinical study with 3 parallel arms, comparing both self-applied hydrotherapy (according to the German non-medical naturopath Sebastian Kneipp) and acupressure in addition to routine care in comparison to routine care alone (waiting list control) in patients with RLS. Fifty-one patients with at least moderate restless-legs syndrome will be randomized. Patients in the hydrotherapy group will be trained in the self-application of cold knee/lower leg affusions twice daily for 6 weeks. The acupressure group will be trained in the self-application of 6-point-acupressure therapy once daily for 6 weeks. Both interventions take approximately 20 minutes daily. The 6-week mandatory study intervention phase, which is in addition to the patient preexisting routine care treatment, is followed by a 6-week follow-up phase with optional interventions. The waitlist group will not receive any study intervention in addition to their routine care before the end of week 12. Outcome parameters including RLS-severity, disease and health-related quality of life (RLS-QoL, SF-12), Hospital Anxiety and Depression Score in German version, general self-efficacy scale, and study intervention safety will be measured at baseline and after 6 and 12 weeks. The statistical analyses will be descriptive and exploratory. CONCLUSION: In the case of clinically relevant therapeutic effects, feasibility, and therapeutic safety, the results will be the basis for planning a future confirmatory randomized trial and for helping to develop further RLS self-treatment concepts.

[Pharmacological Treatment for Restless Legs Syndrome].

Restless legs syndrome (RLS) is a neurological disorder that causes insomnia and daytime functional disability due to an urge to move the legs usually accompanied by uncomfortable sensations. Non-pharmacologic treatment includes regular sleep habits and exercise. Iron supplementation is indicated for patients with low serum ferritin levels. Antidepressants, antihistaminergics, and dopamine antagonists should be reduced or discontinued because they induce RLS symptoms. Dopamine agonists and alpha 2-delta ligands are the first-line pharmacological treatments for RLS.

The effect of progressive muscle relaxation exercise on the intensity of symptoms and quality of sleep and quality of life in pregnant women with restless leg syndrome.

OBJECTIVE: This study, accordingly, was conducted with the purpose of investigating the effect of progressive muscle relaxation exercise on the intensity of restless leg syndrome (RLS) and RLS-related quality of life and sleep in pregnant women with RLS. METHODS: This one-centered, parallel randomized controlled study was conducted with 52 pregnant women. 27-28th of pregnancy, progressive muscle relaxation exercises training was shown and they were asked to practice them 3 times a week for 8 weeks. RESULTS: It was found that the RLS Intensity Scale and PSQI posttest mean scores of the women in experiment group are lower on a statically significant level than the mean scores of the women in control group (p = 0.000 and p = 0.001). It was detected that the RLS-Qol posttest mean scores of the women in the experiment group are higher than the mean scores in the control group on a statistically significant level (p = 0.000). CONCLUSIONS: It was seen that progressive muscle relaxation exercises alleviate RLS intensity and symptoms and improve RLS-related quality of life and sleep in pregnant women. PRACTICE IMPLICATION: Progressive muscle relaxation exercises are beneficial for pregnant women and can be easily integrated into practice.

Vitamin D and Restless Legs Syndrome: A Review of Current Literature.

This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vitamin D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interaction of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the paradoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care. Highlights  Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.

Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial.

INTRODUCTION: This study aimed to compare the effect of valerian and gabapentin on restless legs syndrome (RLS) and sleep quality in HD patients. METHODS: In this cross over clinical trial study, 40 HD patients allocated into a valerian and gabapentin group. In the first phase of the study, Group A received valerian and Group B received gabapentin 1 h before bedtime for 1 month. In the second phase, the two groups' treatment regimen was swapped. After a 1-month washout period, the same process was repeated on the crossover groups. RESULTS: After the first phase, the mean score of RLS was lower in the gabapentin group. But there was no statistically significant difference between the two groups in terms of sleep quality score before and after the first and second interventions. CONCLUSION: Gabapentin is more effective than valerian in improving RLS, but both are equally effective in improving sleep quality.

Restless Legs Syndrome and Restless Sleep Disorder in Children.

Restless legs syndrome (RLS) affects 2% of children presenting with symptoms of insomnia, restless sleep, decreased quality of life, and effects on cognition and behavior. The International RLS Study Group and the American Academy of Sleep Medicine have published guidelines for the diagnosis and treatment of RLS in children. Restless sleep disorder has been recently identified in children and presents with frequent movements during sleep and daytime symptoms with polysomnography findings of at least 5 large muscle movements at night. Treatment options for both disorders include iron supplementation, either oral or intravenous with improvement in nighttime and daytime symptoms.

Restless Legs Syndrome and Periodic Limb Movements of Sleep: From Neurophysiology to Clinical Practice.

SUMMARY: This article summarizes restless legs syndrome (RLS), periodic limb movements of sleep, and periodic limb movement disorder. RLS is a common sleep disorder with a prevalence of 5% to 15% in the general population. RLS can present in childhood, and incidence increases with age. RLS can be idiopathic or secondary to iron deficiency, chronic renal failure, peripheral neuropathy, and medications such as antidepressants (with higher rates for mirtazapine and venlafaxine, while bupropion may reduce symptoms at least in the short term), dopamine antagonists (neuroleptic antipsychotic agents and antinausea medications), and possibly antihistamines. Management includes pharmacologic agents (dopaminergic agents, alpha-2 delta calcium channel ligands, opioids, benzodiazepines) and nonpharmacologic therapies (iron supplementation, behavioral management). Periodic limb movements of sleep are an electrophysiologic finding commonly accompanying RLS. On the other hand, most individuals with periodic limb movements of sleep do not have RLS. The clinical significance of the movements has been argued. Periodic limb movement disorder is a distinct sleep disorder that arises in individuals without RLS and is a diagnosis of exclusion.

A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use.

Background: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review. Methods: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents. Results: Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties. Discussion: Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

Alterations of the thalamic nuclei volumes and intrinsic thalamic network in patients with restless legs syndrome.

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. - 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.

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.

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

STUDY OBJECTIVES: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible. METHODS: The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis. RESULTS: Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation. CONCLUSIONS: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed. CITATION: Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(4):811-822.