The psychometric properties of the Pearlin Mastery Scale in persons living with restless legs syndrome.

INTRODUCTION: Restless Legs Syndrome (RLS) is a neurological disorder characterized by an urge to move arms and legs, commonly combined with distress, pain and motor restlessness. It can cause fragmented sleep, daytime symptoms, and decreased quality of life. Pharmacological treatment can suppress symptoms, but not cure. When challenged with illness, people may turn to their inner psychological resources such as self-esteem and mastery. The Pearlin Mastery scale was developed to study stress and coping, is commonly used in people with chronic illnesses, however, not yet validated in people with RLS. AIM: The aim was to test reliability and construct validity of the Pearlin Mastery Scale in persons with RLS. METHODS: A cross-sectional postal survey including the Pearlin Mastery Scale, Restless Legs Syndrome-6 Scale, Pittsburgh Sleep Quality Index and Patient Health Questionnaire was sent out to members (n = 1500) of the national RLS association and 788 (52.5%) agreed to participate. Data were analyzed using classical test theory, Confirmatory factor analysis and Rasch measurement theory analysis. Hypothesis testing for construct validity was done by bivariate correlation analyses. RESULTS: Most respondents were women (65%), retired (71%) and had a mean-age of 70.8 years (SD 11.4). The 7-item version of the Pearlin Mastery Scale showed poor fit to the one factor model. After omitting the two positively worded items (i.e., item 4 and 6), the 5-item version was found to be unidimensional, with satisfactory internal consistency. However, all items showed considerable ceiling effects. No measurement variance was seen regarding age-groups or sex. Higher level of mastery was moderately correlated with less depressive symptoms but only weakly correlated to RLS-related sleep problems. CONCLUSION: The 5-item version of the Pearlin Mastery Scale is suggested to be used in persons with RLS due to its acceptable psychometric properties. The instrument could be applied as an outcome measure for behavioral change interventions aiming to support mastery in RLS.

Iron Deficiency and Restless Sleep/Wake Behaviors in Neurodevelopmental Disorders and Mental Health Conditions.

Iron deficiency (ID) and restlessness are associated with sleep/wake-disorders (e.g., restless legs syndrome (RLS)) and neurodevelopmental disorders (attention deficit/hyperactivity and autism spectrum disorders (ADHD; ASD)). However, a standardized approach to assessing ID and restlessness is missing. We reviewed iron status and family sleep/ID history data collected at a sleep/wake behavior clinic under a quality improvement/quality assurance project. Restlessness was explored through patient and parental narratives and a 'suggested clinical immobilization test'. Of 199 patients, 94% had ID, with 43% having a family history of ID. ADHD (46%) and ASD (45%) were common conditions, along with chronic insomnia (61%), sleep-disordered breathing (50%), and parasomnias (22%). In unadjusted analysis, a family history of ID increased the odds (95% CI) of familial RLS (OR: 5.98, p = 0.0002, [2.35-15.2]), insomnia/DIMS (OR: 3.44, p = 0.0084, [1.37-8.64]), and RLS (OR: 7.00, p = 0.01, [1.49-32.93]) in patients with ADHD, and of insomnia/DIMS (OR: 4.77, p = 0.0014, [1.82-12.5]), RLS/PLMS (OR: 5.83, p = 0.009, [1.54-22.1]), RLS (OR: 4.05, p = 0.01, [1.33-12.3]), and familial RLS (OR: 2.82, p = 0.02, [1.17-6.81]) in patients with ASD. ID and restlessness were characteristics of ADHD and ASD, and a family history of ID increased the risk of sleep/wake-disorders. These findings highlight the need to integrate comprehensive blood work and family history to capture ID in children and adolescents with restless behaviors.

Effect of "He Tiao Du Ren An Shen Acupuncture" on restless leg syndrome: A randomized trial.

BACKGROUND: This study aimed to observe the clinical effects of "He Tiao Du Ren An Shen Acupuncture" (HTDRAS Acupuncture) for treating restless leg syndrome (RLS). METHODS: We randomly divided 66 RLS patients into 2 groups: the observation group received "He Tiao Du Ren An Shen Acupuncture" and the control group received conventional acupuncture. All participants were treated once a day, 6 days a week, with 1 day off, for a total of 1 month. Clinical effectiveness of the 2 groups was compared, neurotransmitter levels, the International Restless Leg Syndrome Scale and the Hamilton Anxiety Scale were assessed in both groups. RESULTS: The curative effect in the observation group was better than that in the control group (P < .05). After treatment, the expression of 5-hydroxytryptamine in the observation group was higher than in the control group (P < .05). The International Restless Leg Syndrome Scale and Hamilton Anxiety Scale scores in observation group were lower than those in control group (P < .05). CONCLUSION: "He Tiao Du Ren An Shen Acupuncture" for RLS is significantly effective and safe. It can effectively improve the levels of 5-hydroxytryptamine in RLS patients, alleviate clinical symptoms and reduce anxiety. This treatment has a high clinical application value and is worthy of clinical promotion.

Cost-effectiveness of TOMAC therapy for medication-refractory restless legs syndrome: an updated analysis based on Extension study data.

AIMS: Patients with medication-refractory restless legs syndrome (RLS) have limited therapeutic options available for symptom relief. Tonic motor activation (TOMAC) presents a novel, non-invasive therapy for this patient population. The aim of this study was to conduct an updated cost-effectiveness analysis of TOMAC therapy based on recently available longer-term follow-up data. MATERIALS AND METHODS: A previously published decision-analytic Markov model was utilized to project strategy-specific costs and outcomes over three-years and lifetime for TOMAC compared to status quo treatment (control). Cohort characteristics were based on 24-week clinical data from the extension cohort of the RESTFUL study, which included longer-term follow-up of RESTFUL completers who were assigned to continue or discontinue TOMAC use (TOMAC and control, respectively). The primary analysis outcome was the incremental cost-effectiveness ratio (ICER) in $ per quality-adjusted life year (QALY) gained, calculated using change in International RLS Study Group Rating Scale (IRLS) score as the effect measure. Extensive sensitivity analyses were performed. RESULTS: TOMAC treatment improved IRLS by 5.9 versus control, resulting in estimated utility improvement of +0.05. Over three-years and lifetime, TOMAC added 0.14 and 0.73 QALYs, at incremental costs of $6,751 and $27,440, resulting in projected ICERs of $47,609 and $37,823 per QALY gained, respectively. TOMAC was found to be cost-effective across all tested sensitivity analyses. LIMITATIONS AND CONCLUSION: The inclusion of longer follow-up data in the current analysis confirms earlier exploratory cost-effectiveness findings and suggest TOMAC therapy may provide a high-value treatment option for patients with medication-refractory RLS.

Restless Legs Syndrome (RLS) is a is a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs, with pronounced implications for patients' quality of life. While pharmaceutical treatment options exist, a substantial proportion of patients are considered refractory to drug treatment. Tonic motor activation (TOMAC) therapy is a novel non-invasive neurostimulation approach that was recently cleared for market in the United States. This study sought to provide an updated economic analysis based on recently available data with longer follow-up. The findings of this study, based on data from the RESTFUL Extension study, suggest TOMAC therapy can be a high-value treatment alternative for refractory patients, providing meaningful quality of life improvement at costs that render it cost-effective in the United States. Future data with further extended follow-up will be useful to further broaden the evidence base underpinning these findings.

Exploring sex differences in periodic leg movements during sleep across the lifespan of patients with restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) are prevalent sleep disorders with significant implications for health and well-being. While previous research has highlighted sex-related disparities in RLS and PLMS prevalence, comprehensive understanding of these differences across the lifespan remains limited. This study aims to explore sex differences in RLS and PLMS across diverse age groups, spanning ages 2 to over 80 years, and to investigate the underlying mechanisms influenced by sex hormones. METHODS: A retrospective analysis was conducted on drug-free patients diagnosed with RLS, including 95 females (age range: 2-83.2 years) and 89 males (age range: 2-79.5 years). Polysomnographic recordings were analyzed to assess leg movement activity, including PLMS index and Periodicity index. RESULTS: A more rapid increase in PLMS index was observed in women starting before age 10, plateauing lower than men until around age 55. An increase in women occurred after 55, lasting over a decade, while in men, PLMS index continued to rise after 75. Conversely, Periodicity index displayed a simpler pattern, increasing progressively from prepuberty to around 35 in males and 45-50 in females. Females maintained a slightly higher Periodicity index than males for over a decade after this age. CONCLUSION: These findings underscore the complex interplay between sex hormones, age, and sleep disorders, highlighting the need for tailored approaches to diagnosis and management across diverse demographic cohorts. Further research is warranted to elucidate the underlying mechanisms and develop targeted interventions to optimize sleep health outcomes.

Iron deficiency-related symptoms in non-anemic whole blood donors.

INTRODUCTION: Whole blood donors are at increased risk for iron deficiency (ID). ID anemia is associated with several symptoms, such as fatigue, cognitive dysfunction, pica, and restless leg syndrome (RLS). However, it is unclear if these symptoms also occur when a donor has developed ID without anemia. This study aims to determine whether non-anemic ID (NAID) is associated with the occurrence of ID-related symptoms. STUDY DESIGNS AND METHODS: We combined data from three studies in whole blood donors (i.e., Donor Insight-III, FIND'EM, and FORTE) to create a substantial sample size (N = 12,143). The self-reported occurrence and severity of ID-related symptoms, such as physical and mental health, fatigue, cognitive functioning, pica, and RLS, was measured using validated questionnaires. Associations were studied using logistic regression modeling with ID-related symptoms derived from the questionnaires as the dependent variable and ferritin level group (0-15 µg/L, 15-30 µg/L, and >30 µg/L) as explanatory variable. RESULTS: After applying inclusion and exclusion criteria, 9829 donors were eligible for analysis. In the models corrected for age, body mass index, Hb level, and cohort, only fatigue was shown to be associated with ferritin levels in men, showing lower odds (OR 1.41, 95% CI 1.11-1.79) for fatigue with higher ferritin levels. CONCLUSION: In these studies, NAID was only associated with self-reported fatigue in male donors. Although selection bias may have led to underestimated associations, ferritin measurements in donors should be primarily considered as a measure to prevent anemia, rather than to prevent or mitigate NAID-related symptoms.

Prevalence of restless legs syndrome during pregnancy and postpartum period.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 %). CONCLUSIONS: 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.

Restless Legs Syndrome Affects Sleep in de novo Parkinson's Disease Patients.

BACKGROUND: Restless legs syndrome (RLS) is common in Parkinson's disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. OBJECTIVE: This study aimed to identify the clinical factors affected by RLS in patients with PD. METHODS: We included 369 de novo PD patients. RLS was assessed by face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RESULTS: RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the sleep/fatigue domain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. CONCLUSIONS: RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.

Rethinking clinical trials in restless legs syndrome: A roadmap.

The number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks. In particular, we recommend developing alternative scoring methods for more accurate RLS diagnosis, thereby improving clinical trial specificity. Furthermore, enhancing the precision of endpoints will increase study effect sizes and mitigate study costs. Suggestions to achieve this include developing online, real-time sleep diaries with high-frequency sampling of nightly sleep latency and the use of PLMs as surrogate markers. Furthermore, to reduce the placebo response, strategies should be adopted that include placebo run-in periods. As RLS is frequently a chronic condition, priority should be given to long-term studies, using a randomized, placebo-controlled, withdrawal design. Lastly, new populations should be investigated to develop targeted treatments such as mild RLS, pregnancy, hemodialysis, or iron-deficient anemia.

Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis.

OBJECTIVE/BACKGROUND: There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. PATIENTS/METHODS: A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. RESULTS: IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham -2.17; mean difference (MD) = -4.42; 95 % confidence interval [CI] -1.57 to -7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = -4.50; p = 0.02) and medication-naïve (MD = -4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = -4.30; 95 % CI -1.36 to -7.24; p = 0.004). CONCLUSIONS: The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants.

Response to iron supplementation is similar between boys and girls with pediatric sleep movement disorders.

OBJECTIVES: This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD). METHODS: Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I). RESULTS: In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes. CONCLUSION: The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

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.

The effect of compression stockings on the complaints well-being and sleep quality of pregnant women with restless legs syndrome: a randomized controlled study.

OBJECTIVE: The aim of this study was to determine the effect of compression stockings on complaints, well-being, and sleep quality in pregnant women with restless legs syndrome. METHODS: This randomized placebo-controlled study was conducted on 63 pregnant women (placebo group [PG]=31; experimental group [EG]=32) at the Perinatology Outpatient Clinic of a Health Research and Application Centre in Turkey. Pregnant women in the experimental group wore compression stockings when they got up in the morning for 3 weeks and took them off at bedtime. Placebo group women wore a placebo stocking. Data were collected using the restless legs syndrome Severity Rating Scale, the Pittsburgh Sleep Quality Index, the World Health Organization-5 Well-Being Index, and the Application Satisfaction Form on the 22nd day of the first interview. Statistical significance was accepted as p<0.05. RESULTS: Post-test mean scores of both the experimental group and placebo group in the restless legs syndrome Severity Rating Scale (post-test:;8.87±5.27, 12.19±5.60; pre-test:;21.28±5.63, 21.0±5.61; p<0.05), the Pittsburgh Sleep Quality Index (post-test:;5.34±3.28, 6.12±3.12; pre-test:;10.15±4.23, 9.61±4.59; p<0.05), and Well-Being Index (post-test:;18.06±4.59, 19.00±4.47; pre-test:;12.71±5.85, 15.09±5.62; p<0.05) showed recovery according to the pre-tests. However, the post-test restless legs syndrome Severity Rating Scale of the experimental group was lower than that of the placebo group (p<0.05). The effect of their application started in 3.93±1.74 days on average in the experimental group, while it started in 5.09±1.55 days in the placebo group (p<0.05). CONCLUSION: Both applications reduced the severity of restless legs syndrome in pregnant women and increased sleep quality and well-being. However, compression stockings were more effective in reducing restless legs syndrome severity. Nurses can use compression and placebo stockings in the care of pregnant women with restless legs syndrome. CLINICAL TRIAL REGISTRATION NUMBER: NCT05795868.

Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility. METHODS: We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). RESULTS: Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (LMX1B, rs35196838, OR 1.14, 95% CI 1.09-1.19, p value = 2.2 × 10-9). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p value = 5.4 × 10-7), depression (rg = 0.35, se = 0.06, p value = 2.17 × 10-8), and intelligence (rg = -0.20, se = 0.06, p value = 4.0 × 10-4). INTERPRETATION: Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024;96:994-1005.

Sleep-related disorders in patients with precapillary pulmonary hypertension.

Precapillary pulmonary hypertension (PcPH) is associated with the development of sleep-related disorders and impairment of sleep quality. With growing recognition of the clinical relevance of sleep-related conditions in PcPH, this narrative review seeks to discuss the spectrum of disorders encountered in clinical practice, pathophysiological mechanisms linking PcPH with sleep-related disorders, and potential therapeutic considerations. Current evidence demonstrates a higher prevalence of impaired sleep quality, sleep-disordered breathing, sleep-related hypoxia, and restless leg syndrome in patients with PcPH. These sleep-related disorders could further lead to impairment of quality of life in a patient population with already a high symptom burden. Recent data suggest that sleep-related hypoxia is strongly linked to worse right ventricular function and higher risk of transplantation or death. However, limited studies have investigated the role of oxygen therapy or positive airway pressure therapy improving symptoms or outcomes. Abnormal iron homeostasis is highly prevalent in PcPH and may contribute to the development of restless legs syndrome/periodic limb movement of sleep. To improve sleep management in PcPH, we highlight future research agenda and advocate close collaboration between pulmonary hypertension specialists and sleep physicians.

Prevalence of depression or depressive state in patients with restless legs syndrome: A systematic review and meta-analysis.

Restless legs syndrome (RLS) is a common sleep-related disorder characterized by limb discomfort and the urge to move them when at rest, especially in the evening or at night. Although depression is often linked to various conditions, no systematic review has assessed depression prevalence in patients with RLS after the latest diagnostic criteria revision. This systematic review and meta-analysis aimed to investigate the depression and depressive state prevalence among patients with RLS. We systematically searched databases up to November 2022 and performed meta-analyses of the depression prevalence using a random-effects model and a meta-regression analysis to explore the relationship between the prevalence and severity of depression and factors such as age and RLS severity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we analyzed 24 studies with 2039 patients. The pooled depression or depressive state prevalence, mostly defined by questionnaire scores, was 30.39 %. Nine studies reported the proportion of patients taking antidepressants (pooled rate: 3.41 %). No specific factors related to the prevalence or severity of depression were identified in patients with RLS. These findings highlight the significant prevalence of depression and underscore the need for future research with standardized diagnostic interviews and consistent methodologies across multi-site studies.

Current and emerging pharmaceutical strategies for the treatment and management of restless legs syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is a sensory-motor sleep disorder that affects up to 13% of adults in the Western world and 2-4% of children. It impairs night sleep with an impact on daily performances and life quality. Thus, moderate-to-severe RLS requires pharmacological treatment. AREAS COVERED: In the present review, which is based on PubMed searches with no time limits, the authors discuss the recommended pharmacotherapy for RLS in addition to other emerging treatment options. The authors provide coverage to the current recommendations for both adults and pediatric patients with RLS. EXPERT OPINION: Current evidence suggests removing all causes of secondary RLS, including iron deficiency, chronic renal failure, drugs, and treating other sleep disorders that may worsen symptoms. Also, intermittent RLS should be addressed with behavioral measures and on-demand therapy. For chronic persistent RLS, α2δ calcium channel ligands are a first-line pharmacological approach, whereas dopamine agonists are associated with increased risk and should be spared. When RLS is refractory to first-line treatment, polytherapy, or opioid monotherapy should be considered. Nonetheless, some patients may not reach sustained symptom relief. Further research is needed to better understand the pathophysiology of RLS and to develop newer more effective drugs.

Effects of Dietary Supplementation in Patients with Restless Legs Syndrome: A Systematic Review.

Restless legs syndrome (RLS) is a common neurological disorder. It disrupts sleep and well-being and is often associated with other conditions. This review examines the potential of dietary supplements to manage RLS symptoms and reduce reliance on medications. A total of 10 randomized clinical trials involving 482 participants were analyzed, focusing on the impact of various supplements on symptom severity, sleep quality, and daytime sleepiness. Findings suggest some supplements may have positive results. Magnesium oxide and vitamin B6 significantly improved sleep quality and RLS symptoms, with magnesium showing greater effectiveness. Vitamin D supplementation did not show significant benefits. Oral iron has promising results, indicating potential efficacy but issues related to compliance and absorption. Both vitamins C and E positively affect RLS symptoms, likely due to their antioxidant properties. Valerian improved RLS and sleep but did not show a statistically significant improvement. Despite these encouraging results, a high risk of bias was noted in half of the studies, emphasizing the need for more rigorous research. Overall, this review suggests that dietary supplements may be a promising approach to managing RLS. However, further investigation is required to confirm the efficacy and safety.

Effect of dairy products fortified with vitamin d3 on restless legs syndrome in women with premenstrual syndrome, abdominal obesity and vitamin d deficiency: a pilot study.

BACKGROUNDS: Restless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D3 on RLS in women with PMS. MATERIALS AND METHODS: We conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires. RESULTS: The results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19-28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05). CONCLUSION: Fortifying dairy products with vitamin D3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups.