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.

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.

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.

Restless leg syndrome in systemic lupus erythematosus: Associations with disease activity, quality of life and depression.

OBJECTIVES: The aim of this study was to determine the prevalence of restless leg syndrome (RLS) among patients with SLE, describe their clinical characteristics, examine its impact on health-related quality of life (HRQoL), and evaluate its association with depression. METHODS: A total of 124 SLE patients were recruited, with data on demographics, and clinical features collected. RLS diagnosis was based on the international RLS study group criteria, while depression was assessed by the patient health questionnaire. HRQoL was assessed by a disease-specific validated questionnaire, the LupusQoL, pain intensity was examined through the pain visual analogue scale, and disease activity was evaluated via the patient global assessment. These variables were compared between SLE patients with RLS and without RLS using t-tests or Wilcoxon and the chi-square test of independence for categorical variables. A p-value ≤0.05 was considered statistically significant. RESULTS: Among the SLE patients (mean age 48, 87.1 % women), 32 % had RLS. The SLE patients with RLS were found to have a longer delay in diagnosis (1 vs 0.5 years; p = 0.019) and were less likely to be employed (65 % vs 45 %, p = 0.040) compared to non-RLS patients. In addition, RLS patients were more likely to have coexisting Major Depressive Disorder (MDD) (p = 0.019), higher levels of pain (p = 0.006) and disease activity based on patient global assessment (p = 0.014). Further, most of the domains of LupusQoL were significantly lower in the RLS patients group suggesting a worse HRQoL. CONCLUSION: RLS was present in one-third of the SLE cohort, significantly impairing HRQoL and correlating with depression, higher pain, and increased disease activity. These findings underscore the importance of early RLS detection and management in SLE patients.

Prevalence and clinical profile of patients with restless legs syndrome in Parkinson's disease: A meta-analysis.

INTRODUCTION: Restless legs syndrome (RLS) is a sensorimotor disorder of sleep/wake regulation characterized by an urge to move the legs accompanied by a wide range of sensory symptoms, mainly affecting the lower limbs. An increased incidence of RLS has been demonstrated in Parkinson's disease (PD) and has been associated with severe motor and non-motor manifestations. We aimed to provide a reliable estimate of RLS prevalence and the clinical features associated with its occurrence in PD (PD-RLS). METHODS: We performed a systematic literature search up to January 2024 using PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with or without RLS, and these proportions were used to estimate the prevalence of PD-RLS. Clinical profile associated with PD-RLS was explored by comparing the clinical characteristics of PD patients with and without RLS. RESULTS: Forty-six studies were included in the meta-analysis. Pooled RLS prevalence was 20 % of a total sample of 6990 PD patients and was associated with female sex, mixed motor phenotype, worse motor disturbances and functional disability, and a wide range of non-motor symptoms such as sleep disorders, cognitive and autonomic dysfunctions, and more severe neuropsychiatric manifestations. Sensitivity analyses indicated significant associations of PD-RLS with variables related to dopaminergic therapy. No association was found with serum ferritin, serum iron and hemoglobin levels. CONCLUSIONS: The prevalence of PD-RLS exceeds that reported in the general population, suggesting the existence of a relationship between the two disorders. Dopaminergic treatment seems to play an ambivalent role relieving, worsening or "mimicking" RLS manifestations. However, the clinical profile of PD-RLS patients, characterized by a greater severity of non-motor symptoms, also suggests that neurotransmitter systems other than the dopaminergic one are involved in PD-RLS etiology.

Sleep disturbances and associated factors in patients with Parkinson's disease.

AIMS: This study aimed to describe clinical characteristics and sleep quality of Parkinson's Diseases (PD) patients and identify associated factors with sleep quality. METHODS: A cross-sectional study was conducted at the National Geriatric Hospital, Hanoi, Vietnam, from December 2022 to April 2023. A total of 130 Parkinson's disease patients undergoing treatment at the hospital were invited. Demographic and clinical characteristics were obtained. The diagnosis of sleep disorders was based on the standards outlined in the DSM-V. A multivariate logistic regression model was employed. RESULTS: 90.9 % experienced sleep disorder, with the significant types including insomnia (76.2 %) and restless legs syndrome (56.2 %). The majority of patients suffered two (33.1 %) and one kind of sleep disorder (32.3 %). Most patients experienced sleep disorders after diagnosis of PD (80.0 %). Only having shoulder and neck pain was positively associated with a likelihood of having sleep disturbances (OR=4.87, 95 %CI=1.18-20.15). CONCLUSION: This study found a high rate of sleep disorders among PD patients in our sample. Shoulder and neck pain was found to be associated with a risk of sleep disorders. Pain management should be performed to improve the sleep quality of PD patients.

Medication refractory restless legs syndrome: Real-world experience.

BACKGROUND: Restless Legs Syndrome (RLS), impacting 5-13% of the population, poses challenges in long-term management. A knowledge gap exists in predicting resistance to first-line therapies. OBJECTIVE: To identify demographic and clinical factors predictive of refractory cases. METHODS: This retrospective study, conducted at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas (January 2018 to September 2023) identified all patients with RLS evaluated during the pre-specified period and compared clinical and demographic data between medication-refractory ("malignant") group and "benign" cohort. RESULTS: Among 132 patients with RLS, 23 (17.4%) were categorized as medication-refractory. This cohort was characterized by a significantly lower mean age at onset (39.3 vs. 53.5 years, p = 0.0005), longer disease duration (26.7 vs. 14.0 years), and a higher prevalence of a positive family history of RLS among first-degree relatives compared to the "benign" group (56.5% vs. 15.5%, p = 0.003). Furthermore, compared to the "benign" group, in the refractory group dopamine agonists were initiated as the primary medication at a significantly higher rate (p = 0.006). CONCLUSION: Our study found that a younger age at disease onset, prolonged disease duration, initial use of dopamine agonists, and a positive family history increased the likelihood of refractory RLS. We caution against the use of dopamine agonists, especially in young patients with RLS. Additionally, botulinum toxin might be considered a viable second-line treatment, especially for patients with otherwise medically-refractory RLS.

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.

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 Non-Pharmacological Methods Used for Restless Leg Syndrome in Pregnancy on the Severity of the Syndrome and Sleep: A Systematic Review and Meta-Analysis.

Background: Non-pharmacological methods are primarily recommended for the treatment and care of pregnant women with restless legs syndrome. This study aimed to determine the effectiveness of non-pharmacological methods in reducing the severity of restless legs syndrome and improving sleep quality in pregnant women, based on the results of previous studies. Methods: A systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies was conducted. Studies published between 14 February 2022 and 22 March 2023 in DergiPark, Turkish Clinics, ULAKBIM, Higher Education Council National Thesis Center, ProQuest Dissertations, EBSCOhost (Medline, CINAHL), OVID-LWW, Web of Science, PubMed, Scopus, and ClinicalStudys.gov databases were identified by keywords. Results: Six articles with a total sample size of 359 (intervention group: 312; control group: 107) were included in the meta-analysis. The combined results of these studies showed that non-pharmacological methods significantly reduced the severity of restless legs syndrome (MD: -13.00, Z = 7.29, P < .0001). In the subgroup analysis performed based on the type of intervention methods used, relaxing background music, progressive muscle relaxation exercises, sleep hygiene training, and hot and cold water applications were found to be effective. In addition, this meta-analysis showed that non-pharmacological methods significantly improved sleep quality (MD: -3.73, Z = 12.49, P < .00001). Conclusion: By using a non-pharmacological method with proven effectiveness, it is possible to reduce the discomfort associated with pregnancy-related restless legs syndrome and improve sleep quality.

Sleep duration, napping behaviors and restless legs syndrome during pregnancy and the trajectories of ultrasonographic measures of fetal growth: Findings from the NICHD Fetal Growth Studies-Singletons.

OBJECTIVES: Given the plausible mechanisms and the lacking of empirical evidence, the study aims to investigate how gestational sleep behaviors and the development of sleep disorders, such as restless legs syndrome, influence ultrasonographic measures of fetal growth. METHODS: The study included 2457 pregnant women from the NICHD Fetal Growth Studies - Singletons (2009-2013), who were recruited between 8-13 gestational weeks and followed up to five times during pregnancy. Women were categorized into six groups based on their total sleep hours and napping frequency. The trajectory of estimated fetal weight from 10-40weeks was derived from three ultrasonographic measures. Linear mixed effect models were applied to model the estimated fetal weight in relation to self-reported sleep-napping behaviors and restless legs syndrome status, adjusting for age, race and ethnicity, education, parity, prepregnancy body mass index category, infant sex, and prepregnancy sleep-napping behavior. RESULTS: From enrollment to near delivery, pregnant women's total sleep duration and nap frequency declined and restless legs syndrome symptoms frequency increased generally. No significant differences in estimated fetal weight were observed by sleep-napping group or by restless legs syndrome status. Results remained similar in sensitivity analyses and stratified analyses by women's prepregnancy body mass index category (normal vs. overweight/obese) or by infant sex. CONCLUSIONS: Our data indicate that there is no association between sleep during pregnancy-assessed as total sleep duration and napping frequency, nor restless legs syndrome symptoms-and fetal growth from weeks 10 to 40 in healthy pregnant women.

Sleep regulation and host genetics.

Due to the multifactorial and complex nature of rest, we focus on phenotypes related to sleep. Sleep regulation is a multifactorial process. In this chapter, we focus on those phenotypes inherent to sleep that are highly prevalent in the population, and that can be modulated by lifestyle, such as sleep quality and duration, insomnia, restless leg syndrome and daytime sleepiness. We, therefore, leave in the background those phenotypes that constitute infrequent pathologies or for which the current level of scientific evidence does not favour the implementation of practical approaches of this type. Similarly, the regulation of sleep quality is intimately linked to the regulation of the circadian rhythm. Although this relationship is discussed in the sections that require it, the in-depth study of circadian rhythm regulation at the molecular level deserves a separate chapter, and this is how it is dealt with in this volume.

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

The global and regional prevalence of restless legs syndrome among adults: A systematic review and modelling analysis.

Background: Restless legs syndrome (RLS) is a prevalent neuro-sensory disorder that impairs quality of life. In this systematic review and modelling study, we estimated the global and regional prevalence of RLS and its associated factors. Methods: We searched PubMed, Embase, and Medline for population-based studies on RLS prevalence published up to 12 November 2023. The included studies reported prevalence using the International Restless Leg Syndrome Study Group's (IRLSSG) minimal diagnostic criteria without limitations on frequency, duration, or severity. We applied a multilevel multivariable mixed-effects meta-regression to generate the age-specific and sex-specific prevalence of RLS for high socio-demographic index (H-SDI) and low and middle socio-demographic index (LM-SDI) regions. We pooled odds ratios (ORs) for RLS associated factors using random-effects models. Finally, we derived the regional prevalence and cases of RLS based on an associated factor-based model. Results: From 52 articles across 23 countries, the global RLS prevalence in 2019 was estimated to be 7.12% (95% confidence interval (CI) = 5.15-9.76) among adults 20-79 years of age, equating to 356.07 million (95% CI = 257.61-488.09) affected individuals. Prevalence was similar in H-SDI (7.29%; 95% CI = 5.04-10.41) and LM-SDI (7.10%; 95% CI = 5.16-9.70) regions, with the majority of cases in LM-SDI countries (323.06 million; 90.73%). Europe had the highest (7.60%; 95% CI = 5.44-10.52) and Africa the lowest regional prevalence (6.48%; 95% CI = 4.70-8.87). The Western Pacific Region, meanwhile, had the most cases (111.91 million; 95% CI = 80.93-153.42). Factors positively associated with RLS included advanced age (OR = 1.13; 95% CI = 1.04-1.24), smoking (OR = 1.46; 95% CI = 1.29-1.64), depression (OR = 1.71; 95% CI = 1.26-2.32), and diabetes (OR = 1.54; 95% CI = 1.19-1.97). Conclusions: A considerable global burden of RLS exists. Effective strategies are needed to increase awareness and optimise resource allocation to address this often-overlooked condition. High-quality epidemiological investigations employing standardised and rigorous criteria for RLS are essential for addressing RLS burden more effectively. Registration: PROSPERO: CRD42020161860.

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

The ethos brief index-validation of a brief questionnaire to evaluate wellness based on a holistic perspective in patients with restless legs syndrome.

PURPOSE: The aim of this study was to validate the Ethos Brief Index (EBI) in patients with Restless Legs Syndrome (RLS). METHODS: A cross-sectional design, including 788 subjects with RLS (65% women, 70.8 years, SD 11.3) from the Swedish RLS Association, was used. A postal survey was sent out to collect data regarding socio demographics, comorbidities, and RLS-related treatment data. Questionnaires included were EBI, the Restless Legs Syndrome-6 Scale (RLS-6), Restless Legs Syndrome-Quality of Life questionnaire (RLSQoL), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). The validity and reliability of the EBI were investigated using Rasch and confirmatory factor analysis (CFA) models. Measurement invariance, unidimensionality, and differential item functioning (DIF) across age and gender groups, as well as insomnia, daytime sleepiness, RLS-related QoL and RLS severity were assessed. RESULTS: The results supported the unidimensionality of the EBI in the CFA (i.e., explaining 61.5% of the variance) and the Rasch model. The reliability of the EBI was confirmed using composite reliability and Cronbach's alpha. No DIF was identified for gender, age, insomnia, daytime sleepiness, RLS severity or RLS-related QoL. CONCLUSION: The EBI showed good validity and reliability and operated equivalently for male and female patients with RLS. Accordingly, healthcare professionals can use the EBI as a psychometrically sound tool to explore and identify patient-centered problems related to the whole life situation.

Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study.

STUDY OBJECTIVES: An estimated 3% of the population has clinically significant restless legs syndrome. Given the limited pharmacological options in the arsenal, there is a need for a therapeutic agent with a better side effect profile. METHODS: Twelve treatment naive adults (10 women and 2 men with a median age of 41.5 [32-48.5] years) with primary restless legs syndrome were recruited in our open-label pilot study; magnesium citrate 200 mg was administered daily for 8 weeks. Serum magnesium levels, International Restless Legs Syndrome Study Group Rating Scale, Kohnen quality of life scale, and multiple suggested immobilization tests (three 1-hour tests) were performed before and after supplementation. Paired t tests and Wilcoxon signed-rank tests were used for data analysis. Pearson and Spearman's analyses assessed the association between magnesium levels and restless legs syndrome variables. RESULTS: Participants had a significant reduction in International Restless Legs Syndrome Study Group Rating Scale scores (6.67 [2.33-11] P = .006) and improved Kohnen quality of life scores (8.5 [2.09-14], P = .014) without notable differences in serum magnesium levels (P = .3). The median periodic limb movements during wakefulness index (30.40 [5.20, 122.40] to 8.63 [0.32, 17.47] P = .043) and self-reported discomfort score (19 [14, 30.5] to 6 [0, 8] P = .0010) of all 3 multiple suggested immobilization test trials also demonstrated improvement. Serum magnesium levels negatively correlated with multiple suggested immobilization test self-reported scores and the periodic limb movements during wakefulness indices. CONCLUSIONS: Despite the limitations of open-label design, our study's positive results indicate the need for a placebo-controlled trial with a larger sample size. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Effect of Magnesium Citrate Supplementation in Restless Legs Syndrome (RLS); URL: https://clinicaltrials.gov/ct2/show/study/NCT04462796; Identifier: NCT04462796. CITATION: Gorantla S, Ravisankar A, Trotti LM. Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study. J Clin Sleep Med. 2024;20(8):1357-1361.

Prevalence of restless legs syndrome in adults with epilepsy: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Epilepsy is a common neurological disorder that significantly contributes to the worldwide disease burden. Restless legs syndrome is sleep-related movement disorder that causes uncomfortable sensations in the legs with an irresistible urge to move them. The aim of this study is to comprehensively assess the current evidence to estimate the prevalence of restless legs syndrome (RLS) in adults with epilepsy (AWE) and to compare it to healthy controls. METHODS: PubMed, Medline, Scopus, and Web of Science databases were searched for observational studies reporting the prevalence of RLS in AWE. The modified Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. Comprehensive Meta-Analysis software (version 3.0) was used to perform data analysis. The heterogeneity of the studies was assessed using the I2 index. The pooled prevalence of RLS in AWE and the odds ratio were calculated based on the random-effect model. Sensitivity analysis was assessed. A funnel plot and Egger's test were used to investigate publication bias. Subgroup analysis and univariate meta-regression analysis were done. RESULTS: Based on the analysis of 17 studies (2262 AWE patients), the prevalence of RLS was 14.9 % (95%CI, 10.4%-21 %). This rate was highest in the Americas (35.3 %; 95 % CI: 19.7-54.9 %) and lowest in Asian countries (11.6 %). The risk of RLS was significantly higher in AWE patients compared to health controls (12 studies, OR = 2.09; 95 % CI: 1.53-2.85, I2 = 91.69 %, P < 0.001). subgroup analysis showed Variations in RLS rates between studies depending on quality scores, methodology, and diagnostic criteria. The funnel plot and Egger's test suggest there was publication bias. Sensitivity analysis showed that none of the studies on their own significantly affected the results. CONCLUSIONS: This meta-analysis provides the first pooled estimate of RLS prevalence in AWE. RLS occurs in 15 out of every 100 AWE patients, and the risk is high compared to healthy controls. However, the findings need to be confirmed in future studies owing to limitations in the analysis and study design.