The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome.

OBJECTIVE: Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α-melanocyte-stimulating hormone (α-MSH) and ß-endorphin in RLS patients and controls. METHODS: Forty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α-MSH, ß-MSH, and ß-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale. RESULTS: RLS participants were 52.7 ± 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 ± 9.0. Controls had similar age and sex. Plasma ACTH, α-MSH, and ß-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 ± 11.5 vs 12.7 ± 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF ß-MSH was significantly higher in painful than nonpainful RLS or controls (48.2 ± 24.8 vs 32.1 ± 14.8 vs 32.6 ± 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF α-MSH was higher in RLS than controls (34.2 ± 40.9 vs 20.3 ± 11.0pg/ml, p = 0.062). CSF ß-EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 ± 3.4 vs 10.8 ± 3.1 vs 12.3 ± 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF α- and ß-MSH to CSF ß-endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007). INTERPRETATION: CSF ß-MSH is increased and CSF ß-endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024;95:688-699.

Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case-Control Study.

Brain iron deficiency (ID) and, to a degree, systemic ID have been implicated in restless leg syndrome (RLS) pathogenesis. Previously, we found increased ferritin in neuron-derived extracellular vesicles (NDEVs) in RLS, suggesting a mechanism for depleting intracellular iron by secreting ferritin-loaded NDEVs. In this study, we hypothesized that increased NDEV ferritin occurs even in RLS accompanied by systemic ID and that neuronal intracellular iron depletion in RLS also manifests as NDEV abnormalities in other iron regulatory proteins, specifically, decreased transferrin receptor (TfR) and increased ferroportin. To address these hypotheses, we studied 71 women with ID anemia, 36 with RLS, and 35 without RLS. Subjects with RLS again showed higher NDEV ferritin and also decreased TfR, suggesting diminished neuronal capacity for iron uptake. Findings inform a more complete understanding of the pathogenic role of neuronal iron homeostasis and dissociate it from peripheral ID. ANN NEUROL 2024;96:560-564.

Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, ß-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is ß-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.

Intronic elements associated with insomnia and restless legs syndrome exhibit cell-type-specific epigenetic features contributing to MEIS1 regulation.

A highly evolutionarily conserved myeloid ecotropic viral integration site 1 (MEIS1) intronic region is strongly associated with restless legs syndrome (RLS) and insomnia. To understand its regulatory function, we dissected the region by analyzing chromatin accessibility, enhancer-promoter contacts, DNA methylation and expression quantitative trait locus (eQTLs) in different human neural cell types and tissues. We observed specific activity with respect to cell type and developmental maturation, indicating a prominent role for distinct highly conserved intronic elements in forebrain inhibitory neuron differentiation. Two elements were hypomethylated in neural cells with higher MEIS1 expression, suggesting a role of enhancer demethylation in gene regulation. MEIS1 eQTLs showed a striking modular chromosomal distribution, with forebrain eQTLs clustering in intron 8/9. Clustered regularly interspersed short palindromic repeats interference targeting of individual elements in this region attenuated MEIS1 expression, revealing a complex regulatory interplay of distinct elements. In summary, we found that MEIS1 regulation is organized in a modular pattern. Disease-associated intronic regulatory elements control MEIS1 expression with cell type and maturation stage specificity, particularly in the inhibitory neuron lineage. The precise spatiotemporal activity of these elements likely contributes to the pathogenesis of insomnia and RLS.

BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.

Manganese (Mn) is an essential mineral, but excess exposure can cause dopaminergic neurotoxicity. Restless legs syndrome (RLS) is a common neurological disorder, but the etiology and pathology remain largely unknown. The purpose of this study was to identify the role of Mn in the regulation of an RLS genetic risk factor BTBD9, characterize the function of BTBD9 in Mn-induced oxidative stress and dopaminergic neuronal dysfunction. We found that human subjects with high blood Mn levels were associated with decreased BTBD9 mRNA levels, when compared with subjects with low blood Mn levels. In A549 cells, Mn exposure decreased BTBD9 protein levels. In Caenorhabditis elegans, loss of hpo-9 (BTBD9 homolog) resulted in more susceptibility to Mn-induced oxidative stress and mitochondrial dysfunction, as well as decreased dopamine levels and alternations of dopaminergic neuronal morphology and behavior. Overexpression of hpo-9 in mutant animals restored these defects and the protection was eliminated by mutation of the forkhead box O (FOXO). In addition, expression of hpo-9 upregulated FOXO protein levels and decreased protein kinase B levels. These results suggest that elevated Mn exposure might be an environmental risk factor for RLS. Furthermore, BTBD9 functions to alleviate Mn-induced oxidative stress and neurotoxicity via regulation of insulin/insulin-like growth factor signaling pathway.

The long-term effect of work schedule, shift work disorder, insomnia and restless legs syndrome on headache among nurses: A prospective longitudinal cohort study.

BACKGROUND: The preset study aimed to explore whether work schedules and sleep disorders predict the onset of headache. METHODS: A longitudinal study was conducted with questionnaire data from 2014 (baseline) and 2017 (follow-up) on work schedule, number of night shifts, number of quick returns, insomnia, shift work disorder (SWD), restless legs syndrome (RLS) and validated headache diagnoses among 1560 Norwegian nurses. Associations were explored by multivariate regression analyses. RESULTS: Work related factors at baseline did not predict onset of headache three years later. In the adjusted logistic regressions, insomnia at baseline predicted increased risk of new onset of migraine (odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.08-2.33), chronic headache (OR = 2.02; 95% CI = 1.04-4.66) and medication-overuse headache (OR = 3.79; 95% CI = 1.26-11.42) at follow-up. SWD at baseline predicted new onset of migraine (OR = 1.64; 95% CI = 1.07-2.50) and RLS at baseline predicted new onset of headache ≥1 day per month (OR = 1.55; 95% CI = 1.01-2.36) and migraine (OR = 1.55; 95% CI = 1.03-2.32) at follow-up. No factors predicted tension-type headache. CONCLUSIONS: Overall, work related factors did not predict the onset of headache three years later, whereas insomnia, SWD and RLS at baseline all increased the risk of future headaches.

Perceptions of exercise and restless legs syndrome: Results from a nationwide survey.

Restless legs syndrome is a prevalent, sensorimotor sleep disorder temporarily relieved by movement, with evidence of symptomatic improvement with regular exercise. The present study describes perceptions of the effects of exercise on symptoms of restless legs syndrome. Participants (N = 528) completed a mixed-methods (i.e. numerical and narrative), nationwide survey including items assessing personal experiences with exercise and restless legs syndrome (both positive and negative), as well as restless legs syndrome diagnosis, restless legs syndrome severity, and demographic and clinical characteristics. Responses varied widely on specific experiences with exercise, but a higher percentage of participants indicated positive experiences with exercise than those who reported negative experiences (72%-40%, respectively) with exercise. Further, 54% of respondents reported that exercise only improves restless legs syndrome, while 24% reported exercise only worsens symptoms. Participants described that any abrupt change in exercise routine would almost always elicit restless legs syndrome symptoms (e.g. hiking for a long time, stopping an exercise routine), and that a consistent pattern of exercise improved restless legs syndrome symptoms with an overall beneficial effect on the frequency of symptomatic bouts. Participants further described time of day as impactful for their exercise experience, with > 50% indicating morning exercise improves symptoms and evening exercise worsens symptoms. Participants described several questions that they wanted answered regarding the evidence for exercise in restless legs syndrome and specific exercise prescription recommendations. The present study describes information crucial to the creation of stakeholder-informed health promotion programs for individuals with restless legs syndrome to optimize personalized treatment plans that could prevent and manage symptoms.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

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.

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.

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.

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.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

INTRODUCTION: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. METHODS: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RESULTS: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. CONCLUSION: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Daytime impulsiveness, attention, and learning in the restless legs syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is a sensorimotor condition characterized by disturbing sensations and the desire to move, often localized in the legs. Cognitive changes and impulsivity can be present in RLS, although the potential effect of commonly co-occurring attention-deficit/hyperactivity disorders (ADHD) or dopamine agonist (DA) use on these are unclear. METHOD: Twenty-three RLS patients and 22 healthy controls were included. Rey Auditory Verbal Learning Test (RAVLT), Continuous Performance Test (CPT), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), State and Trait Anxiety Inventory (STAI), and Adult Attention Deficit Self-Evaluation Scale (ASRS) were administered. Performance was compared between RLS patients and controls accounting for the presence of attention-deficit/hyperactivity disorder (ADHD) and DA use. RESULTS: Age, education, BDI, ESS, STAI, and ASRS scores were similar for control and RLS groups. Control and RLS groups performed similarly on auditory verbal learning and general attention tests. In the CPT, commission error was significantly higher and response time was significantly shorter in the RLS group compared to controls (p = .014 and p = .010, respectively). These significant differences persisted after adjusting for ADHD and DA usage. CONCLUSION: In this study, RLS patients were more impulsive than the healthy individuals independent of ADHD and DA use. However, learning and attention performances of the patients are not affected.

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.

Sleep pattern and disorders among pregnant women in Ibadan, Southwest Nigeria.

BACKGROUND: Sleep is essential for pregnant women's and the offspring's health and wellbeing. Poor sleep and disorders have been linked with adverse fetal outcomes and delivery conditions. However, pregnant women often experience several forms of sleep disruption, which has been scarcely reported in low and middle-income countries (LMIC), including Nigeria where the influence of lifestyle factors has also been lacking. We investigated sleep patterns and disorders and the associated factors among pregnant women in Southwest, Nigeria. METHOD: A cross-sectional study was conducted among five hundred (500) pregnant women attending Adeoyo Maternity Teaching Hospital. A semi-structured questionnaire was used to examine different domains of sleep and associated disorders, namely sleep quality (Pittsburgh Sleep Quality Index (> 5 and ≤ 5)), insomnia (Insomnia Severity Index (> 8 and ≤ 8)), restless leg syndrome (Restless Leg Syndrome Rating Scale (> 10 and ≤ 10). Significant covariates such as physical activity, minimum dietary diversity, smoking and alcohol intake were also assessed. We conducted bivariate and multivariate analysis at p < 0.05 significance level. RESULTS: The mean age of participants was 30.4 ± 4.8 years. The pattern of sleep disorder in pregnant were poor sleep quality (50%), restless leg syndrome (58.2%) and insomnia (33.4%). Being currently married (AOR = 6.13; 95% CI: (1.65-22.23)), increasing gestational age: second trimester (AOR = 8.25;95% CI: (1.78-38.17)) to third trimester (AOR = 10.98; 95% CI: (2.44-49.48)) increased the odds of poor sleep quality. Factors associated with restless leg syndrome were marital status [AOR = 3.60; 95% CI; (1.25-10.35)], religion, rigorous physical activities [AOR = 1.52; 95% CI: (1.05-2.21)] and alcohol consumption [AOR = 3.51; 95% CI: (1.00-12.27)]. Factors associated with insomnia were maternal age [AOR = 1.83; 95% CI: (1.11-3.01)], income [AOR = 2.99 (1.26-7.16)] and rigorous physical activity [AOR = 2.55 (1.61-4.02)]. CONCLUSION: Poor sleep quality, restless leg syndrome and insomnia were typical among pregnant women in Ibadan, Southwest Nigeria. Thus, awareness and education on the importance of sleep and its risk and protective factors, such as alcohol consumption, smoking, rigorous activity and spousal and family support, should be increased to reduce poor sleep quality and sleep disorders (restless leg syndrome and insomnia) during the pregnancy period.

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.

Construction and Initial Examination of Inter-Rater Reliability of a Structured Clinical Interview for DSM-5-TR Sleep Disorders (SCISD) - Kid.

STUDY OBJECTIVES: To construct and evaluate the inter-rater reliability of the Structured Clinical Interview for DSM-5-TR Sleep Disorders - Kid (SCISD-Kid). METHOD: The SCISD-Kid was modeled on the adult SCISD-R and accounted for pediatric developmental and sociocultural factors. Fifty sleep-disturbed children (Mage = 11.9, SD = 2.9) and 50 caregivers responded to the final SCISD-Kid. Video recordings were double-scored to evaluate inter-rater reliability. RESULTS: The final SCISD-Kid contained approximately 90 questions. Eight of the nine covered disorders had prevalence rates sufficient for analyses for both samples (i.e., k > 2). Inter-rater reliability was examined using Cohen kappa coefficients (κ); reliability estimates ranged from excellent to good. For youth, restless legs syndrome yielded the lowest reliability (.48), while nightmare disorder, narcolepsy, and NREM sleep arousal disorder - sleepwalking type showed the highest reliability (1.00). Across caregivers, NREM sleep arousal disorder - sleep terror type (.49) and hypersomnolence (.54) had the lowest reliability. In contrast, circadian rhythm - delayed sleep phase type, nightmare disorder, and NREM sleep arousal disorder - sleepwalking type showed the highest reliability (1.00). CONCLUSIONS: The SCISD-Kid is a promising tool for screening sleep disorders. It showed good to excellent reliability across both samples. Next steps for validation will be discussed.

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.

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.