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 disorders in chronic kidney disease.

Sleep disorders are highly prevalent in chronic kidney disease (CKD) but are often under-recognized. Restless legs syndrome, which is common in CKD owing to issues with dopamine metabolism and is exacerbated by iron deficiency and uraemia, can lead to poor sleep quality and increased daytime fatigue. Insomnia is also prevalent in CKD, particularly in patients requiring dialysis, with increased sleep latency and sleep fragmentation being reported. The cause of insomnia in CKD is multifactorial - poor sleep habits and frequent napping during dialysis, uraemia, medications and mood disorders have all been suggested as potential contributing factors. Sleep apnoea and CKD are also now recognized as having a bi-directional relationship. Sleep apnoea is a risk factor for accelerated progression of CKD, and fluid overload, which is associated with kidney failure, can lead to both obstructive and central sleep apnoea. The presence of obstructive sleep apnoea in CKD can exacerbate the already heightened cardiovascular morbidity and mortality in these patients, as well as leading to daytime fatigue and reduced quality of life. Increased awareness, timely diagnosis and appropriate therapeutic interventions are essential to reduce the negative impact of sleep disorders in patients with kidney disease.

Risk factors affecting the sleep quality of patients on dialysis: A single-center cross-sectional study.

Sleep quality is among the common complication in patients on dialysis and serious affect their health and quality of life; however, other associated risk factors are unclear. This study aimed to investigate the risk factors affecting sleep quality in patients on dialysis. Data were collected from 260 patients who met the inclusion criteria at out hospital from May 2023 to October 2023. Questionnaires were completed by patients, and biochemical indicators were obtained from past medical records. Univariate and multifactor analyses were used to find factors influencing sleep quality in patients on dialysis. Simple linear regression results showed that female, type of kidney primary disease, high systolic blood pressure (SBP), pruritus, pruritus frequency, restless legs syndrome (RLS), anxiety, and depression were associated with poor sleep quality. Blood biochemical parameters showed that low sodium and calcium levels and high ferritin levels were associated with poor sleep quality. Multiple linear regression statistics showed that female, pruritus, RLS, high SBP, depression, and high ferritin levels were associated with poor sleep quality. This study showed that female, chronic nephritis syndrome, high SBP, pruritus, RLS, low mood. and high ferritin levels were associated with poor sleep quality. Future development of individual nursing and targeted therapies is key to improving sleep quality in patients on dialysis.

Global prevalence of restless legs syndrome among hemodialysis patients: A systematic review and meta-analysis.

OBJECTIVES: Restless legs syndrome (RLS) is a common complaint in patients undergoing hemodialysis (HD). Despite the fact that the estimated prevalence of RLS among HD patients is widely reported, these results varied significantly in the relevant literature. Due to this limitation, the aim of this study was to determine the global prevalence of RLS among HD patients. METHODS: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. We searched the electronic databases: Cochrane Library, PubMed, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. A random effects model was employed to calculate pooled prevalence rates. RESULTS: The global pooled prevalence of RLS in HD patients was 27.2% (95% CI: 24.8-29.7). Stratified analyses demonstrated that included studies with sample size <100 had the highest pooled prevalence of RLS. The prevalence of RLS using clinical interviews and questionnaires was 28.7% (95% CI: 25.2-32.2) and 25.9% (95% CI: 22.8-29.1), respectively. RLS prevalence is higher in females (29.7%, 95% CI: 26.2-33.2) HD patients than in males (23.5%, 95% CI: 20.9-26.0), and the African region has the highest prevalence in the world when the diagnostic criteria were restricted to the 2003 version of International RLS Study Group criteria, the prevalence of RLS was highest (28.9%, 95% CI: 25.9-31.9). CONCLUSION: Our results revealed a high RLS prevalence in HD patients worldwide. However, the prevalence of RLS among HD patients varied significantly based on sample size, data collection method, gender, diagnostic criteria, and geographical region.

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.

Restless legs syndrome is prevalent in adults with cystic fibrosis and impacts sleep quality.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder that is prevalent in chronic inflammatory conditions. RLS prevalence, risk factors, and impact on sleep in CF have not been extensively characterized to date. METHODS: An initial cohort was examined, including 75 persons with CF (PwCF) and 75 control subjects, to look at the prevalence and severity of RLS. A second validation cohort of 191 PwCF was then enrolled from two CF centers to examine risk factors for RLS. A diagnosis of RLS was made according to the International RLS Study Group (IRLSSG) criteria. Sleep quality was identified using the Pittsburgh sleep quality index (PSQI). Epworth sleepiness scale (ESS) was used to measure daytime sleepiness. We then analyzed laboratory and clinical risk factors and sleep symptoms for potential risk factors for RLS. RESULTS: In the initial cohort, 36 % of PwCF had RLS, and 9 % of these had significant RLS. In contrast, only 15 % of controls had RLS, and none had significant RLS. In the second larger validation cohort with 191 subjects, a comparable prevalence of RLS was identified. Higher hemoglobin A1c, use of SSRI/SNRI medications, worse PSQI and ESS sleep quality scores, lower lung function, and higher antibiotic usage were significantly associated with a diagnosis of RLS. By multivariate multinominal logistic regression analysis, higher HbA1c and worse PSQI global sleep quality scores were independent predictors of significant RLS. CONCLUSIONS: RLS is highly prevalent in CF. Higher HbA1c and poor sleep quality, signified by higher PSQI, were each independent predictors of RLS.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Association of low serum ferritin levels with augmentation in patients with restless legs syndrome: A systematic review and meta-analysis.

BACKGROUND: Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation. METHODS: We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed. RESULTS: Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227). CONCLUSIONS: A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.

Analysis of influencing factors of anxiety and depression in maintenance hemodialysis patients and its correlation with BDNF, NT-3 and 5-HT levels.

Objective: The aim of this study is to examine the factors that contribute to anxiety and depression in individuals undergoing maintenance hemodialysis (MHD), as well as their association with serum levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and serotonin (5-HT). Methods: In May 2020 and June 2022, 120 MHD patients who received MDH treatment at our hospital were enrolled. The control group was composed of 60 healthy adults (>18) who completed the physical examination at the same time. The serum levels of BDNF, NT-3, and 5-HT in patients and clinical data of MHD patients with different degrees of anxiety and depression were compared. The Pearson correlation was used to evaluate the correlation between anxiety and depression scores and serum BDNF, NT-3,5-HT levels in patients with MHD. Multivariate analysis was employed to analyze the risk factors of anxiety and depression in MHD patients. Results: The incidence of anxiety and depression in 120 MHD patients was 34.17% (41/120) and 64.17% (77/120), respectively. The levels of serum NT-3 and 5-HT in the anxiety group were higher than those in the non-anxiety and control group, and the levels of serum NT-3 in the non-anxiety group were higher than those in the control group (P < 0.05). The levels of serum BDNF, NT-3 and 5-HT in the depressed group were higher than those in the non-depressed group and control group, and the levels of serum NT-3 in the non-depressed group were higher than those in the control group (P < 0.05). SAS score was positively correlated with serum NT-3 and 5-HT levels, while the SDS score was negatively correlated with serum BDNF and positively correlated with serum NT-3 and 5-HT levels. Female, rural household registration, and restless leg syndrome were independent risk variables for anxiety in patients with MHD (P < 0.05). Rural household registration, economic deterioration, fatigue, insomnia, and vascular pain were independent variables of depression risk in patients with MHD. Conclusion: Anxiety and depression in patients with MHD are closely related to the levels of serum BDNF, NT-3, and 5-HT. Female, rural household registration, more than eight dialysis times/month, insomnia, and restless leg syndrome are the risk factors for anxiety in patients with MHD. Rural household registration, economic deterioration, fatigue, insomnia, and vascular pain are the risk factors for depression in patients with MHD. The clinical implication of these findings suggests that these indexes may perhaps serve as biological indicators of anxiety and depression amongst patients undergoing MHD. Such investigation can hence contribute to early detection, monitoring, and potentially enable the depiction of novel therapeutic strategies for managing these adverse states.

Restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting. OBJECTIVE: This article outlines the epidemiology, pathophysiology, diagnosis and management of RLS, with a focus on the primary care setting. DISCUSSION: RLS is a clinical diagnosis, although mimics exist. Brain iron deficiency, dopaminergic dysfunction and genetics underpin the poorly understood pathophysiology of this common condition. After repleting iron stores, reviewing any exacerbating medications and attending to non-pharmacological management options, there are pharmacological options that prove to be effective, although with class-specific effects that need to be considered.

Restless legs syndrome: From clinic to personalized medicine.

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder that impairs sleep, mood and quality of life. RLS is defined by an urge to move the legs at rest that increases in the evening and at night, and is frequently associated with metabolic and cardiovascular diseases. Symptoms frequency, age at RLS onset, severity, familial history and consequences of RLS vary widely between patients. A genetic susceptibility, iron deficiency, dopamine deregulation, and possible hypo-adenosinergic state may play a role in the pathophysiology of RLS. Polysomnographic recordings found often periodic leg movements during sleep and wakefulness in patients with RLS. RLS can be classified as primary or comorbid with major diseases: iron deficiency, renal, neurological, rheumatological and lung diseases. First-line treatments are low-dose dopamine agonists, and alpha-2-delta ligands depending on the clinical context, and second/third line opiates for pharmacoresistant forms of RLS. Augmentation syndrome is a serious complication of dopamine agonists and should be prevented by using the recommended low dose. Despite an increase in knowledge, RLS is still underdiagnosed, poorly recognized, resulting in substantial individual health burden and socioeconomic coast, and education is urgently needed to increase awareness of this disabling disorder.

A cross-sectional study on restless legs syndrome (RLS) in polycythemia vera (PV): is iron deficiency the only culprit?

INTRODUCTION: In polycythemia vera (PV) patients undergoing phlebotomy, iron deficiency (ID) may develop. ID has been linked to restless legs syndrome (RLS), and in one study, 29.6% of PV patients had RLS. We aimed to evaluate the frequency of RLS in PV and to evaluate factors that might play a role in RLS development among PV and essential thrombocythemia (ET) patients. METHODS: We consecutively included PV cases as the patient group, and ET and ID patients and healthy subjects (HSs) were included as controls. Those with conditions that could lead to RLS were excluded. All subjects were questioned according to the diagnostic criteria of the International Restless Legs Syndrome Study Group. RESULTS: Twenty-seven PV, 23 ET, and 22 ID patients and 23 HSs were included. RLS was detected in 25.9%, 34.8%, and 45.5% of PV, ET, and ID patients, respectively. None of the HSs had RLS. In univariate analysis, interferon-α and anagrelide use, magnesium levels, and the Leeds assessment of neuropathic symptoms and signs (LANSS) scores had a significant impact on RLS in PV and ET patients (p = 0.014, p = 0.032, p = 0.036, and p = 0.003, respectively). CONCLUSION: RLS was more common among PV and ET patients than HSs, which was irrespective to the iron status. RLS was more frequent in ET patients than that observed in PV cases, indicating that ID may not be the only causative factor for RLS development in PV. Further prospective studies are needed to determine the prevalence and risk factors of RLS developing in PV and ET.

Ferric carboxymaltose effects on restless legs syndrome and on brain iron in patients with iron deficiency anemia.

OBJECTIVE: Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM. METHODS: This is a randomized, double-blinded, placebo-controlled study. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗. RESULTS: A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028). CONCLUSION: This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.

History of Sleep Disorders in Chronic Kidney Disease: First Approach.

OBJECTIVES: In this study, we examined the history of sleep disorders in chronic kidney disease, 60 years after the advent of hemodialysis and renal transplant of genetically nonrelated organs, which have spurred a critical mass of data. MATERIALS AND METHODS: We analyzed selected literature on sleep disorders in chronic kidney disease from 1959 onward. RESULTS: Sleep disturbances are present in the general population. They cause loss of renal function and progressive nephron loss. Insomnia, sleep apnea, restless leg syndrome, and periodic limb movements represent sleep disturbances in chronic kidney disease. These symptoms manifest early in chronic kidney disease and are a rule in patients on dialysis and kidney transplant recipients. Sleep disturbances cause fatigue, excessive daily sleepiness, impaired daytime function, impaired health-related quality of life, increased morbidity, and increased mortality. CONCLUSIONS: Sleep disorders affect most patients with chronic kidney disease. No ascertained pharmacological therapy exists, and even a successful transplant does not totally restore a refreshing sleep. Longer nocturnal hemodialysis is of benefit. Sleep apnea may be cured with continuous positive airway pressure.

The effect of nonpharmacologic interventions for muscle cramps and restless-leg syndrome in hemodialysis patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: We performed a meta-analysis to evaluate the effect of the nonpharmacologic interventions on muscle related symptoms including cramping and restless leg syndrome in hemodialysis patients. METHODS: Articles published between 2002 and 2022 were searched in six databases. The standardized mean differences were determined by the upper and lower limits of 95% confidence intervals. Publication bias was assessed by conducting the Egger test and examined visually using a funnel plot. RESULTS: Fourteen studies were included in this meta-analysis. The types of interventions included exercise (n = 5), aromatherapy (n = 5), reflexology (n = 3), massage (n = 1), and acupressure (n = 1). The methodological quality assessment revealed 13 studies were strong quality, while only one study was moderate quality. The Egger test indicated no significant publication biases. CONCLUSION: Healthcare professionals can use non-pharmacological methods to manage muscle-related symptoms because of not only beneficial effects but also it is practical, well-tolerated, easy integrated into the treatment and care.

Restless leg syndrome in patients with chronic kidney disease: a hospital-based study from Upper Egypt.

OBJECTIVES: Chronic kidney disease (CKD) is a common cause of restless leg syndrome (RLS). RLS is under-recognized, misdiagnosed and undertreated disorder in our locality. In this study, we aimed to determine the prevalence of RLS due to CKD and its predictors. METHODS: This cross-sectional study included 520 patients [male = 200; female = 320; age: 48.45 ± 3.63yrs; uremia duration: 6.44 ± 1.65yrs; CKD5D = 400; CKD3D = 120). RLS diagnosis was done by clinical interviewing according to International RLS Study Group criteria. All underwent detailed biochemical testing and iron and ferritin levels' measurements. Insomnia, depression and anxiety severities were assessed using insomnia sleep index (ISI), Beck Depression Inventory (BDI-II) and State-Trait Anxiety Inventory for Adults (STAI-AD) scales. RESULTS: RLS was found in 22.31% [ESKD = 26%, CKD3D = 10%]. Insomnia, depression and anxiety were found in 76.15%, 91.15% and 44.23%, respectively. Insomnia was correlated with depression (r = 0.488, p = 0.001) and anxiety (r = 0.360, p = 0.006) but not RLS. Multiple linear regression analysis showed that ESKD (OR = 3.8, 95%CI = 2.5-8.5, p = 0.001), inadequate dialysis (OR = 4.6, 95%CI = 3.5-8.6, p = 0.001), hyperparathyroidism (OR = 5.1, 95%CI 3.2-13.7, p = 0.0001) and peripheral neuropathy (OR = 5.6, 95%CI = 3.8-12.8, p = 0.0001) were independently associated with RLS. CONCLUSION: The prevalence of RLS with CKD is 22.31%. It is 2.6 times more frequent and severe with ESKD compared to CKD3D. It seems that RLS may occur early with CKD and becomes worse with progressive kidney impairment. Also, insomnia, depression and anxiety are common with CKD, however, their severities were not correlated with RLS. Predictors for RLS were ESKD, inadequacy of dialysis, hyperparathyroidism and peripheral neuropathy.

Hyperhidrosis in sleep disorders - A narrative review of mechanisms and clinical significance.

Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.