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

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

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.

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.

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.

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.

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.

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 metabolic biomarker panel of restless legs syndrome in peritoneal dialysis patients.

BACKGROUND: Restless legs syndrome (RLS) is a neuromotor disorder, and dialysis patients are more likely to develop RLS. RLS often causes sleep disorders, anxiety and depression in patients. It will increase the risk of death and severely affect the life of patients. At present, RLS has not received enough recognition and attention, and the misdiagnosis rate can reach more than 10%. METHODS: The discovery set selected 30 peritoneal dialysis (PD) patients and 27 peritoneal dialysis patients with RLS (PD-RLS). A metabolomics method based on ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method (UPLC-Q-TOF/MS) was used to analyze the differential metabolites of the two groups. 51 PD patients and 51 PD-RLS patients were included in the validation set. The receiver operating characteristic (ROC) analysis was used to evaluate the early diagnostic biomarkers, and the correlation between the differential metabolites and laboratory test indexes was analyzed to explore the biological function of the differential metabolites. RESULTS: Through the integrated analysis, four metabolites can be used as markers for the diagnosis of PD-RLS, including Hippuric acid, Phenylacetylglutamine, N,N,N-Trimethyl-L-alanyl-L-proline betaine and Threonic acid. Through ROC analysis, it is found that they can be used as a metabolic biomarker panel, and the area under the curve of this combination is more than 0.9, indicating that the panel has good diagnostic and predictive ability. CONCLUSION: Metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the potential biomarkers, and provide a theoretical basis for the early diagnosis, prevention and treatment on PD-RLS.

A network meta-analysis of the effectiveness and safety of drugs for restless legs syndrome in dialysis patients.

OBJECTIVE: To evaluate the efficacy and safety of nine pharmacological interventions for restless legs syndrome (RLS) in dialysis patients. METHODS: An electronic database was used to retrieve eligible trials from PubMed, Cochrane, Embase, and Web of Science. Stata 14.2 software was used to perform network meta-analysis. The primary measure was the RLS score, and the secondary measure was used to evaluate the side effects of the drug. The surface under the cumulative ranking curve method was used to rank the merits of intervention measures. A comparison of the two interventions is shown on a league table. RESULTS: Finally, nine randomized controlled trials (RCTs) with a total of 377 participants were included. From the results of the network meta-analysis, all treatments ranked higher than placebo in terms of improving clinical symptoms, but only vitamin C (standardized mean difference [SMD] = -1.47 95% confidence interval [CI] -2.89, -0.05) showed significant differences compared with placebo. In terms of safety, there were no serious adverse reactions to any of the treatments compared to placebo. CONCLUSION: Currently, existing evidence suggests that vitamin C may be the most ideal drug to improve the symptoms of RLS in dialysis patients.

Restless legs syndrome due to brainstem stroke: A systematic review.

Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases PubMed and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in patients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.

Relationship between presence of spinal cord lesion and restless legs syndrome in multiple sclerosis.

BACKGROUND: Even though the prevalence of restless leg syndrome in multiple sclerosis (MS) is known to vary between 12.5% and 60%, the underlying pathophysiological mechanism remains unclear. AIM: This study aims to investigate the relationship between spinal cord lesions and restless leg syndrome in MS. MATERIALS AND METHODS: In total, 959 persons with MS were enrolled in this study. Demographic and clinical data of persons with MS were recorded by interviewing and medical records. Neurologists blind to the presence of restless leg syndrome evaluated MRI scans for the presence of demyelinating lesions in the brainstem and spinal cord. RESULTS: The restless leg syndrome was detected in 222 participants (23.15%). Restless leg syndrome was not significantly linked to mean age, body mass index, gender, and MS duration, but persons with MS with restless leg syndrome have a higher disability level (p = 0.044). In addition, no difference in the brainstem and thoracic cord was found between persons with MS with and without restless leg syndrome, while there is a significant relationship between the presence of cervical cord lesion and restless leg syndrome. CONCLUSION: Higher disability scores and characteristics of lesion patterns in the spinal cord could explain higher rates of restless leg syndrome in persons with MS. Considering the negative effects of restless leg syndrome, the increased awareness and treatment of restless leg syndrome among persons with MS is essential for better managing.

Clinical characteristics of periodic limb movements during sleep categorized by continuous positive airway pressure titration polysomnography in patients with obstructive sleep apnea.

PURPOSE: The presence of periodic limb movements during sleep (PLMS) varies among patients with obstructive sleep apnea (OSA) undergoing treatment with continuous positive airway pressure (CPAP). The factors associated with this variation are unknown. METHODS: PLMS were defined as a periodic leg movements index of > 15/h. Patients with OSA and PLMS were categorized into four groups depending on diagnostic and CPAP titration polysomnography (PSG). A multinomial logistic regression analysis was performed using a non-PLMS group as the reference category. RESULTS: This study included 861 patients with OSA who underwent a full-night CPAP titration PSG. The proportions of the subjects with PLMS on both PSGs (persistent PLMS), those with CPAP-emergent PLMS, and those with CPAP-resolved PLMS were 12.9%, 9.2%, and 3.9%, respectively. Compared with the non-PLMS group, the persistent group was more likely to be of older age and male sex and has a higher body mass index and restless legs syndrome (RLS). Patients in the CPAP-emergent group were also older and more likely to have RLS as well as more severe apnea. Patients in the CPAP-resolved group were more likely to be women, of older age, have a higher body mass index, but less severe apnea. CONCLUSIONS: PLMS elicited by CPAP are more likely to occur in older patients with more severe sleep apnea and comorbid RLS, whereas OSA patients in which PLMS resolve after CPAP are more likely to be women and have milder sleep apnea. Persistent PLMS share clinical characteristics with PLMS in general population.

Prevalence and associated factors of restless leg syndrome (RLS) in Pakistani women during pregnancy.

There is a dearth of literature studying restless leg syndrome (RLS) among pregnant patients in Pakistan. The objective of this study was to determine the prevalence and associated factors of RLS among pregnant Pakistani patients. It was conducted in 2018 among 478 women attending ante-natal check-up in the outpatient department of five hospitals in Karachi, Pakistan. Individuals were interviewed for socio-demographic information, the key criteria for RLS and its associated factors. RLS was reported in 54 (11%) individuals based on International Restless Legs Syndrome Study Group (IRLSSG) criteria. The mean age was 33.44 ± 4.42 years. Association between pregnant women with RLS and those without reveals statistically significant differences with increasing age (p=.01), gravida (p<.01) and para (p<.001). RLS was significant among working women (p=.001), during third trimester (p=.001), with insomnia (p<.001), use of tobacco (p<.001) and among women with gestational diabetes (p<.001), hypertension (p<.001). The study showed a low prevalence of RLS among women during pregnancy. It further reported gestational diabetes, hypertension, insomnia and tobacco use to be independently linked to RLS. Impact StatementWhat is already known on this subject? Pregnancy has been demonstrated to be strongly associated with development of secondary restless leg syndrome (RLS). RLS in pregnancy has also been shown to portend poor maternal and neonatal outcomes such as postpartum depression and preterm birth. Various conditions and lifestyle factors in pregnancy have been shown to be associated with the development of RLS, but there are variations in these across different populations.What do the results of this study add? The prevalence of RLS was only reported twice in pregnant patients in Pakistan and our research helps to address this data shortage. In addition, the results of our study document a strong association of RLS with gestational hypertension and gestational diabetes and also show that smoking and exercise were correlated with RLS during pregnancy, both of which were previously unstudied in the pregnant Pakistani population.What are the implications of these findings for clinical practice and/or further research? Demonstrating the prevalence of RLS in pregnant Pakistani patients highlights the need to screen these patients, particularly those with associated conditions identified in our findings, for RLS during antenatal visits and to treat their condition to improve maternal and neonatal outcomes.

Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature.

Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55-86%) and restless legs syndrome (8-45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep-wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life.

Impact of Medium Cut-Off Dialyzers on Patient-Reported Outcomes: COREXH Registry.

INTRODUCTION: A new generation of hemodialysis (HD) membranes called medium cut-off (MCO) membranes possesses enhanced capacities for middle molecule clearance, which have been associated with adverse outcomes in this population. These improvements could potentially positively impact patient-reported outcomes (PROs). OBJECTIVE: The objective of this study was to evaluate the impact of MCO membranes on PROs in a cohort of HD patients in Colombia. METHODS: This was a prospective, multicenter, observational cohort study of 992 patients from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. Changes in Kidney Disease Quality of Life 36-Item Short Form Survey (KDQoL-SF36) domains, Dialysis Symptom Index (DSI), and restless legs syndrome (RLS) 12 months after switching to MCO membranes were compared with time on high-flux membranes. Repeated measures of ANOVA were used to evaluate changes in KDQoL-SF36 scores; severity scoring was used to assess DSI changes over time; Cochran's Q test was used to evaluate changes in frequency of diagnostic criteria of RLS. RESULTS: During 12 months of follow-up, 3 of 5 KDQoL-SF36 domains improved compared with baseline: symptoms (p < 0.0001), effects of kidney disease (p < 0.0001), and burden of kidney disease (p < 0.001). The proportion of patients diagnosed with RLS significantly decreased from 22.1% at baseline to 10% at 12 months (p < 0.0001). No significant differences in the number of symptoms (DSI, p = 0.1) were observed, although their severity decreased (p = 0.009). CONCLUSIONS: In conventional HD patients, the expanded clearance of large middle molecules with MCO-HD membranes was associated with higher health-related quality of life scores and a decrease in the prevalence of RLS.

Venous leg symptoms, ecchymosis, and coldness in patients with peripheral varicose vein: A multicenter assessment and validation study (VEIN-VIOLET study).

OBJECTIVES: We aimed to evaluate peripheral varicose vein symptoms including ecchymosis and coldness by using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaire. METHODS: A total of 1120 patients were enrolled to the analysis after the exclusion of 199 patients who did not match the inclusion criteria. Patients were asked to answer the VEINES-Sym questionnaire and questions about ecchymosis and coldness. Scores of ecchymosis and coldness were calculated similar to VEINES-Sym questionnaire. Classifications of peripheral varicose vein were made according to the clinical part of clinical, etiological, anatomical, and pathophysiological classification system and patients with grade 2 or higher were considered as positive for peripheral varicose vein. RESULTS: Frequency of symptoms present in the VEINES-Sym instrument, ecchymosis and coldness were significantly higher in patients with peripheral varicose vein. Mean score of each symptom was significantly lower in peripheral varicose vein patients including scores of ecchymosis and coldness. Logistic regression analysis revealed that presence of hemorrhoids and all symptoms in VEINES-Sym questionnaire except restless leg were significantly and independently associated with peripheral varicose vein. Besides, ecchymosis (odds ratio: 2.04, 95% confidence interval: 1.34-3.08, p = 0.008) but not coldness was significantly and independently associated with peripheral varicose vein. There was also significant correlation of VEINES-Sym score with ecchymosis (r = 0.43, p < 0.001) and coldness (r = 0.47, p < 0.001). CONCLUSIONS: Venous leg symptoms present in VEINES-Sym questionnaire except restless legs, presence of hemorrhoids and ecchymosis are significantly and independently associated with peripheral varicose vein. Not only ecchymosis but also coldness has shown an independent association with total VEINES-Sym score.

Movement Disorders in Chronic Kidney Disease - A Descriptive Review.

OBJECTIVES: The objective of this study is to describe the mechanism of damage to subcortical structures in chronic kidney disease (CKD) and to describe the range of movement disorders associated with CKD. MATERIALS AND METHODS: We have reviewed the Medline literature up to January of 2020 using key words movement disorders and chronic kidney disease. The reviewed articles were studied for mechanisms of subcortical damage in CKD as well as type of the reported movements, their frequency and updated treatment. RESULTS: The search revealed 183 articles most of them dealing with restless legs syndrome. The damage to basal ganglia in CKD resulted from several mechanisms including accumulation of nitro tyrosine caused by reactive oxygen species and action of uremic toxins leading to endothelial damage and dysfunction of blood-brain barrier. Involuntary movements in CKD include restless legs syndrome (RLS), myoclonus, asterixis, dystonia, chorea, tremor, and Parkinsonism. CONCLUSIONS: Chronic kidney disease can cause several abnormal involuntary movements via damaging basal ganglia and subcortical structures. The most common movement disorders in CKD are RLS, myoclonus and asterixis. Restless legs syndrome and myoclonus when severe, need and respond to treatment. Movement disorders in CKD improve with improvement of kidney function.

Comparative efficacy and acceptability of treatments for restless legs syndrome in end-stage renal disease: a systematic review and network meta-analysis.

BACKGROUND: Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients and impairs health and quality of life significantly. However, the optimal treatment of RLS in ESRD patients is uncertain and less studied compared with idiopathic RLS patients. METHODS: We conducted a systematic review and network meta-analysis to compare the efficacy and acceptability of treatments for RLS in ESRD patients. Randomized controlled trials (RCTs) by February 2019 in the PubMed, Cochrane Library, Embase and ClinicalTrials.gov were reviewed. RLS severity reduction was treated as treatment efficacy, and adverse events were treated as acceptable. Both outcomes were appraised using a random effects model expressed as standardized mean differences and odds ratios with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to obtain a hierarchy of interventions. RESULTS: A total of 12 RCTs were included, comprising 9 interventions and 498 participants. All the interventions significantly improved RLS severity without critical side effects compared with placebo. Gabapentin achieved the greatest decrease of RLS severity [standardized mean difference (SMD) = 1.95, 95% CI 0.81-3.09 (SUCRA: 79.3%)], despite its frequent adverse events [SMD = 0.18, 95% CI 0.02-1.50 (19.9%)]. The combination therapy of exercise plus dopamine agonist had better efficacy [SMD = 1.60, 95% CI 0.08-3.12 (59.8%)] and acceptability [SMD = 1.41, 95% CI 0.01-142.53 (63.9%)] compared with that of vitamin C plus vitamin E [SMD = 1.50, 95% CI 0.47-2.54 (56.6%); SMD = 0.32, 95% CI 0.04-2.86 (32.5%)]. CONCLUSIONS: This network meta-analysis supports that gabapentin is the most effective treatment for RLS in ESRD patients. Exercise plus dopamine agonist is a favorable combination therapy concerning side effects. Future large RCTs with long-term treatment outcomes are necessary.

Itch and Ache on Dialysis: New Approaches to Manage Uremic Pruritus and Restless Legs.

BACKGROUND: Uremic pruritus (UP) and restless legs syndrome (RLS) are highly prevalent complaints among patients with end-stage renal disease (ESRD) undergoing chronic dialysis. These chronic troublesome symptoms lead to a significant decrease in quality of life (QOL) and increase in mortality rate. Despite their distressing characteristics, these symptoms usually remain under-recognized by healthcare providers. Therefore, careful history intake, and stepwise treatment are essential. Numerous pharmacological and non-pharmacological treatments have been demonstrated to help in controlling these 2 conditions. SUMMARY: In this review, we discuss the latest findings regarding UP and RLS among ESRD patients on maintenance dialysis. We also examine different treatment options in this group of patients. The majority of these patients do not have the opportunity to receive a kidney transplant and need other treatments for these burdensome symptoms in order to improve their QOL and prognosis. Key Messages: UP and RLS are common but underdiagnosed conditions in ESRD patients on maintenance dialysis that are related to a decline in patients' QOL and poor prognosis. The pathophysiology of these conditions remains not well understood. Therefore, controversies still exist on treatment options. Treating these conditions provides an opportunity to improve the health-related QOL and outcomes of dialysis patients.

Sleep disturbances among older adults following traumatic brain injury.

Sleep disturbances are common sequelae of traumatic brain injury (TBI) that are associated with poorer recovery. This is important among older adults, who fare worse following TBI relative to younger adults and have a higher prevalence of sleep disorders. The objective of this study was to assess the risk of newly-diagnosed sleep disorders following TBI among adults ≥65 years. Using a large commercial insurance database, older adults diagnosed with TBI between 2008-2014 (n = 78,044) and non-TBI controls (n = 76,107) were identified. The first dates of diagnosis of four common sleep disorders (hypersomnia, insomnia, obstructive sleep apnea, and restless legs syndrome) and a composite of any sleep disorder were identified. To compare groups, this study used a difference-in-differences (DID) approach, accounting for pre-index differences between cohorts and the trends in sleep diagnoses over time. Individuals with TBI were more likely to have any newly-diagnosed sleep disorder before (14.1% vs 9.4%, p < 0.001) and after (22.7% vs 14.1%, p < 0.001) the index date. In fully adjusted DID models, TBI was associated with an increased risk of insomnia (rate ratio (RR) = 1.17; 95% confidence interval (CI) = 1.08-1.26) and any sleep disorder (RR = 1.13; 95% CI = 1.08-1.19). Following TBI among older adults, screening and education on sleep disorders should be considered.