The Relationship between Serum Selenium Levels and Restless Leg Syndrome in Chronic Kidney Disease Patients.

Background and Objectives: Chronic kidney disease (CKD) is a global public health issue with rising incidence linked to substantial morbidity and mortality. Selenium, an antioxidant trace element, has been linked to low serum levels in end-stage renal disease. Restless Leg Syndrome (RLS), a sleep disorder, is prevalent in CKD patients and significantly impacts their quality of life. The objective of this study was to examine the correlation between serum selenium levels and the prevalence of restless leg syndrome in individuals with chronic kidney disease. Materials and Methods: Forty-six CKD patients undergoing serum selenium level assessments between 1 January 2020 and 28 February 2022, at the Hitit University Faculty of Medicine Department of Nephrology Outpatient Clinic or Hemodialysis Unit, were included. Patients over 18 years of age with no history of hematological or oncological diseases or acute or chronic inflammatory conditions were included in the study groups. Patients taking selenium supplements were excluded. Demographic data, comorbidities, and laboratory values were collected, and RLS presence and severity were evaluated. Statistical analyses include descriptive statistics, correlation analysis, the Mann-Whitney U test, Student's t test, and Chi-square test. Results: Among the 46 patients, 16 (34.78%) had RLS symptoms. The patient group included 34.78% predialysis, 34.78% peritoneal dialysis, and 30.44% hemodialysis patients, with a median age of 47.98 years. There was no difference in age, gender, and Charlson comorbidity between patients with or without RLS (p = 0.881, p = 0.702, p = 0.650). RLS prevalence varied across CKD subgroups, with hemodialysis patients having a higher prevalence (p = 0.036). Clinical parameters such as blood urea nitrogen, creatinine, calcium, phosphorus, platelet counts, and parathyroid hormone levels exhibited significant differences between patients with and without RLS (p < 0.05). Serum selenium levels were not significantly different between patients with and without RLS (p = 0.327). Conclusions: With an increased comorbidity burden, CKD poses a significant healthcare challenge. When accompanied by RLS, this burden can be debilitating. The difference in CKD stages between groups has shed light on a critical determinant of RLS in this population, emphasizing the role of the chronic kidney disease stage. In our study, serum selenium levels were not associated with the presence and severity of RLS. However, prospective studies with larger numbers of participants are needed to draw a definitive conclusion.

Chronic pulmonary disease is associated with pain spreading and restless legs syndrome in middle-aged women-a population-based study.

INTRODUCTION: Recent studies suggest an increased prevalence of chronic pain conditions and restless legs syndrome (RLS) in patients with chronic pulmonary disease (CPD). We analyzed the prevalence and risk factors for pain and RLS in a population-based sample of females with comorbid CPD. METHOD: Questionnaire-based data from 2745 women aged 18-64 years were analyzed regarding comorbid CPD status (severe bronchitis, emphysema, asthma). Pain status was assessed according to symptoms reflecting severity (Visual Analogue Scale, VAS rating 0-10) and duration and spreading (limited spread or widespread) of pain. A diagnosis of RLS was defined by four validated diagnostic criteria. Anthropometrics and co-morbidities were assessed as covariates in univariate and multivariate analyses. RESULTS: Widespread pain was overrepresented in women with CPD (44.6 vs. 24.6%, p < 0.001). The odds ratio for widespread pain in women with CPD was 1.6 (95% confidence interval (CI) 1.2-2.2, p < 0.001) in the fully adjusted model. Severe pain (VAS rating ≥ 7) was more prevalent in females with known CPD (28.8 vs. 15.4%, p < 0.001, odd ratio 1.4 (95% CI 1.0-1.9, p = 0.029)). The prevalence of RLS was 37.4 and 23.8% in subjects with or without CPD, respectively (p < 0.001). In multivariate analysis, CPD was associated with a 30% risk increase for RLS (odds ratio 1.3 (95% CI 1.0-1.7, p = 0.04)). CONCLUSION: This population-based study identified CPD as an independent risk factor for severe and widespread pain as well as for RLS. Further research addressing pathophysiological mechanisms linking CPD and chronic pain conditions/RLS is warranted.

Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?

BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA. METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m, Age >50 years, Neck circumference >40 cm, and male Gender. RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64-0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI, 0.92-0.98) to exclude an AHI >15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87-0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively. CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of <2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for screening for sleep apnea (ie, before surgery).

Reduced daytime intramuscular blood flow in patients with restless legs syndrome/Willis-Ekbom disease.

AIM: The aim of this study was to examine possible signs of impairment of the microcirculation in the lower extremities of female patients suffering from primary restless legs syndrome (RLS)/Willis-Ekbom disease. METHODS: This study was performed in eight female patients, mean age 48 years (range 21-65), diagnosed with primary RLS but otherwise healthy. Eight healthy female control subjects, mean age 47 years (range 27-64), were also included in the study. Laser Doppler flowmetry was used to determine intramuscular blood flow by placing an optical single fiber in the tibialis anterior muscle belly. The studies were performed between 08.00 and 10.00 hours and 20.00 and 22.00 hours. Blood flow was expressed in perfusion units. RESULTS: The median intramuscular blood flow in the RLS patients' tibialis anterior muscles, recorded from both legs, was significantly higher in the morning, at 17.9 perfusion units, than in the evening, at 12.1 perfusion units (P = 0.004). Corresponding values for the healthy controls were 13.1 perfusion units and 12.0 perfusion units, a non-significant difference. The relative fold changes of microcirculation in the RLS group compared to healthy age-matched controls were 0.7 ± 0.3 and 1.1 ± 0.6, respectively (P = 0.04). CONCLUSION: Our results suggest that in female patients with primary RLS, the microcirculation in the tibialis anterior muscle is higher in the morning compared with in the evening.

An analysis of YouTube videos about restless leg syndrome: Choosing the right guide.

Individuals often resort to YouTube as a means of accessing insights into their medical conditions and potential avenues for treatment. Among prevalent and incapacitating afflictions within the general populace, restless leg syndrome assumes significance. The focal objective of this investigation is to scrutinize the caliber inherent in videos pertaining to restless leg syndrome disseminated via the YouTube platform. The sorting of videos was accomplished by gauging their pertinence subsequent to conducting a search for "restless leg syndrome" on YouTube, specifically on the 20th of August, 2023. The evaluation encompassed videos curated from the selection of the top 50 English language videos deemed most relevant. The review process entailed the comprehensive assessment of relevance and content by 2 distinct medical professionals operating independently. Furthermore, pertinent descriptive attributes of each video, such as upload date, view count, likes, dislikes, and comments, were meticulously documented within the dataset. To ascertain video quality, the DISCERN Score, global quality score, and Journal of the American Medical Association rating scales were employed as evaluative tools. Significant statistical disparities were observed in terms of DISCERN scores between videos uploaded by medical doctors and those uploaded by individuals without medical qualifications (P < .001). Correspondingly, upon comparing the 2 aforementioned groups, videos uploaded by healthcare professionals exhibited statistically superior quality scores in both the Journal of the American Medical Association and global quality score assessments (P < .001 for both comparisons). The informational quality regarding restless leg syndrome on YouTube presents a spectrum of variability. Notably, videos that offer valuable insights, as well as those that could potentially mislead viewers, do not display discernible variations in terms of their viewership and popularity. For patients seeking reliable information, a useful and safe approach involves favoring videos uploaded by medical professionals. It is imperative to prioritize the professional identity of the content uploader rather than being swayed by the video's popularity or the quantity of comments it has amassed.

Restless legs syndrome among subjects having chronic liver disease: A systematic review and meta-analysis.

Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown.

Health-related quality of life and restless legs syndrome among women in Sweden.

AIM: Restless legs syndrome (RLS) is a common neurological movement disorder with a female preponderance, an increasing prevalence with age and comorbidity. Previous studies on the relationship between health-related quality of life (HRQOL) and RLS are still sparse but knowledge is increasing. The aim of this study was to evaluate the unique impact of RLS on HRQOL in a population-based sample. METHODS: A random sample of 5000 women aged 25-64 years was selected from the general Swedish population. The women were sent diagnostic questions on RLS together with the Short Form 12 (SF-12) questionnaire for assessment of physical and mental HRQOL. The unique burden of RLS on HRQOL was analyzed by excluding RLS-positive women from four self-reported diagnostic groups (diabetes, depression, heart problems, muscle and joint pain) and by excluding subjects with these diagnoses from the group of RLS-positive women. RESULTS: Compared with mental SF-12 scores for the RLS-negative women in our population, mental HRQOL of the RLS sample in our study was lower in every age group but not significantly lower in the age group 35-44 years. Physical SF-12 scores for RLS-positive women were also below scores for RLS-negative women in every age group but significance was only found in women between 45 and 54 years. A unique burden of RLS on HRQOL remained after statistical adjustment for comorbidities. CONCLUSION: RLS-positive women had an impaired mental HRQOL compared to RLS-negative women in the studied population. The physical aspects of HRQOL were less affected among RLS-positive women. The impaired well-being among women with RLS further strengthens the importance of identifying women with this condition and evaluating their need for medication or other actions in order to improve their quality of life.

A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome.

Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome (RLS). We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit. Sixty patients with primary RLS (seven males, age 46 (9) years, S-ferritin < or =45 microg/L) recruited from a cohort of 231 patients were randomly assigned in a 12-months double-blind, multi-centre study of iron sucrose 1000 mg (n = 29) or saline (n = 31). The primary efficacy variable was the RLS severity scale (IRLS) score at week 11. Median IRLS score decreased from 24 to 7 (week 11) after iron sucrose and from 26 to 17 after placebo (P = 0.123, N.S. for between treatment comparison). The corresponding scores at week 7 were 12 and 20 in the two groups (P = 0.017). Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose (Kaplan-Meier estimate, log rank test P = 0.0006) suggesting an iron induced superior long term RLS symptom control. Iron sucrose was well tolerated. This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase (7 weeks) and during long-term follow up in patients with variable degree of iron deficiency. Further studies on target patient groups, dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS.

Restless legs syndrome is common among female patients with fibromyalgia.

BACKGROUND: The prevalence of restless legs syndrome (RLS) among the general population is 2-15%, and with fibromyalgia syndrome (FMS) 2%. Both RLS and FMS are more common among women. The aim of our study was to evaluate the prevalence of RLS in a group of female patients diagnosed with FMS and to compare the occurrence of symptoms of daytime sleepiness and experienced sleep disorders between fibromyalgia patients with or without RLS. METHOD: Three hundred and thirty-two female patients, 20-60 years old, diagnosed with FMS at Skonviks Rehab between 2002 and 2006, answered a questionnaire mailed to their home address. The questionnaire consisted of the international RLS study group criteria as well as of questions concerning symptoms of insomnia and daytime sleepiness measured according to the Epworth Sleepiness Scale. RESULTS: Nearly 64% of the women were also suffering from RLS. More patients suffering from both RLS and FMS were affected by problems of initiating and maintaining sleep than those suffering from FMS only. More patients suffering from both RLS and FMS did not feel refreshed on awakening compared with those suffering from FMS without RLS. The patients with concomitant RLS and FMS were more often hypersomnolent than those suffering from FMS only. CONCLUSION: This study shows that 64% of a group of female patients diagnosed with fibromyalgia also concurrently suffered from RLS. Compared with patients who suffer from FMS only, patients with both FMS and RLS more often experience sleep disturbances and pronounced daytime sleepiness.

[Sleep-related movement disorders]. / Søvnrelaterte bevegelsesforstyrrelser.

BACKGROUND: Restless legs syndrome is a common cause of sleep problems; the condition is often associated with periodic limb movement during sleep. The syndrome is probably under-diagnosed and under-treated. MATERIAL AND METHODS: The article is based on literature identified through a search in PubMed, a review of international recommendations and our own clinical experience. RESULTS: The restless leg syndrome is common, with a prevalence of about 10 %. Many of these patients are affected by sleep disturbances and have periodic limb movement during sleep (PLMS). Restless legs and the associated sleep disturbances can be effectively treated with dopaminagonists. Because of the augmentation risk, the lowest necessary dose should be maintained. PLMS also occurs in other sleep disorders. Periodic limb movement disorder (PLMD) is defined as PLMS combined with sleep disturbances and/or sleepiness during daytime without a known cause. The clinical relevance of PLMD for sleep disturbances is not clear. INTERPRETATION: The restless legs syndrome is a common cause of sleep disturbance; good treatment options are available.

Skeletal muscle morphology and aerobic capacity in patients with obstructive sleep apnoea syndrome.

BACKGROUND: Despite the fact that patients with obstructive sleep apnoea syndrome (OSAS) often have symptoms at the level of skeletal muscle such as fatigue, the question of whether the structural, cellular and functional properties of limb skeletal muscles are affected has not been fully examined. OBJECTIVE: The aim was to examine physiological and muscular parameters in patients with OSAS and to assess the relationship between these parameters and the clinical symptoms. METHOD: Eighteen patients with OSAS and 16 controls participated. Aerobic capacity was assessed using a submaximal test. Fibre type distribution and fibre area were analyzed on muscle biopsies taken from the tibialis anterior. The microvascularization was assessed using the following parameters: (1) the number of capillaries per fibre (CAF), (2) CAF per fibre area (CAFA), (3) capillary to fibre perimeter exchange (CFPE) index, which represents the interface between muscle fibre and capillaries, and (4) length of capillary/perimeter of the fibre (LC/PF) index or capillary tortuosity, which represents the percent of muscle fibre perimeter in contact with the wall of the microvessel. RESULTS: The OSAS group had significantly lower predicted relative maximal oxygen uptake (p = 0.0047) which was inversely correlated to the apnoea/hypopnoea index (AHI; r = -0.6, p = 0.017). There was a significantly higher CFPE index for slow type I fibres (p = 0.007) and fast type II fibres (p = 0.0126) and a significantly higher LC/PF index for type I fibres (p = 0.0003) and type II fibres (p = 0.0285) in OSAS patients compared to controls. CONCLUSION: OSAS patients have a higher muscle microvascularization and a lower aerobic capacity than controls. Furthermore the aerobic capacity was inversely correlated to AHI.

Comparison of Subjective Sleep Quality of Long-Term Residents at Low and High Altitudes: SARAHA Study.

STUDY OBJECTIVES: To study the effect of altitude on subjective sleep quality in populations living at high and low altitudes after excluding cases of restless legs syndrome (RLS). METHODS: This population-based study was conducted at three different altitudes (400 m, 1,900-2,000 m, and 3,200 m above sea level). All consenting subjects available from random stratified sampling in the Himalayan and sub-Himalayan regions of India were included in the study (ages 18 to 84 years). Sleep quality and RLS status were assessed using validated translations of Pittsburgh Sleep Quality Index (PSQI) and Cambridge Hopkins RLS diagnostic questionnaire. Recent medical records were screened to gather data for medical morbidities. RESULTS: In the total sample of 1,689 participants included, 55.2% were women and average age of included subjects was 35.2 (± 10.9) years. In this sample, overall 18.4% reported poor quality of sleep (PSQI ≥ 5). Poor quality of sleep was reported more commonly at high altitude compared to low altitude (odds ratio [OR] = 2.65; 95% CI = 1.9-3.7; P < .001). It was more frequently reported among patients with RLS (29.7% versus 17.1% without RLS; P < .001). Other factors that were associated with poor quality of sleep were male sex, smoking, chronic obstructive pulmonary disease (COPD), and varicose veins. Binary logistic regression indicated that COPD (OR = 1.97; 95% CI = 1.36-2.86; P < .001), high altitude (OR = 2.22; 95% CI = 1.55-3.18; P < .001), and RLS (OR = 1.66; 95% CI = 1.12-2.46; P = .01) increased the odds for poor quality of sleep. CONCLUSIONS: This study showed that poor quality of sleep was approximately twice as prevalent at high altitudes compared to low altitudes even after removing the potential confounders such as RLS and COPD.

Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome.

BACKGROUND AND AIMS: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. METHODS: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. RESULTS: CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (ß=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (ß=3.1±1.3, p=0.018). CONCLUSIONS: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. IMPLICATIONS: CWP is associated with activated stress markers that may deteriorate sleep.

Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report.

BACKGROUND: Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children. METHODS: A literature search was performed to identify papers appearing in MEDLINE from its inception to July 2016. The following inclusion criteria were used: human research on the treatment of RLS or periodic limb movements (PLM) with iron, sample size of at least five, and published in English. Two task force members independently evaluated each paper and classified the quality of evidence provided. RESULTS: A total of 299 papers were identified, of these 31 papers met the inclusion criteria. Four studies in adults were given a Class I rating (one for IV iron sucrose, and three for IV ferric carboxymaltose); only Class IV studies have evaluated iron treatment in children. Ferric carboxymaltose (1000 mg) is effective for treating moderate to severe RLS in those with serum ferritin <300 µg/l and could be used as first-line treatment for RLS in adults. Oral iron (65 mg elemental iron) is possibly effective for treating RLS in those with serum ferritin ≤75 µg/l. There is insufficient evidence to make conclusions on the efficacy of oral iron or IV iron in children. CONCLUSIONS: Consensus recommendations based on clinical practice are presented, including when to use oral iron or IV iron, and recommendations on repeated iron treatments. New iron treatment algorithms, based on evidence and consensus opinion have been developed.

Comorbidity in restless legs syndrome among a sample of Swedish adults.

BACKGROUND: Restless legs syndrome (RLS) is a neurological movement disorder, which often causes sleep problems. However, the comorbidity of this disorder is not well known. This study aimed to document the prevalence of RLS in the general population of Sweden and to identify factors associated with this condition. METHODS: A cross-sectional study was performed in Sweden. One thousand subjects aged 18-90 years old underwent telephone interviews. The questionnaire assessed such factors as sleep variables, depressive mood, treatment of diabetes mellitus, and treatment with drugs for depression during the previous four-week period. RLS was diagnosed based on the minimal criteria provided by the International RLS Study Group. RESULTS: The prevalence of RLS was 5% (5.7% in women, 3.5% in men). Severe or very severe RLS symptoms during the previous week were noted by 64% of the RLS subjects. Factors associated with RLS were insomnia, excessive daytime sleepiness, periodic limb movements in sleep, and depressed mood. Those affected by RLS were not more often consumers of drugs for depression than non-RLS subjects. CONCLUSIONS: RLS is prevalent in the general population in Sweden. RLS negatively influenced sleep and was associated with depressed mood. Antidepressive drug treatment was not associated with RLS.

Skeletal muscle morphology in patients with restless legs syndrome.

AIM: The aim of the study was to assess the cellular and structural properties of skeletal muscle in restless legs syndrome (RLS). METHOD: Twenty patients and 16 controls were included. Aerobic performance was assessed using a submaximal test. On muscle biopsies taken from the tibialis anterior, fiber distribution and fiber area were analyzed together with parameters surveying the microvascularization, especially the tortuosity, which is expressed as a percent of muscle fiber perimeter in contact with the wall of the microvessel, length of capillary/perimeter of fiber (LC/PF) index. RESULTS: The RLS group had significantly lower predicted maximal oxygen uptake (p = 0.01) and significantly higher LC/PF index (p = 0.01) compared to the controls. CONCLUSION: The higher capillary tortuosity in RLS patients indicates the occurrence of significant remodeling in capillary geometry in RLS.

High prevalence of restless legs syndrome/Willis Ekbom Disease (RLS/WED) among people living at high altitude in the Indian Himalaya.

BACKGROUND: At high altitude, prevalence of restless legs syndrome has been found to be greater than expected in small population-based studies, which did not use validated tools for identification of RLS. However, it is not known as to whether this increased prevalence is associated with altitude or increased risk factors for RLS in these populations or errors in identification of RLS. METHOD: This population based, door-to-door study was conducted at low altitude (400 m above sea level) and high altitudes (1900-2000 m and 3200 m above sea level) using random stratified sampling in Himalayan and sub-Himalayan region of India. Subjects between 18 and 84 years were screened for restless-legs-syndrome using the validated Cambridge-Hopkins RLS diagnostic questionnaire. Medical comorbidities were ascertained from their medical records. Their anthropometric measurements were obtained and wake resting oxygen saturation was monitored using finger pulse-oximeter. Physical activity during leisure time was evaluated by using the Goldin leisure time exercise questionnaire. RESULTS: A total of 1689 subjects were included. Average age of the included subjects was 35.2 years; 55.2% were women. RLS was identified in 9.4% subjects with higher prevalence among women (13.6% women vs. 4.1% men; P < 0.001). RLS was significantly more prevalent at higher altitudes (12.2% at 1900-2000 m and 11.8% at 3200 m) compared to low altitude (2.5% at 400 m). The low altitude prevalence matched that reported in prior studies of RLS in India. Subjects with medical disorders sometimes related to RLS (eg, peripheral neuropathy, COPD, varicose veins and anemia) also had higher prevalence of RLS. Binary logistic regression controlling for female gender, number of pregnancies, peripheral neuropathy, varicose veins, anemia showed that high altitude independently significantly increased the likelihood of RLS (OR: 5.4, 95% CI: 2.8, 10.4). CONCLUSION: RLS is about five times more prevalent at high than low altitudes even when controlling for effects of other medical conditions associated with increased risk of RLS.

Perceived sleep deficit is a strong predictor of RLS in multisite pain - A population based study in middle aged females.

BACKGROUND: Chronic pain conditions as well as Restless Legs Syndrome (RLS) are known to be associated with subjectively and objectively disturbed sleep. RLS has been recently described as highly prevalent in multisite pain and the role of sleep as a modifying factor in this RLS phenotype is unknown. This study aimed to investigate if perceived sleep deficit and other sleep related parameters predict RLS in subjects with multisite pain. CURRENT KNOWLEDGE/STUDY RATIONALE: We have recently demonstrated a strong association between Restless Legs Syndrome (RLS) and number of pain locations. In the current analysis we hypothesized that impaired sleep predicts RLS in subjects with multisite pain. METHOD: Questionnaire-based data from 2727 randomly selected women aged 18-64 years were used to analyze RLS symptoms, self-reported sleep quality, and the degree of daytime sleepiness (Epworth Sleepiness Scale (ESS)) in relation to type, degree and localization of body pain. Potential confounders including anthropometrics, pain localization, co-morbidities, and medication were adjusted for in the Generalized Linear Models (GLM). RESULTS: Perceived sleep deficit ≥90min (OR 2.4 (1.5-3.8), p<0.001) and frequent nocturnal awakenings (OR 2.3 (1.4-3.6), p<0.001) were the strongest sleep related predictors for RLS in subjects with multisite pain. Additional factors include prolonged sleep latency (≥30min, OR 1.8 (1.1-2.8), p=0.01) and daytime symptoms like elevated daytime sleepiness (ESS score ≥9, OR 1.8 (1.2-2.7), p=0.005). Accordingly, RLS diagnosis was associated with impaired sleep quality (TST (Total Sleep Time) -8.2min, sleep latency +8.0min, and number of awakenings from sleep +0.4, p<0.01). ESS score increased with RLS diagnosis (+0.74, p<0.01) and number of pain locations (0.5, 1.7, and 1.8 for 1, 3, and 5 pain areas, p<0.001). In addition, confounders like pain severity, the history of psychiatric disease, and current smoking were associated with impaired sleep quality in this group of females. CONCLUSIONS: Perceived sleep deficit and sleep fragmentation are the strongest sleep related predictors of RLS in multisite pain. Potential implication of our results are that clinical management programmes of RLS in subjects with multisite pain need to consider both sleep quality and sleep quantity for individually tailored treatment regimes. STUDY IMPACT: RLS, pain, and sleep disorders are highly interrelated. Our study strongly suggests that clinical management of RLS in patients with multisite pain needs to consider sleep quality as an independent risk factor.