Risk Of Restless Legs Syndrome Research Articles

Risk of Restless Legs Syndrome Following Tension-Type Headache: A Nationwide Population-Based Cohort Study.

Migraine and restless legs syndrome (RLS) appear to be associated, but the relationship between tension-type headache (TTH) and RLS is unknown. This nationwide, population-based, retrospective cohort study explored the potential association between TTH and RLS.We identified 15,504 patients with newly diagnosed TTH from 2000 to 2007 and 62,016 individuals without TTH who were selected by frequency matched based on sex, age, and the index year. The study participants were followed until diagnosed with RLS, withdrawal from the NHI program, or the end of 2011. Cox proportional hazard models were used to identify risk factors for RLS in TTH patients.After adjusting for sex, age, comorbidity, and medications, TTH was significantly associated with an increased risk of RLS (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.22–2.02). The risk was most prominent in patients aged 20 to 39 years in the TTH group, which exhibited a 2.60-fold higher risk (95% confidence interval = 1.53–4.42) of RLS compared with the non-TTH group. The TTH group had a higher risk of RLS than that of the non-TTH group regardless of sex.Tension-type headache appears to be associated with an increased risk of developing RLS. This similarity to migraines may indicate that headache and RLS have a coincident pathophysiological mechanism, a possibility requiring further study. Clinicians should be more attentive to RLS as a possible comorbidity in patients with TTH.

Association Between Vitamin D Receptor rs731236 (Taq1) Polymorphism and Risk for Restless Legs Syndrome in the Spanish Caucasian Population.

Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS.We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay.The frequencies of the rs731236AA genotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P < 0.005 and < 0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS.These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.

A peripheral pathway to restless legs syndrome? Clues from familial amyloid polyneuropathy

BackgroundThe relationship between restless legs syndrome (RLS) and peripheral neuropathy remains unclear. In order to clarify this relationship, we investigated if RLS is increased in familial amyloid polyneuropathy related to transthyretin (TTR-FAP) and investigated factors associated with RLS in this population. MethodsRLS frequency was compared between TTR-FAP patients and controls. Secondly, TTR-FAP patients with and without RLS were compared regarding demographic and clinical characteristics. ResultsRLS frequency was significantly increased in TTR-FAP, with 18/98 (18.4%) cases contrasting with 5/104 (4.8%) controls (p-value 0.002). This difference remained significant after adjusting for confounders. In TTR-FAP patients, female sex (p-value 0.037), obesity (p-value 0.036) and weight excess (p-value 0.048) were associated with RLS, contrary to other classical RLS risk factors. ConclusionsRLS frequency is increased in TTR-FAP, thus supporting an association between RLS and neuropathy. This may represent a peripheral pathway in RLS pathogenesis. Furthermore, our results suggest that female sex and obesity/weight excess may be risk factors for RLS development among TTR-FAP patients.

Restless legs syndrome: associated non-motor symptoms and medical comorbidities: a controlled study

Introduction: Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by discomfort or pain, predominantly in the legs, resulting in an urge to move during times of rest. These disturbances are often accompanied by sleep fragmentation, which can significantly increase medical comorbidities over time and can have a detrimental effect on a patient’s overall quality of life. In this retrospective study, we examined the temporal relationship between the time of RLS diagnosis and the onset of non-motor symptoms (NMS) and medical comorbidities. Patients and methods: Thirty-six RLS patients were evaluated for age at: symptom onset, time of diagnosis, time of occurrence of NMS, and medical comorbidities. We used structured interviews, validated questionnaires, and past medical records to aggregate and verify patient data. There was no clinical evidence to suggest secondary RLS in any patient at time of diagnosis. Results: Twenty-five patients were diagnosed as having RLS alone and eleven were diagnosed with RLS and Parkinson’s disease (RLS + PD). In the RLS + PD group, irrespective of which disorder presented first, we found that patients exhibited symptoms of RLS at a significantly later age than those patients with RLS alone (P,0.05). The incidence and severity of NMS were significantly higher in the RLS + PD group compared to RLS alone and controls (P,0.001). Increased risk of RLS was identified in patients exhibiting mood changes and sleep deficits, and these risk factors manifested 5 and 10 years prior, respectively, to their diagnosis. Conclusion: Primary RLS develops earlier in those patients who only have RLS compared to those who later also develop PD. Mood and sleep impairment can be present years prior to the diagnosis of RLS. Other medical comorbidities associated with RLS included hypertension, hyperlipidemia, arthritis, chronic pain, and diabetes.

Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome.

Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS.We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs.The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.

Increased prevalence of restless legs syndrome in patients with Crohn’s disease

To determine (a) the incidence of restless legs syndrome (RLS) in patients with Crohn's disease (CD), (b) whether and how the occurrence and severity of RLS is related to severity of CD, and (c) how RLS influences the quality of life of CD patients. We carried out a cross-sectional questionnaire study in a random selection of 144 CD patients and 80 controls. Differences were calculated using a χ-test (categorical data), an independent T-test (continuous data, normal distribution), or a Mann-Whitney U-test (continuous data, non-normal distribution). Logistic regression analysis was carried out to establish the relation between CD and RLS after adjusting for risk factors. The prevalence of RLS was 25.7% (37/144) in CD patients compared with 12.5% (10/80) in the control group (P=0.02). CD patients using caffeine and patients with arthralgias had a higher risk for RLS. A higher score on the modified Harvey Bradshaw Index and CD-related surgery were also associated with a higher risk for RLS. CD-related surgery was also associated with a more severe course of RLS. Patients and controls with RLS had a lower score on 'physical functioning', one of the subcategories of the RAND-36 quality-of-life questionnaire. RLS occurs more frequently in patients with CD compared with healthy individuals. A more severe course of CD seems to be associated with a higher risk for RLS. The presence of RLS has a negative influence on quality of life, mainly interfering with physical activities of daily life.

Genetic markers of Restless Legs Syndrome in Parkinson disease.

Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype. Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models. None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p=0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York. RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities.

Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome.

Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.

Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD.

To examine association between periodic leg movements (PLM) and 13 single nucleotide polymorphisms (SNPs) in 6 loci known to increase risk of restless legs syndrome (RLS). Stanford Center for Sleep Sciences and Medicine and Clinical Research Unit of University of Wisconsin Institute for Clinical and Translational Research. Adult participants (n = 1,090, mean age = 59.7 years) from the Wisconsin Sleep Cohort (2,394 observations, 2000-2012). A previously validated automatic detector was used to measure PLMI. Thirteen SNPs within BTBD9, TOX3/BC034767, MEIS1 (2 unlinked loci), MAP2K5/SKOR1, and PTPRD were tested. Analyses were performed using a linear model and by PLM category using a 15 PLM/h cutoff. Statistical significance for loci was Bonferroni corrected for 6 loci (P < 8.3 × 10(-3)). RLS symptoms were categorized into four groups: likely, possible, no symptoms, and unknown based on a mailed survey response. Prevalence of PLMI ≥ 15 was 33%. Subjects with PLMs were older, more likely to be male, and had more frequent RLS symptoms, a shorter total sleep time, and higher wake after sleep onset. Strong associations were found at all loci except one. Highest associations for PLMI > 15/h were obtained using a multivariate model including age, sex, sleep disturbances, and the best SNPs for each loci, yielding the following odds ratios (OR) and P values: BTBD9 rs3923809(A) OR = 1.65, P = 1.5×10(-8); TOX3/BC034767 rs3104788(T) OR = 1.35, P = 9.0 × 10(-5); MEIS1 rs12469063(G) OR = 1.38, P = 2.0 × 10(-4); MAP2K5/SKOR1 rs6494696(G) OR = 1.24, P = 1.3×10(-2); and PTPRD(A) rs1975197 OR = 1.31, P = 6.3×10(-3). Linear regression models also revealed significant PLM effects for BTBD9, TOX3/BC034767, and MEIS1. Co-varying for RLS symptoms only modestly reduced the genetic associations. Single nucleotide polymorphisms demonstrated to increase risk of RLS are strongly linked to increased PLM as well, although some loci may have more effects on one versus the other phenotype.

Medications associated with restless legs syndrome: a case–control study in the US Renal Data System (USRDS)

ObjectiveThe objective of this study was to determine the association between the usage of four classes of “at-risk” medications (antidepressants, neuroleptics, antihistamines, and antiemetics with dopamine blockade) and restless legs syndrome (RLS) in dialysis patients within the United States Renal Data System (USRDS). MethodsThis was a case–control design within a national (United States) patient registry of all patients with end-stage renal disease (ESRD) in the USRDS anytime during the period of 1 October 2006 to 31 December 2010, inclusive. A total of 16,165 ESRD patients (3234 cases; 12,931 age-, sex-, and race-matched controls) were studied. ResultsAll four classes of “at-risk” medications see widespread use among patients in the USRDS. All were associated with increased odds of an RLS diagnosis (range of odds ratios, 1.47–2.28; all p < 0.0001) during the period of observation. Results were unchanged when controlling for time on hemodialysis. Usage of more than one class of medication increased the odds for having RLS. ConclusionsESRD patients often receive medication intended for relief of conditions associated with their disease, such as depression and psychological issues, pruritus, and gastroparesis; however, such medications may increase the risk of RLS. Given the high prevalence of RLS in ESRD patients, these medications should only be used when their benefits clearly outweigh the risk of development of the troubling and distressing symptoms of RLS.

Multimorbidity and the risk of restless legs syndrome in 2 prospective cohort studies.

Our aim was to evaluate the association between the cumulative effect of comorbidity and the risk of restless legs syndrome (RLS) in 2 population-based German cohort studies. The Dortmund Health Study (DHS) (n = 1,312; median follow-up time: 2.1 years) and the Study of Health in Pomerania (SHIP) (n = 4,308; median follow-up time: 5.0 years) were used for the analyses. RLS was assessed at baseline and follow-up according to the RLS minimal criteria. A comorbidity index was calculated as a sum of the following conditions: diabetes, hypertension, myocardial infarction, obesity, stroke, cancer, renal disease, anemia, depression, thyroid disease, and migraine. The relationship between comorbidity and incident RLS was analyzed with multivariate logistic regression models. An increase in the number of comorbid conditions at baseline predicted prevalent RLS (DHS: trend odds ratio [OR] = 1.24, 95% confidence interval [CI] 0.99-1.56; SHIP: trend OR = 1.34, 95% CI 1.18-1.52) and incident RLS (DHS: trend OR = 1.32, 95% CI 1.04-1.68; SHIP: trend OR = 1.59, 95% CI 1.37-1.85) after adjustment for several covariates. The ORs for incident RLS associated with 3 or more comorbid diseases (DHS: OR = 2.51, 95% CI 1.18-5.34; SHIP: OR = 4.30, 95% CI 2.60-7.11) were higher than the ORs for any single disease. Multimorbidity was a strong risk factor for RLS in these 2 population-based cohort studies. The results support the hypothesis that cumulative disease burden is more important than the presence of a specific single disease in the pathophysiology of RLS.

Prospective study of obesity, hypertension, high cholesterol, and risk of restless legs syndrome.

Because previous cross-sectional studies suggest an association between metabolic disorders and restless legs syndrome (RLS), we prospectively evaluated whether obesity, hypercholesterolemia, and hypertension were associated with increased risk of RLS. Our study consisted of 42,728 female participants from the Nurses' Health Study II and 12,812 male participants from the Health Professionals Follow-up Study, free of RLS at baseline (2002 for men and 2005 for women), and free of diabetes and arthritis through follow-up (2002-2008 for men and 2005-2009 for women). RLS symptoms were assessed using the International RLS Study Group's standardized questionnaire. We considered RLS symptoms a "case" if the symptoms occurred ≥5 times/month and met International RLS Study Group criteria. We found that obesity was associated with an increased risk RLS among both men and women (P difference for sex >0.5). The pooled multivariate-adjusted odds ratio (OR) for RLS was 1.57 (95% confidence interval [CI]: 1.33-1.85; P trend <0.0001) for body mass index >30 versus ≤23 kg/m(2) and 1.56 (95% CI: 1.29-1.89; P trend = 0.0001) comparing two extreme waist circumference quintiles, adjusting for age, ethnicity, smoking, physical activity, use of antidepressant, and other covariates. A similar significant association was found for high cholesterol; the pooled adjusted OR for total serum cholesterol >240 versus <159 mg/dL was 1.33 (95% CI: 1.11-1.60; P trend = 0.002). There was no significant association between hypertension and RLS risk (adjusted OR: 0.90; 95% CI: 0.79-1.02). In this large, prospective study, we found that obesity and high cholesterol, but not high blood pressure, were significantly associated with an increased risk of developing RLS. © 2014 International Parkinson and Movement Disorder Society.

Restless legs syndrome and multiple sclerosis: a population based case−control study in Catania, Sicily

A population-based case-control study in the city of Catania, Sicily, was carried out to determine restless legs syndrome (RLS) prevalence and its association with multiple sclerosis (MS). Patients were randomly selected from a cohort of MS patients resident in the study area and a group of age and sex matched controls was enrolled from the general population. RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria. In total, 152 MS patients and 431 controls were included in the study. A significantly higher prevalence of RLS amongst MS patients (14.5%) compared with controls (6.0%) was detected, corresponding to an almost threefold increased risk (odds ratio 2.7, 95% confidence interval 1.4-5.0) of developing RLS. Spinal cord lesions in MS patients were associated with a higher risk of RLS (odds ratio 3.7, 95% confidence interval 1.1-13.5). RLS was strongly associated with MS, with a significantly higher risk in patients presenting spinal cord lesions.

The solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, rs3794087 variant and assessment risk for restless legs syndrome

ObjectiveA glutamatergic dysfunction has been postulated to play a role in restless legs syndrome (RLS) pathophysiology, as glutamate concentrations have been found to increase in the thalamus of RLS patients. The aim of our study was to investigate the possible association between the single nucleotide polymorphism (SNP) rs3794087 in the solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, related with glutamate transport and the risk for RLS. MethodsWe studied the allelic and genotype frequencies of the SNP rs3794087 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. ResultsThe rs3794087 genotype and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, and family history of RLS. ConclusionsThe results of our study suggest that the rs3794087 polymorphism is not related to the risk for RLS.

Multimorbidity and the risk of restless legs syndrome in two prospective cohort studies

The majority of studies analysing the associations between chronic diseases and RLS is of cross-sectional design and focus on the presence of individual conditions only. The cumulative effect of existing co-morbidities has not been considered. Aim of this analysis was to evaluate the association between multimorbidity and the risk of RLS in two population-based cohort studies. Two independently conducted, population-based prospective cohort studies, the Dortmund Health Study (DHS, n = 1312/1122 (baseline/follow-up), median follow-up time: 2.1 years) and the Study of Health in Pomerania (SHIP, n = 4308/3300, median follow-up time: 5.0 years) were used for the analyses. RLS was assessed in both studies at baseline and follow-up according to the RLS minimal criteria. A co-morbidity index was calculated as a sum of the following conditions: diabetes mellitus, hypertension, myocardial infarction, obesity, stroke, cancer, renal disease, anemia, depression, thyroid disease, and migraine. The independent relationship between co-morbidities and incident RLS was analyzed with multivariate logistic regression models. Pooled odds ratios were calculated using a fixed-effect model and the Mantel–Haenszel method. An increase in the number of co-morbid conditions at baseline was associated both with prevalent RLS (DHS: trend odds ratio (OR) = 1.24, 95% CI 0.99–1.56; SHIP: trend OR = 1.34, 95% CI 1.18–1.52) and incident RLS (DHS: trend OR = 1.32, 95% CI 1.04–1.68; SHIP: trend OR = 1.59, 95% CI 1.37–1.85) after adjustment for age, gender, education, alcohol consumption, smoking, and physical activity. The ORs for incident RLS associated with three or more co-morbid diseases (DHS: OR = 2.51, 95% CI 1.18–5.34; SHIP: OR = 4.30, 95% CI 2.60–7.11) were the highest of all the ORs, and they were also greater than the pooled ORs calculated for the single diseases (DHS: OR = 1.43, 95% CI 1.18–1.73; SHIP: OR = 1.56, 95% CI 1.39–1.75). Multimorbidity is a strong risk factor for RLS in two independently conducted population-based cohort studies. The association was stronger for incident RLS than for prevalent RLS, and the presence of three or more diseases increased the risk clearly beyond that of any single disorder. The results support the hypothesis that the cumulative disease burden is more important than the presence of a specific single disease in the pathophysiology of RLS. We are indebted to all participants for their outstanding commitment and cooperation, to the entire staff of each study for their expert and unfailing assistance. Data collection in the Dortmund Health Study was supported by the German Migraine & Headache Society and by unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster. SHIP is part of the Community Medicine Research Net of the University of Greifswald (available at http://medizin.uni-greifswfald.de/cm) and was funded by grant ZZ9603 from the Federal Ministry of Education and Research, Berlin, and the Ministers of Cultural and Social Affairs of the Federal State of Mecklenburg West Pomerania, Schwerin.

Lifestyle factors and risk of restless legs syndrome: Prospective Cohort study

We conducted a prospective study to examine the association between lifestyle factors (i.e., obesity, physical activity, smoking, intake of alcohol and caffeine, and overall diet quality) and the risk of developing restless legs syndrome (RLS). The study population included 12,812 men participating in Health Professionals Follow-up Study and 42,728 women participating in the Nurses’ Health study II, free of RLS at baseline (2002 for the HPFS and 2005 for the NHS II) and free of diabetes and arthritics through follow-up. RLS was assessed via a set of questions recommended by International Restless Legs Syndrome Study group. The Information was collected on height, weight, level of physical activity, dietary intake, and smoking status via questionnaires. During 4–6 years of follow-up, we identified 1,538 incident RLS cases. Participants with normal weight, and who were physically active, non-smoker, and with some alcohol consumption tended to have a lower risk of developing RLS. When we combined the effects of these four factors together, we observed a dose response relationship between the increased number of healthy lifestyle factors and a low risk of RLS: the adjusted pooled relative risk was 0.60 (95% CI: 0.42–0.86) for 4 vs.0 healthy factors ( P trend = 0.01), after adjusting for age, depression, and other potential confounders. In contrast, we did not observe significant associations between caffeine consumption, diet quality, as assessed by the Alternate Healthy Eating Index, and altered RLS risk in men and women. Several modified lifestyle factors may play an important role in RLS risk. Funding by government grant: 5R01NS062879-02 (PI: Xiang Gao). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Restless legs syndrome and its association with poor sleep quality, mood disorders, and one year cardiovascular mortality in patients on chronic dialysis

Introduction Restless legs syndrome (RLS) is common among uremic patients.We assessed RLS and its association with sleep quality, psychological well-being, and one year cardiovascular mortality in patients on chronic hemodialysis (HD) and peritoneal dialysis (PD). Materials and methods Patients on chronic HD and PD were consecutively included from two medical centers in Isfahan city (Iran).Diagnosis of RLS was based on the International Restless Legs Syndrome Study Group criteria, confirmed by the validated Cambridge-Hopkins questionnaire.Patients also completed the Pittsburgh Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale (HADS). Laboratory tests were done for iron state, kidney function, and electrolytes.Patients were followed for one year, cardiovascular mortality and new events were recorded.Univariate and multivariate analyses were performed to analyze the data. Results Ninety patients were evaluated (53 males, age = 54.2 ± 15.2 years, disease duration = 5.3 ± 4.5 years).RLS was diagnosed in 26.6% of the patients (35.1% in females vs.20.7% in males, P = 0.019).Poor sleep quality was frequent in 86.6% of the cases in each group of the HD and PD patients.RLS severity was associated with poor sleep quality (r = 0.503, P = 0.009) and depression (r = 0.380, P = 0.05).Both anxiety and depression were also associated with poor sleep quality (r = 0.463 and 0.478, respectively, P 0.001).In multivariate analysis, having RLS ( β = 1.334, P = 0.007), anxiety ( β = 0.291, P = 0.005), and depression ( β = 0.246, P = 0.020), were independently associated with poor sleep quality.No specific association between laboratory tests’ results and overall sleep quality was observed.One year new cardiovascular events (26.0% vs.12.3%, P = 0.113) and subsequent mortality (13.0% vs.7.6%, P = 0.347) were more frequent, though not statistically significant, in those with RLS than those without RLS. Conclusion Among patients on chronic dialysis, RLS and poor sleep quality are highly frequent.Mood disorders and RLS are important independent predictors of poor sleep quality.On the other hand, RLS may be associated with increased risk of cardiovascular risk and mortality in dialysis patients.Further studies with larger sample size and longer follow-ups are required for better understanding of risk factors and also cardiovascular risk of RLS and poor sleep quality in these patients. Acknowledgements Authors are thankful to Prof. Richard Allen from the Johns Hopkins University and Dr. Mohammad Saadatnia from the Isfahan University of Medical Sciences for helping us in designing the study.

Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis

BackgroundThe prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea. MethodsOur study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists. ResultsOf the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P=.042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06±8.43years vs 62.46±11.05years; P=.049) and had higher pain scores (visual analog scale [VAS], 4.69±2.52 vs 2.72±2.12; P=.002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups. ConclusionsThe prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.

Excessive daytime sleepiness in type 2 diabetes

To examine excessive daytime sleepiness (EDS) in type 2 diabetes. Patients (N = 110) were evaluated regarding Epworth Sleepiness Scale (EDS), sleep quality (Pittsburgh Sleep Quality Index), depressive symptoms (Beck Depression Inventory), Restless Legs Syndrome (RLS), risk of obstructive sleep apnea (OSA) (Berlin questionnaire), and comorbidity severity (Charlson Comorbidity Index). Patients were compared with individuals with arterial hypertension and without diabetes. Diabetic patients had more EDS, depressive symptoms, and higher comorbidity severity than hypertensive patients (p < 0.005). In diabetic patients, poor quality sleep (53.3%), and high risk of OSA (40.9%) and RLS (14.5%) were found; EDS (55.5%) was associated with depressive symptoms present in 44.5% individuals (OR = 1.08; 95% CI: 1.01-1.15), and remained so after data were controlled for age, gender, body mass index, and glycated hemoglobin (OR = 2.27; 95% CI 1.03-5.03). Sleep abnormalities are frequent. EDS affects most of the patients and is independently associated with depressive symptoms. Adequate antidepressant therapy should be tested for the effects on EDS.

Association between restless legs syndrome and hypertension: a preliminary population‐based study in South Tyrol, Italy

Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an irresistible urge to move the legs accompanied by paresthesia and/or dysesthesia that begins or worsens in the evening and night and that is partially or totally relieved by movement. Many studies have investigated the association between RLS and cardiovascular risk factors, particularly hypertension, leading to conflicting results. The aim of this study was to assess the association between RLS and hypertension considering also other cardiovascular risk factors that could act as confounders. In all, 1709 participants of an on-going adult population-based study performed in South Tyrol, northern Italy, were enrolled. RLS was assessed through face-to-face interviews according to current International Restless Legs Syndrome Study Group diagnostic criteria. The presence of hypertension was self-reported and determined by questionnaires administered by trained study nurses. The association between RLS and hypertension was not significant after adjustment for age, sex, diabetes mellitus, history of myocardial infarction, raised blood lipids and body mass index (odds ratio 1.24, 95% CI 0.85-1.80, P = 0.271). Despite the small sample size of this study, RLS and hypertension were not associated in our adult population after adjustment for possible confounding factors. The presence of other cardiovascular risk factors could play a role as a confounder of this association.