Association Of Restless Legs Syndrome Research Articles

454 Association of Restless Legs Syndrome with Adverse Perinatal Outcomes

454 Association of Restless Legs Syndrome with Adverse Perinatal Outcomes

456 Association of Restless Legs Syndrome in Pregnancy with Cardiovascular Health 2-7 years after first birth

456 Association of Restless Legs Syndrome in Pregnancy with Cardiovascular Health 2-7 years after first birth

Association of Restless Legs Syndrome with Glycemic Control and Psychological Status in Adults with Type 2 Diabetes: A Systematic Review

Background: Evidence is still lacking regarding the association of restless leg syndrome (RLS) on glycemic control and psychological status in diabetic patients.
 Aims: To summarize the evidence regarding the association of RLS with glycemic control and psychological status in adults with type 2 diabetes.
 Methods: The literature search compassed all English-published studies from inception till the 21st of May 2023 on the electronic databases of MEDLINE/PubMed, Cochrane Library, Web of Science, and ProQuest. The search terms included “Diabetes Mellitus, Type 2” AND "restless legs syndrome”. We created a narrative synthesis for the outcomes and pooling of the glycated hemoglobin (HbA1c) levels.
 Results: Sixteen studies were included. Pooling of the HbA1c levels showed a lack of significant differences between the RLS+ve and RLS-ve groups. Seven out of eight studies showed a significant decrease in sleep quality. Three studies assessed the quality of life and found a marked decrease in RLS+ve patients. Two studies out of four found a significant association of RLS with depression, while the other two found a non-significant increase with RLS.
 Conclusion: There is no evidence that RLS in type 2 diabetic patients is associated with poor glycemic control. The evidence suggests that RLS is associated with a reduction in sleep quality and quality of life. The evidence is inconclusive regarding the association of RLS with depression due to the low number of studies. Physicians should be aware of the associated disorders with RLS in diabetic patients and endeavour to identify and alleviate them.

SUBCLINICAL TARGET ORGAN DAMAGE IN PATIENTS WITH RESTLESS LEGS SYNDROME. A PRELIMINARY OBSERVATIONAL STUDY

Objective: Restless legs syndrome (RLLS) is a frequent and often underdiagnosed type of insomnia. Since other types of insomnia present a strict association with cardiovascular disease, our study aimed to evaluate the possible association of RLLS with some early markers of cardiovascular organ damage. Design and method: Patients with other types of insomnia and those with central nervous system diseases were excluded. Twenty-eight patients (mean age: 63,1±13,9 years; 28.6% males) participated in the study. Fourteen subjects with diagnosis of RLLS according to International diagnostic criteria (Allen RP et al. 2014 Sleep Medicine) (disease mean duration 9.6±9.2 years; International Restless Legs Scale score 22.9±5.2) were matched for sex, age and major cardiovascular risk factors with 14 controls. In both groups, peripheral Blood Pressure (pBP), central Blood Pressure (cBP) and Pulse Wave Velocity (PWV) were assessed by the SphygmoCorXCEL. Carotid Intima-Media Thickness (cIMT) and the carotid Distensibility Coefficient (cCD) were assessed by ultrasound connected with an image acquisition and analysis system (CardiovascularSuite). Results: We did not find any significant difference between the two groups in the indices of subclinical vascular damage. In the RLS group, blood pressure measurements significantly correlated with all the markers of subclinical vascular damage, particularly pSBP was associated with PWV (r = 0.53, p = 0.009), Pulse Pressure correlated with cIMT (r = 0.58, p = 0.01) and cDBP was inversely related to cDC (r = -0.53; p = 0.03). Conclusions: Our data did not show significant differences in markers of early vascular damage between patients with RLS and matched controls. As expected, the markers of vascular damage were associated with BP. The present is only a pilot study; further studies with a larger sample size are required to confirm our findings.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

ASSOCIATION OF BONE MINERAL PROFILE WITH RESTLESS LEG SYNDROME IN PATIENTS WITH END STAGE RENAL DISEASE.

Background: Restless leg syndrome (RLS) is one of the problem hemodialysis patients may encounter. This study was done to find out the association of restless legs syndrome (RLS) in end stage renal disease patients with serum calcium, phosphorus and parathyroid hormone levels. Methods: This cross-sectional observational study was done at The Kidney Centre, postgraduate Training Institute Karachi, Pakistan from Jan to June 2020. One hundred and twelve patients on three per week hemodialysis for more than three months at our hemodialysis centre were face to face interviewed as per International Restless Legs Syndrome Study Group criteria (IRLSSG) for the presence of RLS symptoms. Their demographic data and laboratory values were recorded from history chart and computer records. The bone mineral profile in this study includes serum calcium (corrected for albumin), serum phosphate levels and serum intact Parathyroid hormone (iPTH) levels. Statistical analyses were done by using SPSS-21. Results: In our study, 38.4% patients had RLS. Serum phosphorus levels were significantly higher in patients with RLS as compared to those who didn’t have RLS. No significant association of serum calcium and Parathyroid hormone (PTH) levels with RLS was found. Conclusion: There is a high prevalence of RLS in ESRD patients as compared to general population. Serum phosphorus levels need to be observed and corrected along with maintenance of calcium and PTH levels to improve symptoms of RLS in these patients.

Restless Legs Syndrome Among Sudanese Patients With Type 2 Diabetes Mellitus: A Case-Control Study.

BackgroundThere is increasing awareness about the association of restless legs syndrome (RLS) with type 2 diabetes. This study assessed RLS and its associations among patients with diabetes.Material and methodsThis case-control study was conducted among 160 subjects (82 patients with diabetes and 78 controls) attending a diabetic clinic in Omdurman, Sudan, during the period from June 2018 to September 2019. A structured questionnaire was used to collect demographic factors, diabetic neuropathy, nephropathy, retinopathy, and macrovascular complications. The neck circumference was measured to assess adiposity, and a blood sample was taken for the glycated hemoglobin (HbA1c) estimation. The local ethical committee approved the research, and the Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY) was used for data analysis. A P-value of <0.05 was considered significant.ResultsThere were 82 patients with type 2 diabetes and 78 controls matched for age and sex. Restless legs syndrome was higher among patients with diabetes (31.7% vs. 10.3%%) with a significant statistical difference, P-<0.05. A direct positive relationship was found between restless legs syndrome and diabetic neuropathy (Wald=5.48, P-value=0.019, 95%CI 1.70-410.76), no relationship was found between RLS, diabetic retinopathy, glycated hemoglobin, sex, and neck circumference, P-values (0.757, 0.804, 0.317, and 0.361 respectively).ConclusionRestless legs syndrome was prevalent among patients with type 2 diabetes and was more common among patients with diabetic neuropathy, no relationship was found between restless legs syndrome, age, sex, neck circumference, HbA1c, and retinopathy

Association of Restless Legs Syndrome With Risk of Suicide and Self-harm

Restless legs syndrome (RLS) is a common neurologic disorder that has been previously found to be associated with higher odds of suicidal ideation. In the context of the increasing suicide rate in the United States, the evidence regarding the association between RLS and the risk of suicide and self-harm is limited. To investigate the association between RLS and risk of suicide and self-harm. This cohort study was performed using Truven Health MarketScan national claims data from 2006 to 2014; the baseline data were from 2006 to 2008, and the follow-up data covered 6 years (January 1, 2009, to December 31, 2014). Included were 24 179 nonpregnant participants with RLS and 145 194 age- and sex-matched participants without RLS at baseline (2006-2008), who were free of suicide, self-harm, cardiovascular disease, or cancer at study baseline. Data analysis was performed from February 1, 2018, to January 1, 2019. Diagnosis of RLS, as identified by the International Classification of Diseases, Ninth Revision code. Incident suicide and self-harm event, identified by the International Classification of Diseases, Ninth Revision diagnosis code. Among 169 373 participants in the current analysis, the mean (SD) age was 49.4 (9.1) years; 53 426 (31.5%) participants were men. During a mean (SD) follow-up duration of 5.2 (2.2) years, 119 incident suicide and self-harm cases were identified. Individuals with RLS had a higher risk of suicide or self-harm compared with those without RLS (adjusted hazard ratio, 2.66; 95% CI, 1.70-4.15), after adjusting for lifestyle factors (eg, alcohol and obesity), presence of chronic diseases (eg, depression, insomnia, diabetes, chronic kidney disease, peripheral neuropathy, iron-deficiency anemia, and Parkinson disease), and use of medications. Excluding those with depression, insomnia, obstructive sleep apnea, and other common chronic conditions, the significant association between RLS and suicide or self-harm persisted (adjusted hazard ratio, 4.14; 95% CI, 2.17-7.92). Restless legs syndrome was associated with a high risk of suicide and self-harm, and the risk was independent of most identified diseases and conditions.

Restless legs syndrome and cerebrovascular/cardiovascular events: Systematic review and meta-analysis.

We performed a systematic review and meta-analysis to evaluate the proposed association of restless legs syndrome (RLS) with cerebrovascular/cardiovascular outcomes. We calculated the corresponding odds ratios on the prevalence of cerebrovascular/cardiovascular risk factors and standardized mean differences on the reported mean age at baseline between RLS patients and controls. We also calculated the corresponding risk ratios and adjusted for potential confounders hazard ratios (HRsadjusted ) on the reported outcomes of interest between RLS patients and controls. We identified 8 eligible studies (644506 patients, mean age: 60.2years, 36.2% males; 3.3% with RLS). RLS patients were found to have significantly higher prevalence of hypertension (P=.002), diabetes (P=.003) and hyperlipidemia (P=.010) compared to controls. In the unadjusted analyses of prospective observational studies, RLS patients were found to have significantly higher risk for cerebrovascular ischaemia (P=.01) and all-cause mortality (P=.04) compared to controls during follow-up, while in the adjusted for potential confounders analyses RLS patients were only found to have a higher risk of all-cause mortality (HR adjusted=1.52, 95% CI: 1.17-1.97, P=.002). The present report does not provide evidence for an increased risk of cerebrovascular and cardiovascular events in RLS patients, which highlights the vast presence of confounding factors.

Association of restless legs syndrome and mortality in end-stage renal disease: an analysis of the United States Renal Data System (USRDS)

BackgroundObjective of the study is to assess prevalence and survival among end stage renal disease patients with restless legs syndrome (RLS) within a national database (USRDS).MethodsA case-control, retrospective analysis was performed. Differences in characteristics between the groups, RLS and those with no sleep disorder (NSD), were determined using χ2 tests. Cox proportional hazard regression was used to assess survival between those with RLS and propensity score matched controls.ResultsCases of restless legs syndrome were defined as patients that had received an ICD-9 code of 333.94 at any point during their treatment (n = 372). RLS group demonstrated a significantly higher proportion of patients with major depressive disorder, dysthymic disorder, anxiety, depression, minor depressive disorder, and psychological disorder. The difference between the survival was not statistically significant in those without sleep disorder as compared to those with RLS (HR =1.16±0.14, p = 0.3).ConclusionsTrue prevalence of RLS in dialysis patients can only be estimated if knowledge gap for care providers in diagnosis of RLS is addressed. RLS patients also have increased incidence of certain psychological disorders which needs to be addressed.

Restless Legs Syndrome and Sleep-Wake Disturbances in Pregnancy.

To estimate the association of restless legs syndrome (RLS) and its frequency with sleep-wake disturbances in pregnancy. A cohort of 1,563 women in their third trimester of pregnancy were recruited from prenatal clinics between March 2007 and December 2010. Demographic, pregnancy, and delivery data were extracted from medical records and sleep information was collected with questionnaires. To diagnose RLS, we used standardized criteria of RLS symptoms and frequency that were developed by the International Restless Legs Study Group. Logistic regression models were constructed to investigate the association of RLS and its frequency with sleep-wake disturbances (poor sleep quality, daytime sleepiness, poor daytime function) and delivery outcomes. Overall 36% of the pregnant women had RLS, and half had moderate to severe symptoms. Compared to women without RLS, those with RLS were more likely to have poor sleep quality (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7-2.9), poor daytime function (OR 1.9, 95% CI 1.4-2.4), and excessive daytime sleepiness (OR 1.6, 95% CI 1.3-2.0). A dose-response relationship also was evident between RLS frequency and each of the sleep-wake disturbances. There was no evidence for any association between RLS and delivery outcomes. RLS is a significant contributor to poor sleep quality, daytime sleepiness, and poor daytime function, all common and often debilitating conditions in pregnancy. Obstetric health care providers should be aware of these associations and screen women for RLS. A commentary on this article appears in this issue on page 857.

Restless legs syndrome and periodic leg movements in patients with movement disorders: Specific considerations.

Restless legs syndrome is a frequent neurological disorder with potentially serious and highly distressing treatment complications. The role and potential implications of periodic leg movements during sleep range from being a genetic risk marker for restless legs syndrome to being a cardiovascular risk factor. The diagnosis of restless legs syndrome in patients with daytime movement disorders is challenging and restless legs syndrome needs to be differentiated from other sleep-related movement disorders. This article provides an update on the diagnosis of restless legs syndrome as an independent disorder and the role of periodic leg movements and reviews the association of restless legs syndrome with Parkinson's disease and other movement disorders. © 2017 International Parkinson and Movement Disorder Society.

The Association of Restless Legs Syndrome to History of Gestational Diabetes in an Appalachian Primary Care Population.

Restless legs syndrome (RLS) is a burdensome sensorimotor disorder that has been linked to diabetes and obesity. However, the relationship of RLS to gestational diabetes mellitus (GDM), a common pregnancy complication strongly associated with obesity and a harbinger of diabetes, remains unknown. In this study, we examined the association of RLS to history of GDM in a sample of older female primary care patients. Participants were community-dwelling women aged ≥ 40 years drawn from an anonymous survey study of West Virginia adult primary care patients. Data gathered included detailed information on demographics, lifestyle factors, reproductive history, sleep patterns, and medical history; the survey also included an RLS diagnostic questionnaire. Women who were pregnant or had missing data on key variables were excluded from the analyses. Of the 498 participants included in the final analytic sample, 24.5% met diagnostic criteria for RLS (17.9% with symptoms at least once/week). After adjustment for demographics, lifestyle characteristics, body mass index, diabetes and other comorbid conditions, parity, and other factors, those reporting history of GDM were almost three times as likely to meet criteria for RLS (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.3, 5.3). This association increased in magnitude with increasing symptom frequency (adjusted OR for RLS symptoms ≥ 3×/week = 4.8, CI 2.1, 11.2, p for trend = 0.004). History of GDM was strongly and positively related to RLS in this study of older female primary care patients, offering further support for a possible role of metabolic dysregulation in RLS development.

Association of incident restless legs syndrome with outcomes in a large cohort of US veterans.

Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all-cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow-up time of 8.1 years (interquartile range: 7.0-8.5 years)] with baseline estimated glomerular filtration rate ≥ 60 mL min(-1) 1.73 m(-2), a propensity-matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all-cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2). Associations were examined using Cox models. The mean ± SD age of the propensity-matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min(-1) 1.73 m(-2). Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome-negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70-2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26-4.84) and 3.89 (3.07-4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74-3.66)] compared with restless legs syndrome-negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart disease, stroke and chronic kidney disease.

Association of restless legs syndrome, pain, and mood disorders in parkinson's disease

Purpose/Aims: The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. Methods: This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Results: Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients’ comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Conclusions: Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis

BackgroundRestless legs syndrome (RLS) is a common comorbidity in patients undergoing hemodialysis, but clinical factors predictive of RLS risk and severity have not been identified. The aims of this multicenter cross-sectional study were to document RLS prevalence and severity in patients undergoing hemodialysis and to identify associated risk factors. MethodsOne-hundred and fifty-nine stable patients on maintenance hemodialysis were enrolled (113 men, 46 women; mean age: 68 ± 11 years; mean duration of dialysis: 54 ± 60 months). Diagnosis of RLS was based on the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG), and RLS severity was assessed using the IRLSSG Severity Scale. Potential factors associated with RLS and IRLSSG Severity Scale score were assessed by univariate and multivariate regression analyses. ResultsRLS affected 22% of the study population. The RLS subgroup had a significantly longer duration of hemodialysis and higher cardiothoracic ratio compared to the non-RLS subgroup. The RLS subgroup also had significantly higher serum levels of high-sensitivity C-reactive protein, interleukin-6, ferritin, N-terminal pro-B-type natriuretic peptide, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and a significantly lower transferrin saturation level compared to the non-RLS subgroup, suggesting a chronic inflammatory state and associated oxidative stress in comorbid patients. Serum 8-OHdG level was an independent risk factor for high IRLSSG Severity Scale score. ConclusionThis study confirms the high prevalence of RLS among hemodialysis patients and identifies the oxidative stress marker serum 8-OHdG as a significant independent predictor of RLS severity. Further studies are needed to identify detailed risk factors and the pathophysiological role of oxidative stress in RLS.

The association of Restless Legs Syndrome with hypertension and cardiovascular disease.

Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder that appears to be surprisingly common in the community. Periodic limb movements in sleep are typically encountered in more than 80% of RLS patients and comprise involuntary muscular jerks in the lower limbs, such as flexion of the knees or ankles. Iron deficiency and dopaminergic neuronal dysfunction in the central nervous system are currently thought to be the likely pathophysiological culprits. There is evidence linking RLS to hypertension and cardiovascular disease. This short review will first present a synopsis of epidemiological, clinical, and pathophysiological data concerning the syndrome, and then information on the possible links between RLS and cardiovascular disorders

Critical periodic limb movement disorder followed by cardio-pulmonary arrest (CPA) two months later: a case report

One of the causes of epidemiological association of restless legs syndrome and cardiovascular disease is thought of as periodic limb movement during sleep associated with substantial elevation in heart rate (HR) and blood pressure. We describe a pacemaker-implanted patient with bradycardiac atrial fibrillation (AF), who was diagnosed with periodic limb movement disorder without marked HR elevation on polysomnographic examination, and progressed to CPA two months later. A 79-year old man came to our clinic because of daytime sleepiness. He had multiple histories, a cardiac pace-maker for bradycardiac AF and old myocardial infarction, hypertension, diabetes mellitus, coagulation factor deficiency, and renal failure. Polysomnography showed short sleep latency (1 min) with few respiratory events (AHI = 4.3) and few arousals (arousal index = 8.0). Sleep structure was poor with increased N1, decreased N2 and R. Periodic leg movement (PLM) during sleep index was 93.0. Heart rate increments for PLM without arousal and PLM with arousal are 0.585 ± 2.006 (0–36) and 1.029 ± 1.834 (0–10), respectively. Percentage of PLMs with HR elevation was only 27.8%. This patient is a good example of critical PLM, with higher PLM index, decreased percentage of PLM associated HR elevation and decreased HR increments. This was not an industry supported study. The author has indicated no financial conflict of interest.

A time sequence analysis of the relationship between cardiovascular risk factors, vascular diseases and restless legs syndrome in the general population

Previous cross-sectional studies regarding the association of restless legs syndrome (RLS) with cardiovascular morbidity are controversial. Our aim was to evaluate prospectively the relationship of cardiovascular risk factors and vascular diseases with incident RLS in the general population. The results are from two prospective population-based cohort studies: the Dortmund Health Study (n=1312, median follow-up of 2.1years) and the Study of Health in Pomerania (n=4308, median follow-up of 5.0years). RLS status was assessed twice according to the minimal criteria. Diabetes, hypertension, myocardial infarction and stroke, as well as currently taken medications, were assessed as self-reports. Body mass index and serum total cholesterol were also measured. The independent risks associated with each outcome were estimated by multivariable logistic regression models adjusted for comorbidities and behavioural factors. Obesity was an independent risk factor of incident RLS in the Dortmund Health Study, and higher body mass index was an independent risk factor in both studies. Diabetes, hypertension and hypercholesterolaemia were independent predictors of incident RLS in the Study of Health in Pomerania. The vascular comorbidity index, defined by the number of concurrent cardiovascular risk factors and vascular diseases, showed a positive association with incident RLS in both studies. RLS at baseline was not a significant predictor of any subsequent cardiovascular risk factors and/or vascular diseases in any of the studies. Cardiovascular risk factors and diseases predict the subsequent development of RLS in the general population. The presence of RLS is not a significant risk factor of cardiovascular morbidity.

Painful polyneuropathy associated with restless legs syndrome. Clinical features and sensory profile

The association of restless legs syndrome (RLS) with polyneuropathy, and its prevalence, have been evaluated differently throughout various studies. As subtypes of polyneuropathy characterized by neuropathic pain seem to be preferentially associated with RLS, we intended to investigate the prevalence and the features of RLS occurring with painful neuropathy, and to define whether there is a specific sensory phenotype. We prospectively investigated 58 consecutive patients with distal symmetric polyneuropathy and neuropathic pain or dysesthesia, using a bedside protocol for sensory assessment. RLS was diagnosed with an interview assessing the International RLS Study Group diagnostic criteria. Overall, RLS was reported by 21 patients (36.2%), but it was occurring at the time of the evaluation in 12 patients (20.7%), significantly more than in controls. RLS was chronic in nine patients and remitting-intermittent in 12 patients. No difference was demonstrated between patients with or without RLS. Comparing patients with chronic RLS and remitting-intermittent RLS, the latter had more severe electrophysiological changes, whereas hyperalgesia, suggesting central sensitization, was significantly more frequent in chronic RLS patients. RLS is frequently associated with painful polyneuropathy, in keeping with the hypothesis that its occurrence is favored by small fiber involvement. It represents a heterogeneous entity, differentiated in chronic and remitting-intermittent subtypes, possibly conditioned by indolent or aggressive neuropathy course and phenomena of central sensitisation.