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Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder negatively impacting sufferers' quality of sleep and health-related quality of life. The pathophysiology of RLS is poorly understood and research focusing on the link between RLS and inflammation has been limited. Our study aimed to investigate whether chronic inflammation markers C-reactive protein (CRP) and soluble urokinase-type plasminogen activator receptor (suPAR), as well plasma levels of five different cytokine-specific autoantibodies (c-aAb), i.e. modulators of inflammation, associate with RLS in otherwise healthy individuals. CRP, suPAR and c-aAb were measured in plasma samples of participants from the Danish Blood Donor Study in 2010. Returning donors between 2015 and 2018 completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment, resulting in datasets with RLS assessment and values for CRP (N = 3564), suPAR (N = 2546) and c-aAb (N = 1478). We performed logistic regression models using the CRP, suPAR or c-aAb as the independent variable and RLS status as the dependent variable, adjusted for appropriate covariates. Our study indicates that a high concentration of CRP is associated with RLS, while an increased probability of experiencing frequent RLS symptoms in those with an elevated plasma suPAR level appears to be mediated through lifestyle factors. We additionally report that a high titer of autoantibodies specific against the cytokine interferon-alpha was associated with RLS. Our results support the existence of links between systemic inflammation and RLS, though further RLS studies on CRP, suPAR and c-aAb in larger cohorts are warranted to confirm our findings and further reveal the hitherto underexplored links between RLS and inflammation. [ABSTRACT FROM AUTHOR]

Background: Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby impacting quality of sleep in sufferers. The pathophysiology of RLS is poorly understood but inflammation has been proposed as possibly being involved. The neutrophil-to-lymphocyte ratio (NLR) can be used as an inflammation marker but results from small studies have been inconclusive in determining whether NLR is associated with RLS. We aimed to assess whether an association between NLR and RLS exists in a large cohort of healthy individuals. Methods: Neutrophils and lymphocytes were measured in blood samples of 13,055 individuals from the Danish Blood Donor Study, all of whom completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment. Results: In the sample, 661 individuals were determined as current RLS cases (5.1%). A higher proportion of individuals with RLS were females (62.5% vs 47.5%; P<0.001) and RLS cases were older than controls (P<0.001), but no differences in body mass index (BMI), smoking or alcohol consumption were found between the two groups. An increased NLR was observed in RLS cases compared to controls (median NLR: 1.80 vs 1.72; P = 0.033). In an unadjusted logistic regression model, increased NLR was associated with RLS (OR = 1.10 per NLR unit increase [95%CI:1.01–1.20]; P = 0.032); however, the association was not significant in multivariate models adjusting for sex and age (P = 0.094) or sex, age, alcohol consumption, smoking status and BMI (P = 0.107). Conclusion: We found no association between RLS and NLR among Danish blood donors after adjusting for sex, age, alcohol consumption, smoking status and BMI. Further studies are needed to determine whether inflammation is a risk factor for RLS. [ABSTRACT FROM AUTHOR]

Background: Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby often impacting quality of sleep in sufferers. The aetiology of RLS is not completely understood although iron dysregulation has been suggested as a likely pathway. The relationship between RLS and the iron regulatory protein hepcidin has not been studied in large cohorts. We aimed to assess whether an association between plasma hepcidin variation and RLS exists in a large cohort of healthy individuals.Methods: Plasma hepcidin levels were measured in 9708 Danish blood donors from the Danish Blood Donor Study all of whom correctly completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment.Results: A total of 466 blood donors were determined as current RLS cases in the sample (4.8%). RLS cases had a significantly higher proportion of females (56.7% vs 46.7%; P < 0.001) and were older (median age [IQR] 40.6 years vs 38.0 years; P = 0.010) than controls. RLS cases were also more frequent smokers (P = 0.004). No significant differences were found in body mass index (BMI), alcohol consumption, time of donation and donation history between cases and controls. No difference in plasma hepcidin levels was observed between RLS cases and controls (median concentration [IQR]: 10.5 ng/ml [6.3-16.4] in RLS cases vs 10.5 ng/ml [6.0-16.5] in controls). Using a logistic regression model, we found that hepcidin levels were not associated with RLS after adjusting for age, sex, alcohol consumption, smoking status, donation time and donation history (OR = 1.00 [0.99-1.02] per 1 ng/ml increase of hepcidin; P = 0.429).Conclusion: Our study in Danish blood donors did not find an association between RLS and plasma hepcidin levels. Our findings suggest that plasma hepcidin's role as a potential diagnostic biomarker of RLS is inadequate. [ABSTRACT FROM AUTHOR]