Restless legs syndrome and conditions associated with metabolic dysregulation, sympathoadrenal dysfunction, and cardiovascular disease risk: A systematic review

Kim E. Innesa, b, , , Terry Kit Selfea, b, c, , Parul Agarwala, d, a Department of Community Medicine, West Virginia University School of Medicine, PO Box 9190, Morgantown, WV 26506-9190, USAb Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System, PO Box 800782, McLeod Hall, Charlottesville, VA 22908-0782, USAReceived 1 February 2011. Revised 7 April 2011. Accepted 11 April 2011. Available online 5 July 2011.View full text Restless legs syndrome (RLS) is a distressing sleep and sensorimotor disorder that affects a large percentage of adults in the western industrialized world and is associated with profound reductions in quality of life. However, the etiology of RLS remains incompletely understood. Enhanced understanding regarding both the antecedents and sequelae of RLS could shed new light on the pathogenesis of RLS. Evidence from an emerging body of literature suggests associations between RLS and diabetes, hypertension, obesity, and related conditions linked to sympathetic activation and metabolic dysregulation, raising the possibility that these factors may likewise play a significant role in the development and progression of RLS, and could help explain the recently documented associations between RLS and subsequent cardiovascular disease. However, the relation between RLS and these chronic conditions has received relatively little attention to date, although potential implications for the pathogenesis and treatment of RLS could be considerable. In this paper, we systematically review the recently published literature regarding the association of RLS to cardiovascular disease and related risk factors characterized by sympathoadrenal and metabolic dysregulation, discuss potential underlying mechanisms, and outline some possible directions for future research.

prs.rt("abs_end");Restless legs syndrome; RLS; Ekbom disease; Cardiovascular disease; Hypertension; Diabetes; Impaired glucose tolerance; Obesity; Weight gain; Dyslipidemia; Autonomic dysfunction; HPA axis dysfunction

Figures and tables from this article:

Table 1. Summary table of study characteristics. N = 30 studies (1995-2010).

Abbreviations: CVD = cardiovascular disease; DM = diabetes; DM2 = type 2 diabetes; dx = diagnosis; IGT = impaired glucose tolerance: IRLSSG = international restless legs syndrome study group; Min freq/sev = minimum frequency and/or severity; pts = patients; pts = patients; VA = veterans administration; w/ = with.

View Within ArticleTable 2. Relation of RLS to cardiovascular disease. Summary of study characteristics and findings (N = 15 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CAD = Coronary artery disease; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD = International Classification of Diseases; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infraction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); pt = patient; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleTable 3. Relation of RLS to hypertension: Summary of study characteristics and findings (N = 17 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DBP = diastolic blood pressure; DM = diabetes mellitus; DM2 = type 2 diabetes; DM1 = type 1 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); Pt = patient; RLS = restless legs syndrome; SBP = systolic blood pressure; SDB = Sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.* Calculated from data provided in paper.

View Within ArticleTable 4. Relation of RLS to diabetes and impaired glucose tolerance: Summary of study characteristics and findings (N=26 studies (1995-2010)).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BG = blood glucose; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HOMA = homeostasis model assessment; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; IGT = impaired glucose tolerance; ICSD = international classification of sleep disorders; IGR = impaired glucose regulation; IGT = impaired glucose tolerance; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MONICA = monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% Confidence Interval); pts = patients; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = Strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.*Calculated from data provided in table.

View Within ArticleTable 5. Relation of RLS to obesity, weight gain, and dyslipidemia: Summary of study characteristics and findings (N=18 studies with data on the association of RLS to obesity/weight gain, 7 studies with data on the association of RLS to lipid profiles).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICSD = international classification of sleep disorders; IRLS = intl RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = Monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% confidence interval); RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

prs.rt('data_end');

View the original article here

Restless legs syndrome and conditions associated with metabolic dysregulation, sympathoadrenal dysfunction, and cardiovascular disease risk: A systematic review

Kim E. Innesa, b, , , Terry Kit Selfea, b, c, , Parul Agarwala, d, a Department of Community Medicine, West Virginia University School of Medicine, PO Box 9190, Morgantown, WV 26506-9190, USAb Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System, PO Box 800782, McLeod Hall, Charlottesville, VA 22908-0782, USAReceived 1 February 2011. Revised 7 April 2011. Accepted 11 April 2011. Available online 5 July 2011.View full text Restless legs syndrome (RLS) is a distressing sleep and sensorimotor disorder that affects a large percentage of adults in the western industrialized world and is associated with profound reductions in quality of life. However, the etiology of RLS remains incompletely understood. Enhanced understanding regarding both the antecedents and sequelae of RLS could shed new light on the pathogenesis of RLS. Evidence from an emerging body of literature suggests associations between RLS and diabetes, hypertension, obesity, and related conditions linked to sympathetic activation and metabolic dysregulation, raising the possibility that these factors may likewise play a significant role in the development and progression of RLS, and could help explain the recently documented associations between RLS and subsequent cardiovascular disease. However, the relation between RLS and these chronic conditions has received relatively little attention to date, although potential implications for the pathogenesis and treatment of RLS could be considerable. In this paper, we systematically review the recently published literature regarding the association of RLS to cardiovascular disease and related risk factors characterized by sympathoadrenal and metabolic dysregulation, discuss potential underlying mechanisms, and outline some possible directions for future research.

prs.rt("abs_end");Restless legs syndrome; RLS; Ekbom disease; Cardiovascular disease; Hypertension; Diabetes; Impaired glucose tolerance; Obesity; Weight gain; Dyslipidemia; Autonomic dysfunction; HPA axis dysfunction

Figures and tables from this article:

Table 1. Summary table of study characteristics. N = 30 studies (1995-2010).

Abbreviations: CVD = cardiovascular disease; DM = diabetes; DM2 = type 2 diabetes; dx = diagnosis; IGT = impaired glucose tolerance: IRLSSG = international restless legs syndrome study group; Min freq/sev = minimum frequency and/or severity; pts = patients; pts = patients; VA = veterans administration; w/ = with.

View Within ArticleTable 2. Relation of RLS to cardiovascular disease. Summary of study characteristics and findings (N = 15 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CAD = Coronary artery disease; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD = International Classification of Diseases; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infraction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); pt = patient; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleTable 3. Relation of RLS to hypertension: Summary of study characteristics and findings (N = 17 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DBP = diastolic blood pressure; DM = diabetes mellitus; DM2 = type 2 diabetes; DM1 = type 1 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); Pt = patient; RLS = restless legs syndrome; SBP = systolic blood pressure; SDB = Sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.* Calculated from data provided in paper.

View Within ArticleTable 4. Relation of RLS to diabetes and impaired glucose tolerance: Summary of study characteristics and findings (N=26 studies (1995-2010)).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BG = blood glucose; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HOMA = homeostasis model assessment; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; IGT = impaired glucose tolerance; ICSD = international classification of sleep disorders; IGR = impaired glucose regulation; IGT = impaired glucose tolerance; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MONICA = monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% Confidence Interval); pts = patients; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = Strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.*Calculated from data provided in table.

View Within ArticleTable 5. Relation of RLS to obesity, weight gain, and dyslipidemia: Summary of study characteristics and findings (N=18 studies with data on the association of RLS to obesity/weight gain, 7 studies with data on the association of RLS to lipid profiles).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICSD = international classification of sleep disorders; IRLS = intl RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = Monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% confidence interval); RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

prs.rt('data_end');

View the original article here

Restless legs syndrome and conditions associated with metabolic dysregulation, sympathoadrenal dysfunction, and cardiovascular disease risk: A systematic review

Kim E. Innesa, b, , , Terry Kit Selfea, b, c, , Parul Agarwala, d, a Department of Community Medicine, West Virginia University School of Medicine, PO Box 9190, Morgantown, WV 26506-9190, USAb Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System, PO Box 800782, McLeod Hall, Charlottesville, VA 22908-0782, USAReceived 1 February 2011. Revised 7 April 2011. Accepted 11 April 2011. Available online 5 July 2011.View full text Restless legs syndrome (RLS) is a distressing sleep and sensorimotor disorder that affects a large percentage of adults in the western industrialized world and is associated with profound reductions in quality of life. However, the etiology of RLS remains incompletely understood. Enhanced understanding regarding both the antecedents and sequelae of RLS could shed new light on the pathogenesis of RLS. Evidence from an emerging body of literature suggests associations between RLS and diabetes, hypertension, obesity, and related conditions linked to sympathetic activation and metabolic dysregulation, raising the possibility that these factors may likewise play a significant role in the development and progression of RLS, and could help explain the recently documented associations between RLS and subsequent cardiovascular disease. However, the relation between RLS and these chronic conditions has received relatively little attention to date, although potential implications for the pathogenesis and treatment of RLS could be considerable. In this paper, we systematically review the recently published literature regarding the association of RLS to cardiovascular disease and related risk factors characterized by sympathoadrenal and metabolic dysregulation, discuss potential underlying mechanisms, and outline some possible directions for future research.

prs.rt("abs_end");Restless legs syndrome; RLS; Ekbom disease; Cardiovascular disease; Hypertension; Diabetes; Impaired glucose tolerance; Obesity; Weight gain; Dyslipidemia; Autonomic dysfunction; HPA axis dysfunction

Figures and tables from this article:

Table 1. Summary table of study characteristics. N = 30 studies (1995-2010).

Abbreviations: CVD = cardiovascular disease; DM = diabetes; DM2 = type 2 diabetes; dx = diagnosis; IGT = impaired glucose tolerance: IRLSSG = international restless legs syndrome study group; Min freq/sev = minimum frequency and/or severity; pts = patients; pts = patients; VA = veterans administration; w/ = with.

View Within ArticleTable 2. Relation of RLS to cardiovascular disease. Summary of study characteristics and findings (N = 15 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CAD = Coronary artery disease; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD = International Classification of Diseases; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infraction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); pt = patient; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleTable 3. Relation of RLS to hypertension: Summary of study characteristics and findings (N = 17 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DBP = diastolic blood pressure; DM = diabetes mellitus; DM2 = type 2 diabetes; DM1 = type 1 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); Pt = patient; RLS = restless legs syndrome; SBP = systolic blood pressure; SDB = Sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.* Calculated from data provided in paper.

View Within ArticleTable 4. Relation of RLS to diabetes and impaired glucose tolerance: Summary of study characteristics and findings (N=26 studies (1995-2010)).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BG = blood glucose; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HOMA = homeostasis model assessment; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; IGT = impaired glucose tolerance; ICSD = international classification of sleep disorders; IGR = impaired glucose regulation; IGT = impaired glucose tolerance; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MONICA = monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% Confidence Interval); pts = patients; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = Strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.*Calculated from data provided in table.

View Within ArticleTable 5. Relation of RLS to obesity, weight gain, and dyslipidemia: Summary of study characteristics and findings (N=18 studies with data on the association of RLS to obesity/weight gain, 7 studies with data on the association of RLS to lipid profiles).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICSD = international classification of sleep disorders; IRLS = intl RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = Monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% confidence interval); RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

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Epidemiology of restless legs syndrome: A synthesis of the literature

a Stanford Sleep Epidemiology Research Center, Stanford University, School of Medicine, 3430 West Bayshore Road, Palo Alto, CA 94303, United Statesb Stanford University, School of Medicine, Stanford, CA 94305, United Statesc Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, United StatesReceived 12 January 2011. Revised 8 May 2011. Accepted 9 May 2011. Available online 26 July 2011.View full text Restless legs syndrome (RLS) has gained considerable attention in the recent years: nearly 50 community-based studies have been published in the last decade around the world. The development of strict diagnostic criteria in 1995 and their revision in 2003 helped to stimulate research interest on this syndrome. In community-based surveys, RLS has been studied as: 1) a symptom only, 2) a set of symptoms meeting minimal diagnostic criteria of the international restless legs syndrome study group (IRLSSG), 3) meeting minimal criteria accompanied with a specific frequency and/or severity, and 4) a differential diagnosis. In the first case, prevalence estimates in the general adult population ranged from 9.4% to 15%. In the second case, prevalence ranged from 3.9% to 14.3%. When frequency/severity is added, prevalence ranged from 2.2% to 7.9% and when differential diagnosis is applied prevalence estimates are between 1.9% and 4.6%. In all instances, RLS prevalence is higher in women than in men. It also increases with age in European and North American countries but not in Asian countries. Symptoms of anxiety and depression have been consistently associated with RLS. Overall, individuals with RLS have a poorer health than non-RLS but evidence for specific disease associations is mixed. Future epidemiological studies should focus on systematically adding frequency and severity in the definition of the syndrome in order to minimize the inclusion of cases mimicking RLS.

prs.rt("abs_end");Epidemiology; Restless legs syndrome; Community; Primary Care; Mental disorders; IllnessRLS, Restless legs syndrome; IRLSSG, International Restless Legs Syndrome Study Group; DIS, Difficulty initiating sleep; DMS, Difficulty maintaining sleep; NRS, non-restorative sleep; ESS, Epworth Sleepiness Scale

Figures and tables from this article:

Fig. 1. Changes in RLS prevalence rates in North America and Europe general population according to used definitions. *Prevalence rates for differential diagnosis came from primary care samples. Prevalence estimates are based on samples including participants from 18 to =65 years.

View Within ArticleFig. 2. a. Prevalence of RLS in men – North America and Europe. Included 12 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 23,282 men aged =18 are included in the scatter plot. b. Prevalence of RLS in men – Asia. Included 5 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 8081 men aged =18 are included in the scatter plot. c. Prevalence of RLS in women – North America and Europe. Included 12 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 26,150 women aged =18 are included in the scatter plot. d. Prevalence of RLS in women – Asia. Included 6 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 11,253 women aged =18 are included in the scatter plot.

View Within ArticleTable 1. Prevalence for restless leg syndrome or symptoms in the general population.

ECA = Epidemiologic Catchment Area; HPFS = Health Professionals Follow-up Study; ICSD = International classification of sleep disorders; IRLSSG = International restless legs syndrome study group; M = Men; NHANES = National Health and Nutrition Examination Survey; NHS II = Nurses' Health Study II; NIH = National Institutes of Health; RLS = Restless legs syndrome; t/mo = times per month; t/wk = times per week; unkn = unknown; W = Women.

View Within ArticleTable 2. Prevalence for restless legs syndrome or symptoms in clinical settings.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

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Epidemiology of restless legs syndrome: A synthesis of the literature

a Stanford Sleep Epidemiology Research Center, Stanford University, School of Medicine, 3430 West Bayshore Road, Palo Alto, CA 94303, United Statesb Stanford University, School of Medicine, Stanford, CA 94305, United Statesc Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, United StatesReceived 12 January 2011. Revised 8 May 2011. Accepted 9 May 2011. Available online 26 July 2011.View full text Restless legs syndrome (RLS) has gained considerable attention in the recent years: nearly 50 community-based studies have been published in the last decade around the world. The development of strict diagnostic criteria in 1995 and their revision in 2003 helped to stimulate research interest on this syndrome. In community-based surveys, RLS has been studied as: 1) a symptom only, 2) a set of symptoms meeting minimal diagnostic criteria of the international restless legs syndrome study group (IRLSSG), 3) meeting minimal criteria accompanied with a specific frequency and/or severity, and 4) a differential diagnosis. In the first case, prevalence estimates in the general adult population ranged from 9.4% to 15%. In the second case, prevalence ranged from 3.9% to 14.3%. When frequency/severity is added, prevalence ranged from 2.2% to 7.9% and when differential diagnosis is applied prevalence estimates are between 1.9% and 4.6%. In all instances, RLS prevalence is higher in women than in men. It also increases with age in European and North American countries but not in Asian countries. Symptoms of anxiety and depression have been consistently associated with RLS. Overall, individuals with RLS have a poorer health than non-RLS but evidence for specific disease associations is mixed. Future epidemiological studies should focus on systematically adding frequency and severity in the definition of the syndrome in order to minimize the inclusion of cases mimicking RLS.

prs.rt("abs_end");Epidemiology; Restless legs syndrome; Community; Primary Care; Mental disorders; IllnessRLS, Restless legs syndrome; IRLSSG, International Restless Legs Syndrome Study Group; DIS, Difficulty initiating sleep; DMS, Difficulty maintaining sleep; NRS, non-restorative sleep; ESS, Epworth Sleepiness Scale

Figures and tables from this article:

Fig. 1. Changes in RLS prevalence rates in North America and Europe general population according to used definitions. *Prevalence rates for differential diagnosis came from primary care samples. Prevalence estimates are based on samples including participants from 18 to =65 years.

View Within ArticleFig. 2. a. Prevalence of RLS in men – North America and Europe. Included 12 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 23,282 men aged =18 are included in the scatter plot. b. Prevalence of RLS in men – Asia. Included 5 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 8081 men aged =18 are included in the scatter plot. c. Prevalence of RLS in women – North America and Europe. Included 12 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 26,150 women aged =18 are included in the scatter plot. d. Prevalence of RLS in women – Asia. Included 6 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 11,253 women aged =18 are included in the scatter plot.

View Within ArticleTable 1. Prevalence for restless leg syndrome or symptoms in the general population.

ECA = Epidemiologic Catchment Area; HPFS = Health Professionals Follow-up Study; ICSD = International classification of sleep disorders; IRLSSG = International restless legs syndrome study group; M = Men; NHANES = National Health and Nutrition Examination Survey; NHS II = Nurses' Health Study II; NIH = National Institutes of Health; RLS = Restless legs syndrome; t/mo = times per month; t/wk = times per week; unkn = unknown; W = Women.

View Within ArticleTable 2. Prevalence for restless legs syndrome or symptoms in clinical settings.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

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Epidemiology of restless legs syndrome: A synthesis of the literature

a Stanford Sleep Epidemiology Research Center, Stanford University, School of Medicine, 3430 West Bayshore Road, Palo Alto, CA 94303, United Statesb Stanford University, School of Medicine, Stanford, CA 94305, United Statesc Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, United StatesReceived 12 January 2011. Revised 8 May 2011. Accepted 9 May 2011. Available online 26 July 2011.View full text Restless legs syndrome (RLS) has gained considerable attention in the recent years: nearly 50 community-based studies have been published in the last decade around the world. The development of strict diagnostic criteria in 1995 and their revision in 2003 helped to stimulate research interest on this syndrome. In community-based surveys, RLS has been studied as: 1) a symptom only, 2) a set of symptoms meeting minimal diagnostic criteria of the international restless legs syndrome study group (IRLSSG), 3) meeting minimal criteria accompanied with a specific frequency and/or severity, and 4) a differential diagnosis. In the first case, prevalence estimates in the general adult population ranged from 9.4% to 15%. In the second case, prevalence ranged from 3.9% to 14.3%. When frequency/severity is added, prevalence ranged from 2.2% to 7.9% and when differential diagnosis is applied prevalence estimates are between 1.9% and 4.6%. In all instances, RLS prevalence is higher in women than in men. It also increases with age in European and North American countries but not in Asian countries. Symptoms of anxiety and depression have been consistently associated with RLS. Overall, individuals with RLS have a poorer health than non-RLS but evidence for specific disease associations is mixed. Future epidemiological studies should focus on systematically adding frequency and severity in the definition of the syndrome in order to minimize the inclusion of cases mimicking RLS.

prs.rt("abs_end");Epidemiology; Restless legs syndrome; Community; Primary Care; Mental disorders; IllnessRLS, Restless legs syndrome; IRLSSG, International Restless Legs Syndrome Study Group; DIS, Difficulty initiating sleep; DMS, Difficulty maintaining sleep; NRS, non-restorative sleep; ESS, Epworth Sleepiness Scale

Figures and tables from this article:

Fig. 1. Changes in RLS prevalence rates in North America and Europe general population according to used definitions. *Prevalence rates for differential diagnosis came from primary care samples. Prevalence estimates are based on samples including participants from 18 to =65 years.

View Within ArticleFig. 2. a. Prevalence of RLS in men – North America and Europe. Included 12 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 23,282 men aged =18 are included in the scatter plot. b. Prevalence of RLS in men – Asia. Included 5 studies that had provided prevalence by age groups for men. These studies are based on minimal IRLSSG criteria. A total of 8081 men aged =18 are included in the scatter plot. c. Prevalence of RLS in women – North America and Europe. Included 12 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 26,150 women aged =18 are included in the scatter plot. d. Prevalence of RLS in women – Asia. Included 6 studies that had provided prevalence by age groups for women. These studies are based on minimal IRLSSG criteria. A total of 11,253 women aged =18 are included in the scatter plot.

View Within ArticleTable 1. Prevalence for restless leg syndrome or symptoms in the general population.

ECA = Epidemiologic Catchment Area; HPFS = Health Professionals Follow-up Study; ICSD = International classification of sleep disorders; IRLSSG = International restless legs syndrome study group; M = Men; NHANES = National Health and Nutrition Examination Survey; NHS II = Nurses' Health Study II; NIH = National Institutes of Health; RLS = Restless legs syndrome; t/mo = times per month; t/wk = times per week; unkn = unknown; W = Women.

View Within ArticleTable 2. Prevalence for restless legs syndrome or symptoms in clinical settings.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

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From restless legs syndrome to Willis-Ekbom disease: A condition reaches full age

 

From restless legs syndrome to Willis-Ekbom disease: A condition reaches full age

 

From restless legs syndrome to Willis-Ekbom disease: A condition reaches full age

 

Restless legs syndrome – Theoretical roles of inflammatory and immune mechanisms

Theories for restless legs syndrome (RLS) pathogenesis include iron deficiency, dopamine dysregulation and peripheral neuropathy. Increased prevalence of small intestinal bacterial overgrowth (SIBO) in controlled studies in RLS and case reports of post-infectious RLS suggest potential roles for inflammation and immunological alterations.

A literature search for all conditions associated with RLS was performed. These included secondary RLS disorders and factors that may exacerbate RLS. All of these conditions were reviewed with respect to potential pathogenesis including reports of iron deficiency, neuropathy, SIBO, inflammation and immune changes. A condition was defined as highly-associated if there was a prevalence study that utilized an appropriate control group. Small case reports were recorded but not included as definite RLS-associated conditions.

Fifty four diseases, syndromes and conditions have been reported to cause and/or exacerbate RLS. Of these, 38 have been reported to have a higher prevalence than age-matched controls, 9 have adequate sized reports and have general acceptance as RLS-associated conditions and 7 have been reported in case report form. Overall, 42 of the 47 RLS-associated conditions (89%) have also been associated with inflammatory and/or immune changes. In addition, 43% have been associated with peripheral iron deficiency, 40% with peripheral neuropathy and 32% with SIBO. Most of the remaining conditions have yet to be studied for these factors.

The fact that 95% of the 38 highly-associated RLS conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms. Inflammation can be responsible for iron deficiency and hypothetically could cause central nervous system iron deficiency-induced RLS. Alternatively, an immune reaction to gastrointestinal bacteria or other antigens may hypothetically cause RLS by a direct immunological attack on the central or peripheral nervous system.

Fig. 1. Potential interplay of pathologic factors in secondary RLS. Abbreviations: RLS: restless legs syndrome; Inflam & Immune: inflammation and/or altered immunity; SIBO: small intestinal bacterial overgrowth; Neuropathy: peripheral neuropathy.

View Within Article

Fig. 2.  [26], [55], [56] and [125] of hepcidin synthesis in the setting of inflammation and theoretical consequences for developing CNS iron deficiency and subsequent RLS. Hepcidin is the main hormone involved in regulation of iron levels and has been shown to be produced by the liver in humans and in the brain in animal models. Increased hepcidin levels lead to iron deficiency. Interleukin-6 is the main cytokine that can increase hepcidin levels. Lipopolysaccharides which are breakdown products of gram negative bacteria stimulate hepcidin synthesis. Hypoxia also stimulates hepcidin synthesis. Hepcidin binds to ferroportin on human choroid plexus cells and decrease availability of iron for the CNS. Not shown – Bacteria may also utilize iron and cause iron deficiency.57 Abbreviations: LPS: lipopolysaccharides.

View Within Article

Table 1. Iron deficiency, small intestinal bacterial overgrowth (SIBO), inflammation and/or immunological alterations and peripheral neuropathy in conditions associated with restless legs syndrome (RLS). References are categorized as either: a controlled study (CS); an observational case series (OS); a laboratory study (LS) which uses defined assays but does not have a control group; or a review article (RA). Highly-associated conditions are defined as RLS conditions shown to have a statistically higher prevalence than controls. This table does not include seven single case reports associated with RLS (see result section).

Additional abbreviations: ADHD: attention-deficit/hyperactivity disorder; COPD: chronic obstructive pulmonary disease; NS: not studied.

View Within Article

Copyright © 2011 Elsevier Ltd. All rights reserved.

View the original article here

Restless legs syndrome – Theoretical roles of inflammatory and immune mechanisms

Theories for restless legs syndrome (RLS) pathogenesis include iron deficiency, dopamine dysregulation and peripheral neuropathy. Increased prevalence of small intestinal bacterial overgrowth (SIBO) in controlled studies in RLS and case reports of post-infectious RLS suggest potential roles for inflammation and immunological alterations.

A literature search for all conditions associated with RLS was performed. These included secondary RLS disorders and factors that may exacerbate RLS. All of these conditions were reviewed with respect to potential pathogenesis including reports of iron deficiency, neuropathy, SIBO, inflammation and immune changes. A condition was defined as highly-associated if there was a prevalence study that utilized an appropriate control group. Small case reports were recorded but not included as definite RLS-associated conditions.

Fifty four diseases, syndromes and conditions have been reported to cause and/or exacerbate RLS. Of these, 38 have been reported to have a higher prevalence than age-matched controls, 9 have adequate sized reports and have general acceptance as RLS-associated conditions and 7 have been reported in case report form. Overall, 42 of the 47 RLS-associated conditions (89%) have also been associated with inflammatory and/or immune changes. In addition, 43% have been associated with peripheral iron deficiency, 40% with peripheral neuropathy and 32% with SIBO. Most of the remaining conditions have yet to be studied for these factors.

The fact that 95% of the 38 highly-associated RLS conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms. Inflammation can be responsible for iron deficiency and hypothetically could cause central nervous system iron deficiency-induced RLS. Alternatively, an immune reaction to gastrointestinal bacteria or other antigens may hypothetically cause RLS by a direct immunological attack on the central or peripheral nervous system.

Fig. 1. Potential interplay of pathologic factors in secondary RLS. Abbreviations: RLS: restless legs syndrome; Inflam & Immune: inflammation and/or altered immunity; SIBO: small intestinal bacterial overgrowth; Neuropathy: peripheral neuropathy.

View Within Article

Fig. 2.  [26], [55], [56] and [125] of hepcidin synthesis in the setting of inflammation and theoretical consequences for developing CNS iron deficiency and subsequent RLS. Hepcidin is the main hormone involved in regulation of iron levels and has been shown to be produced by the liver in humans and in the brain in animal models. Increased hepcidin levels lead to iron deficiency. Interleukin-6 is the main cytokine that can increase hepcidin levels. Lipopolysaccharides which are breakdown products of gram negative bacteria stimulate hepcidin synthesis. Hypoxia also stimulates hepcidin synthesis. Hepcidin binds to ferroportin on human choroid plexus cells and decrease availability of iron for the CNS. Not shown – Bacteria may also utilize iron and cause iron deficiency.57 Abbreviations: LPS: lipopolysaccharides.

View Within Article

Table 1. Iron deficiency, small intestinal bacterial overgrowth (SIBO), inflammation and/or immunological alterations and peripheral neuropathy in conditions associated with restless legs syndrome (RLS). References are categorized as either: a controlled study (CS); an observational case series (OS); a laboratory study (LS) which uses defined assays but does not have a control group; or a review article (RA). Highly-associated conditions are defined as RLS conditions shown to have a statistically higher prevalence than controls. This table does not include seven single case reports associated with RLS (see result section).

Additional abbreviations: ADHD: attention-deficit/hyperactivity disorder; COPD: chronic obstructive pulmonary disease; NS: not studied.

View Within Article

Copyright © 2011 Elsevier Ltd. All rights reserved.

View the original article here

Restless legs syndrome – Theoretical roles of inflammatory and immune mechanisms

Theories for restless legs syndrome (RLS) pathogenesis include iron deficiency, dopamine dysregulation and peripheral neuropathy. Increased prevalence of small intestinal bacterial overgrowth (SIBO) in controlled studies in RLS and case reports of post-infectious RLS suggest potential roles for inflammation and immunological alterations.

A literature search for all conditions associated with RLS was performed. These included secondary RLS disorders and factors that may exacerbate RLS. All of these conditions were reviewed with respect to potential pathogenesis including reports of iron deficiency, neuropathy, SIBO, inflammation and immune changes. A condition was defined as highly-associated if there was a prevalence study that utilized an appropriate control group. Small case reports were recorded but not included as definite RLS-associated conditions.

Fifty four diseases, syndromes and conditions have been reported to cause and/or exacerbate RLS. Of these, 38 have been reported to have a higher prevalence than age-matched controls, 9 have adequate sized reports and have general acceptance as RLS-associated conditions and 7 have been reported in case report form. Overall, 42 of the 47 RLS-associated conditions (89%) have also been associated with inflammatory and/or immune changes. In addition, 43% have been associated with peripheral iron deficiency, 40% with peripheral neuropathy and 32% with SIBO. Most of the remaining conditions have yet to be studied for these factors.

The fact that 95% of the 38 highly-associated RLS conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms. Inflammation can be responsible for iron deficiency and hypothetically could cause central nervous system iron deficiency-induced RLS. Alternatively, an immune reaction to gastrointestinal bacteria or other antigens may hypothetically cause RLS by a direct immunological attack on the central or peripheral nervous system.

Fig. 1. Potential interplay of pathologic factors in secondary RLS. Abbreviations: RLS: restless legs syndrome; Inflam & Immune: inflammation and/or altered immunity; SIBO: small intestinal bacterial overgrowth; Neuropathy: peripheral neuropathy.

View Within Article

Fig. 2.  [26], [55], [56] and [125] of hepcidin synthesis in the setting of inflammation and theoretical consequences for developing CNS iron deficiency and subsequent RLS. Hepcidin is the main hormone involved in regulation of iron levels and has been shown to be produced by the liver in humans and in the brain in animal models. Increased hepcidin levels lead to iron deficiency. Interleukin-6 is the main cytokine that can increase hepcidin levels. Lipopolysaccharides which are breakdown products of gram negative bacteria stimulate hepcidin synthesis. Hypoxia also stimulates hepcidin synthesis. Hepcidin binds to ferroportin on human choroid plexus cells and decrease availability of iron for the CNS. Not shown – Bacteria may also utilize iron and cause iron deficiency.57 Abbreviations: LPS: lipopolysaccharides.

View Within Article

Table 1. Iron deficiency, small intestinal bacterial overgrowth (SIBO), inflammation and/or immunological alterations and peripheral neuropathy in conditions associated with restless legs syndrome (RLS). References are categorized as either: a controlled study (CS); an observational case series (OS); a laboratory study (LS) which uses defined assays but does not have a control group; or a review article (RA). Highly-associated conditions are defined as RLS conditions shown to have a statistically higher prevalence than controls. This table does not include seven single case reports associated with RLS (see result section).

Additional abbreviations: ADHD: attention-deficit/hyperactivity disorder; COPD: chronic obstructive pulmonary disease; NS: not studied.

View Within Article

Copyright © 2011 Elsevier Ltd. All rights reserved.

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When gender matters: Restless legs syndrome. Report of the “RLS and woman” workshop endorsed by the European RLS Study Group

Mauro Manconia, , , Jan Ulfbergb, Klaus Bergerc, Imad Ghorayebd, Jan Wesströme, Stephany Fuldaf, Richard P. Alleng, Thomas Pollmächerf, ha Sleep and Epilepsy Center, Neurocenter (EOC) of Southern Switzerland, Civic Hospital, Lugano, Via Tesserete 46, 6900 Lugano, Switzerlandb Department of Medicine, Uppsala University, Uppsala, Swedenc Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germanyd Clinical Neurophysiology Department, Centre Hospitalier et Universitaire de Bordeaux, Bordeaux cedex, Francee Center for Clinical Research Dalarna, Department of Women's and Children's Health, Uppsala University, Swedenf Max Planck Institute of Psychiatry, Munich, Germanyg Center of Mental Health, Klinikum Ingolstadt, Ingolstadt, Germanyh Department of Neurology, Johns Hopkins University, Bayview Medical Center, Baltimore, MD, USAReceived 13 May 2011. Revised 30 August 2011. Accepted 30 August 2011. Available online 9 November 2011.View full text Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

prs.rt("abs_end");Restless legs syndrome; Gender; Female; Sleep; Insomnia; Pregnancy; Estrogens; Menopause; Quality of life

Figures and tables from this article:

Fig. 1. Epidemiological results on RLS and pregnancy. Histograms show the prevalence trend of RLS in a group of 606 women surveyed at the end of pregnancy. In the period before pregnancy, 60 women already experienced RLS symptoms in their life (in a non pregnancy period) and were classified as “pre-existing RLS”. The remaining 546 women had never experienced RLS symptoms before and were classified as “healthy”. During the first assessed pregnancy (2nd histogram) 101 women, out of the 546 “healthy” ones, developed a transient RLS form strictly related to the pregnancy and were classified as “pregnancy-related RLS”. All these 101 women with a new form of pregnancy-related RLS form, except 6 women, recovered after delivery (3rd histogram). Fifty nine of the same pregnancy-related RLS group suffered again RLS symptoms during a further following pregnancy. After a mean follow up of 7 years, 25 out of the 101 women who experienced the symptoms during the first pregnancy (pregnancy-related RLS group) developed a chronic apparently idiopathic RLS form even out of pregnancy. Elaborated data from the study of Cesnik et al.37

View Within ArticleFig. 2. Prevalence of RLS among women in two age groups and according to number of children born in the German general practioner study.43

View Within ArticleFig. 3. Median serum ferritin by age for major USA gender and population groups.

View Within ArticleFig. 4. Prevalence of clinically significant RLS by gender and age from large European and United States population-based samples. (Slightly modified from Allen et al).21

View Within ArticleTable 1. Studies on the prevalence of RLS performed in random samples of the general population of different countries, using the IRLSSG criteria to assess the diagnosis.

View Within ArticleTable 2. Epidemiological studies published in literature on RLS prevalence that included an assessment on the quality of life.

Abbreviations: EQ-5D VAS, visual analogue scale score for the EQ-5D, a quality of life questionnaire developed by the EuroQoL Group; HRQoL, health related quality of life; MCS, mental component score of the SF-36; RLS, restless legs syndrome; PCS, physical component score of the SF-36; SF-36, SF-12, short form health survey.

View Within ArticleTable 3. Studies exploring the role of estrogens in RLS.

Abbreviations: AC, active controlled; CO, crossover; DB, double blind; HRT, hormone replacement therapy; IQR, interquartile range; PC, placebo controlled; PG, parallel group; PLM, periodic leg movements; R, randomized; SD, standard deviation.

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When gender matters: Restless legs syndrome. Report of the “RLS and woman” workshop endorsed by the European RLS Study Group

Mauro Manconia, , , Jan Ulfbergb, Klaus Bergerc, Imad Ghorayebd, Jan Wesströme, Stephany Fuldaf, Richard P. Alleng, Thomas Pollmächerf, ha Sleep and Epilepsy Center, Neurocenter (EOC) of Southern Switzerland, Civic Hospital, Lugano, Via Tesserete 46, 6900 Lugano, Switzerlandb Department of Medicine, Uppsala University, Uppsala, Swedenc Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germanyd Clinical Neurophysiology Department, Centre Hospitalier et Universitaire de Bordeaux, Bordeaux cedex, Francee Center for Clinical Research Dalarna, Department of Women's and Children's Health, Uppsala University, Swedenf Max Planck Institute of Psychiatry, Munich, Germanyg Center of Mental Health, Klinikum Ingolstadt, Ingolstadt, Germanyh Department of Neurology, Johns Hopkins University, Bayview Medical Center, Baltimore, MD, USAReceived 13 May 2011. Revised 30 August 2011. Accepted 30 August 2011. Available online 9 November 2011.View full text Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

prs.rt("abs_end");Restless legs syndrome; Gender; Female; Sleep; Insomnia; Pregnancy; Estrogens; Menopause; Quality of life

Figures and tables from this article:

Fig. 1. Epidemiological results on RLS and pregnancy. Histograms show the prevalence trend of RLS in a group of 606 women surveyed at the end of pregnancy. In the period before pregnancy, 60 women already experienced RLS symptoms in their life (in a non pregnancy period) and were classified as “pre-existing RLS”. The remaining 546 women had never experienced RLS symptoms before and were classified as “healthy”. During the first assessed pregnancy (2nd histogram) 101 women, out of the 546 “healthy” ones, developed a transient RLS form strictly related to the pregnancy and were classified as “pregnancy-related RLS”. All these 101 women with a new form of pregnancy-related RLS form, except 6 women, recovered after delivery (3rd histogram). Fifty nine of the same pregnancy-related RLS group suffered again RLS symptoms during a further following pregnancy. After a mean follow up of 7 years, 25 out of the 101 women who experienced the symptoms during the first pregnancy (pregnancy-related RLS group) developed a chronic apparently idiopathic RLS form even out of pregnancy. Elaborated data from the study of Cesnik et al.37

View Within ArticleFig. 2. Prevalence of RLS among women in two age groups and according to number of children born in the German general practioner study.43

View Within ArticleFig. 3. Median serum ferritin by age for major USA gender and population groups.

View Within ArticleFig. 4. Prevalence of clinically significant RLS by gender and age from large European and United States population-based samples. (Slightly modified from Allen et al).21

View Within ArticleTable 1. Studies on the prevalence of RLS performed in random samples of the general population of different countries, using the IRLSSG criteria to assess the diagnosis.

View Within ArticleTable 2. Epidemiological studies published in literature on RLS prevalence that included an assessment on the quality of life.

Abbreviations: EQ-5D VAS, visual analogue scale score for the EQ-5D, a quality of life questionnaire developed by the EuroQoL Group; HRQoL, health related quality of life; MCS, mental component score of the SF-36; RLS, restless legs syndrome; PCS, physical component score of the SF-36; SF-36, SF-12, short form health survey.

View Within ArticleTable 3. Studies exploring the role of estrogens in RLS.

Abbreviations: AC, active controlled; CO, crossover; DB, double blind; HRT, hormone replacement therapy; IQR, interquartile range; PC, placebo controlled; PG, parallel group; PLM, periodic leg movements; R, randomized; SD, standard deviation.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

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View the original article here

When gender matters: Restless legs syndrome. Report of the “RLS and woman” workshop endorsed by the European RLS Study Group

Mauro Manconia, , , Jan Ulfbergb, Klaus Bergerc, Imad Ghorayebd, Jan Wesströme, Stephany Fuldaf, Richard P. Alleng, Thomas Pollmächerf, ha Sleep and Epilepsy Center, Neurocenter (EOC) of Southern Switzerland, Civic Hospital, Lugano, Via Tesserete 46, 6900 Lugano, Switzerlandb Department of Medicine, Uppsala University, Uppsala, Swedenc Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germanyd Clinical Neurophysiology Department, Centre Hospitalier et Universitaire de Bordeaux, Bordeaux cedex, Francee Center for Clinical Research Dalarna, Department of Women's and Children's Health, Uppsala University, Swedenf Max Planck Institute of Psychiatry, Munich, Germanyg Center of Mental Health, Klinikum Ingolstadt, Ingolstadt, Germanyh Department of Neurology, Johns Hopkins University, Bayview Medical Center, Baltimore, MD, USAReceived 13 May 2011. Revised 30 August 2011. Accepted 30 August 2011. Available online 9 November 2011.View full text Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

prs.rt("abs_end");Restless legs syndrome; Gender; Female; Sleep; Insomnia; Pregnancy; Estrogens; Menopause; Quality of life

Figures and tables from this article:

Fig. 1. Epidemiological results on RLS and pregnancy. Histograms show the prevalence trend of RLS in a group of 606 women surveyed at the end of pregnancy. In the period before pregnancy, 60 women already experienced RLS symptoms in their life (in a non pregnancy period) and were classified as “pre-existing RLS”. The remaining 546 women had never experienced RLS symptoms before and were classified as “healthy”. During the first assessed pregnancy (2nd histogram) 101 women, out of the 546 “healthy” ones, developed a transient RLS form strictly related to the pregnancy and were classified as “pregnancy-related RLS”. All these 101 women with a new form of pregnancy-related RLS form, except 6 women, recovered after delivery (3rd histogram). Fifty nine of the same pregnancy-related RLS group suffered again RLS symptoms during a further following pregnancy. After a mean follow up of 7 years, 25 out of the 101 women who experienced the symptoms during the first pregnancy (pregnancy-related RLS group) developed a chronic apparently idiopathic RLS form even out of pregnancy. Elaborated data from the study of Cesnik et al.37

View Within ArticleFig. 2. Prevalence of RLS among women in two age groups and according to number of children born in the German general practioner study.43

View Within ArticleFig. 3. Median serum ferritin by age for major USA gender and population groups.

View Within ArticleFig. 4. Prevalence of clinically significant RLS by gender and age from large European and United States population-based samples. (Slightly modified from Allen et al).21

View Within ArticleTable 1. Studies on the prevalence of RLS performed in random samples of the general population of different countries, using the IRLSSG criteria to assess the diagnosis.

View Within ArticleTable 2. Epidemiological studies published in literature on RLS prevalence that included an assessment on the quality of life.

Abbreviations: EQ-5D VAS, visual analogue scale score for the EQ-5D, a quality of life questionnaire developed by the EuroQoL Group; HRQoL, health related quality of life; MCS, mental component score of the SF-36; RLS, restless legs syndrome; PCS, physical component score of the SF-36; SF-36, SF-12, short form health survey.

View Within ArticleTable 3. Studies exploring the role of estrogens in RLS.

Abbreviations: AC, active controlled; CO, crossover; DB, double blind; HRT, hormone replacement therapy; IQR, interquartile range; PC, placebo controlled; PG, parallel group; PLM, periodic leg movements; R, randomized; SD, standard deviation.

View Within ArticleCopyright © 2011 Elsevier Ltd. All rights reserved.

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