New onset of restless legs syndrome in pregnancy in a prospective multiracial cohort: Incidence and risk factors.

OBJECTIVE: To determine whether the incidence and risk factors of restless legs syndrome (RLS) in pregnancy differ by race/ethnicity, we estimated relative risks of demographic, socioeconomic, and nutritional factors in association with risk of any incident RLS in pregnancy in a cohort of 2,704 healthy pregnant women without prior RLS. METHODS: Using data from the multicenter, multiracial National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons, we examined the incidence of RLS from early pregnancy to near delivery through up to 6 assessments. Multivariable Poisson models with robust variance were applied to estimate relative risks (RRs). RESULTS: The cumulative incidence of RLS in pregnancy was 18.1% for all women, 20.3% for White women, 15.4% for Black women, 17.1% for Hispanic women, and 21.1% for Asian women. Among Hispanic women, older age (RR [reference ≤25 years]: 25-35 years, 1.51; 95% confidence interval [CI] 1.05-2.16; ≥35 years, 1.58; 95% CI 0.93-2.68), anemia (RR [reference no]: yes, 2.47; 95% CI 1.31-4.64), and greater total skinfolds of the subscapular and triceps sites, independent of body mass index (RR [reference quartile 1]: quartile 5, 2.54; 95% CI 1.30-4.97; p trend = 0.01) were associated with higher risk of RLS, while multiparity was associated with a lower risk (RR [reference nulliparity]: 0.69; 95% CI 0.50-0.96). In Black women, greater skinfolds and waist circumference were associated with higher risk of pregnancy RLS, although the trends were less clear. CONCLUSIONS: The incidence of RLS in pregnancy was high and differed by race/ethnicity, which is likely accounted for by differences in other risk factors, such as age, parity, and nutritional factors.

Clinical features and subtypes of restless legs syndrome in Chinese population: a study of 359 patients.

BACKGROUND: The clinical spectrum of restless legs syndrome (RLS) has not been described in a Chinese population. We aim to evaluate the detailed clinical profile in a cohort of unselected RLS patients in China. METHODS: We enrolled RLS patients continuously according to the diagnostic criteria. Laboratory examinations were performed to exclude mimics and notable comorbidities. RESULTS: A total of 359 patients with RLS were enrolled. RLS symptoms were mostly symmetrical (65.2%), and purely unilateral RLS was not common (5.6%); however, unilateral dominant RLS was relatively more common. Only 1.1% of RLS patients reported no unpleasant sensations in the legs. The largest proportion of RLS patients described their uncomfortable sensation as indescribable (43.5%) and reported soreness (40.4%). In all, 8.9% of RLS patients described their abnormal sensation as painful, and 34.5% of RLS patients reported their symptoms fluctuated with seasonal trends. This population had a higher likelihood of an RLS family history. RLS patients with summer exacerbation had a younger age at RLS onset and longer disease duration (p < 0.01). Iron deficiency without anemia was common in Chinese RLS patients. Early-onset RLS patients were more likely to have a positive family history (p < 0.01), more summer worsening of symptoms (p < 0.01) and more severely disturbed peripheral iron status (p < 0.01) when compared to late-onset RLS patients. CONCLUSION: The subjective description is somewhat different, with Chinese RLS patients reporting less pain and more soreness than patients from Western countries. Seasonal fluctuation and iron deficiency without anemia are frequently seen in Chinese RLS patients and predict some other features. Differentiating these various subtypes can facilitate optimal management.

Individual and socio-demographic factors related to presenting problem and diagnostic impressions at a pediatric sleep clinic.

OBJECTIVE: Individual and socio-demographic factors have been found to be associated with sleep disturbances in children. Few studies have examined these factors among children presenting for care at pediatric sleep clinics. This study examined individual and socio-demographic factors in association with presenting problems and diagnostic impressions for new patients at an interdisciplinary pediatric sleep clinic. METHODS: Data were collected from electronic medical records of 207 consecutive patients (54% male, 59% White, Meanage = 7.73, SD = 5.62). RESULTS: Older age, female gender, and White race were associated with higher likelihood of presenting with difficulty falling asleep; younger age, male gender, and Black race were associated with higher likelihood of presenting with obstructive sleep apnea (OSA)-related concerns. Older age was associated with diagnostic impressions of inadequate sleep hygiene, insufficient sleep, circadian rhythm disorder/delayed sleep phase disorder, periodic limb movement disorder/restless legs syndrome, and insomnia, while younger age was associated with provisional OSA and behavioral insomnia of childhood (BIC) diagnoses. Male gender was associated with provisional OSA. White race was associated with BIC. Age-based analyses were also conducted to further understand the findings within a developmental context. CONCLUSIONS: Age- and gender-related findings converged with prevalence literature on pediatric sleep disorders. Race was only associated with presenting concern and BIC, and one association for neighborhood disadvantage was found within the age-based analysis. Results suggest a potential service delivery gap, with racial/ethnic minority youth being less likely to present for sleep services, despite prevalence data on the increased likelihood of sleep disturbances among these youth.

Willis-Ekbom disease is not associated with poor cardiovascular health in adults.

BACKGROUND: Willis-Ekbom disease (WED), also called restless legs syndrome (RLS), is a neurologic sensorimotor disease that may be associated with cardiovascular disease. Given high morbidity and mortality rates of cardiovascular disease worldwide, we assessed the relation between WED/RLS and cardiovascular health risks in a native South American population. We prospectively analyzed data from The Atahualpa Project of Ecuadorian adults aged 40 years and older. Physicians interviewed consented persons on the health behavior and health factors of the American Heart Association (AHA) for ideal cardiovascular health in adults and underwent fasting laboratory blood collection and blood pressure evaluation. Certified neurologists conducted face-to-face interviews using the International Restless Legs Syndrome Study Group (IRLSSG) field instrument. Persons testing positive for WED/RLS and age-and sex-matched controls underwent confirmatory physical examinations conducted by a neurologist and a sleep specialist to whom IRLSSG designation was blinded. FINDINGS: Of 665 persons, 94 (14 %) tested positive in IRLSSG; 40 (6 %) had a diagnosis of WED/RLS after neurologic examination and interview. Patients with WED/RLS were younger (53.5 vs 59.9 years, P = .001), without significant differences in sex ratios. Among AHA risk factors, only obesity was significantly more prevalent among patients with WED/RLS (42.5 % vs 23.5 %, P = .01). However, after adjustment for confounders, body mass index was not significantly associated with WED/RLS. CONCLUSIONS: In adult Amerindians, although obesity and body mass index were associated with WED/RLS on univariate analyses, the association was not present after adjustment for confounders. No other significant associations were found between WED/RLS and AHA cardiovascular metrics.

Pramipexole for Chinese people with primary restless legs syndrome: a 12-week multicenter, randomized, double-blind study.

BACKGROUND: Restless legs syndrome (RLS) often responds to agents that enhance dopamine neurotransmission. The present 12-week study aimed to evaluate the efficacy and adverse events of pramipexole (PPX) for the treatment of adult, Chinese people with primary RLS. METHODS: A total of 204 Chinese people with RLS were randomly assigned to receive either the placebo or PPX (flexibly titrated from 0.25 mg to 0.75 mg), 2 h to 3 h before bedtime for 12 weeks. The primary measuring outcomes were the International RLS Study Group Rating Scale (IRLS) and the Clinical Global Impressions-Improvement (CGI-I) scale. The secondary outcome was adverse events. RESULTS: One hundred and ninety participants completed the study. At 12 weeks, the adjusted mean (SE) change from baseline was greater for PPX (vs placebo) for the IRLS score (-13.2 ± 0.7 vs -9.4 ± 0.6; p <0.01), and (-12.1 ± 0.6 vs -8.3 ± 0.6; p <0.01) at the end of one month follow-up after treatment. The CGI-I rating of "very much improved" or "much improved" in the percentage of participants (61.8% vs 34.3%; p <0.01), and (51.0% vs 26.5%; p <0.01) after week 12, and one month follow-up of treatment, respectively. The proportion of adverse events was 60.8% in the PPX group and 45.1% in the placebo group. No deaths related to PPX treatment were recorded. CONCLUSIONS: In summary, the present study showed that PPX is efficacious and well tolerated in Chinese people with primary RLS.

Racial differences in the prevalence of restless legs syndrome in a primary care setting.

STUDY OBJECTIVE: To assess the prevalence of restless legs syndrome (RLS) in a primary care clinic and in African American (AA) and non-African American (NAA) racial groups. METHODS: We examined the prevalence of RLS using 1-on-1 interviews in general medicine clinics. Subjects were interviewed using John Hopkins Telephone Diagnostic Interview. All interviews were conducted by trained physicians. RESULTS: A total of 190 patients were interviewed: 103 AA (58.3% were female) and 87 NAA (59.8% were female). The overall prevalence of definite RLS was 22.6%. The average age was 53 years (standard deviation, 15) in AA and 50 years (standard deviation, 13) in NAA. Among AA, the diagnosis of RLS was definite in 11.65%, probable in 3.88%, negative in 83.5%, and unknown in 0.97%. Among NAA, patients were either identified as definite RLS (35.63%) or not RLS (64.37%); no patients were diagnosed as probable RLS or unknown. Logistic regression analysis was done to determine whether age, race, and sex were statistically significant predictors of an RLS diagnosis. When accounting for the other variables, the association between NAA and RLS prevalence was statistically significant (P = 0.002). CONCLUSION: Restless legs syndrome is common among primary care clinic patients. Its prevalence in the NAA population is approximately 3 times higher than in the AA group. We found the association between NAA race and RLS prevalence to be statistically significant. Larger studies are needed to further examine the relation between race and RLS prevalence.

Prevalence of sleep disorders by sex and ethnicity among older adolescents and emerging adults: relations to daytime functioning, working memory and mental health.

The study determined the prevalence of sleep disorders by ethnicity and sex, and related daytime functioning, working memory, and mental health among older adolescent to emerging adult college students. Participants were U.S.A. undergraduates (N = 1684), aged 17-25, recruited from 2010 to 2011. Participants completed online questionnaires for all variables. Overall, 36.0% of the sample screened positive for sleep disorders with insomnia, restless legs syndrome, and periodic limb movement disorder being the most prevalent. Women reported more insomnia and daytime impairment. African-Americans reported more early morning awakenings and less daytime impairment. Students with insomnia symptoms or restless legs syndrome tended to have lower working memory capacities. Students with nightmares or parasomnias had greater odds for mental disorders. In an older adolescent to emerging adult college student sample, sleep disorders may be a common source of sleep disturbance and impairment. Certain sleep disorders may be associated with lower working memory capacity and poor mental health.

Ethnic differences in the prevalence and predictors of restless legs syndrome between Hispanics of Mexican descent and non-Hispanic Whites in San Diego county: a population-based study.

STUDY OBJECTIVES: To investigate the prevalence and predictors of RLS in Hispanics of Mexican descent (HMD) and non-Hispanic whites (NHW). DESIGN: A population-based random digit dialing telephone questionnaire. SETTING: San Diego County California PARTICIPANTS: 1,754 HMD and 1,913 NHW adults ≥ 18 years of age able to participate in a telephone interview in English or Spanish. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: RLS was defined by the presence of all 4 criteria of the International Restless Legs Study Group. Sleepiness was measured by the Epworth Sleepiness Scale. Acculturation was evaluated using the Short Acculturation Scale for Hispanics. Risk factors for RLS were by self-report. The survey was conducted in the subject's language of choice. RLS prevalence was significantly lower in HMD than in NHW (14.4% vs.18.3%, p = 0.002). High acculturation HMD had a significantly greater RLS prevalence than the low acculturation group (17.4% vs. 12.8%, p = 0.008). Predictors of RLS varied between HMD and NHW. Female gender (OR 1.40, 95% CI 1.04, 1.90, p = 0.027), smoking (OR 1.82, 95% CI 1.27, 2.61, p = 0.001), and acculturation (OR 1.47, 95% CI 1.10, 1.97, p = 0.009) were independent predictors of RLS in HMD, while only older age (OR 1.01, 95% CI 1.0, 1.02) was an independent predictor of RLS for NHW. CONCLUSION: The prevalence of RLS was significantly lower in HMD than in NHW, and significantly greater in high acculturation HMD. Our data suggest that risk factors for RLS vary by race/ethnicity and acculturation is an independent risk for RLS in HMD.

A community-based investigation on restless legs syndrome in a town in China.

OBJECTIVE: To assess the prevalence and severity of restless legs syndrome (RLS) in a town in China and to explore potential factors correlated with the severity of the disease. METHODS: Face-to-face home interviews were conducted among a random sample of 2101 residents in one town in China, all aged 16 years and above. An individual questionnaire was administered to all participants to obtain a diagnosis of RLS and other information. An additional questionnaire was then handed out to each patient diagnosed with RLS to collect information on RLS severity and potential factors correlating with RLS severity. RESULTS: The prevalence of RLS in the studied population was 7.2%. The prevalence in women was significantly higher than in men and increased with age. Diabetes mellitus, anemia, arthritis, and varicose veins were also associated with RLS. Among the 152 patients, 21.7% were classified as having severe RLS. Multiple correlation analysis reveals that RLS severity was positively correlated with longer disease duration, number of cigarettes smoked per day, and level of work-related physical activity, but negatively correlated with level of leisure time physical activity. CONCLUSIONS: RLS is common in the studied population. Lifestyle factors may be associated with RLS severity.

Family study of restless legs syndrome in Quebec, Canada: clinical characterization of 671 familial cases.

OBJECTIVES: To fully ascertain the familial aggregation of restless legs syndrome (RLS) and to characterize the clinical features of familial RLS (fRLS) cases. DESIGN: A case series survey with a high response rate. SETTING: Academic research center. PARTICIPANTS: Consecutive RLS probands (n = 249) were followed up in a specialized sleep center for 15 years. A total of 671 cases of fRLS met the current standard diagnostic criteria, including 192 probands characterized using multidimensional clinical assessments and 479 affected family members assessed by their responses to a structured questionnaire telephone diagnostic interview. MAIN OUTCOME MEASURES: Sibling and offspring relative risk ratio and clinical and genetic features of patients with fRLS and families. RESULTS: Our data showed that RLS aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6 (95% confidence interval, 2.8-4.4), and an offspring relative risk of 1.8 (1.0-2.7). Familial RLS is a chronic disorder with a mean (SD) disease duration of 24 (16) years and a wide range of age of onset (mean [SD], 28 [15] years), with most family members having early-onset disease but mild to moderate RLS symptoms. Our clinical data also indicated that fRLS is more prominent among women who also had increased incidence of anemia/iron deficiency, arthritis, and number of pregnancies. Pregnancy-related RLS seems to be a characteristic feature of fRLS, and afflicted women tend to have a much younger age of onset. CONCLUSIONS: Restless legs syndrome significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease.

Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders.

STUDY OBJECTIVES: Conflicting reports on prevalence of RLS exist in Asian countries due to differences in sampling strategies and assessment instruments. We assessed the prevalence, correlates, quality of life, and psychiatric comorbidity of RLS in South Korea. DESIGN/SETTING: Cross-sectional nationwide survey. PARTICIPANTS: Nationally representative sample of 6,509 Korean adults aged 18-64. MEASUREMENT & RESULTS: Face-to-face interviews based on the Korean translation of the four features of RLS defined by the International RLS Study Group (IRLSSG), the Korean version of Composite International Diagnostic Interview (K-CIDI), and EuroQol (EQ-5D) were conducted for all participants. The weighted prevalence of RLS in South Korea was 0.9% (men, 0.6%; women, 1.3%). Subjects with RLS had a lower quality of life according to EQ-5D than those without RLS. Adjusted odds ratio for lifetime diagnosis of DSM-IV major depressive disorder (2.57, 95% confidence interval [1.33, 4.96]), panic disorder (18.9 [4.72, 75.9]) and posttraumatic stress disorder (3.76 [1.32, 10.7]) suggest strong association between RLS and DSM-IV depression and anxiety disorders. CONCLUSIONS: Prevalence of RLS estimated based on the IRLSSG diagnostic criteria is substantially lower in South Korea than in Western countries. Differences in culture and risk factors that affect the expression of RLS may vary across the countries.

Autosomal-dominant locus for Restless Legs Syndrome in French-Canadians on chromosome 16p12.1.

We describe an autosomal-dominant locus for Restless Legs Syndrome (RLS) in a French-Canadian (FC) pedigree. Genome-wide microsatellite scan and linkage analysis were used in this study. The locus maps to chromosome 16p12.1 and spans 1.18 Mega bases. The maximum multipoint LOD scores are of 3.5 over the total of 10 markers. Evidence for the same locus was also found in a smaller FC pedigree sime095. The analysis of the sequence of 8 annotated genes within the region did not reveal any pathogenic mutations. Copy number variation and karyotype analyses did not reveal any chromosomal abnormality in the region. Further analyses of the region are necessary to find the genetic cause of RLS in this family.

Periodic limb movements during sleep: population prevalence, clinical correlates, and racial differences.

STUDY OBJECTIVE: There is growing interest in the study of periodic limb movements during sleep and their potential clinical correlates. The aim of the present analysis is to address the lack of population-based studies using polysomnographic (PSG) measures to determine the prevalence of period limb movements during sleep in specific racial groups as well as the general population. SETTINGS AND PARTICIPANTS: A community-based sample of 592 participants drawn from the general population of tricounty Detroit (mean age = 41.9 +/- 12.6 years; 52.9% F; 31.5% African American). All individuals were assessed using objective and subjective measures in the sleep laboratory. MEASUREMENTS: Participants were evaluated during a 24-h laboratory assessment, including a polysomnogram and multiple sleep latency test. Periodic leg movements were scored using standard criteria. Reports of sleep disturbance and daytime sleepiness were also assessed using standardized measures including the Global Sleep Assessment Questionnaire (GSAQ) and the Epworth Sleepiness Scale (ESS). RESULTS: The overall prevalence of periodic limb movements during sleep (PLMSI >15) was 7.6%. African Americans had a lower prevalence of PLMSI >15 than Caucasians (4.3% vs. 9.3%; chi2= 4.5, P < 0.05). Regardless of race, symptoms of insomnia were significantly higher in individuals with PLMSI >15 than in those with PLMSI < or =15 (45% vs. 25%; chi2= 6.84, P < 0.01). CONCLUSION: This is the first study to determine the prevalence of PLMS in a population-based sample using standardized objective criteria. A key finding of the present study is that racial differences in this PSG parameter do exist, with African Americans being less likely to have elevated PLMS.

Epidemiology of restless legs syndrome in Korean adults.

STUDY OBJECTIVES: To investigate the prevalence of restless legs syndrome (RLS) in Korea. DESIGN: A large population-based telephone interview method using the Korean version of the Johns Hopkins telephone diagnostic interview for the RLS. SETTING: A computer aided telephone interview method. PARTICIPANTS: A total of 5,000 subjects (2,470 men and 2,530 women) were interviewed in depth. A representative sample aged 20 to 69 years was constituted according to a stratified, multistage random sampling method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Of the respondents, 373 respondents (7.5%) of the population (pop) met the criteria for the definite or probable RLS groups: 194 (3.9% of pop) respondents fulfilled the criteria for definite RLS and 179 (3.6% of pop) respondents fulfilled the criteria for probable RLS. The prevalence of RLS was generally higher for women than men (4.4% vs. 3.3% for definite, 8.7% vs. 6.2% for definite plus probable). About 90% of RLS individuals were experiencing symptoms at the time of the interview and this was similar for both RLS groups. Seventy-four respondents (1.48%) reported symptoms were moderately or severely distressing and were therefore classified as RLS "sufferers." Of those with a diagnosis of RLS sufferer, 24.3% reported being treated for their symptoms, compared to 12.4% of RLS not designated a "sufferer." CONCLUSION: RLS is common and underdiagnosed in Korea with nearly 1% of the population reporting disturbed sleep related to their RLS. These results are comparable to other countries.

Family-based association study of the restless legs syndrome loci 2 and 3 in a European population.

Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family-based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846-D9S171 in a subset of South European trios and with a haplotype at D9S156-D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS.

Prevalence of restless legs syndrome among native South Americans residing in coastal and mountainous areas.

OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native South Americans and identify the impact of geographic location. PARTICIPANTS AND METHODS: An epidemiological telephone survey of RLS symptoms involving natives from coastal and mountainous areas was performed during July 2, 2004, through September 28, 2004. The process consisted of 2 phases: the creation of the epidemiological instrument and the telephone survey. RESULTS: Five hundred adults, 250 from the mountainous regions and 250 from the coastal region (190 men and 310 women; age range, 25-85 years) were interviewed and subsequently divided on the basis of International Restless Legs Syndrome Study Group criteria into those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m above sea level (3.2% [8/250]) was significantly higher than that for adults living in the coastal region at 4 m above sea level (0.80% [2/250]; P = .002). The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-85 years). CONCLUSION: Native South American adults have a prevalence of RLS well below that reported in populations with European ancestry but similar to that in Asian and Turkish populations. Furthermore, in Ecuador, geographic differences were identified in areas of similar population density.

Race and restless legs syndrome symptoms in an adult community sample in east Baltimore.

BACKGROUND & PURPOSE: Due to the relative absence of African-Americans seeking treatment for restless legs syndrome (RLS) in specialty clinics, a lower prevalence of RLS among African-Americans than Caucasians has been suggested. We compared the prevalence of RLS in African-Americans and Caucasians in a biracial community sample as part of Wave IV of the Baltimore Health and Mental Health Study. METHODS: Subjects included 1071 adults [358 African-Americans (35.0%), and 633 Caucasians (61.8%), and 33 others]. Diagnosis of RLS was based on endorsement of RLS symptoms on a seven-item RLS questionnaire during a household interview. Adjusted odds and 95% confidence intervals were calculated based on logistic regression models with diagnosis of RLS as the main outcome variables and African-American race as the main predictor while adjusting for other relevant sociodemographic and/or health-related variables. RESULTS: The prevalence of RLS in this population was 4.1%. The rates were similar for African-Americans (4.7%) and Caucasians (3.8%). After adjustment for age, gender, medical comorbidities, and socioeconomic status, no difference in the prevalence of RLS was found between African-Americans and Caucasians. CONCLUSION: RLS is comparably prevalent among African-American and Caucasian adults in the general population. Barriers affecting access to care settings for African-American RLS patients should be investigated in the future.