Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized,placebo-controlled polysomnographic study

ObjectiveTo assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236).MethodsSixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3 mg/24 h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings.ResultsMean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48, 7.28], p < 0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: ?3.12 (95% CI [?5.36, ?0.88], p = 0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS = 0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity.ConclusionsRotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances.     

Assessing health-related quality of life in patients with restless legs syndrome in Korea: Comparison with other chronic medical diseases

BackgroundThere have been few quality of life (QoL) studies of patients with restless legs syndrome (RLS) in Asian countries. We studied the QoL of patients with RLS and compared it to normal controls and patients with hypertension, type 2 diabetes, or osteoarthritis in Korea.MethodsA total of 215 RLS patients (141 female; mean age 51.7 ± 13.5) were enrolled. All patients completed the questionnaires, including all the Korean versions of SF-36, RLS QoL, the International RLS Severity scale (IRLS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory-2 (BDI-2). These results were compared with the scores from normal controls (N = 214) and from patients with hypertension (196), uncomplicated type 2 diabetes (185), or osteoarthritis of the knee (177).ResultsThe SF-36 QoL in patients with RLS was lower than that of the normal controls, and even lower than patients with hypertension or diabetes, but higher than those with osteoarthritis. The SF-36 Qol of RLS patients showed a significantly negative correlation with the severity of RLS symptoms (r = ?0.430, p < 0.001) and the severity of depression (r = ?0.565, p < 0.001), but was not significantly related to gender, age, or age-of-symptom onset (early or late-onset). Step-wise multiple regression identified three factors related to SF-36 QoL: depression (46.5% of RLS had responses on BDI-2 indicating depression) (β = ?.899, p < 0.001), RLS symptom severity (K-IRLS) (β = ?.718, p < 0.001), and gender (female) (β = ?6.128, p = 0.007).ConclusionsThese findings show that RLS has a considerable impact on the QoL of Koreans, which is comparable with studies of western countries. The QoL impairment relates to the degree of depression with RLS for Koreans.     

Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality of life

ObjectiveThis study investigates the prevalence and the association between restless legs syndrome (RLS) and a large variety of health variables in two well-characterized random samples from the general population in Reykjavik, Iceland, and Uppsala, Sweden.MethodsUsing the national registries of inhabitants, a random sample from adults aged 40 and over living in Reykjavík, Iceland (n = 939), and Uppsala, Sweden (n = 998), were invited to participate in a study on the prevalence of COPD (response rate 81.1% and 62.2%). In addition, the participants were asked to answer the following questionnaires: International RLS Rating Scale, Short Form-12, the Epworth Sleepiness Scale, and questions about sleep, gastroeosophageal reflux, diabetes and hypertension, as well as pharmacological treatment. Interleukin-6 (IL-6), C-reactive protein (CRP) and ferritin were measured in serum.ResultsRLS was more commonly reported in Reykjavik (18.3%) than in Uppsala (11.5%). Icelandic women reported RLS almost twice as often as Swedish women (24.4 vs. 13.9% p = 0.001), but there was no difference in prevalence of RLS between Icelandic and Swedish men. RLS was strongly associated with sleep disturbances and excessive daytime sleepiness. Subjects with RLS were more likely to be ex- and current smokers than subjects without RLS (p < 0.001). Respiratory symptoms and airway obstruction were more prevalent among those reporting RLS and they also estimated their physical quality of life lower than those without RLS (p < 0.001). RLS was not associated with symptoms of the metabolic syndrome like hypertension, obesity, markers of systemic inflammation (IL-6 and CRP) or cardiovascular diseases. Ferritin levels were significantly lower in RLS participants (p = 0.0002), but not (p = 0.07) after adjustment for center, age, sex and smoking history.ConclusionRestless legs syndrome was twice as common among Icelandic women compared to Swedish women. No such difference was seen for men. RLS was strongly associated with smoking and respiratory symptoms, decreased lung function, sleep disturbances, excessive daytime sleepiness, and physical aspects of life quality. RLS was not associated with markers of the metabolic syndrome like hypertension, obesity, cardiovascular diseases or biomarkers of systemic inflammation.     

Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

Voxel-based morphometry in unmedicated patients with restless legs syndrome

BackgroundThe pathophysiology of restless legs syndrome (RLS) is not yet understood. A prior voxel-based morphometry (VBM) study reported gray matter increase in the pulvinar of the thalamus in a group of patients, most of whom were on medical treatment. Since there is evidence that medication can change the volume of cerebral structures, the question arises as to whether the reported morphometric alterations are caused by the RLS itself or, alternatively, are a consequence of drug treatment. To address this issue, we performed VBM in unmedicated RLS patients.MethodsFourteen patients with idiopathic RLS with no (n = 11) or only minimal (n = 3) treatment exposure in the past and 14 age- and sex-matched healthy subjects were investigated. All subjects were free of psychotropic drugs for at least 4 months. Morphological data were analyzed by using optimized VBM.ResultsWe did not detect any structural changes except for slightly increased gray matter density in the ventral hippocampus (p = 0.046 on the left and p = 0.055 on the right side) and in the middle orbitofrontal gyrus (p = 0.046 on the right and p = 0.097 on the left side).ConclusionOur study could not confirm the findings of a prior study. A possible explanation for the divergent findings is the difference between the populations examined. Since, in our study, essentially treatment-naïve patients were investigated, it is possible that the prior findings reflect treatment-induced effects on cerebral morphology in RLS.     

Effect of adenotonsillectomy on c-reactive protein levels in children with obstructive sleep apnea: A meta-analysis

ObjectiveChildren with obstructive sleep apnea syndrome (OSAS) have increased systemic inflammation, as assessed by c-reactive protein (CRP), and are at risk for substantial end-organ damage. Previous studies assessing the effect of adenotonsillectomy (T&A) on CRP in children with OSAS have yielded conflicting results. Therefore, the purpose of the current investigation was to perform a meta-analysis of the effect of T&A on CRP in children with OSAS and explore possible moderating factors.MethodsMultiple databases (PubMed, CINAHL, and Cochrane) were searched for relevant studies. Effective size was calculated with standardized mean differences (SMD) and analyzed with random-effects model. Moderators were examined with mixed-effects models.ResultsOverall, T&A significantly reduced CRP (SMD = −0.79, 95% CI −1.33 to −0.25). We found significant between-study heterogeneity (Cochran’s Q = 54.6, df = 7, p < 0.001; I2 = 90.7%, 95% CI 77.5–98.2%; and H2 = 10.7, 95% CI 4.5–55.7). We did not find evidence of publication bias or significant effects of tested moderators (study year, study size, age, gender, obesity, apnea–hypopnea index, oxygen nadir, pre-surgical CRP, follow-up duration).ConclusionsThe results of the current study indicate that T&A significantly reduces CRP levels in children with OSAS. Despite the presence of significant between-study heterogeneity, we did not identify any significant moderating factors.     

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized,double-blind,placebo-controlled study

ObjectiveTo evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS).MethodsPatients with moderate to severe RLS having periodic limb movements in bed index (PLMI) ? 5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75 mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6 weeks after starting treatment.ResultsThe analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p = 0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline ? 15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p = 0.0005), a significant improvement in both Patient Global Impression (PGI; p < 0.0001) and Clinical Global Impressions (CGI-I; p = 0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p = 0.0016), when compared with those of placebo group at week 6.ConclusionsPramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder.     

Association of low ferritin with PLM in the Wisconsin Sleep Cohort

ObjectiveThe origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation.MethodsWe included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels.ResultsAfter controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447).ConclusionsAn association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency.     

A prospective study of C-reactive protein as a state marker in Cardiac Syndrome X

Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal epicardial coronary arteries seen on invasive angiography, is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We sought to establish if C-reactive protein (CRP) levels varied with disease severity and so whether it is a state or trait marker. We studied 16 CSX patients with typical angina pectoris, normal coronary arteries and an electrically positive exercise stress test (EST) and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up at a subsequent visit with repeated exercise stress testing and CRP measurement. We found that CRP levels were significantly higher in the CSX group compared to the HC (1.5 [0.8–4.5] v 0.8 [0.4–1.4] mg/L, p = 0.02). This elevation in CRP persisted throughout the study length. CRP correlated with time to symptoms on EST at enrolment and at the second visit (r = −0.690, df = 10, p = 0.013 and r = −0.899, df = 4, p = 0.015, respectively). At the follow-up visit, 50% of CSX patients developed electrically and symptomatically negative ESTs. The mean CRP of this group was significantly lower than that of the CSX patients with ongoing symptoms and positive ESTs (1.2 ± 0.2 v 2.8 ± 0.6 mg/L, p = 0.018) and did not differ significantly from that of healthy controls. CRP levels also dropped in patients whose symptoms improved while they increased in patients who became more symptomatic (p = 0.027). We conclude that the results of this small study support the concept of CSX being an inflammatory-mediated condition with CRP levels prospectively varying with functional measures of disease severity. This indicates that CRP is a state marker in CSX.     

A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: Polysomnographic evaluation of periodic leg movements and sleep disturbance

Objective: To evaluate, both polysomnographically and by subjective scales, the efficacy and safety profile of pramipexole for restless legs syndrome (RLS) via a 3-week, double-blind, placebo-controlled, parallel-group, dose-ranging study.Methods: At baseline and after 3 weeks, periodic limb movements (PLM) and sleep parameters were assessed by polysomnography, and patients self-assessed their sleep disturbance and overall RLS severity using the international RLS study group rating scale (IRLS). Four pramipexole doses were evaluated: 0.125, 0.25, 0.50, and 0.75 mg/d. Data from 107 patients were included in the intent-to-treat (ITT) analysis.Results: For pramipexole recipients, the primary outcome measure, PLM per hour in bed asleep or awake (the PLM index, or PLMI), decreased by a median of ?26.55 to ?52.70 depending on dosage group, vs. ?3.00 for placebo (p < 0.01 or ?0.001 for each group vs. placebo; Wilcoxon–Mann–Whitney test). Improvements in the secondary endpoints of PLM while asleep and while awake were also significantly superior for pramipexole. At 3 weeks, all pramipexole doses reduced the median for PLM while asleep to levels considered normal (<5 PLM/h). Except for delta-sleep time and awakenings/arousals, sleep parameters remained unchanged or favored pramipexole. Median sleep latency was reduced by ?5.00 to ?11.75 min in the pramipexole groups, vs. ?2.00 for placebo (p < 0.05 for all groups except 0.25 mg/d). Median total sleep time increased by 25.75–66.75 min, vs. 25.50 (p < 0.05 for 0.50 mg/d), and median time in stages 2–4/rapid eye movement (REM) sleep increased by 37.00–68.00 min, vs. 26.75 (p < 0.05 for 0.50 mg/d). By subjective IRLS ratings, all pramipexole doses were significantly superior to placebo. Safety analysis demonstrated no dose-dependent increase in adverse events, and no drug-related increase in daytime somnolence was observed.Conclusions: Pramipexole is effective and well tolerated in RLS, most notably among objective measures, for reducing PLM and decreasing sleep latency. Although other sleep parameters showed lesser, usually insignificant change, patients’ subjective ratings of RLS severity and sleep disturbance were significantly improved (p ? 0.0023).     

C-reactive protein and depression in persons with Human Immunodeficiency Virus infection: The Positive Living with HIV (POLH) Study

BackgroundHuman Immunodeficiency Virus (HIV) infection has been frequently associated with chronic inflammation as well as depression. C-reactive protein (CRP) is positively associated with depression in people without HIV infection. We tested the hypothesis of an independent relationship between CRP and depression in a cohort of HIV-positive people.MethodsA cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 18–60 years residing in the Kathmandu Valley, Nepal. The latex agglutination turbidimetric method was used to measure serum CRP concentrations and the Beck Depression Inventory (BDI)-I method was used to measure depression, with a cut off of ⩾20 indicating likely depression. The relationship between CRP concentrations and depression symptoms was assessed using both multiple linear regression analysis and multiple logistic regression analysis, with adjustment for potential socio-demographic, cardiovascular, life-style, and HIV-related clinical and treatment confounding factors.ResultsTwenty-six percent participants (men: 23%; women: 29%) met criteria for depression. In multiple regression analysis, the authors observed a linear relation between serum CRP concentrations and BDI score (beta for 1 unit change in ln(CRP) = 1.13, p = 0.001) in HIV-positive participants. In a logistic regression analysis, participants with serum CRP levels > 3 mg/L had a 2.3-fold higher odds of depression symptoms compared to those with serum CRP level ⩽ 3 mg/L (p = 0.005). In analyses stratified by sex, associations were stronger in men than in women. For example, CRP > 3 mg/L was associated with a 3.6-fold higher odds of depression in men (p = 0.002), while in women the odds ratio was 1.7 (p = 0.33).ConclusionWe found a linear relationship between serum CRP concentrations and depression symptoms score in HIV-positive people, and evidence that risk of depression is elevated among HIV-positive men with a high level of inflammation (CRP > 3 mg/L). Further prospective study to confirm the role of inflammation in depression among HIV-positive people is warranted.     

Valid measures of periodic leg movements (PLMs) during a suggested immobilization test using the PAM-RL leg activity monitors require adjusting detection parameters for noise and signal in each recording

Objective and backgroundIndividuals with restless legs syndrome (RLS) (Willis-Ekbom disease [WED]) usually have periodic leg movements (PLMs). The suggested immobilization test (SIT) measures sensory and motor features of WED during wakefulness. Surface electromyogram (EMG) recordings of the anterior tibialis (AT) are used as the standard for counting PLMs. However, due to several limitations, leg activity meters such as the PAM-RL were advanced as a potential substitute. In our study, we assessed the validity of the measurements of PLM during wakefulness (PLMW) in the SIT for PAM-RL using both default and custom detection threshold parameters compared to AT EMG.MethodsData were obtained from 39 participants who were diagnosed with primary WED and who were on stable medication as part of another study using the SIT to repeatedly evaluate WED symptoms over 6–12 months. EMG recordings and PAM-RL, when available, were used to detect PLMW for each SIT. Complete PAM-RL and polysomnography (PSG) EMG data were available for 253 SITs from that study. The default PAM-RL (dPAM-RL) detected leg movements based on manufacturer’s noise (resting) and signal (movement) amplitude criteria developed to accurately detect PLM during sleep (PLMS). The custom PAM-RL (cPAM-RL) similarly detected leg movements except the noise and movement detection parameters were adjusted to match the PAM-RL data for each SIT.ResultsThe distributions of the differences between either dPAM-RL or cPAM-RL and EMG PLMW were strongly leptokurtic (Kurtosis >2) with many small differences and a few unusually large differences. These distributions are better described by median and quartile ranges than mean and standard deviation. Despite an adequate correlation (r = 0.66) between the dPAM-RL and EMG recordings, the dPAM-RL on average significantly underscored the number of PLMW (median: quartiles = −13: −51.2, 0.0) and on Bland–Altman plots had a significant magnitude bias with greater underscoring for larger average PLMW/h. There also was an adequate correlation (r = 0.70) between cPAM-RL and EMG but with minimal underscoring of PLMW (median quartiles = 0.0; −20, 10) and no significant magnitude bias. Two scorers independently scoring 13% of the SITs showed an adequate interscorer reliability of 0.96–0.98.ConclusionsOur study confirms our expectation that measuring PLMW in a SIT using dPAM-RL is not valid and that adjustments to the detection threshold criteria are required. The PAM-RL, using parameters customized for each SIT provided a valid and reliable measure of PLMW with minimal magnitude bias compared to the AT EMG recordings.     

Inflammatory biomarkers and emotional approach coping in men with prostate cancer

ObjectiveEmotion-regulating coping is associated with improvements in psychological and physical health outcomes. Yet in the context of prostate cancer-related stressors, limited research has characterized associations of emotion-regulating coping processes (emotional expression, emotional processing) and inflammatory processes that are related to disease risk. This investigation examined the relation of Emotional Approach Coping (EAC) with markers of inflammation to test the hypothesis that higher EAC scores at study entry (T1) would be associated with lower proinflammatory markers four months later (T2), specifically sTNF-RII, CRP, and IL-6.MethodsForty-one men (M age = 66.62 years; SD = 9.62) who had undergone radical prostatectomy or radiation therapy for localized prostate cancer within two years completed questionnaires, including assessments of EAC, at T1, and provided blood samples for immune assessments at T2.ResultsWhen controlling for relevant biobehavioral controls, emotional processing predicted lower IL-6 (B = −.66, p < .01), sTNF-RII (B = −.43, p < .05), and CRP (B = −.43, p < .10), whereas emotional expression was significantly associated with higher levels of sTNF-RII (B = .55, p < .05). Associations of emotional expression and IL-6 (B = .38, p < .10), and CRP (B = .44, p < .10) approached significance. Probing interactions of emotional processing and expression (though only approaching significance) suggested that expression of emotion is associated with higher inflammation (CRP and sTNF-RII) only in the context of low emotional processing.ConclusionsAttempts at emotion regulation via emotional processing appear to modulate inflammatory processes. Understanding, making meaning of, and working through emotional experience may be a promising target of intervention to reduce inflammation with potential effects on psychological and cancer outcomes in men with prostate cancer.     

Autonomic complaints in patients with restless legs syndrome

BackgroundData regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS).MethodsWe compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 items in six domains scored from 0 to 3. The total score and domain scores were transformed to 0–100 points. Subjects with neurodegenerative disorders (i.e., dementia, Parkinsonism) were excluded.ResultsThe RLS group was younger (mean ± standard deviation, 77.9 ± 8.0 vs 80.5 ± 7.9 years; P = .03) and included more women (84% vs 69%; P = .04). The mean SCOPA-AUT total score was higher in the RLS group compared with the control group (20 ± 11 vs 16 ± 9; P = .005). Additionally the RLS group had abnormalities in gastrointestinal, cardiovascular, and pupillomotor domains. When comparing the percentage of subjects with any complaint on individual questions (score of ⩾1), the RLS group had a greater number of subjects with sialorrhea, constipation, early abdominal fullness, lightheadedness when standing, and heat intolerance.ConclusionsAutonomic complaints, especially gastrointestinal, cardiovascular, and oversensitivity to light, were significantly increased in subjects with RLS. Causes for autonomic dysfunction in RLS require further investigation.     

Topography of sensory symptoms in patients with drug-naïve restless legs syndrome

ObjectivesWe aimed to describe the sensory topography of restless legs syndrome (RLS) sensory symptoms and to identify the relationship between topography and clinical variables.MethodsEighty adult patients with drug-naïve RLS who had symptoms for more than 1 year were consecutively recruited. During face-to-face interviews using a structured paper and pencil questionnaire with all participants, we obtained clinical information and also marked the topography of RLS sensory symptoms on a specified body template, all of which were subsequently inputted into our in-house software. The RLS sensory topography patterns were classified according to localization, lateralization, and symmetry. We investigated if these sensory topography patterns differed according to various clinical variables.ResultsThe lower extremities only (LE) were the most common location (72.5%), and 76.3% of participants exhibited symmetric sensory topography. Late-onset RLS showed more asymmetric sensory distribution compared with early-onset RLS (P = .024). Patients whose sensory symptoms involved the lower extremities in addition to other body parts (LE-PLUS) showed more severe RLS compared with those involving the LE (P = .037).ConclusionRLS sensory symptoms typically were symmetrically located in the lower extremities. LE-PLUS or an asymmetric distribution more often occurred in patients with more severe RLS symptoms or late-onset RLS.     

Self-reported experiences of everyday discrimination are associated with elevated C-reactive protein levels in older African-American adults

Self-reported experiences of “everyday” discrimination have been linked to indices of cardiovascular disease and overall mortality and findings have been particularly pronounced for African-American populations. However, the biological mechanisms underlying these associations remain unclear. C-reactive protein (CRP), a marker of inflammation, is a known correlate of cardiovascular and other health outcomes and has also been linked to several psychosocial processes. To our knowledge, no studies have examined the association between experiences of discrimination and CRP. We examined the cross-sectional association between self-reported experiences of discrimination and CRP in a sample of 296 older African-American adults (70% female, mean age = 73.1). Experiences of discrimination were assessed with the 9-item everyday discrimination scale and CRP was assayed from blood samples. In linear regression models adjusted for age, sex and education, experiences of discrimination were associated with higher levels of CRP (B = .10, p = .03). This association remained significant after additional adjustments for depressive symptoms (B = .10, p = .04), smoking, and chronic health conditions (heart disease, diabetes, hypertension) that might influence inflammation (B = .11, p = .02). However, results were attenuated when body mass index (BMI) was added to the model (B = .09, p = .07). In conclusion, self-reported experiences of everyday discrimination are associated with higher levels of CRP in older African-American adults, although this association is not completely independent of BMI.     

Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome

ObjectivesWe aimed to determine the importance of oxidative stress in the pathogenesis of restless legs syndrome (RLS) by quantification of advanced oxidation protein products and total thiol levels (as markers of oxidative protein damage), nitric oxide levels (as an antioxidant and endothelial function), and malondialdehyde levels (as a marker of lipid peroxidation) in patients with RLS.Design and methodsA total of 22 patients with primary RLS were enrolled in the study and 20 age-and-gender-matched healthy subjects were enrolled as a control group. Serum nitric oxide, malondialdehyde, thiol levels, and plasma advanced oxidation protein products levels were determined by spectrophotometric methods.ResultsSerum nitric oxide and thiol levels were lower in the patient group than in controls (p = 0.007 and p = 0.017, respectively). Plasma advanced oxidation protein products levels and serum malondialdehyde levels were found to be higher in patients with RLS than in controls (p = 0.017 and p = 0.008, respectively). Serum malondialdehyde level was found to be positively correlated with plasma advanced oxidation protein products levels (p = 0.039). Serum thiol level was found to be negatively correlated with plasma advanced oxidation protein products levels (p = 0.030).ConclusionsIncreased advanced oxidation protein products, malondialdehyde levels, and decreased thiol and nitric oxide levels, may suggest that patients with RLS are under oxidative stress. Although both lipid peroxidation and protein oxidation may have a role in atherosclerosis in RLS, those factors may be related to the pathogenesis of RLS.     

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

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

Acute phase protein and cytokine levels in serum and saliva: A comparison of detectable levels and correlations in a depressed and healthy adolescent sample

Recent research has examined associations between inflammation and mental health, and has increasingly focused on utilising younger samples to characterise the temporal relationship between inflammatory responses and the emergence of other symptoms. These studies have typically used blood to measure inflammation, although rates of detection for many inflammatory markers appear to be low. Saliva is a safe and low-cost alternative, and adult research has shown that levels of some salivary markers correlate well with those in serum. However, no research has examined this association in young people. This study examined 16 inflammatory markers in serum and saliva in 17 depressed adolescents and 18 healthy controls, aged 13–18 years. In general, detection rates were higher in saliva compared to in serum. When non-detectable levels were excluded, serum levels of C-reactive protein (CRP) correlated with salivary CRP (r = 0.424, p = 0.015), and this correlation appeared to only exist for those individuals with high levels of serum CRP (r = 0.599, p = 0.014). However, when non-detectable levels were included as zero, salivary levels of CRP, interleukin (IL)-2, IL-12p70, and interferon (IFN)-γ correlated with their serum counterparts. No significant clinical group differences in any acute phase proteins or cytokines were present. This study suggests that saliva can be used to measure inflammation in studies with adolescent participants, especially CRP, as it appears to correlate with systemic inflammation for those individuals who are expected to have high levels of inflammation. Implications for future directions in research on salivary inflammatory markers are discussed.