International Restless Legs Syndrome Severity Scale Research Articles

Restless Legs Syndrome Prevalence and Clinical Correlates Among Psychiatric Inpatients: A Multicenter Study.

BackgroundThere are only limited reports on the prevalence of restless legs syndrome (RLS) in patients with psychiatric disorders. The present study aimed to evaluate the prevalence and clinical correlates in psychiatric inpatients in Germany and Switzerland.MethodsThis is a multicenter cross-sectional study of psychiatric inpatients with an age above 18 years that were diagnosed and evaluated face-to-face using the International RLS Study Group criteria (IRLSSG) and the International RLS severity scale (IRLS). In addition to sociodemographic and biometric data, sleep quality and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). In addition to univariate statistics used to describe and statistically analyze differences in variables of interest between patients with and without RLS, a logistic model was employed to identify predictors for the occurrence of RLS.ResultsThe prevalence of RLS in a sample of 317 psychiatric inpatients was 16.4%, and 76.9% of these were diagnosed with RLS for the first time. RLS severity was moderate to severe (IRLS ± SD: 20.3 ± 8.4). The prevalences in women (p = 0.0036) and in first-degree relatives with RLS (p = 0.0108) as well as the body mass index (BMI, p = 0.0161) were significantly higher among patients with RLS, while alcohol consumption was significantly lower in the RLS group. With the exception of atypical antipsychotics, treatment with psychotropic drugs was not associated with RLS symptoms. Regarding subjective sleep quality and mood, scores of the PSQI (p = 0.0007), ISI (p = 0.0003), and ESS (p = 0.0005) were higher in patients with RLS, while PHQ-9 scores were not different. A logistic regression analysis identified gender (OR 2.67; 95% CI [1.25; 5.72]), first-degree relatives with RLS (OR 3.29; 95% CI [1.11; 9.73], ESS score (OR 1.09; 95% CI [1.01; 1.17]), and rare alcohol consumption (OR 0.45; 95% CI [0.22; 0.94] as predictors for RLS.ConclusionsClinically significant RLS had a high prevalence in psychiatric patients. RLS was associated with higher BMI, impaired sleep quality, and lower alcohol consumption. A systematic assessment of restless legs symptoms might contribute to improve the treatment of psychiatric patients.

Prevalence and predictors of restless legs syndrome in non-pregnant Saudi women of childbearing age.

This study assessed the prevalence of restless legs syndrome (RLS) and its correlates and severity among non-pregnant Saudi women of childbearing age. Consecutive non-pregnant female visitors (age 15-44 years) of the primary care centers of the female University campus at King Saud University (n = 1,136) were interviewed face-to-face to determine the presence and severity of RLS using the International Restless Legs Syndrome (IRLS) Study Group criteria and IRLS severity scale. A total of 271 participants (24%) were diagnosed with RLS. Of these cases, severe/very severe RLS was diagnosed in 13% and mild/moderate in 87%. None of these participants had been diagnosed or treated for RLS before. Subjects with RLS were older, had a higher body mass index, and a higher prevalence of vitamin D deficiency and diabetes mellitus than those without RLS. Multivariate binary logistic regression analysis identified the following independent predictors of RLS: age (OR 1.03 [1.009-1.051], p = 0.004), vitamin D deficiency (OR 2.147 [1.612-2.86], p < 0.001), and diabetes mellitus (OR 4.408 [1.946-9.982], p < 0.001). Our results indicate that RLS is very common and underdiagnosed among non-pregnant Saudi women of a childbearing age-attending primary care cents. RLS was linked to age, vitamin D deficiency, and diabetes mellitus.

Short-interval intracortical inhibition is decreased in restless legs syndrome across a range of severity

BackgroundDecreased short-interval intracortical inhibition (SICI) to transcranial magnetic stimulation (TMS) of the primary motor cortex was described in subjects with restless legs syndrome/Willis-Ekbom disease (RLS/WED). It remained to be determined whether the magnitude of SICI decrease would be similar across levels of RLS/WED severity. Moreover, it was unknown whether, in addition to decreases in SICI, changes in cortical thickness or area could be detected in subjects with RLS/WED compared to controls. The objective of this study was to compare SICI, cortical thickness, and cortical area in subjects with idiopathic mild to moderate RLS/WED, severe to very severe RLS/WED, and controls. MethodsThe severity of RLS/WED was assessed by the International Restless Legs Syndrome Severity Scale (IRLSS). SICI and 3T magnetic resonance imaging (MRI) data of subjects with RLS/WED and controls were compared. A receiver operating characteristic curve for SICI was designed for discrimination of participants with RLS/WED from controls. Cortical thickness and area were assessed by automated surface-based analysis. ResultsSICI was significantly reduced in patients with mild to moderate and severe to very severe RLS/WED, compared to controls (one-way analysis of variance: F = 9.62, p < 0.001). Receiver operating characteristic curve analysis predicted RLS/WED when SICI was above 35% (area under the curve = 0.79, 95% CI 0.67–0.91, p < 0.001). Analyses of the whole brain and of regions of interest did not reveal differences in gray matter thickness or area between controls and subjects with RLS/WED. ConclusionSICI is an accurate cortical biomarker that can support the diagnosis of RLS/WED even in subjects with mild symptoms, but cortical thickness and area were not useful for discriminating subjects with this condition from controls.

Characterization of painful Restless Legs Syndrome sensations in an English-speaking South African population.

Background and aims Restless Legs Syndrome (RLS) is characterised by unusual sensations in the legs which can be described as painful in up to 60% of RLS patients. The purpose of this study was to characterise and examine whether the presence of pain influenced the words used to describe the sensations of RLS in an English speaking population. Methods RLS participants (n=55) were divided according to whether or not painful RLS sensations were reported upon questioning. They completed the McGill Pain Questionnaire (MPQ), the International Restless Legs Syndrome Severity Scale (IRLS) and selected descriptors from a list of previously published RLS terms. Results Thirty-five percent of the RLS patients had painful sensations. The participants with painful RLS had higher Pain Rating Index (PRI) scores [median (interquartile range) 21 (17-28) vs. 14 (7.5-21) p=0.0008] and IRLS scores [23 (17-28) vs. 18 (11.5-22.5) p=0.0175] than the participants with non-painful RLS. Patients with painful RLS symptoms selected more pain-related literature terms, chose significantly different words in eight of the MPQ subclasses (both sensory and affective) and selected more intense descriptors from certain MPQ subclasses than the non-painful RLS group. The terms that characterised painful RLS were "aching", "painful", "cramping" and "unbearable". Conclusions Descriptors of RLS sensations are changed by the presence of pain, which may indicate an aetiological difference in the patients who have painful RLS. Clinically, patients complaining of cramping and painful sensations may be diagnosed with a condition that mimics RLS. Thus, it is important that the most accurate set of descriptors for RLS are used to enable recognition of RLS and optimised treatment according to the RLS phenotype. Implications The diagnosis of RLS may be improved by overcoming language and cultural barriers and obtaining differential diagnostic terms for painful conditions mimicking RLS.

Validation of the self-administered version of the international Restless Legs Syndrome study group severity rating scale – The sIRLS

IntroductionThe International Restless Legs Study Group (IRLSSG) has developed the IRLS (International Restless Legs Syndrome Severity Scale) and validated it as a clinician/researcher administered scale to be used when both patient and examiner are present. The IRLSSG recognized the need for a self-completing scale that can be used economically in clinical practice and in large population-based studies. In this study the validity and the reliability of the IRLS as a self-administered scale (sIRLS) is assessed. MethodsEstablished RLS patients were recruited by eight centers in four countries and consented to participate in this study. The validity of the sIRLS was assessed by patients completing the sIRLS before a clinician administered the IRLS. The reliability of the sIRLS was assessed by patients completing the sIRLS again, two weeks after the first one, provided no change had occurred. ResultsOverall, 173 patients were recruited and 164 of them were included in the analyses. The sIRLS showed satisfactory scaling assumptions and no relevant floor or ceiling effect. One factor explained 61.3% of the variance. Cronbach's alpha was 0.93 and the item homogeneity index was 0.59. Intraclass correlation coefficient between the sIRLS and the IRLS was 0.94. The sIRLS standard error of measurement was 3.61 (½ SD at baseline = 4.11). The results mostly overlapped those of the IRLS analyzed in parallel. DiscussionThe sIRLS is a reliable, valid and precise instrument that showed tight association with the IRLS. These findings support the use of the sIRLS for self-evaluation of RLS severity. The responses obtained on the sIRLS and the IRLS scale varied slightly. Therefore, we recommend that either the sIRLS or the IRLS scale be used as the only scale for serial measures over time.

Efficacy of ferric carboxymaltose (FCM) 500 mg dose for the treatment of Restless Legs Syndrome

IntroductionThere have been four randomized, placebo-controlled, double-blinded studies of intravenous (IV) iron in Restless Legs Syndrome (RLS), all of which delivered a final total dose of 1000 mg of iron. The purpose of this study was to evaluate effects of a lesser total dose (500 mg of iron). MethodsSubjects with idiopathic RLS were enrolled in a randomized, double-blinded, placebo-controlled study. Subjects received either 500 mg ferric carboxymaltose (FCM) or placebo as a single infusion (Phase I). Subjects who were previously on medication were off any RLS medications for at least two weeks prior to baseline assessment. The primary outcome variable was a change-from-baseline at week six on the International RLS Severity Scale (IRLSS) and a subject-completed Visual Analog Scale of Severity (VAS). Phase II of the study involved long-term (30 weeks) follow-up after completing the six week efficacy phase. ResultsAt week six post infusion, FCM, compared to placebo recipients, showed no significantly greater change-from-baseline for both primary outcome measures (IRLSS scale, FCM 500 mg vs. placebo: −8.3 ± 7.5 vs. −4.8 ± 8.7, p = 0.100; VAS, FCM 500 mg vs. placebo: −23.4 ± 24.1 vs. −13.3 ± 23.1, p = 0.077). None of the secondary outcome variables showed a significant difference at week six. Seven (21.9%) of the 32 subjects treated with iron in Phase I remained free from further RLS medications at 30 weeks. No serious adverse effects were found in this study. ConclusionsThis study did not show significant benefit from a single 500 mg FCM treatment for RLS symptoms. The two previous, well-controlled, trials of 1000 mg FCM showed significant treatment benefits which suggested that there may have been a clinically relevant total dose required to achieve a clinical response.

Clinical efficacy of ferric carboxymaltose treatment in patients with restless legs syndrome

ObjectiveThere have been three randomized, placebo-controlled, double-blind studies of intravenous iron in restless legs syndrome (RLS), with differing outcomes. The one positive study used ferric carboxymaltose (FCM) at a total dose of 1000 mg. The purpose of this study was to replicate and extend the findings from the prior FCM study. MethodsNon-anemic, idiopathic RLS patients were enrolled in a randomized, double-blinded, placebo-controlled study and received either 1000 mg FCM or placebo as a single infusion (phase I). Subjects were off any RLS medications for at least two weeks prior to baseline assessment. The primary outcome variable was change from baseline at week 6 on the International Restless Legs Syndrome Severity (IRLSS) scale and a subject-completed, visual analog scale (VAS) of severity. Phase II of the study involved long-term (30 weeks) follow-up after completion of the six-week efficacy phase. ResultsAt week 6 postinfusion, FCM compared to placebo recipients showed significantly greater change from baseline for both primary outcome measures (IRLSS scale, −11.9 ± 8.04 vs −7.88 ± 5.89, p = 0.03; VAS, −40.6 ± 22.7 vs −21.3 ± 20.0, p = 0.001). None of the secondary outcome variables showed a significant difference at week 6. After six weeks of treatment, the FCM group had 19 (59.4%) responders, of which 12 had IRLSS scores <10 (“remitters”). Twelve (37.5%) of the 32 subjects treated with iron in phase I remained free of further RLS medications at 30 weeks. There were no serious adverse events observed in this study. ConclusionTwo studies now support the value of FCM treatment both in the short term (six weeks) and long term (30 weeks) for improving RLS symptoms.

Intravenous iron administration in restless legs syndrome : An observational study in geriatric patients.

This observational study was carried out to investigate the effect of intravenous (i.v.) iron administration on the clinical symptoms of restless legs syndrome (RLS) in geriatric outpatients over 65 years old. In this study geriatric outpatients (mean 4.5 ± 3.4 comorbidities and 5.7 ± 4.4 drugs taken) were recruited according to the following inclusion criteria: ≥ 65 years, diagnosis of RLS due to iron deficiency, i.e. ferritin < 50µg/l or transferrin saturation (TFS) < 16 %) as well as no other iron therapy within 2 weeks prior to the study. Of the patients 7 (41 %) received 500mg ferric carboxymaltose (FCM) and 10 patients (59 %) received iron gluconate (62.5mg) based on the degree of iron deficiency. As assessed by the international RLS severity scale (IRLS) symptoms were recorded 3 times: at the beginning of iron therapy (t0), after 2 weeks (t1) and after 12 weeks (t2). A total of 17 patients (13 female, 4 male, mean age 73.2 ± 5.9 years) were included. The IRLS score significantly improved in all patients as shown by an average decrease from 30.2 (± 4.3) to 20.2 (± 4.7) (p < 0.001) after 2 weeks of i.v. iron treatment and to 23.2 ± 6.6 (p < 0.001) after 12 weeks. There was a high correlation between ferritin values and the IRLS score (C 0.729, p < 0.001). The part of the IRLS referring to activities of daily living (ADL) improved from a median of 3 (scores 3-4) to 2 (scores 2-3, p = 0.001) after 2 weeks (effect size - 0.6). In this study group of geriatric outpatients i.v. administration of iron was associated with a significant improvement of symptoms in RLS as assessed by the IRLS score 2 weeks after treatment. In geriatric patients with RLS associated with iron deficiency, i.v. iron administration should be considered regarding improvement of RLS symptoms and ADL.

Increased frequency and severity of restless legs syndrome in patients with neuromyelitis optica spectrum disorder

ObjectivesTo investigate the comorbidity of restless legs syndrome (RLS) and neuromyelitis optica spectrum disorder (NMOSD). MethodsThis study enrolled 159 NMOSD patients and 153 age- and gender-matched healthy controls. All participants completed a questionnaire based on the updated International Restless Legs Syndrome Study Group consensus criteria, the International RLS Severity scale, Epworth Sleepiness Scale, Fatigue Severity Scale, and Pittsburgh Sleep Quality Index, and were subsequently interviewed by a neurologist. The frequency and features of RLS were compared between NMOSD patients and healthy controls. The clinical and radiological characteristics of the NMOSD patients with and without RLS were also compared. ResultsThe frequency and severity of RLS were significantly higher in NMOSD patients than in healthy controls (p = 0.015 for both) and NMOSD patients with RLS had a longer disease duration and more severe disability than those without RLS. ConclusionsThis study indicated importance of considering RLS in NMOSD patients.

Sternberg working memory performance following treatment with pramipexole in patients with moderate-to-severe restless legs syndrome

ObjectivesWe recently reported that the P300 amplitude related to the Sternberg working memory (WM) task was significantly lower in drug-naïve severe restless legs syndrome (RLS) patients than controls. Here, we evaluated the effects of pramipexole on the Sternberg WM task performance by event-related potential (ERP) study. MethodsThirteen drug-naïve RLS patients (52.0 ± 9.48 years) were enrolled in the study. Pramipexole was administered over a period of 12 weeks every night 1 h before bedtime. Two ERP studies were carried out: the first was performed just before giving the first dose of pramipexole and the second was conducted at 12–16 weeks after commencement of pramipexole administration. P300 amplitudes and reaction times were compared before and after treatment considering brain regions and memory load as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude. ResultsAfter treatment with pramipexole, the International RLS Severity Scale (IRLS) score was significantly decreased. Sleep quality and depression were also significantly improved. Omission error was significantly reduced without significant change of commission error. Reaction time was significantly shortened, regardless of memory load size, following treatment with pramipexole. Parietal P300 amplitude was significantly increased after treatment with pramipexole for all memory load sizes. Increase of frontal P300 amplitude was significantly correlated with improvement of sleep duration, IRLS, Insomnia Severity Index, and Pittsburgh Sleep Quality Index score. ConclusionOur study suggested that pramipexole improves WM performance in patients with RLS in addition to improving RLS symptoms, sleep disturbance, and depression.

Effect of Pramipexole on Cognitive Functions in Restless Legs Syndrome

Address for correspondence Ki-Young Jung, MD, PhD Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82-2-2072-4988 Fax: +82-2-2072-7424 E-mail: jungky10@gmail.com Objectives: Neuropsychological evaluations have revealed cognitive dysfunction in restless legs syndrome (RLS) patients, especially frontal lobe functions. Although dopamine agonists improve RLS sensory symptoms and periodic leg movements during sleep, there was no study regarding the effects of dopamine agonist on cognition in patients with RLS. Methods: Sixteen drug-naive RLS patients were enrolled. They underwent sleep questionnaires, Beck Depression Inventory, and neuropsychological evaluation, consisting of Rey Complex Figure Test and recognition trial (RCFT), Korean-California Verbal Learning Test, Controlled Oral Word Association Test (COWAT) before and after treatment with pramipexole (PMP). PMP was administered over a period of 12 weeks every night 1 h before bedtime. Paired Student’s t-test and Spearman’s correlation analysis were used for analyses. Results: After treatment with PMP, the International RLS Severity Scale score was significantly decreased. Sleep quality and depression also significantly improved after the treatment. RCFT immediate recall, COWAT phoneme word frequency, and digit symbol coding scores significantly improved compared to those before the treatment (17.72±7.84 vs. 20.13±7.33, p=0.05; 36.50±12.62 vs. 41.50±12.58, p=0.03; 68.19±21.11 vs. 73.81±21.11, p=0.02, respectively). There were no significant correlations between changes in clinical variables and in cognitive functions before and after the treatment. Conclusions: This study suggests that treatment with PMP in RLS patients improves not only RLS sensory symptoms, but also cognitive functions. J Korean Sleep Res Soc 2014;11(1):16-20

Lower molecular weight intravenous iron dextran for restless legs syndrome

Various techniques used to assess brain iron concentrations have demonstrated the presence of low iron stores in patients with restless legs syndrome (RLS). Previous open-label and randomized studies generally support the value of iron treatment for RLS symptoms. Only one of these studies assessed iron therapy response to changes in brain iron status. The current study was designed to assess the effect of iron therapy on RLS symptoms and on CSF measures of brain iron status. Idiopathic RLS patients drawn from the Korean population received four weekly intravenous (IV) doses of 250 mg low-molecular weight iron dextran for a total dose of 1g. One week after the last dose, any subject on RLS medication tapered off the RLS medications. Blood and CSF samples were taken to measure iron parameters at baseline and again, three weeks after the last dose. We have been following their response to the drug for two years after treatment. Twenty-five patients (age 55.2 ± 9.3, 18 female) enrolled in this study without serious adverse reactions. Seventeen of the 25 patients (68%) showed moderate or complete improvement of all RLS symptoms after treatment based on the Korean-translated versions of the International RLS Severity scale (K-IRLS). Changes in the K-IRLS did not correlate significantly with changes in CSF ferritin. The response to IV iron could not be predicted by patients' demographics, or by blood or CSF iron baseline characteristics. RLS symptom improvement started between one and six weeks after treatment and the treatment benefits lasted from one month to 22 months. Fourteen patients, (56%) completely stopped all medications, for a mean duration of 31.3 ± 33.1 weeks. These results are comparable to those from a prior study with high molecular weight dextran. Intravenous low-molecular weight iron dextran produced significant improvement of RLS symptoms in a majority of patients without any significant adverse effects. Serious anaphylaxis occurs with high molecular weight, but rarely, if ever, with this low molecular weight dextran. Given apparent comparable efficacy the low molecular weight and not the high molecular weight iron dextran, should be considered for RLS treatment. Although changes in CSF ferritin were seen following therapy, these changes were not related to clinical improvements.

Restless Legs Syndrome in Liver Transplant Recipients

Background: The prevalence of restless legs syndrome (RLS) is approximately 10% in general population. This condition is more prevalent in certain diseases and we previously reported the prevalence of RLS in chronic liver disease population to be 62%. Objectives: Our aim was to assess the self-reported prevalence of RLS using an RLS symptom specific questionnaire in liver transplant patients. Methods: Subjects were a convenience sample in transplant clinic. They completed a validated survey for core RLS symptoms and if positive went on to completed a telephone survey using the validated International RLS Severity Scale Questionnaire (IRLS) and the Johns Hopkins RLS QoL survey to measure the effect of RLS symptoms on daily activities. Results: 40 patients surveyed, RLS was found in 16 subjects (40%) with moderate severity {17 (SD + 7.2, high score 31)}. Hepatitis C as indication for liver transplant was more likely associated with RLS (p = 0.05). Calcium channel blockers were protective (p = 0.032) while antidopaminergic agent use was statistically significant for RLS symptom (p = 0.005). On multiple linear regression analysis, diabetes (p = 0.024) and use of antidepressants/antihistamines (p = 0.049) were associated with RLS. Quality of Life (QoL) surveys specific to RLS suggested RLS symptoms resulted in significantly diminished QoL, with an average QoL score of 80 (SD + 11.7). Conclusion: There was a very high prevalence of RLS in our liver transplant patients with majority experiencing moderate or severe symptoms. The explanation for this higher prevalence is likely due to combination of comorbidites as well as medications that can trigger RLS.

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

There 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. A 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). The 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). These 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.

Investigating the response to intravenous iron in restless legs syndrome: An observational study

To investigate the effect of intravenous (IV) iron (500 mg ferric carboxymaltose [FCM] as a single dose) on restless legs syndrome (RLS) severity on a day-to-day basis. Twenty patients with RLS and absolute or functional iron deficiency or low normal serum ferritin (<45 μg/l) were included. Change of RLS severity was evaluated using the International RLS severity scale (IRLS) and the RLS-severity diary (RLS-SD) which evaluates symptom severity over a 6-h period on an 11-point numerical Likert scale, four times a day. Twelve patients reported that IV FCM improved RLS ("responders"). IRLS score decreased from 30.1 (± 5.9) to 23.07 (± 9.5) (p=0.001) in the whole group and from 28.3 (± 6.1) to 18.3 (± 8.0) (p=0.002) in the responder group three weeks after IV FCM treatment. A clinically relevant effect of IV iron on RLS severity could be seen as early as day eight. The responder group differed from the non-responder group in tendency by being younger (p=0.064), having a lower serum ferritin level at baseline (p=0.097), and presenting a lower number of comorbid conditions. FCM led to a considerable improvement in RLS in the responder group within about one week. These findings are clinically relevant, especially for patients with severe RLS symptoms and iron deficiency, since a change or uptitration of RLS-specific medication can be avoided or postponed in these patients due to the rapid response to IV FCM treatment.

Efficacy and safety of dopamine agonists in restless legs syndrome

Restless legs syndrome (RLS) is a common neurological disorder causing considerable impairment to daily living. This article is an overview of a comprehensive Cochrane meta-analysis on the efficacy and safety of dopamine agonists (DAs), the first-line treatment of RLS. CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for double-blind randomized controlled trials (RCTs) of DAs vs placebo. Thirty-five placebo-controlled RCTs (total number of patients=6954) were eligible. The likelihood of bias was considered to be low. The mean treatment duration of the RCTs was 10.3 (standard deviation 7.3) weeks, with treatment durations up to seven months. Overall, DAs showed a moderate improvement in the International RLS Severity Scale score (mean difference -5.7 points [95% confidence interval, CI, -6.7 to -4.7; P<0.00001]) and the Clinical Global Impression-Improvement response (risk ratio 1.44 [95% CI 1.34-1.54; P<0.00001]) compared with placebo. Periodic limb movements decreased by -22.38/h (95% CI -27.8 to -16.9; P<0.00001) for DAs compared with placebo. Sleep quality and disease-specific quality of life increased slightly to moderately. Safety data confirmed the established safety characteristics of DAs. Augmentation, a specific side-effect of dopaminergic treatment of RLS, was not assessed adequately. This meta-analysis showed that DAs have moderate efficacy in the treatment of RLS. Actively controlled and long-term studies are still lacking. Large-scale comparative studies are needed to identify the most efficient treatments for this chronic disorder.

Electrophysiologic disturbances during daytime in patients with restless legs syndrome: Further evidence of cognitive dysfunction?

Backgrounds It has been reported that patients with restless legs syndrome (RLS) may have cognitive deficit. The authors performed EEG and ERP analysis during daytime to identify electrophysiologic relations with cognitive dysfunction in unmedicated RLS patients. Methods Seventeen drug naive RLS patients (53.7 ± 9.6 years) and 13 age-matched healthy controls participated in the present study. EEG was recorded during the waking–resting state and during a visual oddball task. RLS severities were determined using the International RLS Severity Scale. Stanford sleepiness scale (SSS) and bothersomeness visual analog scale (VAS) scores were determined immediately after ERP sessions. EEG power spectra and P300 amplitude and latency were compared for patients and controls. Clinical variables were correlated with P300 findings. Results Waking–resting EEG showed that RLS patients had significantly higher beta activity in frontocentral regions than controls. SSS scores were not different in the two groups. But the bothersomeness VAS scores of RLS patients were significantly higher than those of controls. Furthermore, P300 latency was significantly longer in patients, and patients had significantly lower P300 amplitudes in frontal and central locations. In addition, P300 latency was found to be significantly correlated with bothersomeness during the ERP test, whereas P300 amplitude showed no such tendency. Conclusions Our study supports the notion that RLS patients have an underlying cognitive dysfunction. Significant correlations found between P300 latency and bothersomeness, a lack of sleepiness during the ERP test, and increased beta activity in resting state EEGs suggest that a combination of inattention and cortical dysfunction underlie cognitive dysfunction in RLS.

Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study

BackgroundRestless legs syndrome (RLS) is a chronic disorder with substantial impact on quality of life similar to that seen in diabetes mellitus or osteoarthritis. Little is known about the psychological characteristics of RLS patients although psychological factors may contribute to unfavourable treatment outcome.MethodsIn an observational cross-sectional design, we evaluated the psychological features of 166 consecutive RLS patients from three outpatient clinics, by means of the Symptom Checklist 90-R (SCL-90-R) questionnaire. Additionally, the Beck Depression Inventory-II (BDI-II) and the International RLS Severity Scale (IRLS) were measured. Both treated and untreated patients were included, all patients sought treatment.ResultsUntreated patients (n = 69) had elevated but normal scores on the SCL-90-R Global Severity Index (GSI; p = 0.002) and on the sub-scales somatisation (p < 0.001), compulsivity (p = 0.003), depression (p = 0.02), and anxiety (p = 0.004) compared with a German representative sample. In the treated group, particularly in those patients who were dissatisfied with their actual treatment (n = 62), psychological distress was higher than in the untreated group with elevated scores for the GSI (p = 0.03) and the sub-scales compulsivity (p = 0.006), depression (p = 0.012), anxiety (p = 0.031), hostility (p = 0.013), phobic anxiety (p = 0.024), and paranoid ideation (p = 0.012). Augmentation, the most serious side effect of dopaminergic, i.e. first-line treatment of RLS, and loss of efficacy were accompanied with the highest psychological distress, as seen particularly in the normative values of the sub-scales compulsivity and anxiety. Generally, higher RLS severity was correlated with higher psychological impairment (p < 0.001).ConclusionSeverely affected RLS patients show psychological impairment in multiple psychological domains which has to be taken into account in the treatment regimen.

Health Economic Burden of Patients with Restless Legs Syndrome in a German Ambulatory Setting

The primary characteristics of restless legs syndrome (RLS), including severe sleep disorders, restlessness in the evening and discomfort while at rest, have substantial impact on normal daily activities. Because of the high prevalence of RLS in the general population, it is necessary to evaluate the economic impact of RLS. To determine the health economic burden of patients with RLS in Germany. A total of 519 RLS patients (mean age: 65.2 +/- 11.1 years) in different stages of disease were recruited in five health centres (university hospitals, district hospitals and office-based neurologists) by applying the diagnostic criteria of the International Restless Legs Syndrome Study Group. A questionnaire was administered that assessed healthcare resource consumption as well as socioeconomic, demographic, clinical and health status. In addition, the International RLS severity scale (IRLS), Epworth Sleepiness Scale (ESS), EQ-5D and Beck Depression Inventory (BDI) were addressed in the assessment. Direct and indirect costs (euro, year 2006 values) were derived from various German economic resources and calculated from the perspective of the healthcare and transfer payment providers. We calculated average total costs over the 3-month observation period. It was determined that average total costs were euro2090 for this period. The average direct medical and non-medical costs from the perspective of the health insurance provider were determined to be euro780, with euro300 attributed to drug costs and euro354 to hospitalization costs. Average total indirect costs amounted to euro1308 and were calculated based on productivity loss, using the human capital approach. As cost-driving factors we identified disease severity according to the IRLS (p < 0.01) and ESS (p < 0.04). Health-related quality of life was determined to be substantially affected by RLS; the mean EQ-5D visual analogue scale (VAS) was 55.6, considerably lower than that of the age-matched general population. RLS places a notable financial burden on society as well as on patients and their families. More detailed studies are needed to evaluate the health economic impact of this disorder.

Rotigotine transdermal delivery for the treatment of restless legs syndrome

Importance of the field: Rotigotine is a non-ergot dopamine agonist devised to be applied transdermally as a patch. It is currently licensed for treatment of early (USA and Europe) and advanced (Europe) Parkinson's disease, as well as for the treatment of moderate to severe restless legs syndrome (RLS) (Europe). Constant drug delivery and ease of use due to the application of an adhesive patch once daily are the potential advantages of the rotigotine patch for the treatment of RLS.Areas covered in this review: The evidence on the efficacy, tolerability and safety of rotigotine in the treatment of RLS is reviewed. Source material was identified using a PubMed search using the key words ‘rotigotine’ (up to September 2009) and using data from rotigotine trials being submitted or published in abstract form. This review focuses only on publications related to rotigotine for the treatment of RLS.What the reader will gain: In the drug trials summarized here, rotigotine transdermal patch is efficacious for the treatment of RLS, using dosages between 1 and 3 mg/24 h, up to 30% of severely affected patients reached freedom of symptoms with an IRLS (International Restless Legs Syndrome Severity Scale) of zero. Safety and tolerability are similar to other non-ergot dopamine agonists, except for application site reactions, which may limit practicability. Retrospective analysis of augmentation were 1.5% in placebo-controlled 6-month trials and 2.9% in a 1-year open trial.Take home message: The rotigotine transdermal patch can provide ‘around the clock’ treatment for moderate to severe RLS. Further comparative studies need to clarify whether continuous low-dose dopamine-agonist therapy will have any influence on augmentation rates.