Parkinson’s disease sleep scale, sleep logs, and actigraphy in the evaluation of sleep in parkinsonian patients

The aim of this study was to compare the results of the day-to-day self-evaluation of sleep quality by sleep logs with Parkinson’s disease sleep scale (PDSS) in Parkinson’s disease (PD) patients. Actigraphy was used as an independent analysis of nighttime activity interfering with sleep. A total of 71 idiopathic PD patients and 21 age- and sex-matched normal individuals lacking any type of sleep disturbance were recruited. Sleep was evaluated by PDSS, 7-d sleep log and actigraphy. Sleep logs and PDSS showed reduced sleep quality and daytime somnolence scores in moderate/severe PD patients as compared to healthy controls. Significant correlations were found between sleep quality in sleep logs and all domains of PDSS sleep quality, except for the presence of nocturia, which correlated with nocturnal activity. PD severity and depression were the only predictors of reduced sleep quality. The retrospective and day-to-day sleep self-evaluations were coincident. Reduced sleep quality was related to increased PD severity and depression scores

Frequency of impulse control behaviours associated with dopaminergic therapy in restless legs syndrome.

BACKGROUND: Low doses of dopamine agonists (DA) and levodopa are effective in the treatment of restless legs syndrome (RLS). A range of impulse control and compulsive behaviours (ICBs) have been reported following the use of DAs and levodopa in patients with Parkinson's disease. With this study we sought to assess the cross-sectional prevalence of impulse control behaviours (ICBs) in restless legs syndrome (RLS) and to determine factors associated with ICBs in a population cohort in Germany. METHODS: Several questionnaires based on validated and previously used instruments for assessment of ICBs were mailed out to patients being treated for RLS. Final diagnoses of ICBs were based on stringent diagnostic criteria after psychiatric interviews were performed. RESULTS: 10/140 RLS patients of a clinical cohort (7.1%) were finally diagnosed with ICBs, 8 of 10 on dopamine agonist (DA) therapy, 2 of 10 on levodopa. 8 of the 10 affected patients showed more than one type of abnormal behaviour. Among those who responded to the questionnaires 6/140 [4.3%] revealed binge eating, 5/140 [3.6%] compulsive shopping, 3/140 [2.1%] pathological gambling, 3/140 [2.1%] punding, and 2/140 [1.4%] hypersexuality in psychiatric assessments. Among those who did not respond to questionnaires, 32 were randomly selected and interviewed: only 1 patient showed positive criteria of ICBs with compulsive shopping and binge eating. ICBs were associated with higher DA dose (p = 0.001), younger RLS onset (p = 0.04), history of experimental drug use (p = 0.002), female gender (p = 0.04) and a family history of gambling disorders (p = 0.02), which accounted for 52% of the risk variance. CONCLUSION: RLS patients treated with dopaminergic agents and dopamine agonists in particular, should be forewarned of potential side effects. A careful history of risk factors should be taken.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Rating of daytime and nighttime symptoms in RLS: validation of the RLS-6 scale of restless legs syndrome/Willis-Ekbom disease

Background: The International Restless Legs Scale (IRLS) is the most widely used of the scales rating the severity of restless legs syndrome/Willis-Ekbom disease (RLS/WED). It has been well validated and is the primary end point for most of the therapeutic and nontherapeutic studies of RLS/WED. It has excellent psychometric properties, although it does not capture the severity of RLS under a wide variety of circumstances and times of day. Moreover, the IRLS has a large placebo effect. Methods: The Restless Legs Syndrome-6 Scale (RLS-6), however, takes another potentially valuable approach. Six items are rated on a 0-10 scale from no symptoms at 0 to very severe at 10. In addition to questions on satisfaction with sleep and sleepiness, the scale rates the severity of RLS for the past week under four separate circumstances: while falling asleep, during the night, during the day while sitting or lying, and during the day when moving around. The purpose of the current study is to report the validation of the RLS-6 under baseline and therapeutic conditions. Results: The RLS-6 seems to be an acceptable, reliable, precise, valid, and responsive instrument for the assessment of RLS severity in a specific and pragmatic manner. Conclusions: At present, we view the RLS-6 not as a replacement for the IRLS but as a supplement, as each scale provides information not captured by the other.S

Validation of the Kohnen Restless Legs Syndrome-Quality of Life instrument

Background: Due to the symptoms and the sleep disturbances it causes, Restless Legs Syndrome (RLS) has a negative impact on quality of life. Measurement of such impact can be performed by means of questionnaires, such as the Kohnen Restless Legs Syndrome-Quality of Life questionnaire (KRLS-QoL), a specific 12-item instrument that is self-applied by patients. The present study is aimed at performing a first formal validation study of this instrument. Methods: Eight hundred ninety-one patients were included for analysis. RLS severity was assessed by the International Restless Legs Scale (IRLS), Restless Legs Syndrome-6 scales (RLS-6), and Clinical Global Impression of Severity. In addition the Epworth Sleepiness Scale (ESS) was assessed. Acceptability, dimensionality, scaling assumptions, reliability, precision, hypotheses-related validity, and responsiveness were tested. Results: There were missing data in 3.58% patients. Floor and ceiling effects were low for the subscales, global evaluation, and summary index derived from items 1 to 11 after checking that scaling assumptions were met. Exploratory parallel factor analysis showed that the KRLS-QoL may be deemed unidimensional, ie, that all components of the scale are part of one overall general quality of life factor. Indexes of internal consistency (alpha = 0.88), item-total correlation (rS = 0.32-0.71), item homogeneity coefficient (0.41), and scale stability (ICC = 0.73) demonstrated a satisfactory reliability of the KRLS-QoL. Moderate or high correlations were obtained between KRLS-QoL scores and the IRLS, some components of the RLS-6, inter-KRLS-QoL domains, and global evaluations. Known-groups validity for severity levels grouping and responsiveness analysis results were satisfactory, the latter showing higher magnitudes of response for treated than for placebo arms. Conclusions: The KRLS-QoL was proven an acceptable, reliable, valid, and responsive measure to assess the impact of the RLS on quality of life.S

Combined Analysis of CSF Tau, Aβ42, Aβ1–42% and Aβ1–40ox% in Alzheimer's Disease, Dementia with Lewy Bodies and Parkinson's Disease Dementia

We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox% levels for differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1–42% and Aβ1–40ox% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1–40ox% and CSF alpha-synuclein for the diagnosis of DLB

Effects of short- and long-term variations in RLS severity on perceived health status - the COR-study.

In a cohort study among 2751 members (71.5% females) of the German and Swiss RLS patient organizations changes in restless legs syndrome (RLS) severity over time was assessed and the impact on quality of life, sleep quality and depressive symptoms was analysed. A standard set of scales (RLS severity scale IRLS, SF-36, Pittsburgh Sleep Quality Index and the Centre for Epidemiologic Studies Depression Scale) in mailed questionnaires was repeatedly used to assess RLS severity and health status over time and a 7-day diary once to assess short-term variations. A clinically relevant change of the RLS severity was defined by a change of at least 5 points on the IRLS scale. During 36 months follow-up minimal improvement of RLS severity between assessments was observed. Men consistently reported higher severity scores. RLS severity increased with age reaching a plateau in the age group 45-54 years. During 3 years 60.2% of the participants had no relevant (±5 points) change in RLS severity. RLS worsening was significantly related to an increase in depressive symptoms and a decrease in sleep quality and quality of life. The short-term variation showed distinctive circadian patterns with rhythm magnitudes strongly related to RLS severity. The majority of participants had a stable course of severe RLS over three years. An increase in RLS severity was accompanied by a small to moderate negative, a decrease by a small positive influence on quality of life, depressive symptoms and sleep quality

PO104 placebo and nocebo responses in RLS : a meta-analysis

Objective: Our goals were to estimate the placebo and nocebo responses in restless legs syndrome (RLS). Methods: Databases were searched up to October 2015. Randomised, double-blind, placebo-controlled trials of RLS patient were included. ‘Placebo response’ was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. ‘Nocebo response’ was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Results: We included 5046 participants. Pooled placebo response effect size was −1.41 (95%CI:−1.56-−1.25), corresponding to −6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95%CI:40.47%–50.29%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacological interventions and idiopathic RLS, and in industry funded and unpublished studies. The placebo response was considerable smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors. Conclusions: The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.info:eu-repo/semantics/publishedVersio

Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (≥300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations:Results of the open-label phase of the TOLEDO study

Introduction: The randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP). Methods: All patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO. Results: Eighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n = 4) and fatigue (n = 2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n = 55) showed a mean (SD) change from DBP baseline in daily OFF time of-3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (+/- SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543 mg (+/- 674) and levodopa dose by 273 mg (+/- 515). Conclusions: The safety and efficacy of APO infusion were demonstrated with long-term use for persistent motor fluctuations, allowing substantial reductions in oral PD medication

Tau protein, A beta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid((1-42)) (Abeta42), promising results for the diagnosis of Alzheimer's disease ( AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases. Copyright (C) 2005 S. Karger AG, Basel