The European Academy for Cognitive Behavioural Therapy for Insomnia : An initiative of the European Insomnia Network to promote implementation and dissemination of treatment

Insomnia, the most prevalent sleep disorder worldwide, confers marked risks for both physical and mental health. Furthermore, insomnia is associated with considerable direct and indirect healthcare costs. Recent guidelines in the US and Europe unequivocally conclude that cognitive behavioural therapy for insomnia (CBT‐I) should be the first‐line treatment for the disorder. Current treatment approaches are in stark contrast to these clear recommendations, not least across Europe, where, if any treatment at all is delivered, hypnotic medication still is the dominant therapeutic modality. To address this situation, a Task Force of the European Sleep Research Society and the European Insomnia Network met in May 2018. The Task Force proposed establishing a European CBT‐I Academy that would enable a Europe‐wide system of standardized CBT‐I training and training centre accreditation. This article summarizes the deliberations of the Task Force concerning definition and ingredients of CBT‐I, preconditions for health professionals to teach CBT‐I, the way in which CBT‐I should be taught, who should be taught CBT‐I and to whom CBT‐I should be administered. Furthermore, diverse aspects of CBT‐I care and delivery were discussed and incorporated into a stepped‐care model for insomnia.Peer reviewe

Biomarkers of conversion to alpha-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving \u3b1-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal \u3b1-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest \u3b1-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of \u3b1-synucleinopathy patients with isolated RBD might develop

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement. Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R)

Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1

Peer reviewe

Augmentation in restless legs syndrome is associated with low ferritin

Background and purpose: Augmentation is a major problem with dopaminergic therapy for restless legs syndrome (RLS), and predictors of augmentation have not yet been identified. We aimed to analyze the relationship between baseline ferritin level and occurrence of augmentation in a retrospective analysis of a prospective double-blind trial of cabergoline versus levodopa on augmentation in RLS. Patients and methods: Patients who experienced augmentation were compared to patients who did not experience augmentation. Results: Augmentation symptoms causing premature discontinuation from the study or which were tolerated (n = 36, ferritin: 85 + 59 ng/ml) were associated with lower levels of serum ferritin compared to patients without augmentation (n = 302, ferritin: 118 + 108 ng/ml, p = 0.0062). Conclusions: Ferritin as a marker of iron storage may play an important role in the pathophysiology of RLS and may prove to be a biomarker for the development of augmentation under dopaminergic therapy. (C) 2007 Elsevier B.V. All rights reserved

Restless legs syndrome: Diagnostic assessment and the advantages and risks of dopaminergic treatment

In the past few years, major advances have been made in the field of restless legs syndrome (RLS). New tools have been developed to assess the presence and severity of RLS and its complications. Furthermore new concepts of the phenotype are emerging. With a high likelihood a slight dopaminergic hypofunction contributes essentially to the pathophysiology of most phenotypes of RLS. Dopaminergic substitution either with L-DOPA or with dopamine agonists ameliorates symptoms in the large majority of patients. Too high of doses of either type of drug may be involved in the development of augmentation caused by treatment-induced alterations in doparninergic neurotransmission. Dopaminergic agents are currently the agents of first choice to treat RLS, and large multicenter trials support the evidence of efficacy. Very careful tailoring of the dose is required to avoid the development of treatment complications, specifically augmentation

Cabergoline compared to levodopa in the treatment of patients with severe Restless Legs Syndrome: Results from a multi-center, randomized, active controlled trial

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Methods: Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to disconfirmation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline. (c) 2007 Movement Disorder Society

One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome

Background: Long-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome. Methods: Efficacy and safety of rotigotine (0.5-4 mg/24 h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed. Results: Of 310 patients who finished the controlled trial, 295 (mean age 58 +/- 10 years, 66% females) with a mean IRLS score of 27.8 +/- 5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate = 74.6%) completed the 12-month follow-up period. The mean daily dose was 2.8 +/- 1.2 mg/24 h with 4 mg/24 h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0 mg/24 h. The IRLS total score improved by -17.4 +/- 9.9 points between baseline and end of Year 1 (p < 0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p < 0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as "good" or "very good" by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients. Conclusion: Rotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication. (c) 2008 Elsevier B.V. All rights reserved.Schwarz Biosciences GmbH; UCB-Group, Monheim, German