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Background: Upper respiratory infections have been suggested as a risk factor for spontaneous cervical artery dissection (sCeAD). If this is the case, public health measures implemented to contain the spread of SARS-CoV-2, which also reduced other communicable diseases such as influenza, might be associated with a reduction in cervical artery dissection incidence. Aims: We determined the incidence of sCeAD before, during and after the COVID-19 pandemic, and the associated public health measures. Methods: All patients suffering an sCeAD and seen in Innsbruck Austria, between January 2002 to December 2016 (pre-COVID comparators) and between January 2020 to August 2022 were recorded through two individual prospective cohort studies. We compared admission rates, demographic, and clinical characteristics of sCeAD patients in pre-COVID-19 and COVID-19 times. Results: In total, 249 sCeAD patients were admitted prior to the COVID-19 pandemic compared to 20 during its course. Baseline characteristics of sCeAD subjects did not differ in subjects admitted during and prior to the pandemic. Following the introduction of public health measures for the pandemic, there was a marked decrease of sCeAD admissions from 16.5 per year to 6.3 per year (p = 0.012). Since the measures were ended the number of sCeAD admissions increased again. In contrast, the number of all ischemic stroke patients treated at the Medical University of Innsbruck did not alter during the pandemic. (N per year: 633 in 2015, 687 in 2017, 684 in 2019, 731 in 2020, and 717 in 2021). Conclusion: The incidence of sCeAD fell markedly during the pandemic and this may have resulted from the public health measures introduced and a subsequent reduction in upper respiratory infections. Our study provides indirect evidence for a role of infection in the pathogenesis of sCeAD. Data access statement: Anonymized data not published within this article will be made available by request from any qualified investigator.

Sleep disorders, daytime sleepiness, and autonomic dysfunction are commonly reported among patients with multiple system atrophy and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness, and autonomic function.Twenty patients with multiple system atrophy (n = 7) and PD (n = 13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and 2-night video-polysomnography were followed by administration of the Multiple Sleep Latency Test. Rapid eye movement sleep without atonia was quantified in the chin, flexor digitorum superficialis, tibial anterior, and sternocleidomastoid muscles.Rapid eye movement sleep behavior disorder was associated with orthostatic hypotension (The relationship of autonomic dysfunction with rapid eye movement sleep without atonia in PD and multiple system atrophy is accounted for by shared brainstem neuropathology and likely identifies patients in a more advanced stage of disease. Excessive daytime sleepiness is found exclusively in PD and may be secondary to levodopa treatment and not related to α-synuclein disease.Eckhardt C, Fanciulli A, Högl B, et al. Analysis of sleep, daytime sleepiness, and autonomic function and multiple system atrophy and Parkinson disease: a prospective study.

Over three decades of evidence indicate that dopamine (DA) D

Zusammenfassung Hintergrund Sechs bis zehn Prozent aller Patienten mit einer obstruktiven Schlafapnoe leiden trotz adäquater nächtlicher Überdrucktherapie oder einer effektiven Alternativtherapie an einer residualen exzessiven Tagesschläfrigkeit (rETS). Die Differentialdiagnose der rETS stellt im klinischen Alltag eine interdisziplinäre Herausforderung dar. Fragestellung Entwicklung eines übersichtlichen Leitfadens für die Erkennung, die differentialdiagnostischen Abwägungen und die Möglichkeiten der weiterführenden Behandlung der rETS in der klinischen Praxis. Material und Methode MeSH-Analyse basierte Recherche und interdisziplinäre Abstimmung von Fachvertreter:innen der Inneren Medizin und Pneumologie, Neurologie sowie Psychiatrie und Psychotherapie. Ergebnisse SPAIN-Checkliste zur systematischen differentialdiagnostischen Exploration der rETS mit den Parametern: S chlafverhalten, P sychische Ursachen, A namnese der Medikation, I nternistische Ursachen und N eurologische Ursachen. Schlussfolgerungen Die rETS sollte als behandlungswürdiges Symptom erkannt werden. Sie verlangt nach einer interdisziplinären Abklärung und der individuellen Abstimmung der Behandlung auf die Bedürfnisse der Betroffenen.

In the last few years, plastic has become an issue of current interest as tremendous ecological effects from plastic littering have become visible. Taking the role of consumers into account, activities comprising purchasing decisions and political engagement are expected to help prevent plastic pollution. The goal of this study was to examine antecedents of three potential plastic reduction activities: purchasing, activism, and policy support. Based on well-established psychological models of pro-environmental behaviour (i.e. theory of planned behaviour, norm activation model), an online survey (N = 648) was administered and analysed via structural equation modelling. Results revealed that personal norms were a relevant predictor of all three intentions. Whereas sufficiency orientation and collective efficacy predicted only activism intention and policy support intention, perceived behavioural control was the strongest predictor of purchasing intentions. Regarding behaviour, people with high activism intentions and sufficiency orientation were more likely to choose a plastic-free incentive instead of the conventional shopping voucher. This study highlights psychological antecedents of plastic reduction. An integrated model showed that rational cost–benefit considerations as well as morality serve as drivers of reducing plastic consumption. Implications for the promotion of plastic-free consumption are discussed.

Study Objectives To investigate the frequency and characteristics of large muscle group movements (LMMs) during sleep in healthy adults. Methods LMMs were scored following the International Restless Legs Syndrome Study Group criteria in 100 healthy participants aged 19–77 years. A LMM was defined as a temporally overlapping increase in EMG activity and/or the occurrence of movement artifacts in at least two channels. LMM indices and durations in total sleep time (TST), NREM and REM sleep, and association with arousals, awakenings, and/or respiratory events were calculated. Correlations of LMMs indices and durations with sleep architecture, respiratory and motor events, and subjective sleep quality were investigated. Results Median LMMs index in TST was 6.8/h (interquartile range (IQR), 4.5–10.8/h), median mean duration 12.4 s (IQR 10.7–14.4 s). Mean LMMs duration was longer in NREM (median 12.7 s, IQR 11.1–15.2 s) versus REM sleep (median 10.3 s, IQR 8.0–13.5s), p Conclusions This is the first study providing normative data on LMMs frequency in healthy adults. LMMs are a ubiquitous phenomenon often associated with other events. Correlation with arousals and respiratory events suggests a potential clinical significance of LMMs in adults that awaits further investigation.

While a growing body of studies suggests a link between sleep disturbances and neurodegenerative diseases’ (NDDs) development, prior studies have been hindered by small sample sizes, short follow-up times and a lack of objective sleep measures.In this cohort study, patients who underwent polysomnography (PSG) at the Innsbruck Sleep Disorders Unit from January 2004 to December 2007, aged ≥18 years, without NDDs at baseline or within five years post PSG, and with at least five years clinical follow-up were included. The main outcome measure was NDDs diagnosis at least five years after polysomnography, assessed until December 2021.Of 1454 patients assessed for eligibility, 999 (68.7%) met inclusion criteria (683 (68.3%) men; median age 54.9 (interquartile range, IQR 33.9-62.7) years. Seventy-five patients (7.5%) developed NDDs, 924 (92.5%) remained disease-free after 12.8 (IQR 9.9-14.6) years median follow-up. After adjusting for demographic, sleep, and clinical covariates, each percent decrease in sleep efficiency, N3 sleep, or REM sleep was associated with 1.9%, 6.5%, and 5.2% increased risk of incident NDDs (hazard ratio, HR, 1.019, CI:1.002-1.035; HR 1.065, CI:1.007-1.118; HR 1.052, CI:1.012-1.085,), respectively whereas one percent decrease in night-time wakefulness represented a 2.2% reduced risk (HR 0.978, CI:0.958-0.997). Random forest analysis identified wake, followed by N3 and REM sleep percentages, as the most important feature associated with NDDs development. Additionally, multiple sleep features combination offered more robust discrimination of incident NDDs compared to single sleep stages.These findings support contribution of sleep architecture changes to NDDs pathogenesis and provide insights into the temporal window during which these changes are detectable, pointing to sleep as early NDDs marker and potential target of neuroprotective strategies.

Video-polysomnography (VPSG) and prolonged video-EEG-monitoring (pVEEG-M) are neurophysiological investigation modalities. Depending on indication either is performed, but occasionally patients undergo both (during the same or separate stays). We sought to assess the reasons and potential benefits of dual diagnostic assessments with both modalities.A retrospective chart-review was performed to identify patients who underwent both VPSG and pVEEG-M during the 10 year period between 2007 and 2017. One-hundred-nine patients were identified who had undergone both studies. Patients were grouped according to indication and outcome.One-hundred-nine patients had both, a VPSG and pVEEG-M, in 62 (56.9%) the studies were performed because of separate diagnoses independent from each other. In 47 patients (43.1%) investigation with both modalities was needed to clarify the suspected diagnosis or to refute differential diagnoses. Out of these 47, 11 (10.1% of the whole group) arrived a new final diagnosis whereas in 36 (33%) the primary diagnosis was corroborated with the second modality.In the majority of cases VPSG plus pVEEG-M were indicated to diagnose or monitor different comorbid diseases (e.g. sleep-related breathing disorder and epilepsy). In the other cases, performing both modalities was useful to achieve a higher diagnostic accuracy or to refute differential diagnoses.VPSG and pVEEG-M are neurophysiological investigations which complement each other, especially in case of two different comorbid diseases in a single patient, to rule out differential diagnosis or when a higher diagnostic certainty is seeked.

An overlooked and little-understood potential site for meaningful engagement among assisted living residents with dementia is the salon. This thesis addresses this knowledge gap by 1) examining salon experiences in relation to resident appearance, self-identity, and engagement opportunities; 2) identifying processes and factors related to salon experiences; and 3) viewing salon experiences and their meaning through the lens of embodied selfhood. Qualitative interview and fieldnote data from the study, Meaningful Engagement and Quality of Life in Persons Living with Dementia in Assisted Living were analyzed, guided by grounded theory method and informed by the sensitizing concepts of embodiment, self-narrative, and social identity. Several processes were identified comprising the salon experience that, collectively, provided engagement in a form of embodied selfhood meaningful to residents with dementia, and as such, helped residents maintain their personhood and sense of self. Findings point to the importance of care partner facilitation of resident salon experiences.

Differentiation of central disorders of hypersomnolence (DOH) is challenging but important for patient care. This study aimed to investigate whether biomarkers derived from sleep structure evaluated both by manual scoring as well as with artificial intelligence (AI) algorithms allow distinction of patients with different DOH. We included video-polysomnography data of 40 narcolepsy type 1 (NT1), 26 narcolepsy type 2 (NT2), 23 patients with idiopathic hypersomnia (IH) and 54 participants with subjective excessive daytime sleepiness (sEDS). Sleep experts manually scored sleep stages. A previously validated AI algorithm was employed to obtain automatic hypnograms and hypnodensity graphs (where each epoch is represented as a mixture of sleep stage probabilities). One-thousand-three features describing sleep architecture and instability were extracted from manual/automatic hypnogram and hypnodensity graphs. After feature selection, random forest classifiers were trained and tested in a 5-fold-cross-validation scheme to distinguish groups pairwise (NT1-vs-NT2, NT1-vs-IH, …) and single groups from the pooled remaining ones (NT1-vs-rest, NT2-vs-rest,…). The accuracy/F1-score values obtained in the test sets were: 0.74 ± 0.04/0.79 ± 0.05 (NT1-vs-NT2), 0.89 ± 0.09/0.91 ± 0.08 (NT1-vs-IH), 0.93 ± 0.06/0.91 ± 0.07 (NT1-vs-sEDS), 0.88 ± 0.04/0.80 ± 0.07 (NT1-vs-rest), 0.65 ± 0.10/0.70 ± 0.09 (NT2-vs-IH), 0.72 ± 0.12/0.60 ± 0.10 (NT2-vs-sEDS), 0.54 ± 0.19/0.38 ± 0.13 (NT2-vs-rest), 0.57 ± 0.11/0.35 ± 0.18 (IH-vs-sEDS), 0.71 ± 0.08/0.35 ± 0.10 (IH-vs-rest) and 0.76 ± 0.08/0.71 ± 0.13 (sEDS-vs-rest). The results confirm previous findings on sleep instability in patients with NT1 and show that combining manual and automatic AI-based sleep analysis could be useful for better distinction of NT2 from IH, but no precise sleep biomarker of NT2 or IH could be identified. Validation in a larger and multi-centric cohort is needed to confirm these findings.

Objective: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. Methods: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan–Meier survival analysis. Results: A 5′-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5′ risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3′ of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3′ variant rs356182) had an opposite direction of effect in iRBD compared to PD. Interpretation: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3′ of SNCA. Several 5′ SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies. ANN NEUROL 2020;87:584–598.

Within society, problem awareness related to plastic pollution is high. Nevertheless, plastic production and consumption is constantly increasing. Plastic consumption expresses two sides of a coin: consumers appreciate plastic packaging for its practicability and other benefits, likewise they also experience concern especially related to pollution with waste and microplastic. In the current work, we systematically investigated valence- (Study 1; sample size [N] = 103) and risk- (Study 2; N = 105) related attitudes towards plastic packaging, plastic waste, and microplastic. Therefore, we measured participants’ attitudes implicitly and explicitly. By using single-category implicit association tests, we revealed that packaging and microplastic were automatically evaluated as ‘bad’ and neutral regarding risk, and waste as ‘bad’ and ‘risky’. Explicit responses in both studies highlighted an overall negative evaluation of all plastic forms. Thereby, packaging was rated as less ‘bad’, ‘unpleasant’, ‘unpractical’, and ‘risky’ (in general and for the environment) than waste and microplastic. The latter was evaluated as much riskier for human health than packaging and waste. Environmental risk ratings were generally very high. In comparison to other materials (paper, glass, metal), plastic was generally rated as worse and riskier. We conclude that attitudes related to plastic mirror high problem awareness and, therefore, plastic-reduction interventions should support consumers in acting according to their attitudes rather than addressing only awareness and attitude change.

The severity of the ongoing opioid crisis, recently exacerbated by the COVID-19 pandemic, emphasizes the importance for individuals suffering from opioid use disorder (OUD) to have access to and receive efficacious, evidence-based treatments. Optimal treatment of OUD should aim at blocking the effects of illicit opioids while controlling opioid craving and withdrawal to facilitate abstinence from opioid use and promote recovery. The present work analyses the relationship between buprenorphine plasma exposure and clinical efficacy in participants with moderate to severe OUD using data from two clinical studies (39 and 504 participants). Leveraging data from placebo-controlled measures assessing opioid blockade, craving, withdrawal and abstinence, we found that buprenorphine plasma concentrations sustained at 2–3 ng/ml (corresponding to ≥70% brain mu-opioid receptor occupancy) optimized treatment outcomes in the majority of participants, while some individuals (e.g., injecting opioid users) needed higher concentrations. Our work also included non-linear mixed effects modeling and survival analysis, which identified a number of demographic, genetic and social factors modulating treatment response and retention. Altogether, these findings provide key information on buprenorphine plasma levels that optimize clinical outcomes and increase the likelihood of individual treatment success. NLM identifiers: NCT02044094, NCT02357901.

Plastic pollution is ubiquitous in the environment. One initiative that tackles this global environmental problem is the “Plastic Free July,” a worldwide campaign encouraging consumers to reduce th...

ZUSAMMENFASSUNGDas Restless-legs-Syndrom (RLS) ist eine der häufigsten neurologischen Erkrankungen. Gutachterliche Fragestellungen bei RLS-Patienten nehmen seit den vergangenen Jahren stetig zu. Daher hat die AG Motorik und Schlaf der Deutschen Gesellschaft für Schlafforschung und Schlafmedizin (DGSM) 2006 erstmals Empfehlungen zur Begutachtung und sozialmedizinischen Einschätzung des RLS erarbeitet. Im Folgenden werden die spezifischen Empfehlungen zur Beurteilung des RLS im Rahmen gutachterlicher Verfahren in einer Neubearbeitung vorgestellt. Diese Empfehlungen stellen eine Grundlage zur Vereinheitlichung und Qualitätssicherung in der Begutachtung des RLS dar, sie sollen jedoch nicht in die individuelle Freiheit und Verantwortung des jeweils beauftragten Gutachters eingreifen. Da bisher keine evidenzbasierten Studien über das RLS vorliegen, die die Besonderheiten der gutachterlichen Situation berücksichtigen, sind diese Empfehlungen als Konsensusdokument konzipiert.

ZUSAMMENFASSUNGDie Rapid-Eye-Movement (REM)-Schlafverhaltensstörung (RBD) ist eine Parasomnie, bei der es zu einem unwillkürlichen Ausleben von Trauminhalten während des REM-Schlafes kommt. Die physiologische Muskelatonie während des REM-Schlafes ist aufgehoben. Die Mehrheit (> 90 %) der Patienten mit einer isolierten RBD (iRBD) entwickeln im weiteren Verlauf eine alpha-Synukleinopathie (M. Parkinson, Demenz mit Lewy-Körperchen, Multisystematrophie). Liegt eine RBD vor, führt die Degeneration von Schaltkreisen des Nucleus subcoeruleus, die inhibierend auf die medulläre Formatio reticularis und in die spinalen Vorderhörner einwirken, dazu, dass Bewegungen während des REM-Schlafs möglich werden. Um die Diagnose einer RBD stellen zu können, ist der Nachweis einer fehlenden Muskeltonusabsenkung während des REM-Schlafes (REM-sleep without atonia, RWA) notwendig, was nur mit Hilfe einer Videopolysomnografie möglich ist. Grundvoraussetzung für die Beurteilung von Verhaltensauffälligkeiten und Vokalisationen ist die zeitsynchrone Aufzeichnung von Video und Ton. Kurative oder krankheitsmodulierende Therapien existieren nicht. Groß angelegte Behandlungsstudien, die einen Effekt in der symptomatischen Behandlung nachweisen, liegen ebenfalls nicht vor, sodass Therapieempfehlungen meist auf Expertenmeinungen und Daten retrospektiver Fallserien basieren. Dabei zeigten sich Melatonin 3–12 mg und Clonazepam 0,25–2 mg als wirksam. Da die RBD ein Frühstadium einer neurodegenerativen Erkrankung darstellt, bietet sie sich in der Zukunft als Ausgangspunkt für neuroprotektive Studien an.

STUDY OBJECTIVES: The objective of this study was to evaluate interrater reliability between manual sleep stage scoring performed in 2 European sleep centers and automatic sleep stage scoring performed by the previously validated artificial intelligence–based Stanford-STAGES algorithm. METHODS: Full night polysomnographies of 1,066 participants were included. Sleep stages were manually scored in Berlin and Innsbruck sleep centers and automatically scored with the Stanford-STAGES algorithm. For each participant, we compared (1) Innsbruck to Berlin scorings (INN vs BER); (2) Innsbruck to automatic scorings (INN vs AUTO); (3) Berlin to automatic scorings (BER vs AUTO); (4) epochs where scorers from Innsbruck and Berlin had consensus to automatic scoring (CONS vs AUTO); and (5) both Innsbruck and Berlin manual scorings (MAN) to the automatic ones (MAN vs AUTO). Interrater reliability was evaluated with several measures, including overall and sleep stage-specific Cohen’s κ. RESULTS: Overall agreement across participants was substantial for INN vs BER (κ = 0.66 ± 0.13), INN vs AUTO (κ = 0.68 ± 0.14), CONS vs AUTO (κ = 0.73 ± 0.14), and MAN vs AUTO (κ = 0.61 ± 0.14), and moderate for BER vs AUTO (κ = 0.55 ± 0.15). Human scorers had the highest disagreement for N1 sleep (κ(N1) = 0.40 ± 0.16 for INN vs BER). Automatic scoring had lowest agreement with manual scorings for N1 and N3 sleep (κ(N1) = 0.25 ± 0.14 and κ(N3) = 0.42 ± 0.32 for MAN vs AUTO). CONCLUSIONS: Interrater reliability for sleep stage scoring between human scorers was in line with previous findings, and the algorithm achieved an overall substantial agreement with manual scoring. In this cohort, the Stanford-STAGES algorithm showed similar performances to the ones achieved in the original study, suggesting that it is generalizable to new cohorts. Before its integration in clinical practice, future independent studies should further evaluate it in other cohorts. CITATION: Cesari M, Stefani A, Penzel T, et al. Interrater sleep stage scoring reliability between manual scoring from two European sleep centers and automatic scoring performed by the artificial intelligence–based Stanford-STAGES algorithm. J Clin Sleep Med. 2021;17(6):1237–1247.

In crimes facilitated by γ-hydroxybutyric acid (GHB) administration, the frequent occurrence of anterograde amnesia of the victims as well as the short detection window and variations of endogenous GHB concentrations complicate obtaining analytical proof of GHB administration. Because elevated endogenous organic acid concentrations have been found in the urine of patients with succinic semialdehyde deficiency (leading to accumulation of GHB in human specimens) and after GHB ingestion, we searched for an alternative way to prove GHB administration via detection of elevated organic acid concentrations in blood plasma and urine. We collected blood and urine samples from narcolepsy patients (n = 5) treated with pharmaceuticals containing GHB sodium salt (1.86-3.72 g GHB as free acid per dose). Although GHB was detectable only up to 4 h in concentrations greater than the commonly used cutoff levels in blood plasma, 3,4-dihydroxybutyric acid (3,4-DHB) could be detected up to 12 h in blood plasma in concentrations exceeding initial concentrations of the same patient before GHB ingestion. Furthermore, four of the five patients showed an increase above endogenous levels described in the scientific literature. In urine, GHB concentrations above commonly used cutoff levels could be observed 4.5-9.5 h after GHB intake. Creatinine standardized initial concentrations were reached again for glycolic acid (GA), 3,4-DHB, and 2,4-dihydroxybutyric (2,4-DHB) acid at 6.5-22, 11.5-22, and 8.5-70 h after GHB intake, respectively. Therefore, 2,4-DHB, 3,4-DHB, and GA are promising and should be further investigated as potential biomarkers to prolong the detection window of GHB intake.

Objective Sleep complaints are frequent after acute COVID-19. Aim of this study was to videopolysomnographically evaluate sleep and sleep disorders after SARS-Cov2 infection. Methods Patients with suspected sleep disorders after acute COVID-19 underwent video-polysomnography (v-PSG) at the Sleep Disorders Clinic, Department of Neurology, Medical University Innsbruck. V-PSG was conducted 4.2 (SD = 1.3) months after diagnosis of SARS-CoV-2 infection. Results Eleven patients [nine men, age 52.5 (SD = 11.7) years; BMI 29 (SD = 5.2) kg/m2] were included. At 60 days follow-up after diagnosis, persisting breathing complaints were present in 7/11 (64%) patients. After v-PSG four patients (36%) were diagnosed with obstructive sleep apnea (OSA). Respiratory frequency during sleep was normal and no tachypnea, thoracoabdominal asynchrony, or periodic deep sighing were detected. Four patients (36%) showed REM sleep without atonia (RWA), and two additional patients showed an RWA index within the highest range of normality. Conclusion We report videopolysomnographic findings in a series of eleven patients after acute COVID-19. A major finding of this study was the presence of isolated RWA, a recognized prodromal stage of RBD, in more than one third of the patients. Future videopolysomnographic investigations including quantification of RWA in patients after COVID-19 will give more insights into a possible acute or post-infectious CNS pathology related to the SARS-CoV-2 infection.

Movements during sleep characterize sleep disorders, which can disturb sleep or its onset, impacting sleep quantity and quality. Video-polysomnography is the current gold standard to assess movements during sleep, but its availability is limited. Using data recorded with a 3D time of flight sensor, we developed a novel method of encoding temporal and spatial information of automatically identified movements during sleep. In a cohort of 20 insomnia patients and 18 controls, we showed that this novel method holds important information able to discriminate the groups. Future studies will explore the methodology in the context of other sleep disorders.

Background: Individuals with rapid eye movement (REM)-sleep behavior disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear.Methods: The full coding sequence, exon-intron boundaries and 5′ and 3′ untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing. A total of 350 RBD patients and 869 controls were sequenced, and regression and burden models were used to examine the association between LRRK2 variants and RBD.Results: No pathogenic mutations that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H-p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI 0.44–0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant, p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% CI 1.05–1.56, p = 0.029). Burden analysis identified associations with domains and exons that were derived by the variants of the protective haplotype, and no burden of other rare variants was identified.Conclusions: Carriers of the LRRK2 p.N551K-p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD-causing mutations probably have minor or no role in RBD. Additional work is needed to confirm these results and to identify the mechanism associated with reduced risk for RBD.

The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was diagnosed in half of patients (n = 27). Patients with moderate or severe CSA were randomized to cardiac resynchronization therapy (CRT) versus right ventricular pacing (RVP) in a double-blinded cross-over design and re-scheduled for a follow-up PSG within 3 to 5 months. After crossing-over of stimulation mode another PSG was conducted 3 to 5 months later. CRT led to a significant increase in left ventricular ejection fraction and significant reduction in left ventricular end systolic volumes and N-terminal pro brain natriuretic peptide plasma levels, whereas no significant effects were observed with ongoing RVP. CSA was significantly improved after 3.9 (3.2 to 4.4) months of CRT: apnea-hypopnea index decreased from 39.1 (32.1 to 54.0) events per hour at baseline to 22.2/h (10.9 to 36.7) by CRT (p

STUDY OBJECTIVES: Reduced gray matter volume in the posterior cingulate cortex (PCC) has recently been found in patients with non–rapid eye movement (NREM) parasomnia, providing a neuroanatomical substrate for the arousal state dissociation. It remains unclear whether PCC changes in NREM parasomnias might also play a role in cognitive or affective dysfunction in these patients. The aim of this exploratory study was to investigate neurobehavioral correlates of PCC abnormalities in patients with NREM parasomnia. METHODS: The Reinforcement Sensitivity Theory of Personality Questionnaire and the Stress Coping Questionnaire were used to assess personality and stress coping in 15 patients with NREM parasomnia and 15 age- and sex-matched healthy controls. Patients’ left PCC gray matter volume was quantified with voxel-based morphometry on 3 Tesla T1-weighted magnetic resonance imaging data. RESULTS: In the Reinforcement Sensitivity Theory of Personality Questionnaire, increased trait reactivity of the behavioral inhibition system and goal-drive persistence contributed most to the discrimination of patients and controls. In the Stress Coping Questionnaire, patients showed an increased negative coping trait (ie, anxious rumination) related to an increase in adjusted left PCC volume. CONCLUSIONS: The results suggest subclinical behavioral abnormalities in patients with NREM parasomnias. Such traits might trigger maladaptive emotion regulation processes related to a relative PCC volume increase. The findings encourage further longitudinal studies on this topic, which can provide insights into the causal relations underlying the PCC volume–behavior correlation. Such future studies will have a more direct implication for the clinical management of patients with NREM parasomnias. CITATION: Ramm M, Urbanek A, Failing A, et al. Increased behavioral inhibition trait and negative stress coping in non–rapid eye movement parasomnias. J Clin Sleep Med. 2020;16(10):1737–1744.

Addressing the prevalent topic of plastic pollution, an intervention to break people’s consumption patterns was implemented. It was investigated if Lent could work as a ‘window of opportunity’ of h...

The physical, social, psychological, and economic burden of opioid use disorder (OUD) is substantial. As of the year 2019, the predominant focus of OUD research was outcomes such as retention and abstinence. We report herein the effects of extended-release buprenorphine (BUP-XR), the first FDA-approved subcutaneously injected, monthly treatment for OUD, on patient-centered outcomes.Patient-centered outcomes were collected during an open-label safety study of participants with OUD (NCT# 02510014) evaluating BUP-XR. Measures collected during the study included the EQ-5D-5L, SF-36v2, Treatment Effectiveness Assessment (TEA), Addiction Severity Index-Lite (ASI-Lite), employment/insurance status questionnaire, and Medication Satisfaction Questionnaire (MSQ). Changes from baseline to end of study week 49 were analyzed using mixed models for repeated measures. "Baseline" was defined as the value collected prior to the first BUP-XR injection. Results presented are for those participants who initiated treatment on BUP-XR during the open-label study and were eligible to receive up to 12 injections.Four hundred twelve participants were included in analyses; 206 participants discontinued BUP-XR prematurely. Mean EQ-5D-5L scores remained stable from baseline to end of study. Statistically significant improvements from baseline to end of study were noted for the SF-36v2 mental component summary score (difference = 5.0, 95%CI: 3.5-6.5) and 7 of 8 domain scores (P .05 for all comparisons); the SF-36v2 physical component summary remained stable from baseline to end of study. The TEA total score (difference = 9.3 points, 95%CI: 8.0-10.5) and 4 of 4 domain scores (difference = 2-3 points per domain) significantly improved from baseline to end of study. Significant improvements (P .05 for all comparisons) on the ASI-Lite were seen for all problem areas except alcohol use from baseline to end of study. Employment rate increased 7% whereas health insurance status remained stable from baseline to end of study. Medication satisfaction measured using the MSQ was88% at end of study.Treatment with BUP-XR monthly injections for up to 12 months in this cohort of treatment-seeking individuals with OUD led to positive PCOs and high treatment satisfaction, which correspond to personal recovery.

The European Union does not have an integrated, hierarchically ordered public administration (PA) but is governed by a multilevel administrative system. Formally independent national PAs are the main executors of EU policies and, in order to effectively realize EU policies, they have to interact across vertical and horizontal levels of the governance system. Thus, EU integration has substantially changed the functional demands on national administrations when it comes to EU policy execution. This chapter therefore asks if EU integration has caused changes in the positioning of women in national PAs. To answer the question, specific functional demands of EU multilevel administration are theoretically linked to images feminist PA theory formulates in contrast to the dominant principles of modern PAs. The observation that feminist PA images fit the specific functional demands of multilevel administration leads to the expectation that women’s leadership is more likely in EU policy coordination than in classic modern PAs. In a plausibility test based on original data from a central administrative coordination network and the two lead ministries in German EU policy coordination, the expectation is shown to bear fruitful insights for future research.

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.

One in ten adults in Europe have chronic insomnia, which is characterised by frequent and persistent difficulties initiating and/or maintaining sleep and daily functioning impairments. Regional differences in practices and access to healthcare services lead to variable clinical care across Europe. Typically, a patient with chronic insomnia (a) will usually present to a primary care physician; (b) will not be offered cognitive behavioural therapy for insomnia—the recommended first-line treatment; (c) will instead receive sleep hygiene recommendations and eventually pharmacotherapy to manage their long-term condition; and (d) will use medications such as GABA receptor agonists for longer than the approved duration. Available evidence suggests that patients in Europe have multiple unmet needs, and actions for clearer diagnosis of chronic insomnia and effective management of this condition are long overdue. In this article, we provide an update on the clinical management of chronic insomnia in Europe. Old and new treatments are summarised with information on indications, contraindications, precautions, warnings, and side effects. Challenges of treating chronic insomnia in European healthcare systems, considering patients’ perspectives and preferences are presented and discussed. Finally, suggestions are provided—with healthcare providers and healthcare policy makers in mind—for strategies to achieve the optimal clinical management.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment, abnormal jerks and movements during REM sleep. Isolated RBD (iRBD) is recognized as the early stage of alpha-synucleinopathies, i.e. dementia with Lewy bodies, Parkinson's disease and multiple system atrophy. The certain diagnosis of iRBD requires video-polysomnography, evaluated by experts with time-consuming visual analyses. In this study, we propose automatic analysis of movements detected with 3D contactless video as a promising technology to assist sleep experts in the identification of patients with iRBD. By using automatically detected upper and lower body movements occurring during REM sleep with a duration between 4s and 5s, we could discriminate 20 iRBD patients from 24 patients with sleep-disordered breathing with an accuracy of 0.91 and F1-score of 0.90. This pilot study shows that 3D contactless video can be successfully used as a non-invasive technology to assist clinicians in identifying abnormal movements during REM sleep, and therefore to recognize patients with iRBD. Future investigations in larger cohorts are needed to validate the proposed technology and methodology.

Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

Rapid eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies. RBD also defines more severe forms of alpha-synucleinopathies. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we performed the first genome-wide association study of RBD, identifying five RBD risk loci. Expression analyses highlight SNCA-AS1 and SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Genetic risk score and other analyses provide further insights into RBD genetics, highlighting RBD as a unique subpopulation that will allow future early intervention.

Study objectives To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification. Methods We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls’ v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. automatic and artifact-corrected 3-s Sleep Innsbruck Barcelona (SINBAR) index in REM sleep periods (RSPs, i.e. manually selected portions of REM sleep); and ii) v-PSG-documented RBD behaviors. We quantified RWA with other (semi)-automated methods requiring less human intervention than the reference one: the indices proposed by the SINBAR group (the 3-s and 30-s phasic flexor digitorum superficialis (FDS), phasic/”any”/tonic mentalis), and the REM atonia, short and long muscle activity indices (in mentalis/submentalis/FDS muscles). They were calculated in whole REM sleep (i.e. REM sleep scored following international guidelines), in RSPs, with and without manual artifact correction. Area under curves (AUC) discriminating iRBD from controls were computed. Using published cut-offs, the indices’ sensitivity and specificity for iRBD identification were calculated. Apnea-hypopnea index in REM sleep (AHIREM) was considered in the analyses. Results RWA indices from FDS muscles alone had the highest AUCs and all of them had 100% sensitivity. Without manual RSP selection and artifact correction, the “30-s phasic FDS” and the “FDS long muscle activity” had the highest specificity (85%) with AHIREM < 15/h. RWA indices were less reliable when AHIREM≥15/h. Conclusions If AHIREM