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Michal Bechny,1,2 Giuliana Monachino,1,2 Luigi Fiorillo,2 Julia van der Meer,3 Markus H Schmidt,3,4 Claudio LA Bassetti,3 Athina Tzovara,1,3 Francesca D Faraci2 1Institute of Computer Science, University of Bern, Bern, Switzerland; 2Institute of Digital Technologies for Personalized Healthcare (Meditech), University of Applied Sciences and Arts of Southern Switzerland, Lugano, Switzerland; 3Department of Neurology, University Hospital of Bern, Bern, Switzerland; 4Ohio Sleep Medicine Institute, Dublin, OH, USACorrespondence: Michal Bechny, Institute of Digital Technologies for Personalized Healthcare, East Campus USI-SUPSI, Via la Santa 1, CH-6962 Lugano-Viganello, Lugano, Switzerland, Tel +41 (0)58 666 65 10, Email bechnymichal@gmail.comPurpose: This study aims to enhance the clinical use of automated sleep-scoring algorithms by incorporating an uncertainty estimation approach to efficiently assist clinicians in the manual review of predicted hypnograms, a necessity due to the notable inter-scorer variability inherent in polysomnography (PSG) databases. Our efforts target the extent of review required to achieve predefined agreement levels, examining both in-domain (ID) and out-of-domain (OOD) data, and considering subjects’ diagnoses.Patients and Methods: A total of 19,578 PSGs from 13 open-access databases were used to train U-Sleep, a state-of-the-art sleep-scoring algorithm. We leveraged a comprehensive clinical database of an additional 8832 PSGs, covering a full spectrum of ages (0– 91 years) and sleep-disorders, to refine the U-Sleep, and to evaluate different uncertainty-quantification approaches, including our novel confidence network. The ID data consisted of PSGs scored by over 50 physicians, and the two OOD sets comprised recordings each scored by a unique senior physician.Results: U-Sleep demonstrated robust performance, with Cohen’s kappa (K) at 76.2% on ID and 73.8– 78.8% on OOD data. The confidence network excelled at identifying uncertain predictions, achieving AUROC scores of 85.7% on ID and 82.5– 85.6% on OOD data. Independently of sleep-disorder status, statistical evaluations revealed significant differences in confidence scores between aligning vs discording predictions, and significant correlations of confidence scores with classification performance metrics. To achieve κ ≥ 90% with physician intervention, examining less than 29.0% of uncertain epochs was required, substantially reducing physicians’ workload, and facilitating near-perfect agreement.Conclusion: Inter-scorer variability limits the accuracy of the scoring algorithms to ~80%. By integrating an uncertainty estimation with U-Sleep, we enhance the review of predicted hypnograms, to align with the scoring taste of a responsible physician. Validated across ID and OOD data and various sleep-disorders, our approach offers a strategy to boost automated scoring tools’ usability in clinical settings.Keywords: automated sleep scoring, uncertainty quantification, explainable AI, polysomnography, sleep medicine

Zhongxing Zhang,1 Yves Dauvilliers,2– 4 Giuseppe Plazzi,5,6 Geert Mayer,7 Gert Jan Lammers,8,9 Joan Santamaria,10 Markku Partinen,11 Sebastiaan Overeem,12,13 Rafael del Rio Villegas,14 Karel Sonka,15 Rosa Peraita-Adrados,16 Raphaël Heinzer,17 Aleksandra Wierzbicka,18 Birgit Högl,19 Mauro Manconi,20 Eva Feketeova,21 Antonio Martins da Silva,22 Jitka Bušková,23 Claudio LA Bassetti,24,25 Lucie Barateau,2– 4 Fabio Pizza,5,26 Elena Antelmi,5,6 Jari K Gool,8,9 Rolf Fronczek,8,9 Carles Gaig,10 Ramin Khatami1,24 1Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, Aargau, Switzerland; 2Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, Montpellier, France; 3National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia, and Kleine-Levin Syndrome, Montpellier, France; 4Institute for Neurosciences of Montpellier INM, Univ Montpellier, INSERM, Montpellier, France; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 6IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 7Neurology Department, Hephata Klinik, Schwalmstadt, Germany; 8Sleep Wake Center SEIN Heemstede, Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands; 9Department of Neurology and Clinical Neurophysiology, Leiden University Medical Center, Leiden, the Netherlands; 10Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; 11Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland; 12Sleep Medicine Center Kempenhaeghe, Heeze, the Netherlands; 13Eindhoven University of Technology, Eindhoven, the Netherlands; 14Neurophysiology and Sleep Disorders Unit, Hospital Vithas Nuestra Señora de América, Madrid, Spain; 15Neurology Department and Centre of Clinical Neurosciences, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 16Sleep and Epilepsy Unit – Clinical Neurophysiology Service, University General Hospital Gregorio Marañón, Research Institute Gregorio Marañón, University Complutense of Madrid, Madrid, Spain; 17Center for Investigation and Research in Sleep, Lausanne University Hospital, Lausanne, Vaud, Switzerland; 18Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland; 19Neurology Department, Sleep Disorders Clinic, Innsbruck Medical University, Innsbruck, Austria; 20Neurology Department, EOC, Ospedale Regionale di Lugano, Lugano, Ticino, Switzerland; 21Neurology Department, Medical Faculty of P. J. Safarik University, University Hospital of L. Pasteur Kosice, Kosice, Slovak Republic; 22Serviço de Neurofisiologia, Hospital Santo António/Centro Hospitalar Universitário do Porto and UMIB-Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; 23Department of Sleep Medicine, National Institute of Mental Health, Klecany, Czech Republic; 24Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 25Department of Neurology, Sechenov First Moscow State University, Moscow, Russia; 26Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyCorrespondence: Yves Dauvilliers, National Reference Network for Narcolepsy, Sleep-Disorders Center, Department of Neurology, Hopital Gui de Chauliac, INSERM U1061, Montpellier, UM1, France, Email ydauvilliers@yahoo.fr Ramin Khatami, Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, CH-5017, Switzerland, Email ramin.khatami@barmelweid.chPurpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990– 2018) and the factors associated with the delay in Europe.Patients and Methods: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay.Results: The mean age at EDS onset and diagnosis of our patients was 20.9± 11.8 (mean ± standard deviation) and 30.5± 14.9 years old, respectively. Their mean and median diagnostic delay was 9.7± 11.5 and 5.3 (interquartile range: 1.7− 13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤ 2-year) and long (≥ 13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay.Conclusion: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.Keywords: cataplexy, diagnostic delay, misdiagnosis, symptom onset, machine learning

Sleep-disordered breathing (SDB) is linked to cognitive dysfunction. Although SDB is common in stroke patients, the impact of SDB and its early treatment on cognitive functioning after stroke remains poorly investigated. Therefore, we explored the association between SDB and post-stroke cognitive functioning, including the impact of early SDB treatment with adaptive servo-ventilation (ASV) on cognitive recovery from acute event to 3 months post-stroke. We used data from two studies, which included ischaemic stroke patients (n = 131) and no-stroke controls (n = 37) without SDB (apnea-hypopnea index, AHI <5/h) and with SDB (AHI≥20/h). Cognitive functioning was assessed within 7 days and 3 months post-stroke in stroke patients, or at study inclusion in no-stroke control group, respectively. Stroke patients with SDB were randomized to ASV treatment (ASV+) or usual care (ASV-). Linear regression adjusted for main confounders assessed the impact of SDB and its treatment on cognitive recovery. The intention-to-treat analysis did not show significant associations of SDB ASV+ (n = 30) versus SDB ASV- (n = 29) with cognitive recovery. In an exploratory subanalysis, compliant SDB ASV+ (n = 14) versus SDB ASV- showed improvements with ASV in visual memory and cognitive flexibility. Combining the stroke and non-stroke datasets, SDB (n = 85) versus no-SDB (n = 83) was associated with deficits in visual memory and response inhibition independently of stroke. SDB ASV- versus no-SDB (n = 51) was associated with less improvement in visual memory. There was no substantial evidence for benefits of intention-to-treat ASV on cognitive recovery. Exploratory analysis indicated that compliant ASV treatment could benefit visual memory and cognitive flexibility, whereas untreated SDB could contribute to a poor recovery of visual memory., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over 1 year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a adherence metric to evaluate the usability of the wearable device, we found an overall adherence rate of 80% over 1 year. We calculated daily physical activity, heart rate, and sleep parameters from 2 weeks of greatest adherence to compare NT1 (n = 20) and HC (n = 9) participants. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p = .007) and awakening index (p = .025), as well as standard deviation of time in bed (p = .044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p = .019), and sleep latency (p = .001), as well as a lower peak heart rate (p = .008), heart rate standard deviation (p = .039) and high-intensity activity (p = .009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Purpose: The European Academy of Neurology (EAN) was a merger from two parent societies: the European Neurological Association (ENS, founded in 1986) and the European Federation of Neurological Societies (EFNS, founded in 1987)., Methods: This article was written by nine former presidents, three of whom were also founders of the ENS, and is based on recollections and documents. It follows up on a review of the ENS history stored in the EAN archive., Results: The first European society (ENS) was founded by eight individual European academic clinician-neuroscientists aiming at joining with other qualified European neuroscientists on an individual membership basis. After 1990 members were also invited from behind the former Iron Curtain. A principal goal was holding neurology meetings (700 participants in 1988 and over 3000 in 2010), promoting collaborative research projects with exchange of junior neuroscientists, and providing teaching and education independent from nationality. Health politics were not part of the agenda. The executive boards (4-year term) were staffed with academic scientists from all subspecialties of neurology. Numerous bursaries and fellowships were established for junior neurologists. The impact of ENS members on research activities of young investigators was appreciated by academia at large. After years of negotiations ENS and EFNS joint efforts resulted in forming the EAN covering all fields of neurology and neuroscience under one roof., Conclusion: The basic principles of the ENS were successfully integrated into the new EAN in particular documented by the number of individual members rising to over 4000 in 2024., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data., Methods: Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue., Results: Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369)., Conclusions: The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors report article publishing charges, statistical analysis, and writing assistance were provided by Idorsia Pharmaceuticals Ltd. Antonio Olivieri reports a relationship with Idorsia Pharmaceuticals Ltd that includes: employment and equity or stocks. Guy Braunstein reports a relationship with Idorsia Pharmaceuticals Ltd that includes: employment and equity or stocks. Pierre-Philippe Luyet reports a relationship with Idorsia Pharmaceuticals Ltd that includes: employment. Johann Laurent reports a relationship with Idorsia Pharmaceuticals Ltd that includes: employment. William V McCall reports a relationship with Idorsia Pharmaceuticals Ltd that includes: consulting or advisory. William V McCall reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. William V McCall reports a relationship with Carelon that includes: consulting or advisory. Claudio Bassetti reports a relationship with Bioproject that includes: consulting or advisory. Claudio Bassetti reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Claudio Bassetti reports a relationship with Jazz Pharmaceuticals Inc that includes: consulting or advisory. Claudio Bassetti reports a relationship with Idorsia Pharmaceuticals Ltd that includes: consulting or advisory. Jan Hedner reports a relationship with Somnomed that includes: funding grants. Jan Hedner reports a relationship with Desitin GmbH that includes: funding grants., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Framework: Sleep capital contributes to individual and societal wellbeing, productivity, and economic outcomes and involves a novel aspect of brain capital. It encompasses the quality and quantity of sleep as integral components that influence cognitive abilities, mental and brain health, and physical health, affecting workplace productivity, learning, decision-making, and overall economic performance. Here, we bring a framework to understand the complex relationship between sleep quality, health, wellbeing, and economic productivity. Then we outline the multilevel impact of sleep on cognitive abilities, mental/brain health, and economic indicators, providing evidence for the substantial returns on investment in sleep health initiatives. Moreover, sleep capital is a key factor when considering brain health across the lifespan, especially for the aging population., Discussion: We propose specific elements and main variables to develop specific indexes of sleep capital to address its impacts on health, wellbeing and productivity., Conclusion: Finally, we suggest policy recommendations, workplace interventions, and individual strategies to promote sleep health and brain capital. Investing in sleep capital is essential for fostering a healthier, happier, fairer and more productive society., Competing Interests: DISCLOSURES All authors indicate they have no conflicts of interest related to this paper, and the writing of the review did not receive any specific funding. CFR III is the co-inventor of the Pittsburgh Sleep Quality Index (PSQI), and receives royalty only when for-profit entities use the PSQI for research. The current manuscript received no funding., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future., Methods: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN., Results: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future., Conclusions: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Purpose: Neurology residency programmes, which were first established at the beginning of the 20th century, have become mandatory all over Europe in the last 40-50 years. The first European Training Requirements in Neurology (ETRN) were published in 2005 and first updated in 2016. This paper reports the most recent revisions of the ETRN., Methods: Members of the EAN board performed an in depth revision of the ETNR 2016-version, which was reviewed by members of the European Board and Section of Neurology of the UEMS, the Education and Scientific Panels, the Resident and Research Fellow Section and the Board of the EAN, as well as the presidents of the 47 European National Societies., Results: The new (2022) ETRN suggest a 5-year training subdivided in three phases: a first phase (2 years) of general neurology training, a second phase (2 years) of training in neurophysiology/neurological subspecialties and a third phase (1 year) to expand clinical training (e.g., in other neurodisciplines) or for research (path for clinical neuroscientist). The necessary theoretical and clinical competences as well as learning objectives in diagnostic tests have been updated, are newly organized in four levels and include 19 neurological subspecialties. Finally, the new ETRN require, in addition to a programme director, a team of clinician-educators who regularly review the resident's progress. The 2022 update of the ETRN reflects emerging requirements for the practice of neurology and contributes to the international standardization of training necessary for the increasing needs of residents and specialists across Europe., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke., Methods: In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events., Results: Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36])., Conclusions: Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739., Competing Interests: Disclosures Dr Reichlin has received grants from Abbott Laboratories, Biosense Webster, Inc, Biotronik, Boston Scientific Corporation, and Medtronic, and severs as a consultant. Dr Baillieul has received a grant from the European Respiratory Society. The other authors report no conflicts.

Background: Magnetic resonance imaging (MRI) findings in meningoencephalitis have mainly been described in terms of their diagnostic value rather than their prognostic potential, except for herpes simplex virus (HSV) encephalitis. The aims of our study were to describe frequency and anatomic locations of MRI abnormalities specific to limbic, circadian and motor systems in a cohort of meningoencephalitis patients, as well as to investigate the prognostic value of these MRI findings., Methods: A secondary, selective analysis of a retrospective database including all meningitis, meningoencephalitis and encephalitis cases treated between 2016 and 2018 in the University hospital of Bern, Switzerland was performed. Patients with meningitis of any cause, bacterial or autoimmune causes of encephalitis were excluded., Results: MRI scans and clinical data from 129 meningoencephalitis cases found that the most frequent causes were tick-borne encephalitis (TBE, 42%), unknown pathogens (40%), VZV (7%), and HSV1 (5%). At discharge, median modified Rankin Score (mRS) was 3 (interquartile range, IQR, 1), 88% of patients had persisting signs and symptoms. After a median of 17 months, median Glasgow Outcome Score (GOS) was 5 (IQR 1), 39% of patients still had residual signs or symptoms. All patients with HSV, 27% with TBE and 31% of those with meningoencephalitis of unknown etiology had fluid-attenuated inversion recovery (FLAIR) and to a lesser extent diffusion-weighted imaging (DWI) lesions in their initial MRI, with highly overlapping anatomical distribution. In one fifth of TBE patients the limbic system was affected. Worse outcome was associated with presence of DWI and/or FLAIR lesions and lower normalized apparent diffusion coefficient (ADC) signal intensities., Conclusion: Presence of FLAIR lesions, restricted diffusion as well as the extent of ADC hypointensity in initial MRI are parameters which might be of prognostic value regarding the longterm clinical outcome for patients with meningoencephalitis of viral and of unknown origin. Although not described before, affection of limbic structures by TBE is possible as shown by our results: A substantial proportion of our TBE patients had FLAIR signal abnormalities in these regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abbuehl, Branca, Ungureanu, Federspiel, Leib, Bassetti, Hakim and Dietmann.)

Background and Objective: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy., Methods: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups., Results: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups., Conclusion: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:YW reports honoraria for educational presentations and consultations from Angelini Pharma, Arvelle Therapeutics, Bayer AG, BIAL, Bioprojet, Eisai, Idorsia Pharmaceuticals, JAZZ Pharmaceuticals, LivaNova, Novartis and UCB Pharma. SG received compensation for professional services from Abbott, Abbvie, Bial, Medtronic, UCB and Zambon; research grants from Abbott, Boston Scientific, MagVenture, German Research Council and German Ministry of Education and Health. MG received honoraria and educational grants from Precisis, LivaNova, Abbott, Medtronic, Boston Scientific and Nevro. CB, KS, DC, AZ, AK and AS declare no conflict of interest. JK performed consultations for Medtronic and Boston Scientific. FR is a consultant for Stryker, Brainlab, Icotec and Spineart and receives royalties from Spineart., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The diagnosis of sleep-wake disorders (SWDs) is challenging because of the existence of only few accurate biomarkers and the frequent coexistence of multiple SWDs and/or other comorbidities. The aim of this study was to assess in a large cohort of well-characterized SWD patients the potential of a data-driven approach for the identification of SWDs., Methods: We included 6958 patients from the Bernese Sleep Registry and 300 variables/biomarkers including questionnaires, results of polysomnography/vigilance tests, and final clinical diagnoses. A pipeline, based on machine learning, was created to extract and cluster the clinical data. Our analysis was performed on three cohorts: patients with central disorders of hypersomnolence (CDHs), a full cohort of patients with SWDs, and a clean cohort without coexisting SWDs., Results: A first analysis focused on the cohort of patients with CDHs and revealed four patient clusters: two clusters for narcolepsy type 1 (NT1) but not for narcolepsy type 2 or idiopathic hypersomnia. In the full cohort of SWDs, nine clusters were found: four contained patients with obstructive and central sleep apnea syndrome, one with NT1, and four with intermixed SWDs. In the cohort of patients without coexisting SWDs, an additional cluster of patients with chronic insomnia disorder was identified., Conclusions: This study confirms the existence of clear clusters of NT1 in CDHs, but mainly intermixed groups in the full spectrum of SWDs, with the exception of sleep apnea syndromes and NT1. New biomarkers are needed for better phenotyping and diagnosis of SWDs., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives/background: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1., Patients/methods: We reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months., Results: We describe the cases of one male (age 10) and two female (age 22 and 10) patients., Conclusions: We argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena S. Wenz reports a relationship with University of Bern that includes: funding grants. Ulf Kallweit reports a relationship with Bioprojet, Jazz Pharmaceuticals, Takeda Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Rolf Fronczek reports a relationship with Takeda Pharmaceuticals, Bioprojet that includes: consulting or advisory. Rolf Fronczek reports a relationship with Jazz Pharmaceuticals that includes: funding grants. Gert Jan Lammers reports a relationship with Bioprojet, Jazz Pharmaceuticals, Takeda Pharmaceuticals, NLS Pharmaceutics that includes: consulting or advisory and speaking and lecture fees., (Copyright © 2023. Published by Elsevier B.V.)

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B)., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Introduction: Cardiovascular parameters characterizing blood pressure (BP), heart rate (HR), endothelial function and arterial stiffness predict cerebro-cardiovascular events (CCVE) in the general population. Considering the paucity of data in stroke patients, we assessed these parameters as potential predictors of recurrent CCVE at acute stroke stroke., Patients and Methods: This is a secondary outcome analysis of a prospective observational longitudinal Sleep Deficiency & Stroke Outcome Study (ClinicalTrials.gov Identifier: NCT02559739). The study consecutively recruited acute ischemic stroke patients. Cardiovascular parameters (blood pressure variability [BPV], heart rate variability [HRV], endothelial function, and arterial stiffness) were assessed within the first week post-stroke. Future CCVE were recorded over a 3-year follow-up. Multivariate Cox regression analysis was used to investigate the prognostic value of 48 cardiovascular parameters regarding CCVE risk., Results: Out of 447 recruited patients, 359 were included in this analysis. 20% of patients developed a future CCVE. A high variability of systolic BP ( n  = 333) and nocturnal HR (non-linear parameters; n  = 187) at acute stroke predicted CCVE risk after adjustment for demographic parameters, cardiovascular risk factors and mean BP or HR, respectively. Endothelial dysfunction ( n  = 105) at acute stroke predicted CCVE risk after adjustment for age and sex, but not after adjustment for cardiovascular risk factors. Diurnal HR and arterial stiffness at acute stroke were not associated with CCVE risk., Conclusion: High blood pressure variability, high nocturnal HRV and endothelial function contribute to the risk for future CCVE after stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Filchenko, Mürner, Dekkers, Baillieul, Duss, Brill, Horvarth, Heldner, Rexhaj, Bernasconi, Bassetti and Schmidt.)

Patients with Parkinson's disease (PD) tend to sleep more frequently in the supine position and less often change head and body position during sleep. Besides sleep quality and continuity, head and body positions are crucial for glymphatic system (GS) activity. This pilot study evaluated sleep architecture and head position during each sleep stage in idiopathic PD patients without cognitive impairment, correlating sleep data to patients' motor and non-motor symptoms (NMS). All patients underwent the multi-night recordings, which were acquired using the Sleep Profiler headband. Sleep parameters, sleep time in each head position, and percentage of slow wave activity (SWA) in sleep, stage 3 of non-REM sleep (N3), and REM sleep in the supine position were extracted. Lastly, correlations with motor impairment and NMS were performed. Twenty PD patients (65.7 ± 8.6 y.o, ten women) were included. Sleep architecture did not change across the different nights of recording and showed the prevalence of sleep performed in the supine position. In addition, SWA and N3 were more frequently in the supine head position, and N3 in the supine decubitus correlated with REM sleep performed in the same position; this latter correlated with the disease duration (correlation coefficient = 0.48, p -value = 0.03) and motor impairment (correlation coefficient = 0.53, p -value = 0.02). These preliminary results demonstrated the importance of monitoring sleep in PD patients, supporting the need for preventive strategies in clinical practice for maintaining the lateral head position during the crucial sleep stages (SWA, N3, REM), essential for permitting the GS function and activity and ensuring brain health.

Simultaneously acquiring broad clinical knowledge and scientific expertise is a major challenge for young clinical scientists. Female researchers may face additional hurdles in their career, for example, due to unconscious bias. We aimed to address clinical, research, and gender-related challenges among young female clinical neuroscientists. We implemented a peer-led networking group dedicated to increasing clinical and scientific knowledge, improve soft skills, and encourage exchange between fellow residents. In monthly meetings, two participants hold short presentations on a clinical topic or scientific method, followed by a discussion and feedback to the presenter. Afterwards, participants network and discuss challenges they face in their daily experience. Nine neurology residents at a Swiss University Hospital with ≤3 years of training participated in the Connecting Women in Neurosciences project from August 2020 to June 2021. In a qualitative evaluation, participants reported they felt empowered by these meetings and profited from their new network. We identified several challenges in combining clinical and research activities, some of which participants perceived to be gender-related. In addition to women-only meetings, we will promote events addressing all interested researchers. Peer-to-peer networking is an easy and low-budget intervention to encourage female residents to engage in research activities, profit from each other's expertise, and promote interdisciplinary teamwork. It can provide a protected environment to discuss and overcome in particular gender-related challenges. We encourage young colleagues to regularly engage in structured networking activities with their local peers., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

No abstract available.

Sleep is crucial in rehabilitation processes, promoting neural plasticity and immune functions. Nocturnal body postures can indicate sleep quality and frequent repositioning is required to prevent bedsores for bedridden patients after a stroke or spinal cord injury. Polysomnography (PSG) is considered the gold standard for sleep assessment. Unobtrusive methods for classifying sleep body postures have been presented with similar accuracy to PSG, but most evaluations have been done in research lab environments. To investigate the challenges in the usability of a previously validated device in a clinical setting, we recorded the sleep posture of 17 patients with a sensorized mattress. Ground-truth labels were collected automatically from a PSG device. In addition, we manually labeled the body postures using video data. This allowed us also to evaluate the quality of the PSG labels. We trained neural networks based on the VGG-3 architecture to classify lying postures and used a self-label correction method to account for noisy labels in the training data. The models trained with the video labels achieved a higher classification accuracy than those trained with the PSG labels (0.79 vs. 0.68). The self-label correction could further increase the models' scores based on video and PSG labels to 0.80 and 0.70, respectively. Unobtrusive sensors validated in clinics can, therefore, potentially improve the quality of care for bedridden patients and advance the field of rehabilitation.

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: The declining incidence of stroke, ischaemic heart disease (IHD) and dementia (the 'triple threat') in Norway encourages further investigation. The risks and trends of the three conditions were analysed using data from the Global Burden of Disease study., Methods: Global Burden of Disease 2019 estimations were used for age-, sex- and risk-factor-specific incidence and prevalence of the 'triple threat', their risk-factor-attributed deaths and disability combined, their age-standardized rates per 100,000 population in 2019 and their changes during 1990-2019. Data are presented as means and 95% uncertainty intervals., Results: In 2019, 71.1 thousand Norwegians were living with dementia, 157.2 thousand with IHD and 95.2 thousand with stroke. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease) and 8.0 thousand (7.0 to 9.1) with stroke (12.9% decrease) in Norway. During 1990-2019, their age-standardized incidence rates decreased significantly-dementia by -5.4% (-8.4% to -3.2%), IHD by -30.0% (-31.4% to -28.6%) and stroke by -35.3% (-38.3% to -32.2%). There were significant declines in the attributable risks to both environmental and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990-2019., Conclusions: The risk of the 'triple threat' conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.

Study Objectives: Isolated rapid eye movement sleep behavior disorder (iRBD) is a parasomnia characterized by dream enactment. It represents a prodromal state of α-synucleinopathies, like Parkinson's disease. In recent years, biomarkers of increased risk of phenoconversion from iRBD to overt α-synucleinopathies have been identified. Currently, diagnosis and monitoring rely on self-reported reports and polysomnography (PSG) performed in the sleep lab, which is limited in availability and cost-intensive. Wearable technologies and computerized algorithms may provide comfortable and cost-efficient means to not only improve the identification of patients with iRBD but also to monitor risk factors of phenoconversion. In this work, we review studies using these technologies to identify iRBD or monitor phenoconversion biomarkers., Methods: A review of articles published until May 31, 2022 using the Medline database was performed. We included only papers in which participants with RBD were part of the study population. The selected papers were divided into four sessions: actigraphy, gait analysis systems, computerized algorithms, and novel technologies., Results: In total, 25 articles were included in the review. Actigraphy, wearable accelerometers, pressure mats, smartphones, tablets, and algorithms based on PSG signals were used to identify RBD and monitor the phenoconversion. Rest-activity patterns, core body temperature, gait, and sleep parameters were able to identify the different stages of the disease., Conclusions: These tools may complement current diagnostic systems in the future, providing objective ambulatory data obtained comfortably and inexpensively. Consequently, screening for iRBD and follow-up will be more accessible for the concerned patient cohort., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Contradictory evidence on the impact of single sleep-wake-disturbances (SWD), such as sleep-disorderd breating (SDB) or insomnia, in patients with stroke, on the risk of subsequent cardio- and cerebrovascular events (CCE) and death, exists. Very recent studies in the general population suggest that the presence of multiple SWD increases cardio-cerebrovascular risk. Hence, the aim of this study was to asssess whether a novel score capturing the burden of multiple SWD, a so called "sleep burden index", is predictive for subsequent CCE including death in a prospectively followed cohort of stroke patients., Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) were prospectively recruited. Four SWD were analyzed: (i) SDB with respirography; (ii) insomnia (defined using the insomnia severity index [ISI]); (iii) restless legs syndrome (RLS; defined using the International RLS Study Group rating scale); and (iv) self-estimated sleep duration at 1 and 3 months. A "sleep burden index", calculated using the mean of z-transformed values from assessments of these four SWD, was created. The occurrence of CCE was recorded over a mean ± standard deviation (SD) follow-up of 3.2 ± 0.3 years., Results: We assessed 437 patients (87% ischemic stroke, 13% TIA, 64% males) with a mean ± SD age of 65.1 ± 13.0 years. SDB (respiratory event index ≥ 5/h) was present in 66.2% of these patients. Insomnia (ISI ≥ 10), RLS and extreme sleep duration affected 26.2%, 6.4% and 13.7% of the patients 3 months post-stroke. Seventy out of the 437 patients (16%) had at least one CCE during the follow-up. The sleep burden index was associated with a higher risk for subsequent CCE, including death (odds ratio 1.80 per index unit, 95% confidence interval 1.19-2.72; p = 0.0056)., Conclusion: The presence of multiple SWDs constitutes a risk for subsequent CCE (including death) within the first 3 years following stroke. Larger systematic studies should assess the utility of the sleep burden index for patients' risk stratification in clinical practice., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

AASM guidelines are the result of decades of efforts aiming at standardizing sleep scoring procedure, with the final goal of sharing a worldwide common methodology. The guidelines cover several aspects from the technical/digital specifications, e.g., recommended EEG derivations, to detailed sleep scoring rules accordingly to age. Automated sleep scoring systems have always largely exploited the standards as fundamental guidelines. In this context, deep learning has demonstrated better performance compared to classical machine learning. Our present work shows that a deep learning-based sleep scoring algorithm may not need to fully exploit the clinical knowledge or to strictly adhere to the AASM guidelines. Specifically, we demonstrate that U-Sleep, a state-of-the-art sleep scoring algorithm, can be strong enough to solve the scoring task even using clinically non-recommended or non-conventional derivations, and with no need to exploit information about the chronological age of the subjects. We finally strengthen a well-known finding that using data from multiple data centers always results in a better performing model compared with training on a single cohort. Indeed, we show that this latter statement is still valid even by increasing the size and the heterogeneity of the single data cohort. In all our experiments we used 28528 polysomnography studies from 13 different clinical studies., (© 2023. The Author(s).)

Understanding which factors predict the outcome of internet-based cognitive behavioral therapy for insomnia (iCBT-I) may help to tailor this intervention to the patient's needs. We have conducted a secondary analysis of a randomized, controlled trial comparing a multicomponent iCBT-I (MCT) and an online sleep restriction therapy (SRT) for 83 chronic insomnia patients. The difference in the Insomnia Severity Index from pre- to post-treatment and from pre-treatment to follow-up at 6 months after treatment was the dependent variable. Prognostic and treatment-predictive factors assessed at baseline were analyzed with multiple linear regression. The shorter duration of insomnia, female gender, high health-related quality of life, and the higher total number of clicks had prognostic value for a better outcome. Other factors were found to be prognostic for outcome at the follow-up assessment: treatment with benzodiazepines, sleep quality, and personal significance of sleep problems. A high level of dysfunctional beliefs and attitudes about sleep (DBAS) was a moderator for better effects in the MCT at post-treatment assessment. Various prognostic factors (e.g., duration of insomnia, gender, or quality of life) may influence the success of treatment. The DBAS scale may be recommended to select patients for MCT rather than SRT.

Background and Purpose: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations., Methods: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors., Results: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome., Conclusions: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19., (© 2022 European Academy of Neurology.)

Study Objectives: The first reports of narcolepsy with cataplexy in Russia were made by Mankovsky (The pathogenesis of narcolepsy (the case of epidemic encephalitis with cataplexy) published in the Sovremennaya psihonevrologia) in 1925. The largest series of patients (n = 110) was reported by A. Vein (doctoral thesis: Hypersomnia Syndrome) in 1964. However, until today, narcolepsy remained relatively unknown in Russia. The aim of this study is to report clinical and polysomnography (PSG)/multiple sleep latency test (MSLT) results in the Russian population and compare them with the European Narcolepsy Network (EU-NN) data (n = 1099) reported., Methods: Eleven sleep centers from Russia agreed to participate and completed a questionnaire including 58 questions concerning demographic, clinical, PSG, and MSLT data., Results: There were 89 patients with a mean age of 35.6 ± 16.9 years (± here and further indicates standard deviation), 58% males, and 42% females. Narcolepsy started at a mean age of 25.6 ± 14.6 years (range 5-74 years). The mean Epworth Sleepiness Scale score was 18.4 ± 3.5 points (range: 11-24). Sleep paralysis was reported by 59.1%, and hallucinations by 82% of patients. In MSLT, ≥ 2 sleep-onset REM (rapid eye movement) periods (SOREMPs) were found in 81.6%. No center provided human leukocyte antigen (HLA) or cerebral spinal fluid hypocretin data., Conclusions: Clinical and neurophysiological data from this first study of the Russian Narcolepsy Network suggest a similar profile to the recently reported EU-NN data. The more severe and higher percentage of patients with cataplexy and presenting with both excessive daytime sleepiness and cataplexy may reflect low awareness of narcolepsy in Russia., Clinical Trial Registration: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/ct2/show/NCT05375890; Name: Clinical and Neurophysiological Characteristics of Narcolepsy; Identifier: NCT05375890., Citation: Kuts A, Poluektov M, Zakharov A, et al. Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network. J Clin Sleep Med . 2023;19(2):355-359., (© 2023 American Academy of Sleep Medicine.)

Background and Purpose: The development of high-quality clinical practice guidelines (CPGs) takes substantial time, effort, and resources. During the past years, the European Academy of Neurology (EAN) guideline production was significantly increased, so the need to develop clear, transparent, and methodologically solid criteria for prioritizing guideline topics became apparent. With this paper, we aim to define a set of criteria to be applied for prioritizing topics for future EAN guidelines, as well as the procedure for their implementation., Methods: After review of the literature, we identified a recent systematic review that reported on the main prioritization criteria used by health organizations. Based on these, we developed a list of 20 preliminary criteria, which were voted on through a Delphi consensus procedure, including 160 stakeholders. Finally, we established a working procedure on how to submit and select new guideline topic proposals within the EAN. This procedure was reviewed by the EAN Scientific Committee and the Board., Results: The first round, 61.3% of the participants voted, and 86% of them participated in the second round. Seven criteria were approved with this procedure. After the selection of the criteria, a prioritization procedure was launched, and the first 30 topics are reported in this paper. This bottom-up process that involved the whole EAN community was followed by a top-down process, using additional criteria for further selection by the EAN board members., Conclusions: We describe the development of prioritization criteria to be applied in the process of topic selection for future EAN CPGs. We will perform regular reviews and adjustments of the process., (© 2022 European Academy of Neurology.)

Objective: In the absence of systematic and longitudinal data, this study prospectively assessed both frequency and evolution of sleep-wake disturbances (SWD) after stroke., Methods: In 437 consecutively recruited patients with ischemic stroke or transient ischemic attack (TIA), stroke characteristics and outcome were assessed within the 1 st week and 3.2 ± 0.3 years (M±SD) after the acute event. SWD were assessed by interview and questionnaires at 1 and 3 months as well as 1 and 2 years after the acute event. Sleep disordered breathing (SDB) was assessed by respirography in the acute phase and repeated in one fifth of the participants 3 months and 1 year later., Results: Patients (63.8% male, 87% ischemic stroke and mean age 65.1 ± 13.0 years) presented with mean NIHSS-score of 3.5 ± 4.5 at admission. In the acute phase, respiratory event index was >15/h in 34% and >30/h in 15% of patients. Over the entire observation period, the frequencies of excessive daytime sleepiness (EDS), fatigue and insomnia varied between 10-14%, 22-28% and 20-28%, respectively. Mean insomnia and EDS scores decreased from acute to chronic stroke, whereas restless legs syndrome (RLS) percentages (6-9%) and mean fatigue scores remained similar. Mean self-reported sleep duration was enhanced at acute stroke (month 1: 07:54 ± 01:27h) and decreased at chronic stage (year 2: 07:43 ± 01:20h)., Conclusions: This study documents a high frequency of SDB, insomnia, fatigue and a prolonged sleep duration after stroke/TIA, which can persist for years. Considering the negative effects of SWD on physical, brain and mental health these data suggest the need for a systematic assessment and management of post-stroke SWD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, neither financially nor non-financially., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Three papers currently published in SLEEP using two different mouse models of narcolepsy, including either Hcrt-tTa;TetO diptheria toxin-A (DTA) or Hypocretin knock-out (Hcrt-KO) mice, suggest important gender differences in narcolepsy expression. Specifically, these recent data corroborate previous findings in mice demonstrating that females show more cataplexy events and more total cataplexy expression than males. Moreover, in the neurotoxic DTA mouse model, females show earlier onset of cataplexy expression than males during active Hcrt cell loss. Finally, females show a doubling of cataplexy during estrous compared to other phases of the estrous cycle. These findings are reviewed in the broader context of prior published literature, including reported gender differences in Hcrt expression and hormonal influences on sleep and wakefulness. Although similar findings have not been reported in humans, a systematic evaluation of gender differences in human narcolepsy has yet to be performed. Taken together, these animal data suggest that more research exploring gender differences in human narcolepsy is warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Changes in sleep architecture following ischemic stroke have been poorly investigated. Our objective was to explore changes of sleep structure in patients with ischemic stroke or transient ischemic attack in order to verify a possible predictive value of sleep with respect to clinical outcome., Methods: Patients recruited in the prospective SAS-CARE study received two polysomnographies (PSG) in the acute and chronic phases after stroke/TIA. Sleep parameters were compared between the two time-points and matched with a non-stroke population randomly selected from the HypnoLaus cohort., Results: Of the 169 patients investigated with PSG in the acute phase, 104 were again studied 3 months after stroke symptom onset and compared with 162 controls. The acute phase of stroke/TIA was associated with sleep disruption, which significantly improved in the chronic phase, but remained worse than controls (total sleep time improve from 318.8 ± 90.8 to 348.4 ± 81.5 min, compared to 388.2 ± 71.3 in controls, sleep latency from 49.9 ± 58.4 to 27.9 min, compared to 20.2 ± 22 in controls, sleep efficiency from 58.2 ± 18.1% to 27.9 ± 36.4 min, compared to 83.4 ± 10.3% in controls, wakefulness after sleep onset percentage from 36.5 ± 17.3 to 29.3 ± 15.6, compared to 13.2 ± 9.2 in controls). The percentage of REM sleep was negatively associated with stroke severity, whereas stroke topography did not correlate with sleep parameters., Conclusions: This study confirmed a severe sleep disruption in the acute phase of stroke. Although a significant improvement of sleep quality was observed during the three months after stroke, sleep architecture did not normalize. In particular, sleep efficiency and REM sleep seem to be particularly affected by stroke in the acute phase, with a relative preservation of NREM sleep. We suggest that these sleep architecture changes represent a persistent marker of brain damage due to stroke. Further studies are needed to assess the relationship with stroke topographic and outcome., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults')., Methods: Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness., Results: At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour., Conclusions: In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg. Older patients particularly require this dose to improve daytime functioning. Older patients are not at an increased risk of adverse events or residual effects the next morning after night-time administration of daridorexant, even at 50 mg. The dose of daridorexant does not need to be decreased for older patients., Clinical Trial Registration: ClinicalTrials.gov (NCT03545191) [first posted: 4 June, 4 2018], https://clinicaltrials.gov/ct2/show/NCT03545191 ., (© 2022. The Author(s).)

We aimed to determine the role of the European Psychiatric Association (EPA) and the European Academy of Neurology (EAN) in the management of post-COVID conditions. This is a joint statement from the EAN and the EPA on post-COVID. It is published in the official journals of the two associations, the European Journal of Neurology and European Psychiatry .

Background and Purpose: Brain health is essential for health, well-being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations., Methods: The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non-disease-, non-age-centred holistic and positive approach ('one brain, one life, one approach') to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage., Results: The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people-centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health., Conclusions: By adopting this 'one brain, one life, one approach' strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well-being of individuals is enhanced by maintaining brain health through the life course., (© 2022 European Academy of Neurology.)

Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted., (© 2022. The Author(s).)

Background: The EAN was founded in 2014 with the mission of reducing the burden of neurological disorders., Methods: In 2019 the society defined four strategic priorities: education, science, membership, and advocacy. This paper reviews the EAN development in the last 3 years., Results: The outbreak of COVID-19 pandemic in 2020 had a profound impact on the entire world and triggered profound changes in the EAN including the implementation of new digital technologies. Education The virtual congress in 2020 was the best attended in history (43,844 registrations). The European Training Requirements for Neurology was revised. A mentorship program and a student section were created. A state-of-the-art eLearning platform will be launched in 2022. Research To assess neurological manifestations of COVID-19 an international registry (ENERGY) was created. Studies on the burden of neurological disorders and sleep disorders, respectively, were started. The first EAN science school took place in 2022. Membership The EAN includes 45,000 members and 47 national societies. New task forces were created on gender and diversity, tele- and general neurology. Advocacy In 2022 the EAN supported the adoption of the Global Action Plan on epilepsy and other neurological disorders by the WHO and the neurological community in the Ukraine. The same year the EAN launched a Brain Health Strategy promoting a non-disease and -age centred, lifelong holistic approach ('one brain, one life, one approach')., Conclusion: The ongoing pandemic and wars demonstrate the fragility of our political and health systems and the need for people centeredness, international collaborations, solidarity, and digitalization. The EAN will continue promoting excellence in neurological care, science and education as well as brain health for all., (© 2022 European Academy of Neurology.)

Background and Purpose: Advances in medicine have resulted in treatments that can extend the survival of patients with prolonged disorders of consciousness (PDOC) for several years. However, several diagnostic and prognostic uncertainties remain, particularly in the care of pediatric patients. In the absence of international guidelines, we aimed to explore physicians' decision-making when managing pediatric patients with PDOC., Methods: We conducted a qualitative study using semistructured, individual interviews and employed an inductive thematic analytical approach to explore physicians' subjective experiences and decision-making when managing pediatric patients with PDOC. We recruited a purposive sample of 19 Italian-speaking physicians currently or previously employed in intensive care units or pediatric, internal medicine, or neurology departments in Switzerland., Results: Participants stated that making clinical decisions involving pediatric patients with PDOC is extremely challenging, because the decisional process requires finding a balance between several contending factors. We found that physicians experienced ambivalence in three domains of care (time, goals of care, and target of care), and that they were aware of the risk of self-fulfilling prophecies for both prognosis and main clinical outcomes., Conclusions: Our study confirmed that experienced clinicians acknowledge the complex nature and challenge of clinical decision-making in the care of pediatric patients with PDOC. More research is warranted to improve and expand existing guidelines aimed at assisting and facilitating clinical and ethical decision-making, and improving physicians' awareness of the factors affecting their decisions when dealing with patients with PDOC., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Seven thousand rare diseases have been identified; most of them are of genetic origin. The diagnosis of a neurogenetic disease is difficult, and management and training programs are not well defined through Europe. To capture and assess care needs, the Neurogenetics Panel of the European Academy of Neurology (EAN) has performed an explorative survey., Methods: The survey covering multiple topics of neurogenetics was sent to all neurologists and neuropediatricians affiliated with the EAN practicing in Europe., Results: We collected answers from 239 members based in 40 European member states. Even though most of the responders were aware of neurogenetic diseases, when we came to amenability of carrying out a complete genetic diagnosis, almost one-third of the responders declared they were not happy with the current way of ordering genetic analyses in their countries. Furthermore, although single-gene analysis is diffusely present in Europe, whole exome and genome sequencing are not easily accessible, with considerable variabilities among countries. Almost 10% of the responders did not know if presymptomatic and prenatal diagnosis was available in their countries, and 47.3% were not aware of which newborn screening programs were available. Finally, 96.3% of responders declared that there is a need for education and training in neurogenetics., Conclusions: We believe that this survey may be of importance for all European stakeholders in neurogenetics in identifying key priorities, targeting areas to encourage education/travel fellowships, and educational seminars in the future, because this area will only accelerate, and diagnostic requirements will expand., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation., Methods: Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography., Results: Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1-Q3]: 39.1 [36.1-44.1]), language (31.8 [31.0-43.8]), and executive functions (43.8 [35.5-48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6-61.0], language: 55.7 [42.3-61.1], executive functions: 51.3 [50.1-56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8-55.9]) and executive (49.5 [44.3-55.1]) deficits and no verbal memory deficits (48.1 [42.5-54.7]) at 1 month compared with controls (59.0 [47.0-64.5]; 59.6 [51.1-61.3]; 52.5 [44.2-55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5-51.9]), language (47.5 [41.8-54.1]), and executive functions (48.2 [46.2-59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7-59.9]; 57.0 [51.2-62.9]; 57.4 [51.2-60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border., Conclusions: All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.