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Serena Scarpelli,1 Valentina Alfonsi,1 Milena Camaioni,1 Maurizio Gorgoni,1,2 Antonio Albano,3 Alessandro Musetti,4 Maria Catena Quattropani,5,6 Giuseppe Plazzi,7,8 Luigi De Gennaro,1,2 Christian Franceschini3 1Department of Psychology, University of Rome Sapienza, Rome, Italy; 2Body and Action Lab, IRCCS Fondazione Santa Lucia, Rome, Italy; 3Department of Medicine and Surgery, Faculty of Medicine and Surgery, University of Parma, Parma, Italy; 4Department of Humanities, Social Sciences and Cultural Industries, University of Parma, Parma, Italy; 5Department of Educational Sciences, University of Catania, Catania, Italy; 6Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 7Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 8IRCCS Institute of Neurological Sciences, Bologna, ItalyCorrespondence: Serena Scarpelli, Department of Psychology, University of Rome Sapienza, Via dei Marsi 78, Rome, 00185, Italy, Tel +39 06 49917508, Email serena.scarpelli@uniroma1.itPurpose: COVID-19 pandemic waves have strongly influenced individuals’ behaviors and mental health. Here, we analyzed longitudinal data collected in the Spring 2020 and 2021 from a large Italian sample with the aim of assessing changes in dream features between the first and third wave. Specifically, we evaluated the modifications of pandemic dream activity as a function of the general distress variations over time. Also, we detected the best explanatory variables of nightmare frequency and distress.Materials and Methods: Participants previously involved in the web survey during the first wave of the pandemic were asked to complete a new online survey on sleep and dream features available in Spring 2021 (N=728). Subjects decreasing their level of psychological general distress in the third (T3) vs the first (T1) pandemic wave were defined as “Improved” (N=330). In contrast, participants with an unchanged or increased level of general distress were defined as “Not Improved” (N=398).Results: Statistical comparisons revealed that dream recall frequency, nightmare frequency, lucid dream frequency, and emotional intensity show a reduction in T3 than T1. Moreover, the Improved group is characterized by lower nightmare rate and nightmare distress than Not Improved people. Our findings confirmed that beyond the trait-like variables (ie, age, sex), specific sleep-related measures are related to nightmare features. In particular, poor sleep hygiene was one of the best determinants of nightmare distress among Not Improved subjects.Conclusion: Our findings revealed that people experienced an adaptation to the pandemic during the third wave. We also strengthen the notion that nightmares and their variations over time are strongly related to human well-being, suggesting that specific trait-like and sleep-related factors could modulate the relationship between mental health and nightmare features.Keywords: nightmare, distress, sleep, pandemic, third wave, clinical psychology

Giorgia Varallo,1 Carlos Suso-Ribera,2 Ada Ghiggia,3 Marco Veneruso,4 Roberto Cattivelli,5 Anna Guerrini Usubini,6,7 Christian Franceschini,1 Alessandro Musetti,8 Giuseppe Plazzi,9,10 Jacopo Maria Fontana,11 Paolo Capodaglio,11,12 Gianluca Castelnuovo6,7 1Department of Medicine and Surgery, University of Parma, Parma, 43121, Italy; 2Department of Basic and Clinical Psychology and Psychobiology, Jaume I University, Castellon de la Plana, 12071, Spain; 3Department of Life Sciences, University of Trieste, Trieste, 34127, Italy; 4Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; 5Department of Psychology, University of Bologna, Bologna, 40127, Italy; 6Department of Psychology, Catholic University of Milan, Milan, 20123, Italy; 7Istituto Auxologico Italiano IRCCS, Psychology Research Laboratory, San Giuseppe Hospital, Verbania, 28824, Italy; 8Department of Humanities, Social Sciences and Cultural Industries, University of Parma, Parma, 43125, Italy; 9Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy; 10IRCCS Istituto delle Scienze Neurologiche di Bologna (ISNB), Bologna, 40139, Italy; 11Istituto Auxologico Italiano IRCCS, Orthopaedic Rehabilitation Unit and Research Laboratory in Biomechanics and Rehabilitation, San Giuseppe Hospital, Verbania, 28824, Italy; 12Department of Surgical Sciences, Physical and Rehabilitation Medicine, University of Turin, Turin, 10121, ItalyCorrespondence: Jacopo Maria Fontana, San Giuseppe Hospital, Strada Cadorna 90, Verbania, 28824, Italy, Tel +39 0323 514 331, Email j.fontana@auxologico.itPurpose: Individuals with fibromyalgia and obesity experience significant impairment in physical functioning. Pain catastrophizing, kinesiophobia, and pain acceptance have all been identified as important factors associated with the level of disability. The objective of this study was to evaluate the role of pain catastrophizing, kinesiophobia, and pain acceptance as mediators of the association between perceived pain severity and physical functioning in individuals with fibromyalgia and obesity.Patients and Methods: In this cross-sectional study, 165 women with fibromyalgia and obesity completed self-report questionnaires of perceived pain severity (ie, Numeric Pain Rating Scale), pain catastrophizing (ie, Pain Catastrophizing Scale), kinesiophobia (ie Tampa Scale of Kinesiophobia), pain acceptance (ie, Chronic Pain Acceptance Questionnaire), and perceived physical functioning (ie, Physical Functioning subscale of the Fibromyalgia Impact Questionnaire). In addition, a performance-based test (ie, 6-minute walking test) was conducted to assess objective physical functioning. Two multiple mediation analyses were performed.Results: Pain acceptance and kinesiophobia mediated the relationship between pain severity and self-reported physical functioning. Pain catastrophizing and kinesiophobia mediated the relationship between pain severity and performance-based functioning.Conclusion: Pain acceptance, kinesiophobia, and pain catastrophizing should be addressed in rehabilitative intervention to improve physical functioning. Interestingly, the subjective and objective aspects of physical functioning are influenced by different factors. Therefore, interventions for women with fibromyalgia and obesity should focus on factors related to both subjective and performance-based physical functioning.Keywords: chronic pain, fear-avoidance model, fibromyalgia, functioning, obesity, psychological flexibility model

Brigitte Holzinger,1,2 Franziska Nierwetberg,1 Frances Chung,3 Courtney J Bolstad,4 Bjørn Bjorvatn,5 Ngan Yin Chan,6 Yves Dauvilliers,7 Colin A Espie,8 Fang Han,9 Yuichi Inoue,10 Damien Leger,11 Tainá Macêdo,12 Kentaro Matsui,13,14 Ilona Merikanto,15,16 Charles M Morin,17 Sérgio A Mota-Rolim,18 Markku Partinen,19 Giuseppe Plazzi,20,21 Thomas Penzel,22 Mariusz Sieminski,23 Yun Kwok Wing,6 Serena Scarpelli,24 Michael R Nadorff,4,25 Luigi De Gennaro24,26 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Medical University Vienna, Postgraduate Master ULG Sleep Coaching, Vienna, Austria; 3Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 4Mississippi State University, Mississippi State, MS, USA; 5Department of Global Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People’s Republic of China; 7Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 8Sir Jules Thorn Sleep & Circadian Neuroscience Institute (SCNi), University of Oxford, Oxford, UK; 9Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Tokyo Medical University, Tokyo, Japan; 11Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 12Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 13Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 14Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 15SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 16Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 17École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, QC, Canada; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 23Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 24Department of Psychology, Sapienza University of Rome, Rome, Italy; 25Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Brigitte Holzinger, Tel +43 699 101 99 042, Email brigitte.holzinger@meduniwien.ac.atPurpose: The COVID-19 pandemic affects mental health and sleep, resulting in frequent nightmares. Therefore, identifying factors associated with nightmare frequency is important, as it can indicate mental health issues. The study aimed to investigate increases in nightmare frequency comparing the pre-pandemic and pandemic period, and identify its risk factors. Further, the mediating role of post-traumatic stress disorder symptoms between the pandemic and nightmares is explored.Patients and Methods: For this cross-sectional survey data were obtained via self-rating online survey (ICOSS: details in Partinen et al, 2021), which was open to anyone older than 18 years. The final volunteer sample consisted of 15,292 participants, divided according to their nightmare frequency (high: ≥ 1– 2 nights/week; low: < 1– 2 nights/week). A total of 9100 participants were excluded if answers on variables of interest were missing or receiving rewards for participation. Chi-square tests identified changes of nightmare frequency. Predictors of high nightmare frequency were assessed using logistic regression and presented as Odds Ratios. Post-hoc mediation models were used to investigate the role of post-traumatic stress symptoms (PTSS).Results: The mean age was 41.63 (SD=16.55) with 64.05% females. High nightmare frequency increased significantly from 13.24% to 22.35% during the pandemic. Factors associated with it included self-reported PTSS (OR=2.11), other mental disorders and various sleep disorders or problems. Financial burden due to the pandemic, confinement, having had COVID-19, and work situation during the pandemic were associated with nightmare frequency, those relations were partly mediated through PTSS.Conclusion: Our results display the pandemic influence on nightmare frequency, which in turn connects to multiple mental health and sleep factors. These relations were partly mediated through PTSS. The COVID-19 pandemic appears to have caused traumatization of a substantial proportion of society. Health care workers should consider nightmares in their screening routines, as it might indicate PTSS and/or other mental and sleep disorders.Keywords: COVID-19, nightmares, mental health, sleep, post-traumatic stress disorder, collective trauma

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

Anna Guerrini Usubini,1,2 Grazia Terrone,3 Giorgia Varallo,1,2 Roberto Cattivelli,4 Giuseppe Plazzi,5,6 Gianluca Castelnuovo,1,2 Adriano Schimmenti,7 Alessandro Musetti,8 Christian Franceschini9 1Istituto Auxologico Italiano IRCCS, Psychology Research Laboratory, Milan, Italy; 2Department of Psychology, Catholic University of Milan, Milan, Italy; 3Department of History, Cultural Heritage, Education and Society, University of Rome Tor Vergata, Rome, Italy; 4Department of Psychology, University of Bologna, Bologna, 40127, Italy; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy; 6IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bologna, 40139, Italy; 7Faculty of Human and Social Sciences, UKE—Kore University of Enna, Cittadella Universitaria, Enna, Italy; 8Department of Humanities, Social Sciences and Cultural Industries, University of Parma, Parma, Italy; 9Department of Medicine and Surgery, University of Parma, Parma, ItalyCorrespondence: Alessandro Musetti, Department of Humanities, Social Sciences and Cultural Industries, University of Parma, Borgo Carissimi 10, Parma, 43121, Italy, Tel +39 0521 034820, Email alessandro.musetti@unipr.itPurpose: The present study aimed to explore the mediating role of emotion dysregulation and problematic Internet use in the relationship between negative affect and excessive daytime sleepiness.Methods: This cross-sectional study included 664 Italian adults aged between 18 and 70 years (M = 32.13; SD = 11.71). Participants were asked to complete the Depression Anxiety Stress Scale, the Difficulties in Emotion Regulation Scale, the Compulsive Internet Use Scale-7, and the Epworth Sleepiness Scale to assess negative affect, emotion dysregulation, problematic internet use, and excessive daytime sleepiness, respectively.Results: According to our results there are significant associations between negative affect, emotion dysregulation, problematic Internet use, and daytime sleepiness. Moreover, the structural equation model showed good fit indices. Emotion dysregulation and problematic Internet use partially mediated the relationship between negative mood and excessive daytime sleepiness.Conclusion: By exploring the role of emotion dysregulation on the association between excessive daytime sleepiness and its possible predictors, our study might represent an important step toward the implementation of psychological intervention for reducing excessive daytime sleepiness. Emotion dysregulation appears to play a significant role in explaining the relationship between negative affect, problematic Internet use, and excessive daytime sleepiness. Thus, it should be considered a treatment target for reducing excessive daytime sleepiness.Keywords: negative affect, psychological distress, excessive daytime sleepiness, emotion dysregulation, problematic Internet use

BACKGROUND Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides. METHODS We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-seIective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, >20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate. RESULTS Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients. CONCLUSIONS In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.). [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's Disease (PD) frequently exhibit non-motor symptoms, particularly sleep disturbances. Sleep disorders in PD patients are intricately linked to the pathogenesis and progression of PD itself, exacerbating neurodegenerative processes and worsening patient quality of life., Objectives: This review underscores the significance of sleep disorders in PD, highlighting their prevalence, impact on disease progression, and the bidirectional relationship between sleep disruption and neurodegeneration. It aims to enhance clinician awareness for better diagnosis and management of sleep-related comorbidities in PD., Methods: A comprehensive literature search was conducted in PubMed and Scopus using key terms such as "sleep disorders", "Parkinson's disease", "REM sleep behavior disorder", "restless legs syndrome", "insomnia", "obstructive sleep apnea", "excessive daytime sleepiness", "circadian rhythm disorders", "sleep and neurodegeneration"., Results: Sleep disorders are prevalent in PD affecting up to 90% of patients. Conditions such as insomnia, REM sleep behavior disorder, restless legs syndrome, obstructive sleep apnea, excessive daytime sleepiness, and circadian rhythm disorders are commonly reported. These disorders are linked to multifactorial biological mechanisms and are associated with more severe disease phenotypes. Of note, several evidence shows that sleep abnormalities may contribute to neuroinflammation and neurodegeneration, further accelerating the disease course., Conclusions: Sleep disturbances are critical non-motor symptoms in PD. Early diagnosis and tailored management of sleep disorders are essential for improving clinical outcomes and potentially offering neuroprotective benefits., (© 2024 International Parkinson and Movement Disorder Society.)

Study Objectives: The role of actigraphy in central disorders of hypersomnolence (CDH) is expanding but evidence of reliability with polysomnography (PSG) is scarce and provided only during nighttime. We explored the agreement between actigraphy and continuous 24-hour PSG at CDH diagnosis., Methods: Forty-four consecutive drug-naïve patients (28 narcolepsy and 16 idiopathic hypersomnia [IH]) underwent actigraphy during 24 hours of free-running PSG, during multiple sleep latency test (MSLT) and 13 of them also during maintenance of wakefulness test (MWT). Daytime and nighttime sleep features and MSLT and MWT mean sleep latencies (mSL) were estimated with the actigraphic algorithms by Cole-Kripke (CK), Sadeh (Sad), and University of California San Diego (UCSD). Agreement to corresponding PSG measures was assessed with Bland-Altman plots., Results: Nighttime-total sleep time (TST) in narcolepsy was significantly underestimated with CK (bias 27.8 minutes, 95% CI 13.7 to 41.9) and Sad (bias 56.7 minutes, 95% CI 38.8/74.5). Daytime-TST was overestimated in IH and narcolepsy with all algorithms (CK: bias -42.2, 95% CI -67/-17.4; Sad: bias -30.2 minutes, 95% CI -52.7/-7.7; UCSD bias -86.9 minutes, 95% CI -118.2/-55.6). 24-hour-TST was overestimated by CK and UCSD in IH (CK: bias -58.5 minutes, 95% CI -105.5/-11.5; UCSD: bias -118.8 minutes, 95% CI -172.5/-65), and by UCSD in narcolepsy (bias -68.8 minutes, 95% CI -109.3/-38.2). In the entire cohort, actigraphy overestimated MSLT mSL but not MWT mSL., Conclusions: Conventional actigraphic algorithms overestimate 24-hour TST in IH and underestimate nighttime TST in narcolepsy. These discrepancies call for the cautious application of actigraphy in the diagnostic process of CDH and the development of new quantitative signal analysis approaches., (© 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.)

Objective: To assesses the prevalence and co-occurrence of anxiety, depressive symptoms, suicidal thoughts, and hopelessness in patients with narcolepsy type 1 (NT1)., Patients/methods: In this cross-sectional study, 127 patients with NT1 (mean age 38.2 ± 15.5 years, 53.5 % female) and 131 controls (mean age 37.4 ± 14.3 years, 59.5 % female) matched for age, sex, and education, filled in the following validated questionnaires: Beck Depression Inventory-II (BDI), State-Trait Anxiety Inventory (STAI), and Beck Hopelessness Scale (BHS). Comparisons between groups and multivariable logistic regression analyses were performed., Results: Patients with NT1 presented significantly higher scores in BDI, suicidal thoughts (BDI-item-9), STAI-trait, STAI-state, and BHS than controls. Adjusted for age, sex, and educational level, NT1 was significantly associated with depressive symptoms (BDI≥13; OR 3.23, 95%CI 1.71-6.10), trait anxiety symptoms (STAI-trait≥38; OR 1.91, 95%CI 1.14-3.21), co-occurrence of BDI≥13 with STAI-trait≥38 (OR 2.72, 95%CI 1.47-5.05), and with STAI-state≥38 (OR 2.24, 95%CI 1.17-4.30), and moderate to severe hopelessness (BHS≥9; OR 2.95, 95%CI 1.55-5.63)., Conclusions: Patients with NT1 present a multidimensional psychiatric burden and comorbidity between symptoms of depression and anxiety and suicidal thoughts, a concern that deserves tailored interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Plazzi reports a relationship with Jazz Pharmaceuticals that includes: board membership. Giuseppe Plazzi reports a relationship with Bioprojet that includes: board membership. Giuseppe Plazzi reports a relationship with Centessa Pharmaceuticals, LLC that includes: board membership. Giuseppe Plazzi reports a relationship with Takeda Pharmaceutical Company Limited that includes: board membership. Giuseppe Plazzi reports a relationship with Idorsia Pharmaceuticals Ltd that includes: board membership. Fabio Pizza reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Fabio Pizza reports a relationship with Jazz Pharmaceuticals Inc that includes: speaking and lecture fees. Fabio Pizza reports a relationship with Bioprojet that includes: travel reimbursement. Elena Antelmi reports a relationship with Bioprojet that includes: speaking and lecture fees and travel reimbursement. Elena Antelmi reports a relationship with Jazz Pharmaceuticals Inc that includes: speaking and lecture fees and travel reimbursement. Elena Antelmi reports a relationship with Polifarma that includes: speaking and lecture fees. Francesco Biscarini reports a relationship with Bioprojet that includes: travel reimbursement. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Study Objectives: Pseudocataplexy is a rare functional neurological disorder that mimics cataplexy, pathognomonic for narcolepsy type 1 (NT1). We describe the psychiatric comorbidity and personality traits of patients with pseudocataplexy versus NT1 cases., Methods: The case-control observational study enrolled consecutive patients with pseudocataplexy and a control group of age-matched consecutive NT1 patients. The diagnostic work-up included a structured interview, 48-hour polysomnography, multiple sleep latency test, cataplexy provoking test, and hypocretin-1 measurement in cerebrospinal fluid. All participants were administered Beck Depression Inventory, State-Trait Anxiety Inventory, Patient Health Questionnaire-15 (PHQ-15), Personality Inventory for DSM-5 brief form, and quality-of-life (QoL) measurement by 36-item Short Form health survey (SF-36)., Results: Fifteen patients with pseudocataplexy and 30 with NT1 were included. Despite the suspicion of possible cataplexy, none of the pseudocataplexy participants fulfilled international diagnostic criteria for NT1. Pseudocataplexy patients presented higher rates of moderate state anxiety (40% vs. 10%, p = 0.018), medium level of somatic symptoms, defined by PHQ-15 score > 10 (66.7% vs. 16.7%, p = 0.003), and a trend towards moderate-to-severe depressive symptoms (33.3% vs. 10%, p = 0.054) compared to NT1. No significant differences in personality traits emerged. Pseudocataplexy patients had worse QoL profiles in almost all SF-36 domains including physical (mean ± SD: 37.7 ± 9.88 vs. 51.13 ± 7.81, p < 0.001) and mental (mean ± SD: 33.36 ± 12.69 vs.42.76 ± 11.34, p = 0.02) summary scores., Conclusions: Patients with pseudocataplexy present more severe psychiatric symptoms and a lower QoL profile in comparison with patients with NT1. The severe somatoform and affection impairment in pseudocataplexy may explain the poorer QoL and should require a tailored therapeutic approach., (© The Author(s) 2023. 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.)

The aim of the present study was to examine gender and age-specific effects on subjective daytime sleepiness (as measured by the Epworth Sleepiness Scale), body weight and eating behaviour in patients with central disorders of hypersomnolence. Based on the European Narcolepsy Network database, we compared 1035 patients with narcolepsy type I and 505 patients with other central disorders of hypersomnolence ("narcoleptic borderland"), including narcolepsy type II (N = 308) and idiopathic hypersomnia (N = 174), using logistic regression and general linear models. In the entire study population, the Epworth Sleepiness Scale was higher in women (N = 735, mean age = 30 years, mean Epworth Sleepiness Scale = 16.6 ± SD 3.9) than in men (N = 805, mean age = 32 years, mean Epworth Sleepiness Scale = 15.8 ± SD 4.4). In women with narcolepsy type I (N = 475), both Epworth Sleepiness Scale and body mass index increased in parallel with age. In women of the narcoleptic borderland (N = 260), the Epworth Sleepiness Scale markedly peaked in their early 30s, while body mass index only started to rise at that age. This rise in body mass index following the Epworth Sleepiness Scale peak cannot be explained by sleepiness-induced uncontrolled eating, as self-reported uncontrolled eating was negatively associated with the Epworth Sleepiness Scale in this group. We propose that the narcoleptic borderland harbours a unique cluster of women in their fertile years with an unexplored aetiology requiring further investigation towards tailored interventions., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Study Objectives: This study aimed to identify novel markers of narcolepsy type 1 (NT1) using between-nap opportunity periods ('Lights On') and in-nap opportunity periods ('Lights Off') features of Multiple Sleep Latency Test (MSLT) recordings. We hypothesized that NT1 could be identified both from sleep-wake instability and patterns of sleepiness during wakefulness. Further, we explored if MSLTs from NT1 and narcolepsy type 2 (NT2) patients could be distinguished despite having the same diagnostic thresholds., Methods: We analyzed 'Lights On' and 'Lights Off' periods of the MSLT, extracting 163 features describing sleepiness, microsleep, and sleep stage mixing using data from 177 patients with NT1, NT2, Idiopathic Hypersomnia (IH), and Subjective Hypersomnia (sH) from three sleep centers. These features were based on automated probabilistic sleep staging, also denoted as hypnodensities, using U-Sleep. Hypersomnias were differentiated using either or both features from 'Lights On' and 'Lights Off'., Results: Patients with NT1 could be distinguished from NT2, IH, and sH using features solely from 'Lights On' periods with a sensitivity of 0.76 and specificity of 0.71. When using features from all periods of the MSLT, NT1 was distinguished from NT2 alone with a sensitivity of 0.77 and a specificity of 0.84., Conclusions: The findings of this study demonstrate microsleeps and sleep stage mixing as potential markers of the sleep attacks and unstable sleep-wake states common in NT1. Further, NT1 and NT2 could be frequently distinguished using 'Lights Off' features., (© 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.)

Introduction: Adolescents' health and well-being are seriously threatened by suicidal behaviors, which have become a severe social issue worldwide. Suicide is one of the leading causes of mortality for adolescents in low and middle-income countries, with approximately 67,000 teenagers committing suicide yearly. Although an association between sleep disturbances (SDs) and suicidal behaviors has been suggested, data are still scattered and inconclusive. Therefore, to further investigate this association, we conducted a meta-analysis to verify if there is a link between SDs and suicidal behaviors in adolescents without diagnosed psychiatric disorders., Methods: PubMed, CENTRAL, EMBASE, and PsycINFO were searched from inception to August 30th, 2024. We included studies reporting the estimation of suicidal behaviors in adolescents from 12 to 21 years of age, with SDs and healthy controls. The meta-analysis was based on odds ratio (OR, with a 95% confidence interval ([CI]), estimates through inverse variance models with random-effects., Results: The final selection consisted of 19 eligible studies from 9 countries, corresponding to 628,525 adolescents with SDs and 567,746 controls. We found that adolescents with SDs are more likely to attempt suicide (OR: 3.10; [95% CI: 2.43; 3.95]) and experience suicidal ideation (OR: 2.28; [95% CI 1.76; 2.94]) than controls., Conclusion: This meta-analysis suggests that SDs are an important risk factor for suicidal ideation and suicide attempts in healthy adolescents. The findings highlight the importance of early identification of SDs to prevent suicidal behaviors in this population., Systematic Review Registration: PROSPERO, identifier CRD42023415526., Competing Interests: GP has received honoraria for advisory board and consulting fees from Bioprojet, Jazz, Takeda, and Idorsia. FP has received honoraria for presentations from Jazz Pharmaceuticals, for participation in the advisory board by Tadeka, and for meeting attendance support from Bioprojet. The remaining 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 Baldini, Gnazzo, Rapelli, Marchi, Pingani, Ferrari, De Ronchi, Varallo, Starace, Franceschini, Musetti, Poletti, Ostuzzi, Pizza, Galeazzi and Plazzi.)

To investigate potential sex-related differences in patients with narcolepsy type 1, we carried out an analysis of baseline data from 93 women and 89 men with narcolepsy type 1 who participated in the TElemedicine for NARcolepsy (TENAR) trial. The following data were considered: sociodemographics; diagnostic (disease history, polysomnography, orexin, human leukocyte antigen) and clinical features, including sleepiness (Epworth Sleepiness Scale), cataplexy and other narcolepsy symptoms; disease severity (Narcolepsy Severity Scale); pharmacological treatment; depressive symptoms (Beck Depression Inventory); and self-reported relevance of eight narcolepsy-related issues. We found that, compared with men, significantly more women reported automatic behaviours (55.4% versus 40%) and had higher Epworth Sleepiness Scale (median 10 versus 9) and Beck Depression Inventory scores (median 10.5 versus 5), and there was a trend for a higher Narcolepsy Severity Scale total score in women (median 19 versus 18, p = 0.057). More women than men were officially recognized as having a disability (38% versus 22.5%) and considered 5/8 narcolepsy-related issues investigated as a relevant problem. More severe sleepiness and a greater narcolepsy-related burden in women could mirror sex differences present in the general population, or may be related to suboptimal management of narcolepsy type 1 or to more severe depressive symptoms in women. Future studies and guidelines should address these aspects., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Narcolepsy type 1 is a chronic central disorder of hypersomnolence, and it is frequently accompanied by overweight, but the association between narcolepsy type 1 and eating disorders is controversial. Our study aims to compare patients with narcolepsy type 1 and controls on the symptomatology of eating disorders and to evaluate the association between clinical factors. This is a cross-sectional study, with consecutive recruitment of patients with narcolepsy type 1 attending the Outpatient Clinic for Narcolepsy at the IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy) for routine follow-up visits. Healthy subjects from general populations were recruited as controls. Patients underwent a questionnaire-based assessment using the Eating Disorder Examination Questionnaire (EDE-Q), Binge Eating Scale (BES), Italian Night Eating Questionnaire (I-NEQ), Epworth Sleepiness Scale (ESS), and Narcolepsy Severity Scale (NSS). One hundred and thirty-eight patients with narcolepsy type 1 and 162 controls were enrolled. This study showed that individuals with narcolepsy type 1 reported higher scores on the EDE-Q, I-NEQ, and a higher body mass index (BMI) than the controls. The logistic regression analysis results, with EDE-Q positivity as a dependent variable, demonstrate a significant association with antidepressant drugs, female sex, and the use of sodium oxybate. We found an association between antidepressant drug consumption, the NSS total score, and female sex with BES positivity as the dependent variable. The logistic regression analysis for I-NEQ positivity found an association with antidepressant drug use. This study shows that patients with narcolepsy type 1 frequently present with comorbid eating disorder symptomatology, mainly night eating syndrome. Investigating the possible presence of eating disorders symptomatology through questionnaires is fundamental during the assessment of patients with narcolepsy type 1., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention., (© 2024 European Sleep Research Society.)

Stretch syncope (SS) is a benign, uncommon, distinct condition described mainly in adolescent males. It is responsible for paroxysmal events started by stereotyped stretching actions with neck hyperextension, culminating in alteration of consciousness. Motor manifestations are often present and may be associated with a generalized slowing of the electroencephalographic activity, challenging the diagnosis. Despite a few cases reported in the literature, different mechanisms have been implied in the pathogenesis, involving both local and systemic hemodynamic phenomena. Here, we report on an 8-year-old girl with self-induced SS, providing new insights into the related neurophysiological profile and discussing the possible etiology. Our evidence of transient and dynamic vascular impairment supports the hypothesis of SS as a multifactorial disorder., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. We obtained written and verbal consent from the subject and her legally authorized representative (biological parent)., (© The Author(s) 2024.)

Background: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential., Methods: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires., Results: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found., Conclusions: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI., (© 2024. The Author(s).)

Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep-wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive-compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PATRIZIA CONGIU reports financial support was provided by Fidia Farmaceutici S.p.a. PATRIZIA CONGIU reports financial support was provided by Pandas Italia ODV. PATRIZIA CONGIU reports financial support was provided by Fondazione di Sardegna. Professor Giuseppe Plazzi is part of the editorial board of Sleep Medicine journal If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence often arising in childhood and adolescence. NT1 has a significant, but poorly defined, psychological impact. We aimed to investigate the psycho-social functioning of children and adolescents with NT1. We performed a cross-sectional, child and parent-reported questionnaire survey in 37 children and adolescents (6-17 years) with NT1, compared with age- and sex-matched controls. Questionnaires (SSHS, ESS-CHAD, CDI, MASC, CBCL, CRS-R, and SNAP-IV) evaluated various aspects of behavioural and emotional profiles, sleep habits, and daytime sleepiness. Subsequently, NT1 intra-group analysis was performed to investigate the effect of sex (males vs females) and pharmacological treatment (treated vs non-treated) on psychological features. The NT1 questionnaires total scores were then correlated with the clinical characteristics (age, body mass index [BMI], ESS-CHAD score, cerebrospinal hypocretin-1 [Hcrt-1] levels, and diagnostic delay). Patients with NT1 showed a higher tendency to depressive symptoms, anxiety, somatisation, inattention, hyperactivity, oppositional/defiant problems, and other maladaptive behaviours compared with controls. Among NT1 patients, females showed a higher propensity to anxiety, and non-treated patients displayed higher depressive symptoms. Psychological symptoms increased with age, BMI, and daytime sleepiness in patients with NT1, while a younger age was associated with more frequent somatisation symptoms. Lower cerebrospinal Hcrt-1 levels correlated with poorer social competencies, daily activities, and inattention. Diagnostic delay was associated with a higher impact of depressive symptoms and behavioural problems. NT1 in children and adolescents is associated with poorer functioning in multiple psychological domains calling for a multidisciplinary approach and monitoring to reduce disease burden and to prevent psychiatric consequences., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Restless Legs Syndrome (RLS) is a complex sensorimotor disorder, classified among the sleep-related movement disorders. Although sensory symptoms appear as key features of the disorder, they are still poorly characterized from a clinical perspective and conceptualized from a pathophysiological point of view. In this review, we aim to describe the clinical and functional substrates of RLS, focusing mainly on its sensory symptoms and on their neurophysiological and anatomical correlates. Knowledge of both subjective sensory symptoms and objective sensory signs are still controversial. Current data also indicate that the sensory component of RLS seems to be subserved by anomalies of sensorimotor integration and by mechanism of central sensitization. Overall, electrophysiological findings highlight the involvement of multiple generators in the pathogenesis of RLS, eventually resulting in an increased nervous system excitability and/or alterations in inhibition within the somatosensory and nociceptive pathways. Structural and functional neuroimaging data show the involvement of several crucial areas and circuits, among which the thalamus appears to play a pivotal role. A holistic approach looking at brain connectivity, structural or functional abnormalities, and their interplay with molecular vulnerability and neurotransmitter alterations is warranted to disentangle the complex framework of RLS., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The neurological condition known as narcolepsy type 1 (NT1) is an uncommon condition marked by extreme daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nocturnal sleep, and low or undetectable levels of orexin in the CSF fluid. NT1 has been hypothesized to be an immunological disorder; its treatment is currently only symptomatic, and misdiagnosis is not uncommon. This study compares the N -glycome of NT1 patients with healthy controls in search of potential glycan biomarkers using LC-MS/MS. A total of 121 candidate N -glycans were identified, 55 of which were isomeric N -glycan structures and 65 were not. Seventeen N -glycan biomarker candidates showed significant differences between the NT1 and control cohorts. All of the candidate glycan biomarkers were isomeric except HexNAc 6 Hex 7 Fuc 0 NeuAc 1 (6701) and HexNAc 6 Hex 7 Fuc 1 NeuAc 2 (6712). Therefore, with isomeric and nonisomeric structures, a total of 20 candidate N -glycan biomarkers are reported in this study, and interestingly, all are either sialylated or sialylated-fucosylated and upregulated in NT1 relative to the control. The distribution levels of all the identified N -glycans show that the sialylated glycan type is the most abundant in NT1 and is majorly disialylated, although the trisialylated subtype is three-fold higher in NT1 compared to the healthy control. The first isomers of HexNAc 5 Hex 6 Fuc 0 NeuAc 3 (5603), HexNAc 6 Hex 7 Fuc 0 NeuAc 2 (6702), and HexNAc 6 Hex 7 Fuc 1 NeuAc 4 (6714) expressed a high level of fold changes (FC) of 1.62, 2.19, and 2.98, respectively. These results suggest a different N -glycome profile of NT1 and a relationship between sialylated glycan isomers in NT1 disease development or progression. The revelation of N -glycan expression alterations in this study may improve NT1 diagnostic methods, understanding of NT1 pathology, and the development of new targeted therapeutics., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep-related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep-related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non-sleep-related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep-onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin-receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background and Objectives: Restless legs syndrome (RLS) has been associated with anxiety, depression, insomnia, lifestyle factors and infections. We aimed to study the prevalence of symptoms of RLS during the COVID-19 pandemic versus pre-pandemic. We hypothesized that pre-existing RLS symptoms worsened and pandemic-related factors may have triggered new symptoms of RLS., Methods: Adults (≥18 years) from fifteen countries across four continents participated in an online survey between May and August 2020. The harmonized questionnaire included a validated single question on RLS with response alternatives from 1 to 5 on a scale from never to every/almost every evening or night. Other measures were the Insomnia Severity Index (ISI), measures of symptoms of anxiety (GAD-2) and depression (PHQ-2), and questions on different pandemic-related factors., Results: Altogether, 17 846 subjects (63.8 % women) were included in the final analyses. The mean age was 41.4 years (SD 16.1). During the pandemic, symptoms of RLS (≥3 evenings/nights per week) were more common 9.1 % (95 % CI 8.7-10.1) compared to 5.4 % (95 % CI 4.9-6.0) before the pandemic (P < 0.0001). Alltogether 1.3 % (95 % CI 1.1-1.6) respondents had new-onset symptoms (≥3 evenings/nights per week). Moderate-severe insomnia was strongly associated with RLS symptoms. The occurrences of new-onset RLS symptoms were 5.6 % (95 % CI 0.9-13.0) for participants reporting COVID-19 and 1.1 % (95 % CI 0.7-1.5) for non-COVID-19 participants. In the fully adjusted logistic regression model, the occurrence of new-onset RLS symptoms was associated with younger age, social restrictions and insomnia severity. In a similar analysis, RLS symptoms (≥3 evenings/nights per week) were associated with lower education, financial hardship, sleep apnea symptoms, use of hypnotics, insomnia severity, symptoms of depression and possible post-traumatic stress disorder., Discussion: Our findings indicate that RLS symptoms were more common during the pandemic than before. Usually, the prevalence of RLS increases with age. However, during the pandemic, new-onset symptoms of RLS were more common in younger age groups. This may be due to the pandemic-related factors being more pronounced in the younger compared to the older. The association between insomnia, psychiatric symptoms and RLS warrants clinical attention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Markku Partinen reports financial support was provided by Signe and Ane Gyllenberg Foundation. Other from Takeda, personal fees and other from MSD, personal fees and other from Orion, personal fees and other from Umecrine, personal fees from Lundbeck, Other from Teva, outside the submitted work. Ilona Merikanto reports financial support was provided by Signe and Ane Gyllenberg Foundation. Courtney J. Bolstad reports financial support was provided by South Texas Veterans Healthcare System. Yuichi Inoue reports personal fees and other from Astellas Pharma, personal fees from Eisai, other from Idorsia Pharmaceuticals Japan, grants from Koike Medical, personal fees from Otsuka Pharmaceutical, grants from Philips Japan, outside the submitted work. Frances Chung – Dr. Chung reports grants from Ontario Ministry of Health Innovation Grant, grants from University Health NetworkFoundation, personal fees from Masimo Inc and Takeda Pharma, outside the submitted work; In addition, University Health Network has a patent STOP-Bang questionnaire pending. Thomas Penzel – Dr. Penzel reports personal fees from Jazz Pharmaceuticals, personal fees from Bayer Healthcare, personal fees from Neuwirth, personal fees from Löwenstein Medical, outside the submitted work; and Shareholder of The Siestagroup GmbH, Advanced Sleep Research GmbH, Nukute. Giuseppe Plazzi – Dr. Plazzi reports personal fees from UCB pharma, personal fees from Jazz pharmaceuticals, personal fees from Bioprojet, personal fees from Idorsia, personal fees from Takeda, outside the submitted work. YK Wing – personal fees from Eisai Co, Ltd, for delivering a lecture and sponsorship from Lundbeck HK Ltd and Aculys Pharma, Japan, outside the submitted work. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management., Objective: This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts., Methods: Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey., Results: Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%)., Conclusions: These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies conducted from January 2000 to October 2022. We classified cognitive tests assessing memory, executive function, and attention by cognitive domain. Between-group differences were analyzed as standardized mean differences (Cohen's d ), and Cohen's d for individual tests were integrated according to cognitive domain and clinical disease group. Eighty-seven studies were screened for inclusion; 39 satisfied inclusion criteria, yielding 73 comparisons ( k ): NT1, k  = 60; NT2, k  = 8; IH, k  = 5. Attention showed large impairment in people with NT1 ( d = -0.90) and IH ( d = -0.97), and moderate impairment in NT2 ( d = -0.60). Executive function was moderately impaired in NT1 ( d = -0.30) and NT2 ( d = -0.38), and memory showed small impairments in NT1 ( d = -0.33). A secondary meta-analysis identified sustained attention as the most impaired domain in NT1, NT2, and IH ( d ≈ -0.5 to -1). These meta-analyses confirm that cognitive impairments are present in NT1, NT2, and IH, and provide quantitative confirmation of reports of cognitive difficulties made by patients and clinicians. These findings provide a basis for the future design of studies to determine whether cognitive impairments can improve with pharmacologic and nonpharmacologic treatments for narcolepsy and IH., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background and Purpose: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities., Methods: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up., Results: Thirty-nine patients, 10 antiD+ and 29 antiD-, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α-syn was detected in 93.1% of antiD- versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non-motor symptoms, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score, DAT-SPECT, or polysomnographic features., Conclusions: Patients with antidepressant-related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB)., Methods: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion., Results: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters., Interpretation: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)