Article
Cell Biology
Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Summary: This study examined the use of a dual-orexin receptor antagonist in opioid withdrawal and found that it may have potential benefits for improving sleep and withdrawal outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Neurosciences
Dou Yin, Sheng Chen, Jun Liu
Summary: Autoimmune neurologic diseases are a new type of immune-mediated diseases with diverse clinical manifestations. Sleep disturbances, including excessive daytime sleep, RBD, and narcolepsy, have been reported to have a significant negative impact on the quality of life in patients with autoimmune neurologic diseases. These sleep disturbances can be either initial symptoms or persistent throughout the disease course, and they are believed to be associated with underlying pathophysiological mechanisms.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Sara Alvente, Chiara Berteotti, Stefano Bastianini, Viviana Lo Martire, Gabriele Matteoli, Alessandro Silvani, Giovanna Zoccoli
Summary: The study found that in orexin-deficient mouse models, higher arterial pressure during sleep and smaller differences in arterial pressure between sleep and wakefulness are mediated by alterations in cardiovascular sympathetic control.
Review
Clinical Neurology
Kiran Maski, Emmanuel Mignot, Giuseppe Plazzi, Yves Dauvilliers
Summary: This review summarizes the current knowledge about disrupted nighttime sleep and sleep instability in narcolepsy. Disrupted nighttime sleep is a key symptom of narcolepsy that has received less attention compared to excessive daytime sleepiness and cataplexy. The intrinsic sleep instability of narcolepsy leads to frequent spontaneous wakings and sleep stage transitions, contributing to disrupted nighttime sleep. Multimodal treatment, including behavioral therapies, counseling on sleep hygiene, and medication, can effectively manage disrupted nighttime sleep, with strong evidence showing improvement with sodium oxybate.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Article
Multidisciplinary Sciences
Takuya Ogawa, Yuta Kajiyama, Hideaki Ishido, Shigeru Chiba, Gajanan S. Revankar, Tomohito Nakano, Seira Taniguchi, Takashi Kanbayashi, Kensuke Ikenaka, Hideki Mochizuki
Summary: This study investigated the association between cerebrospinal fluid (CSF) orexin levels and sleep disturbances in patients with Parkinson's disease (PD). The results showed decreased CSF orexin levels in patients with PD, but these levels did not correlate with any clinical characteristics. The study suggests that understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.
Article
Multidisciplinary Sciences
Shi-Bin Li, Valentina Martinez Damonte, Chong Chen, Gordon X. Wang, Justus M. Kebschull, Hiroshi Yamaguchi, Wen-Jie Bian, Carolin Purmann, Reenal Pattni, Alexander Eckehart Urban, Philippe Mourrain, Julie A. Kauer, Gregory Scherrer, Luis de Lecea
Summary: Sleep quality declines with age and this study identified hyperexcitable hypocretin/orexin (Hcrt/OX) neurons as drivers of sleep fragmentation during aging. Activation of Hcrt neurons increased wakefulness and aged Hcrt neurons showed hyperexcitability and impaired M-current. Disruption of Kcnq2/3 genes in young mice led to sleep destabilization resembling aging-associated sleep fragmentation.
Review
Clinical Neurology
Ramona Cordani, Marco Veneruso, Flavia Napoli, Natascia Di Iorgi, Claudia Milanaccio, Alessandro Consales, Nicola Disma, Elisa De Grandis, Mohamad Maghnie, Lino Nobili
Summary: Craniopharyngiomas, a rare type of brain tumor, can cause sleep disorders due to hypothalamic involvement. This systematic review examines the underlying mechanisms and potential treatment strategies for sleep disorders in patients with craniopharyngioma. A high prevalence of excessive daytime sleepiness, narcolepsy, and sleep-disordered breathing was found in these patients. The review also suggests a possible diagnostic algorithm for accurately identifying and treating sleep disorders in this population.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Lucie Barateau, Regis Lopez, Sofiene Chenini, Anna Laura Rassu, Lytissia Mouhli, Cloe Dhalluin, Isabelle Jaussent, Yves Dauvilliers
Summary: This study aimed to determine the factors associated with disrupted nocturnal sleep (DNS) in patients with narcolepsy type 1 (NT1) and evaluate the effect of medication on DNS and its severity. The results showed that DNS severity was associated with disease severity, sleep quality, and sleep instability. Treatment led to improvements in DNS and reduced sleepiness and depressive symptoms.
Review
Pharmacology & Pharmacy
Marieke Vringer, Birgitte Rahbek Kornum
Summary: Narcolepsy type 1 and type 2 are characterized by excessive daytime sleepiness and reduced quality of life, with current treatments focused on improving daytime sleepiness and reducing cataplexy. Targeting Hcrt receptors shows promise in alleviating symptoms, but careful consideration of potential side effects is required. Immunotherapies may target the core pathophysiology of narcolepsy, but further research is needed to identify the optimal therapeutic target.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Biochemistry & Molecular Biology
Chijung Hung, Akihiro Yamanaka
Summary: Orexin, a neuropeptide synthesized in the neurons of the lateral hypothalamus, regulates feeding behavior and is crucial for sleep/wakefulness regulation. It sends axons throughout the brain and spinal cord, integrating inputs from various brain regions and projecting to sleep/wakefulness-regulating neurons. Lack of orexin results in sleep fragmentation and cataplexy-like behavior similar to narcolepsy. Recent studies using optogenetics and chemogenetics have emphasized the role of orexin neuron activity in sleep/wakefulness regulation. Recording of orexin neuron activity using electrophysiological methods reveals specific activity patterns across sleep/wakefulness states. Other co-transmitters released from orexin neurons also contribute to sleep/wakefulness regulation.
Review
Clinical Neurology
Jari K. Gool, Eva M. van Heese, Mink S. Schinkelshoek, Aniek Remmerswaal, Gert Jan Lammers, Karin D. van Dijk, Rolf Fronczek
Summary: This study assessed the effect of opioid use on narcolepsy type 1 symptom severity through a literature review and questionnaire study. The results showed that opioids could improve narcolepsy symptom severity, with the most significant improvements seen in sleep quality and excessive daytime sleepiness.
Editorial Material
Clinical Neurology
Tomi Sarkanen, Gabriele Sved, Maria Juujarvi, Anniina Alakuijala, Markku Partinen
Summary: This article reports four cases of false positives and misdiagnosis of narcolepsy due to measurement of orexin levels using enzyme immune assay (EIA), therefore strongly discouraging the use of orexin EIA measurement in a clinical setting.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Article
Multidisciplinary Sciences
Anja Holm, Marie-Laure Possovre, Mojtaba Bandarabadi, Kristine F. Moseholm, Jessica L. Justinussen, Ivan Bozic, Rene Lemcke, Yoan Arribat, Francesca Amati, Asli Silahtaroglu, Maxime Juventin, Antoine Adamantidis, Mehdi Tafti, Birgitte R. Kornum
Summary: This study found that miR-137 regulates sleep-wake states by targeting the Hcrt gene. Inhibition of miR-137 increases Hcrt expression and prolongs wakefulness, and this interaction is evolutionarily conserved in different species. Additionally, the study showed that miR-137 expression is regulated by IL-13, and Hcrt gene expression is regulated by miR-137.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Louise Piilgaard, Laura Rose, Camille Gylling Hviid, Kristi A. Kohlmeier, Birgitte Rahbek Kornum
Summary: This study investigated the effect of sex on NT1 symptoms and sleep-wake characteristics using NT1 mice. The findings showed that females exhibited higher behavioral state instability, more wakefulness and less sleep during the dark phase, and decreased REM sleep compared to males. The study also identified a new type of behavioral arrest called delta attacks.
Article
Clinical Neurology
Regis Lopez, Lucie Barateau, Anna Laura Rassu, Elisa Evangelista, Sofiene Chenini, Sabine Scholz, Isabelle Jaussent, Yves Dauvilliers
Summary: The study aims to evaluate alternative measures of the multiple sleep latency test (MSLT) for identifying hypocretin-deficiency in patients with hypersomnolence, including narcolepsy patients. The results show that compared to the current neurophysiological standard criteria, alternative MSLT measures are more effective in identifying hypocretin-deficient patients with hypersomnolence and narcolepsy. Daytime REM sleep duration is highlighted as a relevant neurophysiological biomarker of hypocretin-deficiency, which can be used in clinical and research settings.
Article
Clinical Neurology
Anita D'Anselmo, Sergio Agnoli, Marco Filardi, Fabio Pizza, Serena Mastria, Giovanni Emanuele Corazza, Giuseppe Plazzi
Summary: The study explored psychological distress associated with COVID-19 restrictions and its relationship with depressive symptoms and creativity in patients with narcolepsy type 1 (NT1). Results showed that patients with NT1 experienced improvements in subjective sleepiness while controls reported worsening sleep quality during the lockdown. Depression and NT1 symptom severity were significant predictors of COVID-19-related distress. Creative performance, particularly generative fluency, was found to reduce the detrimental effect of depression on the patients' wellbeing. In contrast, creative originality was a disadvantageous moderator in the relationship between NT1 symptom severity and distress associated with the traumatic event.
JOURNAL OF SLEEP RESEARCH
(2022)
Article
Clinical Neurology
Yves Dauvilliers, Karel Sonka, Richard K. Bogan, Markku Partinen, Rafael Del Rio Villegas, Nancy Foldvary-Schaefer, Roman Skowronski, Abby Chen, Jed Black, Franck Skobieranda, Michael J. Thorpy
Summary: The study evaluated the effectiveness of LXB monotherapy in reducing cataplexy and increasing cataplexy-free days in patients with narcolepsy. The results showed that LXB was able to effectively reduce cataplexy attacks and increase the number of days without cataplexy. These findings are clinically significant for understanding the role of LXB in narcolepsy treatment and the transition from other anticataplectic medications.
Review
Clinical Neurology
Lucie Barateau, Fabio Pizza, Giuseppe Plazzi, Yves Dauvilliers
Summary: This article discusses the clinical features, diagnosis, pathophysiology, and treatment of narcolepsy type 1 and 2, with a focus on recent findings. It highlights the role of low hypocretin-1/orexin-A levels as a diagnostic marker for narcolepsy type 1 and the autoimmune destruction of hypocretin neurons as the underlying cause of the disease. Narcolepsy type 2, on the other hand, is less well-defined, with limited biomarkers and unclear etiology. Current treatments for narcolepsy are symptomatic, but new psychostimulants and non-peptide hypocretin receptor-2 agonists hold promise for revolutionizing the management of this rare sleep disorder.
JOURNAL OF SLEEP RESEARCH
(2022)
Article
Clinical Neurology
Jari K. Gool, Zhongxing Zhang, Martijn S. S. L. Oei, Stephanie Mathias, Yves Dauvilliers, Geert Mayer, Giuseppe Plazzi, Rafael del Rio-Villegas, Joan Santamaria Cano, Karel Sonka, Markku Partinen, Sebastiaan Overeem, Rosa Peraita-Adrados, Raphael Heinzer, Antonio Martins da Silva, Birgit Hoegl, Aleksandra Wierzbicka, Anna Heidbreder, Eva Feketeova, Mauro Manconi, Jitka Buskova, Francesca Canellas, Claudio L. Bassetti, Lucie Barateau, Fabio Pizza, Markus H. Schmidt, Rolf Fronczek, Ramin Khatami, Gert Jan Lammers
Summary: In this study, data-driven algorithms were used to identify distinct patient subgroups within the population of central disorders of hypersomnolence. The results challenge the inclusion of sleep-onset REM periods in diagnostic criteria for individuals without cataplexy and provide new variables for more reliable diagnostic categories that better represent different patient phenotypes.
Correction
Clinical Neurology
Yves Dauvilliers, Karel Sonka, Richard K. Bogan, Markku Partinen, Rafael Del Rio Villegas, Nancy Foldvary-Schaefer, Roman Skowronski, Abby Chen, Jed Black, Franck Skobieranda, Michael J. Thorpy
Article
Clinical Neurology
Ilona Merikanto, Yves Dauvilliers, Frances Chung, Yun Kwok Wing, Luigi De Gennaro, Brigitte Holzinger, Bjorn Bjorvatn, Charles M. Morin, Thomas Penzel, Christian Benedict, Adrijana Koscec Bjelajac, Ngan Yin Chan, Colin A. Espie, Harald Hrubos-Strom, Yuichi Inoue, Maria Korman, Anne-Marie Landtblom, Damien Leger, Kentaro Matsui, Sergio Mota-Rolim, Michael R. Nadorff, Giuseppe Plazzi, Catia Reis, Juliana Yordanova, Markku Partinen
Summary: An international survey study reveals that post-acute sequelae of COVID-19 symptoms are more prevalent among severe cases and long-lasting sleep problems are at the core of these symptoms. Understanding the importance of sleep-related symptoms has clinical relevance in diagnosing and treating long-COVID.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Clinical Neurology
Regis Lopez, Lucie Barateau, Sofiene Chenini, Anna Laura Rassu, Yves Dauvilliers
Summary: This study evaluated the feasibility, acceptability, and usefulness of home nocturnal infrared video recording in assessing the frequency and complexity of non-rapid eye movement sleep parasomnias in adults, as well as monitoring treatment response.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Clinical Neurology
Regis Lopez, Lucie Barateau, Anna Laura Rassu, Elisa Evangelista, Sofiene Chenini, Sabine Scholz, Isabelle Jaussent, Yves Dauvilliers
Summary: The study aims to evaluate alternative measures of the multiple sleep latency test (MSLT) for identifying hypocretin-deficiency in patients with hypersomnolence, including narcolepsy patients. The results show that compared to the current neurophysiological standard criteria, alternative MSLT measures are more effective in identifying hypocretin-deficient patients with hypersomnolence and narcolepsy. Daytime REM sleep duration is highlighted as a relevant neurophysiological biomarker of hypocretin-deficiency, which can be used in clinical and research settings.
Article
Clinical Neurology
Dieter Kunz, Yves Dauvilliers, Heike Benes, Diego Garcia-Borreguero, Giuseppe Plazzi, Dalma Seboek Kinter, Preciosa Coloma, Magdalene Rausch, Mouna Sassi-Sayadi, Stephen Thein
Summary: In this 40-week extension study, Daridorexant was found to be safe and well-tolerated for long-term treatment of insomnia disorder. It improved sleep and daytime functioning, with the most pronounced effects observed with the 50 mg dose.
Article
Clinical Neurology
Marie-Laure Ancelin, Isabelle Jaussent, Karen Ritchie, Alain Besset, Joanne Ryan, Yves Dauvilliers
Summary: This study examines the association between BDNF variants and promoter I methylation with sleep disturbances in older adults. The results show that wake time after sleep onset (WASO) is associated with four SNPs in participants not taking psychotropic drugs, while the associations are either not significant or in the reverse direction in participants taking drugs. Higher BDNF methylation levels are found in participants with long WASO, and this varies depending on psychotropic drug use.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Clinical Neurology
Sofiene Chenini, Lucie Barateau, Lily Guiraud, Marie-Lou Rollin, Regis Lopez, Isabelle Jaussent, Severine Beziat, Yves Dauvilliers
Summary: One-third of patients with restless legs syndrome reported a decrease in symptoms during cognitive activities, and this improvement was confirmed during a sustained cognitive task.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Clinical Neurology
Yves Dauvilliers, Thomas Roth, Richard Bogan, Michael J. Thorpy, Anne Marie Morse, Asim Roy, Jordan Dubow, Jennifer Gudeman
Summary: This study evaluated the efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) compared to placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2). The results showed significant improvements in sleep latency, sleep quality, nocturnal arousals, and daytime sleepiness for both NT1 and NT2 subgroups treated with ON-SXB compared to placebo.
Article
Clinical Neurology
Tobias Di Marco, Thomas E. Scammell, Michael Meinel, Dalma Seboek Kinter, Alexandre N. Datta, Gary Zammit, Yves Dauvilliers
Summary: The study aimed to explore the effect of daridorexant, a dual orexin receptor antagonist, on nighttime wake bouts and their correlation with daytime functioning. Results showed that daridorexant reduced the number and duration of long wake bouts during the night compared with placebo, corresponding with improved daytime functioning.
Article
Clinical Neurology
Andrea Zagaria, Scarpelli Serena, Alessandro Musetti, Giada Rapelli, Luigi De Gennaro, Giuseppe Plazzi, Christian Franceschini
Summary: This study investigated changes in sleep problems during the COVID-19 pandemic and found a link between sleep hygiene practices and sleep disruptions. Improving sleep hygiene practices may help mitigate the negative impact of the COVID-19 pandemic on sleep.
JOURNAL OF SLEEP RESEARCH
(2023)
Review
Immunology
Roland S. Liblau, Daniela Latorre, Birgitte R. Kornum, Yves Dauvilliers, Emmanuel J. Mignot
Summary: Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by the loss of certain hypothalamic neurons. It is suspected to have an immune-mediated basis, supported by genetic evidence and increased incidence after vaccination. The search for antigens recognized by pathogenic T cell response in NT1 is ongoing, and animal models provide insights into the roles of autoreactive T cells.
NATURE REVIEWS IMMUNOLOGY
(2023)