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1. REM sleep in narcolepsy

Author

Thorpy, Michael J, Siegel, Jerome M, and Dauvilliers, Yves

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Neurosciences, Mental Health, Brain Disorders, Rare Diseases, Sleep Research, Behavioral and Social Science, Humans, Narcolepsy, Sleep, REM, Polysomnography, REM Sleep Behavior Disorder, Cataplexy, Antidepressants, Dream, Hypnagogic hallucination, Hypnopompic hallucination, Neurobiology, Oxybate, Sleep-onset rapid eye movement period, Stimulant, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.

Published
2024

2. Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals

Author

Xue, Pei, Merikanto, Ilona, Delale, Eva A., Bjelajac, Adrijana, Yordanova, Juliana, Chan, Rachel N. Y., Korman, Maria, Mota-Rolim, Sérgio A., Landtblom, Anne-Marie, Matsui, Kentaro, Reis, Catia, Penzel, Thomas, Inoue, Yuichi, Nadorff, Michael R., Holzinger, Brigitte, Morin, Charles M., Espie, Colin A., Plazzi, Giuseppe, De Gennaro, Luigi, Chung, Frances, Bjorvatn, Bjørn, Wing, Yun Kwok, Dauvilliers, Yves, Partinen, Markku, and Benedict, Christian

Published
2024
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3. Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction

Author

Schormair, Barbara, Zhao, Chen, Bell, Steven, Didriksen, Maria, Nawaz, Muhammad S., Schandra, Nathalie, Stefani, Ambra, Högl, Birgit, Dauvilliers, Yves, Bachmann, Cornelius G., Kemlink, David, Sonka, Karel, Paulus, Walter, Trenkwalder, Claudia, Oertel, Wolfgang H., Hornyak, Magdolna, Teder-Laving, Maris, Metspalu, Andres, Hadjigeorgiou, Georgios M., Polo, Olli, Fietze, Ingo, Ross, Owen A., Wszolek, Zbigniew K., Ibrahim, Abubaker, Bergmann, Melanie, Kittke, Volker, Harrer, Philip, Dowsett, Joseph, Chenini, Sofiene, Ostrowski, Sisse Rye, Sørensen, Erik, Erikstrup, Christian, Pedersen, Ole B., Topholm Bruun, Mie, Nielsen, Kaspar R., Butterworth, Adam S., Soranzo, Nicole, Ouwehand, Willem H., Roberts, David J., Danesh, John, Burchell, Brendan, Furlotte, Nicholas A., Nandakumar, Priyanka, Earley, Christopher J., Ondo, William G., Xiong, Lan, Desautels, Alex, Perola, Markus, Vodicka, Pavel, Dina, Christian, Stoll, Monika, Franke, Andre, Lieb, Wolfgang, Stewart, Alexandre F. R., Shah, Svati H., Gieger, Christian, Peters, Annette, Rye, David B., Rouleau, Guy A., Berger, Klaus, Stefansson, Hreinn, Ullum, Henrik, Stefansson, Kari, Hinds, David A., Di Angelantonio, Emanuele, Oexle, Konrad, and Winkelmann, Juliane

Published
2024
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4. Are rare heterozygous SYNJ1 variants associated with Parkinson’s disease?

Author

Senkevich, Konstantin, Parlar, Sitki Cem, Chantereault, Cloe, Yu, Eric, Ahmad, Jamil, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Waters, Cheryl, Monchi, Oury, Dauvilliers, Yves, Dupré, Nicolas, Miliukhina, Irina, Timofeeva, Alla, Emelyanov, Anton, Pchelina, Sofya, Greenbaum, Lior, Hassin-Baer, Sharon, Alcalay, Roy N., and Gan-Or, Ziv

Published
2024
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5. Genotype–phenotype correlation in PRKN-associated Parkinson’s disease

Author

Menon, Poornima Jayadev, Sambin, Sara, Criniere-Boizet, Baptiste, Courtin, Thomas, Tesson, Christelle, Casse, Fanny, Ferrien, Melanie, Mariani, Louise-Laure, Carvalho, Stephanie, Lejeune, Francois-Xavier, Rebbah, Sana, Martet, Gaspard, Houot, Marion, Lanore, Aymeric, Mangone, Graziella, Roze, Emmanuel, Vidailhet, Marie, Aasly, Jan, Gan Or, Ziv, Yu, Eric, Dauvilliers, Yves, Zimprich, Alexander, Tomantschger, Volker, Pirker, Walter, Álvarez, Ignacio, Pastor, Pau, Di Fonzo, Alessio, Bhatia, Kailash P., Magrinelli, Francesca, Houlden, Henry, Real, Raquel, Quattrone, Andrea, Limousin, Patricia, Korlipara, Prasad, Foltynie, Thomas, Grosset, Donald, Williams, Nigel, Narendra, Derek, Lin, Hsin-Pin, Jovanovic, Carna, Svetel, Marina, Lynch, Timothy, Gallagher, Amy, Vandenberghe, Wim, Gasser, Thomas, Brockmann, Kathrin, Morris, Huw R., Borsche, Max, Klein, Christine, Corti, Olga, Brice, Alexis, Lesage, Suzanne, and Corvol, Jean Christophe

Published
2024
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6. Estimation bias and agreement limits between two common self-report methods of habitual sleep duration in epidemiological surveys

Author

Korman, Maria, Zarina, Daria, Tkachev, Vadim, Merikanto, Ilona, Bjorvatn, Bjørn, Bjelajac, Adrijana Koscec, Penzel, Thomas, Landtblom, Anne-Marie, Benedict, Christian, Chan, Ngan Yin, Wing, Yun Kwok, Dauvilliers, Yves, Morin, Charles M., Matsui, Kentaro, Nadorff, Michael, Bolstad, Courtney J., Chung, Frances, Mota-Rolim, Sérgio, De Gennaro, Luigi, Plazzi, Giuseppe, Yordanova, Juliana, Holzinger, Brigitte, Partinen, Markku, and Reis, Cátia

Published
2024
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8. Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy

Author

Ollila, Hanna M, Sharon, Eilon, Lin, Ling, Sinnott-Armstrong, Nasa, Ambati, Aditya, Yogeshwar, Selina M, Hillary, Ryan P, Jolanki, Otto, Faraco, Juliette, Einen, Mali, Luo, Guo, Zhang, Jing, Han, Fang, Yan, Han, Dong, Xiao Song, Li, Jing, Zhang, Jun, Hong, Seung-Chul, Kim, Tae Won, Dauvilliers, Yves, Barateau, Lucie, Lammers, Gert Jan, Fronczek, Rolf, Mayer, Geert, Santamaria, Joan, Arnulf, Isabelle, Knudsen-Heier, Stine, Bredahl, May Kristin Lyamouri, Thorsby, Per Medbøe, Plazzi, Giuseppe, Pizza, Fabio, Moresco, Monica, Crowe, Catherine, Van den Eeden, Stephen K, Lecendreux, Michel, Bourgin, Patrice, Kanbayashi, Takashi, Martínez-Orozco, Francisco J, Peraita-Adrados, Rosa, Benetó, Antonio, Montplaisir, Jacques, Desautels, Alex, Huang, Yu-Shu, Jennum, Poul, Nevsimalova, Sona, Kemlink, David, Iranzo, Alex, Overeem, Sebastiaan, Wierzbicka, Aleksandra, Geisler, Peter, Sonka, Karel, Honda, Makoto, Högl, Birgit, Stefani, Ambra, Coelho, Fernando Morgadinho, Mantovani, Vilma, Feketeova, Eva, Wadelius, Mia, Eriksson, Niclas, Smedje, Hans, Hallberg, Pär, Hesla, Per Egil, Rye, David, Pelin, Zerrin, Ferini-Strambi, Luigi, Bassetti, Claudio L, Mathis, Johannes, Khatami, Ramin, Aran, Adi, Nampoothiri, Sheela, Olsson, Tomas, Kockum, Ingrid, Partinen, Markku, Perola, Markus, Kornum, Birgitte R, Rueger, Sina, Winkelmann, Juliane, Miyagawa, Taku, Toyoda, Hiromi, Khor, Seik-Soon, Shimada, Mihoko, Tokunaga, Katsushi, Rivas, Manuel, Pritchard, Jonathan K, Risch, Neil, Kutalik, Zoltan, O’Hara, Ruth, Hallmayer, Joachim, Ye, Chun Jimmie, and Mignot, Emmanuel J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Prevention, Vaccine Related, Influenza, Autoimmune Disease, Immunization, Pneumonia & Influenza, Emerging Infectious Diseases, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Inflammatory and immune system, Good Health and Well Being, Humans, Autoimmunity, Influenza, Human, Influenza A Virus, H1N1 Subtype, Autoimmune Diseases, Influenza Vaccines, Narcolepsy, FinnGen
Abstract

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Published
2023

9. Guidelines for the assessment and management of residual sleepiness in obstructive apnea-hypopnea syndrome: Endorsed by the French Sleep Research and Medicine Society (SFRMS) and the French Speaking Society of Respiratory Diseases (SPLF)

Author

Barateau, Lucie, Baillieul, Sébastien, Andrejak, Claire, Bequignon, Émilie, Boutouyrie, Pierre, Dauvilliers, Yves, Gagnadoux, Frédéric, Geoffroy, Pierre-Alexis, Micoulaud-Franchi, Jean-Arthur, Montani, David, Monaca, Christelle, Patout, Maxime, Pépin, Jean-Louis, Philip, Pierre, Pilette, Charles, Tamisier, Renaud, Trzepizur, Wojciech, Jaffuel, Dany, and Arnulf, Isabelle

Published
2024
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16. Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions

Author

Matsui, Kentaro, Chung, Frances, Bjelajac, Adrijana Koscec, Merikanto, Ilona, Korman, Maria, Mota-Rolim, Sérgio, Cunha, Ana Suely, Bjorvatn, Bjørn, Xue, Pei, Benedict, Christian, Morin, Charles M., Espie, Colin A., Landtblom, Anne-Marie, Penzel, Thomas, De Gennaro, Luigi, Holzinger, Brigitte, Hrubos-Strøm, Harald, Leger, Damien, Bolstad, Courtney J., Nadorff, Michael R., Plazzi, Giuseppe, Reis, Catia, Chan, Ngan Yin, Wing, Yun Kwok, Yordanova, Juliana, Dauvilliers, Yves, Partinen, Markku, and Inoue, Yuichi

Published
2023
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17. Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals

Author

Xue, Pei, Merikanto, Ilona, Chung, Frances, Morin, Charles M., Espie, Colin, Bjorvatn, Bjørn, Cedernaes, Jonathan, Landtblom, Anne-Marie, Penzel, Thomas, De Gennaro, Luigi, Holzinger, Brigitte, Matsui, Kentaro, Hrubos-Strøm, Harald, Korman, Maria, Leger, Damien, Mota-Rolim, Sérgio, Bolstad, Courtney J., Nadorff, Michael, Plazzi, Giuseppe, Reis, Catia, Chan, Rachel Ngan Yin, Wing, Yun Kwok, Yordanova, Juliana, Bjelajac, Adrijana Koscec, Inoue, Yuichi, Partinen, Markku, Dauvilliers, Yves, and Benedict, Christian

Published
2023
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22. Somnambulism

Author

Cordani, Ramona, Lopez, Regis, Barateau, Lucie, Chenini, Sofiene, Nobili, Lino, and Dauvilliers, Yves

Published
2024
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24. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy.

Author

Rosenberg, Russell, Thorpy, Michael J, Dauvilliers, Yves, Schweitzer, Paula K, Zammit, Gary, Gotfried, Mark, Bujanover, Shay, Scheckner, Brian, and Malhotra, Atul

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Trials and Supportive Activities, Brain Disorders, Sleep Research, Clinical Research, Lung, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Carbamates, Disorders of Excessive Somnolence, Humans, Incidence, Narcolepsy, Phenylalanine, Randomized Controlled Trials as Topic, Sleep Apnea, Obstructive, Treatment Outcome, solriamfetol, Sunosi, JZP-110, safety, sleep, apnea, lung, narcolepsy, OSA, Clinical Sciences, Other Medical and Health Sciences, Psychology, Neurology & Neurosurgery, Clinical sciences
Abstract

Study objectivesThis post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment.MethodsParticipants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups.ResultsCommon early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity.ConclusionsCommon early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606.CitationRosenberg R, Thorpy MJ, Dauvilliers Y, et al. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.

Published
2022

27. The association of insomnia with long COVID: An international collaborative study (ICOSS-II)

Author

Chen, Si-Jing, Morin, Charles M., Ivers, Hans, Wing, Yun Kwok, Partinen, Markku, Merikanto, Ilona, Holzinger, Brigitte, Espie, Colin A., De Gennaro, Luigi, Dauvilliers, Yves, Chung, Frances, Yordanova, Juliana, Vidović, Domagoj, Reis, Catia, Plazzi, Giuseppe, Penzel, Thomas, Nadorff, Michael R., Matsui, Kentaro, Mota-Rolim, Sergio, Leger, Damien, Landtblom, Anne-Marie, Korman, Maria, Inoue, Yuichi, Hrubos-Strøm, Harald, Chan, Ngan Yin, Bjelajac, Adrijana Koscec, Benedict, Christian, and Bjorvatn, Bjørn

Published
2023
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28. Recommandations pour le bilan et la prise en charge de la somnolence résiduelle dans le syndrome d’apnées-hypopnées obstructives du sommeil

Author

Barateau, Lucie, Baillieul, Sébastien, Andrejak, Claire, Bequignon, Émilie, Boutouyrie, Pierre, Dauvilliers, Yves, Gagnadoux, Frédéric, Geoffroy, Pierre-Alexis, Micoulaud-Franchi, Jean-Arthur, Montani, David, Monaca, Christelle, Patout, Maxime, Pépin, Jean-Louis, Philip, Pierre, Pilette, Charles, Tamisier, Renaud, Trzepizur, Wojciech, Jaffuel, Dany, and Arnulf, Isabelle

Published
2023
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30. Association between hypersomnolence and the COVID-19 pandemic: The International COVID-19 Sleep Study (ICOSS)

Author

Sarkanen, Tomi, Partinen, Markku, Bjorvatn, Bjørn, Merikanto, Ilona, Benedict, Christian, Nadorff, Michael R., Bolstad, Courtney J., Espie, Colin, Matsui, Kentaro, Chung, Frances, Morin, Charles M., Wing, Yun Kwok, Penzel, Thomas, Macêdo, Tainá, Mota-Rolim, Sérgio, Holzinger, Brigitte, Plazzi, Giuseppe, De Gennaro, Luigi, Landtblom, Anne-Marie, Inoue, Yuichi, Sieminski, Mariuz, Leger, Damien, and Dauvilliers, Yves

Published
2023
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34. Hyperarousal features in the sleep architecture of individuals with and without insomnia

Author

Di Marco, Tobias, primary, Scammell, Thomas E., additional, Sadeghi, Kolia, additional, Datta, Alexandre N., additional, Little, David, additional, Tjiptarto, Nurkurniati, additional, Djonlagic, Ina, additional, Olivieri, Antonio, additional, Zammit, Gary, additional, Krystal, Andrew, additional, Pathmanathan, Jay, additional, Donoghue, Jacob, additional, Hubbard, Jeffrey, additional, and Dauvilliers, Yves, additional

Published
2024
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41. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Author

Krohn, Lynne, Heilbron, Karl, Blauwendraat, Cornelis, Reynolds, Regina H., Yu, Eric, Senkevich, Konstantin, Rudakou, Uladzislau, Estiar, Mehrdad A., Gustavsson, Emil K., Brolin, Kajsa, Ruskey, Jennifer A., Freeman, Kathryn, Asayesh, Farnaz, Chia, Ruth, Arnulf, Isabelle, Hu, Michele T. M., Montplaisir, Jacques Y., Gagnon, Jean-François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Bernardini, Andrea, Högl, Birgit, Stefani, Ambra, Ibrahim, Abubaker, Šonka, Karel, Kemlink, David, Oertel, Wolfgang, Janzen, Annette, Plazzi, Giuseppe, Biscarini, Francesco, Antelmi, Elena, Figorilli, Michela, Puligheddu, Monica, Mollenhauer, Brit, Trenkwalder, Claudia, Sixel-Döring, Friederike, Cochen De Cock, Valérie, Monaca, Christelle Charley, Heidbreder, Anna, Ferini-Strambi, Luigi, Dijkstra, Femke, Viaene, Mineke, Abril, Beatriz, Boeve, Bradley F., Scholz, Sonja W., Ryten, Mina, Bandres-Ciga, Sara, Noyce, Alastair, Cannon, Paul, Pihlstrøm, Lasse, Nalls, Mike A., Singleton, Andrew B., Rouleau, Guy A., Postuma, Ronald B., and Gan-Or, Ziv

Published
2022
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43. Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

Author

Ambati, Aditya, Hillary, Ryan, Leu-Semenescu, Smaranda, Ollila, Hanna M., Lin, Ling, During, Emmanuel H., Farber, Neal, Rico, Thomas J., Faraco, Juliette, Leary, Eileen, Goldstein-Piekarski, Andrea N., Huang, Yu-Shu, Han, Fang, Sivan, Yakov, Lecendreux, Michel, Dodet, Pauline, Honda, Makoto, Gadoth, Natan, Nevsimalova, Sona, Pizza, Fabio, Kanbayashi, Takashi, Peraita-Adrados, Rosa, Leschziner, Guy D., Hasan, Rosa, Canellas, Francesca, Kume, Kazuhiko, Daniilidou, Makrina, Bourgin, Patrice, Ryec, David, Vicario, José L., Hogl, Birgit, Hong, Seung Chul, Plazzi, Guiseppe, Mayer, Geert, Landtblom, Anne Marie, Dauvilliers, Yves, Arnulf, Isabelle, and Mignot, Emmanuel Jean-Marie

Published
2021

44. Neural network an1alysis of sleep stages enables efficient diagnosis of narcolepsy

Author

Stephansen, Jens B., Olesen, Alexander N., Olsen, Mads, Ambati, Aditya, Leary, Eileen B., Moore, Hyatt E., Carrillo, Oscar, Lin, Ling, Han, Fang, Yan, Han, Sun, Yun L., Dauvilliers, Yves, Scholz, Sabine, Barateau, Lucie, Hogl, Birgit, Stefani, Ambra, Hong, Seung Chul, Kim, Tae Won, Pizza, Fabio, Plazzi, Giuseppe, Vandi, Stefano, Antelmi, Elena, Perrin, Dimitri, Kuna, Samuel T., Schweitzer, Paula K., Kushida, Clete, Peppard, Paul E., Sorensen, Helge B. D., Jennum, Poul, and Mignot, Emmanuel

Subjects
Computer Science - Neural and Evolutionary Computing
Abstract

Analysis of sleep for the diagnosis of sleep disorders such as Type-1 Narcolepsy (T1N) currently requires visual inspection of polysomnography records by trained scoring technicians. Here, we used neural networks in approximately 3,000 normal and abnormal sleep recordings to automate sleep stage scoring, producing a hypnodensity graph - a probability distribution conveying more information than classical hypnograms. Accuracy of sleep stage scoring was validated in 70 subjects assessed by six scorers. The best model performed better than any individual scorer (87% versus consensus). It also reliably scores sleep down to 5 instead of 30 second scoring epochs. A T1N marker based on unusual sleep-stage overlaps achieved a specificity of 96% and a sensitivity of 91%, validated in independent datasets. Addition of HLA-DQB1*06:02 typing increased specificity to 99%. Our method can reduce time spent in sleep clinics and automates T1N diagnosis. It also opens the possibility of diagnosing T1N using home sleep studies., Comment: 21 pages (not including title or references), 6 figures (1a - 6c), 6 tables, 5 supplementary figures, 9 supplementary tables

Published
2017
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45. Pitolisant 40 mg for excessive daytime sleepiness in obstructive sleep apnea patients treated or not by CPAP: Randomised phase 3 study.

Author

Dauvilliers, Yves, Craig, Sonya Elizabeth, Bonsignore, Maria R., Barbé, Ferran, Verbraecken, Johan, Asin, Jerryl, Georgiev, Ognian, Tiholov, Rumen, Caussé, Christian, Lecomte, Jeanne‐Marie, Schwartz, Jean‐Charles, Lehert, Philippe, Randerath, Winfried, and Pépin, Jean‐Louis

Subjects
*CONTINUOUS positive airway pressure, *SLEEP apnea syndromes, *EPWORTH Sleepiness Scale, *LEAST squares, *DROWSINESS, *CLINICAL trials
Abstract

Summary Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine‐3 receptor antagonist, is efficacious at doses up to 20 mg once daily in OSA treated or not with continuous positive airway pressure (CPAP). We assessed the efficacy and safety of pitolisant at doses up to 40 mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double‐blind, placebo‐controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up‐titration scheme, 10, 20 or 40 mg once daily) or placebo for 12 weeks. The primary endpoint was a change in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. Secondary endpoints included a change in reaction time using the Oxford Sleep Resistance test (OSleR), Clinical Global Impression of Change (CGI‐C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4 years, 77.3% male; mean apnea‐hypopnea index [AHI] 27.0 events/h) were randomised to receive pitolisant (n = 242; 50% received CPAP) or placebo (n = 119; 48.7% CPAP). After the dose‐adjustment phase (week 3), 88.8% of patients received pitolisant 40 mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference −2.6 (95% CI: −3.4; −1.8; p < 0.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI‐C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40 mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Nightmare frequency is a risk factor for suicidal ideation during the COVID‐19 pandemic.

Author

Bolstad, Courtney J., Holzinger, Brigitte, Scarpelli, Serena, De Gennaro, Luigi, Yordanova, Juliana, Koumanova, Silvia, Mota‐Rolim, Sérgio, Benedict, Christian, Bjorvatn, Bjørn, Chan, Ngan Yin, Chung, Frances, Dauvilliers, Yves, Espie, Colin A., Inoue, Yuichi, Korman, Maria, Koscec Bjelajac, Adrijana, Landtblom, Anne‐Marie, Matsui, Kentaro, Merikanto, Ilona, and Morin, Charles M.

Subjects
DREAMS, SUICIDE risk factors, SUICIDAL ideation, SUICIDE prevention, NIGHTMARES
Abstract

Summary: 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. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Association between idiopathic hypersomnia and a genetic variant in the PER3 gene.

Author

Cherasse, Yoan, Taira, Yuki, Rassu, Anna Laura, Barateau, Lucie, Evangelista, Elisa, Muratani, Masafumi, Funato, Hiromasa, Yanagisawa, Masashi, and Dauvilliers, Yves

Subjects
SINGLE nucleotide polymorphisms, SLEEP duration, IDIOPATHIC diseases, GENETIC variation, CENTRAL nervous system, CIRCADIAN rhythms
Abstract

Summary: We aim to identify genetic markers associated with idiopathic hypersomnia, a disabling orphan central nervous system disorder of hypersomnolence that is still poorly understood. In our study, DNA was extracted from 79 unrelated patients diagnosed with idiopathic hypersomnia with long sleep time at the National Reference Center for Narcolepsy‐France according to very stringent diagnostic criteria. Whole exome sequencing on the first 30 patients with idiopathic hypersomnia (25 females and 5 males) allowed the single nucleotide variants to be compared with a control population of 574 healthy subjects from the French Exome project database. We focused on the identification of genetic variants among 182 genes related to the regulation of sleep and circadian rhythm. Candidate variants obtained by exome sequencing analysis were then validated in a second sample of 49 patients with idiopathic hypersomnia (37 females and 12 males). Our study characterised seven variants from six genes significantly associated with idiopathic hypersomnia compared with controls. A targeted sequencing analysis of these seven variants on 49 other patients with idiopathic hypersomnia confirmed the relative over‐representation of the A➔C variant of rs2859390, located in a potential splicing‐site of PER3 gene. Our findings support a genetic predisposition and identify pathways involved in the pathogeny of idiopathic hypersomnia. A variant of the PER3 gene may predispose to idiopathic hypersomnia with long sleep time. [ABSTRACT FROM AUTHOR]

Published
2024
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