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https://www.readbyqxmd.com/read/28526554/the-roles-of-orexins-in-sleep-wake-regulation
#1
REVIEW
Michihiro Mieda
Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Multiple approaches, including molecular genetic, electrophysiological, pharmacological, and neuroanatomical studies have suggested that orexins play critical roles in the maintenance of wakefulness by regulating the function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness...
May 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28522101/cardiovascular-fitness-in-narcolepsy-is-inversely-related-to-sleepiness-and-the-number-of-cataplexy-episodes
#2
Martin Matoulek, Vladimír Tuka, Magdalena Fialová, Soňa Nevšímalová, Karel Šonka
OBJECTIVE: Cardiopulmonary fitness depends on daily energy expenditure or the amount of daily exercise. Patients with narcolepsy spent more time being sleepy or asleep than controls; thus we may speculate that they have a lower quantity and quality of physical activity. The aim of the present study was thus to test the hypothesis that exercise tolerance in narcolepsy negatively depends on sleepiness. PATIENTS AND METHODS: The cross-sectional study included 32 patients with narcolepsy with cataplexy, 10 patients with narcolepsy without cataplexy, and 36 age- and gender-matched control subjects, in whom a symptom-limited exercise stress test with expired gas analysis was performed...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28507129/nonpeptide-orexin-type-2-receptor-agonist-ameliorates-narcolepsy-cataplexy-symptoms-in-mouse-models
#3
Yoko Irukayama-Tomobe, Yasuhiro Ogawa, Hiromu Tominaga, Yukiko Ishikawa, Naoto Hosokawa, Shinobu Ambai, Yuki Kawabe, Shuntaro Uchida, Ryo Nakajima, Tsuyoshi Saitoh, Takeshi Kanda, Kaspar Vogt, Takeshi Sakurai, Hiroshi Nagase, Masashi Yanagisawa
Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or pharmacologic orexin replacement ameliorates symptoms in mouse models of narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R-selective agonist, YNT-185. This study validates the pharmacological activity of this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain slice preparations. Intraperitoneal, and intracerebroventricular, administration of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin neuron-ablated mice, but not in orexin receptor-deficient mice...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28490912/update-on-the-treatment-of-narcolepsy-clinical-efficacy-of-pitolisant
#4
REVIEW
Michael W Calik
Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone ("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate)...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28472332/the-spectrum-of-rem-sleep-related-episodes-in-children-with-type-1-narcolepsy
#5
Elena Antelmi, Fabio Pizza, Stefano Vandi, Giulia Neccia, Raffaele Ferri, Oliviero Bruni, Marco Filardi, Gaetano Cantalupo, Rocco Liguori, Giuseppe Plazzi
Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11...
May 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28460015/rare-missense-mutations-in-p2ry11-in-narcolepsy-with-cataplexy
#6
Matilda Degn, Yves Dauvilliers, Karin Dreisig, Régis Lopez, Corinne Pfister, Sylvain Pradervand, Birgitte Rahbek Kornum, Mehdi Tafti
The sleep disorder narcolepsy with cataplexy is characterized by a highly specific loss of hypocretin (orexin) neurons, leading to the hypothesis that the condition is caused by an immune or autoimmune mechanism. All genetic variants associated with narcolepsy are immune-related. Among these are single nucleotide polymorphisms in the P2RY11-EIF3G locus. It is unknown how these genetic variants affect narcolepsy pathogenesis and whether the effect is directly related to P2Y11 signalling or EIF3G function. Exome sequencing in 18 families with at least two affected narcolepsy with cataplexy subjects revealed non-synonymous mutations in the second exon of P2RY11 in two families, and P2RY11 re-sequencing in 250 non-familial cases and 135 healthy control subjects revealed further six different non-synonymous mutations in the second exon of P2RY11 in seven patients...
April 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28454896/-did-you-climax-or-are-you-just-laughing-at-me-rare-phenomena-associated-with-orgasm
#7
REVIEW
Anna E Reinert, James A Simon
INTRODUCTION: The study of the human orgasm has shown a core set of physiologic and psychological symptoms experienced by most individuals. The study of normal sheds light on the abnormal and has spotlighted rare physical and psychological symptoms experienced by some individuals in association with orgasm. These phenomena are rare and, as is typical of rare phenomena, their documentation in the medical literature is largely confined to case studies. AIM: To identify peri-orgasmic phenomena, defined as unusual physical or psychological symptoms subjectively experienced by some individuals as part of the orgasm response, distinct from the usual or normal orgasm response...
April 25, 2017: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/28449899/comorbidity-of-narcolepsy-with-cataplexy-and-transverse-myelitis-a%C3%A2-common-autoimmune-background-a-case-report
#8
Rosa Peraita-Adrados, Julia Romero-Martínez, Juan A Guzmán-De Villoria, Laura Lillo-Triguero, María Luisa Martínez-Ginés
No abstract text is available yet for this article.
May 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28449891/the-european-medicines-agency-review-of-pitolisant-for-treatment-of-narcolepsy-summary-of-the-scientific-assessment-by-the-committee-for-medicinal-products-for-human-use
#9
Marta Kollb-Sielecka, Pierre Demolis, Joseph Emmerich, Greg Markey, Tomas Salmonson, Manuel Haas
On 31 March 2016, the European Commission issued a decision for a marketing authorisation valid throughout the European Union (EU) for pitolisant (Wakix) for the treatment of narcolepsy with or without cataplexy in adults. Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. The dose should be selected using an up-titration scheme depending on individual patient response and tolerance and should not exceed 36 mg/day. The main evidence of efficacy of pitolisant was based on two Phase III clinical trials...
May 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28445807/rewiring-brain-circuits-to-block-cataplexy-in-murine-models-of-narcolepsy
#10
REVIEW
Meng Liu, Carlos Blanco-Centurion, Priyattam J Shiromani
Narcolepsy was first identified almost 130 years ago, but it was only 15 years ago that it was identified as a neurodegenerative disease linked to a loss of orexin neurons in the brain. It is unclear what causes the orexin neurons to die, but our strategy has been to place the gene for orexin into surrogate neurons in the validated mouse models of narcolepsy, and test whether it can block narcolepsy symptoms, such as cataplexy. In both the orexin knockout and the orexin-ataxin-3 mouse models of narcolepsy we have found that cataplexy can be blocked if the surrogate neurons are part of the circuit responsible for cataplexy...
April 23, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28443381/pharmacological-management-of-narcolepsy-with-and-without-cataplexy
#11
Ulf Kallweit, Claudio L Bassetti
Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#12
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28396432/serotonin-neurons-in-the-dorsal-raphe-mediate-the-anticataplectic-action-of-orexin-neurons-by-reducing-amygdala-activity
#13
Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Olivia A Masseck, Stefan Herlitze, Mitsuhiro Yoshioka, Takeshi Sakurai, Michihiro Mieda
Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28366327/underutilization-of-the-mslt-in-sleepy-patients-with-a-short-onset-rem-period-soremp-in-the-sleep-clinic
#14
Alyssa Cairns, Richard Bogan
OBJECTIVE/BACKGROUND: A nocturnal sleep onset REM period (defined as REM onset latency ≤ 15 min; SOREMP) occurs rarely and research has shown that the phenomenon is specific for type 1 and 2 narcolepsy. However, little is known about the meaningfulness of the phenotype in general sleep clinic patients because those that exhibit the phenomenon often present with few traditional narcolepsy symptoms. As such, this study aimed to (1) evaluate the rate of eventual MSLT testing for those with a SOREMP on routine PSG when the phenomenon occurred in the absence of potential explanatory factors and (2) quantify the stability of the SOREMP phenotype...
April 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28366326/assessing-sleepiness-and-cataplexy-in-children-and-adolescents-with-narcolepsy-a-review-of-current-patient-reported-measures
#15
REVIEW
Khadra Benmedjahed, Y Grace Wang, Jérémy Lambert, Christopher Evans, Steve Hwang, Jed Black, Murray W Johns
OBJECTIVE: The objective of this study was to review patient-reported outcome measures assessing excessive daytime sleepiness (EDS) or cataplexy in children or adolescents to determine their usefulness and limitations in pediatric narcolepsy assessment. METHODS: Searches were performed in Embase and Medline for pediatric measures of EDS and cataplexy that are either patient- or proxy-reported, and searches of http://www.clinicaltrials.gov/ were conducted for studies in narcolepsy that included at least one patient-reported measure...
April 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28364512/nocturnal-dynamics-of-sleep-wake-transitions-in-patients-with-narcolepsy
#16
Xiaozhe Zhang, Jan W Kantelhardt, Xiao Song Dong, Dagmar Krefting, Jing Li, Han Yan, Frank Pillmann, Ingo Fietze, Thomas Penzel, Long Zhao, Fang Han
Introduction: We investigate how characteristics of sleep-wake dynamics in humans are modified by narcolepsy, a clinical condition that is supposed to destabilize sleep-wake regulation. Subjects with and without cataplexy are considered separately. Differences in sleep scoring habits as a possible confounder have been examined. Aims and Methods: Four groups of subjects are considered: narcolepsy patients from China with (n = 88) and without (n = 15) cataplexy, healthy controls from China (n = 110) and from Europe (n = 187, 2 nights each)...
February 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364477/temporal-changes-in-the-cerebrospinal-fluid-level-of-hypocretin-1-and-histamine-in-narcolepsy
#17
Régis Lopez, Lucie Barateau, Elisa Evangelista, Sofiene Chenini, Philippe Robert, Isabelle Jaussent, Yves Dauvilliers
Study Objectives: To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. Methods: From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28343142/circuit-mechanisms-of-sleepiness-and-cataplexy-in-narcolepsy
#18
REVIEW
Sara Pintwala, John Peever
Narcolepsy is a debilitating sleep disorder caused by loss of orexin neurons in the lateral hypothalamus. Excessive daytime sleepiness and cataplexy are the major complaints in narcolepsy, and are associated with impaired quality of life. Although it is unclear how orexin loss causes sleepiness and cataplexy, animal models have been instrumental in identifying the neurobiological underpinnings of narcolepsy because they reliably recapitulate disease symptoms. Current evidence indicates that orexin cell loss causes sleepiness and cataplexy by destabilizing the ability of the circuits that initiate and sustain normal levels of arousal and motor activity...
March 23, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28332559/the-immunogenetics-of-narcolepsy-associated-with-a-h1n1-pdm09-vaccination-pandemrix-supports-a-potent-gene-environment-interaction
#19
I L Bomfim, F Lamb, K Fink, A Szakács, A Silveira, L Franzén, V Azhary, M Maeurer, N Feltelius, N Darin, T Hallböök, L Arnheim-Dahlström, I Kockum, T Olsson
The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252...
March 23, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28258080/measurement-of-narcolepsy-symptoms-the-narcolepsy-severity-scale
#20
Yves Dauvilliers, Severine Beziat, Carole Pesenti, Regis Lopez, Lucie Barateau, Bertrand Carlander, Gianina Luca, Mehdi Tafti, Charles M Morin, Michel Billiard, Isabelle Jaussent
OBJECTIVE: To validate the Narcolepsy Severity Scale (NSS), a brief clinical instrument to evaluate the severity and consequences of symptoms in patients with narcolepsy type 1 (NT1). METHODS: A 15-item scale to assess the frequency and severity of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep was developed and validated by sleep experts with patients' feedback. Seventy untreated and 146 treated adult patients with NT1 were evaluated and completed the NSS in a single reference sleep center...
April 4, 2017: Neurology
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