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https://www.readbyqxmd.com/read/27919403/trace-amine-associated-receptor-1-agonists-as-narcolepsy-therapeutics
#1
Sarah W Black, Michael D Schwartz, Tsui-Ming Chen, Marius C Hoener, Thomas S Kilduff
BACKGROUND: Narcolepsy, a disorder of rapid eye movement (REM) sleep, is characterized by excessive daytime sleepiness and cataplexy, a loss of muscle tone triggered by emotional stimulation. Current narcolepsy pharmacotherapeutics include controlled substances with abuse potential or drugs with undesirable side effects. As partial agonists at trace amine-associated receptor 1 (TAAR1) promote wakefulness in mice and rats, we evaluated whether TAAR1 agonism had beneficial effects in two mouse models of narcolepsy...
October 18, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27909987/orexin-ox2-receptor-antagonists-as-sleep-aids
#2
Laura H Jacobson, Sui Chen, Sanjida Mir, Daniel Hoyer
The discovery of the orexin system represents the single major progress in the sleep field of the last three to four decades. The two orexin peptides and their two receptors play a major role in arousal and sleep/wake cycles. Defects in the orexin system lead to narcolepsy with cataplexy in humans and dogs and can be experimentally reproduced in rodents. At least six orexin receptor antagonists have reached Phase II or Phase III clinical trials in insomnia, five of which are dual orexin receptor antagonists (DORAs) that target both OX1 and OX2 receptors (OX2Rs)...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27905666/spectral-electroencephalography-profile-of-rapid-eye-movement-sleep-at-sleep-onset-in-narcolepsy-type-1
#3
F Pizza, R Ferri, S Vandi, F Rundo, M Iloti, G Neccia, G Plazzi
BACKGROUND AND PURPOSE: The sleep-onset rapid eye movement (REM) period (SOREMP), the hallmark of narcolepsy, may be a specific state and not the simple anticipation of REM sleep. METHODS: We analyzed the electroencephalographic spectral content in untreated patients with narcolepsy type 1 (NT1) during the sleep-onset period (SOP) and during nocturnal REM sleep in two consecutive nocturnal recordings from 31 patients with NT1 (mean age 34 ± 15 years, 18 males) and a single nocturnal recording from 36 controls (mean age 38 ± 13 years, 21 males)...
December 1, 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#4
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27857041/narcolepsy-with-cataplexy-in-a-child-with-charcot-marie-tooth-disease-case-report
#5
(no author information available yet)
We report an 8-year-old boy diagnosed with both CMT1 and narcolepsy, which were not reported simultaneously presenting in one person. The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing. Narcolepsy had not been diagnosed until the frequently falling caused by sudden and transient episodes of legs weakness triggered by emotion was found. Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency...
September 18, 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/27855741/normal-morning-mch-levels-and-no-association-with-rem-or-nrem-sleep-parameters-in-narcolepsy-type-1-and-type-2
#6
Maren Schrölkamp, Poul J Jennum, Steen Gammeltoft, Anja Holm, Birgitte R Kornum, Stine Knudsen
STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid (CSF) MCH levels, in contrast to previously reported normal evening/afternoon levels...
November 14, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27810187/impact-of-sodium-oxybate-modafinil-and-combination-treatment-on-excessive-daytime-sleepiness-in-patients-who-have-narcolepsy-with-or-without-cataplexy
#7
Jed Black, Todd Swick, Richard Bogan, Chinglin Lai, Lawrence P Carter
BACKGROUND: Effects of sodium oxybate (SXB) on patients with narcolepsy with cataplexy (NC) or without cataplexy (NWOC) have not been separately evaluated in clinical trials. METHODS: Retrospective analysis evaluated data from a phase 3, randomized, placebo-controlled trial of SXB, modafinil, and SXB + modafinil versus placebo in adult NC patients (n = 95) or NWOC patients (n = 127). NC patients were identified based on medical history, concomitant medications, and sleep-onset REM periods on nocturnal polysomnography...
August 2016: Sleep Medicine
https://www.readbyqxmd.com/read/27810179/diurnal-and-nocturnal-cardiovascular-variability-and-heart-rate-arousal-response-in-idiopathic-hypersomnia
#8
Emilia Sforza, Frédéric Roche, Jean Claude Barthélémy, Vincent Pichot
OBJECTIVES: Autonomic nervous system dysfunction has been described in narcolepsy with cataplexy affecting sympathetic functions. In this study we analyzed whether altered diurnal and nocturnal cardiovascular control is present in idiopathic hypersomnia (IH). METHODS: Fourteen drug-free patients aged 26.2 ± 7 years and 14 age-matched controls were examined. Clinical data, 24-h polysomnography, heart rate (HR) variability, and the HR response to spontaneous arousal were available...
August 2016: Sleep Medicine
https://www.readbyqxmd.com/read/27807903/effect-of-sodium-oxybate-on-disrupted-nighttime-sleep-in-patients-with-narcolepsy
#9
Thomas Roth, Yves Dauvilliers, Diane Guinta, Sarah Alvarez-Horine, Efim Dynin, Jed Black
This post hoc analysis evaluated the dose-related effects of sodium oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of sodium oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or sodium oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses...
November 3, 2016: Journal of Sleep Research
https://www.readbyqxmd.com/read/27807183/efficacy-of-sodium-oxybate-on-rem-sleep-behavior-disorder-in-a-patient-with-narcolepsy-type-1
#10
Geert Mayer
No abstract text is available yet for this article.
November 2, 2016: Neurology
https://www.readbyqxmd.com/read/27765468/memory-consolidation-in-sleep-disorders
#11
Nicola Cellini
In recent years sleep-related memory consolidation has become a central topic in the sleep research field. Several studies have shown that in healthy individuals sleep promotes memory consolidation. Notwithstanding this, the consequences of sleep disorders on offline memory consolidation remain poorly investigated. Research studies indicate that patients with insomnia, obstructive sleep apnea, and narcolepsy often exhibit sleep-related impairment in the consolidation of declarative and procedural information...
September 25, 2016: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/27668524/smoking-prevalence-and-its-clinical-correlations-in-patients-with-narcolepsy-cataplexy
#12
Pavla Peřinová, Eva Feketeová, David Kemlink, Petra Kovalská, Karolína Chlebušová, Jiří Nepožitek, Veronika Ibarburu, Eva Králíková, Soňa Nevšímalová, Karel Šonka
Narcolepsy-cataplexy (NC) is a chronic neurological disease with suggested autoimmune etiopathogenesis. Nicotine stimulates central nervous system and smoking increases the risk of autoimmune diseases. Assessment of smoking habits and its correlation to clinical parameters among 87 adult NC patients (38 male, 49 female) included night polysomnography and multiple sleep latency test. In our sample, 43.7% NC patients were regular smokers, and 19.5% former smokers compared to 22.2%, and 12.6%, respectively, in the general population...
2016: Prague Medical Report
https://www.readbyqxmd.com/read/27559330/narcolepsy-following-yellow-fever-vaccination-a-case-report
#13
Richard E Rosch, Michael Farquhar, Paul Gringras, Deb K Pal
Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27549768/management-of-narcolepsy
#14
REVIEW
Lucie Barateau, Régis Lopez, Yves Dauvilliers
Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms...
October 2016: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/27538328/-narcolepsy-with-cataplexy-type-1-narcolepsy
#15
Yves Dauvilliers, Régis Lopez
Narcolepsy with cataplexy or narcolepsy type 1 in a rare, disabling sleep disorder, with a prevalence of 20 to 30 per 100,000. Its onset peaks in the second decade. The main features are excessive daytime sleepiness and cataplexy or sudden less of muscle tone triggered by emotional situations. Other less consistent symptoms include hypnagogic hallucinations, sleep paralysis, disturbed nighttime sleep, and weight gain. Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime polysomnography (multiple sleep latency tests) are useful to document mean sleep latency below 8 min and at least two sleep-onset REM periods...
June 2016: La Revue du Praticien
https://www.readbyqxmd.com/read/27486325/a-clinician-s-guide-to-recurrent-isolated-sleep-paralysis
#16
REVIEW
Brian A Sharpless
This review summarizes the empirical and clinical literature on sleep paralysis most relevant to practitioners. During episodes of sleep paralysis, the sufferer awakens to rapid eye movement sleep-based atonia combined with conscious awareness. This is usually a frightening event often accompanied by vivid, waking dreams (ie, hallucinations). When sleep paralysis occurs independently of narcolepsy and other medical conditions, it is termed "isolated" sleep paralysis. Although the more specific diagnostic syndrome of "recurrent isolated sleep paralysis" is a recognized sleep-wake disorder, it is not widely known to nonsleep specialists...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27470330/shining-evolutionary-light-on-human-sleep-and-sleep-disorders
#17
REVIEW
Charles L Nunn, David R Samson, Andrew D Krystal
Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates...
2016: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/27359185/the-icsd-3-and-dsm-5-guidelines-for-diagnosing-narcolepsy-clinical-relevance-and-practicality
#18
Chad Ruoff, David Rye
Narcolepsy is a chronic neurological disease manifesting as difficulty with maintaining continuous wake and sleep. Clinical presentation varies but requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid-eye movement (REM) sleep dissociation (e.g., cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. Narcolepsy with cataplexy is associated with reductions of cerebrospinal fluid (CSF) hypocretin due to destruction of hypocretin peptide-producing neurons in the hypothalamus in individuals with a specific genetic predisposition...
July 20, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27305985/evaluation-of-polygenic-risks-for-narcolepsy-and-essential-hypersomnia
#19
Maria Yamasaki, Taku Miyagawa, Hiromi Toyoda, Seik-Soon Khor, Xiaoxi Liu, Hitoshi Kuwabara, Yukiko Kano, Takafumi Shimada, Toshiro Sugiyama, Hisami Nishida, Nagisa Sugaya, Mamoru Tochigi, Takeshi Otowa, Yuji Okazaki, Hisanobu Kaiya, Yoshiya Kawamura, Akinori Miyashita, Ryozo Kuwano, Kiyoto Kasai, Hisashi Tanii, Tsukasa Sasaki, Yutaka Honda, Makoto Honda, Katsushi Tokunaga
In humans, narcolepsy is a sleep disorder that is characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities. Essential hypersomnia (EHS) is another type of sleep disorder that is characterized by excessive daytime sleepiness without cataplexy. A human leukocyte antigen (HLA) class II allele, HLA-DQB1*06:02, is a major genetic factor for narcolepsy. Almost all narcoleptic patients are carriers of this HLA allele, while 30-50% of EHS patients and 12% of all healthy individuals in Japan carry this allele...
June 16, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27198946/autonomic-dysfunction-in-primary-sleep-disorders
#20
REVIEW
Mitchell G Miglis
The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder...
March 2016: Sleep Medicine
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