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Narcolepsy

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https://www.readbyqxmd.com/read/28108192/epidemiology-and-pathophysiology-of-childhood-narcolepsy
#1
REVIEW
Thomas J Dye, Neepa Gurbani, Narong Simakajornboon
It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602...
December 21, 2016: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#2
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28105535/the-neuropeptide-orexin-a-inhibits-the-gabaa-receptor-by-pkc-and-ca-2-camkii-dependent-phosphorylation-of-its-%C3%AE-1-subunit
#3
Divya Sachidanandan, Haritha P Reddy, Anitha Mani, Geoffrey J Hyde, Amal Kanti Bera
Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain. Only discovered in 1998, the orexins are already known to regulate several behaviours. Most prominently, they help to stabilise the waking state, a role with demonstrated significance in the clinical management of narcolepsy and insomnia. Orexins bind to G-protein-coupled receptors (predominantly postsynaptic) of two subtypes, OX1R and OX2R. The primary effect of Ox-OXR binding is a direct depolarising influence mediated by cell membrane cation channels, but a wide variety of secondary effects, both pre- and postsynaptic, are also emerging...
January 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28102151/pleiotropic-genetic-effects-influencing-sleep-and-neurological-disorders
#4
REVIEW
Olivia J Veatch, Brendan T Keenan, Philip R Gehrman, Beth A Malow, Allan I Pack
Research evidence increasingly points to the large impact of sleep disturbances on public health. Many aspects of sleep are heritable and genes influencing traits such as timing, EEG characteristics, sleep duration, and response to sleep loss have been identified. Notably, large-scale genome-wide analyses have implicated numerous genes with small effects on sleep timing. Additionally, there has been considerable progress in the identification of genes influencing risk for some neurological sleep disorders. For restless legs syndrome, implicated variants are typically in genes associated with neuronal development...
February 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28098924/-hypernatremia-caused-by-treatment-with-ghb-obtained-via-a-doctor-s-prescription
#5
I M Rood, C G W Seijger, J A van Waarde, M M R de Maat, J C Verhave, M J Blans
In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced...
2017: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/28095967/intravenous-immunoglobulin-therapy-in-pediatric-narcolepsy-a-nonrandomized-open-label-controlled-longitudinal-observational-study
#6
Michel Lecendreux, Johanna Berthier, Jennifer Corny, Olivier Bourdon, Claire Dossier, Christophe Delclaux
STUDY OBJECTIVES: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. METHODS: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls)...
January 11, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28090682/pituitary-macrotumor-causing-narcolepsy-cataplexy-in-a-dachshund
#7
S Schmid, A Hodshon, S Olin, I Pfeiffer, S Hecht
Familial narcolepsy secondary to breed-specific mutations in the hypocretin receptor 2 gene and sporadic narcolepsy associated with hypocretin ligand deficiencies occur in dogs. In this report, a pituitary mass is described as a unique cause of narcolepsy-cataplexy in a dog. A 6-year-old male neutered Dachshund had presented for acute onset of feeding-induced cataplexy and was found to have a pituitary macrotumor on magnetic resonance imaging (MRI). Cerebral spinal fluid hypocretin-1 levels were normal, indicating that tumor effect on the ventral lateral nucleus of the hypothalamus was not the cause of the dog's narcolepsy-cataplexy...
January 15, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28087755/%C3%A2-pitolisant-for-narcolepsy
#8
(no author information available yet)
▼Pitolisant (Wakix-Bioprojet Pharma) is a new treatment for adults with narcolepsy with or without cataplexy. It was licensed for use in the EU in March last year and has orphan drug status.(1) Here, we consider the evidence for pitolisant for the treatment of narcolepsy in adults and how it fits with current management strategies.
January 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28087252/novel-method-for-evaluation-of-eye-movements-in-patients-with-narcolepsy
#9
Julie A E Christensen, Lykke Kempfner, Helle L Leonthin, Mathias Hvidtfelt, Miki Nikolic, Birgitte Rahbek Kornum, Poul Jennum
BACKGROUND: Narcolepsy causes abnormalities in the control of wake-sleep, non-rapid-eye-movement (non-REM) sleep and REM sleep, which inlcudes specific eye movements (EMs). In this study, we aim to evaluate EM characteristics in narcolepsy as compared to controls using an automated detector. METHODS: We developed a data-driven method to detect EMs during sleep based on two EOG signals recorded as part of a polysomnography (PSG). The method was optimized using the manually scored hypnograms from 36 control subjects...
December 21, 2016: Sleep Medicine
https://www.readbyqxmd.com/read/28075285/narcolepsy-drug-could-help-food-addicts-lose-weight
#10
(no author information available yet)
A drug used to treat the sleep disorder narcolepsy could help people addicted to food to lose weight, say UK researchers.
January 11, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28065388/a-systematic-review-of-cognitive-function-and-psychosocial-well-being-in-school-age-children-with-narcolepsy
#11
REVIEW
Jane E Blackwell, Hetaf A Alammar, Anna R Weighall, Ian Kellar, Hannah M Nash
In August 2010, concerns were raised about an increase in the incidence rate of narcolepsy diagnosis in children and adolescents. Narcolepsy is a chronic neurological sleep disorder characterised by excessive daytime sleepiness and attacks of muscle weakness which are often precipitated by strong emotions, known as cataplexy. We systematically examined and updated the scientific literature on the consequences of narcolepsy on cognitive function and psychosocial well-being in school-age children. Eight studies published between 2005 and 2015 were eligible for inclusion in this review...
July 18, 2016: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28063707/a-novel-vaccinological-evaluation-of-intranasal-vaccine-and-adjuvant-safety-for-preclinical-tests
#12
Eita Sasaki, Madoka Kuramitsu, Haruka Momose, Kouji Kobiyama, Taiki Aoshi, Hiroshi Yamada, Ken J Ishii, Takuo Mizukami, Isao Hamaguchi
Vaccines are administered to healthy humans, including infants, so the safety and efficacy must be very high. Therefore, evaluating vaccine safety in preclinical and clinical studies, according to World Health Organization guidelines, is crucial for vaccine development and clinical use. A change in the route of administration is considered to alter a vaccine's immunogenicity. Several adjuvants have also been developed and approved for use in vaccines. However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy...
January 4, 2017: Vaccine
https://www.readbyqxmd.com/read/28057302/unraveling-the-neurobiology-of-sleep-and-sleep-disorders-using-drosophila
#13
L Chakravarti, E H Moscato, M S Kayser
Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28012092/the-hypocretin-orexin-neuronal-networks-in-zebrafish
#14
Idan Elbaz, Talia Levitas-Djerbi, Lior Appelbaum
The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28012091/hypocretins-and-arousal
#15
Shi-Bin Li, William J Giardino, Luis de Lecea
How the brain controls vigilance state transitions remains to be fully understood. The discovery of hypocretins, also known as orexins, and their link to narcolepsy has undoubtedly allowed us to advance our knowledge on key mechanisms controlling the boundaries and transitions between sleep and wakefulness. Lack of function of hypocretin neurons (a relatively simple and non-redundant neuronal system) results in inappropriate control of sleep states without affecting the total amount of sleep or homeostatic mechanisms...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27997037/descending-projections-from-the-basal-forebrain-to-the-orexin-neurons-in-mice
#16
Lindsay J Agostinelli, Loris L Ferrari, Carrie E Mahoney, Takatoshi Mochizuki, Bradford B Lowell, Elda Arrigoni, Thomas E Scammell
The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and GABAergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata)...
December 20, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27995693/risks-of-neurological-and-immune-related-diseases-including-narcolepsy-after-vaccination-with-pandemrix-a-population-and-registry-based-cohort-study-with-over-2%C3%A2-years-of-follow-up
#17
I Persson, F Granath, J Askling, J F Ludvigsson, T Olsson, N Feltelius
No abstract text is available yet for this article.
January 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27994353/diagnosis-and-management-of-narcolepsy-in-the-indian-scenario
#18
Sachin Sureshbabu, Abdul Muniem, Manvir Bhatia
INTRODUCTION: The diagnosis and management of narcolepsy in the Indian context needs to be revisited especially in the wake of concerns raised by sleep medicine experts that the entity could be formidably underdiagnosed, as well as undertreated in our setting. MATERIALS AND METHODS: The history, clinical records, polysomnographic/multiple sleep latency test data, and treatment records of five hundred consecutive patients attending a dedicated sleep clinic between the years 2013 and 2016 were retrospectively analyzed...
October 2016: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/27981901/molecular-insights-of-creb-and-map-k-phosphorylation-by-modafinil-in-wake-related-brain-areas
#19
Ramsés Jiménez-Moreno, Adrián Amaury Farret-Ramos, Adriana Valle-Ayala, Niurka Trujillo-Paredes, Eric Murillo-Rodríguez
BACKGROUND: Modafinil (MOD) is a waking-promoting compound that is used for treatment of sleep disorders such as sleepiness and narcolepsy. Despite its efficiency, there are missing pieces of evidence regarding the mechanism of action of MOD at molecular level. For example, current data have demonstrated that MOD induces alertness by activating several wake-related neurotransmitter receptors, including dopamine 1 (D1) receptor. Nevertheless, an intriguing point highlights that MOD might be activating intracellular elements bounded to D1 receptor, such as cAMP response element-binding (CREB) or mitogen-activated protein kinase (MAP-K) expression...
December 14, 2016: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/27965038/increased-anxiety-but-normal-fear-and-safety-learning-in-orexin-deficient-mice
#20
Radwa Khalil, Markus Fendt
The loss of orexin neurons in humans leads to the disease narcolepsy, characterized by daytime sleepiness and cataplexy. Recent data suggest that orexin is also involved in emotional processing. The goal of the present study was to evaluate fear and safety learning as well as unconditioned fear (anxiety) in orexin-deficient animals. Orexin-deficient mice are an established animal model used to investigate the neuropathology and potential treatments for narcolepsy. Here, we present novel data showing that orexin-deficient mice express increased anxiety in the open field, light-dark box test and carnivore odor-induced avoidance, but are normal in fear and safety learning...
December 10, 2016: Behavioural Brain Research
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