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https://www.readbyqxmd.com/read/28445807/rewiring-brain-circuits-to-block-cataplexy-in-murine-models-of-narcolepsy
#1
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
#2
Ulf Kallweit, Claudio L Bassetti
Introduction 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...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28433385/perioperative-risks-of-narcolepsy-in-patients-undergoing-general-anesthesia-a-case-control-study
#3
Alexandre N Cavalcante, Ryan E Hofer, Maja Tippmann-Peikert, Juraj Sprung, Toby N Weingarten
STUDY OBJECTIVE: To compare the perioperative outcomes between patients with narcolepsy and matched controls undergoing anesthetic management. DESIGN: Retrospective 2:1 matched study design. SETTING: Large tertiary medical center. PATIENTS: Narcoleptic patients who underwent general anesthesia from January 1, 2011, through September 30, 2015, were matched with controls by age, sex, and type and year of surgery. MEASUREMENTS: Medical records were reviewed for episodes of respiratory depression during phase I recovery and for other meaningful perioperative outcomes...
April 19, 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28428181/irish-mp-calls-for-key-documents-on-pandemrix-to-be-handed-to-lawyers-representing-children-with-narcolepsy
#4
Clare Dyer
No abstract text is available yet for this article.
April 20, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28427008/lateral-hypothalamic-circuits-for-sleep-wake-control
#5
REVIEW
Takayuki Yamashita, Akihiro Yamanaka
The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in controlling instinctive behavior such as sleep-wake cycle and feeding behavior. LHA is a heterogeneous structure that contains spatially intermingled, genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX) neuron is the key cell type that promotes waking, and specific loss of OX neurons results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are known to be active during rapid eye movement (REM) sleep and stimulation of these neurons promotes REM sleep...
April 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28425082/discriminating-between-positional-and-non-positional-obstructive-sleep-apnea-using-some-clinical-characteristics
#6
Abderrahim Oulhaj, Sharina Al Dhaheri, Brenda Bin Su, Mohammed Al-Houqani
PURPOSE: The primary objective of this paper was to identify significant factors associated with positional Obstructive Sleep Apnea (POSA) and to provide a clinical tool for discriminating non positional from POSA. Secondary objectives were about estimating the prevalence of POSA, comparing the polysomnographic variables across POSA and non-POSA patients. METHODS: This was a cross sectional study on 278 patients who completed an overnight sleep study for OSA assessment...
April 19, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#7
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
#8
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 10, 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
#9
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
#10
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/28364570/excessive-fragmentary-myoclonus-what-do-we-know
#11
REVIEW
Jiří Nepožitek, Karel Šonka
Excessive fragmentary myoclonus (EFM) is a polysomnographic finding registered by the surface electromyography (EMG) and characterized as a result of the muscle activity consisting of sudden, isolated, arrhythmic, asynchronous and asymmetric brief twitches. The EMG potentials are defined by the exact criteria in The International Classification of the Sleep Disorders, 3rd edition and they appear with high intensity in all sleep stages. Clinical significance of EFM is unclear. It was observed in combination with other diseases and features such as obstructive and central sleep apnea, narcolepsy, periodic limb movements, insomnia, neurodegenerative disorders and peripheral nerve dysfunction...
2017: Prague Medical Report
https://www.readbyqxmd.com/read/28364512/nocturnal-dynamics-of-sleep-wake-transitions-in-patients-with-narcolepsy
#12
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/28364500/antibodies-against-hypocretin-receptor-2-are-rare-in-narcolepsy
#13
Maria Pia Giannoccaro, Patrick Waters, Fabio Pizza, Rocco Liguori, Giuseppe Plazzi, Angela Vincent
Study Objectives: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Methods: Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied...
February 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364477/temporal-changes-in-the-cerebrospinal-fluid-level-of-hypocretin-1-and-histamine-in-narcolepsy
#14
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/28364459/anti-tribbles-pseudokinase-2-trib2-immunization-modulates-hypocretin-orexin-neuronal-functions
#15
Susumu Tanaka, Yoshiko Honda, Makoto Honda, Hisao Yamada, Kazuki Honda, Tohru Kodama
Study Objectives: Recent findings showed that 16%-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of immunoglobulin-G purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. Methods: Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364448/cerebrospinal-fluid-biomarkers-of-neurodegeneration-are-decreased-or-normal-in-narcolepsy
#16
Poul Jørgen Jennum, Lars Østergaard Pedersen, Justyna Maria Czarna Bahl, Signe Modvig, Karina Fog, Anja Holm, Birgitte Rahbek Kornum, Steen Gammeltoft
Objectives: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. Methods: Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1)...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364420/cd4-t-cell-reactivity-to-orexin-hypocretin-in-patients-with-narcolepsy-type-1
#17
Melanie Ramberger, Birgit Högl, Ambra Stefani, Thomas Mitterling, Markus Reindl, Andreas Lutterotti
Introduction: Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease. Methods: We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay...
March 1, 2017: Sleep
https://www.readbyqxmd.com/read/28350795/fine-mapping-of-the-human-leukocyte-antigen-locus-as-a-risk-factor-for-alzheimer-disease-a-case-control-study
#18
Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, Jennifer S Yokoyama
BACKGROUND: Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28343142/circuit-mechanisms-of-sleepiness-and-cataplexy-in-narcolepsy
#19
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/28334952/dnmt1-mutations-found-in-hsanie-patients-affect-interaction-with-uhrf1-and-neuronal-differentiation
#20
Martha Smets, Stephanie Link, Patricia Wolf, Katrin Schneider, Veronica Solis, Joel Ryan, Daniela Meilinger, Weihua Qin, Heinrich Leonhardt
DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic neuropathies with dementia and hearing loss (HSANIE) and autosomal dominant cerebellar ataxia deafness and narcolepsy (ADCA-DN) and is associated with global hypomethylation and site specific hypermethylation...
April 15, 2017: Human Molecular Genetics
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