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Oscar Arias-Carrion, Emmanuel Ortega-Robles, Benito de Celis-Alonso, Artur Palasz, Eric Murillo-Rodriguez, Miguel A Mendez-Rojas, Jose Salas-Pacheco, Elias Manjarrez
Adult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone, is subject to complex regulations. Hypocretin/orexin neurons are implicated in the regulation of sleep and arousal states among other functions. Here, we found orexin afferent projections in the rat subventricular zone, which is a neurogenic region. We therefore studied in detail the origin of the orexinergic innervation to the subventricular zone in rats. Post-mortem retrograde tracing combined with immunofluorescence procedures indicate orexinergic projections toward the subventricular zone...
March 13, 2018: CNS & Neurological Disorders Drug Targets
Alexander Neergaard Olesen, Matteo Cesari, Julie Anja Engelhard Christensen, Helge Bjarup Dissing Sorensen, Emmanuel Mignot, Poul Jennum
OBJECTIVE: To evaluate rapid eye movement (REM) muscular activity in narcolepsy by applying five algorithms to electromyogram (EMG) recordings, and to investigate its value for narcolepsy diagnosis. PATIENTS/METHODS: A modified version of phasic EMG metric (mPEM), muscle activity index (MAI), REM atonia index (RAI), supra-threshold REM EMG activity metric (STREAM), and Frandsen method (FR) were calculated from polysomnography recordings of 20 healthy controls, 18 clinic controls (subjects suspected with narcolepsy but finally diagnosed without any sleep abnormality), 16 narcolepsy type one without REM sleep behavior disorder (RBD), nine narcolepsy type one with RBD, and 18 narcolepsy type two...
April 2018: Sleep Medicine
Monica Moresco, Mariangela Lecciso, Darina Ocadlikova, Marco Filardi, Silvia Melzi, Birgitte Rahbek Kornum, Elena Antelmi, Fabio Pizza, Emmanuel Mignot, Antonio Curti, Giuseppe Plazzi
BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course...
April 2018: Sleep Medicine
Alexis Roman, Soraya Meftah, Sébastien Arthaud, Pierre-Hervé Luppi, Christelle Peyron
Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. The three latter symptoms together with a short REM sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates...
March 7, 2018: Sleep
Marco Filardi, Fabio Pizza, Elena Antelmi, Raffaele Ferri, Vincenzo Natale, Giuseppe Plazzi
Study Objectives: Sodium oxybate (SXB) is a GABAergic agent widely used as off-label treatment in pediatric type 1 narcolepsy (NT1). Here we aimed at analyzing by wrist actigraphy the sleep/wake profile of NT1 children and adolescents in drug-naïve condition and after 1 year of SXB treatment. As secondary aim, we investigated changes on sleepiness, cataplexy and children's anthropometric profile after 1 year of SXB treatment. Methods: Twenty-four drug-naïve NT1 children underwent seven days of actigraphy during the school week...
March 7, 2018: Sleep
Monica Moresco, Fabio Pizza, Elena Antelmi, Giuseppe Plazzi
Narcolepsy type 1 (NT1) is a rare chronic neurologic disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations and disrupted nocturnal sleep, usually with onset during childhood/adolescence. Pediatric NT1 is associated with limitations on children's activities and achievements, especially poor performance at school, difficulty with peers due to disease symptoms and comorbidities including depression, obesity, and precocious puberty. NT1 disease is caused by the selective loss of hypocretin-producing neurons in the lateral hypothalamus, most probably related to an autoimmune pathophysiology...
March 5, 2018: Current Drug Metabolism
V Pauly, E Frauger, M Lepelley, M Mallaret, Q Boucherie, J Micallef
AIM: The aim was to characterize patterns of Methylphenidate (MPH) use in France in both children and adults over a three year period. METHODS: Using the French General Health Insurance database limited to two areas covering approximately 4 million individuals, we made up a cohort of incident MPH users between July 2010 and June 2013. Splitting them into distinct age groups ( [18-24]; [25;49]; >=50 years olds for adults and less than 6 years old, [6-11] and [12;17] for children), we described these populations at MPH initiation and during follow-up according to duration of treatment, quantities dispensed, and co-prescription with Central Nervous System (CNS) drugs...
March 7, 2018: British Journal of Clinical Pharmacology
Sheldon H Preskorn
This column is the fifth in a series examining the advances being made in central nervous system drug development because of advances in molecular pharmacology and an improved understanding of the neurobiology underlying disturbances in brain function including psychiatric illnesses. This column covers the special animal and human studies conducted as part of the development of suvorexant, which is the first in the class of dual orexin 1 and 2 receptor antagonists to be approved; it has an indication for the treatment of disturbances in sleep onset and maintenance...
March 2018: Journal of Psychiatric Practice
Mink S Schinkelshoek, Isabelle M Smolders, Claire E Donjacour, Wisse P van der Meijden, Erik W van Zwet, Rolf Fronczek, Gert Jan Lammers
Narcolepsy type 1 is characterised by an increase in body weight after disease onset, frequently leading to obesity. It was suggested that this weight gain may be counteracted by treatment with sodium oxybate. We here provide longitudinal body mass index data of patients with narcolepsy type 1 after starting treatment with sodium oxybate, compared with patients in whom treatment with modafinil was initiated. Eighty-one individuals with narcolepsy type 1 fulfilled the entry criteria for this retrospective study: 59 had newly started treatment with sodium oxybate and 22 had newly started modafinil...
March 4, 2018: Journal of Sleep Research
Alexander Cohen, Jay Mandrekar, Erik K St Louis, Michael H Silber, Suresh Kotagal
STUDY OBJECTIVE: To assess comorbidities in a community-based cohort of narcolepsy. METHODS: A 2000-2014 community-based narcolepsy cohort was identified in Olmsted County, Minnesota. Records were reviewed by a certified sleep specialist for accuracy of diagnosis, and comorbidities were extracted and analyzed. Comorbidities in narcolepsy subjects, both at diagnosis and upon follow-up, were compared with those in unaffected and age- and sex-matched cohort using conditional logistic regression...
March 2018: Sleep Medicine
Motahareh Rouhi Ardeshiri, Narges Hosseinmardi, Esmaeil Akbari
Involvement of amygdalo-hippocampal substructures in patients with narcolepsy due to deficiencies in the orexinergic system, and the presence of hippocampus-dependent memory impairments in this disorder, have led us to investigate the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. We used a 200-Hz high-frequency stimulation protocol in anesthetized rats. We studied the long-term synaptic plasticity of perforant path-dentate gyrus granule cells following the inactivation of orexin receptors before and after tetanic stimulation...
February 21, 2018: Neurobiology of Learning and Memory
Anne Marie Morse, Kothare Sanjeev
Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction...
February 15, 2018: Medical Sciences: Open Access Journal
A V Strobel, H Tankisi, N B Finnerup, A Fuglsang-Frederiksen, P Jennum, K B Svendsen, F I Kirov, M Otto
BACKGROUND: Idiopathic REM sleep behaviour disorder (iRBD) has been recognised as a significant biomarker for developing a neurodegenerative alpha-synucleinopathy, which is why iRBD is considered to be a prodromal state for alpha-synucleinopathies including Parkinson's disease (PD). Many patients with PD suffer from complaints of pain and present impaired somatosensory function. We hypothesized that pain perception and somatosensory function could be altered already in a preclinical stage of PD including iRBD...
February 2018: Sleep Medicine
Paul Kim, Emmanuel During, Mitchell Miglis
Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy...
February 13, 2018: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
L Lerousseau
Excessive daytime sleepiness is a major symptom in cases of the obstructive sleep apnea-hypopnea syndrome. Most often, it is vastly improved by treatment with continuous positive airway pressure (CPAP). The most effective way to confirm its disappearance is through wakefulness maintenance testing. If residual sleepiness remains, despite CPAP, further diagnostic investigation must be carried out. Firstly, it must be assessed whether the treatment is fully effective (apnea hypopnea index<10/h) by examining flow limitations under treatment (polysomnography) and whether it is sufficiently used (>6h/night)...
February 14, 2018: Revue des Maladies Respiratoires
Helle Sadam, Arno Pihlak, Anri Kivil, Susan Pihelgas, Mariliis Jaago, Priit Adler, Jaak Vilo, Olli Vapalahti, Toomas Neuman, Dan Lindholm, Markku Partinen, Antti Vaheri, Kaia Palm
BACKGROUND: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. METHODS: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA)...
February 2, 2018: EBioMedicine
Geoffrey Lawrence, Rexford Muza
Background: Excessive daytime sleepiness (EDS) is a complaint common to many aspects of medicine. There are primary and secondary causes for EDS, with secondary causes including a large number of common conditions. Primary causes, such as narcolepsy, are much rarer. When assessing for primary hypersomnia, restricted or fragmented sleep must be ruled out. This process involves assessment of sleeping habits using a sleep diary and/or actigraphy. Clinicians are suspicious of the accuracy with which patients use the former...
January 2018: Journal of Thoracic Disease
Yuki Omori, Takashi Kanbayashi, Aya Imanishi, Ko Tsutsui, Yohei Sagawa, Yuka S Kikuchi, Masahiro Takeshima, Kazuhisa Yoshizawa, Sachiko Uemura, Tetsuo Shimizu
Purpose: Myotonic dystrophy type 1 (DM1) is often characterized by excessive daytime sleepiness (EDS) and sleep-onset rapid eye movement periods caused by muscleblind-like protein 2. The EDS tends to persist even after treatment of sleep apnea. We measured the cerebrospinal fluid (CSF) orexin levels in DM1 patients with EDS and compared the clinical characteristics with narcolepsy type 1 and idiopathic hypersomnia (IHS) patients. Patients and methods: We measured the CSF orexin levels in 17 DM1 patients with EDS and evaluated subjective sleepiness using the Epworth Sleepiness Scale (ESS), objective sleepiness using mean sleep latency (MSL), and sleep apnea using apnea-hypopnea index (AHI)...
2018: Neuropsychiatric Disease and Treatment
Michał Danek, Janusz Danek, Aleksander Araszkiewicz
Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder)...
December 30, 2017: Psychiatria Polska
Kiran Maski, Judith Owens
PURPOSE OF REVIEW: This article provides an overview of the clinical features, diagnosis, and treatment of insomnia, restless legs syndrome, periodic limb movements of sleep, parasomnias, narcolepsy, and sleep-related breathing disorders among children and adolescents. RECENT FINDINGS: Pediatric presentations of sleep disorders differ from adult presentations, making diagnosis challenging. Specific clinical syndromes, such as cataplexy in children with narcolepsy type 1, can have an altogether different presentation compared to adult-onset symptoms, contributing to diagnostic delays and potential misdiagnoses...
February 2018: Continuum: Lifelong Learning in Neurology
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