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https://www.readbyqxmd.com/read/28726523/investigational-therapies-for-the-treatment-of-narcolepsy
#1
Stefano de Biase, Annacarmen Nilo, Gian Luigi Gigli, Mariarosaria Valente
Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy...
July 20, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28677318/the-cost-utility-of-sodium-oxybate-as-narcolepsy-treatment
#2
K Bolin, P Berling, P Wasling, H Meinild, J Kjellberg, P Jennum
AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon...
July 5, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28675258/narcolepsy-cataplexy-and-psychosis-a-case-study
#3
F Canellas-Dols, C Delgado, C Arango-Lopez, R Peraita-Adrados
AIMS: To report a challenging patient a girl who developed narcolepsyy with cataplexy (NT1) and a psychosis during adolescence. To discuss diagnostic and therapeutic challenges of the comorbid cases. CASE REPORT: A 14-year-old girl was referred to Sleep and Epilepsy Unit for excessive daytime sleepiness, impaired nocturnal sleep, binge eating and weight gain, over the last year. After being diagnosed with a NT1 the patient was treated with modafinil and sodium oxybate...
July 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28673794/giggle-incontinence-evolution-of-concept-and-treatment
#4
REVIEW
Bridget Linehan Logan, Samantha Blais
BACKGROUND: Giggle incontinence is a sudden and involuntary episode of urinary incontinence that is provoked by an episode of laughter. Decades of case studies and small research studies have formed the basis of what is known about giggle incontinence; however, much remains unknown about this type of incontinence, leaving the recommendations for clinical management somewhat unguided. METHODS: A systematic review of 22 articles on the topic of "giggle incontinence" and related terms was conducted, including all published articles and commentaries since the term was first seen in print in 1959...
June 7, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28668666/ghb-levels-in-breast-milk-of-women-with-narcolepsy-with-cataplexy-treated-with-sodium-oxybate
#5
Emily C Barker, Michelle Puchowicz, John Letterio, Kristine Higgins, Katherine M Sharkey
OBJECTIVE: To determine GHB levels in breast milk of women taking sodium oxybate (Xyrem) for treatment of narcolepsy and cataplexy. METHODS: Two women with narcolepsy and cataplexy treated with sodium oxybate before pregnancy collected breast milk for analysis of GHB concentration after resuming sodium oxybate postpartum. One woman collected samples across two consecutive nights (doses: 3.0 gm and 4.5 gm twice per night) five months after delivering her first child; the other collected samples on three separate days (doses: 2...
June 1, 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28666745/the-clinical-spectrum-of-childhood-narcolepsy
#6
REVIEW
Emanuela Postiglione, Elena Antelmi, Fabio Pizza, Michel Lecendreux, Yves Dauvilliers, Giuseppe Plazzi
Narcolepsy type 1 is a life-long, severe, multifaceted disease often arising in childhood or adolescence. Beyond the classical symptoms (excessive daytime sleepiness, cataplexy, hallucinations, sleep paralysis and nocturnal fragmented sleep), metabolic, endocrinological, psychiatric and psychosocial aspects must be considered. Despite the increased awareness after H1N1 pandemic influenza and vaccination, narcolepsy is still misdiagnosed and unrecognized. The peculiar presentation of symptoms in narcoleptic children could in part explain the misdiagnoses...
May 8, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#7
Christoph Boss, Catherine Roch
The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists...
June 28, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28630298/hypocretin-orexin-is-critical-in-sustaining-theta-gamma-rich-waking-behaviors-that-drive-sleep-need
#8
Anne Vassalli, Paul Franken
Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrt(ko/ko) mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ (1.0 to 4.0 Hz) power rebound like WT littermates, spontaneous waking fails to induce a δ power reflecting prior waking duration. This correlates with impaired θ (6...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28619187/safety-and-efficacy-of-long-term-use-of-sodium-oxybate-for-narcolepsy-with-cataplexy-in-routine-clinical-practice
#9
Panagis Drakatos, Dimosthenis Lykouras, Grainne D'Ancona, Sean Higgins, Nadia Gildeh, Raluca Macavei, Ivana Rosenzweig, Joerg Steier, Adrian J Williams, Rexford Muza, Brian D Kent, Guy Leschziner
BACKGROUND: Sodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments. MATERIALS AND METHODS: This was a retrospective single centre study including patients with severe narcolepsy with cataplexy refractory to other treatments, who were initiated on sodium oxybate between 2009 and 2015...
July 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28619175/sodium-oxybate-treatment-in-narcolepsy-and-its-effect-on-muscle-tone
#10
Geert Mayer, Andrea Rodenbeck, Karl Kesper
AIMS: To estimate the effect of the compound sodium oxybate (SO) on chin muscle tone in sleep, a re-analysis of the results of the international multicenter study SXB-15 was performed, applying a validated semi-automatic analysis of muscle tone. This analysis distinguishes short (<0.5 s) and long (>0.5 s) muscle activity indices per hour (SMI, LMI) in 116 patients with narcolepsy-cataplexy. While stable stimulant medication was permitted, tricyclics and SSRIs were withdrawn. Polysomnographies were performed at baseline (V5), four weeks after titration of SO to 4...
July 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28574146/niemann-pick-type-c-as-a-cause-of-progressive-intellectual-and-neurological-deterioration-in-childhood
#11
Anne Marie Winstone, Lesley Ann Stellitano, Christopher Michael Verity
AIM: To describe the cases of Niemann-Pick type C (NP-C) disease in a United Kingdom epidemiological study of progressive intellectual and neurological deterioration in childhood. METHOD: Paediatricians notified cases via the British Paediatric Surveillance Unit between 1997 and 2015. RESULTS: Fifty-three NP-C patients were identified: 29 females, 24 males. Fifteen cases had a systemic presentation (neonatal jaundice and/or hepatosplenomegaly)...
June 2, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28568319/narcolepsy-with-cataplexy-and-pregnancy-a-case-control-study
#12
Elena Calvo-Ferrandiz, Rosa Peraita-Adrados
This was a retrospective case-control study in 25 patients with narcolepsy with cataplexy and 75 women in the control group. Patients completed the questionnaire by Maurovich-Horvat et al. (J. Sleep Res., 2013, 22: 496-512). We personally interviewed 25 patients with narcolepsy with cataplexy using the administered questionnaire regarding conception, pregnancy, delivery, perinatal and breastfeeding periods. Patients with narcolepsy with cataplexy reported 59 pregnancies versus 164 in the control group. In 16 cases (27...
June 1, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28549585/cystamine-mediated-inhibition-of-protein-disulfide-isomerase-triggers-aggregation-of-misfolded-orexin-a-in-the-golgi-apparatus-and-prevents-extracellular-secretion-of-orexin-a
#13
Issei Fujita, Mizuki Nobunaga, Takahiro Seki, Yuki Kurauchi, Akinori Hisatsune, Hiroshi Katsuki
Orexins (orexin-A and orexin-B) are neuropeptides that are reduced in narcolepsy, a sleep disorder that is characterized by excessive daytime sleepiness, sudden sleep attacks and cataplexy. However, it remains unclear how orexins in the brain and orexin neurons are reduced in narcolepsy. Orexin-A has two closely located intramolecular disulfide bonds and is prone to misfolding due to the formation of incorrect disulfide bonds. Protein disulfide isomerase (PDI) possesses disulfide interchange activity. PDI can modify misfolded orexin-A to its native form by rearrangement of two disulfide bonds...
May 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526554/the-roles-of-orexins-in-sleep-wake-regulation
#14
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
#15
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
#16
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 30, 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
#17
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
#18
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...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28460015/rare-missense-mutations-in-p2ry11-in-narcolepsy-with-cataplexy
#19
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...
June 1, 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
#20
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
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