WorldWideScience

Sample records for cataplexy

  1. Obesity accompanies narcolepsy with cataplexy but not narcolepsy without cataplexy

    Czech Academy of Sciences Publication Activity Database

    Šonka, K.; Kemlink, D.; Bušková, J.; Pretl, M.; Srutková, Z.; Horvát, E. M.; Vodička, Pavel; Poláková, Veronika; Nevšímalová, S.

    2010-01-01

    Roč. 31, č. 5 (2010), s. 631-634. ISSN 0172-780X Grant ostatní: GA MŠk(CZ) 0021620816; GA MŠk(CZ) 0021620849 Keywords : narcolepsy with cataplexy * Body Mass Index * sleepiness Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.621, year: 2010

  2. Baclofen for narcolepsy with cataplexy: two cases

    Directory of Open Access Journals (Sweden)

    Lee EK

    2015-07-01

    Full Text Available Elliott Kyung Lee,1,2 Alan Bruce Douglass1,2 1Department of Psychiatry, Faculty of Medicine, Institute of Mental Health Research, University of Ottawa, 2Royal Ottawa Mental Health Center, Ottawa, ON, Canada Abstract: Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydroxybutyrate (GHB. GHB is the most effective treatment for cataplexy, but is expensive and can have significant side effects. A recent report of a murine model of narcolepsy-cataplexy suggests R-baclofen has potential efficacy against cataplexy. We report on two narcolepsy patients with multiple daily cataplexy episodes, one of whom had been effectively treated with GHB, but had to discontinue it for unrelated medical reasons. Both subsequently tried baclofen and experienced almost complete resolution of cataplexy. This report suggests baclofen can be an effective treatment for cataplexy in humans and warrants further study. Keywords: hypersomnolence, gamma hydroxybutyrate, excessive daytime sleepiness

  3. Narcolepsy/Cataplexy and Occult Neuroblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-11-01

    Full Text Available Investigators at the University of Chicago and Northwestern University, Chicago, IL; University Hospital Southampton, UK; and Kiev Paediatric Hospital, Ukraine, report three children with narcolepsy and cataplexy subsequently diagnosed with neuroblastoma.

  4. Narcolepsy/Cataplexy and Occult Neuroblastoma

    OpenAIRE

    J Gordon Millichap

    2013-01-01

    Investigators at the University of Chicago and Northwestern University, Chicago, IL; University Hospital Southampton, UK; and Kiev Paediatric Hospital, Ukraine, report three children with narcolepsy and cataplexy subsequently diagnosed with neuroblastoma.

  5. Baclofen for narcolepsy with cataplexy: two cases

    OpenAIRE

    Lee EK; Douglass AB

    2015-01-01

    Elliott Kyung Lee,1,2 Alan Bruce Douglass1,2 1Department of Psychiatry, Faculty of Medicine, Institute of Mental Health Research, University of Ottawa, 2Royal Ottawa Mental Health Center, Ottawa, ON, Canada Abstract: Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydrox...

  6. Anomalous hypothalamic responses to humor in cataplexy.

    Directory of Open Access Journals (Sweden)

    Allan L Reiss

    Full Text Available BACKGROUND: Cataplexy is observed in a subset of patients with narcolepsy and affects approximately 1 in 2,000 persons. Cataplexy is most often triggered by strong emotions such as laughter, which can result in transient, yet debilitating, muscle atonia. The objective of this study was to examine the neural systems underlying humor processing in individuals with cataplexy. METHODOLOGY/PRINCIPAL FINDINGS: While undergoing functional Magnetic Resonance Imaging (fMRI, we showed ten narcolepsy-cataplexy patients and ten healthy controls humorous cartoons. In addition, we examined the brain activity of one subject while in a full-blown cataplectic attack. Behavioral results showed that participants with cataplexy rated significantly fewer humorous cartoons as funny compared to controls. Concurrent fMRI showed that patients, when compared to controls and in the absence of overt cataplexy symptoms, showed pronounced activity in the emotional network including the ventral striatum and hypothalamus while viewing humorous versus non-humorous cartoons. Increased activity was also observed in the right inferior frontal gyri--a core component of the inhibitory circuitry. In comparison, the one subject who experienced a cataplectic attack showed dramatic reductions in hypothalamic activity. CONCLUSIONS: These findings suggest an overdrive of the emotional circuitry and possible compensatory suppression by cortical inhibitory regions in cataplexy. Moreover, during cataplectic attacks, the hypothalamus is characterized by a marked decrease in activity similar to that observed during sleep. One possible explanation for these findings is an initial overdrive and compensatory shutdown of the hypothalamus resulting in full cataplectic symptoms.

  7. Role of the medial prefrontal cortex in cataplexy

    OpenAIRE

    Oishi, Yo; Williams, Rhiannan H.; Agostinelli, Lindsay; Arrigoni, Elda; Fuller, Patrick M.; Mochizuki, Takatoshi; Saper, Clifford B.; Scammell, Thomas E.

    2013-01-01

    Narcolepsy is characterized by chronic sleepiness and cataplexy - episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knockout mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and...

  8. A Consensus Definition of Cataplexy in Mouse Models of Narcolepsy

    OpenAIRE

    Scammell, Thomas E.; Willie, Jon T.; Guilleminault, Christian; Siegel, Jerome M.

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of...

  9. Narcolepsy with cataplexy in monozygotic twins

    OpenAIRE

    Goulart, Leonardo I.; Pedrazolli, Mário; Martori, Alexandre H.; Eckeli, Alan; Heidi H. Sander

    2014-01-01

    Introduction: This paper describes narcolepsy with cataplexy in two monozygotic twin sisters. Objective: To clinically illustrate the involvement of neurological, genetic and immunologic systems in narcolepsy. Material and methods: We performed a restropective study of these patients that were followed in the sleep medicine ambulatory clinic of the Faculdade de Medicina de Ribeirao Preto. Results: These sisters are two of the few cases in the literature concordant for narcolepsy with cataleps...

  10. Hypocretin deficiency develops during onset of human narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Savvidou, Andri; Knudsen, Stine; Olsson-Engman, Mia;

    2013-01-01

    Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans.......Although hypothesized through animal studies, a temporal and causal association between hypocretin deficiency and the onset of narcolepsy with cataplexy (NC) has never been proven in humans....

  11. Olfactory Dysfunction in Narcolepsy with and without Cataplexy

    Czech Academy of Sciences Publication Activity Database

    Bušková, J.; Klaschka, Jan; Šonka, K.; Nevšímalová, S.

    2010-01-01

    Roč. 11, č. 6 (2010), s. 558-561. ISSN 1389-9457 Institutional research plan: CEZ:AV0Z10300504 Keywords : narcolepsy * cataplexy * narcolepsy without cataplexy * RBD * olfactory dysfunction Subject RIV: FH - Neurology Impact factor: 3.430, year: 2010

  12. A case of cataplexy without narcolepsy

    Science.gov (United States)

    Tun, Shwe Zin

    2016-01-01

    A 6-year-old girl has episodic altered behaviour and collapses started. Earlier spells were associated with dizziness. During the first event, she looked blank while playing and almost fell to the ground. She was hot to the touch, looking pale. Her eyes were seen “rolling” with the events. There was no history of excessive sleepiness or symptoms of underlying sleep disorder. She had an ambulatory electroencephalography (EEG) and multiple sleep latency test (MSLT). While obtaining the ambulatory EEG, a clinical event appeared at her school in the morning. The patient sat down first, she looked as if she was asleep, laid down, gazing and did not respond. Her pupils were dilated and the eyes were moving. The 24-hour EEG revealed rapid eye movement (REM) sleep during the attack. The results of the MSLT revealed sleep onset REM in one of the five naps without a feature of pathological sleepiness. This might be a case of cataplexy without narcolepsy.

  13. The clinical spectrum of narcolepsy with cataplexy: a reappraisal.

    Science.gov (United States)

    Sturzenegger, Christian; Bassetti, Claudio L

    2004-12-01

    In the absence of a golden standard for the diagnosis of narcolepsy, the clinical spectrum of disorder remains controversial. The aims of this study were (1) to determine frequency and characteristics of sleep-wake symptoms in patients with narcolepsy with cataplexy, (2) to compare clinical characteristics with results of ancillary tests, and (3) to identify factors that discriminate narcolepsy from other conditions with excessive daytime sleepiness (EDS). We prospectively studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic hypersomnia (H), and 40 normal controls (No). Based on suggested and published criteria, we differentiated between narcoleptics with definite cataplexy (N) and narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment consisted of questionnaires [all patients and controls, including the Ullanlinna Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new narcolepsy score based on five questions was developed. Data were compared with those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant differences between N and NpC (including mean sleep latency on MSLT), but none between N and N-hd. A score of sleep propensity during active situations (SPAS) and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of flying, and history of sleep shouting discriminated N from H and No (P paralysis, hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1 levels and a history of definite cataplexy identify similar subgroups of narcoleptics. Specific questions on severity of EDS (SPAS score) and characteristics of cataplexy allow the recognition of subgroups of narcoleptics and their differentiation from non-narcoleptic EDS patients, including those reporting cataplexy-like episodes. The existence of co-occurring symptoms supports the hypothesis of a distinct

  14. Narcolepsy-Cataplexy: Is Streptococcal Infection a Trigger?

    OpenAIRE

    Natarajan, Niranjana; Jain, Sejal V.; Chaudhry, Hina; Hallinan, Barbara E.; Simakajornboon, Narong

    2013-01-01

    Narcolepsy-cataplexy is an uncommon sleep disorder which may present in childhood. We report a case of an 8-year-old presenting with narcolepsy-cataplexy following a streptococcal infection. Autoimmune etiology for narcolepsy has been suggested. In our patient increased anti-streptolysin O and anti-DNAse B titers were noted. As suggested by recent cases, the streptococcal infection was likely a trigger for narcolepsy onset in this genetically predisposed child. The patient was initially diagn...

  15. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy

    DEFF Research Database (Denmark)

    Andlauer, Olivier; Moore, Hyatt; Hong, Seung-Chul; Dauvilliers, Yves; Kanbayashi, Takashi; Nishino, Seiji; Han, Fang; Silber, Michael H; Rico, Tom; Einen, Mali; Kornum, Birgitte R; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Poli, Francesca; Plazzi, Giuseppe; Mignot, Emmanuel

    2012-01-01

    To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1.......To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1....

  16. Complex Movement Disorders at Disease Onset in Childhood Narcolepsy with Cataplexy

    Science.gov (United States)

    Plazzi, Giuseppe; Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of…

  17. Cataplexy and monoamine oxidase deficiency in Norrie disease.

    Science.gov (United States)

    Vossler, D G; Wyler, A R; Wilkus, R J; Gardner-Walker, G; Vlcek, B W

    1996-05-01

    Norrie disease (ND) is an X-linked recessive disorder causing ocular atrophy, mental retardation, deafness, and dysmorphic features. Virtually absent monoamine oxidase (MAO) type-A and -B activity has been found in some boys with chromosome deletions. We report the coexistence of cataplexy and abnormal REM sleep organization with ND. Three related boys, referred for treatment of medically refractory atonic spells and apneas, underwent extended EEG-video-polysomnographic monitoring. They demonstrated attacks of cataplexy and inappropriate periods of REM sleep during which they were unarousable. One boy also had generalized tonic-clonic seizures. Previous testing revealed that all three have complete ND gene deletions. In all subjects, platelet MAO-B activity was absent, serum serotonin levels were markedly increased, and plasma catecholamine levels were normal. Data from the canine narcolepsy syndrome model implicate abnormal catecholaminergic and cholinergic activities in the pathogenesis of cataplexy. Our findings suggest that abnormal MAO activity or an imbalance between serotonin and other neurotransmitter levels may be involved in the pathogenesis of human cataplexy. PMID:8628463

  18. Narcolepsy with Cataplexy Masked by the Use of Nicotine

    OpenAIRE

    Ebben, Matthew R.; Krieger, Ana C.

    2012-01-01

    This report describes a case of narcolepsy with cataplexy masked by the chronic use of cigarettes and nicotine patches. It has been described that narcoleptic smokers report relief of symptoms by smoking tobacco cigarettes.1 In addition, a case describing partial treatment of sleepiness using a nicotine patch in an adolescent with narcolepsy was recently reported in this journal.2 Our case adds to the growing literature that nicotine may be used to manage symptoms associated with narcolepsy.

  19. Cataplexy with Normal Sleep Studies and Normal CSF Hypocretin: An Explanation?

    Science.gov (United States)

    Drakatos, Panagis; Leschziner, Guy

    2016-03-01

    Patients with narcolepsy usually develop excessive daytime sleepiness (EDS) before or coincide with the occurrence of cataplexy, with the latter most commonly associated with low cerebrospinal fluid (CSF) hypocretin-1 levels. Cataplexy preceding the development of other features of narcolepsy is a rare phenomenon. We describe a case of isolated cataplexy in the context of two non-diagnostic multiple sleep latency tests and normal CSF-hypocretin-1 levels (217 pg/mL) who gradually developed EDS and low CSF-hypocretin-1 (< 110 pg/mL). PMID:26564387

  20. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Luca, Gianina; Haba-Rubio, José; Dauvilliers, Yves;

    2013-01-01

    The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy dia...

  1. Successful treatment of cataplexy in patients with early-infantile Niemann-Pick disease type C: use of tricyclic antidepressants.

    Science.gov (United States)

    Cak, Halime Tuna; Haliloğlu, Göknur; Düzgün, Gökçen; Yüce, Aysel; Topçu, Meral

    2014-11-01

    Cataplexy is a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions such as anger, laugh, humor or surprise and it is considered to represent the physiologic atonia of rapid eye movement sleep. On the other hand, Niemann-Pick type C is a neurodegenerative lysosomal storage disease, characterized by the accumulation of cholesterol and glycosphingolipids. Cataplexy is a relatively specific and common neurologic sign seen in almost 50% of all patients with Niemann-Pick type C. The aim of this report is to demonstrate the successful treatment of cataplexy with the use of a tricyclic antidepressant imipiramine, in two patients between the ages 6-9, with mild to moderate mental retardation, molecularly diagnosed as Niemann-Pick type C 1 and currently under miglustat treatment and to discuss the possible mechanisms of drug action in the light of cataplexy and Niemann-Pick type C pathophysiology. PMID:25139345

  2. Narcolepsy with cataplexy after A/H1N1 vaccination – A case reported from Cuba

    OpenAIRE

    Mesa, Yaimi Rosales; Meira e Cruz, Miguel Gonçalves

    2014-01-01

    Narcolepsy with cataplexy is a rare sleep disorder with a neurological basis which has been recently linked to H1N1 vaccination either in children or adults. Cases from Europe, United States and Brasil were registered. Authors describe a case report of a 15 years old boy who developed narcolepsy with cataplexy after H1N1 vaccination in Havana. As far as it is concerned this is the first case reported from Cuba.

  3. Reward-based behaviors and emotional processing in human with narcolepsy-cataplexy

    OpenAIRE

    Bayard, Sophie; Yves A Dauvilliers

    2013-01-01

    Major advances in the past decade have led a better understanding of the pathophysiology of narcolepsy with cataplexy (NC) caused by the early loss of hypothalamic hypocretin neurons. Although a role for hypocretin in the regulation of sleep/wakefulness state is widely recognized, other functions, not necessarily related to arousal, have been identified. Hence, the hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing, emotion and mood regulation, and ad...

  4. Reward-based behaviors and emotional processing in human with narcolepsy-cataplexy

    OpenAIRE

    Yves A Dauvilliers

    2013-01-01

    ajor advances in the past decade have led a better understanding of the pathophysiology of narcolepsy with cataplexy caused by the early loss of hypothalamic hypocretin neurons. Although a role for hypocretin in the regulation of sleep/wakefulness state is widely recognized, other functions, not necessarily related to arousal, have been identified. Hence, the hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing, emotion and mood regulation, and addictio...

  5. A Missense Mutation in Myelin Oligodendrocyte Glycoprotein as a Cause of Familial Narcolepsy with Cataplexy

    OpenAIRE

    Hor, Hyun; Bartesaghi, Luca; Kutalik, Zoltán; Vicário, José L.; de Andrés, Clara; Pfister, Corinne; Lammers, Gert J.; Guex, Nicolas; Chrast, Roman; Tafti, Mehdi; Peraita-Adrados, Rosa

    2011-01-01

    Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy. Familial narcolepsy accounts for less than 10% of all narcolepsy cases. However, documented multiplex families are very rare and causative mutations have not been identified to date. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest ever reported family, which has 12 affected members, and sequenced coding regions of the genome (exome sequencing) ...

  6. Obstetric Management of a Patient with Narcolepsy and Cataplexy: A Case Report

    OpenAIRE

    S. Ajayi; R. Kinagi; Haslett, E.

    2012-01-01

    We report the management of a patient who suffers from narcolepsy and cataplexy and presented to the clinic at 14 weeks of gestation. Her symptoms were resistant to modafinil but controlled with clomipramine and amphetamine. Discussion concerning mode of delivery for these patients is scarce in the literature. We discuss some issues surrounding the antenatal management and counselling regarding mode of delivery and postpartum care.

  7. Orexin gene transfer into the amygdala suppresses both spontaneous and emotion-induced cataplexy in orexin-knockout mice.

    Science.gov (United States)

    Liu, Meng; Blanco-Centurion, Carlos; Konadhode, Roda Rani; Luan, Liju; Shiromani, Priyattam J

    2016-03-01

    Narcolepsy is a chronic sleep disorder linked to the loss of orexin-producing neurons in the hypothalamus. Cataplexy, a sudden loss of muscle tone during waking, is an important distinguishing symptom of narcolepsy and it is often triggered by strong emotions. The neural circuit underlying cataplexy attacks is not known, but is likely to involve the amygdala, a region implicated in regulating emotions. In mice models of narcolepsy, transfer of the orexin gene into surrogate neurons has been successful in ameliorating narcoleptic symptoms. However, it is not known whether this method also blocks cataplexy triggered by strong emotions. To examine this possibility, the gene encoding mouse prepro-orexin was transferred into amygdala neurons of orexin-knockout (KO) mice (rAAV-orexin; n = 8). Orexin-KO mice that did not receive gene transfer (no-rAAV; n = 7) or received only the reporter gene (rAAV-GFP; n = 7) served as controls. Three weeks later, the animal's sleep and behaviour were recorded at night (no-odour control night), followed by another recording at night in the presence of predator odour (odour night). Orexin-KO mice given the orexin gene transfer into surrogate amygdala neurons had significantly less spontaneous bouts of cataplexy, and predator odour did not induce cataplexy compared with control mice. Moreover, the mice with orexin gene transfer were awake more during the odour night. These results demonstrate that orexin gene transfer into amygdala neurons can suppress both spontaneous and emotion-induced cataplexy attacks in narcoleptic mice. It suggests that manipulating amygdala pathways is a potential strategy for treating cataplexy in narcolepsy. PMID:26741960

  8. Control of motoneuron function and muscle tone during REM sleep, REM sleep behavior disorder and cataplexy/narcolepsy.

    Science.gov (United States)

    Peever, J

    2011-12-01

    REM sleep triggers a potent suppression of postural muscle tone - i.e., REM atonia. However, motor control during REM sleep is paradoxical because overall brain activity is maximal, but motor output is minimal. The skeletal motor system remains quiescent during REM sleep because somatic motoneurons are powerfully inactivated. Determining the mechanisms triggering loss of motoneuron function during REM sleep is important because breakdown in REM sleep motor control underlies sleep disorders such as REM sleep behavior disorder (RBD) and cataplexy/narcolepsy. For example, RBD is characterized by dramatic REM motor activation resulting in dream enactment and subsequent patient injury. In contrast, cataplexy a pathognomonic symptom of narcolepsy - is caused by the involuntary onset of REM-like atonia during wakefulness. This review highlights recent work from my laboratory that examines how motoneuron function is lost during normal REM sleep and it also identifies potential biochemical mechanisms underlying abnormal motor control in both RBD and cataplexy. First, I show that both GABAB and GABAA/glycine mediated inhibition of motoneurons is required for generating REM atonia. Next, I show that impaired GABA and glycine neurotransmission triggers the cardinal features of RBD in a transgenic mouse model. Last, I show that loss of an excitatory noradrenergic drive onto motoneurons is, at least in part, responsible for the loss of postural muscle tone during cataplexy in narcoleptic mice. Together, this research indicates that multiple transmitters systems are responsible for regulating postural muscle tone during REM sleep, RBD and cataplexy. PMID:22205591

  9. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B; Gammeltoft, S; Jennum, P J

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  10. Reward-based behaviors and emotional processing in human with narcolepsy-cataplexy

    Directory of Open Access Journals (Sweden)

    Sophie eBayard

    2013-05-01

    Full Text Available ajor advances in the past decade have led a better understanding of the pathophysiology of narcolepsy with cataplexy caused by the early loss of hypothalamic hypocretin neurons. Although a role for hypocretin in the regulation of sleep/wakefulness state is widely recognized, other functions, not necessarily related to arousal, have been identified. Hence, the hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing, emotion and mood regulation, and addiction. Although studies on hypocretin-deficient mice have shown that hypocretin plays an essential role in reward-seeking, depression-like behavior and addiction, results in human narcolepsy remained subject to debate. Most of studies revealed that hypocretin-deficient narcolepsy patients either drug-free or medicated with psychostimulant had preferences towards risky choices in a decision-making task under ambiguity together with higher frequency of depressive symptoms and binge eating disorder compared to controls. However, human studies mostly reported the lack of association with pathological impulsivity and gambling, and substance and alcohol abuse in the context of narcolepsy-cataplexy. Prospective larger studies are required to confirm these findings in drug-free and medicated patients with narcolepsy. Inclusion of patients with other central hypersomnias without hypocretin deficiency will provide answer to the major question of the role of the hypocretin system in reward-based behaviors and emotional processing in humans.

  11. White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

    Science.gov (United States)

    Park, Yun K; Kwon, Oh-Hun; Joo, Eun Yeon; Kim, Jae-Hun; Lee, Jong M; Kim, Sung T; Hong, Seung B

    2016-04-01

    Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy. PMID:26610427

  12. Neocortical 40 Hz oscillations during carbachol-induced rapid eye movement sleep and cataplexy.

    Science.gov (United States)

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Chase, Michael H; Falconi, Atilio

    2016-02-01

    Higher cognitive functions require the integration and coordination of large populations of neurons in cortical and subcortical regions. Oscillations in the gamma band (30-45 Hz) of the electroencephalogram (EEG) have been involved in these cognitive functions. In previous studies, we analysed the extent of functional connectivity between cortical areas employing the 'mean squared coherence' analysis of the EEG gamma band. We demonstrated that gamma coherence is maximal during alert wakefulness and is almost absent during rapid eye movement (REM) sleep. The nucleus pontis oralis (NPO) is critical for REM sleep generation. The NPO is considered to exert executive control over the initiation and maintenance of REM sleep. In the cat, depending on the previous state of the animal, a single microinjection of carbachol (a cholinergic agonist) into the NPO can produce either REM sleep [REM sleep induced by carbachol (REMc)] or a waking state with muscle atonia, i.e. cataplexy [cataplexy induced by carbachol (CA)]. In the present study, in cats that were implanted with electrodes in different cortical areas to record polysomnographic activity, we compared the degree of gamma (30-45 Hz) coherence during REMc, CA and naturally-occurring behavioural states. Gamma coherence was maximal during CA and alert wakefulness. In contrast, gamma coherence was almost absent during REMc as in naturally-occurring REM sleep. We conclude that, in spite of the presence of somatic muscle paralysis, there are remarkable differences in cortical activity between REMc and CA, which confirm that EEG gamma (≈40 Hz) coherence is a trait that differentiates wakefulness from REM sleep. PMID:26670051

  13. Heart rate variability during carbachol-induced REM sleep and cataplexy.

    Science.gov (United States)

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Velasquez, Noelia; Brando, Victoria; Falconi, Atilio; Chase, Michael H; Migliaro, Eduardo R

    2015-09-15

    The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD). In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state. PMID:25997581

  14. Para neoplastic cataplexy: evolution of PET with [{sup 18}F] -F.D.G. imaging; Cataplexie paraneoplasique: evolution de l'imagerie TEP au [18F]-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Farida, K.; Fernandez, P.; Guyot, M.; Jeandot, R.; Allard, M. [Service de medecine nucleaire, CHU de Bordeaux, (France); Sibon, I. [service de neurologie, CHU de Bordeaux, (France)

    2009-05-15

    Cataplexy is sudden and transient episode of loss of muscle tone, often triggered by emotions. We find it in the Gelineau disease but it can be constitutes an exceptional clinical expression of para-neoplasic syndromes. We report the evolution of the PET imaging for a patient during a para-neoplasic syndrome secondary to a testes teratoma associated to the presence of antibodies anti-Ma2. Different aspects of the {sup 18}F-F.D.G. fixation can be observed during the para-neoplasic syndromes affecting the central nervous system. Their values in term of prognosis and help to the therapy decision are still to define. (N.C.)

  15. Association of narcolepsy-cataplexy with HLA-DRB1 and DQB1 in Mexican patients: A relationship between HLA and gender is suggested

    Directory of Open Access Journals (Sweden)

    Haro Reyes

    2008-08-01

    Full Text Available Abstract Background Narcolepsy-cataplexy is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hallucinations and sleep paralysis. Its aetiology is unknown, but it is positively associated with the human leukocyte antigens (HLA in all studied populations. The purpose of the present study was to investigate the association of HLA class II DRB1/DQB1 alleles with narcolepsy-cataplexy in Mexican Mestizo patients. Methods This is a case-control study of consecutive patients and ethnically matched controls. We included 32 patients diagnosed with typical narcolepsy-cataplexy, of the National Institute of Neurology, of the Institute of Psychiatry and at the Center of Narcolepsy at Stanford University. As healthy controls, 203 Mexican Mestizos were included. DRB1 alleles were identified using sequence based typing. A PCR-SSOP reverse dot blot was used for DQB1 typing. Allele frequency was calculated by direct counting and the significance of the differences was assessed using the Yates Chi square. Odds ratio and confidence intervals were evaluated. Results HLA-DRB1*1501 (OR = 8.2; pc DQB1*0602 (OR = 8.4; pc DQB1*0602+ patients from the analysis, DQB1*0301 was also found increased (OR = 2.7; p = 0.035; pc = NS. DQB1*0602/DQB1*0301 genotype was present in 15.6% of the cases (OR = 11.5; p = 0.00035, conferring a high risk. DRB1*0407 (OR = 0.2; p = 0.016 pc = NS and DQB1*0302(OR = 0.4; p = 0.017, pc = NS were found decreased in the patients. The gender stratification analysis showed a higher risk in females carrying DRB1*1501 (OR = 15.8, pc DQB1*0602 (OR = 19.8, pc DRB1 & p = 0.0012, pc = 0.017 for DQB1. The susceptibility alleles found in Mexicans with narcolepsy are also present in Japanese and Caucasians; DRB1*04 linked protection has also been shown in Koreans. A stronger HLA association is suggested in females, in accordance with the sexual dimorphism claimed previously. Conclusion This knowledge may

  16. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus.

    Science.gov (United States)

    Saariaho, Anna-Helena; Vuorela, Arja; Freitag, Tobias L; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

    2015-09-01

    Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination. PMID

  17. 发作性睡病患者呼吸中枢低氧反应性与临床表现的相关性%Decreased hypoxic ventilatory chemoresponsiveness and clinical features in patients with narcolepsy cataplexy

    Institute of Scientific and Technical Information of China (English)

    张晓喆; 董霄松; 李静; 韩芳; 闫涵; 安培; 赵龙; 高占成

    2014-01-01

    Objective To explore the relationship between hypoxic responsiveness of the patients with narcolepsy-cataplexy and their clinical features.Methods A total of 113 patients with narcolepsycataplexy (narcolepsy group) at Peking University People's Hospital from June 2007 to May 2008 and 128 gender-age matched volunteers (control group) were recruited.And their status of human leukocyte antigen (HLA)-DQB1 * 0602 was examined to differentiate hypercapnic and hypoxic responsiveness.Among them,93 patients with severe hypersomnolence had hypercapnic and hypoxic responsiveness tested before and after the treatment of methylphenidate and another 20 with severe cataplexy did the same before and after the treatment of chlorimiopramine.Results Compared with the control group,the narcolepsy group had depressed hypoxic responsiveness ((-0.135 ± 0.105) vs (-0.223 ± 0.136) L · min-1 · % SpO2-1,P < 0.001).After the treatment of methylphenidate,sleepiness improved significantly in all 93 patients,but their low hypoxic responsiveness did not change ((-0.151 ±0.111) vs (-0.149 ±0.105) L · min-1 · % SpO2-1,P =0.780).After the treatment of chlorimiopramine,cataplexy also improved in 20 patients.However their low hypoxic responsiveness had no change ((-0.114 ±0.054) vs (-0.115 ±0.065) L · min-1 · % SpO2-1,P =0.949).Conclusion Lower hypoxic responsiveness in narcolepsy group is not related with the clinical features of disease.%目的 探讨猝倒型发作性睡病患者呼吸中枢低氧反应性与临床表现的相关性.方法 选择2007年6月至2008年5月北京大学人民医院睡眠中心就诊的伴猝倒且人类白细胞组织相容性抗原(HLA) DQB1* 0602阳性的113例典型发作性睡病患者(发作性睡病组)和128名年龄和性别匹配的健康志愿者(对照组)作为研究对象.分别测定其HLA-DQB1*0602状态、高CO2反应性[分钟通气量(VE)降低量与CO2分压(PCO2)下降量的比值]和低O2反应性[VE降

  18. Highlights from the 15th International Congress of Twin Studies/Twin Research: Differentiating MZ Co-twins Via SNPs; Mistaken Infant Twin-Singleton Hospital Registration; Narcolepsy With Cataplexy; Hearing Loss and Language Learning/Media Mentions: Broadway Musical Recalls Conjoined Hilton Twins; High Fashion Pair; Twins Turn 102; Insights From a Conjoined Twin Survivor.

    Science.gov (United States)

    Segal, Nancy L

    2015-02-01

    Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16-19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor. This article is dedicated to the memory of Elizabeth (Liz) Hamel, DZA twin who met her co-twin for the first time at age seventy-eight years. Liz and her co-twin, Ann Hunt, are listed in the 2015 Guinness Book of Records as the longest separated twins in the world. PMID:25662422

  19. A Case of REM Sleep Behavior Disorder, Narcolepsy-Cataplexy, Parkinsonism, and Rheumatoid Arthritis

    OpenAIRE

    Cosentino, Filomena I. I.; Angela Distefano; Giuseppe Plazzi; Schenck, Carlos H.; Raffaele Ferri

    2014-01-01

    A patient is reported in whom signs and symptoms of REM sleep behavior disorder (RBD) and narcolepsy have been associated for almost two decades with a late development of parkinsonism and rheumatoid arthritis. A 78-year-old male patient in whom RBD was first diagnosed was followed-up by clinical examination, video-polysomnography, multiple sleep latency test, cerebral magnetic resonance imaging, and dopamine transporter imaging by single-photon emission computerized tomography. The patient w...

  20. Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy

    DEFF Research Database (Denmark)

    Kawashima, Minae; Lin, Ling; Tanaka, Susumu; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Plazzi, Giuseppe; Mignot, Emmanuel

    2010-01-01

    Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases.......Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases....

  1. Sodium Oxybate

    Science.gov (United States)

    Sodium oxybate is used to prevent attacks of cataplexy (episodes of muscle weakness that begin suddenly and ... urge to sleep during daily activities, and cataplexy). Sodium oxybate is in a class of medications called ...

  2. A rare presentation of hypothyroidism

    Directory of Open Access Journals (Sweden)

    Betsy Mathew

    2014-02-01

    Full Text Available In this case report, we have brought out a very rare presentation of hypothyroidism in the form of cataplexy and this case is of significance because there have been no similar case reports of hypothyroidism presenting as cataplexy so far. The other highlight of the case is that treatment of hypothyroidism alone resulted in complete freedom from cataplexy without the need for agrypnotic drugs. [Int J Res Med Sci 2014; 2(1.000: 328-329

  3. Status Cataplecticus as Initial Presentation of Late Onset Narcolepsy

    OpenAIRE

    Panda, Samhita

    2014-01-01

    Narcolepsy, one of the important causes of hypersomnia, is an under diagnosed sleep disorder. It has a bimodal age of onset around 15 and 35 years. It is characterized by the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic/ hypnopompic hallucinations, and sleep paralysis. Cataplexy is by far the most predictive feature of narcolepsy. Status cataplecticus is the occurrence of cataplexy repeatedly for hours or days, a rare presentation of narcolepsy. This report describes an elder...

  4. Etiopathogenesis and Neurobiology of Narcolepsy: A Review

    OpenAIRE

    Kumar, Swarup; Sagili, Haritha

    2013-01-01

    Narcolepsy is a chronic lifelong sleep disorder and it often leaves a debilitating effect on the quality of life of the sufferer. This disorder is characterized by a tetrad of excessive daytime sleepiness, cataplexy (brief loss of muscle tone following strong emotion), hypnogogic hallucinations and sleep paralysis. There are two distinct subgroups of Narcolepsy: Narcolepsy with cataplexy and Narcolepsy without cataplexy. For over 100 years, clinicians have recognised narcolepsy, but only in t...

  5. Narcolepsy associated with primary temporal lobe B-cells lymphoma in a HLA DR2 negative subject.

    OpenAIRE

    Onofrj, M; Curatola, L; Ferracci, F; Fulgente, T

    1992-01-01

    Narcolepsy and cataplexy began one year before treatment of a left mid-temporal primary B-cells lymphoma in a HLA DR2 negative man. Treatment with radio therapy and immunosuppression induced regression of the lymphoma and disappearance of narcolepsy and cataplexy.

  6. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized that...... rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...

  7. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...

  8. Sleep physiology: setting the right tone.

    Science.gov (United States)

    Blumberg, Mark S

    2013-09-23

    Humans prone to cataplexy experience sudden losses of postural muscle tone without a corresponding loss of conscious awareness. The brain mechanisms underlying this debilitating decoupling are now better understood, thanks to a new study using cataplectic mice. PMID:24070441

  9. Narcolepsy and pregnancy

    DEFF Research Database (Denmark)

    Maurovich-Horvat, Eszter; Kemlink, David; Högl, Birgit; Frauscher, Birgit; Ehrmann, Laura; Geisler, Peter; Ettenhuber, Katharina; Mayer, Geert; Peraita-Adrados, Rosa; Calvo, Elena; Lammers, Gert Jan; Van der Heide, Astrid; Ferini-Strambi, Luigi; Plazzi, Giuseppe; Poli, Francesca; Dauvilliers, Yves; Jennum, Poul; Leonthin, Helle; Mathis, Johannes; Wierzbicka, Aleksandra; Puertas, Francisco J; Beitinger, Pierre A; Arnulf, Isabelle; Riha, Renata L; Tormášiová, Maria; Slonková, Jana; Nevšímalová, Sona; Sonka, Karel; Network, European Narcolepsy

    2013-01-01

    In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms...... of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P ...

  10. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    OpenAIRE

    Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï,; Dauvilliers, Yves

    2010-01-01

    BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune comp...

  11. Polysomnographic Assessment of Sleep Comorbidities in Drug-Naïve Narcolepsy-Spectrum Disorders—A Japanese Cross-Sectional Study

    OpenAIRE

    Sasai-Sakuma, Taeko; Kinoshita, Akihiko; Inoue, Yuichi

    2015-01-01

    This is a large cross-sectional study which aimed to investigate comorbidity rate, degree of sleep-related breathing disorder, polysomnigraphically diagnosible rapid eye movement sleep behavior disorder/rapid eye movement sleep without atonia and periodic limb movements during sleep in Japanese drug-naïve patients with narcolepsy-spectrum disorders. A total of 158 consecutive drug naïve patients with narcolepsy with cataplexy, 295 patients with narcolepsy without cataplexy and 395 patients wi...

  12. Clinical and Neurobiological Aspects of Narcolepsy

    OpenAIRE

    Nishino, Seiji

    2007-01-01

    Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amphetamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedativ...

  13. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy.

    Science.gov (United States)

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-08-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep. PMID:23219054

  14. Narcolepsy: a review

    Directory of Open Access Journals (Sweden)

    Akintomide GS

    2011-09-01

    Full Text Available Gbolagade Sunmaila Akintomide1, Hugh Rickards21Department of Neuropsychiatry, University of Birmingham, 2Department of Neuropsychiatry, The Barberry, Edgbaston, Birmingham, UKAbstract: Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone, hypnagogic hallucination, and sleep paralysis. There are two distinct groups of patients, ie, those having narcolepsy with cataplexy and those having narcolepsy without cataplexy. Narcolepsy affects 0.05% of the population. It has a negative effect on the quality of life of its sufferers and can restrict them from certain careers and activities. There have been advances in the understanding of the pathogenesis of narcolepsy. It is thought that narcolepsy with cataplexy is secondary to loss of hypothalamic hypocretin neurons in those genetically predisposed to the disorder by possession of human leukocyte antigen DQB1*0602. The diagnostic criteria for narcolepsy are based on symptoms, laboratory sleep tests, and serum levels of hypocretin. There is no cure for narcolepsy, and the present mainstay of treatment is pharmacological treatment along with lifestyle changes. Some novel treatments are also being developed and tried. This article critically appraises the evidence for diagnosis and treatment of narcolepsy.Keywords: narcolepsy, cataplexy, hypocretin, modafinil, gamma hydroxybutyrate

  15. Neuropsychological findings in childhood narcolepsy.

    Science.gov (United States)

    Posar, Annio; Pizza, Fabio; Parmeggiani, Antonia; Plazzi, Giuseppe

    2014-10-01

    Narcolepsy with cataplexy is a severely disabling disorder very often arising in childhood. Data on neuropsychological impairment in children are scant. We administered standardized neuropsychological tests to 13 children with narcolepsy with cataplexy. Overall, our patients displayed multiple patterns of cognitive and behavioral dysfunction, and often academic failure (7 cases out of 13). All children had a normal full intelligence quotient (IQ), but 3 patients presented a significantly higher and 2 a significantly lower Verbal IQ compared to Performance IQ, respectively. Mean sleep latency was significantly correlated (P emotional symptoms and conduct problems prevailed. Childhood narcolepsy with cataplexy represents a risk factor for subtle and heterogeneous cognitive impairments potentially resulting in academic failure, despite the normal IQ. These children also have a certain psychopathological risk. All this seems to be at least partially detached from the direct effects of daytime sleepiness. PMID:24293310

  16. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    DEFF Research Database (Denmark)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain......'s sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype....

  17. Sleep–Wake Transition in Narcolepsy and Healthy Controls Using a Support Vector Machine

    DEFF Research Database (Denmark)

    Jensen, Julie B; Sorensen, Helge B D; Kempfner, Jacob; Sørensen, Gertrud L; Knudsen, Stine; Jennum, Poul

    2014-01-01

    transformation and were given as input to a support vector machine classifier. The classification algorithm was assessed by hold-out validation and 10-fold cross-validation. The data used to validate the classifier were derived from polysomnographic recordings of 47 narcoleptic patients (33 with cataplexy and 14...... without cataplexy) and 15 healthy controls. Compared with manual scorings, an accuracy of 90% was achieved in the hold-out validation, and the area under the receiver operating characteristic curve was 95%. Sensitivity and specificity were 90% and 88%, respectively. The 10-fold cross-validation procedure...

  18. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency.

    Science.gov (United States)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-02-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy. Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures were: rapid eye movement sleep behaviour disorder symptoms; short and long muscle activations per hour rapid eye movement and non-rapid eye movement sleep; and periodic and non-periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep. Outcome variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin deficiency independently predicted rapid eye movement sleep behaviour disorder symptoms (relative risk = 3.69, P = 0.03), long muscle activations per hour rapid eye movement sleep (ln-coefficient = 0.81, P activations per hour rapid eye movement sleep (ln-coefficient = 1.01, P activity) in rapid eye movement sleep. Our results support the hypothesis that hypocretin deficiency is independently associated with rapid eye movement sleep behaviour disorder in narcolepsy. Thus

  19. Post-H1N1 Flu Vaccination Narcolepsy in Switzerland: A Retrospective Survey in the 30 Sleep-Certified Swiss Centers.

    Science.gov (United States)

    Kallweit, Ulf; Mathis, Johannes; Jenni, Oskar G; Heinzer, Raphaël; Haba-Rubio, José; Baumann, Christian R; Cervena, Katerina; Bassetti, Claudio L A

    2016-01-01

    Narcolepsy-cataplexy is a sleep-wake disorder and suggested to be immune-mediated, involving genetic and environmental factors. The autoimmune process eventually leads to a loss of hypocretin neurons in the lateral hypothalamus. Epidemiological studies in several countries proved an increased incidence of narcolepsy after H1N1 flu vaccination and infection. This survey in 30 sleep centers in Switzerland led to the identification of 9 H1N1-vaccinated children and adults as newly diagnosed narcolepsy. Clinical features included the abrupt and severe onset of sleepiness, cataplexy and sleep fragmentation. PMID:26901055

  20. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

    DEFF Research Database (Denmark)

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-01-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized......, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients...

  1. How Is Narcolepsy Treated?

    Science.gov (United States)

    ... Treatments Living With Clinical Trials Links Related Topics Sleep Deprivation and Deficiency Sleep Studies Send a link to NHLBI to someone ... it with a stimulant. Medicines that help you sleep at night. Medicines ... depression. These medicines also help prevent cataplexy, hallucinations, and ...

  2. Narcolepsy: Autoimmunity, Effector T Cell Activation Due to Infection, or T Cell Independent, Major Histocompatibility Complex Class II Induced Neuronal Loss?

    Science.gov (United States)

    Fontana, Adriano; Gast, Heidemarie; Reith, Walter; Recher, Mike; Birchler, Thomas; Bassetti, Claudio L.

    2010-01-01

    Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of…

  3. Common variants in P2RY11 are associated with narcolepsy

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Kawashima, Minae; Faraco, Juliette;

    2011-01-01

    Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Ameri...

  4. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek;

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in per...

  5. The Psychosocial Problems of Children with Narcolepsy and Those with Excessive Daytime Sleepiness of Uncertain Origin

    Science.gov (United States)

    Stores, Gregory; Montgomery, Paul; Wiggs, Luci

    2007-01-01

    Background: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong…

  6. Narcolepsy: A case from India with polysomnographic findings

    OpenAIRE

    Ravi Gupta; Deepak Goel; Robert Farney; Jim Walker

    2012-01-01

    Narcolepsy is a common sleep disorder with a prevalence of about 0.02%. However, it may remain largely unrecognized in the Indian population owing to the perceived low prevalence. To the best of our knowledge there is only one case of narcolepsy reported from India so far. We present a case of narcolepsy with cataplexy with classical clinical and polysomnographic findings of narcolepsy.

  7. Narcolepsy beyond sleepiness : endocrine, metabolic and other aspects

    NARCIS (Netherlands)

    Donjacour, Claire Elisabeth Henrica Maria

    2014-01-01

    The thesis contains a large study in which eight male hypocretin deficient narcolepsy with cataplexy patients and eight matched controls were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken 2 times 3g per night for 5 consecutive nights. Both groups underwen

  8. Narcolepsy in the older adult: epidemiology, diagnosis and management.

    Science.gov (United States)

    Chakravorty, Sangeeta S; Rye, David B

    2003-01-01

    Narcolepsy is a disorder of impaired expression of wakefulness and rapid-eye-movement (REM) sleep. This manifests as excessive daytime sleepiness and expression of individual physiological correlates of REM sleep that include cataplexy and sleep paralysis (REM sleep atonia intruding into wakefulness), impaired maintenance of REM sleep atonia (e.g. REM sleep behaviour disorder [RBD]), and dream imagery intruding into wakefulness (e.g. hypnagogic and hypnopompic hallucinations). Excessive sleepiness typically begins in the second or third decade followed by expression of auxiliary symptoms. Only cataplexy exhibits a high specificity for diagnosis of narcolepsy. While the natural history is poorly defined, narcolepsy appears to be lifelong but not progressive. Mild disease severity, misdiagnoses or long delays in cataplexy expression often cause long intervals between symptom onset, presentation and diagnosis. Only 15-30% of narcoleptic individuals are ever diagnosed or treated, and nearly half first present for diagnosis after the age of 40 years. Attention to periodic leg movements (PLM), sleep apnoea and RBD is particularly important in the management of the older narcoleptic patient, in whom these conditions are more likely to occur. Diagnosis requires nocturnal polysomnography (NPSG) followed by multiple sleep latency testing (MSLT). The NPSG of a narcoleptic patient may be totally normal, or demonstrate the patient has a short nocturnal REM sleep latency, exhibits unexplained arousals or PLM. The MSLT diagnostic criteria for narcolepsy include short sleep latencies (<8 minutes) and at least two naps with sleep-onset REM sleep. Treatment includes counselling as to the chronic nature of narcolepsy, the potential for developing further symptoms reflective of REM sleep dyscontrol, and the hazards associated with driving and operating machinery. Elderly narcoleptic patients, despite age-related decrements in sleep quality, are generally less sleepy and less likely to

  9. Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population

    DEFF Research Database (Denmark)

    Knudsen, Stine; Jennum, Poul J; Alving, Jørgen;

    2010-01-01

    STUDY OBJECTIVES: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency...... complicate direct comparisons of study results. DESIGN AND PARTICIPANTS: Interviews, polysomnography, multiple sleep latency test, HLA-typing, and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other...... hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602-positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of study results using the ICSD-2 criterion for low CSF hcrt-1 (

  10. Sleeping Beauty Gets an Eye Exam: A Case Report and Literature Review on Narcolepsy

    OpenAIRE

    Jenna Liechty, OD

    2014-01-01

    Background: Narcolepsy, a neurological sleep disorder that affects both adults and children, is caused by the inability of the brain to regulate sleep-wake cycles normally. The common tetrad of symptoms includes excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Ocular symptoms such as blurred vision, diplopia, ptosis, and ocular pain have been reported. Case Report: A ten-year-old female who was diagnosed with narcolepsy at an early age prese...

  11. Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes

    OpenAIRE

    Wu, M.-F.; Nienhuis, R.; Maidment, N.; Lam, H.A.; Siegel, J. M.

    2011-01-01

    Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study, we have compared the effects of treadmill running to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level bey...

  12. Characterization of A11 Neurons Projecting to the Spinal Cord of Mice

    OpenAIRE

    Koblinger, Kathrin; Füzesi, Tamás; Ejdrygiewicz, Jillian; Krajacic, Aleksandra; Bains, Jaideep S.; Whelan, Patrick J.

    2014-01-01

    The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA) to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic) nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement o...

  13. Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium

    OpenAIRE

    Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.

    2009-01-01

    The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiologic...

  14. Narcolepsy: Let the Patient’s Voice Awaken Us!

    OpenAIRE

    Flygare, Julie; Parthasarathy, Sairam

    2014-01-01

    This is a “patient-centered” review about narcolepsy that aims to awaken the reader to the narcolepsy condition and to the trials and tribulations of patients with sleep problems in general. Narcolepsy is a neurological disorder with a classic tetrad of symptoms consisting of excessive daytime sleepiness, cataplexy, sleep onset hallucinations, and sleep paralysis. The diagnosis of narcolepsy and other sleep disorders are often overlooked and could be attributed to other medical or even psychi...

  15. Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity.

    Science.gov (United States)

    Boehmer, L N; Wu, M-F; John, J; Siegel, J M

    2004-08-01

    All Doberman pinschers and Labrador retrievers homozygous for a mutation of the hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal conditions. Degenerative changes and increased display of major histocompatibility complex class II antigens have been linked to symptom onset in genetically narcoleptic Doberman pinschers. This suggests that the immune system may contribute to neurodegenerative changes and narcoleptic symptomatology in these dogs. We therefore attempted to alter the course of canine genetic narcolepsy, as an initial test of principle, by administering a combination of three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune response globally. Experimental dogs were treated with a combination of methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks after birth, and raised in an environment that minimized pathogen exposure. Symptoms in treated and untreated animals were quantified using the food elicited cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to cataplexy onset more than doubled, time spent in cataplexy during tests was reduced by more than 90% and nighttime sleep periods were consolidated. Short-term drug administration to control dogs did not reduce cataplexy symptoms, demonstrating that the drug regimen did not directly affect symptoms. Treatment was stopped at 6 months, after which experimental animals remained less symptomatic than controls until at least 2 years of age. This treatment is the first shown to affect symptom development in animal or human genetic narcolepsy. Our findings show that hcrtr2 mutation is not sufficient for the full symptomatic development of canine genetic narcolepsy and suggest that the immune system may play a role in the development of this disorder. PMID:15246829

  16. Narcolepsy: immunological aspects

    OpenAIRE

    Overeem, Sebastiaan; Black, John Logan; Lammers, Gert Jan

    2008-01-01

    Narcolepsy with cataplexy is a debilitating sleep disorder with an estimated prevalence of about 0.05%. Narcolepsy is caused by a selective loss of hypocretin (orexin) producing neurons in the perifornical hypothalamus. Based on the very strong association with the HLA subtype DQB1*0602, it is currently hypothesized narcolepsy is caused by an autoimmune mediated process directed at the hypocretin neurons. So far however, studies focussing on general markers of (auto)immune activation, as well...

  17. ApoE polymorphisms in narcolepsy

    OpenAIRE

    Kasten Meike; Wieczorek Stefan; Dahmen Norbert; Gencik Martin; Gencikova Alexandra; Epplen Jorg T

    2001-01-01

    Summary Background Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset ne...

  18. Narcolepsy: A case from India with polysomnographic findings

    Directory of Open Access Journals (Sweden)

    Ravi Gupta

    2012-01-01

    Full Text Available Narcolepsy is a common sleep disorder with a prevalence of about 0.02%. However, it may remain largely unrecognized in the Indian population owing to the perceived low prevalence. To the best of our knowledge there is only one case of narcolepsy reported from India so far. We present a case of narcolepsy with cataplexy with classical clinical and polysomnographic findings of narcolepsy.

  19. Nocturnal Temazepam in the Treatment of Narcolepsy

    OpenAIRE

    Kansagra, Sujay; Walter, Robert; Vaughn, Bradley

    2013-01-01

    Narcolepsy is characterized by fragmented nighttime sleep and frequent arousals. One treatment approach to improve daytime symptoms is to consolidate nighttime sleep through decreasing arousals. Sodium oxybate is the first FDA-approved medication that follows this approach. Benzodiazepines are known to also decrease arousals at night and have been proposed to help with sleep fragmentation. In one report, clonazepam was shown to improve cataplexy in 10 of 14 patients with narcolepsy although n...

  20. HYPOCRETIN/OREXIN AND NARCOLEPSY NEW BASIC AND CLINICAL INSIGHTS

    OpenAIRE

    Nishino, Seiji; Okuro, Masashi; Kotorii, Nozomu; ANEGAWA, Emiko; Ishimaru, Yuji; MATSUMURA, Mari; Kanbayashi, Takashi

    2009-01-01

    Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in huma...

  1. Animal Models of Narcolepsy

    OpenAIRE

    Chen, Lichao; Brown, Ritchie E.; McKenna, James T.; McCARLEY, ROBERT W.

    2009-01-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic sy...

  2. Narcolepsy: a review

    OpenAIRE

    Akintomide GS; Rickards H

    2011-01-01

    Gbolagade Sunmaila Akintomide1, Hugh Rickards21Department of Neuropsychiatry, University of Birmingham, 2Department of Neuropsychiatry, The Barberry, Edgbaston, Birmingham, UKAbstract: Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucination, and sleep paralysis. There are two distinct groups of patients, ie, those having narcolepsy with ...

  3. Narcolepsy and Orexins: An Example of Progress in Sleep Research

    OpenAIRE

    De la Herrán-Arita, Alberto K.; Guerra-Crespo, Magdalena; Drucker-Colín, René

    2011-01-01

    Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus. It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy, sleep paralysis, and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (hypocretins) in...

  4. Narcolepsy and Orexins: An Example of Progress in Sleep Research

    OpenAIRE

    RenéDrucker-Colin

    2011-01-01

    Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus (LH). It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement (REM) sleep such as cataplexy, sleep paralysis and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (h...

  5. Psychosis in Patients with Narcolepsy as an Adverse Effect of Sodium Oxybate

    OpenAIRE

    TomiSarkanen; ValterNiemelä; Anne-MarieLandtblom; MarkkuPartinen

    2014-01-01

    Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep–wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. F...

  6. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    International Nuclear Information System (INIS)

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  7. Narcolepsy Following Yellow Fever Vaccination: A Case Report

    Science.gov (United States)

    Rosch, Richard E.; Farquhar, Michael; Gringras, Paul; Pal, Deb K.

    2016-01-01

    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. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.

  8. Narcolepsy: etiology, clinical features, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Jolanta B. Zawilska

    2012-10-01

    Full Text Available [u][/u] Narcolepsy is a chronic hypersomnia characterized by excessive daytime sleepiness (EDS and manifestations of disrupted rapid eye movement sleep stage (cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations. Mechanisms underlying narcolepsy are not fully understood. Experimental data indicate that the disease is caused by a loss of hypocretin neurons in the hypothalamus, likely due to an autoimmune process triggered by environmental factors in susceptible individuals. Most patients with narcolepsy and cataplexy have very low hypocretin-1 levels in the cerebrospinal fluid. An appropriate clinical history, polysomnogram, and multiple sleep latency test are necessary for diagnosis of the disease. Additionally, two biological markers, i.e., cerebrospinal fluid hypocretin-1 levels and expression of the DQB1*0602 gene, are used. The treatment of narcolepsy is aimed at the different symptoms that the patient manifests. Excessive daytime sleepiness is treated with psychostimulants (amphetamine-like, modafinil and armodafinil. Cataplexy is treated with sodium oxybate (GHB, tricyclic antidepressants, or selective serotonin and noradrenaline reuptake inhibitors. Sleep paralysis, hallucinations, and fragmented sleep may be treated with sodium oxybate. Patients with narcolepsy should follow proper sleep hygiene and avoid strong emotions.

  9. Treatment Options for Narcolepsy.

    Science.gov (United States)

    Barateau, Lucie; Lopez, Régis; Dauvilliers, Yves

    2016-05-01

    Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated. PMID:27155860

  10. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Eun Yeon; Tae, Woo Suk; Kim, Sung Tae; Hong, Seung Bong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  11. Natural history, symptoms and treatment of the narcoleptic syndrome.

    Science.gov (United States)

    Parkes, J D; Baraitser, M; Marsden, C D; Asselman, P

    1975-11-01

    This study describes the clinical features, natural history and treatment of 100 patients with narcolepsy. Over half had one or more affected relatives. Symptoms commenced in adolescence or early adult life in most patients, and remissions were uncommon. Narcolepsy occurred several times each day, often in unusual circumstances and sometimes with little warning. The mean total sleep time of narco-leptics was a little over 9 hours in each 24 hour period, as compared with under 8 in normal subjects. Cataplexy occurred in 93 patients, most commonly when subjects were tired. Attacks were similar in nature to physiological weakness with laughter, although other sudden sensory or emotional stimuli did not cause paralysis of voluntary movement nor loss of muscle tone in normal subjects. Half these patients had frequent dreams before the onset of proper sleep, and 62 had sleep paralysis. This was often frightening, with feelings of suffocation, accompanied by dreams, and of uncertain length. A minority of patients with narcolepsy had muscle aches and jerks before sleep, double vision or loss of focus during cataplexy, went sleep-walking by day, and had daytime hallucinations. Amphetamines had been given to 71 patients for periods of up to 33 years with adequate, but rarely complete, control of narcolepsy. Side effects were common and almost half these patients became tolerant, needing higher dosage to control symptoms. Three patients had a cerebrovascular accident whilst taking amphetamines. Imipramine or clomipramine had ben given in combination with amphetamines to 33 patients for periods of up to 6 years with considerable improvement in both cataplexy and sleep paralysis, and few side effects. Sustained or paroxysmal hypertension as a result of amphetamines or combined treatment did not occur. PMID:19899267

  12. Narcolepsy in adolescents.

    Science.gov (United States)

    Sullivan, Shannon S

    2010-12-01

    Narcolepsy is a disorder of children and adolescence, but until recently it was often not identified until adulthood, with a reported time from onset to diagnosis of about a decade. This disorder affects approximately 0.05% of the population and starts in childhood and adolescence about half of the time. With narcolepsy, the boundaries between wake, sleep, and dreams are blurred. The cardinal features of narcolepsy-cataplexy are daytime somnolence, cataplexy (sometimes occurring long after onset of sleepiness), sleep paralysis, and hypnagogic hallucinations. Weight gain, disturbed nocturnal sleep, and social/school functional changes are common; reactive substance use to maintain wakefulness during the day may also be seen. Males and females are equally affected. It is classically associated with HLA DQB1*0602, the most specific genetic marker for narcolepsy across all ethnic groups. CSF hypocretin has recently been found to be depleted in this disorder, and late-breaking data support that the disease is caused by autoimmune destruction of hypocretin-producing neurons in the hypothalamus. There is no known cure for narcolepsy. Therapies include behavioral/ scheduling modification, medications to combat daytime sleepiness and cataplexy, and treatment of concomitant disorders leading to daytime sleepiness. The differential diagnosis for this disorder should include other disorders of excessive daytime sleepiness with a proclivity toward onset in adolescence, such as delayed sleep phase syndrome, obstructive sleep apnea, and insufficient sleep time; substance use; and less commonly neurologic disorders such as Klein Levin syndrome, Prader-Willi syndrome, and others. Immunomodulator therapy and hypocretin replacement are proposed therapies that hold promise for the future. PMID:21302860

  13. The norepinephrine reuptake inhibitor reboxetine is more potent in treating murine narcoleptic episodes than the serotonin reuptake inhibitor escitalopram.

    Science.gov (United States)

    Schmidt, Christian; Leibiger, Judith; Fendt, Markus

    2016-07-15

    One of the major symptoms of narcolepsy is cataplexy, a sudden loss of muscle tone. Despite the advances in understanding the neuropathology of narcolepsy, cataplexy is still treated symptomatically with antidepressants. Here, we investigate in a murine narcolepsy model the hypothesis that the antidepressants specifically blocking norepinephrine reuptake are more potent in treating narcoleptic episodes than the antidepressants blocking of serotonin reuptake. Furthermore, we tested the effects of α1 receptor stimulation and blockade, respectively, on narcoleptic episodes. Orexin-deficient mice were treated with different doses of the norepinephrine reuptake inhibitor reboxetine, the serotonin reuptake inhibitor escitalopram, the α1 receptor agonist cirazoline or the α1 receptor antagonist prazosin. The effect of these treatments on narcoleptic episodes was tested. Additionally, potential treatment effects on locomotor activity in an open-field were tested. Reboxetine (doses ≥0.55mg/kg) as well as escitalopram (doses ≥3.0mg/kg) dose-dependently reduced the number of narcoleptic episodes in orexin-deficient mice. The ED50 for reboxetine (0.012mg/kg) was significantly lower than for escitalopram (0.44mg/kg). Cirazoline and prazosin did not affect narcoleptic episodes. Furthermore, cirazoline but not the other compounds reduced locomotor activity of the mice. The present study strongly supports the hypothesis that a specific blockade of norepinephrine reuptake is more potent in treating cataplexy than a specific blockade of serotonin reuptake. This argues for the development of more specific norepinephrine reuptake inhibitors for the treatment of narcolepsy. PMID:27118715

  14. Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia

    Directory of Open Access Journals (Sweden)

    Seik-Soon Khor

    2013-04-01

    Full Text Available Essential hypersomnia (EHS, a sleep disorder characterized by excessive daytime sleepiness, can be divided into two broad classes based on the presence or absence of the HLA-DQB1*06:02 allele. HLA-DQB1*06:02-positive EHS and narcolepsy with cataplexy are associated with the same susceptibility genes. In contrast, there are fewer studies of HLA-DQB1*06:02 negative EHS which, we hypothesized, involves a different pathophysiological pathway than does narcolepsy with cataplexy. In order to identify susceptibility genes associated with HLA-DQB1*06:02 negative EHS, we conducted a genome-wide association study (GWAS of 125 unrelated Japanese EHS patients lacking the HLA-DQB1*06:02 allele and 562 Japanese healthy controls. A comparative study was also performed on 268 HLA-DQB1*06:02 negative Caucasian hypersomnia patients and 1761 HLA-DQB1*06:02 negative Caucasian healthy controls. We identified three SNPs that each represented a unique locus— rs16826005 (P = 1.02E-07; NCKAP5, rs11854769 (P = 6.69E-07; SPRED1, and rs10988217 (P = 3.43E-06; CRAT that were associated with an increased risk of EHS in this Japanese population. Interestingly, rs10988217 showed a similar tendency in its association with both HLA-DQB1*06:02 negative EHS and narcolepsy with cataplexy in both Japanese and Caucasian populations. This is the first GWAS of HLA-DQB1*06:02 negative EHS, and the identification of these three new susceptibility loci should provide additional insights to the pathophysiological pathway of this condition.

  15. Autonomic Function in Neurodegenerative Diseases

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Jennum, Poul Jørgen

    2013-01-01

    and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches. The increased frequency of transitions may cause increased sympathetic activity during sleep and thereby increased heart rate, or the increased heart rate could be caused...... confirm that hypocretin deficiency affects the autonomic nervous system of patients with narcolepsy and that the hypocretin system is important for proper heart rate modulation at rest.Furthermore, it was shown that hypocretin deficiency and cataplexy are associated with signs of destabilized sleep-wake...

  16. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara;

    2012-01-01

    Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT.......GLY605Ala mutation was subsequently identified. Narcolepsy and deafness were the first symptoms to appear in all pedigrees, followed by ataxia. DNMT1 is a widely expressed DNA methyltransferase maintaining methylation patterns in development, and mediating transcriptional repression by direct binding to...

  17. Common variants in P2RY11 are associated with narcolepsy

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Kawashima, Minae; Faraco, Juliette; Lin, Ling; Rico, Thomas J; Hesselson, Stephanie; Axtell, Robert C; Kuipers, Hedwich; Weiner, Karin; Hamacher, Alexandra; Kassack, Matthias U; Han, Fang; Knudsen, Stine; Li, Jing; Dong, Xiaosong; Winkelmann, Juliane; Plazzi, Giuseppe; Nevsimalova, Sona; Hong, Seung-Chul; Honda, Yutaka; Honda, Makoto; Högl, Birgit; Ton, Thanh G N; Montplaisir, Jacques; Bourgin, Patrice; Kemlink, David; Huang, Yu-Shu; Warby, Simon; Einen, Mali; Eshragh, Jasmin L; Miyagawa, Taku; Desautels, Alex; Ruppert, Elisabeth; Hesla, Per Egil; Poli, Francesca; Pizza, Fabio; Frauscher, Birgit; Jeong, Jong-Hyun; Lee, Sung-Pil; Strohl, Kingman P; Longstreth, William T; Kvale, Mark; Dobrovolna, Marie; Ohayon, Maurice M; Nepom, Gerald T; Wichmann, H-Erich; Rouleau, Guy A; Gieger, Christian; Levinson, Douglas F; Gejman, Pablo V; Meitinger, Thomas; Peppard, Paul; Young, Terry; Jennum, Poul; Steinman, Lawrence; Tokunaga, Katsushi; Kwok, Pui-Yan; Risch, Neil; Hallmayer, Joachim; Mignot, Emmanuel

    2011-01-01

    Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African...... Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y11 gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10¿¹°, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of...

  18. miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine;

    2014-01-01

    STUDY OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency...... controls using quantitative real-time polymerase chain reaction (qPCR) panels. SETTING: University hospital based sleep clinic and research laboratories. PATIENTS: Twelve patients with type 1 narcolepsy, 12 patients with type 2 narcolepsy, 12 patients with idiopathic hypersomnia, and 12 healthy controls...

  19. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine;

    2013-01-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in...... hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised that...

  20. Research progress of immunologic mechanism of narcolepsy

    OpenAIRE

    Hui-Juan WU; Yang, Tao; Zhu, Yan; Yang, Yang; ZHAO Zhong-xin

    2013-01-01

    Narcolepsy is a severe neurological sleep disorder, which is caused by the large loss of Hypocretin (Hcrt)/Orexin producing neurons in the hypothalamus in narcolepsy with cataplexy patients. It is likely the result of an autoimmune process that causes selective destruction of Hcrt neurons in the hypothalamus. It has been known that narcolepsy is associated with the human leukocyte antigens (HLA)-DR2 and HLA-DQB1*0602. Recent epidemic data have shown a robust incidence of disease onset associa...

  1. A new DRB1*1202 allele (DRB1*12022) found in association with DQA1*0102 and DQB1*0602 in two Black narcoleptic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Behar, E.; Grumet, F.C. [Stanford Univ. Blood Center, Palo Alto, CA (United States); Lin, X.; Mignot, E. [Stanford Univ. Sleep Disorders Center, Palo Alto, CA (United States)

    1995-01-01

    DQB1*0602 is a better genetic marker than DR2 for narcolepsy susceptibility across all ethnic groups; for instance, only 75% of African American narcoleptics are DR2+ compared with 96% DQB1*0602+. We studied DRB1 genes of DR2- but DQB1*0602+ African American patients with cataplexy and observed two with an unusual DR12, DQA1*0102, DQB1*0602 haplotype; a new allelic variant of DRB1*1202 has been designated DRB*12022. 8 refs.

  2. Characteristics of rapid eye movement sleep behavior disorder in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Frandsen, Rune Asger Vestergaard; Knudsen, Stine

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients...... of hypocretin deficiency. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Moreover, it is likely that hypocretin deficiency independently predicts periodic limb movements in REM and NREM sleep, probably via involvement...

  3. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress

    Directory of Open Access Journals (Sweden)

    Chow M

    2016-03-01

    Full Text Available Matthew Chow, Michelle CaoDepartment of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University School of Medicine, Stanford, CA, USAAbstract: Much of the understanding of the hypocretin/orexin (HCRT/OX system in sleep–wake regulation came from narcolepsy–cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively, as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep–wake control through complex interactions between monoaminergic/cholinergic (wake-promoting and gamma-aminobutyric acid-ergic (sleep-promoting neuronal systems. Deficiency of HCRT/OX results in loss of sleep–wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.Keywords: hypocretin, orexin, narcolepsy, insomnia, orexin antagonist, orexin agonist

  4. Clinical and Genetic Characteristics of Mexican Patients with Juvenile Presentation of Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Raul E. Piña-Aguilar

    2014-01-01

    Full Text Available Niemann-Pick type C disease (NPC is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology. In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC. Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed. Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes. All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy. Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum. The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348* and p.V1165M in case 3. Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity. This suggests a relative high frequency of mutation carriers as it is reported for European population. Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

  5. Clinical effect of venlafaxine combined with methylphenidate hydrochloride on narcolepsy

    Directory of Open Access Journals (Sweden)

    YAN Bin

    2013-11-01

    Full Text Available This study aims to explore the clinical effect of venlafaxine sustained-release capsules combined with methylphenidate hydrochloride tablets on narcolepsy. Thirty-eight cases of narcoleptic patients were randomly divided into venlafaxine combined with methylphenidate hydrochloride treatment group (observation group, N = 19 and methylphenidate hydrochloride and clomipramine treatment group (control group, N = 19. After a total of 12-week treatment, clinical curative effect and adverse drug reactions were observed in 2 groups of patients. The results showed that effective rate of the treatment for excessive daytime sleepiness (EDS in observation group was higher than that of the control group (15/19 vs 8/19, P = 0.044, and effective rate of the treatment for cataplexy in observation group was higher than that of the control group (13/19 vs 6/19, P = 0.048. The rate of adverse drug reactions in observation group was lower than that in the control group (χ2 = 8.889, P = 0.003. It was indicated that venlafaxine combined with methylphenidate had good curative effect on narcolepsy with EDS and cataplexy symptoms.

  6. REM sleep at its core—Circuits, neurotransmitters and pathophysiology

    Directory of Open Access Journals (Sweden)

    John ePeever

    2015-05-01

    Full Text Available REM sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC activate neurons in the ventral medial medulla (VMM, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG and dorsal paragigantocellular reticular nucleus (DPGi as well as melanin-concentrating hormone (MCH neurons in the hypothalamus and cholinergic cells in the laterodorsal (LDT and pedunculo-pontine tegmentum (PPT in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie cataplexy/narcolepsy and REM sleep behaviour disorder (RBD. This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD.

  7. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.

    Science.gov (United States)

    Chow, Matthew; Cao, Michelle

    2016-01-01

    Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders. PMID:27051324

  8. Value of Multiple Sleep Latency Test Periods and Clinical Correlation

    Directory of Open Access Journals (Sweden)

    Ibrahim Oztura

    2013-08-01

    Full Text Available Aim:Patients with complaints excessive daytime sleepiness were evaluated with Multiple Sleep Latency Test (MSLT electrophysiological findings and researched narcolepsy symptoms like nightmare, hallucinations, cataplexy in this study. Material and Method: To study 26 patients were admitted retrospectively with complaints of excessive daytime sleepiness at Dokuz Eylul University Faculty of Medicine Sleep Clinic in the dates December 2009- December 2010. Cases of narcolepsy symptoms (hallucinations-nightmare-cataplexy and MSLT were evaluated together. The onset of REM sleep (SOREM was counted, than SOREM (+ and SOREM (- patients’ sleep latency and narcolepsy symptoms were compared. All data were analyzed with SPSS 20.0. Results: The mean sleep latency assessed sleep latencies, gradually widening towards the end of the first sleep period, and it has been observed to be statistically significant(p:0.007. Conclusion: The mean sleep latency assessed sleep latencies, gradually widening towards the end of the first sleep period, and it has been observed to be statistically significant(p:0.007 and we thinked that it can be decreased of need to sleep during nap periods. [Cukurova Med J 2013; 38(4.000: 712-718

  9. Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in São Paulo Prevalência do alelo HLA-DQB1*0602 em pacientes com narcolepsia e hipersonolência idiopática atendidos em ambulatório de sonolência em São Paulo

    Directory of Open Access Journals (Sweden)

    Fernando Morgadinho Santos Coelho

    2009-03-01

    Full Text Available OBJECTIVE: Narcolepsy (with and without cataplexy and idiopathic hypersomnia, are disorders with common features but with different HLA-DQB1*0602 allele prevalence. The present study describes the prevalence of HLA-DQB1*0602 allele in narcoleptics with and without cataplexy and in patients with idiopathic hypersomnia. METHOD: Subjects comprised 68 patients who were diagnosed for narcolepsy or idiopathic hypersomnia and 23 healthy controls according to the International Classification of Sleep Disorders-2. Subjects comprised 43 patients with narcolepsy and cataplexy, 11 patients with narcolepsy but without cataplexy, 14 patients with idiopathic hypersomnia and 23 healthy controls. Genotyping of HLA-DQB1*0602 allele was performed for all subjects. RESULTS: The prevalence of the HLA-DQB1*0602 allele was increased in idiopathic hypersomnia and in narcoleptic patients with and without cataplexy when compared to healthy subjects (p = 0.04; p = 0.03 and p OBJETIVO: Narcolepsia (com e sem cataplexia e hipersonolência idiopática são transtornos com características clínicas comuns, mas com prevalências do alelo HLA-DQB1*0602 diferentes. Este estudo descreve a prevalência do alelo HLA-DQB1*0602 em pacientes narcolépticos com e sem cataplexia e em pacientes com hipersonolência idiopática. MÉTODO: A amostra consistiu de 68 pacientes com diagnóstico de narcolepsia ou hipersonolência idiopática e 23 controles saudáveis segundo o International Classification of Sleep Disorders-2. A amostra foi composta de 43 pacientes com narcolepsia e cataplexia, 11 pacientes com narcolepsia e sem cataplexia, 14 pacientes com hipersonolência idiopática e 23 controles saudáveis. A análise da presença do alelo HLA-DQ*0602 foi realizada em todos os sujeitos. RESULTADOS: A prevalência do alelo HLA-DQB1*0602 foi maior nos grupos de pacientes com hipersonolência idiopática e em pacientes narcolépticos com e sem cataplexia quando comparada com a dos sujeitos

  10. Diretrizes brasileiras para o diagnóstico de narcolepsia Brazilian guidelines for the diagnosis of narcolepsy

    Directory of Open Access Journals (Sweden)

    Flávio Alóe

    2010-09-01

    Full Text Available Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography

  11. Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    Vanier Marie T

    2010-06-01

    Full Text Available Abstract Niemann-Pick C disease (NP-C is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood. The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period, gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period, and ataxia not unfrequently following initial psychiatric disturbances (adult form. The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype. Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential

  12. Narcolepsia: actualización en etiología, manifestaciones clínicas y tratamiento Narcolepsy: update on etiology, clinical features and treatment

    Directory of Open Access Journals (Sweden)

    R.M. Pabón

    2010-08-01

    Full Text Available La narcolepsia es una enfermedad que consiste en una alteración en la generación y organización del sueño. Los principales síntomas son la excesiva somnolencia diurna y la cataplejía así como las alucinaciones hipnagógicas, parálisis del sueño y fragmentación del sueño nocturno. La prevalencia de la narcolepsia típica oscila entre el 25 y 50 por cada 100.000 habitantes. Recientemente se ha observado un pico de incidencia en pacientes nacidos en el mes de marzo. Según la nueva clasificación, el test de latencias múltiples de sueño (TLMS es imprescindible para el diagnóstico de narcolepsia sin cataplejía y aconsejable para el diagnóstico de la narcolepsia típica. Hasta ahora se trataban de forma independiente los síntomas, aunque actualmente las más recientes directrices de tratamiento proponen nuevos fármacos que actúan en todo el grupo de síntomas de forma global. La aplicación de nuevos criterios diagnósticos y terapéuticos permitirá un diagnóstico precoz y mejores opciones de tratamiento en esta patología.Narcolepsy is a disease that involves an alteration in the generation and organisation of sleep. The main symptoms are excessive daytime sleepiness and cataplexy, followed by hypnagogic hallucinations, sleep paralysis and disrupted nocturnal sleep. The prevalence of typical narcolepsy oscillates between 25-50: 100.000 in general. Recently there has been a peak incidence in patients born in the month of March. According to the new classification, the Multiple Sleep Latency Test (MSLT is mandatory for diagnosing narcolepsy without cataplexy, and advisable for diagnosing narcolepsy with cataplexy. Until now, the attempt has been made to control each symptom by its own specific treatment. At present, new American and European treatment guidelines propose new drugs that act on all the symptoms. The application of new criteria of diagnosis and treatment has improved the diagnosis, giving better options of treatment.

  13. Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre

    Directory of Open Access Journals (Sweden)

    Fernando Morgadinho Santos Coelho

    2010-10-01

    Full Text Available This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG and Multiple Sleep Latency Test (MSLT were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N - Hypocretin-1 higher than 110pg/ml and Lower (L Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002. DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil. MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N - Hypocretin-1 >110pg/ml e baixa (B - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002. DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem

  14. Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy

    DEFF Research Database (Denmark)

    Christensen, Julie Anja Engelhard; Carrillo, Oscar; Leary, Eileen B.; Peppard, Paul E.; Young, Terry; Sørensen, Helge Bjarup Dissing; Jennum, Poul; Mignot, Emmanuel

    2015-01-01

    extracted from PSGs. The first 15 min of sleep were excluded when a nocturnal SOREMP was recorded. F0.1 measures and receiver operating characteristic curves were used to identify specific (≥98%) features. A data set of 136 patients and 510 sex- and age-matched controls was used for the training. A data set......Objective: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep......-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. Methods: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were...

  15. National narcolepsy survey

    LENUS (Irish Health Repository)

    Doherty, L.

    2010-04-01

    Narcolepsy is characterised by excessive daytime sleepiness and cataplexy and has a prevalence of 25 per 100,000. We suspect this is higher than presently seen in the Republic of Ireland. We aimed to calculate the Irish prevalence of Narcolepsy and to examine current management practices. We conducted an online survey of respiratory physicians, neurologists, paediatric neurologists, and psychiatrists with an interest in sleep disorders (73% response rate). Of this group, a total of 16 physicians managed 180 patients prior to January 2009. A clinical diagnosis alone was reached in 67 (41%) patients, the remainder by polysomnography or multiple sleep latency testing. No patients were diagnosed by cerebro-spinal fluid analysis of hypocretin levels. While 70 (42%) patients received modafanil, only 7 (4%) were treated with sodium oxybate. Even allowing for missing data it is apparent that Narcolepsy is hugely under-diagnosed in Ireland, however, current practises adhere with new international guidelines.

  16. [Narcolepsy in sleepy obese children. Two case reports].

    Science.gov (United States)

    Rives-Lange, C; Karsenty, A; Chantereau, H; Oderda, L; Dubern, B; Lecendreux, M; Tounian, P

    2016-06-01

    Narcolepsy is a disabling disorder, characterized by excessive daytime sleepiness, irresistible sleep attacks, and partial or complete cataplexy. Many cases of obesity and precocious puberty have been reported in narcoleptic children, suggesting that the deficiency of hypocretin in narcolepsy could also be implicated in appetite stimulation. We report the observations of two young girls, who were referred for obesity and who developed narcolepsy accompanied by an abrupt weight gain. In both cases, specific drugs promoted wakefulness and overweight stabilization. Narcolepsy has to be suspected in sleepy obese children and not misdiagnosed as obstructive apnea. A nocturnal polysomnography with multiple sleep latency tests should be performed to confirm the diagnosis and begin specific treatment that is effective for sleep disorders and weight gain. PMID:27133373

  17. Central functions of the orexinergic system

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yang Zhang; Lei Yu; Qian-Xing Zhuang; Jing-Ning Zhu; Jian-Jun Wang

    2013-01-01

    The neuropeptide orexin is synthesized by neurons exclusively located in the hypothalamus.However,these neurons send axons over virtually the entire brain and spinal cord and therefore constitute a unique central orexinergic system.It is well known that central orexin plays a crucial role in the regulation of various basic non-somatic and somatic physiological functions,including feeding,energy homeostasis,the sleep/wake cycle,reward,addiction,and neuroendocrine,as well as motor control.Moreover,the absence of orexin results in narcolepsy-cataplexy,a simultaneous somatic and non-somatic dysfunction.In this review,we summarize these central functions of the orexinergic system and associated diseases,and suggest that this system may hold a key position in somatic-non-somatic integration.

  18. Marian House, Holy Faith Convent, Glasnevin, Dublin 11.

    LENUS (Irish Health Repository)

    Doherty, L.

    2010-04-01

    Narcolepsy is characterised by excessive daytime sleepiness and cataplexy and has a prevalence of 25 per 100,000. We suspect this is higher than presently seen in the Republic of Ireland. We aimed to calculate the Irish prevalence of Narcolepsy and to examine current management practices. We conducted an online survey of respiratory physicians, neurologists, paediatric neurologists, and psychiatrists with an interest in sleep disorders (73% response rate). Of this group, a total of 16 physicians managed 180 patients prior to January 2009. A clinical diagnosis alone was reached in 67 (41%) patients, the remainder by polysomnography or multiple sleep latency testing. No patients were diagnosed by cerebro-spinal fluid analysis of hypocretin levels. While 70 (42%) patients received modafanil, only 7 (4%) were treated with sodium oxybate. Even allowing for missing data it is apparent that Narcolepsy is hugely under-diagnosed in Ireland, however, current practises adhere with new international guidelines.

  19. A case of primary hypersomnia

    Directory of Open Access Journals (Sweden)

    John Dinesh

    2007-01-01

    Full Text Available Primary hypersomnia (PH is a disorder of presumed central nervous system etiology that is associated with a normal or prolonged major sleep episode and excessive sleepiness consisting of prolonged (one or two hour episodes of non-rapid eye movement sleep. It has a similar presentation to narcolepsy, but is not generally associated with cataplexy or sleep-onset rapid eye movement. Although PH is a chronic disorder, fluctuations and spontaneous remissions are known to occur. Treatment with stimulants is beneficial in most patients. We present the case of a 32-year-old Caucasian woman with the classical features of PH. Her condition has progressed over the years and she sleeps for days on end or until aroused. She has been treated with multiple stimulants, with limited success. This case highlights the clinical presentation, diagnostic criteria and treatment modalities of this rare condition.

  20. Type 1 narcolepsy

    DEFF Research Database (Denmark)

    Degn, Matilda; Kornum, Birgitte Rahbek

    2015-01-01

    Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune...... attack, and this is supported by evidence of both environmental and genetic factors pointing toward an involvement of the immune system. However, definitive proof of an autoimmune etiology is still missing. Several different immune-mediated disorders targeting neurons are known, and many of these are...... believed to be caused by autoreactive CD8(+) T cells. In this paper, we review the current knowledge on CD8(+) T cell-mediated neuronal damage on the basis of our understanding of other autoimmune disorders and experimental studies. We identify major histocompatibility complex class I presentation of...

  1. Autonomic Function in Neurodegenerative Diseases

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Jennum, Poul Jørgen

    2013-01-01

    involving brain stem areas, which is consistent with the Braak hypothesis. In the narcolepsy patients, it was shown that a reduced HRR to arousals was primarily predicted by hypocretin deficiency in both rapid-eye-movement (REM) and non-REM sleep, independent of cataplexy and other factors. The results......, which includes the cardiac centre and controls autonomic functions, and therefore autonomic dysfunction may be experienced early in the disease course. Sleep disturbances are also common non-motor complications of PD, and therefore PD patients undergo polysomnography at the Danish Center for Sleep...... narcolepsy patients on autonomic function and on the sleep transition rate. The results showed an attenuated heart rate response (HRR) in PD patients compared to controls and early PD (iRBD patients). Also iRBD patients had an attenuated HRR compared to control subjects, and the method to measure the HRR may...

  2. Sleep in psychogenic nonepileptic seizures and related disorders.

    Science.gov (United States)

    Pavlova, Milena K; Allen, Rebecca M; Dworetzky, Barbara A

    2015-01-01

    Psychogenic nonepileptic seizures (PNES), a form of functional neurological symptom disorder (FNSD), are very rarely seen in genuine, electroencephalography (EEG)-confirmed sleep. However, they are more commonly reported as a nocturnal occurrence, likely from a state that is misidentified as sleep (termed by some as "pseudosleep"). Sleep state can be helpful to distinguish FNSD from other neurological disorders. Pseudo-cataplexy, a form of "psychogenic" narcolepsy, "pseudo-parasomnia" and PNES can have a similar presentation. PNES and posttraumatic stress disorder (PTSD) frequently share previously experienced psychological trauma, and therefore the sleep abnormalities found in PTSD may be similarly present in PNES. Future research should use EEG monitoring to evaluate the sleep physiology of patients with FNSD such as PNES, as insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. PMID:25534169

  3. Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir

    2014-09-01

    Full Text Available Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 271-283

  4. Eating Disorder and Metabolism in Narcoleptic Patients

    Science.gov (United States)

    Chabas, Dorothée; Foulon, Christine; Gonzalez, Jesus; Nasr, Mireille; Lyon-Caen, Olivier; Willer, Jean-Claude; Derenne, Jean-Philippe; Arnulf, Isabelle

    2007-01-01

    Study Objective: To evaluate eating behavior and energy balance as a cause of increased body mass index (BMI) in narcolepsy. Design: Case controlled pilot study. Settings: University hospital Participants: 13 patients with narcolepsy (7 “typical” patients, with HLA DQB1*0602 and clear cut cataplexy, with suspected hypocretin deficiency; and 6 “atypical” narcoleptics, i.e., HLA negative or without cataplexy), and 9 healthy controls matched for age, gender, and ethnicity. Intervention: Energy balance was evaluated by measuring BMI, rest energy expenditure with calorimetry, daily food and water intake, and plasma hormone levels. Eating behavior was evaluated using psychometric tests (EAT-40, EDI2, CIDI-2, MADRS). Results: Patients with narcolepsy (whether typical or not) tended to be overweight and to have a lower basal metabolism than controls. Only patients with typical narcolepsy tended to eat less than controls. Narcoleptic patients who were overweight ate half as much as others, indicating caloric restriction. Plasma glucose, cortisol, thyroid, and sex hormones levels did not differ between groups, while prolactin levels were twice as high in patients with narcolepsy as in controls. Narcoleptic patients had higher EAT-40 scores and more frequent features of bulimia nervosa (independent of depressive mood) than controls, suggesting a mild eating disorder, classified as “Eating Disorder Not Other Specified.” Discussion: Both lower basal metabolism and subtle changes in eating behavior (rather than in calorie intake) could explain the positive energy balance leading to overweight in narcolepsy. Eating behavior changes may be a strategy to control weight or to avoid daytime sleepiness. Citation: Chabas D; Foulon C; Gonzalez J; Nasr M; Lyon-Caen O; Willer JC; Derenne JP; Amulf I. Eating disorder and metabolism in narcoleptic patients. SLEEP 2007;30(10):1267-1273. PMID:17969460

  5. Narcolepsy: current treatment options and future approaches

    Directory of Open Access Journals (Sweden)

    Michel Billiard

    2008-06-01

    Full Text Available Michel BilliardDepartment of Neurology, Gui de Chauliac Hospital, Montpellier, FranceAbstract: The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1 Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2 The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3 A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.Keywords: narcolepsy, treatment, conventional drugs, modafinil, sodium oxybate, future treatments

  6. High bicarbonate levels in narcoleptic children.

    Science.gov (United States)

    Franco, Patricia; Junqua, Aurelie; Guignard-Perret, Anne; Raoux, Aude; Perier, Magali; Raverot, Veronique; Claustrat, Bruno; Gustin, Marie-Paule; Inocente, Clara Odilia; Lin, Jian-Sheng

    2016-04-01

    The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice. PMID:26574184

  7. Executive control of attention in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Sophie Bayard

    Full Text Available BACKGROUND: Narcolepsy with cataplexy (NC is a disabling sleep disorder characterized by early loss of hypocretin neurons that project to areas involved in the attention network. We characterized the executive control of attention in drug-free patients with NC to determine whether the executive deficits observed in patients with NC are specific to the disease itself or whether they reflect performance changes due to the severity of excessive daytime sleepiness. METHODOLOGY: Twenty-two patients with NC compared to 22 patients with narcolepsy without cataplexy (NwC matched for age, gender, intellectual level, objective daytime sleepiness and number of sleep onset REM periods (SOREMPs were studied. Thirty-two matched healthy controls were included. All participants underwent a standardized interview, completed questionnaires, and neuropsychological tests. All patients underwent a polysomnography followed by multiple sleep latency tests (MSLT, with neuropsychological evaluation performed the same day between MSLT sessions. PRINCIPAL FINDINGS: Irrespective of diagnosis, patients reported higher self-reported attentional complaints associated with the intensity of depressive symptoms. Patients with NC performed slower and more variably on simple reaction time tasks than patients with NwC, who did not differ from controls. Patients with NC and NwC generally performed slower, reacted more variably, and made more errors than controls on executive functioning tests. Individual profile analyses showed a clear heterogeneity of the severity of executive deficit. This severity was related to objective sleepiness, higher number of SOREMPs on the MSLT, and lower intelligence quotient. The nature and severity of the executive deficits were unrelated to NC and NwC diagnosis. CONCLUSIONS: We demonstrated that drug-free patients with NC and NwC complained of attention deficit, with altered executive control of attention being explained by the severity of objective

  8. Clinical features of early-onset narcolepsy%早发型发作性睡病的临床特征

    Institute of Scientific and Technical Information of China (English)

    马秀伟; 封志纯; 任晓暾; 侯豫; 王三梅; 张晓妹; 周细中

    2012-01-01

    Ohjective To summarize clinical and electrophysiological manifestations of early-onset narcolepsy in children for improving its clinical diagnosis and management. Methods The clinical record, laboratory test, and management of 9 pediatrie patients with early onset narcolepsy were collected and reviewed. Results Among 9 pediatric patients, five were male and four were female. The onset age ranged from 3 years 4 months to 8 years 5 months (average 5 years 8 months). All patients presented with excessive day time somnolence. Cataplexy appeared in eight patients. No patients complained of hypnagogic hallucinations. Eight patients had mood disorders. All patients had weight gain. Electroencephalogram showed slow background in 3 patients, occasionally spike waves in 4 patients, and normal in 2 patients. Multiple sleep latency test demonstrated a short mean sleep latency ( < 5 min) and two or more sleep onset REM periods (SOREMPs) in 8 patients. Methylphenidate was administered in 8 patients. The excessive daytime sleepiness had been improved in 6 patients but no changes in cataplexy. Conclusions Early on-set narcolepsy might be misdiagnosed easily. Excessive daytime somnolence and cataplexy are the main clinical features. Multiple sleep latency test is important in early diagnosis of narcolepsy. Methylphenidate therapy is effective in some patients.%目的 总结早发型发作性睡病患儿的临床及电生理检查特征,提高临床诊疗水平.方法 对2009年8月至2010年12月期间诊治的9例早发型发作性睡病患儿的临床资料、辅助检查及治疗情况进行回顾性分析.结果 男5例、女4例,发病年龄3岁4个月~8岁5个月(平均5岁8个月).9例患儿均有白天过度睡眠;8例患儿曾出现猝倒;9例患儿均未诉入睡幻觉;8例患儿发病后情绪改变;9例患儿体质量均明显增加.脑电图检查示背景波偏慢3例,偶发尖波4例,正常2例.睡眠潜伏期试验,8例平均睡眠潜伏期<5 min,有2

  9. Clarifying the association of genes within the major histocompatibility complex with narcolepsy

    Energy Technology Data Exchange (ETDEWEB)

    Acton, R.T.; Watson, B.; Rivers, C. [Univ. of Alabama, Birmingham, AL (United States)] [and others

    1994-09-01

    HLA-DR2 and DQwl has been reported to be strongly associated with narcolepsy. The particular phenotype and strength of these associations varies between races. For example DQB*0601 has been reported associated with some African American (AA) narcoleptics while some Caucasian American (CA) narcoleptics do not possess DR2 or DQw1. We have sought to clarify the relationship of MHC genes with narcolepsy in the local CA and AA population. There was no significant difference in the frequency of DR phenotypes in CA or AA narcoleptics compared to race, age, sex and geographic region-matched controls. DR2 was increased in CA cataplexy positive (Cat+) narcoleptics compared to controls (p=0.028, odds ratio (OR)=2.4) and to Cat- narcoleptics (p=<0.001, OR=8.8). DR11 was increased in AA Cat+ narcoleptics compared to controls (p=0.004, OR=11.2) and to Cat- narcoleptics (p=0.002). DQB1*0601 was not significantly associated with narcolepsy in our AA population. We have assessed the frequency of the TNFa (13 alleles, 1.1Mb telomeric to DQ{alpha}), D6S105 (13 alleles, 1kb telomeric of HLA-A), and GLP-1R (19 alleles, 18.5 Mb centromeric of DQ{alpha}), dinucleotide repeats in narcoleptics compared to controls. The TNFa allele 117 was increased in CA Cat+ vs. controls (p=0.003). The GLP-1R allele 144 was increased in CA Cat- vs. controls (p=0.02). In AA narcoleptics, the TNFa allele 109 was significantly increased (p=0.04) along with the D6S105 allele 130 (p=0.02) compared to controls. The D6S105 allele 130 was increased in AA Cat- vs. controls (p=0.03). The GLP-1R allele 154 was significantly decreased in AA Cat+ vs. Cat- (p=0.04). These data suggest that DR and/or DQ genes are not responsible for narcolepsy and that cataplexy is associated with different regions around the MHC in various racial groups.

  10. Semantic priming effect during REM-sleep inertia in patients with narcolepsy.

    Science.gov (United States)

    Mazzetti, Michela; Campi, Claudio; Mattarozzi, Katia; Plazzi, Giuseppe; Tuozzi, Giovanni; Vandi, Stefano; Vignatelli, Luca; Cipolli, Carlo

    2006-12-11

    Patients with narcolepsy-cataplexy (NC) present excessive daytime sleepiness (EDS), cataplexy and an altered architecture of nocturnal sleep, with frequent episodes of REM-sleep at sleep onset (SOREM-sleep). This altered organization of nocturnal sleep may be accompanied by some differences in the functioning of the cognitive processes involved in the access, organization and consolidation of information during sleep. This study attempts to ascertain whether the activation of semantic memory during REM-sleep, as measured using a technique of semantic priming (namely, the facilitation of the activation of strongly-related rather than weakly-related and, overall, unrelated pairs of prime-target words) is different in NC patients compared to normal subjects. A lexical decision task (LDT) was carried out twice in wakefulness (at 10a.m. and after a 24h interval) and twice in the period of sleep inertia following awakening from SOREM and 4th-cycle REM-sleep on 12 NC patients and from 1st- and 4th-cycle REM-sleep on 12 matched controls. Reaction time (RT) to target words, taken as a measure of the semantic priming effect, proved to be longer (a) in NC patients than in control subjects; (b) in the period of REM-sleep inertia than in wakefulness; (c) in the first rather than the second session; and (d) for unrelated compared to weakly-related and, overall, strongly-related prime-target pairs. RT in post-REM-sleep sessions was less impaired, compared to waking sessions, and less dependent on the associative strength of prime-target pairs in NC patients than in normal subjects. Finally, RT of NC patients, although longer than that of normal subjects in waking sessions, significantly improved in the second session, as a consequence of either the amount of exercise or the consolidation advantage provided by REM-sleep for the procedural components of the task. The whole picture suggests a greater effectiveness of the activation of semantic memory during (SO)REM-sleep in NC

  11. From state dissociation to status dissociatus.

    Science.gov (United States)

    Antelmi, Elena; Ferri, Raffaele; Iranzo, Alex; Arnulf, Isabelle; Dauvilliers, Yves; Bhatia, Kailash P; Liguori, Rocco; Schenck, Carlos H; Plazzi, Giuseppe

    2016-08-01

    The states of being are conventionally defined by the simultaneous occurrence of behavioral, neurophysiological and autonomic descriptors. State dissociation disorders are due to the intrusion of features typical of a different state into an ongoing state. Disorders related to these conditions are classified according to the ongoing main state and comprise: 1) Dissociation from prevailing wakefulness as seen in hypnagogic or hypnopompic hallucinations, automatic behaviors, sleep drunkenness, cataplexy and sleep paralysis 2) Dissociation from rapid eye movement (REM) sleep as seen in REM sleep behavior disorder and lucid dreaming and 3) Dissociation from NREM sleep as seen in the disorders of arousal. The extreme expression of states dissociation is characterized by the asynchronous occurrence of the various components of the different states that prevents the recognition of any state of being. This condition has been named status dissociatus. According to the underlying disorders/diseases and to their severity, among status dissociatus we may recognize disorders in which such an extreme dissociation occurs only at night time or intermittently (i.e., autoimmune encephalopathies, narcolepsy type 1 and IgLON5 parasomnia), and others in which it occurs nearly continuously with complete loss of any conventionally defined state of being, and of the circadian pattern (agrypnia excitata). Here, we render a comprehensive review of all diseases/disorders associated with state dissociation and status dissociatus and propose a critical classification of this complex scenario. PMID:26431902

  12. Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate

    Directory of Open Access Journals (Sweden)

    Tomi eSarkanen

    2014-08-01

    Full Text Available Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.Method: We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia.Results: Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone alleviated psychotic symptoms in two cases. Conclusion: Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia however the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.

  13. Polysomnographic study of nocturnal sleep in idiopathic hypersomnia without long sleep time.

    Science.gov (United States)

    Pizza, Fabio; Ferri, Raffaele; Poli, Francesca; Vandi, Stefano; Cosentino, Filomena I I; Plazzi, Giuseppe

    2013-04-01

    We investigated nocturnal sleep abnormalities in 19 patients with idiopathic hypersomnia without long sleep time (IH) in comparison with two age- and sex- matched control groups of 13 normal subjects (C) and of 17 patients with narcolepsy with cataplexy (NC), the latter considered as the extreme of excessive daytime sleepiness (EDS). Sleep macro- and micro- (i.e. cyclic alternating pattern, CAP) structure as well as quantitative analysis of EEG, of periodic leg movements during sleep (PLMS), and of muscle tone during REM sleep were compared across groups. IH and NC patients slept more than C subjects, but IH showed the highest levels of sleep fragmentation (e.g. awakenings), associated with a CAP rate higher than NC during lighter sleep stages and lower than C during slow wave sleep respectively, and with the highest relative amount of A3 and the lowest of A1 subtypes. IH showed a delta power in between C and NC groups, whereas muscle tone and PLMS had normal characteristics. A peculiar profile of microstructural sleep abnormalities may contribute to sleep fragmentation and, possibly, EDS in IH. PMID:23061443

  14. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions

    Directory of Open Access Journals (Sweden)

    Jonathan P Wisor

    2013-10-01

    Full Text Available Modafinil, in its two clinical formulations (Provigil® and Nuvigil®, is a widely prescribed wake-promoting therapeutic agent. It binds competitively to the cell membrane dopamine transporter and is dependent on catecholaminergic (dopaminergic and adrenergic signaling for its wake-promoting effects. The clinical spectrum of effects for modafinil is distinct from the effects seen with other catecholaminergic agents. Relative to other commonly used agents that act through catecholaminergic mechanisms, modafinil has a relatively low abuse potential, produces wakefulness with an attenuated compensatory sleep recovery thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically relevant phenomenological differences between modafinil and agents such as amphetamines and cocaine do not eliminate catecholaminergic effects as a possible mediator of its wake-promoting action; they merely reflect its unique pharmacological profile. Modafinil is an exceptionally weak, but apparently very selective, dopamine transporter inhibitor. The pharmacodynamic response to modafinil, as measured by dopamine levels in brain microdialysate, is protracted relative to other agents that act via catecholaminergic mechanisms. The conformational constraints on the interaction of modafinil with the dopamine transporter—and probably, as a consequence, its effects on trace amine receptor signaling in the catecholaminergic cell—are unique among catecholaminergic agents. These unique pharmacological properties of modafinil should be considered both in seeking to thoroughly understand its putatively elusive mechanism of action and in the design of novel therapeutic agents.

  15. Dante's description of narcolepsy.

    Science.gov (United States)

    Plazzi, Giuseppe

    2013-11-01

    Sleep, sleepiness, and dreaming are expressed throughout Dante Alighieri's (1265-1321) the Divine Comedy from the start of his journey through the afterlife. In the book, Dante complains that he is "full of sleep," and he experiences sudden wake-dreaming transitions, short and refreshing naps, visions and hallucinations, unconscious behaviors, episodes of muscle weakness, and falls which are always triggered by strong emotions. Taken together these signs are highly reminiscent of narcolepsy, a term coined in 1880 by Gélineau to define a disease consisting of daytime irresistible sleep episodes with remarkable dream mentation, sleep paralysis, hallucinations, and cataplexy (falls triggered by strong emotions). Sleep, sleepiness, and episodes of sudden weakness triggered by emotions are Dante's literary fingerprints from his earliest works, pointing to a lifelong autobiographic trait. In the 19th century, Cesare Lombroso speculated that Dante had epilepsy, as he had suffered from frequent spells and hallucinations. However, the multiple emotionally triggered falls Dante experienced in the Divine Comedy contrast with the epileptic seizure he depicted in one of the damned individuals. It is possible that Dante may have intuitively grasped the main features of narcolepsy, but it also is plausible that Dante's sleep, dreams, hallucinations, and falls are clues to a lifelong pathologic trait and that Dante may have known of or had narcolepsy. PMID:24021161

  16. Sleeping Beauty Gets an Eye Exam: A Case Report and Literature Review on Narcolepsy

    Directory of Open Access Journals (Sweden)

    Jenna Liechty, OD

    2014-05-01

    Full Text Available Background: Narcolepsy, a neurological sleep disorder that affects both adults and children, is caused by the inability of the brain to regulate sleep-wake cycles normally. The common tetrad of symptoms includes excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Ocular symptoms such as blurred vision, diplopia, ptosis, and ocular pain have been reported. Case Report: A ten-year-old female who was diagnosed with narcolepsy at an early age presented for a comprehensive eye examination. She was taking Xyrem BID. Entering visual acuity was 20/30 OD, 20/70 OS, 20/25 OU at distance and 20/20 OD, OS, OU at near. Extraocular motilities, confrontation fields, and pupils were unremarkable with the exception of the patient continually falling asleep. A distance pair of glasses was issued: -0.50 DS, -1.25 DS. Conclusions: Narcolepsy is a chronic disorder that can severely affect a patient’s quality of life. Most control their symptoms with a wake-promoting drug. The disease itself, as well as its pharmacological treatment, can produce a range of ocular effects that optometrists should recognize and manage.

  17. Characterization of A11 neurons projecting to the spinal cord of mice.

    Science.gov (United States)

    Koblinger, Kathrin; Füzesi, Tamás; Ejdrygiewicz, Jillian; Krajacic, Aleksandra; Bains, Jaideep S; Whelan, Patrick J

    2014-01-01

    The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA) to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic) nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement of enzymes consistent with traditional DA neuronal phenotypes. Given the abundance of mouse genetic models and tools available to interrogate specific neural circuits and behavior, it is critical first to fully understand the phenotype of A11 cells. We provide evidence that, in addition to tyrosine hydroxylase (TH) that synthesizes L-DOPA, neurons within the A11 region of the mouse contain aromatic L-amino acid decarboxylase (AADC), the enzyme that converts L-DOPA to dopamine. Furthermore, we show that the A11 neurons contain vesicular monoamine transporter 2 (VMAT2), which is necessary for packaging DA into vesicles. On the contrary, A11 neurons in the mouse lack the dopamine transporter (DAT). In conclusion, our data suggest that A11 neurons are DAergic. The lack of DAT, and therefore the lack of a DA reuptake mechanism, points to a longer time of action compared to typical DA neurons. PMID:25343491

  18. The genetic basis of sleep disorders.

    Science.gov (United States)

    Dauvilliers, Yves; Tafti, Mehdi

    2008-01-01

    The contribution of genes, environment and gene-environment interactions to sleep disorders is increasingly recognized. Well-documented familial and twin sleep disorder studies suggest an important influence of genetic factors. However, only few sleep disorders have an established genetic basis including four rare diseases that may result from a single gene mutation: fatal familial insomnia, familial advanced sleep-phase syndrome, chronic primary insomnia, and narcolepsy with cataplexy. However, most sleep disorders are complex in terms of their genetic susceptibility together with the variable expressivity of the phenotype even within a same family. Recent linkage, genome-wide and candidate gene association studies resulted in the identification of gene mutations, gene localizations, or evidence for susceptibility genes and/or loci in several sleep disorders. Molecular techniques including mainly genome-wide linkage and association studies are further required to identify the contribution of new genes. These identified susceptibility genetic determinants will provide clues to better understand pathogenesis of sleep disorders, to assess the risk for diseases and also to find new drug targets to treat and to prevent the underlying conditions. We reviewed here the role of genetic basis in most of key sleep disorders. PMID:19075715

  19. Management of common sleep disorders.

    Science.gov (United States)

    Ramar, Kannan; Olson, Eric J

    2013-08-15

    Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot sleep, those who will not sleep, those with excessive daytime sleepiness, and those with increased movements during sleep. Insomnia, defined as difficulty initiating or maintaining sleep that results in daytime impairment, is diagnosed using history findings and treated with cognitive behavior therapy, with or without sleep hypnotics. Restless legs syndrome is characterized by an urge to move the legs that worsens with rest, is relieved by movement, and often occurs in the evening or at night. Restless legs syndrome is treated based on the frequency of symptoms. Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis. It is diagnosed using a sleep log or actigraphy, followed by overnight polysomnography and a multiple sleep latency test. Narcolepsy is treated with stimulants, such as modafinil; selective serotonin reuptake inhibitors; or gamma hydroxybutyric acid (sodium oxybate). Patients with snoring and witnessed apneas may have obstructive sleep apnea, which is diagnosed using overnight polysomnography. Continuous positive airway pressure is the most common and effective treatment for obstructive sleep apnea. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in the patient acting out dreams with possible harmful consequences. It is diagnosed based on history and polysomnography findings, and treated with environmental safety measures and melatonin or clonazepam. PMID:23944726

  20. Narcolepsy as an Immune-Mediated Disease

    Directory of Open Access Journals (Sweden)

    Alberto K. De la Herrán-Arita

    2014-01-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  1. The European Narcolepsy Network (EU-NN) database.

    Science.gov (United States)

    Khatami, Ramin; Luca, Gianina; Baumann, Christian R; Bassetti, Claudio L; Bruni, Oliviero; Canellas, Francesca; Dauvilliers, Yves; Del Rio-Villegas, Rafael; Feketeova, Eva; Ferri, Raffaele; Geisler, Peter; Högl, Birgit; Jennum, Poul; Kornum, Birgitte R; Lecendreux, Michel; Martins-da-Silva, Antonio; Mathis, Johannes; Mayer, Geert; Paiva, Teresa; Partinen, Markku; Peraita-Adrados, Rosa; Plazzi, Guiseppe; Santamaria, Joan; Sonka, Karel; Riha, Renata; Tafti, Mehdi; Wierzbicka, Aleksandra; Young, Peter; Lammers, Gert Jan; Overeem, Sebastiaan

    2016-06-01

    Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials. PMID:26809504

  2. CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy

    DEFF Research Database (Denmark)

    De la Herrán-Arita, Alberto K; Kornum, Birgitte Rahbek; Mahlios, Josh;

    2013-01-01

    Narcolepsy, a disorder strongly associated with human leukocyte antigen (HLA)-DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement sleep abnormalities. It is caused by the loss of ~70,000 posterior hypothalamic neurons that produce the...... narcolepsy with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1) to patients with narcolepsy and found an increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin (HA) pHA1 epitope specific to the...... 2009 H1N1 strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4(+) T cells with pH1N1 proteins or pHA1275-287 increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data indicate the presence of CD4(+) T cells that are reactive to HCRT...

  3. Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants.

    Directory of Open Access Journals (Sweden)

    Tohei Yokogawa

    2007-10-01

    Full Text Available Sleep is a fundamental biological process conserved across the animal kingdom. The study of how sleep regulatory networks are conserved is needed to better understand sleep across evolution. We present a detailed description of a sleep state in adult zebrafish characterized by reversible periods of immobility, increased arousal threshold, and place preference. Rest deprivation using gentle electrical stimulation is followed by a sleep rebound, indicating homeostatic regulation. In contrast to mammals and similarly to birds, light suppresses sleep in zebrafish, with no evidence for a sleep rebound. We also identify a null mutation in the sole receptor for the wake-promoting neuropeptide hypocretin (orexin in zebrafish. Fish lacking this receptor demonstrate short and fragmented sleep in the dark, in striking contrast to the excessive sleepiness and cataplexy of narcolepsy in mammals. Consistent with this observation, we find that the hypocretin receptor does not colocalize with known major wake-promoting monoaminergic and cholinergic cell groups in the zebrafish. Instead, it colocalizes with large populations of GABAergic neurons, including a subpopulation of Adra2a-positive GABAergic cells in the anterior hypothalamic area, neurons that could assume a sleep modulatory role. Our study validates the use of zebrafish for the study of sleep and indicates molecular diversity in sleep regulatory networks across vertebrates.

  4. Dopamine D[sub 2]-receptors in human narcolepsy. A SPECT study with [sup 123]I-IB. [Single Photon Emission Computed Tomography. Iodobenzamide

    Energy Technology Data Exchange (ETDEWEB)

    Hublin, C. (Department of Ullanlinna Sleep Research Centre, Kivelae Hospital, Helsinki (Finland)); Launes, J. (Department of Neurology, Helsinki University Central Hospital (Finland)); Nikkinen, P. (Department of Clinical Chemistry, Division of Nuclear Medicine, Helsinki University Central Hospital (Finland)); Partinen, M. (Department of Neurological Unit of Kivelae Hospital, Helsinki (Finland))

    1994-09-01

    Increased dopamine D[sub 2] receptor binding in basal ganglia has been reported in human narcolepsy. These studies have been based on post-mortem material of 8 patients, most of them also medicated for narcolepsy. We studied six narcoleptics without stimulant or anticataplectic medication. The patients had an unambiguous history of cataplexy, and they were also studied polygraphically. Single photon emission computed tomography (SPECT) imaging was performed. The D[sub 2] receptor density wad determined by using [sup 123]I-iodobenzamide (IBZM). The control subjects were 8 unmedicated Parkinson patients with one-sided (hemiparkinsonian) clinical symptoms. The D[sub 2] receptor density in them is known to be normal or somewhat increased compared to healthy normals. The striatum/frontal D[sub 2] activity ratio was 1.331 [+-] 0.084 (with phantom study correction 2.101 [+-] 0.300) in the narcoleptic patients, and in the parkinsonian controls 1.321 [+-] 0.052 (2.067 [+-] 0.185) for the asymptomatic side and 1.335 [+-] 0.025 (2.117 [+-] 0.090) for the symptomatic side (i.e. contralateral to the side with the clinical extrapyramidal signs). There was no statistical difference between the groups or between the symptomatic and asymptomatic side in the Parkinson patients. Thus, our results differ from the earlier post-mortem studies. (au) (28 refs.).

  5. Dopamine D2-receptors in human narcolepsy. A SPECT study with 123I-IB

    International Nuclear Information System (INIS)

    Increased dopamine D2 receptor binding in basal ganglia has been reported in human narcolepsy. These studies have been based on post-mortem material of 8 patients, most of them also medicated for narcolepsy. We studied six narcoleptics without stimulant or anticataplectic medication. The patients had an unambiguous history of cataplexy, and they were also studied polygraphically. Single photon emission computed tomography (SPECT) imaging was performed. The D2 receptor density wad determined by using 123I-iodobenzamide (IBZM). The control subjects were 8 unmedicated Parkinson patients with one-sided (hemiparkinsonian) clinical symptoms. The D2 receptor density in them is known to be normal or somewhat increased compared to healthy normals. The striatum/frontal D2 activity ratio was 1.331 ± 0.084 (with phantom study correction 2.101 ± 0.300) in the narcoleptic patients, and in the parkinsonian controls 1.321 ± 0.052 (2.067 ± 0.185) for the asymptomatic side and 1.335 ± 0.025 (2.117 ± 0.090) for the symptomatic side (i.e. contralateral to the side with the clinical extrapyramidal signs). There was no statistical difference between the groups or between the symptomatic and asymptomatic side in the Parkinson patients. Thus, our results differ from the earlier post-mortem studies. (au) (28 refs.)

  6. ApoE polymorphisms in narcolepsy

    Directory of Open Access Journals (Sweden)

    Kasten Meike

    2001-08-01

    Full Text Available Summary Background Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset neuronal degeneration in Alzheimer disease and other neurodegenerative diseases as well. Methods To clarify whether the ApoE4 phenotype predisposes to narcolepsy or associates with an earlier disease onset, we have genotyped the ApoE gene in 103 patients with narcolepsy and 101 healthy controls. Results The frequency of the E4 allele of the ApoE gene was 11% in the patient and 15% in the control groups. Furthermore, the mean age of onset did not differ between the ApoE4+ and ApoE4- patient groups. Conclusion Our results exclude the ApoE4 allele as a major risk factor for narcolepsy.

  7. Diretrizes brasileiras para o tratamento da narcolepsia Brazilian guidelines for the treatment of narcolepsy

    Directory of Open Access Journals (Sweden)

    Flávio Alóe

    2010-09-01

    -controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

  8. Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

    Science.gov (United States)

    2016-09-01

    Rare Disorders; Undiagnosed Disorders; Disorders of Unknown Prevalence; Cornelia De Lange Syndrome; Prenatal Benign Hypophosphatasia; Perinatal Lethal Hypophosphatasia; Odontohypophosphatasia; Adult Hypophosphatasia; Childhood-onset Hypophosphatasia; Infantile Hypophosphatasia; Hypophosphatasia; Kabuki Syndrome; Bohring-Opitz Syndrome; Narcolepsy Without Cataplexy; Narcolepsy-cataplexy; Hypersomnolence Disorder; Idiopathic Hypersomnia Without Long Sleep Time; Idiopathic Hypersomnia With Long Sleep Time; Idiopathic Hypersomnia; Kleine-Levin Syndrome; Kawasaki Disease; Leiomyosarcoma; Leiomyosarcoma of the Corpus Uteri; Leiomyosarcoma of the Cervix Uteri; Leiomyosarcoma of Small Intestine; Acquired Myasthenia Gravis; Addison Disease; Hyperacusis (Hyperacousis); Juvenile Myasthenia Gravis; Transient Neonatal Myasthenia Gravis; Williams Syndrome; Lyme Disease; Myasthenia Gravis; Marinesco Sjogren Syndrome(Marinesco-Sjogren Syndrome); Isolated Klippel-Feil Syndrome; Frasier Syndrome; Denys-Drash Syndrome; Beckwith-Wiedemann Syndrome; Emanuel Syndrome; Isolated Aniridia; Beckwith-Wiedemann Syndrome Due to Paternal Uniparental Disomy of Chromosome 11; Beckwith-Wiedemann Syndrome Due to Imprinting Defect of 11p15; Beckwith-Wiedemann Syndrome Due to 11p15 Translocation/Inversion; Beckwith-Wiedemann Syndrome Due to 11p15 Microduplication; Beckwith-Wiedemann Syndrome Due to 11p15 Microdeletion; Axenfeld-Rieger Syndrome; Aniridia-intellectual Disability Syndrome; Aniridia - Renal Agenesis - Psychomotor Retardation; Aniridia - Ptosis - Intellectual Disability - Familial Obesity; Aniridia - Cerebellar Ataxia - Intellectual Disability; Aniridia - Absent Patella; Aniridia; Peters Anomaly - Cataract; Peters Anomaly; Potocki-Shaffer Syndrome; Silver-Russell Syndrome Due to Maternal Uniparental Disomy of Chromosome 11; Silver-Russell Syndrome Due to Imprinting Defect of 11p15; Silver-Russell Syndrome Due to 11p15 Microduplication; Syndromic Aniridia; WAGR Syndrome; Wolf

  9. Lorsqu’un cas de narcolepsie met à l’épreuve la lutte antidopage When narcolepsy challenges anti-doping programs. Time of controversy as a reconfiguration of argumentation processes

    Directory of Open Access Journals (Sweden)

    Julie Demeslay

    2012-06-01

    Full Text Available Cycliste professionnel depuis plusieurs années, Franck Bouyer voit son quotidien changer en 2003, quand il apprend qu’il est atteint du syndrome de Gélineau. Cette maladie contraint le sportif à prendre tous les jours un traitement stimulant pour stopper la répétition de crises de narcolepsie, de cataplexie et d’hallucinations dont il est victime. Toutefois, le médicament qui lui permet de retrouver un état physiologique « normal » est répertorié par l’Agence mondiale antidopage parmi les produits interdits en compétition. Dans le cadre du processus naissant d’harmonisation des procédures de lutte contre le dopage, il apparaît alors que la réalité de son métier et celle de sa maladie ne sont plus en adéquation. Les demandes d’Autorisations d’usage à des fins thérapeutiques formulées par le sportif donnent à lire une dispute dont la clôture est singulière et provisoire. L’article aborde la manière dont se transforme et se reconfigure cette dispute, qui bascule au fil du temps dans le régime de la controverse puis celui de l’affaire, mais il rend compte aussi des logiques d’actions, des jeux d’acteurs et d’arguments déployés pour juger de la suite à donner à la carrière professionnelle du cycliste.As a professional cyclist with a long career, Franck Bouyer saw his life change in 2003 when he learned that he was suffering from Gelineau’s syndrome. The disease forced the athlete to take a stimulating treatment every day to stop the recurrence of attacks of narcolepsy, cataplexy and hallucinations. However, the medicine which allows him to experience a “normal” physiological state is listed with the World Anti-Doping Agency among prohibited substances in competition. As part of the emerging process of harmonization of procedures for the fight against doping, an inadequacy appears between the realities of his job and his disease. His requests for Therapeutic Use Exemptions, in order to be

  10. Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy

    Directory of Open Access Journals (Sweden)

    Yves A Dauvilliers

    2014-06-01

    Full Text Available Objective: To examine relationships between cerebrospinal fluid (CSF Alzheimer’ disease (AD biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC, estimate diagnostic accuracy, and determine correlations with sleep disturbances. Background: Sleep disturbances are frequent in AD. Interactions between brain β-amyloid (Aβ aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD. Methods: Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment – MCI that converts to AD, 38 other dementias and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF A42, total tau, ptau181, and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients. Results: Lower CSF Aβ42 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD compared to other dementias, with a similar tendency for patients with advanced AD. CSF hypocretin-1 was significantly and independently associated with AD/MCI due to AD, with an OR of 2.70 after full adjustment, exceeding that for Aβ42. Aβ42 correlated positively with hypocretin-1 levels in advanced stage AD. No association was found between sleep disturbances and CSF biomarkers. No patients with NC achieved pathological cutoffs for Aβ42, with respectively one and four patients with NC above tau and P-tau cutoffs and no correlations between hypocretin-1 and other biomarkers. Conclusions: Our results suggest a pathophysiological relationship between Aβ42 and hypocretin-1 in the AD process, with higher CSF hypocretin-1 levels in early disease stages. Further longitudinal studies are needed to validate these biomarker interactions and to determine the cause-effect relationship and the role of wake/sleep behavior in amyloid

  11. Profile of suvorexant in the management of insomnia.

    Science.gov (United States)

    Sutton, Eliza L

    2015-01-01

    Suvorexant, approved in late 2014 in the United States and Japan for the treatment of insomnia characterized by difficulty achieving and/or maintaining sleep, is a dual orexin receptor antagonist and the first drug in its class to reach the market. Its development followed from the 1998 discovery of orexins (also called hypocretins), excitatory neuropeptides originating from neurons in the hypothalamus involved in regulation of sleep and wake, feeding behavior and energy regulation, motor activity, and reward-seeking behavior. Suvorexant objectively improves sleep, shortening the time to achieve persistent sleep and reducing wake after sleep onset, although at approved doses (≤20 mg) the benefit was subjectively assessed as modest. Its half-life of 12 hours is relatively long for a modern hypnotic; however, at approved doses (≤20 mg) next-day sedation and driving impairment were much less apparent than at higher doses. Suvorexant is metabolized by the hepatic CYP3A system and should be avoided in combination with strong CYP3A inhibitors. Drug levels are higher in women and obese people; hence, dosing should be conservative in obese women. Administration with food delays drug absorption and is not advised. No dose adjustment is needed for advanced age, renal impairment, or mild-to-moderate hepatic impairment. Suvorexant in contraindicated in narcolepsy and has not been studied in children. In alignment with the changes begun in 2013 in the labeling of other hypnotics, the United States Food and Drug Administration advises that the lowest dose effective to treat symptoms be used and that patients be advised of the possibility of next-day impairment in function, including driving. Infrequent but notable side effects included abnormal dreams, sleep paralysis, and suicidal ideation that were dose-related and reported to be mild. Given its mechanism of action, cataplexy and rapid eye movement (REM) sleep behavior disorder could potentially occur in some patients

  12. Halothane-induced Hypnosis Is Not Accompanied by Inactivation of Orexinergic Output in Rodents

    Science.gov (United States)

    Gompf, Heinrich; Chen, Jingqiu; Sun, Yi; Yanagisawa, Masashi; Aston-Jones, Gary; Kelz, Max B.

    2009-01-01

    Background One underexploited property of anesthetics is their ability to probe neuronal regulation of arousal. At appropriate doses, anesthetics reversibly obtund conscious perception. However, individual anesthetic agents may accomplish this by altering the function of distinct neuronal populations. Previously we showed that isoflurane and sevoflurane inhibit orexinergic neurons, delaying reintegration of sensory perception as denoted by emergence. Herein we study the effects of halothane. As a halogenated alkane, halothane differs structurally, has a nonoverlapping series of molecular binding partners, and differentially modulates electrophysiologic properties of several ion channels when compared with its halogenated ether relatives. Methods c-Fos immunohistochemistry and in vivo electrophysiology were used to assess neuronal activity. Anesthetic induction and emergence were determined behaviorally in narcoleptic orexin/ataxin-3 mice and control siblings exposed to halothane. Results Halothane-induced hypnosis occurred despite lack of inhibition of orexinergic neurons in mice. In rats, extracellular single-unit recordings within the locus coeruleus showed significantly greater activity during halothane than during a comparable dose of isoflurane. Microinjection of the orexin-1 receptor antagonist, SB-334867-A during the active period slowed firing rates of locus coeruleus neurons in halothane-anesthetized rats, but had no effect on isoflurane-anesthetized rats. Surprisingly, orexin/ataxin-3 transgenic mice, which develop narcolepsy with cataplexy due to loss of orexinergic neurons, did not show delayed emergence from halothane. Conclusion Coordinated inhibition of hypothalamic orexinergic and locus coeruleus noradrenergic neurons is not required for anesthetic induction. Normal emergence from halothane-induced hypnosis in orexin-deficient mice suggests that additional wake-promoting systems likely remain active during general anesthesia produced by halothane

  13. Use of miglustat in a child with late-infantile-onset Niemann-Pick disease type C and frequent seizures: a case report

    Directory of Open Access Journals (Sweden)

    Skorpen Johannes

    2012-11-01

    Full Text Available Abstract Introduction Niemann-Pick disease type C is a rare genetic lysosomal storage disease associated with impaired intracellular lipid trafficking and a range of progressive neurological manifestations. The influence of seizure activity on disease course and response to miglustat therapy is not currently clear. Case presentation Niemann-Pick disease type C homozygous for NPC1 mutation p.S940L [c. 2819 C>T] was diagnosed in a four-and-a-half-year-old Norwegian Caucasian girl. The patient, who died at eight years and seven months of age, had a history of prolonged neonatal jaundice and subsequently displayed progressive neurological manifestations that started with delayed speech, ataxia, and gelastic cataplexy. A regimen of 100mg of miglustat three times a day was initiated when she was four years and 11 months old. She showed decreased neurological deterioration during about three and a half years of treatment. However, she displayed periods of distinct worsening that coincided with frequent epileptic seizures. Anti-epileptic therapy reduced seizure frequency and severity and allowed re-stabilization of her neurological function. Prior to her death, which was possibly due to acute cardiac arrest, seizure activity was well controlled. Conclusions Miglustat delayed the expected deterioration of neurological function in this patient with p.S940L-homozygous late-infantile-onset Niemann-Pick disease type C and provided important quality-of-life benefits. This case demonstrates the importance of effective seizure control therapy in achieving and maintaining neurological stabilization in Niemann-Pick disease type C.

  14. Elevated peripheral visfatin levels in narcoleptic patients.

    Directory of Open Access Journals (Sweden)

    Norbert Dahmen

    Full Text Available OBJECTIVE: Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF. Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients. METHODS: For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females with the diagnosis of narcolepsy according to DSM-IV and the International Classification of Sleep Disorders were examined (BMI mean 30.3+/-5.5, age mean 52.5+/-16.1 years. As a control group 39 unrelated (n = 12 males and n = 27 females healthy volunteers with no sleep disorder according to DSM-IV were included (BMI mean 28.5+/-4.6, age mean 51.1+/-13.6 years. Peripheral visfatin levels were measured using a commercial enzyme immunoassay kit with a measurement range from 0.1-1000 ng/ml. Narcolepsy symptoms, severity and frequency of symptoms as well as the total duration of various aspects of the symptomatology were assessed by unstructured and structured clinical interviews in including the Stanford Center for Narcolepsy Sleep Inventory. RESULTS: Circulating visfatin was found to be significantly increased in HLA DR2 positive narcoleptic patients compared to controls. CONCLUSION: Taken together, our results add to the evidence of disturbed immunological regulation in patients with narcolepsy.

  15. Hypocretinergic and non-hypocretinergic projections from the hypothalamus to the REM sleep executive area of the pons.

    Science.gov (United States)

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H

    2013-01-23

    Within the postero-lateral hypothalamus neurons that utilize hypocretin or melanin-concentrating hormone (MCH) as neuromodulators are co-distributed. These neurons have been involved in the control of behavioral states, and a deficit in the hypocretinergic system is the pathogenic basis of narcolepsy with cataplexy. In this report, utilizing immunohistochemistry and retrograde tracing techniques, we examined the hypocretinergic innervation of the nucleus pontis oralis (NPO), which is the executive site that is responsible for the generation of REM sleep in the cat. The retrograde tracer cholera toxin subunit b (CTb) was administered in pontine regions where carbachol microinjections induced REM sleep. Utilizing immunohistochemical techniques, we found that approximately 1% of hypocretinergic neurons in the tuberal area of the hypothalamus project to the NPO. In addition, approximately 6% of all CTb+ neurons in this region were hypocretinergic. The hypocretinergic innervation of the NPO was also compared with the innervation of the same site by MCH-containing neurons. More than three times as many MCHergic neurons were found to project to the NPO compared with hypocretinergic cells; both neuronal types exhibited bilateral projections. We also identified a group of non-hypocretinergic non-MCHergic neuronal group of neurons that were intermingled with both hypocretinergic and MCHergic neurons that also projected to this same brainstem region. These neurons were grater in number that either hypocretin or MCH-containing neurons; their soma size was also smaller and their projections were mainly ipsilateral. The present anatomical data suggest that hypocretinergic, MCHergic and an unidentified companion group of neurons of the postero-lateral hypothalamus participate in the regulation of the neuronal activity of NPO neurons, and therefore, are likely to participate in the control of wakefulness and REM sleep. PMID:23122879

  16. Hypocretinergic control of spinal cord motoneurons.

    Science.gov (United States)

    Yamuy, Jack; Fung, Simon J; Xi, Mingchu; Chase, Michael H

    2004-06-01

    -induced facilitation of motoneurons may be a critical component of the pathophysiology of cataplexy. PMID:15190106

  17. Catechol-O-methyltransferase, dopamine, and sleep-wake regulation.

    Science.gov (United States)

    Dauvilliers, Yves; Tafti, Mehdi; Landolt, Hans Peter

    2015-08-01

    Sleep and sleep disorders are complex and highly variable phenotypes regulated by many genes and environment. The catechol-O-methyltransferase (COMT) gene is an interesting candidate, being one of the major mammalian enzymes involved in the catabolism of catecholamines. The activity of COMT enzyme is genetically polymorphic due to a guanine-to-adenine transition at codon 158, resulting in a valine (Val) to methionine (Met) substitution. Individuals homozygous for the Val allele show higher COMT activity, and lower dopaminergic signaling in prefrontal cortex (PFC) than subjects homozygous for the Met allele. Since COMT has a crucial role in metabolising dopamine, it was suggested that the common functional polymorphism in the COMT gene impacts on cognitive function related to PFC, sleep-wake regulation, and potentially on sleep pathologies. The COMT Val158Met polymorphism may predict inter-individual differences in brain electroencephalography (EEG) alpha oscillations and recovery processes resulting from partial sleep loss in healthy individuals. The Val158Met polymorphism also exerts a sexual dimorphism and has a strong effect on objective daytime sleepiness in patients with narcolepsy-cataplexy. Since the COMT enzyme inactivates catecholamines, it was hypothesized that the response to stimulant drugs differs between COMT genotypes. Modafinil maintained executive functioning performance and vigilant attention throughout sleep deprivation in subjects with Val/Val genotype, but less in those with Met/Met genotype. Also, homozygous Met/Met patients with narcolepsy responded to lower doses of modafinil compared to Val/Val carriers. We review here the critical role of the common functional COMT gene polymorphism, COMT enzyme activity, and the prefrontal dopamine levels in the regulation of sleep and wakefulness in normal subjects, in narcolepsy and other sleep-related disorders, and its impact on the response to psychostimulants. PMID:25466290

  18. Brain imaging studies of sleep disorder

    International Nuclear Information System (INIS)

    Brain imaging studies of narcolepsy (NA)/cataplexy (CA), a typical sleep disorder, are summarized together with techniques of functional and structural imaging means. single photon emission CT (SPECT) is based on the distribution of tracers labeled by single photon emitters like 99mTc and 123I for seeing the blood flow and receptors. PET using positron emitters like 15O and 18F for blood flow and for glucose metabolism, respectively, is of higher resolution and more quantitative than SPECT. Functional MRI (fMRI) depicts the cerebral activity through signal difference by blood oxygenation level dependence (BOLD) effect, and MR spectroscopy (MRS) depicts and quantifies biomaterials through the difference of their nuclear chemical shifts in the magnetic field. Morphologic imaging studies involve the measurement of the volume of the region of interest by comparison with the reference region such as the whole brain volume. Voxel-based morphometry (VBM) has changed to its more advanced surface-based analysis (SBA) of T1-enhanced image. Diffusion tensor imaging (DTI) is based on the tissue water diffusion. Functional SPECT/PET studies have suggested the decrease of blood flow and metabolic activity in the hypothalamus (HT) and other related regions at the conscious resting state, and locally increased blood flow in cingulate gyrus (CG) and amygdaloid complex (AC) at affective CA/PA seizure. fMRI has suggested the hypoactivity of HT and hyperactivity of AC at the seizure. VBM-based studies have not given the consistent results, but DTI studies have suggested an important participation of AC at the seizure. (T.T.)

  19. [A case of narcolepsy with increased cataplectic attacks after suffering from cerebrovascular disease].

    Science.gov (United States)

    Miura, H; Nakajima, S; Nakamura, H; Ichinowatari, N

    1990-06-01

    It is well known that narcoleptic patients have DR2 and DQw-1 on HLA typing. The development of narcolepsy is considered to depend on the two factors; genetic predispositions and exogenous factors such as head trauma, encephalitis, etc., mainly affecting the brainstem or diencephalon. We reported a 46-year-old man who had occasional sleep attacks after suffering from left thalamic hemorrhage and pontine vascular disorders. Rehabilitation was markedly disturbed due to frequent episodes of cataplectic attacks which was triggered by emotional lability such as laughing, anxiety, and excitement. HLA type examination showed both DR-2 and DQw-1 loci in the proband and his four other siblings. His elder brother also suffered from mild excessive daytime sleepiness during his younger age, but it subsided gradually. Analysis of overnight polysomnography in the patient revealed remarkable paradoxical alpha-blocking and frequent sleep onset REM stages as typically observed in narcoleptic patients. MRI examination showed multiple small hemorrhages and infarctions in the pontine tegmentum, in addition to the left thalamic hemorrhage and multiple subcortical ischemic lesions. Concerning the mechanism of frequent cataplexy in this patient, it is postulated that increased emotional incontinence might have stimulated the descending reticular system in the brainstem which in turn may inhibit anterior horn motor cell activities. Methylphenidate was initially given to the patient, resulting in some relief of attacks, and addition of imipramine dramatically suppressed cataplectic attacks. Imipramine is considered to inhibit the excitatory afferent pathway to the brainstem suppressing the hyperactivity of descending motor inhibitory system due to its anti-muscarinergic action. PMID:2225662

  20. Sleep-stage sequencing of sleep-onset REM periods in MSLT predicts treatment response in patients with narcolepsy.

    Science.gov (United States)

    Drakatos, Panagis; Patel, Kishankumar; Thakrar, Chiraag; Williams, Adrian J; Kent, Brian D; Leschziner, Guy D

    2016-04-01

    Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2. PMID:26541241

  1. Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

    Directory of Open Access Journals (Sweden)

    Mignot Emmanuel

    2007-05-01

    Full Text Available Abstract Background Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT and in dogs with a mutation in hypocretin receptor 2 (HCRTR2. However, little is known about molecular alterations downstream of the hypocretin signals. Results By using microarray technology we have screened the expression of 29760 genes in the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for the canarc-1 [HCRTR-2-2] mutation, and their unaffected heterozygous siblings. We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1 and Proenkephalin (PENK, that together with Suppressor of cytokine signaling 2 (SOCS2, showed reduced expression in narcoleptic brains. The difference was particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2 showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results obtained from microarray experiments were confirmed by real-time RT-PCR. Interestingly, it was previously shown that a single dose of amphetamine-like stimulants able to increase wakefulness in the dogs, also produce an increase in the expression of both TAC1 and PENK in mice. Conclusion These results suggest that TAC1, PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans.

  2. Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Taku Miyagawa

    Full Text Available UNLABELLED: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM sleep abnormalities. A genome-wide association study (GWAS identified a novel narcolepsy-related single nucleotide polymorphism (SNP, which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02. L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN UMIN000003760.

  3. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism

    Directory of Open Access Journals (Sweden)

    Christine eDugovic

    2014-02-01

    Full Text Available In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R and orexin-2 (OX2R receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM and REM sleep following oral dosing (10 and 30 mg/kg at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion. When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic.

  4. Profile of suvorexant in the management of insomnia

    Directory of Open Access Journals (Sweden)

    Sutton EL

    2015-11-01

    action, cataplexy and rapid eye movement (REM sleep behavior disorder could potentially occur in some patients taking this medication. Keywords: insomnia, hypnotic, dual orexin receptor antagonist, orexin, hypocretin 

  5. 103例儿童发作性睡病的临床特点及随访%Respective Analysis of 103 Children with Narcolepsy

    Institute of Scientific and Technical Information of China (English)

    尹悦; 刘肖予; 苗硕; 杨健

    2015-01-01

    Objective To conclude clinical manifestations and treatment in children with narcolepsy.Methods The clinical data of 103 narcolepsy children,which were diagnosed by the in-patient department of pediatrics of the Capital Institute of Pediatrics from January of 2011 to August of 2014 and were analyzed retrospectively.Based on the documentaries home and a-broad,we telephoned follow up these children and make a retrospective analysis.Results Excessive daytime sleepiness appeared in all cases,cataplexy in 27 cases,sleep paralysis in 1 cases,hypnogogic hallucinations in 2 cases.85 patients available and total remission rate is 88.24%.Conclusion sleep paralysis and hypnogogic hallucinations could not be obviously observed,Applica-tion of methylphenidate and health education could get good effects.%目的:总结儿童发作性睡病的临床特点及治疗愈后。方法回顾分析2011年01月至2014年8月首都儿科研究所神经内科主要诊断为发作性睡病的103例病案资料及电话随访结果。结果103例患儿全部现日间睡眠过多症状,27例患儿有明显猝倒表现,1例现睡眠瘫痪,2例现睡眠幻觉。可随访到的85例患儿中47例病情缓解,28例痊愈,其中66例应用盐酸哌甲酯治疗。结论我院观察的儿童发作性睡病患者四联征表现并不明显,药物治疗及非药物治疗控制疾病进展良好。

  6. Narcolepsy and depression Narcolepsia e depressão

    Directory of Open Access Journals (Sweden)

    Carla Adda

    1997-09-01

    Full Text Available Narcolepsy main symptoms include excessive daytime sleepiness and cataplexy. Its chronic course is accompanied by psychosocial impairment added to the difficulties and side effects of stimulants and tricyclics long term use. Depressive complaints are occasionally reported. The aim of this paper was to evaluate objectively the possibility of depression in a sample of 12 narcoleptics (7F;5 M, with mean age of 53 years (12 years SD, using the Beck Depression Inventory (BDI and the Hamilton Rating Scale for Depression (HAM-D. The results showed absence of depressive disorder in 75.0% of the cases according to BDI (or 58.3% according to HAM-D. The remaining patients had mild depression (only one patient presented major depression. The findings showed no correlation between narcolepsy and major depression.Narcolepsia é um distúrbio do sono caracterizado por sonolência diurna excessiva e ataques de cataplexia. Sendo crônico, traz uma série de dificuldades psicossociais às quais se aliam aquelas geradas pelos efeitos colaterais dos estimulantes e tricíclicos utilizados. Queixas depressivas são encontradas ocasionalmente. Esta pesquisa buscou verificar objetivamente a ocorrência de depressão em narcolépticos. Foi avaliado um grupo de 12 pacientes narcolépticos (7F; 5M com média de idade de 53 anos (DP 12 usando-se como instrumentos o Inventário de Beck para Depressão (BDI e a Escala Hamilton de Depressão (HAM-D. Os resultados demonstraram ausência de distúrbio depressivo em 75.0% dos pacientes avaliados pelo BDI e em 58.3% pela HAM-D. Os demais escores evidenciaram depressão leve ou disforia; depressão maior foi encontrada em apenas um caso. Tais achados não sugerem correlação entre narcolepsia e depressão.

  7. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism.

    Science.gov (United States)

    Dugovic, Christine; Shelton, Jonathan E; Yun, Sujin; Bonaventure, Pascal; Shireman, Brock T; Lovenberg, Timothy W

    2014-01-01

    In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R) and orexin-2 (OX2R) receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM) sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM) and REM sleep following oral dosing (10 and 30 mg/kg) at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion). When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg) increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg) did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic. PMID:24592208

  8. Determination of GHB levels in breast milk and correlation with blood concentrations.

    Science.gov (United States)

    Busardò, Francesco Paolo; Bertol, Elisabetta; Mannocchi, Giulio; Tittarelli, Roberta; Pantano, Flaminia; Vaiano, Fabio; Baglio, Giovanni; Kyriakou, Chrystalla; Marinelli, Enrico

    2016-08-01

    The sodium salt of GHB or sodium oxybate is approved and registered in some countries as a therapeutic substance (Xyrem(®)) for the treatment of narcolepsy-associated cataplexy. This study was designed to measure the GHB endogenous levels in blood and breast milk of 20 breastfeeding women. In addition, blood and breast milk samples of a 32-year-old narcoleptic nursing mother, who was on sodium oxybate treatment, were simultaneously collected at 0.5, 1, 3, 4 and 5h following a 4.5g GHB dose and analyzed, in order to establish the safety interval of time to breastfeed. A GC-MS method for the detection and quantification of GHB in blood and breast milk was developed and fully validated. The geometric mean of endogenous GHB levels in blood and breast milk detected at time 0 were 0.57mg/L; 95% Reference Interval (RI): 0.21-1.52mg/L and 0.36mg/L; 95% RI: 0.13-1.03mg/L, respectively. The geometric mean of the concentration of GHB in milk was 37% less (95% RI: from 14 to 53%) compared to that found in the blood. The analysis of blood and breast milk samples collected from the 32 years-old female showed the following results: GHB blood concentration 0.5h after medication intake was 80.10mg/L, reaching the peak 1h after the drug administration (108.34mg/L) and it steadily decreased to reach a level of 1.75mg/L, 5h after the medication intake. The GHB concentration found in breast milk followed the same pattern as for the blood, with the highest concentration being 23.19mg/L, 1h after sodium oxybate administration and the lowest 0.99mg/L, 5h after the medication's intake. The comparison between blood and breast milk GHB levels in the 32-year-old woman, showed significant lower GHB levels in milk at 0.5, 1 and 3h, ranging from 71 to 80% less. It is interesting to note that only at 4 and 5h the difference between blood and breast milk GHB levels fell within the 95% RI (14-53%) of endogenous levels. Taking into consideration the absence of reference values for endogenous GHB in

  9. Approved and investigational uses of modafinil : an evidence-based review.

    Science.gov (United States)

    Kumar, Raminder

    2008-01-01

    Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A

  10. 盐酸托莫西汀治疗儿童发作性睡病66例临床观察%Clinical effect of atomoxetine hydrochloride in 66 children with narcolepsy

    Institute of Scientific and Technical Information of China (English)

    张珅; 丁昌红; 吴沪生; 方方; 王晓慧; 任晓暾

    2015-01-01

    Objective To observe the efficacy and safety of atomoxetine hydrochloride in children with narcolepsy.Method Totally 66 patients with narcolepsy who were conformed international classification of sleep disturbances (ICSD-2) diagnostic criteria treated with atomoxetine hydrochloride seen from November 2010 to December 2014 were enrolled into this study,42 of them were male and 24 female,mean age of onset was 7.5 years (3.75-13.00 years),mean duration before diagnosis was 1.75 years (0.25-5.00 years).Complete blood count,liver and kidney function,multiple sleep latency test (MSLT),polysomnography(PGS),neuroimaging and electroencephalography (EEG) were performed for each patient.For some of the children HLA-DR2 gene and serum markers of infection were tested.The 66 cases were followed up from 2 to 49 months (average 18 months) to observe the clinical efficacy and adverse reactions.Results In 62 cases excessive daytime sleepiness was improved,in 11 cases (16.7%) it was controlled (16.7%),in 29 cases (43.9%)the treatment was obviously effective and in 22 (33.3 %) it was effective;cataplexy occurred in 54 cases,in 18 (33.3%) it was controlled,in 19 (35.2%) the treatment was obviously effective and in 10(18.5%) effective;night sleep disorders existed in 55 cases,in 47 cases it was improved,in 14(25.5%) it was controlled,in 20 (36.4%)the treatment was obviously effective and in 13 (23.6%)effective;hypnagogic or hypnopompic hallucination was present in 13 cases,in only 4 these symptoms were controlled.Sleep paralysis existed in 4 cases,it was controlled in only 1 case.In 18 cases attention and learning efficiency improved.Anorexia occurred in 18 cases,mood disorder in 5 cases,depression in 2 cases,nocturia,muscle tremors,involuntary tongue movement each occurred in 1 case.P-R interval prolongation and atrial premature contraction were found in 1 case.Conclusion Atomoxetine hydrochloride showed good effects in patients with narcolepsy on excessive daytime