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Correlations between subjective and objective features of nocturnal sleep and excessive diurnal sleepiness in patients with narcolepsy
Jiménez-Correa, Ulises;Haro, Reyes;Obdulia González, Rosa;Velázquez-Moctezuma, Javier;
Arquivos de Neuro-Psiquiatria , 2009, DOI: 10.1590/S0004-282X2009000600006
Abstract: objective: to determine the correlations between excessive daytime sleepiness (eds), assessed by the epworth sleepiness scale (ess), and the multiple sleep latency test (mslt) and nocturnal sleep architecture features, clinical symptoms of narcolepsy (csn) and subjective sleep quality (ssq) in patients with narcolepsy. method: twenty three untreated patients were studied and compared with a matched control group. diagnosis of narcolepsy was carried out employing a clinical interview, a polysomnographic (psg) record, and an mslt. results: subjective number of awakenings was the ssq indicator that best correlated with eds (ess and mslt). regarding clinical features, diurnal tiredness and sleep paralysis correlated with ess values. increase in ess was related with decrease in total sleep time, sws, and sleep onset latency. on the other hand, increase in mslt was related with decrease in sws. conclusion: these data suggest that eds in patients with narcolepsy could be impaired by disturbed nocturnal sleep.
Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls  [PDF]
Jiann Wei Yeoh,Erin J. Campbell,Morgan H. James,Brett A. Graham,Christopher V. Dayas
Frontiers in Neuroscience , 2014, DOI: 10.3389/fnins.2014.00036
Abstract: The tight regulation of sleep/wake states is critical for mental and physiological wellbeing. For example, dysregulation of sleep/wake systems predisposes individuals to metabolic disorders such as obesity and psychiatric problems, including depression. Contributing to this understanding, the last decade has seen significant advances in our appreciation of the complex interactions between brain systems that control the transition between sleep and wake states. Pivotal to our increased understanding of this pathway was the description of a group of neurons in the lateral hypothalamus (LH) that express the neuropeptides orexin A and B (hypocretin, Hcrt-1 and Hcrt-2). Orexin neurons were quickly placed at center stage with the demonstration that loss of normal orexin function is associated with the development of narcolepsy—a condition in which sufferers fail to maintain normal levels of daytime wakefulness. Since these initial seminal findings, much progress has been made in our understanding of the physiology and function of the orexin system. For example, the orexin system has been identified as a key modulator of autonomic and neuroendocrine function, arousal, reward and attention. Notably, studies in animals suggest that dysregulation of orexin function is associated with neuropsychiatric states such as addiction and mood disorders including depression and anxiety. This review discusses the progress associated with therapeutic attempts to restore orexin system function and treat neuropsychiatric conditions such as addiction, depression and anxiety. We also highlight potential pitfalls and challenges associated with targeting this system to treat these neuropsychiatric states.
Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre
Coelho, Fernando Morgadinho Santos;Pradella-Hallinan, Márcia;Pedrazzoli, Mario;Soares, Carlos Augusto Senne;Fernandes, Gustavo Bruniera Peres;Gon?alves, André Leite;Tufik, Sergio;Bittencourt, Lia Rita Azeredo;
Arquivos de Neuro-Psiquiatria , 2010, DOI: 10.1590/S0004-282X2010000500007
Abstract: this study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at s?o 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.
Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in S?o Paulo
Coelho, Fernando Morgadinho Santos;Pradella-Hallinan, Márcia;Predazzoli Neto, Mario;Bittencourt, Lia Rita Azeredo;Tufik, Sérgio;
Revista Brasileira de Psiquiatria , 2009, DOI: 10.1590/S1516-44462009000100004
Abstract: 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 < 0.0001, respectively). conclusions: this finding is in accordance with those of previous studies. the gold standard exam of narcolepsy with cataplexy is hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings. the presence of the hla-dqb1* 0602 allele may be important for the differential diagnosis of situations that resemble those sleep disorders such as secondary changes in sleep structure due to drugs' consumption.
Narcolepsy: a review
Akintomide GS,Rickards H
Neuropsychiatric Disease and Treatment , 2011,
Abstract: 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
The role of orexins/hypocretins in alcohol use and abuse: an appetitive-reward relationship  [PDF]
Robyn M. Brown,Andrew J. Lawrence
Frontiers in Behavioral Neuroscience , 2012, DOI: 10.3389/fnbeh.2012.00078
Abstract: Orexins (hypocretins) are neuropeptides synthesized in neurons located in the lateral (LH), perifornical, and dorsomedial (DMH) hypothalamus. These neurons innervate many regions in the brain and modulate multiple other neurotransmitter systems. As a result of these extensive projections and interactions orexins are involved in numerous functions, such as feeding behavior, neuroendocrine regulation, the sleep-wake cycle, and reward-seeking. This review will summarize the literature to date which has evaluated a role of orexins in the behavioral effects of alcohol, with a focus on understanding the importance of this peptide and its potential as a clinical therapeutic target for alcohol use disorders.
Psychosis in Patients with Narcolepsy as an Adverse Effect of Sodium Oxybate  [PDF]
Tomi Sarkanen,Anne-Marie Landtblom,Markku Partinen
Frontiers in Neurology , 2014, DOI: 10.3389/fneur.2014.00136
Abstract: 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.
Effects of Hypocretin/Orexin Cell Transplantation on Narcoleptic-Like Sleep Behavior in Rats  [PDF]
Oscar Arias-Carrión, Eric Murillo-Rodríguez
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095342
Abstract: The sleep disorder narcolepsy is now considered a neurodegenerative disease because there is a massive loss of neurons containing the neuropeptide hypocretin/orexin (HCRT). In consequence, narcoleptic patients have very low cerebrospinal fluid (CSF) levels of HCRT. Studies in animal models of narcolepsy have shown the neurophysiological role of the HCRT system in the development of this disease. For example, the injection of the neurotoxin named hypocretin-2-saporin (HCRT2/SAP) into the lateral hypothalamus (LH) destroys the HCRT neurons, therefore diminishes the contents of HCRT in the CSF and induces narcoleptic-like behavior in rats. Transplants of various cell types have been used to induce recovery in a variety of neurodegenerative animal models. In models such as Parkinson's disease, cell survival has been shown to be small but satisfactory. Similarly, cell transplantation could be employed to implant grafts of HCRT cells into the LH or even other brain regions to treat narcolepsy. Here, we report for the first time that transplantation of HCRT neurons into the LH of HCRT2/SAP-lesioned rats diminishes narcoleptic-like sleep behavior. Therefore, cell transplantation may provide an effective method to treat narcolepsy.
Neuroimaging of sleep and sleep disorders. A book Review.  [PDF]
Anne-Marie Landtblom
Frontiers in Neurology , 2014, DOI: 10.3389/fneur.2014.00151
Abstract: Neuroimaging of sleep and sleep disorders Edited by Eric Nofzinger, Pierre Maquet and Michael J Thorpy Cambridge medicine, Cambridge University Press 2013 Sleep physiology is a field of increasing importance because the recent awareness of how sleep affects us all, whether it is good or bad. Sleep disorders have a big impact on daily life and functioning, but importantly, also other disorders that are not primarily associated with sleep disturbances. Subsequently several disorders should be investigated and treated for sleep symptoms because these can be frequent. Examples here are Parkinson′s disease with frequent day time sleepiness and insomnia. Also, epilepsy is frequently connected to disturbed night sleep in a complex way: antiepileptic drugs can be sedative, but seizures can also occur at night and disturb the night sleep. A focus on increased sleep health for persons with epilepsy can improve seizure control, and should be included in future follow up of such patients. Of course, the impact of sleep deprivation on driving is a well-known problem that often concerns doctors, for example in common diseases like obstructive sleep apnoea syndrome,OSAS, as well as other chronic conditions, also regarding medications, with an impact on alertness. Naturally sleep effects in healthy persons are of great importance in the society, concerning both safety and quality of life.. Besides medicine, also new fields have emerged that do not primarily link to pathological conditions. The effects of sleep deprivation on economic decision making is such an example of research that reveals how sleep can affect human behaviour. Neuroimaging of Sleep and Sleep Disorders is an outstanding book with high relevance to physicians and researchers interested in this area. It has a background part with introductory sections about Neuroimaging of wakefulness and sleep, Neuroimaging, sleep loss and circadian misalignment and Sleep and memory containing the important imaging modalities such as magnetic resonance imaging ( MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), sonography, magnetization transfer imaging (MTI) and combined EEG and functional magnetic resonance imaging (fMRI). The core chapter thoroughly invents imaging experiences in a large variety of disorders and conditions connected to sleep disturbance: insomnia, depression, schizophrenia, narcolepsy (also including cataplexy as an isolated phenomenon), OSAS, parasomnia, central hypoventilation syndrome, fatal familial insomnia, posttraumatic stress disorder,
Narcolepsy-Cataplexy Syndrome
Trakya Universitesi Tip Fakultesi Dergisi , 2003,
Abstract: Narcolepsy-cataplexy syndrome is characterized by irresistible daytime sleepiness, an abrupt decrease in muscle tone aroused by emotion, sleep paralysis, and hypnagogic hallucinations. This rare syndrome mostly affects males and is usually seen in the second decade. A complex interaction of environmental and genetic factors has been implicated in the etiology; also a close relationship has been demonstrated with some HLA subgroups (HLA DQB1*0602, HLA DR2). Moreover, several studies documented an association with hypocretin deficiency. Clinical findings and polygraphic sleep recordings (nocturnal polysomnogram, multiple sleep latency test) are important in the diagnosis. Central nervous system stimulants such as amphetamine and methylphenidate and somnolytic agents such as modafinil are used in the treatment of narcolepsy, while cataplexy is treated with antidepressants.
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