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Narcolepsy
Selected AbstractsHypocretin/orexin and narcolepsy: new basic and clinical insightsACTA PHYSIOLOGICA, Issue 3 2010S. Nishino Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. 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 humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source] Errata: Narcolepsy with Cataplexy Associated with Holoprosencephaly Misdiagnosed as Epileptic Drop AttacksMOVEMENT DISORDERS, Issue 11 2010G Plazzi No abstract is available for this article. [source] Narcolepsy and other non-SAS hypersomnia in sleep breathing disorders clinicPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2001Katsuhisa Banno MD Abstract Four of the 708 snorers (0.56%), referred to our sleep breathing disorders clinic for the past 2 years were diagnosed as having narcolepsy-cataplexy. Detecting HLA DRB1*1501/DQB1*0602 positive was informative for differentiating genuine narcolepsy from non-sleep apnea syndrome (non-SAS) hypersomnia in our clinic. A non-SAS obese boy, diagnosed as having essential hypersomnia syndrome, was found to be HLA DRB1*1502/DQB1*0601 positive. His hypocretin concentration was 206 pg/mL in the cerebrospinal fluid. [source] Narcolepsy: a brain structural abnormality and more of interest to the anaesthetist!ANAESTHESIA, Issue 1 2009A. P. Hall No abstract is available for this article. [source] Reduced amygdala activity during aversive conditioning in human narcolepsyANNALS OF NEUROLOGY, Issue 3 2010Aurélie Ponz PhD Narcolepsy with cataplexy is a sleep-wake disorder caused by a loss of hypothalamic hypocretins. Here we assessed the time course of amygdala activation during aversive conditioning in unmedicated patients with narcolepsy. Unlike healthy matched control subjects, narcolepsy patients had no enhancement of amygdala response to conditioned stimuli and no increase in functional coupling between the amygdala and medial prefrontal cortex. These findings suggest that human narcolepsy is accompanied by abnormal emotional learning, and that, in line with animal data, the hypocretin system and the amygdala are involved in this process. ANN NEUROL 2010;67:394,398 [source] Prevalence of narcolepsy with cataplexy in NorwayACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009M. S. Heier Objectives,,, Narcolepsy is a lifelong disabling disorder that may be alleviated by relevant treatment. Patients frequently report 10,15 years from the first symptoms to the time they get the diagnosis and treatment can be started. In order to offer a sufficient diagnostic and therapeutic service to this patient group, a reliable estimation of the prevalence of the disorder is important. A study of the prevalence of narcolepsy with cataplexy in Norway was therefore undertaken. Materials and methods,,, The Ullanlinna Narcolepsy scale (UNS) was sent to 14548 randomly selected Norwegians between 20 and 60 years. Additionally, the study included telephone interviews and clinical evaluation of responders with ,14 points on the UNS, and in those with suspected narcolepsy, polygraphic sleep recordings and human leucocyte antigen (HLA)-typing. Results,,, A total of 8992 responders answered the questionnaire (response rate 61.8%), 267 had ,14 points on the UNS, 156 were interviewed and 15 had sleep recordings. In two HLADQB1*0602-positive patients sleep recordings were compatible with narcolepsy. Conclusions,,, The results indicate a prevalence of 0.022% and approximately 1000 patients with narcolepsy with cataplexy in Norway. [source] Hypocretin/orexin and narcolepsy: new basic and clinical insightsACTA PHYSIOLOGICA, Issue 3 2010S. Nishino Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. 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 humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source] Physiological functions of glucose-inhibited neuronesACTA PHYSIOLOGICA, Issue 1 2009D. Burdakov Abstract Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K+ or possibly Cl, channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the ,satiety' hormone leptin and stimulated by the ,hunger' hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels. [source] Misleading hallucinations in unrecognized narcolepsyACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2003A. Sz Objective: To describe psychosis-like hallucinatory states in unrecognized narcolepsy. Method: Two patients with hypnagogic/hypnapompic hallucinations are presented. Results: Both patients had realistic and complex , multi-modal and scenic-daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy. Conclusion: We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication. [source] Nonepileptic Disorders Imitating Generalized Idiopathic EpilepsiesEPILEPSIA, Issue 2005Natalio Fejerman Summary:, Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic,clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages. Table 1. Nonepileptic disorders imitating idiopathic generalized epilepsies [source] Problems associated with switch to modafinil , a novel alerting agent in narcolepsyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2000C. Guilleminault Modafinil is a novel medication recently approved for the treatment of narcolepsy and idiopathic hypersomnia. Commonly, patients had already been prescribed medications for their syndrome. This report outlines difficulties encountered in the clinical practice of switching patients to modafinil. Naïve subjects accepted modafinil best. Subjects withdrawn from amphetamine had the most problems and failure to withdraw. Venlafaxine hydrochloride combined well with modafinil to control cataplectic attacks. Usage of a progressive withdrawal protocol may ease the difficulties observed. [source] Diurnal actigraphy and stimulant efficacy in narcolepsyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2005Dorothy Bruck Abstract The aim of this study was to determine whether wrist actigraphy could be used to assess the daytime effects of stimulant medication in the treatment of narcolepsy. Nine subjects with narcolepsy/cataplexy (medicated and unmedicated) were compared with matched control subjects. Data were collected over 4 days in the subjects' home. It was found that the actigraph variable of Immobility (mean duration of periods of no activity) could be used successfully to differentiate medicated and unmedicated phases, correctly classifying 89% of cases. Narcolepsy subjects differed from controls on Immobility both when medicated and unmedicated. During the unmedicated phase the self-reported nap duration was longer and more naps (3.94,naps) were taken. However, the frequency of naps was still high when medicated (2.43,naps). During the unmedicated phase narcolepsy subjects reported more negative mood states (profile of mood states, POMS) than control subjects. However, with the exception of Vigor, scores on the individual mood factors were within the normal range. Total POMS scores were highly correlated with the actigraphic measure of Movement for both narcolepsy conditions as well as controls, with negative mood associated with less movement. It was concluded that the actigraphy variable of Immobility is sensitive enough to detect treatment effects. The relationship between mood and motor activity warrants further investigation in both clinical and non-clinical populations. Copyright © 2004 John Wiley & Sons, Ltd. [source] Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skillsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010E. GALVIN Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. Results: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05. Conclusion: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills. [source] A Multi-Drug Intoxication Fatality Involving Xyrem® (GHB)JOURNAL OF FORENSIC SCIENCES, Issue 2 2009Brianne E. Akins M.S. Abstract:, Gamma-hydroxybutyrate (GHB) is best known as a recreational depressant drug, whose use has also been implicated in drug facilitated sexual assault cases. It is also available as a therapeutic agent (Xyrem®) used for the treatment of daytime sleepiness or cataplexy associated with narcolepsy. This is a report of a case of a 53-year-old woman undergoing treatment with Xyrem® for narcolepsy. The decedent was also prescribed tramadol, gabapentin, cetirizine, modafinil, carisoprodol, and Xyrem®. Toxicological analysis of the blood revealed GHB 165.6 mg/L, and 90.7 mg/L in the urine. Blood GHB concentrations in the range 156,260 mg/L have been reported to induce moderately sound sleep. The combined use of central nervous system depressant drugs, together with her problematic sleep apnea, and snoring (both contraindications for GHB use) were determined to have caused this subject's death. The manner of death was determined to be accidental. [source] Inhibition of neural activity depletes orexin from rat hypothalamic slice cultureJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2010Shotaro Michinaga Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. © 2009 Wiley-Liss, Inc. [source] Investigation of sleep disordersJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2005MJ Davey Abstract: Polysomnography or sleep study is the main investigation for paediatric sleep disorders. It involves the continuous and simultaneous recording of multiple physiological parameters evaluating sleep and respiration. It is most commonly used to diagnose obstructive sleep apnoea and to monitor nocturnal non-invasive ventilation requirements of children. Its role in other sleep related breathing disorders, narcolepsy and parasomnias is discussed. [source] Enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Ramisetti Nageswara Rao Abstract Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with Rs >1.38 was obtained using a mobile phase containing n -hexane,ethanol,TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals. [source] Medico-legal assessment of disability in narcolepsy: an interobserver reliability studyJOURNAL OF SLEEP RESEARCH, Issue 1 2008FRANCESCA INGRAVALLO Summary Impairment because of narcolepsy strongly limits job performance, but there are no standard criteria to assess disability in people with narcolepsy and a scale of disease severity is still lacking. We explored: (1) the interobserver reliability among Italian Medical Commissions making disability and handicap benefit decisions for people with narcolepsy, searching for correlations between the recognized disability degree and patients' features; (2) the willingness to report patients to the driving licence authority and (3) possible sources of variance in judgement. Fifteen narcoleptic patients were examined by four Medical Commissions in simulated sessions. Raw agreement and interobserver reliability among Commissions were calculated for disability and handicap benefit decisions and for driving licence decisions. Levels of judgement differed on percentage of disability (P < 0.001), severity of handicap (P = 0.0007) and the need to inform the driving licence authority (P = 0.032). Interobserver reliability ranged from Kappa = ,0.10 to 0.35 for disability benefit decision and from Kappa = ,0.26 to 0.36 for handicap benefit decision. The raw agreement on driving licence decision ranged from 73% to 100% (Kappa not calculable). Spearman's correlation between percentages of disability and patients' features showed correlations with age, daytime naps, sleepiness, cataplexy and quality of life. This first interobserver reliability study on social benefit decisions for narcolepsy shows the difficulty of reaching an agreement in this field, mainly because of variance in interpretation of the assessment criteria. The minimum set of indicators of disease severity correlating with patients' self assessments encourages a disability classification of narcolepsy. [source] Cognitive deficits in narcolepsyJOURNAL OF SLEEP RESEARCH, Issue 3 2006A. NAUMANN Summary The aim of the investigations was to explore the nature and the severity of cognitive deficits in narcolepsy patients. In two studies, narcolepsy patients were compared with matched control subjects on a range of attention, memory and executive control tasks. Impairments were only observed on attention and executive function tasks which involved higher demands on inhibition or task management abilities whereas relatively routine memory and attention tasks yielded intact performance in narcolepsy patients. The overall pattern of results indicates an executive control deficit in narcolepsy which might be related to a reduction of available cognitive processing resources because of the need for continuous allocation of resources to monitoring and maintenance of vigilance. [source] CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomniaJOURNAL OF SLEEP RESEARCH, Issue 1 2002TAKASHI KANBAYASHI We measured cerebrospinal fluid (CSF) hypocretin-1 levels in 11 patients with narcolepsy,cataplexy, five with narcolepsy without cataplexy and 12 with idiopathic hypersomnia (IHS). All patients were Japanese. As reported in Caucasian patients, undetectable or very low hypocretin-1 levels were observed in most (9 out of 11) Japanese narcolepsy,cataplexy patients. Our hypocretin-deficient narcoleptics included three prepubertal cases within few months after the disease onset. All nine hypocretin-deficient patients were human leuckocyte antigen (HLA) DR2 positive, while two who had normal CSF hypocretin-1 levels were HLA DR2 negative. In contrast, none of the narcolepsy without cataplexy and IHS subjects had undetectable low levels. Low CSF hypocretin-1 is therefore very specific for HLA DR2 positive narcolepsy,cataplexy, and the deficiency is likely to be established at the early stage of the disease. [source] Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth sleepiness scale: Failure of the MSLT as a gold standardJOURNAL OF SLEEP RESEARCH, Issue 1 2000Murray W. Johns SUMMARY Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean±2 SD or by the 2.5 and 97.5 percentiles. The ,rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests. [source] Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations,MOVEMENT DISORDERS, Issue 13 2009Nadège Limousin MD Abstract Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35,60 years, from seven families) and 11 sex-matched patients with iPD (aged 51,65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent. © 2007 Movement Disorder Society [source] Narcolepsy and other non-SAS hypersomnia in sleep breathing disorders clinicPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2001Katsuhisa Banno MD Abstract Four of the 708 snorers (0.56%), referred to our sleep breathing disorders clinic for the past 2 years were diagnosed as having narcolepsy-cataplexy. Detecting HLA DRB1*1501/DQB1*0602 positive was informative for differentiating genuine narcolepsy from non-sleep apnea syndrome (non-SAS) hypersomnia in our clinic. A non-SAS obese boy, diagnosed as having essential hypersomnia syndrome, was found to be HLA DRB1*1502/DQB1*0601 positive. His hypocretin concentration was 206 pg/mL in the cerebrospinal fluid. [source] Comparison in symptoms between aged and younger patients with narcolepsyPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2001Hisakazu Furuta MD Abstract We investigated the age-related changes in symptoms in narcolepsy. Fifty patients, 65-year-old and over (aged group), were recruited from the National Narcolepsy Registry. Thirty-four patients, younger than 65 (younger group), were selected by random sampling. Although there was no difference in the age of disease onset between the two groups, the age of diagnosis was significantly earlier for the younger group. Methylphenidate was used significantly more in the aged group, and modafinil in the younger group. The aged group had lower total scores on the Ullanlinna Narcolepsy Scale, because the scores for cataplexy were significantly less for the aged group. There was no significant difference in excessive daytime sleepiness between the two groups. [source] Narcoleptic canines display periodic leg movements during sleepPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2001Mutsumi Okura MD Abstract Periodic leg movements during sleep (PLMS) is a high prevalent sleep disorder of unknown etiology. The disease is pharmacologically treated with dopaminergic agonists (i.e. D2/D3 agonists) and opiates. Periodic leg movements during sleep often occur in narcoleptic patients. We observed that narcoleptic canines, like narcoleptic humans, also exhibit jerky, unilateral or bilateral slow leg movements during sleep. The movements in dogs are characterized by repetitive dorsiflexions of the ankle, lasting 0.5,1.5 s, and occur at regular intervals of 3,20 s, thus showing similarities to PLMS in humans. The observation that D2/D3 agonists aggravate cataplexy in narcoleptic dogs suggests that altered dopaminergic regulation in canine narcolepsy may play a critical role in both cataplexy and PLMS. Our canines may therefore be an invaluable resource in PLMS research. [source] Differences in electroencephalogram power densities between genuine narcolepsy and secondary narcolepsyPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2000Hiroshi Honma MD Abstract Diagnosing narcolepsy is not always simple. Some patients secondarily show narcoleptic tetrad through irregular sleep patterns or psychotic diseases. The power densities of daytime electroencephalograms in genuine narcolepsy and secondary narcolepsy were analysed and compared. Electroencephalogram power densities for a 6.5-h period after waking in genuine narcoleptic patients were lower than those of secondary narcoleptic patients in the 11.0,12.5 Hz bands. Arousal levels may be lower in genuine narcoleptic patients than in secondary narcoleptic patients. Spectral analysis may be useful in clarifying differences between the two groups. [source] Homeostatic, circadian, and emotional regulation of sleepTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2005Clifford B. Saper Abstract A good night's sleep is one of life's most satisfying experiences, while sleeplessness is stressful and causes cognitive impairment. Yet the mechanisms that regulate the ability to sleep have only recently been subjected to detailed investigation. New studies show that the control of wake and sleep emerges from the interaction of cell groups that cause arousal with other nuclei that induce sleep such as the ventrolateral preoptic nucleus (VLPO). The VLPO inhibits the ascending arousal regions and is in turn inhibited by them, thus forming a mutually inhibitory system resembling what electrical engineers call a "flip-flop switch." This switch may help produce sharp transitions between discrete behavioral states, but it is not necessarily stable. The orexin neurons in the lateral hypothalamus may help stabilize this system by exciting arousal regions during wakefulness, preventing unwanted transitions between wakefulness and sleep. The importance of this stabilizing role is apparent in narcolepsy, in which an absence of the orexin neurons causes numerous, unintended transitions in and out of sleep and allows fragments of REM sleep to intrude into wakefulness. These influences on the sleep/wake system by homeostatic and circadian drives, as well as emotional inputs, are reviewed. Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep. J. Comp. Neurol. 493:92,98, 2005. © 2005 Wiley-Liss, Inc. [source] Reduced amygdala activity during aversive conditioning in human narcolepsyANNALS OF NEUROLOGY, Issue 3 2010Aurélie Ponz PhD Narcolepsy with cataplexy is a sleep-wake disorder caused by a loss of hypothalamic hypocretins. Here we assessed the time course of amygdala activation during aversive conditioning in unmedicated patients with narcolepsy. Unlike healthy matched control subjects, narcolepsy patients had no enhancement of amygdala response to conditioned stimuli and no increase in functional coupling between the amygdala and medial prefrontal cortex. These findings suggest that human narcolepsy is accompanied by abnormal emotional learning, and that, in line with animal data, the hypocretin system and the amygdala are involved in this process. ANN NEUROL 2010;67:394,398 [source] Abnormal activity in reward brain circuits in human narcolepsy with cataplexyANNALS OF NEUROLOGY, Issue 2 2010Aurélie Ponz PhD Objective Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. Methods We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Results and Interpretation Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients. ANN NEUROL 2010;67:190,200 [source] Loss of hypocretin (orexin) neurons with traumatic brain injury,ANNALS OF NEUROLOGY, Issue 4 2009Christian R. Baumann MD Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI. Ann Neurol 2009;66:555,559 [source] | |||||||||||||||||||||||||||||||