Narcolepsy with cataplexy

Dauvilliers, Yves; Arnulf, Isabelle; Mignot, Emmanuel

doi:10.1016/s0140-6736(07)60237-2

Cited by 651 publications

(492 citation statements)

References 118 publications

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“…In agreement, noradrenergic neurons cease to discharge for an extended period during REM sleep, as well as during cataplectic episodes (Wu et al,1999), and antidepressants with a preference towards the noradrenaline transporter display anti-cataplectic activity in patients (Baumann et al,2005;Mignot and Nishino, 2005;Dauvilliers et al,2007). Alternatively, the enhanced activation of histaminergic neurons with tiprolisant alone or, even more in association with modafinil, suppresses DREMs as histaminergic neurons also become silent during REM sleep (Vanni-Mercier et al,2003;Takahashi et al,2006) and abolition of HA-synthesis increases REM sleep (Parmentier et al,2002).…”

Section: Discussionmentioning

confidence: 85%

“…Modafinil, a drug currently used to decrease EDS in narcolepsy (Mignot and Nishino, 2005;Dauvilliers et al, 2007), enhanced t-MeHA levels to a lower extent (42%) but, when associated to tiprolisant, the effect of the H3 receptor inverse agonist was strongly enhanced (216% activation in orexin-/-mice). Noradrenergic neuron activity, assessed by the 4-hydroxy-3-methoxy-phenylglycol/noradrenaline (MHPG/NA) ratio, was also slightly but not significantly decreased in orexin-/-mice and activated by tiprolisant in both WT and orexin-/-mice (43% and 22%, respectively).…”

Section: Tiprolisant Enhances Histaminergic and Noradrenergic Neuron mentioning

confidence: 99%

“…Narcolepsy is a rare disabling sleep disorder with a prevalence of 0.02-0.18%; it is characterized by excessive daytime sleepiness (EDS) and abnormal rapid eye movement (REM or paradoxical) sleep manifestations, including cataplexy (sudden loss of muscle tone triggered by strong emotions), direct transitions from wakefulness to REM sleep (DREMs), sleep paralysis and hypnagogic hallucinations (Baumann et al, 2005;Mignot, 2005;Mignot and Nishino, 2005;Dauvilliers et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

Lin

Dauvilliers

Arnulf

et al. 2008

Neurobiology of Disease

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178

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Abbreviations AbstractNarcolepsy is characterized by excessive daytime sleepiness(EDS), cataplexy, direct onsets of rapid eye movement(REM) sleep from wakefulness(DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H3-receptor agonist. In narcoleptic orexin-/-mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently prescribed wake-promoting drug. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for one week, the Epworth Sleepiness Scale(ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo(p>0.05) and 5.9 with tiprolisant(p<0.001). Excessive daytime sleep, unaffected under placebo, was nearly suppressed on the last days of tiprolisant-dosing. H3-receptor inverse agonists could constitute a novel effective treatment of EDS, particularly when associated with modafinil.

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Section: Discussionmentioning

confidence: 85%

Section: Tiprolisant Enhances Histaminergic and Noradrenergic Neuron mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

Lin

Dauvilliers

Arnulf

et al. 2008

Neurobiology of Disease

Self Cite

247

178

View full text Add to dashboard Cite

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“…Both these findings may be interpreted within the framework of the sequential hypothesis of the consolidation function of sleep (Ambrosini and Giuditta, 2001;Giuditta et al, 1995). Indeed, not only was the effectiveness of post-training night lower in NC patients than in normal subjects, but also the lower improvement of consolidation after post-training night in NC patients with SOREM sleep relative to patients without was not balanced over the subsequent six nights, when the numbers of nights with and without SOREM sleep presumably became fairly equivalent in all patients (as SOREM sleep occurs on around half of the nights: Nykamp et al, 1999;Dauvilliers et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Sleep and time course of consolidation of visual discrimination skills in patients with narcolepsy–cataplexy

Cipolli

Campana

Campi

et al. 2009

Journal of Sleep Research

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SUMMAR Y The level of procedural skills improves in normal individuals when the acquisition is followed by a period of sleep rather than wake. If sleep plays an important role in the consolidation process the advantage it provides should be reduced or delayed when its organization is altered, as in patients with chronic sleep disorders. To test this prediction in patients with narcolepsy-cataplexy (NC), who usually have a more fragmented organization of sleep than normals, we compared the initial, intermediate and delayed level of consolidation of visual skills. Twenty-two drug-naive NC patients and 22 individually-matched controls underwent training at a texture discrimination task (TDT) and were re-tested on the next morning (after a night spent in laboratory with polysomnography) and after another six nights (spent at home). TDT performance was worse in patients than controls at training and at both retrieval sessions and the time course of consolidation was different in NC patients (who improved mainly from next-day to 7th-day retrieval session) compared with controls. Moreover, the lessimproving patients at next-day retrieval had a wider disorganization of sleep, probably because of an episode of rapid eye movement (REM) sleep at sleep onset REM, on post-training night more frequently than more-improving patients. These findings suggest that the time course of the consolidation process of procedural skills may be widely influenced by the characteristics of sleep organization (varying night-by-night much more in NC patients than controls) during post-training night.

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“…1,2 Disrupted nighttime sleep is also frequent and should be considered as the fifth narcolepsy symptom. Following the breakthrough discovery of hypocretin deficiency, narcolepsy with cataplexy was recently renamed Narcolepsy Type 1 (NT1, or hypocretin-deficiency syndrome), according to the third edition of the International Classification of Sleep Disorders.…”

Section: Introductionmentioning

confidence: 99%