Narcolepsy and cataplexy

Stanford University School of Medicine, Stanford Sleep Research Center, Palo Alto, CA, USA.
Handbook of Clinical Neurology 01/2011; 99:783-814. DOI: 10.1016/B978-0-444-52007-4.00007-2
Source: PubMed


The term "narcolepsy" was first coined by Gélineáu in 1880 with the complete description of a patient with excessive daytime sleepiness (EDS), sleep attacks, and episodes of muscle weakness triggered by emotions. In the current international classification, narcolepsy is characterized by "excessive daytime sleepiness that is typically associated with cataplexy and abnormal REM (rapid eye movement) sleep phenomena such as sleep paralysis and hypnagogic hallucinations". Narcolepsy is a chronic neurological condition, but is not a progressive disorder. The major pathophysiology of human narcolepsy has been elucidated recently based on the discovery of narcolepsy genes (hypocretin/orexin ligand and its receptor) in animals. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in many cases. This recent discovery is likely to lead to the development of new diagnostic tests and targeted treatments. As hypocretins are involved various hypothalamic functions, hypocretin-deficient narcolepsy appears now to be a more complex condition than just a simple sleep disorder. This chapter starts with an overview of the clinical aspects of narcolepsy, followed by an update on the pathophysiology. Finally, we discuss the expectations from future narcolepsy research.

11 Reads
  • Source
    • "Orexin receptor antagonism in sleep disorders 3 transition from wakefulness into PS, as seen in human narcolepsy, suggesting a key role of orexinergic signalling in the genesis of this pathology (Nishino and Mignot, 2011). In accordance with these results, postmortem analysis of brains from narcoleptic patients have revealed an extreme reduction in the number of orexin-expressing neurons (Peyron et al., 2000) associated with undetectable levels of orexin A in the cerebrospinal fluid (Nishino et al., 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients' clinical states and may cause lifelong drug dependence. Brain state transitions require the coordinated activity of numerous neuronal pathways and brain structures. It is thought that orexin-expressing neurons play a crucial role in this process. Due to their interaction with the sleep-wake-regulating neuronal population, they can activate vigilance-promoting regions and prevent unwanted sleep intrusions. Understanding the multiple orexin modulatory effects is crucial in the context of pathogenesis of insomnia and should lead to the development of novel treatments. An important step in this process was the synthesis of dual antagonists of orexin receptors. Crucially, these drugs, as opposed to benzodiazepines, do not change the sleep architecture and have limited side-effects. This new pharmacological approach might be the most appropriate to treat insomnia.
    The International Journal of Neuropsychopharmacology 01/2014; 17(1):157-168. DOI:10.1017/S1461145713000552 · 4.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This article begins with a review of the major central nervous system functional systems that allow for optimal alertness during the waking day, and the rapid initiation and good maintenance of sleep at night. Subsequent sections discuss each of the 6 primary circadian rhythm sleep disorders. Attention is paid to known or suspected pathophysiology, diagnostic criteria and assessment methodology, and treatment options. The article concludes with a discussion of challenges that must be met to improve the recognition and treatment of these quite impactful sleep disorders.
    Pediatric Clinics of North America 06/2011; 58(3):621-35. DOI:10.1016/j.pcl.2011.03.014 · 2.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The occurrence of sleep disorder in three half sibling Lipizzaner is described. Sleepiness, swaying, stumbling, carpal joints buckling and falling down onto the carpal joints had been present since early foal age in all of them. Clinical signs had gradually reduced since the age of 2 years in cases 1 and 3. Sleepiness was induced by going out from the stable in adulthood. A physostigmine test was performed in all three affected horses and produced positive results in cases 1 and 3. The result of the test in case 2 was unclear due to the almost continuous sleepiness of the foal. Hypocretin-1 concentration in the cerebrospinal fluid was established using a standardised radioimmunoassay in case 1 (317.85 pg/mL), case 2 (303.43 pg/mL) and five adult control horses (275.2 ± 47.9 [SD] pg/mL) and was considered as normal in all horses. The sire of the affected horses has had 19 other registered offspring who did not show clinical signs of sleep disorder and also dams of all three cases produced healthy foals. Based on the demographic and clinical data together with the responses to the physostigmine challenges, the diagnosis of familial equine narcolepsy was made.
    08/2012; 32(2):99-102. DOI:10.1080/01652176.2012.714089
Show more