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.

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    • "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). "
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    ABSTRACT: Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness and manifestations of disrupted rapid eye movement sleep stage. The pathologic hallmark is loss of hypocretin neurons in the hypothalamus likely triggered by environmental factors in a susceptible individual. Patients with narcolepsy, in addition to excessive daytime sleepiness, can present with cataplexy, sleep paralysis, sleep fragmentation, and hypnagogic/hypnopompic hallucinations. Approximately 60% to 90% of patients with narcolepsy have cataplexy, characterized by sudden loss of muscle tone. Only 15% of patients manifest all of these symptoms together. Narcolepsy can be misdiagnosed as a psychiatric disorder or even epilepsy. An appropriate clinical history, polysomnogram, Multiple Sleep Latency Test, and, at times, cerebrospinal fluid hypocretin levels are necessary for diagnosis. The treatment of narcolepsy is aimed toward the different symptoms that the patient manifests. Excessive daytime sleepiness is treated with amphetamine-like or non-amphetamine-like stimulants. Cataplexy is treated with sodium oxybate, tricyclic antidepressants, or selective serotonin and norepinephrine reuptake inhibitors. Sleep paralysis, hallucinations, and fragmented sleep may be treated with benzodiazepine hypnotics or sodium oxybate. Patients with narcolepsy should avoid sleep deprivation, sleep at regular hours, and, if possible, schedule routine napping.
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