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

ABSTRACT 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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    ABSTRACT: Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.
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