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Narcolepsy is a usually sporadic disorder with a prevalence of 1:2,000—its importance is not just medical, for it has a major psychosocial impact. Narcolepsy, as described by Gélineau in 1880, presents with excessive daytime sleepiness (EDS) and cataplexy.1 These features and typical findings on multiple sleep latency tests (mean sleep latency < 5 to 8 minutes or ≥2 sleep onset REM periods in 70 to 80% of patients) are supported by positivity for HLA DQB1*0602 (85 to 95% of patients). The latter is useful for recognizing narcolepsy without cataplexy.1 Narcolepsy can also be considered as instability among the states of wakefulness, non-REM (NREM) and REM sleep. Such a “state boundary dyscontrol” arises from a cholinergic-aminergic imbalance and a deficiency in transmission of hypothalamic peptides, hypocretins.
Hypocretins (Hcrt or orexins), discovered in 1998 in the posterolateral hypothalamus, are excitatory upon their targets, the monoaminergic and cholinergic cells in the basal forebrain and brainstem, some of which project back and modulate Hcrt signaling. Hcrt regulates arousal, feeding behavior, locomotion and muscle tone, and may play a key role in orchestrating ergotropic behaviors with emotional/motivational content.2 In 1999, a link between Hcrt and narcolepsy was discovered in dogs and rodents. …
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