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Matthew C. Walker

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date: 27 February 2021

Narcolepsy with cataplexy is a specific syndrome of daytime sleepiness, disrupted nocturnal sleep, and episodes of sudden loss of muscle tone—provoked by the anticipation of emotions (in particular laughter)—leading to a tendency to fall, mouth opening, dysarthria or mutism, and facial muscle jerking. It is associated with loss of hypocretin (orexin) neurons in the hypothalamus, hypocretin concentrations in the cerebrospinal fluid below 110 pg/ml, and the HLA genotype DQ B1*0602. A less common form of narcolepsy without cataplexy probably has a different, as yet unknown, pathogenesis. Once established, narcolepsy is lifelong; spontaneous recovery does not occur. Symptomatic treatment—which is essential for school performance, work, driving ability, and quality of life—is with stimulant (e.g. amphetamine) and anticataplectic (e.g. clomipramine) drugs. More recently, sodium oxybate, an anaesthetic, has been used to induce deep sleep overnight, resulting in improvements in all symptoms.

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