Selective loss of hypocretin immunoreactivity has been reported in the hypothalamus of humans ( 99 123). In 1999, independent observers discovered abnormal hypocretin (Hcrt) (orexin) neurotransmission in a canine model of narcolepsy ( 69) and in knockout mice with narcolepsy ( 28). The observation that narcolepsy was associated with human leukocyte antigens (HLA)-DR2 was the first indication of a biologically based source. The first consensus definition of narcolepsy was adopted by participants of the First International Symposium on Narcolepsy in 1975 ( 97). Three reports published in 1963 confirmed the discovery ( 106). In 1960 Vogel reported the occurrence of REM sleep at the onset of sleep in a single narcoleptic subject ( 126). Subsequently, Yoss and Daly ( 135) described the classic narcoleptic tetrad of hypnagogic hallucinations, sleep paralysis, excessive sleepiness, and cataplexy. Adie suggested that narcolepsy was a specific disease entity as opposed to a heterogeneous syndrome ( 01). The term "sleep paralysis" was introduced by Kinnier Wilson, although the phenomenon had been described as "night palsy" by Weir Mitchell in 1876 ( 132). Lowenfeld introduced the term “Kataplectische Starre” (cataplectic spells) to describe these atonic episodes ( 73). Gelineau introduced the term "narcolepsy," derived from the Greek words narcos meaning somnolence and lepsy meaning seized, in his description of sleep attacks and muscle weakness following intense emotion in a 38-year-old wine barrel retailer ( 49). Caffe and Foot described pathologic sleepiness ( 27 46) subsequently, Westphal and Fischer reported episodic loss of muscle tone associated with sleepiness ( 131 45). Excessive sleepiness has been noted by physicians for centuries. It is plausible that Dante's sleep, dreams, hallucinations, and falls are clues to a lifelong pathologic trait and that Dante may have known of or had narcolepsy ( 101). The discovery of a significant decrease of the neurotransmitter hypocretin-1 levels in cerebrospinal fluid in patients with narcolepsy-cataplexy provided a new test to diagnose the condition.The observation that narcolepsy was associated with human leukocyte antigens (HLA)-DR2 was the first indication of a biologically based source.Pediatric narcolepsy has clinical features that may differ from those in the adult, masquerading as behavioral alterations or attention-deficit/hyperactivity disorder.Some patients with otherwise typical features of narcolepsy do not have cataplexy this is a condition referred to as narcolepsy type 2, also known as narcolepsy without cataplexy and in the past monosymptomatic narcolepsy.The classic form of narcolepsy (narcolepsy type 1) features cataplexy, sleep paralysis, and hypnagogic hallucinations, in addition to excessive daytime sleepiness.Narcolepsy is characterized by excessive daytime sleepiness.
In the United States, the annual direct medical costs are 2-fold higher in patients with narcolepsy than in matched controls without narcolepsy ($11,702 vs. Pharmacologic treatment remains symptomatic but increasingly effective.
Most cases of narcolepsy with cataplexy are associated with the loss of approximately 50,000 to 100,000 hypothalamic neurons containing hypocretin. New knowledge of the etiology and mechanism of the disease involving the hypocretins has opened a major pathway to understanding excessive sleepiness not only in narcolepsy but also in other sleep disorders. In this article, the author reviews the current information on narcolepsy, a disease that has progressed in only 50 years from a quasi-psychiatric condition to a true neurologic disorder.
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