Source: Modified from TA Roth, L Merlotti in SA Burton et al (eds), Narcolepsy 3rd International Symposium: Selected Symposium Proceedings, Chicago, Matrix Communications, 1989. Narcolepsy affects about 1 in 4000 people in the United States and appears to have a genetic basis. Recently, several convergent lines of evidence suggest that the hypothalamic neuropeptide hypocretin (orexin) is involved in the pathogenesis of narcolepsy: (1) a mutation in the hypocretin receptor 2 gene has been associated with canine narcolepsy; (2) hypocretin "knockout" mice that are genetically unable to produce this neuropeptide exhibit behavioral and electrophysiologic features resembling human narcolepsy; and (3) cerebrospinal. | Chapter 028. Sleep Disorders Part 11 Source Modified from TA Roth L Merlotti in SA Burton et al eds Narcolepsy 3rd International Symposium Selected Symposium Proceedings Chicago Matrix Communications 1989. Narcolepsy affects about 1 in 4000 people in the United States and appears to have a genetic basis. Recently several convergent lines of evidence suggest that the hypothalamic neuropeptide hypocretin orexin is involved in the pathogenesis of narcolepsy 1 a mutation in the hypocretin receptor 2 gene has been associated with canine narcolepsy 2 hypocretin knockout mice that are genetically unable to produce this neuropeptide exhibit behavioral and electrophysiologic features resembling human narcolepsy and 3 cerebrospinal fluid levels of hypocretin are reduced in most patients who have narcolepsy with cataplexy. The inheritance pattern of narcolepsy in humans is more complex than in the canine model. However almost all narcoleptics with cataplexy are positive for HLA DQB1 0602 Chap. 309 suggesting that an autoimmune process may be responsible. Diagnosis The diagnostic criteria continue to be a matter of debate. Certainly objective verification of excessive daytime somnolence typically with MSLT mean sleep latencies 8 min is an essential if nonspecific diagnostic feature. Other conditions that cause excessive sleepiness such as sleep apnea or chronic sleep deprivation must be rigorously excluded. The other objective diagnostic feature of narcolepsy is the presence of REM sleep in at least two of the naps during the MSLT. Abnormal regulation of REM sleep is also manifested by the appearance of REM sleep immediately or within minutes after sleep onset in 50 of narcoleptic patients a rarity in unaffected individuals maintaining a conventional sleep-wake schedule. The REM-related symptoms of the classic narcolepsy tetrad are variably present. There is increasing evidence that narcoleptics with cataplexy one-half to two-thirds of patients may represent a more homogeneous
