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Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic(More)
Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of(More)
Onset is most typically in the teens, and cases with onset before age 6 or after 40 are rare in Western Europe and North Amer-ica. 3 The disease is extremely tightly associated with human leukocyte antigen (HLA) DQB1*0602 4 , so that DQB1*0602 negative cases without documented loss of hypocretin cells, as measured by cerebrospinal fluid (CSF) hypocretin(More)
Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all(More)
shown that the cause of narcolepsy-cataplexy is the loss of approximately 70,000 hypothalamic neurons producing the neuropeptide hypocretin. Hypocretin knockout mice and hypocretin receptor-2 mutated dogs have narcolepsy-cata-plexy, demonstrating that the loss of hypocretin transmission causes narcolepsy. Since 1983, it has been known that nar-colepsy is(More)
STUDY OBJECTIVES To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1. SETTING University-based sleep clinics and laboratories. PATIENTS Narcolepsy without cataplexy (n = 171) and(More)
Narcolepsy is a disabling neurological sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep manifestations. Recently, the role of cytokines and growth hormone in the regulation of sleep and narcolepsy has been considered, and data suggest that proinflammatory cytokines may be involved in sleep and narcoleptic symptoms. Serum(More)
Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: Narcolepsy-cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals1,2. Narcolepsy was first shown to be tightly associated with(More)
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