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Narcolepsy is a severe neurological sleep disorder, which is caused by the large loss of Hypocretin (Hcrt)/Orexin producing neurons in the hypothalamus in narcolepsy with cataplexy patients. It is likely the result of an autoimmune process that causes selective destruction of Hcrt neurons in the hypothalamus. It has been known that narcolepsy is associated with the human leukocyte antigens <em>(HLA)-DR2</em> and <em>HLA-DQB1*0602</em>. Recent epidemic data have shown a robust incidence of disease onset associated with pandemic H1N1-infection, H1N1 vaccination and streptococcus pyogenes infection. A genome-wide association variants in <em>P2RY11</em> are associated with narcolepsy. Narcolepsy is associated with polymorphisms of the genes encoding T cell receptor-α (TCR-α) and tumor necrosis factor-α (TNF-α). Several cases report successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset, but the effects are not persistent. However, there is no significant evidence of narcolepsy specific antibodies or T cell reactions found, and the relations with cytokines and central nervous system inflammatory cells have not been elaborated well. It is still a big challenge for further study. <br />