The RAS also inhibits the sleep-promoting ventrolateral preoptic area (VLPO), suppressing GABA, which in turn increases the activity of motor neurons and muscle tone. Narcolepsy is classified as follows based on clinical features:ĭuring normal wakefulness, orexin-containing neurons in the lateral hypothalamus increase the activity of the nuclei of the Reticular Activating System (RAS), which increases wake-promoting neurotransmitters in the cortex dopamine, norepinephrine, serotonin, and histamine inhibit REM and acetylcholine is increased in both wakefulness and REM. The mechanism of narcolepsy type 2 is less clear, but it is thought that it may be due to a similar but less severe loss of orexin neurons. Although a specific autoantibody that correlates with disease mechanism in narcolepsy has not yet been identified, this does strongly suggest that narcolepsy type 1 may be an autoimmune disease. Antibodies against streptococcal infections have also been associated with the onset of narcolepsy type 1. Additionally, there was an increase in the number of reported cases of narcolepsy in non-vaccinated patients after wild A(H1N1) pandemic influenza infection. The same adjuvant was, however, also used in Canada but the corresponding increase in reported cases did not occur there. In 2009 there was an increase in the number of cases of narcolepsy type 1 reported in Europe after receiving the European AS03-adjuvanted A(H1N1) pandemic influenza vaccine (Pandemrix) and it was initially thought that the immune response to the adjuvant might have been the cause of the disease. Some patients initially diagnosed with narcolepsy type 2 will develop cataplexy, indicating disease progression. Less commonly, trauma and tumors may result in narcolepsy. Current hypotheses include less destruction of orexin cells, impaired orexin receptor signaling, or an unknown mechanism. The cause of narcolepsy type 2 is not entirely clear. HLA haplotype DQB1*0602 is present in 95% of narcolepsy type 1 patients, but this is also present in about 20% of the general population without narcolepsy. The reason for this is not fully understood, but it is thought to be an autoimmune process possibly triggered by an infection. Narcolepsy type 1 occurs when nearly all of the neurons that contain orexin (also called hypocretin) are lost.
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