Narcolepsy is a chronic condition that causes excessive daytime sleepiness and leads to an increased tendency to fall asleep during daytime activities. In this video, I discuss the symptoms of narcolepsy and explain what may happen in the brain to cause those symptoms to occur. TRANSCRIPT: Narcolepsy is a chronic condition that causes excessive daytime sleepiness and leads to an increased tendency to fall asleep during daytime activities. The majority of people who suffer from narcolepsy also experience cataplexy, which involves brief, sudden episodes of muscle weakness or paralysis---often brought on by strong positive emotions. The muscle weakness in cataplexy may be severe enough to cause someone to fall to the ground and be unable to speak or move for a short period of time despite remaining conscious. Patients with narcolepsy also often experience other sleep-related problems, such as disrupted sleep, sleep paralysis, and hallucinations when falling asleep or waking up. Today, narcolepsy is often classified as narcolepsy type 1 or narcolepsy type 2. Type 1 typically involves narcolepsy with cataplexy, and low levels of a neuropeptide called orexin, also known as hypocretin. Type 2 does not involve cataplexy, and levels of orexin are normal. Narcolepsy type 2 generally has less severe symptoms, but little is known about its cause. Narcolepsy type 1 is linked to a loss of orexin-producing neurons in the hypothalamus, leading to low orexin levels. Orexin neurons have an excitatory effect on several regions of the brain that are involved in promoting wakefulness and suppressing REM sleep. Thus, the loss of these neurons leads to deficiencies in maintaining wakefulness and is linked to the dysregulation of REM sleep. This REM sleep dysregulation is thought to cause episodes of muscle paralysis and other aspects of REM sleep to occur during wakefulness, which is the basis for cataplexy. The cause of the loss of orexin neurons in narcolepsy is not completely understood, but several lines of evidence implicate an autoimmune mechanism. According to this view, a combination of genetic and environmental factors leads to an inflammatory process in the brain that causes the immune-mediated destruction of orexin neurons, bringing about the symptoms of narcolepsy. REFERENCES: Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, Khatami R, Koning F, Kornum BR, Lammers GJ, Liblau RS, Luppi PH, Mayer G, Pollmächer T, Sakurai T, Sallusto F, Scammell TE, Tafti M, Dauvilliers Y. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019 Sep;15(9):519-539. doi: 10.1038/s41582-019-0226-9. Epub 2019 Jul 19. PMID: 31324898. Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S. Narcolepsy. Nat Rev Dis Primers. 2017 Feb 9;3:16100. doi: 10.1038/nrdp.2016.100. PMID: 28179647. Mahoney CE, Cogswell A, Koralnik IJ, Scammell TE. The neurobiological basis of narcolepsy. Nat Rev Neurosci. 2019 Feb;20(2):83-93. doi: 10.1038/s41583-018-0097-x. PMID: 30546103; PMCID: PMC6492289. Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014 Nov;146(5):1387-1394. doi: 10.1378/chest.14-0970. PMID: 25367475.