7:00 Narcolepsy Narcolepsy is a neurological condition where an individual experiences overwhelming daytime sleepiness, and they fall asleep instantly

and involuntarily, even if they've had an adequate nights sleep. The sleep attacks may happen without warning, and can happen repeatedly throughout a day. Symptoms • Drowsiness • Frequent waking from sleepiness • Cataplexy – a loss of muscle function that can range between a slight weakness to complete body collapse, where the person remains conscious the whole time • Sleep paralysis – temporary inability to move or talk when falling asleep or waking up • Hypnagogic hallucinations – vivid, frightening dream-like experiences while falling asleep/dozing • Excessive Daytime Sleepiness (EDS) – try hard to stay awake and are faced with involuntarily sleep attack Only 20-25% of people expeience all symptoms What Happens? The order and length of NREM and REM is disturbed as REM sleep occurs before NREM sleep. Some symptoms of REM sleep (lack of muscle tone, sleep paralyis and dreams) occur at other times. The brain does not pass through the stages of sleep, but just goes in and out of REM sleep. This causes *nighttime sleep to not include much deep sleep so the brain needs to catch up during the day • falling asleep to a deep sleepiness • disorientation when waking up • vivid dreams that they can remember Causes Narcolepsy may be associated with damage to the amygdala. A cerebral protein has recently been discovered that is decreased in a large number or all narcolepsy patients. The protein involved is called hypocretin or orexin. This might explain why nacrolepsy runs in families. Narcolepsy is NOT a psychological disorder but a neurological condition resulting in a fault in the mechanisms controlling the normal, circadian, sleep-wake cycle resulting in REM sleep occurring at inappropriate times. Research on dogs by Mignot and others has suggested a genetic link with the disorder. Dr Emmanuel Mignot has bred a colony of narcoleptic dogs (Labradors and Dobermans ) at his laboratory Stanford University suggesting there is a biological cause of the disorder. In the late 1990s Dr Yanagisawa was testing hypocretin’s use as an appetite suppressant on rats. He bred mice that couldn’t produce hypocretin and found that they ate far less than normal. However, he noticed that over time they actually put on weight rather than lost it as would be expected. When he taped their behaviour he found that instead of being very active at night they were having frequent attacks o cataplexy, as had been observed in narcoleptics. Siegel et al (2000) managed to acquire the preserved brains of 4 narcoleptics and after a close

However. This was subsequently supported by Mignot. however there is a high level of discordance in MZ twins. Mishmina et al (2008) – mutations to same genes in narcoleptic animals and people – gene involved in production of recpetors of hypocretins. In dogs one group of genes (the so called HLA complex on chromosome 11) appears to be responsible for narcolepsy. In humans. further clarification of its precise role is needed. Mahowald and Schenck (2005) report that ‘the absence of hypocretin is neither necessary nor sufficient to explain all the cases of narcolepsy [in humans].examination they were found to have 93% fewer hypocretin neurons than a non-narcoleptic’s brain. Although levels of hypocretin is a major contributory factor. the research by Mignot on dogs does suggest that there are serious issues of generalisation between the two species. injections of hypocretin can reduce the cataplexy experienced by narcoleptic dogs. If one twin as narcolepsy there is only a 30% chance that the other will develop the disorder. . small molecules realeased by hypothalamus– Lin et al – narcoleptic dogs had a mutation of the hypocretin in chromosome 12.05% people in Europe but nearly 2 in japan. REM – link to a malfunction of the system that regulates sleep. Honda et al (1983) found more of one type of HLA in narcoleptic patients Hypocretins – link with narcolepsy – play an important role in maintaining wakefulness. As we’ve already seen. There is clearly a genetic component to narcolepsy but as shown in dogs and with a limited tendency for the disorder to run in human families. and the intrusion of REM into daytime slee HLA – mutation of the immune system on the surface of white blood cells. Genetic influence – only affects 0. Chemelli et al (1999) – made genetically modified animals animals with narcoleptic symptoms caused by lack of hypocretin. It is thought that modafinil stimulates production of hypocretin by the hypothalamus. This explains the lack of muscle tone that accompanies REM sleep. Mignot (1998) – did not run in families – not concurrent in twins Evaluation of narcolepsy research The drug modafinil has been used an effective treatment for some cases of narcolepsy.

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