Narcolepsy: Pathophysiology, Causes and Treatments



Narcolepsy is caused by a neuronal loss of hypocretin (also referred to as orexin). In the brain, hypocretin has an important role in the ventral path with the cortex, being responsible for keeping us awake. Because of the lack of hypocretin in patients with narcolepsy, there are several other neurotransmitters, that are normally released by activation from hypocretin, that are inhibited to. These include: dopamine from the Front Tegmentum, serotonin (5-HT) from the Nucleus Raphe and noradrenaline from the Locus Coeruleus.



Figure 1: An overview of the areas of the brain affected by the lack of hypocretin in patients with narcolepsy.


There are two types of narcolepsy, Type I and Type II. People with Type I narcolepsy are characterized by having hypersomnia and at least one the following symptoms: cataplexies and low levels of hypocretin. In patients with Type II narcolepsy have neither cataplexies nor low levels of hypocretin, but they still, however, possess the symptom of hypersomnia.


In 2009, while the swine flu was making its way across the world, the Pandemrix vaccine that was given to millions unknowingly increased the risk of getting narcolepsy. It might have been strange to a start that the disease seemed to be sporadically occurring among children and teenages, but this sporadicity was not all that random. The HLA(Human Leukocyte Antigen)-DQB1*06:02 was eventually, when the pandemrix vaccine was officially recognised as the catalysator of disease, identified as one important factor. As roughly 25% people have these proteins on their white blood cells, this is not the sole reason for getting narcolepsy, but it is nevertheless a great stepping stone to better understanding the disease and its causes.


In addition to vaccination with the Pandemrix vaccine, narcolepsy also has a tendency to break out as a result of especially vicious forms of tonsillitis.


There are both pharmacological and non-pharmacological treatments to narcolepsy. In the non-pharmacological category there are probably the more stereotyped treatments for a sleeping disorder, including: power naps, sleep hygiene and caffeine, but also meeting with psychologists, counselors, dieticians, physiotherapists and special educators have proven useful in some cases. As for the pharmacological drugs, there are many alternatives with many different uses and with various side effects. These work differently for each person and everything has to be calibrated to suit the individual. There are Central stimulants, methylphenidate, including: ritalin, medikinet, concerta, strattera and elvanse. These require careful regulation and can induce quite strong side effects, but work in a combination with various other drugs. Dextroamphetamine is solely given to adults as it acts sympathomimeticly. There are also modafinils and pitolisants that work in some cases. Pitolisants have little to none side effects but patients risk growing indifferent to the treatment. Sodium oxybate may be given to those bothered by cataplexies and a disrupted night sleep. For cataplexies, antidepressants may also be administered.


In general, narcolepsy is a complex disease which may appear differently among different people. One thing that’s for sure about one person can be entirely different for another. Because of the rarity of the disease, there still isn’t too many fool-proof treatments, especially not designed for children, but this is something that can be hoped for in the future.


Source:

Lecture by specialist physician Attila Szakacs and specialist physician Pontus Wasling

Photo

http://mybraincancerstory.blogspot.com/2018/06/orexinhypocretic-receptor-signalling.html

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