What causes narcolepsy? There are several possible causes. It could be a lack of the chemical hypocretin in the brain, but there are other possible causes as well.
Narcolepsy is a brain disorder that makes people unable to stay awake for long periods at a time. They become very drowsy and can fall asleep suddenly. People who suffer from narcolepsy also have abnormal REM sleep. They have more REM sleep than non-narcoleptics and they dream a lot during the night. There are two levels of narcolepsy: type 1 and type 2. People with type 1 narcolepsy also suffer from cataplexy, which is a loss of muscle function. This can range from a slight weakness to sudden and complete body collapse. Cataplexy can be triggered by a strong emotion, such as laughter. Approximately 300 out of 100,000 people have narcolepsy and about a quarter of those have severe type 1 narcolepsy. It can occur at any age, but it seems most common between 15 and 36. There are medications that can be used to help people cope with narcolepsy, but there is no cure. The word narcolepsy is a combination of the Greek words narke, which means “numbness” and lepsis, which means “attack”.
So, what causes narcolepsy? There does not appear to be a single cause of narcolepsy. However, many people who have narcolepsy have a lack of a chemical in their brain that is called hypocretin, also called orexin. Hypocretin are neurotransmitters, which means they are responsible for transferring an electrical signal from one neuron to another. They are produced by the neurons in the hypothalamus, just behind the eyes and between the ears. The average brain is estimated to have 86 billion neurons and only about 100,000 of these produce hypocretin. They are released from neurons when we are awake and they bind to hypocretin receptors on other neurons, which increases the activity of those neurons. They excite the dopamine, norepinephrine, histamine, and acetylcholine systems, all of which are involved with making people feel awake.
In people who don’t suffer from narcolepsy, hypocretin are produced when we are awake, exciting the neurons in the brain that make us feel awake, and suppress REM sleep. In people who have narcolepsy, the hypocretin produced die and don’t excite the necessary parts of the brain. It becomes impossible for them to regulate REM sleep and feelings of drowsiness persist all the time. Because they can’t regulate their REM sleep, the dreams that we see in REM sleep can become hallucinations that appear at any time of the day. Narcolepsy sufferers can enter REM sleep at any time throughout the day, but it also means that they come in and out of REM sleep through the night as well. They are drowsy all day, but they cannot sleep properly at night.
Being unable to regulate REM sleep can also be the reason why type 1 narcolepsy sufferers experience cataplexy. When non-sufferers sleep, the brain stem and spinal cord paralyze the muscles so that we don’t act out our dreams. This process is blocked when we are awake by norepinephrine and serotonin. Narcolepsy sufferers don’t have the hypocretin to activate these neurons, which means they can enter REM sleep at any time and their brain and spinal cord paralyzes their muscles. The amygdala and the prefrontal cortex are the parts of the brain that regulate emotional response and they are also connected to the part of the brain that paralyzes the muscles. This could be why laughing, or a strong emotion, can bring on sudden cataplexy.
An important question is why narcolepsy sufferers lack hypocretin. It appears that their immune system attacks and kills them. Our immune systems are triggered when bacteria or viruses enter the body. The white blood cells kill the invaders. In people with allergies, the immune system can be triggered by things that are not necessarily a threat. In people with narcolepsy, the immune system produces antibodies against a protein called trib 2. Trib 2 is produced by the part of the brain that also produces hypocretin. When the immune system attacks the trib 2, it kills the neurons in the brain that produce hypocretin, which can cause all of the problems evident in narcolepsy.
Why the immune system does this is not known for definite. It could be caused by a strep throat infection, or some strains of influenza. In Northern Europe in 2010-11, there was an outbreak of the H1N1 strain of influenza, and it was followed by an increase in the number of children with narcolepsy.
However, the immune system attacking the hypocretin neurons isn’t the only cause of narcolepsy. Some sufferers have normal levels of hypocretin. There could be other reasons that have not yet been discovered. Maybe, one day, it will be possibly to fix the disease with gene editing. Until then, though, it is a debilitating disease with no known cure.
Sources
https://www.hopkinsmedicine.org/health/conditions-and-diseases/narcolepsy
https://en.wikipedia.org/wiki/Narcolepsy
https://www.nhs.uk/conditions/narcolepsy/
https://www.nhs.uk/conditions/narcolepsy/causes/
https://en.wikipedia.org/wiki/Orexin
https://healthysleep.med.harvard.edu/narcolepsy/what-is-narcolepsy/science-of-narcolepsy
https://www.nichd.nih.gov/health/topics/sleep/conditioninfo/causes
https://www.mayoclinic.org/diseases-conditions/narcolepsy/symptoms-causes/syc-20375497
https://www.nhs.uk/conditions/narcolepsy/
https://www.nature.com/scitable/blog/brain-metrics/are_there_really_as_many/