Falling Asleep on the Job: The Story of Narcolepsy
Have you ever pulled two all nighters in a row? If you have then you know that afterwards, during the day, you drift off to sleep very easily. You feel physically and mentally exhausted and your body tells you that you need to rest. This is a normal reaction by the body to the lack of sleep. This however is something that people suffering from narcolepsy must deal with on a daily basis even when they have had a full nights sleep. One of the major symptoms they suffer from is overwhelming daytime sleepiness.
Imagine you are in a boring lecture and you start to drift to sleep, usually you can manage to force yourself to wake up. This may be common occurrence but try to imagine falling asleep while driving or walking. These situations seem more rare. A narcoleptic’s body doesn’t care what it is doing when it goes into these paralyzed sleeping episodes. The sudden overwhelming feeling drives the narcoleptic person to fall asleep. One type of episode that they experience is called cataplexy, which is usually caused by some stressful situation or other common activities such as laughing or running (6) . During these periods the person suffers from muscle weakness and paralysis. Although the person appears to be sleeping, they are still conscious, but unable to move. They can hear and feel but cannot react to stimulation. For this reason narcolepsy is a very dangerous condition to have without receiving treatment because serious vehicle accidents can result as well as an general inability to succeed in school (6) .
Another major symptom that affects narcoleptics is called hypnagogic hallucinations, which they experience when they are falling asleep. These hallucinations can include vivid images accompanied by sounds which are often frightening to the person. This symptom can be experienced by non-narcoleptics, but it is so common in narcoleptics that they don’t know if what they experienced was a dream or if they actually experienced the situation (10) . A related symptom is called automatic behavior, which is when the person will not remember doing familiar or boring tasks after they have been done.
Although narcolepsy is a very common disorder, affecting between 1 in 1000 and 1 in 2000 people in the United States, there is still no cure and the only medications available mask some of the symptoms, but they are only effective for a short time (6) . Though their is no cure, scientists have been trying to solve this problem since the ‘discovery’ of the disease 120 years ago. At this point they have a few possible areas that they are studying which have been connected to the disease. The suggestions that have been made so far are causes such as neuronal degeneration, a genetic mutation or an autoimmune disease (6) . These possible causes are varied and have been proven to cause narcolepsy in other animals, but not humans specifically.
Neuronal and axonal degeneration has been seen in narcoleptic canine brains during the onset of the symptoms but no evidence has been seen in humans. Scientists believe that the process of degeneration does take place in the brain, but they do not know the exact cause of it. The degeneration may take place at the onset of the disease with no previous abnormalities in the brain, or the degeneration could actually take place early in development and be triggered by another hormonal or degenerative process, which cause the symptoms to start later in life (6) . Further studies are being performed to try and understand the brain better.
The focus of narcoleptic research is on the periods of sleep that normal people experience as compared to what narcoleptics experience. Every night the normal sleep pattern involves the shift from non-REM sleep to REM sleep. This shift takes place many times throughout the night and the two stages are very distinct. When someone first falls asleep they normally experience non-REM sleep for 90 minutes, when the muscles are relaxed but maintain tone, the brain’s consumption of energy is minimal and breathing is consistent (6) . The shift into REM (rapid eye movement) sleep is marked by an increased heart and breathing rate, maximum energy consumption by the brain and rapid eye movements (6) .
This sleep pattern is common for any person without narcolepsy but for those suffering from the disease, they often skip non-REM sleep and go straight into REM sleep. Scientists have also found that narcoleptics also suffer from loss of muscle tone and severe hallucinations during there sleep, which leads the scientists to believe that there might be a faulty trigger in their REM sleep pattern (6) . When narcoleptics fall asleep during the day they usually slip straight into REM sleep, as well.
One of the animals of most interest to the scientists is the dog. Dogs also suffer from narcolepsy but they seem to pass the trait through recessive genes. So if two narcoleptic dogs are bred, the result is a litter of narcoleptic puppies. This allows the scientists to study fairly large groups of dogs who experience similar narcoleptic problems. The puppies in studies often experience cataplexy when they were excited, as at feeding time, which would cause them to fall stiffly to the ground until they recovered, after a few minutes (6) . The interesting comparison to be made regarding humans, is that most narcoleptics do not have any relatives who also suffer from narcolepsy. Also narcolepsy does not show up in humans until the teens or twenties, which is very different than the experiences that dogs and horses have with the disease (6) .
Some adult horses are afflicted by the disease but the more common occurrence is that foals seem to experience narcoleptic symptoms, usually growing out of them as they age. This disease in horses is scary because “narcoleptic horses have been known to go limp and topple over while being ridden (5) . ” These different experiences with narcolepsy suggest that environmental conditions may play a much more significant role in causing narcolepsy to start, especially since the percentages of people suffering from narcolepsy varies considerable all over the world. In Japan the incidence of this disease is 1 in 600 people, while in Israel the disease affects 1 in 500,000 people (6) .
One study that was performed on the puppies involved electrophysiological studies, to try and figure out what caused the symptoms of narcolepsy (6) . By placing tiny electrodes on the neurons in the brain stem, it was possible to measure the electrical impulses being produced when the cells communicated to one another. From an earlier study done in the 1940’s by Horace W. Magoun of Northwestern University, these scientists knew that when the medial medulla was stimulated with an electrical impulse, the muscle tone vanished and movement was prevented, like during cataplexy (6) .
After the discovery of REM sleep in 1953, scientists were able to make a connection between the medulla and the lack of movement during REM sleep. This area of the medulla was a suppressing area, which was the most active during REM sleep, to prevent sympathetic movement during dreams, but was inactive during the day when the animal was moving (6) . Another area of the brain, the locus coeruleus, was found to act similarly in daily activities. The cells in this part of the brain stem release a chemical used by neurons to communicate, known as norephinephrin, which helps the sympathetic nervous system react to emergency situations (6) . As would be expected, the release of norephinephrin is isolated to times when the animal is active and thus is inactive during REM sleep. The studies in the dogs showed that their locus coeruleus was inactive at the time of cataplexic events, which further backs up the claim that narcoleptics frequently fall into REM sleep immediately (6) .
The main area of the brain on which studies are being focused, is activated during REM sleep. This area of the brain, the amygdala, is in the frontal lobe and has been shown to be involved with emotional reactions to situations. The amygdala interacts with the dorsolateral pontine cholinergic and noradrenergic cell regions of the brain, which are involved in the production of REM sleep in animals (9) . The overall activation of the amygdala causes increases in the Electrocardiogram output and other general changes that also appear at the beginning of a cataplexy event (2) . These changes in the signals in the brain show where some of the narcoleptic symptoms originate.
The most recent studies of narcolepsy have led to fairly conclusive data as to the cause of the disease. A group of people at UCLA studied the postmortem brains of four narcoleptics and compared them to twelve brains from people who did not suffer neurological diseases during life. The focus of the study was on a group of brain cells, located in the hypothalamus, which contained hypocretin/orexin. The study found that in the brains of the narcoleptics 85-95% of these cells were not present. In the normal brains they found 70,000 of these cells, whereas the narcoleptic brains had between 3,000 and 10,000 of these cells (7) .
There are a couple of reasons that could cause these cells to die, but the most likely cause is that the immune system kills these cells. Why would the immune system kill these cells, if they are important to the functioning of the body? A study in Tokyo isolated a particular molecule, one of the human leukocyte antigens (HLAs), which was found in over 100 narcoleptic patients. Although this molecule was found in some of the normal population, it is believed to cause a predisposition for narcolepsy (6) . These molecules are responsible for showing different proteins to the immune system, which is then able to destroy any viruses that are detected. The scientists believed that this one HLA molecule could cause the immune system to attack healthy cells, “because those HLA types when linked to particular antigens may look like naturally occurring proteins in the body (6) . ”
These studies give suffers of narcolepsy some hope for future cures, because at least in theory if hypocretin was administered to people with narcolepsy the symptoms could disappear. There is support to this theory because some preliminary studies have been carried out on narcoleptic dogs and when hypocretin was injected, the daytime sleepiness was reduced and the sleep during the night was more continuous (7) . Although this study did not ultimately find a cure, as of right now, the finding that narcolepsy is definitely a neurological problem affecting cells in the hypothalamus, will help human suffers break free from the misconceptions that they suffer from psychological problems.
A narcoleptic person has to deal with many problems in everyday society, that can make them worry about there ability to lead a normal life. Luckily, if two narcoleptics are planning to have children, the chance of having affected children is only 1 to 2 %, which is 10 to 40 times higher than the normal public, but is still a low percentage (4) . Also the treatments that many narcoleptics depend on to counteract some of their symptoms, may have an adverse affect on a fetus. Narcoleptics have to choose what is more important to their life and future, which can cause a dilemma for them (3) . Hopefully safe treatments will be available within the next ten years, so that narcoleptics can live ‘normal’ lives.
This disease makes many connections to the ideas that we covered during class and may contradict some of the conclusions that we suggested. An interesting idea is the issue of the I-function and its seemingly non-existent role in REM sleep. Narcolepsy seems to go against all of the beliefs that we have about these two ideas. The conscious mind, or I-function, is not supposed to be able to function during REM sleep, but when narcoleptics have cataplexic events they slip straight into REM sleep and have reported that they can feel, hear and sense people around them. They even report being embarrassed if they have these events when their friends are around. Is it possible to feel embarrassed without involving the I-function? You have to be aware of who you are to experience embarrassment.
If we still want to hold onto our ideas about the I-function then we have to question the experiences that narcoleptics endure. Do they actually slip into REM sleep or are the connections in their brains’ different than non-narcoleptics? Maybe what scientists see as the patterns for REM sleep are just reworked in the narcoleptic brain, so that they no longer can fully experience REM sleep. Many studies of the sleeping patterns of narcoleptics has shown that they do not experience much REM sleep during their nighttime sleep, which accounts for some of their sleepiness during the day. Is it possible that even during the cataplexic events, their body does not experience REM sleep? Many studies still need to be done, but it is unlikely that scientists will ever know what is actually occurring in the brain. As you have said before, we are just trying to get it progressively less wrong.
WWW Sources1) Narcolepsy: Questions and Answers , Has a lot of useful beginner information about narcolepsy
2) Sleep States attenuate the Pressor response to central amygdala stimulation, Neurol, 1984, Volume 83, pp 604-617, Very specific information about the influence of one part of brain on symptoms of narcolepsy
4) Narcolepsy Network section on ‘Pathophysiology of Narcolepsy’. Principal and Practice of Sleep Medicine , A nice little explaination
6) Narcolepsy: Althogh people with the disorder do not fall face-first into their soup as in the movies, narcolepsy is still a mysterious disease. But science has new leads. , Siegel really knows what he is talking about.
7) Mystery of Human Narcolepsy Solved , He is the master of these studies
8) University of Pennsylvania Narcolepsy Research Project , A nice summary
10) Living with Narcolepsy , Go info about the lives of Narcoleptics