Hannah Langsdorf

ENG 1020

Fenster

Narcolepsy is a chronic sleep disorder that affects roughly 0.05% of the population. The

word "narcolepsy" derives from the latin roots "narco", meaning sleep or numbness, and "lepsy",

meaning seizure. Being a narcoleptic myself, I find this an accurate description. (Although

narcolepsy has "lepsy" in it, it is by no means a type of seizure.) Narcolepsy involves a loss of

control over sleep-wake cycles due to a deficiency of hypocretin-producing brain cells.

Hypocretin (aka orexin) is a neurotransmitter in our brains that regulates wakefulness, arousal

(alertness, not sexual arousal), and appetite. This hypocretin deficiency leads to "sleep attacks",

hallucinations, sleep paralysis, and sometimes episodes of cataplexy. Research into what causes

this hypocretin deficiency is central to modern day narcolepsy research. Even though the cause

of narcolepsy is heavily researched, finding answers has been slow. Few definitive results have

been found. However, this does not mean to say researchers of narcolepsy are clueless as to its

causes. In recent years, researchers have hypothesized that narcolepsy is caused when the

immune system (for uncertain reasons) attacks perfectly healthy hypocretin-producing brain

cells. However, this hypothesis is more revolutionary than one would think. It would not only

explain how narcolepsy develops it would also classify narcolepsy as an autoimmune disease.

This explanation fits well and explains many of the aspects of narcolepsy that had previously

puzzled researchers, such as why narcolepsy almost always develops in early childhood. (Our

immune systems are most vulnerable during that time.) Linking the immune system to

narcolepsy explains why most cases of narcolepsy develop in early childhood. Despite how

perfectly this hypothesis fits narcolepsy, no concrete evidence has been found to support it. The

debate over whether or not narcolepsy is an autoimmune disease continues to this day, despite
the endless efforts of researchers to resolve it. Countless studies have been conducted in various

laboratories worldwide. Many of these studies at first seem promising, but when other

researchers attempt to recreate them, the desired results are not achieved. This lack of

conclusive evidence for the autoimmune aspect of narcolepsy continues to frustrate researchers

and the narcolepsy community. However, I believe that despite inconclusive research into the

pathoimmunology of narcolepsy, there is already enough evidence to categorize narcolepsy as an

autoimmune disease.

Autoimmune diseases are conditions caused by an abnormal immune response in one's

body, which causes the body to attack otherwise normal, healthy tissues. Under the autoimmune-

hypothesis, narcolepsy fits this definition. Healthy hypocretin cells are attacked by the immune

system, causing narcolepsy to develop. Autoimmune diseases vary in the body part that is

affected as well as how that body part is affected. There are currently 80 recognized autoimmune

diseases. Narcolepsy is not one of them. Autoimmune diseases are vastly different from one

another - there is no "normal" autoimmune disease. However, there are many aspects of

narcolepsy that bear characteristic signs of an autoimmune disease. For example, all autoimmune

diseases are chronic (life-long) and have no cure. Narcolepsy is also chronic and incurable.

Although autoimmune diseases are incurable, there are a variety of treatments. These treatments

either relieve the symptoms of the disease, replace vital substances that the body can no longer

produce on its own, or suppress the immune system. Treatments for narcolepsy fall under all of

these categories. In terms of relieving the symptoms, there are a variety of medications designed

to reduce REM sleep (making sleep attacks less prevalent) or reduce the likelihood of cataplexy

episodes. Other ways to relieve the symptoms of narcolepsy include scheduled naps and changes

in lifestyle. These changes in lifestyle can include dietary changes, exercise, and following a
regular sleep schedule. Nearly every autoimmune disease also includes changes in lifestyle as

treatment. However, just as in narcolepsy, this solution is usually not enough to treat the disease.

Most autoimmune diseases include taking some kind of medication to replace vital substances

the body no longer produces. In the case of narcolepsy, the medications are designed to replace

hypocretin. These medications (including methlyphenidate, mixed amphetamine salts,

dextroamphetamine, and lisdexamfetamine) stimulate the areas of the brain that produce

hypocretin. Likewise, many autoimmune diseases, like diabetes and thyroid disease, have

medications to replace substances the body is now unable to produce on its own. In the case of

diabetes, insulin injections are used to regulate blood sugar. People who suffer from thryoid

disease receive thyroid injections to stabilize their hormone levels. And the list goes on. The

point is, the ways narcolepsy is usually treated (lifestyle changes and/or replacement of needed

substance) is typical of most autoimmune diseases. Another way the characteristics of narcolepsy

align with established autoimmune diseases is by the hypothesized "triggers", or what

contributes to the development of the disease. For years, scientists have been puzzled as to what

causes one to develop narcolepsy. Recent findings have suggested that although genetics

contribute to the development of narcolepsy, it is not the only factor in determining whether one

will develop narcolepsy. Other factors seem to play a much larger role. This includes

environmental irritants, which are anything that could activate an immune response, such as air

pollution. But in the case of narcolepsy, research is leading scientists to believe viruses play the

largest role in the development of narcolepsy. This parallels with many unexplained occurrences

in narcoleptics, such as why they tend to have weaker immune systems. Many people with

narcolepsy also report being sick frequently in childhood due to viral infections. When I was in

Kindergarten, I was constantly getting new viral infections that left my doctors puzzled. I also
have always had a weak immune system. So personally, I find the explanation of viruses to be an

appealing one. The general consensus in the narcolepsy community is that the combination of

genetic susceptibility, the presence of environmental irritants and viruses, and having a weaker

immune system all contribute to the development of narcolepsy. Like narcolepsy, the

development of autoimmune diseases is something that scientists still don't entirely understand.

Obviously, the cause of development varies among autoimmune diseases, but there are general

trends they follow. Generally, autoimmune diseases are triggered by environmental irritants,

chemical irritants, drugs, bacteria, or viruses. Like narcolepsy, people with a family history of

said autoimmune disease will be more likely to develop it. Overall, narcolepsy and official

autoimmune diseases tend to develop due to a combination of genetic predisposition and outside

factors. It is irrefutable that as far as causation goes, narcolepsy bears the classic signs of an

autoimmune disease. Both are thought to be caused by environmental irritants and viruses.

Another way narcolepsy aligns with many autoimmune diseases is that symptoms almost always

develop in childhood. This had previously confused researchers of narcolepsy. However, if

narcolepsy was an autoimmune disease, this would not seem unusual. (As mentioned earlier, our

immune systems are more vulnerable when we are younger. Therefore, most autoimmune

diseases develop in that time.) The correlations between narcolepsy and recognized autoimmune

diseases are profound, and not easily dismissible. Both are chronic incurable diseases that

involve treatment to relieve the symptoms of the disease, lifestyle changes, and replace vital

substances the body no longer produces. Both develop in early childhood and are thought to be

"triggered" by a combination of genetic predisposition and other factors, most notably viruses.

Aside from the many similarities they share, defining narcolepsy as autoimmune disease serves

to explain many of the puzzling aspects of narcolepsy, such as why it develops at such an early
age and is associated with weaker immune systems. I believe these aspects alone serve enough

evidence to categorize it as an autoimmune disease.

If there is an overwhelming amount of evidence to support the autoimmune-hypothesis,

why then is narcolepsy still not classified as an autoimmune disease? The most compelling

argument against this classification is the lack of an "HLA" variant. HLA stands for human

leukocyte antigen. Basically, an HLA is an important immune system cell that is responsible for

identifying foreign cells from cells that belong in your body. This antigen marks cells as "self" or

"non-self". If a cell is marked "non-self", it will be attacked by other cells in the immune system

until it is destroyed. HLAs are the leaders of your immune system, directing it to attack or not

attack parts of your body. Like fingerprints, everyone has a unique variant of HLA. (Variant is

another word for "type", so HLA variants are different types of HLA.) Also like fingerprints, the

types of HLAs that people have can be categorized into groups. In autoimmune diseases, specific

HLA variants are associated with specific autoimmune diseases. For example, HLA-B27 is

commonly found in those suffering from ankylosing spondylitis, juvenile arthritis, and Reiter's

syndrome. Every autoimmune disease is associated with a respective HLA variant. Because of

this, in order to be considered an autoimmune disease, suffers of said disease must have the same

grouping of HLA variant. There are no exceptions to this rule- in classifying autoimmune

diseases, HLA variants have always played a dominant role. Because no HLA variant has been

found in narcolepsy, it is not classified as an autoimmune disease, according to this unofficial

rule. When the autoimmune-hypothesis was first proposed, researchers knew that in order for it

to be valid, an HLA variant associated with narcolepsy must be found. The search for this HLA

variant has been long and fruitless. No such variant has been found... yet. The scientific process

is slow, tedious, and often unrewarding. Answers do not always come easily. But I truly believe
that one day, the HLA variant will be found, and narcolepsy will finally be classified as an

autoimmune disease. It is only a matter of time.

However, as important as the HLA variant has been in the past for identifying

autoimmune diseases, I think it is foolish to consider it the dominant factor. Diseases are

infinitely complicated, and narcolepsy is no exception. As discussed in the second paragraph,

there is an overwhelming amount of evidence for narcolepsy to be autoimmune in nature.

Besides the lack of an HLA variant, there are virtually no other arguments against narcolepsy

qualifying as an autoimmune disease. Anyone who looks at the history of autoimmune diseases

and how they were discovered knows that finding HLA variants is a long and difficult process.

The current lack of an HLA variant in narcolepsy should not be the basis for not classifying it.

Furthermore, saying that narcolepsy is not an autoimmune disease simply because an

HLA variant has not been found (yet) is harmful to those in the narcolepsy community.

Narcolepsy is what is known as an "invisible disease". Like depression and mental illnesses,

those with narcolepsy are often accused of either faking or exaggerating their symptoms, or even

imagining them. Symptoms of invisible diseases are often believed to be just "part of their

personality" by those around them, and the victims themselves often come to believe this too.

And sometimes trying to explain what they're going through is seen as a cry for attention rather

than a cry for help. Those with narcolepsy are often seen as lazy, irresponsible, or bored.

Constantly waking up and falling back asleep leaves narcoleptics in a never-ending stage of

confusion, leaving others to label them as forgetful, scatter-brained, or not embedded in reality.

These labels are not meant to be malicious, but in doing so, many people with narcolepsy remain

undiagnosed because they believe their symptoms are normal, or just who they are as an

individual. It takes an average of 10-15 years for narcolepsy to be diagnosed after symptoms first
appear. It is commonly believed that 50% of those with narcolepsy are never diagnosed, and live

their lives never knowing that what they're going through isn't their fault. In other words, the

phrase that begins this paper, "Narcolepsy is a chronic sleep disorder that affects roughly 0.05%

of the population", may not be true. The percentage of people with narcolepsy could be much

higher than we realize. Not only is narcolepsy a widely misunderstood and underdiagnosed

disease, it is also often misdiagnosed. Symptoms of narcolepsy are often confused with

symptoms of other disorders. Signs of cataplexy in undiagnosed narcoleptics often leads to being

misdiagnosed with a seizure disorder. Hallucinations (due to the narcoleptic constantly shifting

from dream state to wake state) can even lead to being misdiagnosed with schizophrenia or other

psychotic disorders. Other times, sufferers of narcolepsy are correctly diagnosed with depression,

but their doctors fail to realize the underlying culprit. (It's narcolepsy.) The point is, narcolepsy is

a widely misunderstood and unrecognized disease. Even doctors with years of training can fail to

recognize narcolepsy in their patients. Becoming more recognized and understood is key to

helping those with narcolepsy, and diagnosing those who do not realize they have it. If

narcolepsy was categorized as an autoimmune disease, this would make it infinitely more

recognized. Autoimmune diseases, although individually uncommon, are common altogether. An

estimated 20% of Americans have some kind of autoimmune disease. Categorizing narcolepsy as

an autoimmune disease would help scientists to understand it better by comparing it to other

autoimmune diseases. If narcolepsy was added to the list of 80 recognized autoimmune diseases,

it would not be so unknown and alienated. More research on narcolepsy would be conducted

(due to more people being aware of it and gaining interest), and more people would recognize

the symptoms of narcolepsy, leading to earlier diagnoses.

 Overall, I believe the categorization of narcolepsy as an autoimmune disease would solve

most, if not all, of the issues facing the narcolepsy community today. Narcolepsy is too serious

of a disease to be as misunderstood as it has been in the past. The overwhelming amount of

evidence pointing to narcolepsy being autoimmune leads me to believe that narcolepsy is an

autoimmune disease, HLA variant or not. The desperate need for recognition of sufferers of

narcolepsy leads me to believe that this categorization cannot wait. We have to stop waiting for

the HLA variant to appear. It could take years, perhaps even decades. If we keep waiting to

categorize narcolepsy, countless narcoleptics will continue to suffer, undiagnosed and unaware

of their condition. Maybe it's time to stop placing so much emphasis on HLA variants and start

looking at the bigger picture.

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