Hannah

Langsdorf

Fenster

ENG 1020

11/1/16

Tragically, sleep deprivation is commonplace among many students. In my friend group

in high school, everyone complained about the lack of sleep and how tired they felt. This was

understandable, as most were serious students who studied late into the night and forced

themselves out of bed at 6 a.m. everyday. Their complaints echoed my own - I lived in a constant

state of drowsiness; falling asleep in almost all of my classes daily. This, I assumed, was because

I only got 6 hours of sleep on average a night and like most teenagers, often stayed up very late.

For me, school had always been a battleground. In elementary school, my teacher's notes in

report cards were always the same; something along the lines of "she's a hard worker but always

falls asleep in class". In middle school, it only seemed to get worse. No matter how hard I tried, I

would fall asleep during the lesson. Countless hours of instruction were wasted for me every day.

I tried many different tactics: tapping my foot the whole hour, drinking water, eating snacks,

chewing gum, even spraying myself in the face with water. Nothing worked. By my senior year

of high school, I was missing entire class periods; school was a constant cycle of confusion,

drowsiness, and frustration. Luckily, a friend asked me if I had ever considered I may have

narcolepsy. After some research on my own, many appointments with specialists, and a sleep

study, I was finally diagnosed with narcolepsy. I was prescribed Concerta, a stimulant with

methylphenidate. Although narcolepsy is chronic and there is no "miracle drug" that will erase

all symptoms, taking this medication made me more alert and stopped me from having "sleep
attacks", sleep paralysis, hallucinations, and other symptoms of narcolepsy. I finally felt like I

could function normally without fear of falling asleep in inappropriate situations.

In choosing this topic, I am aware there are many who know little to nothing about

narcolepsy. Narcolepsy is a complex disorder that is difficult to summarize, particularly since

much research is still being done. The National Sleep Foundation describes narcolepsy as "a

chronic brain disorder that involves poor control of sleep-wake cycles". This definition is mostly

accurate, although the phrase "poor control" is frustrating as it implies that narcoleptics possess

the ability to control their disorder but choose not to. Like any disorder, narcolepsy is subject to

stereotypes, belittlement and satirization by the media, and is generally misunderstood by the

general public. In order to understand narcolepsy, it is necessary to have a basic understanding of

normal sleep cycles. Although narcolepsy is most known for day-time sleepiness, sleep at

nighttime is equally as disturbed. Normally, people go through 4 stages of sleep at night: stage 1,

stage 2, stage 3, and REM. These stages are cycled through, in order, about 4-6 times a night.

REM is typically reached in 80-110 minutes. The average time to reach REM for narcoleptics is

5 minutes (mine was 2 minutes and 35 seconds). Narcoleptics spend the majority of their time in

REM, and the other stages are usually present but are completely out of order and

disproportionate compared to normal sleepers. They also frequently wake up anywhere from 4-

10+ times during the night, although they may not remember them. This adds further distortion

to sleep cycles. During the day, narcoleptics experience "sleep attacks", hallucinations, sleep

paralysis, and cataplexy, although most do not experience all of these. Most common are "sleep

attacks", in which one suddenly falls asleep without warning, usually immediately to REM.

Sleep attacks occur regardless of the victim's wishes to stay awake. In my personal experience,

exposure to stimuli such as bright light, pain, food, caffeine, and sprays of water to the face do
almost nothing to prevent sleep attacks. Sleep attacks can last anywhere from 5 seconds to 15

minutes. The amount of sleep attacks vary greatly from person to person. Prior to taking

medicine, I usually had 40 sleep attacks a day. On my worst days, I fell into the 100s. Other

symptoms of narcolepsy include hallucinations and sleep paralysis. These symptoms are thought

to occur because narcoleptics are going in and out of REM sleep daily. Your body paralyzes

itself during sleep, and REM is associated with dreaming, which may explain the hallucinations.

Another symptom of narcolepsy is cataplexy. Cataplexy, a sudden loss in muscle tone triggered

by extreme emotions (usually fear or laughter), is prevalent in 70% of people diagnosed with

narcolepsy. Recently, narcolepsy has been organized into sub-categories of Type 1 (narcolepsy

with cataplexy) and Type 2 (narcolepsy without cataplexy). I was diagnosed with Type 2,

although many people in this category later develop cataplexy. But because I have not yet

experienced cataplexy, my research will focus on narcolepsy without cataplexy, although there is

much fascinating research being done on cataplexy.

 As relieved as I was to be diagnosed and my sleeping problems (mostly) solved, I still

had many unanswered questions. Most of my questions about narcolepsy were resolved by

online research or asking my sleep specialist, but many are still unanswered. I'm guessing this is

because sleep science in general is a relatively new field that is lacking in hard research, or that

this new research has not been simplified and made available to the general public. Sleep is

mysterious and narcolepsy is no exception. The cause or causes of narcolepsy are still heavily

debated, and most websites I have been to (WebMD, sleepfoundation.org, mayoclinic, ect.)

reflect this. Most agree that narcolepsy is associated with low levels of orexin (neurotransmitter

that regulates wakefulness and appetite, AKA hypocretin), but other aspects, such as the role the

genetics or the immune system plays, are still heavily debated. In this paper, I will be

investigating whether or not narcolepsy is an autoimmune disease, and why. (However, I started

my research not knowing narcolepsy could be an autoimmune disease, and originally wanted to

cover all possible causes of narcolepsy. But I found this topic to be far too broad, eventually

narrowing my topic down to narcolepsy's possibility of being an autoimmune disease.)

I began my research by typing the phrases "narcolepsy" and "narcolepsy genetic" into

Proquest. There were few articles specifically about narcolepsy, but none of these provided me

with any new information. Other articles only briefly mentioned narcolepsy before going on to

other sleep disorders. Feeling discouraged, I decided to go back to the basics and see if I could

pick up anything that would help me be more specific in the library databases. I went to google

and typed "narcolepsy". I have used google to research narcolepsy previously, but usually only

skimmed the articles. I clicked on the first article from the National Institute of Neurological

Disorders and Stroke (NINDS), titled "Narcolepsy Fact Sheet". There were many sections to the

article, most of which held no new information for me. However, in the "What causes
narcolepsy?" section of the article, new information arose. After discussing that narcolepsy was

most likely caused by the loss of hypocretin-producing cells in the brain, the possibility of

narcolepsy being autoimmune was mentioned:

"Although the reason for such cell loss remains unknown, it appears to be autoimmune in nature

(an autoimmune disorder is when the bodys immune system mistakenly attacks healthy cells or

tissue). That is, the bodys immune system selectively attacks hypocretin-containing brain cells."

As mentioned before, narcolepsy is associated with low levels of orexin (AKA hypocretin;

neurotransmitter responsible for appetite and wakefulness). However, this article suggested that

people with narcolepsy didn't begin with low levels of orexin, and had lost their orexin-

producing neurons due to a malfunction of the immune system, likely at a young age. If this was

true, narcolepsy would fit under the description of an autoimmune disease. But this article only

briefly mentioned this possibility- more information was needed.

Intrigued by this new information, I returned to Proquest and searched the full text for

"narcolepsy autoimmune". This time, I had more success. A couple articles down, I found an

article from Stanford University titled: "Stanford University School of Medicine; Narcolepsy is

an Autoimmune Disorder, Stanford Researcher Says". This article discussed how researchers had

long believed narcolepsy to be an autoimmune disease, and were excited by the findings of

Emmanuel Mignot, a scientist at the Stanford University School of Medicine. Scientists

suspected narcolepsy to be autoimmune due to the brain's loss of hypocretin-producing brain

cells.

At this point, the article was getting quite technical, and I felt I needed a better

understanding of autoimmune diseases before I could continue reading the article. I had known
that autoimmune disorders were characterized by the immune system mistaking a kind of cell as

foreign and thus destroying it, but I did not why or how this occurred. I googled "cause of

autoimmune disorders", and found an article titled "Autoimmune diseases" on healthline.com.

The general consensus seemed to be that autoimmune diseases were genetic- that the particular

kind of cell your immune system destroyed (in the case of narcolepsy: hypocretin cells) was

genetically different than that of "normal" people. This genetic difference caused your immune

system to recognize that cell as foreign. But still, I wondered why the immune system chose to

wait to attack those cells? What caused the sudden destruction of these cells? In the first article I

referenced (from NINDS) as well as others I had read, recent research had suggested that people

develop narcolepsy over time, and were not born with it. Based this article on autoimmune

diseases, it seems this was true for most autoimmune diseases. It was also said that many who

have this genetically different kind of cell never develop the associated autoimmune disease.

Meaning, even if you carry the genes for narcolepsy (or other autoimmune diseases), you may

not develop it. Environmental irritants, bacteria or viruses, drugs, or chemical irritants were said

to be the "triggers" that activated your immune system to attack those cells. (Although not

explicitly stated in the article, I theorized this was because your immune system was more active

when irritated, and more likely to notice your genetically "defective" cells.) Because our immune

systems are more vulnerable in childhood, autoimmune diseases usually develop during that

time. Now, I was beginning to see why scientists were so certain narcolepsy was an autoimmune

disease despite the lack of proof. The NINDS article I first referenced mentioned that narcolepsy

usually developed in childhood, that narcoleptics had poor immune systems, and that narcolepsy

seemed to be somewhat genetic. All of these were classic signs of an autoimmune disease. Now

that I had a basic understanding of autoimmune diseases, I returned to the Stanford article.
 It seemed that while scientists had suspected narcolepsy to be autoimmune for decades,

they had been unable to identify the specific gene responsible. In Mignot's 2013 study, a variant

of the human leukocyte antigen (HLA) gene was shown to be correlated with narcolepsy. From

1,800 people surveyed (who all had the HLA variant gene), 800 of those had narcolepsy. Various

people in this field were quoted, all seeming very optimistic and pleased at this finding. One

quote in particular stood out: "This is a very important finding," said Merrill Mitler, PhD, a sleep

disorders expert and program director at the National Institute of Neurological Disorders and

Stroke, who was not involved in the study. "It puts in place another piece of the puzzle and

shows a way to link [this gene variant] to hypocretin-containing neurons via an autoimmune

attack." It seemed that scientists had finally found the evidence they had been searching for. I am

guessing this information has not yet been made readily available to the public since all scientific

findings must be duplicated and proven correct several times before listed as "fact". New

research and information generally takes some time to be recognized. Nevertheless, I shared the

excitement of the scientists in the (almost) classification of narcolepsy as an autoimmune

disease.

Later in Proquest, (still under the search terms "narcolepsy autoimmune", I was

disappointed to find that the aforementioned study had been retracted in a 2014 issue of Science

News, titled "Study claiming narcolepsy is an autoimmune disease retracted". In order for

scientific studies to be accepted in the scientific community (and presented to the public), they

should be duplicated to prove their credibility. In later studies (intended to "double check" the

findings of Mignot), researchers failed to replicate the results. They did not find participants with

narcolepsy to have higher amounts of the HLA variant gene than normal participants. In other

words, these studies found no correlation of narcolepsy and the HLA variant. For this reason, the
researchers of the Stanford were forced to retract their study. Although frustrating, this does not

entail that narcolepsy is not an autoimmune disease, or even that HLA gene variants are

unrelated. It simply illustrates that the scientific process is a tedious one, and that conclusions are

not always easily reached.

Because I am not a neuroscientist nor an expert on narcolepsy, I often googled things in

articles I was unfamiliar with, such as what an autoimmune disease was. Also worth noting is

that I often found articles (mainly in the databases) that were difficult to decipher and far too

technical for me to understand, or were otherwise unhelpful. However, I feel as though I

expanded my previous knowledge of narcolepsy and was eventually able to understand most of

these articles towards the end of my research. But even so, I felt a bit overwhelmed by some of

the terms and broadness of my topic, even though I thought I knew most things about narcolepsy.

It was honestly a bit frustrating to be only able to focus on this one aspect, and I became a bit

side-tracked at some parts, but it was probably good that I limited my research to the

autoimmune aspect of narcolepsy. During my research, I learned that topics, particularly

scientific ones, are often far broader than predicted. I also learned that the scientific process can

be slow, and there are many setbacks researchers face in their research, even when their results

appear conclusive. I definitely gained a further appreciation for the scientific method and a

renewed enthusiasm for personal research on narcolepsy.

To be honest, I've always dreaded peer editing, but for this research paper it was helpful.

I felt my paper was mostly complete, but through peer editing I realized I needed to reorder some

things, such as the order of my quotations in one part of my paper. It also allowed me to catch

some errors in grammar I had overlooked. It was interesting to read other people's papers and get

a feel for their writing styles. During Judith's library presentation, I didn't learn anything new
because a previous class this semester had gone over the various databases and ways to utilize

the library's resources. Because I had prior knowledge of the library databases, the way I

researched (primarily using Proquest and occasionally Google) did not change. But before I

started school here, I was aware of databases, but felt intimidated by them, as I didn't know how

to use or get access to them. This research project has definitely made me feel more comfortable

navigating library databases, and I feel more knowledgeable in using search terms to constrain

my results.
Citations

@healthline. "Autoimmune Disease." Healthline. N.p., n.d. Web. 23 Oct. 2016.

"Narcolepsy Fact Sheet." U.S National Library of Medicine. U.S. National Library of Medicine,
n.d. Web. 23 Oct. 2016.
"Narcolepsy." -. National Sleep Foundation, n.d. Web. 23 Oct. 2016.
Seppa, Nathan. "Study Claiming Narcolepsy Is An Autoimmune Disease Retracted." Science
News 186.5 (2014): 15. OmniFile Full Text Select (H.W. Wilson). Web. 1 Nov. 2016.
"Stanford University School of Medicine; Narcolepsy is an Autoimmune Disorder, Stanford
Researcher Says." Diabetes Week (2009): 37. ProQuest. Web. 23 Oct. 2016.