What is the Cause?

A person with an autoimmune disease has an immune system that attacks healthy cells. Examples of autoimmune diseases include Multiple Sclerosis, Type 1 Diabetes, and Mellitus Rheumatoid Arthritis. An interesting and significant finding from recent studies show that Narcolepsy may be caused by an autoimmune attack in the body as well. Therefore, narcolepsy may be primarily an autoimmune disease. But is it really?

Researchers determined that the two possible causes of narcolepsy are lack of hypocretin and a different form of the human leukocyte antigen. Hypocretin is a hormone that allows animals and humans to stay awake and alert. Even though the brain cells and system that create hypocretin cells are still in narcoleptic patients, the cells are missing, which can mean one thing: something has to destroy them. Researchers now believe that they are destroyed by the immune system in an autoimmune attack.

This image below shows the difference between the number of hypocretin cells in the hypothalamus of narcoleptic and a non-narcoleptic person. As you can see, a narcoleptic has predominantly less hypocretin cells.

 People with narcolepsy also have a different type of the human leukocyte antigen. HLA allows the immune response to act and permits the immune system to fight off pathogens. Although many studies found no relationship between narcolepsy and the immune system, Professor Mignot from Stanford University was curious and suspected that there is indeed a link. As a result, he created a study to test his idea. Along with Joachim Hallmayer and other colleagues, they focused their analysis on the DNA of four thousand participants. Half of the participants shared the same HLA variant linked to narcolepsy and the other half were actual narcoleptics. According to the results, narcoleptics share a gene that allows T cells to act and destroy pathogens. The gene also permits T cells to know how to respond to intruders that are brought to them from HLA molecules.  According to Nature Genetics, the researchers concluded that T cells and HLA both work together to kill off hypocretin cells in narcoleptics.

Although this is significant news, there are still some doubts and curiosities. According to Mignot,  "We don't know why bodies go haywire and start attacking themselves". Mignot’s study fails to explain why hypocretin cells attract T cells. Also, it doesn’t explain the purpose of the destruction. Despite these failures to answer these questions, knowing that narcolepsy may be caused by an autoimmune attack allow guide researchers to find the cause for narcolepsy and to create more treatments for the victims.

Xyrem: A common Date-Rape Drug?

The Food and Drug Administration has accepted a new treatment for narcolepsy. The administration was not sure whether GHB, gamma hydroxyl butyrate, should be permitted as a prescription drug used to treat narcolepsy as it is commonly used as a “date rape” drug. GHB, or commonly called Xyrem, was initially developed as a anesthetic because it depressed the central nervous system. It was later inhibited because it caused many unnecessary side effects and was abused as a recreational drug.

Although it may be dangerous if used for the wrong purpose such as sexual assault, the manufacturer has proved that it can treat cataplexy, a common symptom of narcolepsy in which muscle weakness takes place. A government advisory panel voted for the permission to sell the medication if and only if the FDA approves it and establishes a risk management plan in order to prevent illegal and dangerous abuse of the drug. Ultimately, Xyrem was not approved as a general drug for narcolepsy when Provigil, another common narcolepsy medicated drug, was recently accepted for the condition. Although Provigil has priority for narcoleptic patients, Xyrem will be used primarily to treat narcoleptics who suffer from dangerous incidences of cataplexy.

Although Xyrem can help narcoleptic patients, the government must be aware of its danger and supplemental usage. GHB has now been placed in the most strictly regulated drug category. A law has been enforced that ensures a person a maximum of twenty years in prison if it illegally made or sold. Despite its dangers, narcoleptics who experience cataplexy may feel safe to know they can be treated. How ironic?

I may be going onto a tangent, but I found an interesting video about GHB's harmful effects and prevalence as a "date rape" drug. Check it out! 

A Narcolepsy Story

Although many questions about narcolepsy have been answered through extensive research and trials, mysteries of the condition still remain. Just like many other disorders and diseases, narcolepsy has symptoms, biological causes, and treatment. But what makes it different? A great way to answer this question is to hear the real life story of a narcoleptic, Anthony Raymond, who experiences daily episodes of sleep. Not only does he mention how he deals with his symptoms, but he also takes into account the emotional distress he faces as a result of narcolepsy. Also, towards the end of the video, Dr. Emmanuel Mignot, the director Stanford's Center for Narcolepsy, explains the causes for narcolepsy and its symptoms. He provides images that can further assist you in understanding what occurs in the brain of a narcoleptic.

Provigil and its Side Effects

Provigil or modafinil is a prescription drug used for the treatment of narcolepsy. What's so great about it? It not only enhances the wakefulness and alertness for narcoleptics, but it also reduces excessive daytime sleepiness and anxiety. However, just like any other medications, provigil has a number of cons related to side effects that it may cause.

The many side effects caused by Provigil have been studied in clinical trials. People who have took Provigil reported having the following side effects:

• headache
• nausea 
• diarrhea
• insomnia 
• heartburn 
• flu-like symptoms
• dry mouth  
• Nosebleeds 
• eye/vision problems
• sore throat

Furthermore, The European Medicines Agency has banned the use of modafinil for patients with high blood pressure due to cardiovascular risks. In 2009, Dr. Nora Volkow, director of the National Institute on Drug Abuse, created a study and determined that Provigil causes changes in the pleasure center of the brain, which can ultimately lead to habit and addiction.

So does Provigil still sound ideal for narcoleptics? Although it may seem that there are so many side effects linked to the medication, it benefits people with narcolepsy more than it can hurt them. They may experience dreadful side effects, but I'm sure its a risk they're willing to take.

Modafinil: narcolepsy agent and weight reducer?

An antipsychotic drug called olanzapine (Zyprexa), used to treat schizophrenia, has caused side effects such as weight gain. James Roerig, Pharm.D., of the University of North Dakota in Fargo, created a study that  tested how modafinil, a narcolepsy agent, can limit the weight gain that olanzapine causes.  During the trial, healthy volunteers were given modafinil and olanzapine for three weeks. It was observed that volunteers who took modafinil and olanzapine experienced half the weight gain than the ones who took olanzapine with a placebo.

                                                                                         

Dr, Roerig explains that olanzapine and other anti-psychotic drugs cause weight gain because they block the H1 histamine receptor, which eventually causes sleepiness, stimulates appetite, and increases food intake. Modafinil, on the other hand, is believed to activate the H1 histamine system and prevent blockage from olanzapine. 

A case report detailed a schizophrenic patient who weighed 280 pounds. In one year, he/she lost 40 pounds when modafinil was added to olanzapine. Then when he/she stopped taking modafinil, the patient gained 30 pounds. After a while when modifinil was started again, he/she lost 10 pounds only in 6 weeks, a shorter time period.

Another study was created in order to investigate how enzymes are affected by these medications. It was found that eight volunteers out of fifty experienced increased liver enzymes. Other trends included reduced energy and protein intake.

Although these studies and trials may show trends, nothing is proved. Also, modafinil may limit weight gain due to olanzapine, but it is not FDA-approved for limiting weight gain in general.

The link between H1N1 vaccine and Narcolepsy

In 2009, swine flu haunted the nation as many experienced unpleasant symptoms such as fever, cough, sore throat, chills, fatigue, diarrhea, and vomiting. As a result of the fear, vaccinations were available for prevention. In 2010, Margaret Chan, the head of the World Health Organization stated that the pandemic flu has ended. 

Even though the pandemic may be over, vaccination used against influenza are thought to cause another problem. The French Agency for Sanitary Control of medicinal products announced that there were 22 cases of narcolepsy after the use of the H1N1 vaccine in Europe. Is this a coincidence or is there really a link between narcolepsy and the influenza vaccine?

Emmanuel Mignot, a sleep researcher at Stanford University, explained that narcolepsy is an autoimmune disease or an occurrence where the immune system attacks healthy and normal cells and tissues. He stated that the immune system attacks and destroys neurons that produce hypocretin, which ultimately affect the sleep cycle. According to Mignot, narcolepsy is hereditary and is greatly influenced by environmental factors that can initiate an autoimmune response.  In his paper, Annals of Neurology, Mignot proposes that one environmental trigger is H1N1. A study in China showed that the greatest number of narcolepsy cases occurred a few months after the flu. Although there is a relationship according to this study, other researchers are unable to find the link between the vaccine and narcolepsy.

Despite inconsistent findings, more studies are being done in order to understand if narcolepsy is truly related to the influenza vaccination. Further analysis can ultimately provide information on the cause of narcolepsy and the destruction of hypocretin cells.

Here is a video from Finland YLA News on the link between the swine flu shot and Narcolepsy in children:

Narcolepsy FAQs

Since this is my first post, I just want to share with you my answers to some  frequently asked questions. Hopefully, it will be a great start as we explore further into Narcolepsy.

What is narcolepsy?

Basically, narcolepsy is a neurological sleep disorder that is characterized by random episodes of sleep and sleepiness.

Other than random bursts of sleep, what other symptoms occur?

People with narcolepsy experience cataplexy during episodes of sleep or drowsiness. Cataplexy is characterized by muscle weakness or the loss of muscle tone. Cataplexy may be accompanied by sleep paralysis, a condition in which people are unable to move or perform other voluntary actions. Also, narcoleptics often hallucinate as they wake up or fall asleep.

How is it caused?

Many people believe that mental illness or psychological problems initiate narcoleptic episodes. But that is not true because the cause is majorly biological. According to the Stanford Center for Narcolepsy, studies show that loss of the neurotransmitter called hypocretin is a major cause of narcolepsy with cataplexy.  Hypocretin is located in the hypothalamus and is responsible for wakefulness and REM sleep. An autoimmune attack in the body may be the reason there is a destruction of hypocretin molecules. Unfortunately, the cause for narcolepsy without cataplexy has not yet been discovered.  Decreaing levels of other neurotransmitters like histamine can affect sleep and narcolopsy as well.

Is it hereditary?

The University of Maryland Medical Center states that narcolepsy may consist of a genetic factor. However, the genetic component is not enough to cause narcolepsy. Only 8-10% of people with narcolepsy have relatives with the same sleep disorder.

Are there any conventional or alternative treatments?

Although there is no cure for narcolepsy, many medications are used in order to reduce or manage episodes and attacks.  Some medicines include Adderall, Dexedrine, Ritalin,  DextroStat, Nuvigil, Provigil, and Xyrem. People with narcolepsy also join support groups and speak to psychologists and therapists so that they can express their emotions and deal with their condition.

Also, here is a video that explores the life of a person who struggles with narcolepsy. It may include other answers to questions you may have.

If you have any other questions, feel free to post a comment and I'll be glad to answer back!