When diagnosed with a new condition, the first question is almost always "How?" We naturally want to know exactly what brought us to that moment. This curiosity may be even stronger with something like narcolepsy, a chronic sleep disorder that is both under-recognized and misunderstood, according to the nonprofit Project Sleep.
While scientists have yet to pinpoint the exact cause of narcolepsy, a majority of cases are tied to low levels of a brain chemical involved in regulating our sleep-wake cycle, according to the Cleveland Clinic. And other factors are thought to play a role in triggering the disease process.
Here's how sleep experts explain the causes of narcolepsy.
What are the signs of narcolepsy?
Before delving into the causes, let's consider what narcolepsy looks like.
Narcolepsy is characterized by excessive daytime sleepiness, hallucinations, sleep paralysis, vivid dreams, and more, says Steven Thau, MD, division chief of the Pulmonary and Sleep Medicine Department and medical director of the Sleep Center at Phelps Hospital/Northwell Health.
It can present at any point in a person's life, but most commonly it initially occurs in a person's teens or 20s, Dr. Thau tells Health.
While each case is different, excessive daytime sleepiness is generally the first symptom to surface. Symptoms such as hallucinations, sleep paralysis, and cataplexy may follow, says Manjamalai Sivaraman, MD, FAASM, a sleep medicine specialist and neurologist at the University of Missouri. The latter may not happen for a few years, if at all.
What are the types of narcolepsy?
There are two main types of narcolepsy: types 1 and 2. There's also a third known as secondary narcolepsy. (More on that one below.)
Narcolepsy type 1 covers anyone who has low levels of hypocretin (a brain chemical that controls wakefulness) and experiences cataplexy (sudden muscle loss), according to the Mayo Clinic. Type 1 makes up about 70% of narcolepsy cases, says Richard Bogan, MD, a medical officer at SleepMed, Inc. and associate clinical professor at the University of South Carolina School of Medicine and the Medical University of South Carolina in Charleston.
People with narcolepsy type 2 may experience all the symptoms of narcolepsy except cataplexy—and their symptoms are often less severe, says the National Institute of Neurological Disorders and Stroke (NINDS). And their hypocretin levels are usually normal.
While there are no known ways to prevent or cure type 1 or type 2 narcolepsy, NINDS notes that lifestyle changes and medications may be helpful for maintaining alertness and managing other symptoms.
What causes narcolepsy?
While the science is still evolving, here's what's known so far.
People with type 1 narcolepsy have very low levels of brain chemicals called hypocretins. These chemicals, first discovered in 1998, are important for a couple of reasons, per the Division of Sleep Medicine at Harvard Medical School. For one thing, they keep people awake and alert. They also prevent people from drifting off into REM (rapid-eye movement) sleep while they're awake.
In people type 1 narcolepsy, however, the nerve cells that produce hypocretins die off, and the resulting dearth of these chemicals leads to sleepiness and poorly regulated REM sleep, per Harvard's Sleep Medicine Division.
Research by two separate investigative teams suggests that type 1 narcolepsy is caused by a severe loss of neurons that produce these chemicals, per a 2015 review in the New England Journal of Medicine.
As for what causes type 2 narcolepsy? It's possible that people who have this form of the disorder may sustain less injury to their neurons than those with type 1, according to that same review, which references a 2009 Sleep study. But data on the disease process involved in type 2 narcolepsy "are quite limited," notes the New England Journal.
Bottom line: Scientists don't fully understand what triggers the loss of hypocretin-producing cells, although it appears that one or more of the following factors may be involved:
Most people with narcolepsy, especially type 1, have a gene variation known as HLA-DQB1*06:02. It is a variation of the HLA-DQB1 gene, which "provides instructions for making part of a protein that plays an important role in the immune system," according the US National Library of Medicine. The risk of narcolepsy associated with this variation and related genes is unclear to researchers at this time.
That same gene variation is found in 50% of people with narcolepsy type 2, but only 12-30% of the general population, according to the New England Journal.
Speaking of risk factors, narcolepsy isn't a disorder that tends to run in the family. According to NINDS, just up to 10% of people with type 1 narcolepsy have a close family member who presents with similar symptoms. If a parent has narcolepsy, the odds of passing it down to a child is only about 1%, says Mayo Clinic.
People with the HLA-DQB1*06:02 gene variation may be at increased risk of developing narcolepsy after being exposed to a trigger, such as an infection, says NINDS. That's based on studies of people after they developed narcolepsy.
Upper airway infections such as streptococcus pyogenes and influenza A (including H1N1) are strongly associated with narcolepsy, per a 2011 study in the Annals of Neurology, especially in cases where it begins in childhood, notes Dr. Sivaraman.
An autoimmune reaction
We know that people with narcolepsy type 1 have low hypocretin levels—but why? A leading theory considers narcolepsy to be an autoimmune disorder.
"There are supporting evidences for autoimmune destruction—the immune system in one's body attacking its own healthy cells—of hypocretin neurons in the hypothalamus of the brain," says Dr. Sivaraman. To break it down, if this theory is true, then a person's own immune system is responsible for the brain lacking in hypocretin.
As Dr. Thau puts it, in this case, "the cells that control wakefulness are damaged."
Currently, researchers are working on using immunotherapy to reverse this loss, Dr. Bogan tells Health. According to a 2020 review published in Current Treatment Options in Neurology, small studies have shown an improvement in symptoms for narcolepsy patients after using immunotherapy treatment, especially those who recently presented with the disease. However, the experiments were uncontrolled and did not have clear endpoints, requiring more research to achieve any definitive answer on the treatment's benefits.
What causes secondary narcolepsy?
Unlike narcolepsy types 1 and 2, doctors do know the "why" behind secondary narcolepsy. This form of narcolepsy occurs when the brain's hypothalamus region gets damaged, according to Harvard's Division of Sleep Medicine.
These people can experience all of the same symptoms as those with types 1 and 2. However, they might also have severe neurological problems and require a large amount of sleep—typically 10 hours or more.
"In rare cases, brain lesions or diseases such as tumors, vascular malformations, strokes or inflammatory diseases of the brain can result in the destruction of the signaling pathways that increase brain activity and promote wakefulness," says Dr. Thau.
According to the National Health Service, secondary narcolepsy causes include:
- A head injury
- A brain tumor
- Multiple sclerosis
- Encephalitis, a rare condition in which the brain swells
As Dr. Thau notes, "a healthy lifestyle and avoiding smoking or the use of illicit drugs decrease the risk of some of the disorders that cause secondary narcolepsy."
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