Narcolepsy is an uncommon sleep disorder that causes sudden waves of daytime sleepiness, among other symptoms.

For a long time, the possible causes of narcolepsy remained a mystery. However, growing evidence suggests that narcolepsy may be an autoimmune disorder.

There is still much to learn about narcolepsy. As we learn about its causes, doctors may be able to better develop ways to prevent and treat it.

Narcolepsy is generally categorized as either type 1 or type 2. Narcolepsy type 1 means a person with narcolepsy also experiences cataplexy, a sudden loss of muscle tone and motor control. Narcolepsy type 2 is not accompanied by cataplexy, and its symptoms tend to be less severe.

The main cause of narcolepsy type 1 is the loss of neurons that produce the brain hormone hypocretin. Hypocretin helps regulate our sleep and wake cycles as well as appetite.

The National Organization of Rare Diseases acknowledges that narcolepsy is likely an autoimmune disorder, but one in which there is still a lot to learn.

Research from 2018 suggests that a few different factors cause the immune system to attack these neurons in narcolepsy type 1. That same study pinpoints a genetic mutation in the human leukocyte antigen (HLA) system as a risk factor for narcolepsy type 1. The HLA system is a key part of our immune system.

Since hypocretin levels in people with narcolepsy type 2 tend to be typical, researchers are unsure of its causes.

Other possible causes of narcolepsy include:

  • brain injury, especially to areas of the brain that control sleep and wake cycles
  • family history, though many people with narcolepsy have no known family history of it
  • hormonal changes
  • Pandemrix, an H1N1 flu vaccine used in Europe in 2009
  • severe infection
  • stress

Autoimmune disorders occur when the body’s immune system mistakenly attacks healthy cells.

The reasons why a person develops an autoimmune disorder aren’t always clear. Stress and physical injury may be risk factors. Genetic mutations play a role as well.

A 2017 study notes that environmental factors, like the H1N1 influenza virus (swine flu) and the Pandemrix vaccine used in that 2009 flu outbreak, may trigger an autoimmune response.

Similarly, a 2015 study suggests that the vaccine produced antibodies that bound to receptors in the brain responsible for sleep. Sensing that the antibodies were a threat, the immune system targeted them and destroyed neurons that produce hypocretin.

The Autoimmune Hypothesis

As researchers looked for clues to the causes of narcolepsy, the so-called autoimmune hypothesis emerged. Unlike better understood autoimmune disorders, like rheumatoid arthritis or lupus, there weren’t any obvious indications of an abnormal immune response in people with narcolepsy.

Still, studies of immune system cells known as T cells in people with narcolepsy suggest that the sleep disorder may be linked to an abnormal immune response triggered by CD4+ and CD8+ T cells. CD4+ cells help fight against infections. CD8+ cells help fight cancer cells and infected cells.

Higher levels of CD4+ cells in people with narcolepsy are well documented. But in a well-known 2018 study, researchers found higher levels of CD8+ cells in the blood of people with narcolepsy.

Their findings suggest that T cells may consider hypocretin-creating neurons a danger and react by signaling the immune system to attack them.

A 2019 study further suggests that certain levels of CD8+ reactivity, along with the HLA mutation, may contribute to the development of narcolepsy.

Can the COVID-19 vaccine cause narcolepsy?

Because the onset of narcolepsy in some people was associated with the 2009 and 2010 H1N1 flu vaccine Pandemrix, concerns of a similar development from the COVID-19 vaccine have surfaced.

However, the H1N1 and COVID-19 vaccines work very differently. There is no evidence that the COVID-19 vaccines produce antibodies that trigger the same immune response that led to a rise in narcolepsy cases after the H1N1 outbreak.

Once the neurons that produce hypocretin are lost, they cannot be restored. As a result, narcolepsy type 1 currently has no cure. However, you can manage symptoms with certain medications and lifestyle adjustments.

The first-line treatment is often a stimulant such as modafinil, according to the National Institute of Neurological Disorders and Stroke. If modafinil isn’t effective, then amphetamine-like stimulants may be necessary.

Other treatments and lifestyle adjustments that may be helpful include:

  • antidepressants
  • sodium oxybate, a sedative taken at night to help treat cataplexy
  • short daytime naps
  • a regular sleep schedule that involves consistently sleeping and waking up at the same time
  • daily exercise
  • no alcohol or caffeine before bedtime

Since evidence is mounting that narcolepsy may be an autoimmune disorder, there is ongoing research into using immunotherapy medications as treatment. But a 2020 study suggests there is still not enough evidence that immunotherapy will be an effective treatment option for narcolepsy.

Having one autoimmune disorder tends to increase the chances of having one or more additional autoimmune conditions. Some of these clusters occur more frequently than other combinations.

For example, type 1 diabetes and celiac disease often accompany each other, partly because they share a gene that predisposes a person to both of these conditions.

The combination of narcolepsy and other autoimmune disorders isn’t yet well understood, but certain conditions may be more likely to surface in people with narcolepsy.

A 2016 study suggests that the rate of autoimmune and other immunopathological diseases was more common in people with narcolepsy than the general population.

Among the other autoimmune disorders accompanying narcolepsy noted in the study were:

Can COVID-19 trigger narcolepsy?

Scientists are still learning about the many short-term and long-term complications associated with COVID-19.

Some studies, including a 2020 study investigating possible nervous-system disorders triggered by COVID-19, suggest that the body’s response to the coronavirus may raise the risk of neurological conditions like narcolepsy and multiple sclerosis.

Ongoing research should reveal more about any possible connections between COVID-19 and neurological diseases. It’s important to know, however, that COVID-19 is a novel coronavirus and not an influenza virus.

Narcolepsy is a rare sleep disorder that causes daytime sleepiness and, in some cases, muscle weakness and a loss of voluntary muscle control. Studies in recent years suggest that narcolepsy may be an autoimmune disorder, primarily triggered by a genetic mutation.

Though narcolepsy is a chronic condition that currently has no cure, researchers are working to learn more about its causes and how to safely and effectively treat it.

As scientists learn more about how the immune system affects the onset of narcolepsy, treatment options like immunotherapy may prove to be the answer.