Narcolepsy

Narcolepsy is a sleep disorder that is often misunderstood. It is characterized by severe and persistent daytime sleepiness that can cause impairments in school, work, and social settings as well as heighten the risk of serious accidents and injuries.

Although rare in comparison to many other sleep disorders, narcolepsy affects hundreds of thousands of Americans, including both children and adults.

Understanding the types of narcolepsy and their symptoms, causes, diagnosis, and treatment can empower patients and their loved ones to cope with it more effectively.

What Is Narcolepsy?

Narcolepsy is a disorder that disrupts sleep-wake processes. Its primary symptom is excessive daytime sleepiness (EDS), which occurs because the brain is unable to properly regulate wakefulness and sleep¹.

Normal sleep unfolds through a series of stages, with rapid eye movement (REM) sleep occurring in the final stage, usually an hour or more after falling asleep. In narcolepsy, REM sleep is irregular and often begins within minutes after falling asleep, which is much earlier than normal.

REM occurs quickly in people with narcolepsy because of changes in the brain that disrupt how sleep works. These disruptions also cause daytime sleepiness and other symptoms of narcolepsy.

What Are the Types of Narcolepsy?

According to the International Classification of Sleep Disorders, Third Edition² (ICSD-3), there are two types of narcolepsy: narcolepsy type 1 (NT1) and type 2 (NT2).

Narcolepsy Type 1

NT1 is associated with the symptom of cataplexy, which is the sudden loss of muscle tone. NT1 was formerly known as “narcolepsy with cataplexy.”

Not all patients who are diagnosed with NT1 experience episodes of cataplexy. NT1 can also be diagnosed when a person has low levels of hypocretin-1, a chemical in the body that helps control wakefulness.

Even when not present at diagnosis, cataplexy eventually occurs³  in a significant number of people with low levels of hypocretin-1.

Narcolepsy Type 2

NT2 was formerly known as “narcolepsy without cataplexy.” People with NT2 have many similar symptoms as people with NT1, but they do not have cataplexy or low levels of hypocretin-1.

If a person with NT2 later develops cataplexy or low hypocretin-1 levels, their diagnosis can be reclassified as NT1. This change in diagnosis is estimated to occur in about 10% of cases.

How Common Is Narcolepsy?

Narcolepsy is relatively rare. NT1 affects between 20 and 67 people per 100,000 in the United States. According to a population based study in Olmstead county Minnesota, NT1 is two to three times more common⁴  than NT2, which is estimated to affect between 20 to 67 people per 100,000.

Calculating the prevalence of narcolepsy is challenging because of underdiagnosis and delays in diagnosis. Many patients are not diagnosed with narcolepsy until years after their first symptoms⁵. As a result, some estimates place the prevalence of narcolepsy as high as 180 per 100,000.

Narcolepsy occurs roughly equally in men and women⁶ and can affect both children and adults. It can occur at any age, but onset has been found to peak at around age 15 and again around age 35.

What Are the Symptoms of Narcolepsy?

The symptoms of narcolepsy can have notable effects during both daytime and night time. The most common symptoms include:

• Excessive daytime sleepiness (EDS): EDS is the cardinal symptom of narcolepsy, affecting all people with the disorder. EDS involves an urge to sleep that can feel irresistible, and it arises most frequently in monotonous situations. Severe drowsiness often causes lapses in attention. Narcolepsy can cause “sleep attacks,” which involve falling asleep without warning. After short naps, people with narcolepsy usually feel temporarily refreshed.
• Automatic behaviors: Trying to avoid sleepiness can trigger automatic behaviors that occur while a person is unaware. For example, a student in class may continue writing but is actually just scrawling lines or gibberish on the page.
• Disrupted nighttime sleep: Sleep fragmentation is common in people with narcolepsy who may awaken multiple times during the night. Other bothersome sleep problems like excess physical movements and sleep apnea are also more common in narcoleptics.
• Sleep paralysis: People with narcolepsy have a higher rate of sleep paralysis, which is a feeling of being unable to move that occurs while falling asleep or waking up.
• Sleep-related hallucinations: Vivid imagery can occur while falling asleep (hypnagogic hallucinations) or when waking up (hypnopompic hallucinations). This may accompany sleep paralysis, which can be particularly disturbing or frightening.
• Cataplexy: Cataplexy is a sudden loss of muscle control. It only occurs in people with NT1 and not NT2. An episode of cataplexy often occurs in response to positive emotions like laughter or joy. Cataplexy normally affects both sides of the body and lasts for a few seconds to a few minutes. Some people with NT1 only have episodes of cataplexy a few times per year, while others can have a dozen or more episodes per day.

Although all people with narcolepsy have EDS, less than a quarter have all of these symptoms. In addition, the symptoms may not occur simultaneously. For example, it’s not uncommon for cataplexy to begin years after a person has started to have EDS.

Are Narcolepsy Symptoms Different In Children?

There is considerable overlap between narcolepsy symptoms in children and adults, but there are important differences as well.

In children, EDS is more likely to appear as restlessness or irritability⁷, which may be interpreted as a behavior problem. At night, children with narcolepsy may sleep longer⁸ and have more active body movements during sleep⁹.

Cataplexy is often more subtle in children, although it occurs in up to 80% of cases¹⁰. It commonly involves the face rather than the body and may be perceived as a facial tic. Cataplexy in children may not be tied to an emotional response. Over time, cataplexy symptoms in children evolve to their more traditional form.

What Are the Effects of Narcolepsy?

The symptoms of narcolepsy can have significant consequences for a patient’s health and wellness. Accidents are a pressing concern as sleep attacks, drowsiness, and cataplexy can be life-threatening when driving or in other environments where safety is critical. It is estimated that people with narcolepsy are three to four times more likely to be involved in a car accident¹¹.

Narcolepsy can also interfere with school and work. Sleepiness and pauses in attention can harm performance and may be interpreted as behavioral problems, especially in children.

Many patients with narcolepsy feel stigma related to the condition that can lead to social withdrawal. Without proper support, this may contribute to mental health disorders and negatively affect school, work, and relationships.

People with narcolepsy are at higher risk of other health conditions including obesity, cardiovascular problems like high blood pressure, and psychiatric issues like depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD).

What Causes Narcolepsy?

Research has started to reveal details about the underlying biology of narcolepsy, but more is known about NT1 than NT2. Even with growing knowledge, the exact causes and risk factors for each condition are not fully understood.

NT1

Narcolepsy type 1 is a disorder marked by the loss of neurons in the brain that are responsible for making hypocretin, also known as orexin, a chemical that helps regulate wakefulness and sleep. People with NT1 have a loss of 90% or more of the normal number of hypocretin-making neurons¹².

A genetically susceptible individual may experience damage to these neurons¹³ in an autoimmune fashion after an environmental trigger.

Some evidence suggests that NT1 fluctuates seasonally with a potential link to influenza (flu) virus. A rise in the onset of NT1 was also seen after the H1N1 epidemic¹⁴ and with a certain brand of vaccine used for H1N1, although this was exceedingly rare. Possible connections to other types of infections have been found as well.

Based on this data, one theory about NT1 is that an external trigger activates the immune system in a way that causes it to attack the brain’s neurons that make hypocretin. However, this autoimmune response inconsistently occurs and therefore is not the only cause.

Researchers have found that as many as 98% of people with NT1 carry a gene variation known as DQB1*0602¹⁵. This gene plays a role in immune function, so this variation could cause a genetic susceptibility to NT1. Although this explanation of NT1 is widely accepted, it is not yet definitively proven¹⁶.

Even though researchers know more than ever about NT1, most individual cases still occur with no clear, direct cause. People with a family history of NT1 have about a 1-2% chance of developing the condition. This is a small risk overall but a significant increase in risk relative to people without a family history.

In rare cases, NT1 occurs because of another medical condition that causes damage to the parts of the brain containing hypocretin-producing neurons. This may be known as secondary narcolepsy, and it can occur from brain trauma or an infection in the central nervous system.

NT2

Little is known about the biology of or risk factors for NT2. Some experts believe that NT2 is simply a less pronounced loss of hypocretin-producing neurons, but people with NT2 are usually not deficient in hypocretin¹⁷. Others think NT2 may primarily be a precursor to NT1, but cataplexy has only been observed to develop in about 10% of cases of people initially diagnosed with NT2.

In some instances, NT2 has been reported following a viral infection, but most cases do not have an established cause. As with NT1, NT2 can arise because of other medical conditions such as head trauma, multiple sclerosis, and other diseases affecting the brain.

How Is Narcolepsy Diagnosed?

Diagnosis of narcolepsy requires careful analysis by a doctor familiar with the disease. Because it is rare and symptoms may be mistakenly attributed to other causes, narcolepsy can go undiagnosed for many years.

The diagnostic process starts with a review of symptoms and medical history. This step helps the doctor understand the patient’s sleep habits and the nature of their EDS. In many cases, especially with children, family members are involved in order to provide more context about the patient’s symptoms.

Tests may be conducted to evaluate EDS and sleep. A test called the Epworth Sleepiness Scale (ESS) is based on the patient’s subjective sense of their symptoms. Polysomnography (PSG), a detailed test in which sensors monitor brain and body activity, may be necessary. This kind of sleep study is done overnight in a specialized clinic.

The day after the PSG test, another exam called the Multiple Sleep Latency Test (MSLT) can be used to objectively assess sleepiness. During the MSLT, the patient is instructed to try to fall asleep at five different intervals while remaining connected to the sensors used in the PSG. People with narcolepsy tend to fall asleep quickly and to rapidly begin REM sleep during the MSLT.

Another test may be used to remove cerebrospinal fluid (CSF) and assess its level of hypocretin. This is done with a procedure called a spinal tap or lumbar puncture. Low levels of hypocretin are indicative of NT1 and help distinguish it from NT2.

Diagnostic Criteria for Narcolepsy

Doctors follow standardized criteria for diagnosing sleep disorders. Standardization helps ensure accurate diagnosis and differentiation between NT1, NT2, hypersomnias, and other conditions that cause EDS.

Criteria for NT1 and NT2 both require significant EDS that lasts for at least three months. For NT1, a patient must have low levels of hypocretin in their CSF or have cataplexy symptoms plus a short time to fall asleep and enter REM sleep on the MSLT. For NT2, a patient must have similar results on the MSLT, but they cannot have cataplexy or low levels of hypocretin.

Other sleep disorders have similar symptoms to those found in NT2, which can make it hard to diagnose. For this reason, it is necessary for the doctor to rule out other conditions by carefully analyzing the patient’s test results and symptoms. Though not enough to diagnose NT2, the presence of short, refreshing naps and interrupted nighttime sleep help distinguish narcolepsy from other hypersomnias.

What Are the Treatments for Narcolepsy?

There is no cure for narcolepsy type 1 or type 2. The goals of treatment for narcolepsy are improving patient safety, reducing symptoms, and enhancing quality of life.

For many people with narcolepsy, the disease remains generally stable over time. In some cases, certain symptoms may improve as the patient ages¹⁸, and rarely, remission of symptoms may happen spontaneously¹⁹. So far, experts do not know why the disease unfolds differently in different people.

Treatments for NT1 and NT2 are similar except that NT2 does not involve potentially taking any medications for cataplexy.

A combination of medical and behavioral approaches can significantly decrease but not eliminate symptoms. Some level of EDS normally persists despite treatment²⁰. All therapies should be carried out under the guidance of a doctor who can best tailor a treatment plan to the patient’s specific situation.

Behavioral Approaches to Treatment

Behavioral approaches are non-medical forms of therapy, and there are multiple ways that they can be incorporated into the daily habits of people with narcolepsy.

• Planning short naps: Because brief naps are refreshing for people with narcolepsy, budgeting time for naps during the day can reduce EDS. Accommodations at school or work may be necessary to make time for naps.
• Having healthy sleep hygiene: To combat poor sleep at night, people with narcolepsy can benefit from good sleep habits. Good sleep hygiene includes a consistent sleep schedule (for bedtime and waking up), a sleep environment with minimal distractions and disruptions, and limited use of electronic devices before bed.
• Avoiding alcohol and other sedatives: Any substance that contributes to sleepiness may worsen daytime narcolepsy symptoms.
• Driving with caution: People with narcolepsy should talk with the doctor about safe driving. Napping before driving and avoiding long or monotonous drives are examples of measures to improve safety.
• Eating a balanced diet: People with narcolepsy have a higher risk of obesity, which makes eating well an important part of their overall health.
• Exercising: Being active can help prevent obesity and may contribute to improved sleep at night.
• Seeking support: Support groups and mental health professionals can promote emotional health and counteract the risks of social withdrawal, depression, and anxiety in people with narcolepsy.

Medications

Although behavioral approaches are frequently helpful, most people with narcolepsy also receive treatment with medications to help control one or more symptoms.

Medications for narcolepsy often provide symptom improvement, but they can also cause side effects. These drugs require a prescription and should be used carefully and according to the instructions provided by a doctor and pharmacist.

Some of the most commonly prescribed medications for narcolepsy include:

• Modafinil and armodafinil: These two wakefulness-promoting drugs are chemically similar and are typically the first therapy for EDS.
• Methylphenidate: This is a type of amphetamine that can reduce EDS.
• Solriamfetol: This drug was approved by the FDA in 2019 and has shown comparable effects on EDS as modafinil²¹.
• Sodium oxybate: This medication can reduce cataplexy, EDS, and nighttime sleep disturbances, but it may take weeks to affect EDS²².
• Pitolisant: Approved by the FDA in 2019, pitolisant is a wakefulness-promoting medication that has also shown a positive effect on cataplexy.

Not all medications work for all patients, and some patients may experience more bothersome side effects or interactions with other drugs. Working closely with the doctor can help identify the medication and dosage with the best balance of benefits and downsides.

Narcolepsy Treatment and Children

Treatment for children with narcolepsy is similar to treatment in adults, but additional precautions may be taken when choosing medications and their dosages. A cardiovascular evaluation is recommended by the American Academy of Pediatrics²³ before children start taking stimulant medications.

Narcolepsy Treatment and Pregnancy

There is limited data about the safety of most drugs used to treat narcolepsy in women who are pregnant, trying to get pregnant, or breastfeeding. A survey found that the majority of experts recommend stopping narcolepsy medications²⁴ when trying to conceive as well as when pregnant and breastfeeding. Discontinuing medication may require changes to behavioral approaches and other accommodations to safely cope with symptoms without medication.