What do we really know about narcolepsy?

Sleep-related illnesses are among those that affect the most people and inexorably impact everyone's daily well-being. It's a proven fact: when we sleep poorly, too much, or not enough, we don't feel well. Thus, narcolepsy is one of those sleep-related illnesses that, when they affect us, all too often make our lives difficult and make our sleep chaotic. Narcolepsy is a rare illness whose causes cannot be treated, but it is possible to live with it, limiting its repercussions.

But what is narcolepsy?

You've probably already heard of narcolepsy ¹ around you or in the media, and for good reason, this sleep disorder is much talked about. And not in a good way, of course. Narcolepsy is a severe wakefulness disorder that significantly disrupts the circadian rhythm. It is also called "Gélineau's disease" in reference to the French physician, Dr. Jean-Baptiste Gélineau , who was one of the very first scientists to document this disease as such. This discovery was made in particular because of (or thanks to, depending on your point of view) a patient who collapsed from sleep during a visit to the Jardin des Plantes in 1880... when a monkey had just made faces at her! Speaking of animals, it is worth noting that narcolepsy was diagnosed in dogs as early as 1972, and was even described as an “autosomal recessive genetic disease” ² ( whose genetic transmission affects both males and females in humans ³ ) for breeds such as the Doberman or the Labrador. This sleep disorder is characterized by episodes of REM sleep that can occur at any time and suddenly, but also by a perpetual feeling of fatigue, as well as daytime sleepiness. In other words, narcolepsy is an irrepressible urge to sleep , anywhere and anytime. It can be accompanied by a cataplexy attack, that is to say a sudden and temporary loss of muscle tone that ends with the victim falling. As you will have understood, a sleep disorder that arrives without warning and at any time is a serious problem that can cause a lot of worries. A disease that must be taken seriously and is the subject of an association to help sufferers ( The French Association of Narcolepsy, Cataplexy and Rare Hypersomnias ⁴ ), narcolepsy has an impact on all aspects of life : personal, professional, family and social.

It is important to know that for a sleep disorder to be considered narcolepsy, it must be accompanied by at least one of the following three factors:

• Cataplexy: This is a sudden and temporary loss of muscle tone, resulting in the individual falling.
• Hypnopompic (when waking up) or hypnagogic (when falling asleep) hallucinations
• Sleep paralysis: This is a sleep disorder (“parasomnia”) which results in an inability to move or perform a voluntary movement, linked to a loss of muscle tone.

In addition to cataplexy, hallucinations, or sleep paralysis, the diagnostic criteria of the DSM IV ( Diagnostic and Statistical Manual of Mental Disorders ⁵ ) also consider that "a minimum duration of at least one month of episodes of drowsiness" is required to characterize narcolepsy. The DSM IV is the " Diagnostic and Statistical Manual of Mental Disorders ^6. " It is the international reference for mental health professionals.

Narcolepsy figures

Why is narcolepsy said to be a rare disease? According to European legislation ⁷ , it is classified as a chronic rare disease because it affects no more than one in two thousand people. In France , this corresponds to a little less than 30,000 individuals, or approximately 1 in 2,800 ⁸ , that is to say 0.028% of the population (for the most meticulous "maths"!). Narcolepsy affects both men and women, especially between the ages of 15 and 35, and regardless of geographical origin. Furthermore, according to INSERM ⁹ (National Institute of Health and Medical Research), "70% of people with narcoleptics also have cataplexy." While the figures for this disease may suggest that it doesn't affect many people, it's probably wise to put this apparent "rarity" into perspective by the fact that many narcoleptics don't know they have it, as narcolepsy is sometimes difficult to diagnose! In fact, only 1 in 5 patients are ever correctly diagnosed. However, according to Professor Damien Léger (sleep specialist and director of sleep and vigilance at the Hôtel-Dieu in Paris), where it took between 15 and 20 years to diagnose narcolepsy a few years ago, "today, only 5 to 10 years are needed" thanks to the establishment of reference centers ¹⁰ following the "Rare Diseases Plan 2004-2008". Therefore, don't hesitate to consult a specialist at these centers if you have any doubts!

What causes narcolepsy?

The causes of narcolepsy are not yet fully understood. However, many studies tend to highlight its status as an autoimmune disease ¹¹ . You have probably already heard this term which refers to a disease where the immune system, supposed to defend our body with courage, turns against its own body and plays very nasty tricks on it by fueling the disease it should prevent! Of course, autoimmune diseases are all the more difficult to treat given their "complicity" with our body's defenses.

These autoimmune disorders are manifested by the destruction and degeneration of brain cells present in the hypothalamus. The neurons attacked are those that secrete hypocretin, a neurotransmitter involved in the sleep mechanism. Thus, the lack of hypocretin is a major cause of narcolepsy ¹² . To these causes, we can add a form of genetic heredity through family history and, to a lesser extent, traumatic brain injuries.

In summary, autoimmune character and genetic predisposition appear to be the two main causes of narcolepsy.

Indeed, a study ¹³ has shown that 85 to 95% of people suffering from narcolepsy have a particular HLA group (system for recognizing an individual's cells): DR15 DQB10602 . This is the marker for the degeneration of neurons that cause the secretion of hypocretin. However, being a carrier of this genetic mark does not necessarily mean that one could suffer from narcolepsy: 20% of the population has this tissue group, and only 0.028% of the population suffers from narcolepsy. This is therefore only an indicator of susceptibility to the disease.

How does narcolepsy manifest itself?

Narcolepsy is characterized by 3 main symptoms , and other “accessories” (not necessary for diagnosis):

• Daytime sleepiness of varying intensity depending on the person.
• Sudden and irrepressible bout of daytime sleepiness that can last from 10 minutes to 1 hour.
• Cataplexy attack (loss of muscle tone leading to a fall, often triggered by strong emotion).
• Sleep paralysis upon waking or falling asleep (inability to move and/or speak for a few moments).
• Hypnagogic (when falling asleep) and hypnopompic (when waking up) hallucinations which can be visual and/or auditory.

Narcolepsy-cataplexy is therefore not a disease that causes people to sleep "too much" and, as such, should not be confused with its distant relative, hypersomnia . The latter can be "idiopathic" (constant excessive daytime sleepiness) or called "Kleine-Levin syndrome" (recurrent hypersomnia associated with behavioral disorders). Narcolepsy is essentially associated with sudden and uncontrollable sleep attacks, as well as poor sleep quality and cataplexy attacks.

How is narcolepsy diagnosed?

Narcolepsy is a difficult disease to diagnose due to its similarities with other sleep disorders (hypersomnia and depression in particular). The diagnosis of narcolepsy is based primarily on clinical signs (hypersomnolence combined at least once with a cataplexy attack) and on the use of polysomnography . This consists of recording the electrical waves of the brain during the phases of sleep at night (falling asleep, sleeping, waking up), but also during daytime sleepiness. This process makes it possible to assess sleep, but also to eliminate other diseases thanks to the respiratory parameters recorded. Polysomnography is often followed by an iterative sleep latency test , which makes it possible to measure the time taken to fall asleep (which is brief in narcoleptics), as well as the rapid onset of REM sleep. The rapid onset of REM sleep is characteristic of a case of narcolepsy and may be revealed during these tests.

Another indicator of narcolepsy can be revealed following a blood test to look for a genetic marker, namely belonging to the HLA group "DR15 DQB10602", the latter being an indicator of predisposition to the disease as we have seen previously.

What are the treatments for narcolepsy?

Narcolepsy is a disease whose causes are not curable. However, don't panic, fortunately, the symptoms of narcolepsy can be treated! Although it is a difficult and restrictive disease to live with, its effects can still be limited through non-drug measures, but also with specially adapted drug treatment ¹⁴ .

Symptomatic drug treatment

Narcolepsy-cataplexy is primarily treated with wakefulness stimulants to combat daytime sleepiness and uncontrollable sleep attacks, as well as with anticataplectics (antidepressants or sodium oxybate, which also act on cataplexy). The main medications prescribed are :

• Modafinil : This is the first-line treatment for excessive daytime sleepiness and is the one best tolerated by patients.
• Methylphenidate : This is a psychostimulant with highly regulated use and is used when modafinil is not effective.
• sodium oxybate : This is a powerful sedative whose use is reserved for adults with narcolepsy who also have cataplexy attacks.
• pitolisant : it is a stimulant of neuronal activity which increases alertness.

Of course, the initial prescription for all these medications must be made by a doctor specializing in neurology, or practicing in a sleep center. Their use must be reported to your pharmacist as well as to any new doctor consulted.

Side effects of drug treatment

Taking these medications is not harmless and unfortunately comes with side effects, even risks ¹⁵ , and they should not be neglected! Here are the main side effects and risks :

• headaches, nausea, dizziness
• digestive disorders, decreased appetite, tachycardia
• syncope, acute chest pain
• acute behavioral disorder, depression, anxiety, sleepwalking attacks
• coma

The use of these medications can help relieve the symptoms of narcolepsy-cataplexy; this is undeniable, and sometimes unavoidable. However, it is important to be aware that, as with any medication, side effects carry risks. Therefore, it is important to be vigilant regarding the dosages and contraindications associated with each of these medications!

Non-drug measures

Education through a lifestyle adapted to the disease is strongly recommended ¹⁶ . By adopting sleep hygiene in line with certain symptoms, it is possible to limit their effects. For example, instead of suffering drowsiness or a sleep attack, it would be better to anticipate them by scheduling naps at regular times and of short duration (around 15 minutes). Beneficial effects could be observed. On the other hand, going to bed at fixed times and eliminating situations of sleep deprivation would reinforce the limitation of symptoms.

While the use of medication, with its risks, unfortunately often proves necessary, implementing sleep hygiene can increase its effectiveness. Thus, narcolepsy can be partly treated by naps and fixed bedtimes , in addition to taking medication.

Sources:

[1] Narcolepsy and Idiopathic Hypersomnia , “Vidal recommendations” website, May 2020 [2] Canine model of narcolepsy: genetic and developmental determinants , TL Baker, AS Foutz et al, Experimental Neurology , March 1982 [3] Transmission of genetic diseases , “Orphanet” website/“Orphaschool” training, 2020 [4] The French Association of Narcolepsy, Cataplexy and Rare Hypersomnia , “ANC-Narcolepsy” website, 2020 [5] Impact of the DSM-IV to DSM-5 Changes on the National Survey on Drug Use and Health , “National Center for Biotechnology Information” website [6] Diagnostic and statistical manual of mental disorders , Kenneth S. Kendler, Robert Freedman et al, 2013-2015 [7] Les Cahiers d'Orphanet , “List of rare diseases and their synonyms”, January 2020 [8] Narcolepsy Cataplexy , Orphanet General Public Encyclopedia, July 2006 [9] Hypersomnia and Narcolepsy , INSERM, September 2017 [10] Rare diseases: the care offer , website of the Ministry of Solidarity and Health, April 2020 [11] Narcolepsy Fact Sheet , website “National Institute of Neurological Disorders and Stroke” (NIH Publication No. 17-1637), February 2020 [12] Narcolepsy , website “SleepFundation.org”, 2020 [13] HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients , E. Mignot, R. Hayduk et al, Sleep, November 1997 [14] Narcolepsy , Pr Y. Dauvilliers, website “ Orphanet » (The portal for rare diseases and orphan drugs), October 2009 [15] Narcolepsy Cataplexy , , “Orphanet” site (professional emergency sheets), 2013 [16] Treatments for Narcolepsy , “Vidal-EurékaSanté” site, October 2019