Narcolepsy

What is narcolepsy?

Narcolepsy, or Gélineau disease, from the name of the French doctor (1828-1906) who described it for the first time, is a sleep disorder characterised by daytime drowsiness and uncontrollable sleeping fits. Other symptoms can add to the clinical picture:

  • cataplexy episodes, sudden and momentary loss of muscle tone, often emotion-triggered, characterising type 1 narcolepsy;
  • hypnagogic hallucinations, sort of waking dream, whether the patient is conscious or not;
  • sleep paralysis, waking but unable to move or speak, which may accompany hallucinations;
  • tendency to obesity;
  • restless sleep…

Narcolepsy is a rare disease, which affects one person in 2,500 in Europe. It occurs most often during adolescence, however a large proportion of patients remain undiagnosed and untreated despite the highly debilitating nature of the disease.

The diagnosis is initially based on evaluation of drowsiness, measured most often using the Epworth sleepiness scale, and in the case of type 1 narcolepsy, the highly revealing presence of cataplexy attacks.

Several tests can confirm the diagnosis: the polysomnography (electroencephalogram recording of a night’s sleep), which shows direct abnormal transitions from waking in REM-sleep, the multiple sleep latency test (MSLT) which confirms mean sleep latency of just 3 to 4 minutes, or even cerebrospinal fluid testing, which reveals very low orexin levels.

Aetiology

The most common form of narcolepsy is caused by the destruction, often during childhood, of a group of neurons in the hypothalamus which secrete a small peptide that regulates wakefulness, called hypocretin or orexin.

A body of scientific evidence suggests that the destruction of orexin neurons is related to an auto-immune mechanism, encouraged by genetic susceptibility. In effect, 92% of people with narcolepsy (vs. around 20% of the general population) are carriers of a specific mutation of the human leukocyte antigen (HLA) system: HLA DQB1*0602. The HLA system is central to immunity and enables the immune system to differentiate self from non-self cells, that is to say foreign to the individual, that have to be destroyed. HLA typing contributes to the narcolepsy diagnosis by revealing an increased risk of developing the disease. A poorly-elucidated auto-immune process is also in all likelihood at the origin of the resurgence of cases of narcolepsy seen in some countries during the H1N1 flu virus pandemic in 2009, and during the related vaccination campaign.

Narcolepsy and REM-sleep

Narcolepsy is a sleep disorder in which the boundary between waking and sleeping is blurred. REM-sleep is a sleep phase discovered by Michel Jouvet in 1959, which is characterized by muscle atony, which means complete muscle relaxation, and lucid numerous dreams. During a physiological night’s sleep, REM-sleep generally comes after light, non-REM sleep or deep sleep. Patients suffering from narcolepsy fall directly into REM-sleep without first going through the non-REM sleep phase.

Treatment

Treatment for narcolepsy involves behavioural and drug therapies:

  • sleep hygiene (going to bed at the same time and napping frequently during the day);
  • psychostimulants: modafinil or amphetamine, which prevent drowsiness by stimulating certain parts of the brain;
  • antidepressants (off label) or sodium oxybate (GHB sodium salt), appear to reduce the frequency of cataplexy attacks;
  • since June 2016, pitolisant, a histamine H3 receptor inverse antagonist/agonist with an effect against drowsiness and cataplexy;

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