• Excessive daytime sleepiness
• Catalepsy
• Hallucinations
• Sleep paralysis
• Alterations in rapid eye movement sleep

In the United States, narcolepsy affects 1 in 2000 people, while it affects 3 million people worldwide [1].

Although narcolepsy can happen at any age, it is typically observed in individuals between the age of 10 and 30 years old.

1. What Is Excessive daytime sleepiness?

Excessive daytime sleepiness is characterized by a constant need to sleep even if the individual had a biologically sufficient night sleep.  

This need to sleep comes suddenly and overwhelmingly and is known as a sleep attack.

2. What Are Alterations in Rapid Eye Movement Sleep?

Sleep is controlled by the brain through the suprachiasmatic nucleus of the hypothalamus. The sleep pattern occurs through repetition of a cycle that comprises 5 phases measured by electroencephalography (ECG) [2]:

• Phase 1: light sleep phase characterized by slow eyes’ movement and muscle relaxation.

• Phase 2: this phase is characterized by the cessation of eyes’ movement and the slowdown of the brain waves such as the electrical pulses associated with wakefulness.

• Phase 3: beginning of deep sleep delta waves. At this stage, the delta waves are interrupted by faster and smaller waves.

• Phase 4: characterized uninterrupted delta waves leading to deep sleep.

• Rapid Eye Movement (REM): this phase is characterized by rapid eye movements, rise in heart and blood pressure, and dreaming.

Although narcoleptics have sufficient REM sleep during the night, they also have a higher REM compared to non-narcoleptics which manifests with the need to sleep during the day [3].

3. What Is Catalepsy?

Catalepsy is an uncontrollable loss of voluntary muscle tone leading to muscle rigidity. It can be triggered by overwhelming emotions such as stress, anger, fear, laughter, or excitement.

However, narcolepsy can manifest without catalepsy and is known as Narcolepsy Type 2, while narcolepsy with catalepsy is known as Narcolepsy Type 1.

4. What Is Sleep Paralysis?

People with narcolepsy experience the loss of voluntary muscle control or the ability to speak while falling asleep and still conscious.

Sleep paralysis is generally followed by full recovery of movements and speech.

5. What Are Hallucinations?

Hallucinations are characterized by hearing, seeing, smelling, tasting, and feeling (touch) things that are not real or do not exist outside an individual mind.

People with narcolepsy experience hallucinations while falling asleep and during sleep paralysis.

6. What Is the Main Cause of Narcolepsy?

Narcolepsy is caused by the loss of neurons that release hypocretins (orexins) in the hypothalamus where the sleep cycle is controlled.

Hypocretins (orexins) are neuropeptides that are released by the orexigenic neurons to regulate the activities of the neurotransmitters acetylcholine, serotonin, and norepinephrine [5][6].

Hypocretins (orexins) also act on the brainstem to inhibit neurons involved in the REM phase of the sleep cycle during wakefulness [7].

Although what causes a reduction in the levels of hypocretins (orexins) are not well known, studies have reported the following factors:

• Family history

Family history appears to be a factor of narcolepsy type 1 as up to 10% of narcolepsy individuals with catalepsy reported having a close relative with similar symptoms [8].

• Autoimmune Diseases

Genetic variations in the human leukocyte antigen (HLA) complex were suggested as a factor promoting autoimmunity that targets orexinergic neurons causing their cell death [9].

The human leukocyte antigen (HLA) complex is a system that regulates the immune system and prevents autoimmunity.

• Brain Injuries and tumors

Brain injuries or tumors can damage the regions of the brain that regulate wakefulness and REM sleep resulting in narcolepsy.

7. How Many Hours of Sleep Do People with Narcolepsy Get?

Narcoleptics sleep the same number of hours at night as non-narcoleptic individuals; however, narcoleptics have a higher REM compared to non-narcoleptics which manifests with the need to sleep during the day (excessive daytime sleepiness) [3].

8. What Is the Most Common Treatment of Narcolepsy?

Due to the loss of orexinergic neurons that cannot be replaced, there is no cure for narcolepsy, however, the combination of lifestyle changes and medications can help treat the symptoms [8].

8.1. Lifestyle Changes

• Excessive daytime sleepiness can be monitored through taking small naps during the day.
• Alcohol and caffeine taken before bedtime can disturb sleep
• Exercising for 20 minutes a day can help improve sleep
• Maintaining a regular sleep schedule can help sleeping better
• Tobacco is a central nervous stimulant that can affect sleep, and therefore, avoiding smoking can help sleeping better
• Relaxation before sleep and environmental factors such as the comfort of the bedding and the room where you sleep, are essential for quality sleep.
• Avoiding large and heavy meals before bedtime can help sleeping better.

8.2. Medications

8.2.1. What Is Modafinil?

Modafinil (Provigil) is used for the treatment of sleepiness. Although the mechanism of action is unknown, modafinil may be involved in the release of hypocretins (orexins) and the neurotransmitter histamine from the hypothalamus [10].

8.2.2. What Is Sodium Oxybate?

Sodium Oxybate (Xyrem) is sodium salt of gamma-hydroxybutyric acid, a neurotransmitter, and a precursor of GABA (gamma-aminobutyric acid), glutamate, and glycine in certain parts of the brain. It is used as a sedative for narcolepsy.

8.2.3. What Are Amphetamine-Like Stimulants?

Amphetamine-Like Stimulants are inhibitors of norepinephrine and dopamine reuptake which increases the extra-synaptic concentrations of the neurotransmitters, norepinephrine, and dopamine and their stimulation of the central nervous system.

The most used amphetamine-like stimulant for narcolepsy is methylphenidate (Ritalin).

8.2.4. What Are Antidepressants?

Antidepressants are used for the treatment of depression and narcolepsy symptoms and act by inhibiting the reuptake of serotonin and norepinephrine reuptake, but also by regulating the activities of other neurotransmitters and their receptors in the brain.

Conclusion

Narcolepsy is caused by the loss of orexigenic neurons in the hypothalamus where they release the neuropeptides hypocretins (orexins) which regulate the ERM phase of the sleep cycle.

The causes for the loss of orexigenic neurons are not well-known and may involve genetic and autoimmune factors.

Unfortunately, narcolepsy is not treatable due to the loss of neurons that cannot be replaced (so far), and therefore, the treatment is symptomatic and involves changes in lifestyle and medications.

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