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Glossary

Terms and phrases to help know narcolepsy

Amygdala -

Region of the brain involved in processing emotions; neurons in its central nucleus (CeA) are active during cataplexy.1

Automatic behaviors -

Performance of routine tasks (e.g., writing, cooking) without awareness or memory.2-4

Cataplexy -

Sudden and brief loss of muscle tone (e.g., knees buckling, jaw sagging) with retained awareness, often triggered by strong emotions or certain situations.2,3,5 Specific to narcolepsy, but not every person with narcolepsy has cataplexy.2,4 Narcolepsy with cataplexy is known as narcolepsy type 1.2

Complete cataplexy -

Complete collapse to the ground; usually takes several seconds to develop and nearly all skeletal muscles are involved.1,5,6

Partial cataplexy -

Only certain muscle groups are involved; facial, head, or neck weakness is common.2

Circadian rhythm -

Biological clock mechanism that regulates the 24-hour cycle in the physiological processes of living beings. It is controlled in part by the SCN in the hypothalamus and is affected by the daily light-dark cycle.8,9

Disrupted nighttime sleep -

The inability to maintain a continuous nocturnal sleep. Frequent awakenings and inappropriate transitions between different states of sleep and wakefulness that occur at night, causing poor quality sleep.2,10

Excessive daytime sleepiness -

The inability to stay awake and alert during the day, resulting in an intense need for sleep or unintentional lapses into drowsiness or sleep. The primary symptom of narcolepsy.2

Histamine -

A monoaminergic neurotransmitter that supports wakefulness. The hypothalamic tuberomammillary nucleus (TMN) is the only neuronal source of histamine in the brain, and histamine is its main transmitter.8,11,12

Hypnagogic/hypnopompic hallucinations -

Vivid, realistic, and usually frightening dream-like events that occur when falling asleep (hypnagogic). When they occur while waking up, they are called hypnopompic hallucinations.2,4,13

Hypocretin -

Also known as orexin; a neuropeptide that supports wakefulness and helps suppress non-REM sleep and REM sleep.11 Low levels of hypocretin cause the boundaries between sleep and wakefulness to become unstable, leading to symptoms of narcolepsy.8,13,14

Hypothalamus -

Primary brain region for regulating the timing of sleep-wake states.9,15,16

Involuntary sleep -

A manifestation of excessive daytime sleepiness. Unintentionally falling asleep due to excessive daytime sleepiness. Also known as “sleep attacks.”2

Lateral hypothalamus (LH) -

Only location in the brain where hypocretin-producing neurons originate.16 Hypocretin neurons of the LH promote wakefulness by activating neurons in the cortex, thalamus, histamine neurons in the TMN of the hypothalamus and regions containing wake-promoting neurons (e.g., norepinephrine, acetylcholine, serotonin, dopamine neurons).8,13,16 Through activation of histamine and other wake-promoting neurons, hypocretin neurons also inhibit non-REM sleep–promoting neurons and REM sleep–promoting neurons to stabilize wakefulness during the day.8,11,17

Melanin-concentrating hormone (MCH) neurons -

Promote and maintain REM sleep at night by inhibiting wake-promoting neurons that suppress REM sleep. 18-20

Microsleep episodes -

Brief, unintentional lapses into sleep or loss of awareness.4,21

Multiple Sleep Latency Test (MSLT) -

A validated objective measure of the physiologic ability or tendency to fall asleep in quiet situations.2,22 The test consists of four or five 20-minute nap opportunities 2 hours apart, typically preceded by an overnight sleep study.2,22,23 The test measures EEG, muscle activity, and eye movements.22 Narcolepsy diagnostic criteria require a mean sleep latency of ≤ 8 minutes and 2 or more SOREMPs on MSLT.2

Narcolepsy type 1 -

Also called narcolepsy with cataplexy, although cataplexy is not always present or obvious; people with narcolepsy type 1 have low levels of hypocretin.2

Narcolepsy type 2 -

Narcolepsy without cataplexy; narcolepsy type 2 is most likely a heterogenous disorder.1 Patients with narcolepsy type 2 may have undetectable to normal hypocretin levels.2

Non-REM sleep -

A state of sleep characterized by slower-frequency, more synchronized neuronal activity and decreased muscle tone.8,24 People usually wake up more easily from light non-REM sleep than from deep non-REM sleep.8 Ranges from light (N1) to deep (N3) stages of sleep. Deep stages help to restore the body.8,25

Orexin -

See hypocretin.

Polysomnography (PSG) -

A multiparameter test that monitors physiologic signals (e.g., electrical activity of the brain [EEG], eye movements, muscle activity, and heart rhythm) during sleep.23,26 Used as a diagnostic tool in sleep medicine.26

REM sleep -

Rapid eye movement sleep; a state of sleep characterized by fast-frequency, desynchronized activity on EEG with distinct features.8,24 Normally occurs 60-90 minutes after sleep onset.27 Dreams commonly occur, and skeletal muscle tone is strongly suppressed to prevent people from acting out their dreams.8,24 Also known as “paradoxical sleep.”24

Sleep paralysis -

Brief loss of voluntary muscle control with retained awareness. Occurs before falling asleep or while waking up and can be frightening.2,13,28

Sleep-onset rapid eye movement period (SOREMP) -

An abnormal sleep phenomenon characterized by REM sleep occurrence within 15 minutes of sleep onset; may occur during nighttime sleep or daytime napping.29

Spinal motor neurons -

Located in the ventral horn of the spinal cord. Convey commands from the CNS processing centers to the effector muscles in the periphery. 30

Suprachiasmatic nucleus (SCN) -

Located in the hypothalamus and coordinates circadian timing (in addition to other circadian rhythms) to align sleep and wakefulness to the daily light-dark cycle.8

Tuberomammillary nucleus (TMN) -

Located in the hypothalamus, it is the only region of the brain where histamine neurons originate.8,12 Histamine neurons promote wakefulness by activating neurons in the cortex, thalamus, and regions containing wake-promoting neurons (e.g., norepinephrine, acetylcholine, serotonin, dopamine neurons).12,31 Histamine neurons also suppress non-REM sleep–promoting neurons and REM sleep–promoting neurons to help stabilize wakefulness during the day.8,12,32

Ventrolateral preoptic area (VLPO) -

The VLPO as well as the median preoptic nucleus (MnPO) are located in the hypothalamus and contain essential neurons for promoting non-REM sleep. These neurons project to all wake-promoting regions to inhibit wakefulness and promote non-REM sleep during the night.8,11 Neurons in the extended VLPO mediate the promotion of REM sleep by inhibiting certain wake-promoting neurons that suppress REM sleep.8

  1. Szabo S, Thorpy M, Mayer G, Peever, J, Kilduff T. Neurobiological and immunogenetic aspects of narcolepsy: implications for pharmacotherapy. Sleep Med Rev. 2019;43:23-36.
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  3. Thorpy M, Morse AM. Reducing the clinical and socioeconomic burden of narcolepsy by earlier diagnosis and effective treatment. Sleep Med Clin. 2017;12(1):61-71.
  4. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  5. Overeem S, van Nues S, van der Zande WL, Donjacour CE, van Mierlo P, Lammers GJ. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 2011;12(1):12-18.
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  7. Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. Cataplexy—clinical aspects, pathophysiology and management strategy. Nat Rev Neurol. 2014;10(7):386-395.
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Performance of routine tasks without awareness.

Sudden and brief loss of muscle tone, often triggered by strong emotions or certain situations. Narcolepsy with cataplexy is known as narcolepsy type 1.

Complete collapse to the ground; nearly all skeletal muscles are involved.

Only certain muscle groups are involved.

Biological clock mechanism that regulates the 24-hour cycle in the physiological processes of living beings. It is controlled in part by the SCN in the hypothalamus and is affected by the daily light-dark cycle.

Frequent awakenings and inappropriate transitions between states of sleep and wakefulness during nighttime sleep.

The inability to stay awake and alert during the day.

A neurotransmitter in the brain that supports wakefulness.

Vivid, realistic, and sometimes frightening dream-like events that occur when falling asleep.

Also known as orexin. A neuropeptide that supports wakefulness and helps suppress non-REM sleep and REM sleep.

Primary brain region for regulating the timing of sleep-wake states.

Unintentionally falling asleep due to excessive daytime sleepiness. Also known as “sleep attacks.”

Brief, unintentional lapses into sleep or loss of awareness.

A validated objective measure of the tendency to fall asleep in quiet situations.

People living with narcolepsy type 1 have low levels of hypocretin.

Narcolepsy without cataplexy; the cause of narcolepsy type 2 is unknown.

A state of sleep characterized by slower-frequency, more synchronized neuronal activity and decreased muscle tone. Deep stages help to restore the body.

A multiparameter test that monitors physiologic signals during sleep; used as a diagnostic tool in sleep medicine.

A state of sleep characterized by fast-frequency, desynchronized activity on EEG, vivid dreams, and loss of muscle tone. Normally occurs 60-90 minutes after sleep onset. Also known as “paradoxical sleep.”

Brief loss of control of voluntary muscles with retained awareness at sleep-wake transitions.

Sleep-onset REM period.

The VLPO as well as the median preoptic nucleus (MnPO) are located in the hypothalamus and contain essential neurons for promoting non-REM sleep. These neurons project to all wake-promoting regions to inhibit wakefulness and promote non-REM sleep during the night.8,11 Neurons in the extended VLPO mediate the promotion of REM sleep by inhibiting certain wake-promoting neurons that suppress REM sleep.8