“All of the sudden, I have this out of the blue urge to sleep.” – Scott

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Sleep-Wake State Instability

Narcolepsy is a disorder characterized by sleep-wake state instability.1

Hypnograms Narcolepsy Infographic

Narcolepsy Sleep-Wake Cycle

In narcolepsy, the sleep-wake cycle is unstable throughout a 24-hour period.3-6 Unstable wakefulness is reflected in an increased frequency of daytime naps.5,7 Rapid transitions to REM sleep during daytime naps are highly suggestive of narcolepsy.7,8 Narcolepsy is also characterized by disrupted nighttime sleep with frequent transitions between wakefulness, REM sleep, and stages of non-REM sleep.7,9

Sleep-wake instability in narcolepsy is characterized by unstable boundaries and frequent and unpredictable transitions between states.3,6,13

During the day, lack of hypocretin in narcolepsy leads to insufficient activation of histamine neurons and wake-promoting neurons outside the hypothalamus, intermittent activation of REM sleep-promoting neurons (REM at the Wrong Time™), and intermittent activation of non-REM sleep-promoting neurons (Non-REM at the Wrong Time™).6,8,14-16 This process causes sleep-wake state instability, which can manifest as unstable boundaries and frequent transitions between states of sleep and wakefulness.3,6,13 Non-REM sleep and elements of REM sleep can intrude into wakefulness and manifest as symptoms of narcolepsy, including excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis.6,8,15,16

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Narcolepsy symptoms reflect the underlying sleep-wake state instability.

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Histamine neurons help to promote and stabilize wakefulness.

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  1. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  2. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  3. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257-1263.
  4. Rogers AE, Aldrich MS, Caruso CC. Patterns of sleep and wakefulness in treated narcoleptic subjects. Sleep. 1994;17(7):590-597.
  5. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68(6):1023–1042
  6. Pizza F, Vandi S, Iloti M, et al. Nocturnal sleep dynamics identify narcolepsy type 1. Sleep. 2015;38(8):1277-1284.
  7. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
  8. Roth T, Dauvilliers Y, Mignot E, et al. Disrupted nighttime sleep in narcolepsy. Sleep Med. 2013;9(9):955-965.
  9. Waihrich ES, Rodrigues RND, Silveira HA, et al. Comparative analysis of multiple sleep latency tests (MSLT) parameters and occurrence of dreaming in patients with daytime sleepiness of narcoleptic and non-narcoleptic origin. Arq Neuropsiquiatr. 2006;64(4):958-962.
  10. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. 2014.
  11. Plazzi G, Serra L, Ferri R. Nocturnal aspects of narcolepsy with cataplexy. Sleep Med Rev. 2008;12(2):109-128.
  12. van der Heide A, Lammers GJ. Narcolepsy. In: Thorpy MJ, Billiard M, eds. Sleepiness: Causes, Consequences and Treatment. Cambridge: Cambridge University Press;2011:111-125.
  13. Pillen S, Pizza F, Dhondt K, Scammell TE, Overeem S. Cataplexy and its mimics: clinical recognition and management. Curr Treat Options Neurol. 2017;19(6):23.
  14. Bassetti C, Aldrich MS. Narcolepsy, idiopathic hypersomnia, and periodic hypersomnias. In. Culebras A, ed. Sleep disorders and neurological disease. Marcel Decker Inc;2000:323-354.
  15. Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE. Behavioral state instability in orexin knock-out mice. J Neurosci. 2004;24(28):6291-6300.

Performance of routine tasks without awareness.

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

Complete collapse to the ground; 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 inappropriate transitions between states of sleep and wakefulness.

The inability to stay awake and alert during the day.

A neurotransmitter that supports wakefulness. The TMN is the only source of histamine in the brain.

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

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

A neuropeptide that supports wakefulness and helps control 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.

Brief, unintentional lapses into sleep or loss of awareness.

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

A state of sleep when muscle tone is decreased. Deep stages help to restore the body.

Overnight study used to diagnose sleep disorders by monitoring sleep stages and cycles to detect disruptions of a normal sleep pattern.

Normally occurs at night and includes vivid dreams. Also known as “paradoxical sleep.”

Daytime and evening habits and routines to help improve nighttime sleep.

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

Sleep-onset REM period.

People with type 1 narcolepsy have low levels of hypocretin.

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