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There’s More to Know About Narcolepsy

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

Normally, the timing and stability of wakefulness, non-REM sleep, and REM sleep are regulated by neurons in the hypothalamus, including hypocretin and histamine neurons.2-5 Narcolepsy is most often caused by loss of hypocretin neurons in the brain, allowing the boundaries between sleep-wake states to become unstable and the transitions between them to become frequent and unpredictable.1,5-8

Narcolepsy symptoms include excessive daytime sleepiness and symptoms of REM sleep dysregulation, such as cataplexy, hypnagogic hallucinations, and sleep paralysis.6,9 These symptoms can have a significant impact, although some manifestations are not always obvious—even to the patient.9-11

As many as 200,000 people in the United States are living with narcolepsy.12 Know Narcolepsy seeks to improve the lives of people living with narcolepsy by advancing the ways we understand the neurobiology of sleep and wakefulness, the pathophysiology of narcolepsy, and the impact of symptoms.

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Signs and symptoms of sleep-wake state instability can manifest in a variety of ways.

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Histamine neurons help to promote and stabilize wakefulness.

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Hcp Scammell Histamine Video
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Thomas Scammell, MD from Beth Israel Deaconess Medical Center, Boston Children's Hospital, and Harvard Medical School, discusses key data from several animal studies that support why histamine plays an important role in disorders characterized by sleep-wake state instability, such as narcolepsy.2,5

The Neurobiology of Normal Sleep and Wakefulness
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Optimal health and cognitive function are due in part to a coordinated sleep-wake system that regulates three distinct and stable states of sleep and wakefulness.5,13-16

The Pathophysiology of Narcolepsy
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Discover how hypocretin loss can cause insufficient activation of histamine and other wake-promoting neurons and insufficient inhibition of non-REM sleep- and REM sleep-promoting neurons, leading to sleep-wake state instability.5,15,17

H10 Mod Video 02 08 16 18 503Pm
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Learn more about histamine neurons, which originate in the hypothalamus, a critical control center for sleep-wake state stability.5,15,18,19

Hcp Scammell Histamine Video

Exploring Histamine in Sleep-Wake State Stability

The Neurobiology of Normal Sleep and Wakefulness

The Neurobiology of Normal Sleep and Wakefulness

The Pathophysiology of Narcolepsy

The Pathophysiology of Narcolepsy

H10 Mod Video 02 08 16 18 503Pm

The Role of Histamine in Sleep and Wakefulness

*The Know Narcolepsy Survey was a three-part survey of 1,654 US adults including those with narcolepsy (n=200), the general public (n=1,203), and physicians (n=251) currently in clinical practice who have treated patients with narcolepsy in the last 2 years. The survey was conducted online in March, April, and August 2018, respectively, by Versta Research on behalf of Harmony Biosciences, LLC. The Narcolepsy Network collaborated on the patient survey.

  1. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  2. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
  3. Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: neural circuits and new medications. Sleep. 2019;42(1): doi: 10.1093/sleep/zsy183.
  4. Schwartz MD, Kilduff TS. The neurobiology of sleep and wakefulness. Psychiatr Clin North Am. 2015;38(4):615-644.
  5. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  6. Thorpy MJ, Dauvilliers Y. Clinical and practical considerations in the pharmacologic management of narcolepsy. Sleep Med. 2015;16(1):9-18.
  7. 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.
  8. Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep. 2002;25(2):197-202.
  9. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed.; 2014.
  10. Overeem S. The clinical features of cataplexy. In: Baumann CR, Bassetti CL, Scammell TE, eds. Narcolepsy: Pathophysiology, Diagnosis, and Treatment. Springer-Verlag New York; 2011:283-290.
  11. Ahmed IM, Thorpy MJ. Clinical evaluation of the patient with excessive sleepiness. In: Thorpy MJ, Billiard M, eds. Sleepiness: causes, consequences and treatment. Cambridge University Press; 2011: 36-47.
  12. National Institutes of Health. Narcolepsy. U.S. Department of Health and Human Services. May 2017. https://catalog.ninds.nih.gov/pubstatic/17-1637/17-1637.pdf. Accessed April 4, 2019.
  13. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378
  14. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
  15. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  16. Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
  17. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
  18. Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol. 2015;11:401-413.
  19. Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci. 2002;22(17):7695-7711.

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.