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There’s More to Know About Narcolepsy

Narcolepsy is a rare, chronic, debilitating neurologic disorder of sleep-wake state instability.1-3

There are as many as 200,000 people living with narcolepsy in the United States.4 It is a neurologic disorder that causes the boundaries between wakefulness, non-REM sleep, and REM sleep to become unstable and the transitions between these states to become frequent and unpredictable,5-9 leading to symptoms including excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep.1,3,7,10,11

These symptoms can be significant, although not always obvious—even to the patient—and sometimes difficult to recognize in practice.1,12,13

Understanding what causes narcolepsy and knowing the various symptoms can help with recognizing the impact of the disorder.

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Understanding the symptoms is important to being able to identify narcolepsy.

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What is the real impact of symptoms on people living with narcolepsy?

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Histamine neurons help regulate the sleep wake system.

Discover their role »
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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.8,9

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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.6,8,15-17

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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.7,8,15

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Learn more about histamine neurons, which originate in the hypothalamus, a critical control center for sleep-wake state stability.8,15,20,21

Exploring Histamine in Sleep-Wake State Stability

The Neurobiology of Normal Sleep and Wakefulness

The Neurobiology of Narcolepsy18,19

The Role of Histamine in Sleep and Wakefulness

*The Know Narcolepsy Survey is 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. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed.; 2014.
  2. Thorpy MJ, Dauvilliers Y. Clinical and practical considerations in the pharmacologic management of narcolepsy. Sleep Med. 2015;16(1):9-18.
  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. 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 May 22, 2018.
  5. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  6. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
  7. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
  8. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-8581.
  9. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-124
  10. Broughton R, Valley V, Aguirre M, Roberts J, Suwalski W, Dunham W. Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. Sleep. 1986;9:205-215.
  11. Roth T, Dauvilliers Y, Mignot E, et al. Disrupted nighttime sleep in narcolepsy. J Clin Sleep Med. 2013;9(9):955-965.
  12. Plazzi G, Serra L, Ferri R. Nocturnal aspects of narcolepsy with cataplexy. Sleep Med Rev. 2008;12(2):109-128.
  13. 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.
  14. 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.
  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. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
  18. Kumar S, Sagili H. Etiopathogenesis and neurobiology of narcolepsy: a review. J Clin Diagn Res. 2014;8(2): 190-195.
  19. Nishino S. Clinical and neurobiological aspects of narcolepsy. Sleep Med. 2007;8(4):373-399.
  20. Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol. 2015;11:401-13.
  21. 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.

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.

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.