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.
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
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
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
Learn more about histamine neurons, which originate in the hypothalamus, a critical control center for sleep-wake state stability.5,15,18,19
Exploring Histamine in Sleep-Wake State Stability
The Neurobiology of Normal Sleep and Wakefulness
The Pathophysiology of Narcolepsy
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.
- Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
- Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
- 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.
- Schwartz MD, Kilduff TS. The neurobiology of sleep and wakefulness. Psychiatr Clin North Am. 2015;38(4):615-644.
- España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
- Thorpy MJ, Dauvilliers Y. Clinical and practical considerations in the pharmacologic management of narcolepsy. Sleep Med. 2015;16(1):9-18.
- 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.
- 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.
- American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed.; 2014.
- 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.
- 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.
- 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.
- Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378
- Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
- Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
- Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
- Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
- Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol. 2015;11:401-413.
- 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.