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about sleep, wakefulness,
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Narcolepsy Clinical Practice Insights and Educational Resources

Managing narcolepsy in clinical practice can be challenging.1,2 Know Narcolepsy is here to help.

Narcolepsy symptoms can have a significant impact, but may not always be obvious — even to the patient.1,3,4 Know Narcolepsy is an online resource that seeks to help healthcare professionals improve the lives of their patients with narcolepsy by offering insight into patient experiences, detailed information about the neurobiology of narcolepsy, as well as tools and resources for their practice.

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Exploring Histamine in Sleep-Wake State Stability

Dr. Thomas Scammell

Neurologist and sleep specialist

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.5,6

The Neurobiology of Normal Sleep and Wakefulness

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.6-10

The Pathophysiology of Narcolepsy

Discover how hypocretin loss can cause insufficient activation of histamine and other wake-promoting neurons and insufficient inhibition of non-REM sleep–promoting neurons and REM sleep–promoting neurons, leading to sleep-wake state instability.6,9,12

The Role of Histamine in Sleep and Wakefulness

Learn more about histamine neurons, which originate in the hypothalamus, a critical control center for sleep-wake state stability.6,9,11

4 Scammell Exploring Histamine
6 Neurobiology of Normal Sleep
5 Pathophysiology of Narcolepsy
7 Role of Histamine
4 Scammell Exploring Histamine

Exploring Histamine in Sleep-Wake State Stability

6 Neurobiology of Normal Sleep

The Neurobiology of Normal Sleep and Wakefulness

5 Pathophysiology of Narcolepsy

The Pathophysiology of Narcolepsy

7 Role of Histamine

The Role of Histamine in Sleep and Wakefulness

  1. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
  2. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  3. 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.
  4. 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.
  5. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
  6. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  7. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
  8. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
  9. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  10. Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
  11. Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol. 2015;11(7):401-413.
  12. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.

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

There's to Know

about sleep, wakefulness,
and narcolepsy