Narcolepsy Is Characterized by Sleep-Wake State Instability1

During the day, unstable wakefulness can occur as excessive daytime sleepiness (EDS) and cataplexy,1,2 the two most common symptoms of narcolepsy3,4

Loss of hypocretin neurons in narcolepsy ultimately leads to sleep-wake state instability1,5

  • During the day, unstable wakefulness can occur due to:
    • - Reduced or inconsistent activation of histamine and other wake-promoting neurons1,5
    • - Periodic activation of REM sleep–promoting neurons and non-REM sleep–promoting neurons1,9,10

Loss of hypocretin neurons causes narcolepsy in most patients3,7,8

  • About 95% of patients with narcolepsy with cataplexy (narcolepsy type 1) are estimated to have low levels of hypocretin3*
  • Approximately 15-20% of patients with narcolepsy without cataplexy (narcolepsy type 2) are estimated to have low levels of hypocretin and are more likely to develop cataplexy3

*Low levels of cerebrospinal fluid (CSF) hypocretin were defined as <110 pg/mL.3

Low levels of CSF hypocretin were defined as ≤110 pg/mL.3

See how EDS and cataplexy can vary»View complementary roles of hypocretin and histamine»


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  3. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed, text revision. American Academy of Sleep Medicine; 2023.
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