Epidemiology


Etiology


  • Narcolepsy Type 1: Caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. This is thought to be an autoimmune process, often linked to the HLA-DQB1 06:02 haplotype. The lack of hypocretin leads to instability in the sleep-wake cycle, causing elements of REM sleep to intrude into wakefulness.
  • Narcolepsy Type 2: The exact cause is less clear, but hypocretin levels are typically normal. It may involve less severe neuronal loss or issues with hypocretin receptor signaling.

Pathophysiology


Clinical features


  • The classic tetrad includes:
    1. Excessive Daytime Sleepiness (EDS): Irresistible “sleep attacks” and persistent drowsiness despite adequate nighttime sleep. Naps are often short and refreshing.
    2. Cataplexy: Pathognomonic for Type 1. It is a sudden, brief loss of muscle tone triggered by strong emotions like laughter, excitement, or anger. Awareness is preserved.
    3. Hypnagogic/Hypnopompic Hallucinations: Vivid, dream-like hallucinations that occur while falling asleep (hypnagogic) or waking up (hypnopompic).
    4. Sleep Paralysis: Inability to move or speak for a few seconds to minutes upon awakening or falling asleep.
  • Onset is typically in adolescence or young adulthood (ages 15-25).

Diagnostics


  • The gold standard for diagnosis involves a combination of clinical evaluation, a nocturnal polysomnography (PSG) followed by a Multiple Sleep Latency Test (MSLT).
  • MSLT findings: Mean sleep latency of ≤ 8 minutes and the presence of ≥ 2 sleep-onset REM periods (SOREMPs). A SOREMP is entering REM sleep within 15 minutes of sleep onset.
  • CSF analysis: Low levels of hypocretin-1 (&lt 110 pg/mL) are diagnostic for Narcolepsy Type 1.

Treatment


General measures

  • Optimize sleep hygiene.
    • Ensure regular sleep periods during the night.
    • Avoid substances that disturb the sleep-wake cycle (e.g., alcohol, antipsychotics, opiates).
  • Consider scheduled naps throughout the day to reduce the urge to sleep.

Medical therapy

  • First-line medications
    • Modafinil: a nonamphetamine CNS stimulant
    • Nighttime sodium oxybate: a sodium salt of gamma hydroxybutyric acid
      • Help control daytime sleepiness by improving nighttime sleep.