Epidemiology

Etiology

Primary narcolepsy

• Narcolepsy type 1
  • Loss of lateral hypothalamic neurons, which produce hypocretin-1 and hypocretin-2 (i.e. orexin A and orexin B) → severe hypocretin (orexin) deficiency → dysregulation of sleep-wake cycles
• Narcolepsy type 2
  • Idiopathic

Secondary narcolepsy

• Cerebral damage (e.g., tumor, stroke, inflammation, vascular malformation)
• Genetic syndromes (e.g., Niemann-Pick disease type C and Prader-Willi syndrome and Angelman syndrome)

Pathophysiology

Clinical features

• Excessive daytime sleepiness: Affected individuals experience an irresistible urge to sleep and sudden, short sleep attacks (< 30 minutes), which may occur in inappropriate situations (e.g., while driving a car).
  • Can occur despite adequate sleep
• Abnormal REM sleep
  • Cataplexy: sudden muscle weakness in a fully conscious person, triggered by strong emotions (e.g., laughing, crying)
  • Sleep paralysis: Complete paralysis occurs for 1–2 minutes after waking or before falling asleep (either during a nocturnal or narcoleptic sleep episode, i.e., begins or ends with REM sleep)
• Sleep hallucinations
  • Hypnagogic hallucinations: vivid, often frightening visual or auditory hallucinations that occur as the patient falls asleep
  • Hypnopompic hallucinations: experienced while waking up (less common than hypnagogic hallucinations)

Diagnostics

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.