Narcolepsy

Definition

Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), sleep paralysis, and hypnagogic/hypnopompic hallucinations due to dysregulation of REM sleep.

Epidemiology

• Prevalence: ~0.02–0.05% globally.
• Onset typically in adolescence or early adulthood (15–30 years).
• Affects men and women equally.
• Both genetic and environmental factors contribute.
• HLA-DQB1*06:02 allele strongly associated with narcolepsy type 1.

Etiology

• Type 1 narcolepsy (with cataplexy): loss of hypocretin (orexin)-producing neurons in the hypothalamus, likely autoimmune-mediated.
• Type 2 narcolepsy (without cataplexy): less understood, normal hypocretin levels.
• Genetic predisposition: HLA association.
• Environmental triggers: infections (e.g., H1N1), stress, brain injury.

Pathophysiology

• Loss of hypocretin/orexin neurons disrupts regulation of sleep-wake cycles.
• Inappropriate intrusion of REM sleep into wakefulness.
• Cataplexy triggered by strong emotions due to abnormal REM atonia.
• Sleep fragmentation and altered circadian rhythm contribute to excessive daytime sleepiness.