Overview
What the Orexin Deficit Changes
Narcolepsy is a disorder of sleep wake regulation, not simply “being tired.” In narcolepsy type 1, loss of hypothalamic neurons that produce hypocretin, also called orexin, dest...
Narcolepsy is a disorder of sleep-wake regulation, not simply “being tired.” In narcolepsy type 1, loss of hypothalamic neurons that produce hypocretin, also called orexin, destabilizes the boundary between wakefulness and rapid eye movement (REM) sleep. Wakefulness becomes difficult to sustain, while REM features can appear at inappropriate times. That mechanism explains the characteristic combination of excessive daytime sleepiness and REM-related phenomena: cataplexy, sleep paralysis, and hallucinations when falling asleep or waking. Narcolepsy type 2 causes the same excessive daytime sleepiness and objective multiple sleep latency test findings but does not include cataplexy or documented low cerebrospinal fluid hypocretin-1. Type 2 is a separate diagnostic category, not a milder version of type 1. The HLA-DQB1*06:02 allele is strongly associated with type 1 and supports an autoimmune mechanism of orexin-neuron loss. It is also common in the general population, so HLA typing cannot diagnose narcolepsy by itself.