A 27-year-old reports sudden episodes of cataplexy (sudden muscle weakness with emotion) and hypnagogic hallucinations. Orexin (hypocretin) levels in CSF are undetectable. Which circuit is disrupted?
- A Lateral hypothalamic orexin neurons that normally stabilise the wake-promoting monoaminergic flip-flop switch ✓
- B Dorsal raphe serotonergic neurons projecting to hippocampus
- C Ventrolateral preoptic (VLPO) GABAergic neurons that inhibit arousal systems
- D Locus coeruleus noradrenergic neurons projecting to the forebrain
Correct answer: A. Lateral hypothalamic orexin neurons that normally stabilise the wake-promoting monoaminergic flip-flop switch
Explanation
Narcolepsy with cataplexy is caused by selective destruction of orexin (hypocretin)-producing neurons in the lateral hypothalamus, likely autoimmune. Orexin neurons normally project to and stabilise wake-promoting monoaminergic systems (locus coeruleus, raphe, TMN), preventing abrupt transitions into REM sleep. Without orexin, the sleep-wake 'flip-flop switch' is unstable, causing sudden intrusion of REM phenomena (cataplexy, hypnagogic hallucinations, sleep paralysis) into wakefulness. VLPO neurons promote sleep; their loss would cause insomnia, not narcolepsy.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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