A 35-year-old man presents with sudden episodes of profound muscle weakness triggered by laughter. He also has excessive daytime sleepiness and reports dream-like hallucinations at sleep onset. Sleep study shows SOREMP (sleep onset REM period) within 15 minutes and a mean sleep latency of 6 minutes on MSLT. What is the pathophysiological basis of his condition?
- A Loss of orexin (hypocretin)-producing neurons in the lateral hypothalamus, typically autoimmune ✓
- B Dopaminergic deficiency in the substantia nigra
- C Cholinergic hyperactivation in the basal forebrain
- D Adenosine accumulation due to impaired adenosine deaminase
Explanation
Narcolepsy type 1 (with cataplexy) is caused by selective, irreversible loss of ~90,000 orexin (hypocretin)-producing neurons in the lateral hypothalamus, typically through an autoimmune mechanism (associated with HLA-DQB1*06:02). Orexin normally stabilises wakefulness and suppresses REM sleep; its absence leads to excessive daytime sleepiness, cataplexy (triggered by strong emotions), sleep paralysis, and hypnagogic/hypnopompic hallucinations (intrusion of REM atonia and dreaming into wakefulness). CSF orexin-A levels below 110 pg/mL confirm the diagnosis. MSLT showing ≥2 SOREMPs with mean latency ≤8 minutes is the polysomnographic criterion.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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