A 35-year-old man undergoing polysomnography shows episodes of sudden loss of muscle tone precipitated by laughter. His sleep study reveals REM sleep intrusion at sleep onset (sleep-onset REM periods, SOREMPs) on multiple nap tests. Which neurotransmitter deficiency is the PRIMARY neurochemical basis?

• A Orexin (hypocretin) deficiency due to autoimmune destruction of lateral hypothalamic neurons ✓
• B Dopamine deficiency in the ventral tegmental area
• C Serotonin deficiency in the dorsal raphe nuclei causing REM disinhibition
• D GABA deficiency in the locus coeruleus causing wakefulness instability

Explanation

Narcolepsy with cataplexy is caused by selective autoimmune destruction of orexin (hypocretin)-producing neurons in the lateral hypothalamus, resulting in undetectable CSF orexin-A levels (<110 pg/mL). Orexin normally stabilizes wakefulness and suppresses REM sleep. Its loss causes REM intrusion into wakefulness (cataplexy, sleep paralysis, hypnagogic hallucinations) and SOREMPs. Dopamine, serotonin, and GABA changes are secondary or regulatory but not the primary pathology.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.