A 28-year-old presents with sudden loss of muscle tone when laughing (cataplexy), excessive daytime sleepiness, and hypnagogic hallucinations. Orexin (hypocretin) levels in CSF are undetectable. Which physiological explanation accounts for cataplexy?

• A Loss of orexinergic inhibition of REM-off noradrenergic neurons, leading to inappropriate REM atonia during wakefulness
• B Excessive GABA release from basal ganglia suppressing motor neurons during emotion
• C Loss of orexinergic excitation of brainstem monoaminergic REM-off neurons, causing inappropriate activation of REM atonia circuits while awake ✓
• D Serotonin excess from raphe nuclei activating spinal inhibitory interneurons

Explanation

Orexin normally excites monoaminergic REM-off neurons (locus coeruleus, raphe) which tonically inhibit REM atonia circuits during wakefulness. In narcolepsy with cataplexy, orexin neurons are destroyed by autoimmunity. Without orexinergic excitation, emotional stimuli that normally increase cholinergic input can inappropriately activate REM atonia (brainstem atonia circuits), causing sudden loss of muscle tone while the person remains awake. Option A has the mechanism backwards; options B and D do not reflect the core circuit.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.