A 45-year-old man presents with excessive daytime sleepiness, cataplexy triggered by laughing, and hypnagogic hallucinations. Polysomnography followed by MSLT shows mean sleep latency of 6 minutes with 4 sleep-onset REM periods (SOREMPs). What is the pathophysiology of his primary diagnosis?

• A Loss of orexin (hypocretin)-producing neurons in the hypothalamic lateral area ✓
• B Deficiency of serotonergic neurons in the raphe nuclei
• C Dysfunction of adenosine clearance in the basal forebrain
• D Autoimmune destruction of dopaminergic neurons in the ventral tegmentum

Explanation

Narcolepsy Type 1 (with cataplexy) is caused by autoimmune destruction of orexin (hypocretin)-producing neurons in the lateral hypothalamus (LH). CSF orexin-1 levels <110 pg/mL are diagnostic. Orexin normally maintains wakefulness and stabilizes REM/wake transitions; its absence causes REM intrusion into wakefulness (cataplexy, hypnagogic hallucinations, sleep paralysis) and excessive daytime sleepiness. The MSLT criterion requires ≥2 SOREMPs with mean sleep latency ≤8 minutes. Treatment: sodium oxybate (for cataplexy and sleep quality), modafinil or pitolisant (for EDS), venlafaxine (for cataplexy).

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.