Orexin and narcolepsy — MRCPsych Paper A MCQ

Instant feedback + full explanation. One question, done properly.

ModerateNeurophysiology and neurochemistryOrexin and narcolepsyMRCPsych Paper A

A 17-year-old boy experiences irresistible daytime sleep attacks. When he laughs, he develops brief bilateral weakness of his jaw and knees while remaining conscious. Which neurochemical abnormality most directly underlies this presentation?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: A — Reduced hypothalamic orexin signalling

The correct answer is A. Irresistible daytime sleep episodes plus emotion-triggered loss of muscle tone with preserved consciousness indicate narcolepsy type 1 with cataplexy. This disorder is associated with selective loss of orexin-producing neurons in the lateral hypothalamus and consequently reduced orexin, also called hypocretin, signalling. Orexin normally stabilises wakefulness and helps prevent inappropriate transitions into rapid eye movement sleep physiology. Noradrenergic and cholinergic systems participate in arousal and REM regulation, but increased noradrenergic signalling or acetylcholine breakdown is not the defining abnormality. Melatonin primarily regulates circadian timing, while dopamine beta-hydroxylase converts dopamine to noradrenaline; increased activity does not explain this characteristic combination of sleep attacks and cataplexy.

Reference: Barateau L, Pizza F, Plazzi G, Dauvilliers Y. Narcolepsies, update in 2023. Revue Neurologique. 2023. https://pubmed.ncbi.nlm.nih.gov/37634997/