A 24-year-old man comes to the physician due to excessive daytime sleepiness. The patient is a college student whose symptoms started around age 12, when he began needing more sleep than his peers to feel refreshed. Two years later, he started having daily episodes of sudden weakness, consistently triggered by laughter or crying, in which his head would nod or his knees would buckle for about 30 seconds. The patient also describes times when he was unable to move for several minutes after awakening from sleep. He mentions nightly dreams that seem very real, often featuring activities that he had been engaged in during the preceding day. If measured, which of the following compounds is most likely to be abnormal in this patient's cerebrospinal fluid?

Question

A 24-year-old man comes to the physician due to excessive daytime sleepiness.  The patient is a college student whose symptoms started around age 12, when he began needing more sleep than his peers to feel refreshed.  Two years later, he started having daily episodes of sudden weakness, consistently triggered by laughter or crying, in which his head would nod or his knees would buckle for about 30 seconds.  The patient also describes times when he was unable to move for several minutes after awakening from sleep.  He mentions nightly dreams that seem very real, often featuring activities that he had been engaged in during the preceding day.  If measured, which of the following compounds is most likely to be abnormal in this patient's cerebrospinal fluid?

Quizplus · Accepted Answer

11ec160b_3b0c_846b_9249_b70924207ce6_MD0001_00 This patient's excessive daytime sleepiness, episodic loss of motor tone triggered by emotion (cataplexy), and inability to move on awakening (sleep paralysis) are highly suggestive of narcolepsy. Narcolepsy with cataplexy is most often caused by the lack of 2 related neuropeptides: hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B), which are produced in neurons located in the lateral hypothalamus. These neuropeptides promote wakefulness and inhibit REM sleep-related phenomena. Hypocretin-1 levels are low to absent in the cerebrospinal fluid (CSF) of patients who have narcolepsy with cataplexy. (Choice A) Low CSF 5-hydroxyindoleacetic acid (a metabolite of serotonin) concentration has been associated with impulsive, destructive behaviors, particularly aggression, suicide, and violence. (Choice B) Detection of elevated amounts of 14-3-3 protein in CSF is helpful in diagnosing Creutzfeldt-Jakob disease, a neurodegenerative disease caused by prions. (Choice C) Altered levels of the primary dopamine metabolite, homovanillic acid, have been linked to many psychiatric conditions, including substance use disorders, psychosis, and mood disorders. CSF concentrations of homovanillic acid are also decreased in patients with Parkinson disease. (Choice E) The level of melatonin in CSF has been shown to decrease with the progression of Alzheimer disease. Educational objective: Hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B) are neuropeptides produced in the lateral hypothalamus that promote wakefulness and inhibit REM sleep-related phenomena. Most patients who have narcolepsy with cataplexy have undetectable levels of hypocretin-1 in their cerebrospinal fluid. __________ References: Narcolepsy: a clinical review. (http://www.ncbi.nlm.nih.gov/pubmed/24830461) Treatment options for narcolepsy. (http://www.ncbi.nlm.nih.gov/pubmed/27155860)

A 24-Year-Old Man Comes to the Physician Due to Excessive