A 62-year-old man is brought to the office by his wife due to recent personality changes and cognitive impairment. The symptoms began 4 months ago with abrupt-onset depression and profound sleepiness. Soon after, the patient began having difficulty remembering names and events. He now cannot prepare his own meals or care for himself. The patient has a history of herpes simplex virus type 1 and takes acyclovir occasionally for recurrent symptoms; medical history is otherwise unremarkable. He has no history of psychiatric disease but has a family history of dementia from his father. The patient has a 40-pack-year smoking history. Temperature is 37.7 C (99.9 F), blood pressure is 118/79 mm Hg, pulse is 72/min, and respirations are 14/min. The patient is oriented only to self. Montreal Cognitive Assessment score is 10/30 (normal: ≥26). Near the end of the examination, the patient startles and jerks his arms when a door closes loudly. Lumbar puncture is recommended. Which of the following findings would be expected in this patient's cerebrospinal fluid?

Question

A 62-year-old man is brought to the office by his wife due to recent personality changes and cognitive impairment.  The symptoms began 4 months ago with abrupt-onset depression and profound sleepiness.  Soon after, the patient began having difficulty remembering names and events.  He now cannot prepare his own meals or care for himself.  The patient has a history of herpes simplex virus type 1 and takes acyclovir occasionally for recurrent symptoms; medical history is otherwise unremarkable.  He has no history of psychiatric disease but has a family history of dementia from his father.  The patient has a 40-pack-year smoking history.  Temperature is 37.7 C (99.9 F), blood pressure is 118/79 mm Hg, pulse is 72/min, and respirations are 14/min.  The patient is oriented only to self.  Montreal Cognitive Assessment score is 10/30 (normal: ≥26).  Near the end of the examination, the patient startles and jerks his arms when a door closes loudly.  Lumbar puncture is recommended.  Which of the following findings would be expected in this patient's cerebrospinal fluid?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d75a_9fba_bc81_87607ad8b9c7_MD0003_00 This previously healthy patient has developed rapidly progressive dementia, myoclonus (eg, startle-induced arm jerking), mood symptoms (eg, depression), and hypersomnia. This presentation is concerning for Creutzfeldt-Jakob disease (CJD), a rapidly fatal disease transmissible by an abnormally folded protein (ie, prion). Cerebrospinal fluid (CSF) findings in patients with CJD may include: Elevated 14-3-3 protein titers (a marker of neuronal cell death not specific for CJD) Elevated tau protein (also seen in other neurodegenerative diseases) No white blood cells, normal glucose, normal or elevated protein (ie, noninflammatory) In addition, real-time quaking-induced conversion (RT-QuIC) is a newer assay performed on CSF in which the abnormally folded proteins are isolated, amplified, and then incubated with normally folded proteins. A prion-induced conformational change in the normal proteins can be observed via fluorescence detection in real time. The RT-QuIC test has greater sensitivity and specificity compared to 14-3-3 and tau analyses, but it is not widely available. (Choice B) Anti-Hu encephalitis is a paraneoplastic syndrome most commonly associated with small cell lung cancer (more common in patients who smoke). It may present with rapid-onset dementia, including personality and behavior changes; however, patients also typically have seizures, hallucinations, and brainstem symptoms (eg, dizziness, nausea), and myoclonus is not usually present. (Choice C) Although anti-NMDA receptor encephalitis can present with rapidly progressive behavior changes, memory dysfunction, and abnormal movements (eg, dyskinesia, chorea, facial twitching), it is also usually accompanied by hallucinations and autonomic instability. In addition, it is most commonly associated with ovarian teratomas. (Choice D) Herpes simplex viral encephalitis can present with rapidly worsening mental status. However, it typically manifests much faster (ie, <1 week) than CJD and is usually accompanied by fever, headache, seizures, and focal neurologic deficits. (Choice E) Low alpha-synuclein may be seen in Parkinson disease (PD) and Lewy body dementia (LBD). Although both can cause behavior changes and cognitive impairment, PD is typified by bradykinesia, resting tremor, and rigidity, and LBD is characterized by hallucinations and parkinsonism. (Choice F) Low hypocretin (also known as orexin) levels are found in patients with narcolepsy type 1. Although narcolepsy can present with excessive daytime sleepiness and movement abnormalities in response to a startle, the movements are typically a transient loss of muscle tone (ie, cataplexy). Patients generally do not have dementia or a decline in ability to care for themselves. Educational objective: Creutzfeldt-Jakob disease is a fatal prion disease that presents with rapidly progressive dementia, myoclonus, mood changes, and sleep disturbances. Cerebrospinal fluid findings are typically noninflammatory and often include high levels of 14-3-3 protein. References: Validation of 14-3-3 protein as a marker in sporadic Creutzfeldt-Jakob disease diagnostic. (http://www.ncbi.nlm.nih.gov/pubmed/25947081) CSF biomarkers in neurodegenerative and vascular dementias. (http://www.ncbi.nlm.nih.gov/pubmed/27016008)

A 62-Year-Old Man Is Brought to the Office by His