WBR0205

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pathology
Sub Category	SubCategory::Neurology, SubCategory::Infectious Disease
Prompt	[[Prompt::A 62-year-old woman is brought to the emergency department (ED) by her husband. He reports that one month ago, the patient had complaints of sleep disorder and decrease in appetite. A few days later, she started to become forgetful. At first, the patient was forgetting minor details like the car keys or appointments. The husband is now more concerned that she has lately been forgetting the names of her children, has developed slurred speech, and has experienced progressive difficulty in walking. The patient's temperature is 37 °C (98.6 °F), blood pressure is 122/82 mmHg, and heart rate is 76/min. Physical exam in the ED is remarkable for confusion, muscular hypokinesis, and atrophy. The physician also notes the presence of involuntary intermittent myoclonic jerks of the lower extremities in response to sound or touch. Cerebrospinal fluid analysis demonstrates elevated 14-3-3 proteins. Brain biopsy of this patient would most likely demonstrate which of the following findings?]]
Answer A	AnswerA::Lymphocytic infiltrate
Answer A Explanation	AnswerAExp::Lymphocytic infiltrates may be observed in brain biopsies of patients with encephalitis. Encephalitis is characterized by the presence of fever and a more rapid onset of symptoms.
Answer B	AnswerB::Alpha-synuclein deposits
Answer B Explanation	AnswerBExp::Alpha-synuclein deposits are observed in brain biopsies of patients with Lewy body dementia. Lewy body dementia is characterized by the presence of dementia, early parkinsonism, and visual hallucinations.
Answer C	AnswerC::Beta-pleated sheets
Answer C Explanation	AnswerCExp::Beta-pleated sheets are observed in brain biopsies of patients with Creutzfeldt-Jakob disease (CJD).
Answer D	AnswerD::Pick bodies
Answer D Explanation	[[AnswerDExp::Pick bodies are aggregates of tau proteins that are characteristic of Pick's disease. Patients with Pick's disease present with frontotemporal atrophy that causes dementia, parkinsonism, change in personality, and aphasia. Elevation of 14-3-3 protein in CSF is not typical in Pick's disease.]]
Answer E	AnswerE::Beta-amyloid deposits
Answer E Explanation	[[AnswerEExp::Beta-amyloid deposits correspond to the composition of senile plaques, which are pathological changes characteristic of Alzheimer disease. Manifestations of Alzheimer disease include slowly progressive dementia and late disability. The patient's symptoms are progressing relatively rapidly, which is not consistent with Alzheimer disease.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Creutzfeldt-Jakob disease (CJD) is a neurodegenerative spongiform encephalopathy caused by transmissible prions. In CJD, normal prions (PrPc) misfold into an abnormal form (PrPSc). PrPSc has high amounts of beta-pleated sheet content that renders it stable and resistant to digestion by proteases. Consequently, PrPSc accumulates in the brain. The majority of CJD cases are sporadic, but a variant of the disease (vCJD) associated with dietary exposure to infected animals is also described. The exact cause of infection and predisposition to the disease is unknown, but a combination of both genetic and environmental factors has been speculated. The majority of patients with CJD are between 50-70 years. Clinical manifestations are usually progressive, with an onset of non-specific symptoms that include fatigue, sleep disorders, and anorexia. The disease progresses relatively rapidly, and patients then develop focal neurologic signs, visual loss, and amyotrophy with worsening memory loss. In advanced disease, patients are mute, akinetic, and confused. The presence of episodic myoclonic jerking (startle myoclonus) in response to touch or sound on physical examination is characteristic. Routine work-up is usually unremarkable, but patients may have elevated levels of tau protein or 14-3-3 protein in their cerebrospinal fluid (CSF). Electroencephalogram (EEG) may be normal or may show sharp wave complexes (periodic, biphasic, or triphasic). There is no treatment for patients with CJD and the prognosis is very poor. It is a universally fatal disease, and 80% of patients die in less than 1 year of diagnosis. Prions in dead brain may still be transmissible even after death and may pose a significant health hazard during autopsy of infected patients. Educational Objective: Creutzfeldt-Jakob disease is characterized by rapidly progressive dementia, and is caused by prions which are proteins folded as beta pleated sheets. References: Johnson RT, Gibbs CJ. Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. N Engl J Med. 1998; 339:1994-2004. Ironside JW. Variant Creutzfeldt-Jakob disease: an update. Folia Neuropathol. 2012;50(1):50-6. First Aid 2014 page 483]]
Approved	Approved::Yes
Keyword	WBRKeyword::Creutzfeldt-Jakob disease, WBRKeyword::Dementia, WBRKeyword::Prion, WBRKeyword::Startle myoclonus, WBRKeyword::Myoclonus, WBRKeyword::Spongiform encephalopathy, WBRKeyword::Beta-pleated sheet
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