WBR0595

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology, MainCategory::Pathophysiology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 78-year-old man is brought by his daughter to the physician's office for visual hallucinations. She tells the physician that her father has not been able to recognize his relatives and has recently been unable to distinguish place and time. Upon further questioning, the patient's daughter also explains that the patient has lately developed a new resting tremor and has recently had frequent falls. She also explains that his symptoms are progressing at a relatively rapid rate. The physician initially suspects a psychiatric illness and prescribes haloperidol. Several days later, the patient is brought back, and the physician is told that the patient's symptoms have in fact worsened. What is the feature of this patient's condition on histopathological examination?]]
Answer A	AnswerA::Faintly eosinophilic bodies that do not contain a radial filamentous substructures
Answer A Explanation	AnswerAExp::DLB is characterized by Lewy bodies that are described as fainly eosinophilic bodies that do not contain a radial filamentous substructure.
Answer B	AnswerB::Lewy bodies in pigmented brainstem nuclei that are sharply demarcated by a surrounding halo
Answer B Explanation	[[AnswerBExp::Parkinson's disease is characterized by Lewy bodies that are different than those observed in DLB. Lewy bodies in Parkinson's disease are found in the pigmented brainstem nuclei and are sharply demarcated by a surrounding halo. They typically contain a radial filamentous substructures.]]
Answer C	AnswerC::Extracellular protein accumulation due to abnormal proteolytic processing of beta-amyloid deposits
Answer C Explanation	AnswerCExp::Alzheimer's disease is characterized by the amyloid deposition of extracellular proteins due to abnormal proteolytic processing of beta-amyloid deposits.
Answer D	AnswerD::Replacement of a normal protein by a protease-resistant isoform rich in beta-sheet structure
Answer D Explanation	[[AnswerDExp::Creutzfeldt-Jakob disease (CJD) is a rapidly progressive form of dementia with characteristic myoclonus. It has a very poor prognosis with rapid progression. Pathologically, it is characterized by the replacement of normal protein by a protease-resistant isoform rich in beta-sheet structure.]]
Answer E	AnswerE::Dopamine overflow that causes cortical and subcortical imbalance
Answer E Explanation	[[AnswerEExp::Schizophrenia is a psychiatric illness that is thought to be a result of dopamine overflow that causes an imbalance between the cortical and the subcortical systems. Antipsychotics are dopamine antagonists that typically improve symptoms of schizophrenia.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Dementia with Lewy bodies (DLB) is a relatively common neurodegenerative disorder and a frequent cause of dementia. It is characterized by rapid progression (compared with Alzheimer's disease), visual hallucinations (compared with auditory hallucinations observed in schizophrenia), symptoms of Parkinsonism, and featurs of psychosis. Frequent falls occur early in the disease as compared with the delayed falls observed in Parkinson's disease. It is postulated that DLB is caused by the dopaminergic and acetylcholinergic pathway destruction. As a result, patients with DLB are especially susceptible to neuroleptics that often have anti-dopaminergic properties. Administration of neuroleptics often exacerbates extrapyramidal symptoms and makes the management of psychotic symptoms very difficult in patients with DLB. This phenomenon is called "neuroleptic sensitivity" and is in fact a hallmark of DLB. On histopathological examination, DLB is characterized by the presence of Lewy bodies in neurons of the cerebral cortex, which are faintly eosinophilic structures without a sharply demarcated halo around them and do not contain a radial filamentous substructure. In contrast, Parkinson's disease is also characterized by the presence of Lewy bodies; but they often have a well-demarcated halo around them and contain a radial filamentous substructure. Educational Objective: Dementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized by dementia, visual hallucinations, frequent falling, and symptoms of Parkinsonism. Neuroleptic sensitivity, defined as worsening of symptoms following neuroleptic administration, is characteristic of DLB. On histopathological examination, Lewy bodies are found and are distinguished from Lewy bodies of Parkinson's disease by their faintly eosinophilic appearance, the absence of a well-demarcated surrounding halo, and the absence of a radial filamentous substructure. References: Mrak RE, Griffin WS. Dementia with lewy bodies: definition, diagnosis, and pathogenic relationship to Alzheimer's disease. Neuropsychiatr Dis Treat. 2007; 3(5):619-625. Baskys A. Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. J Clin Psychiatry. 2004; 65 Suppl 11:16-22. First Aid 2014 page 483]]
Approved	Approved::No
Keyword	WBRKeyword::Dementia with lewy bodies, WBRKeyword::Lewy body dementia, WBRKeyword::Parkinson's disease, WBRKeyword::Falling, WBRKeyword::Falls, WBRKeyword::Visual hallucinations, WBRKeyword::Hallucinations, WBRKeyword::Dementia, WBRKeyword::Histopathological examination
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