WBR0595

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology, MainCategory::Pathophysiology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 78 year old male patient 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 cannot distinguish place and time. Upon further questioning, the patient's daughter also explains that the patient has lately developed a new resting tremor, has been falling frequently, and that his symptoms are progressing at a relatively rapid rate. At the time, the physician suspects a psychiatric illness and thus prescribes haloperidol. Several days later, the physician is told that the patient's symptoms have in fact worsened. What is the most likely pathological feature in this patient's condition?]]
Answer A	AnswerA::Faintly eosinophilic bodies with absence of radial filamentous substructures
Answer A Explanation	AnswerAExp::DLB is characterized by Lewy bodies that are described as fainly eosinophilic bodies that do not show 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 contains Lewy bodies that are different than those seen in DLB. Lewy bodies in Parkinson's disease are found in the pigmented brainstem nuclei and are sharply demarcated by a surrounding halo with radial filamentous substructure.]]
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 dementia with characteristic myoclonus. It has a very poor prognosis with rapid progression to dementia and death. Pathologically, it is characterized by the replacement of a normal protein by a protease-resistant isoform rich in beta-sheet structure]]
Answer E	AnswerE::Dopamine overflow that causes a cortical and subcortical imbalance
Answer E Explanation	[[AnswerEExp::Schizophrenia is a psychiatric illness believed to be caused by "the dopamine hypothesis", whereby dopamine overflow causes an imbalance between the cortical and the subcortical systems. As such, antipsychotics act as dopamine antagonists to improve symptoms of schizophrenia.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Lewy body dementia, also called dementia with Lewy bodies (DLB) is considered a relatively common neurodegenerative disorder and a frequent cause of dementia that is notably more rapid than Alzheimer's disease. It is also characterized by a fluctuating condition, hallucinations that are usually visual - in contrast to auditory hallucinations commonly seen in schizophrenia. Additionally, DLB has symptoms of Parkinsonism and frequent falling that occur early in the disease as compared to the delayed falls seen in Parkinsonism. Nonetheless, the onset of symptoms of Parkinonism in DLB are relatively delayed in comparison to the onset of other symptoms. Iit is postulated that DLB is caused by the dopaminergic and acetylcholinergic pathway destruction. As a result, patients with DLB are especially susceptible to anti-psychotics due to their anti-dopaminergic properties that exacerbate their extrapyramidal symptoms and makes the management of psychotic symptoms very difficult in patients with DLB. This phenomenon is called "neuroleptic sensitivity" that is in fact a hallmark of DLB. The pathologic features of DLB are the presence of Lewy bodies in neurons of the cerebral cortex that are faintly eosinophilic with the absence of both the sharply demarcated halo around them and 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 with the presence of a radial filamentous substructure. Educational Objective: Lewy body dementia is a neurodegenerative disorder characterized by dementia, visual hallucinations, frequent falling, and Parkinsonian symptoms. Sensitivity to neuroleptics defined as worsening of symptoms following neuroleptic intake is characteristic of lewy body dementia. Pathologically, Lewy bodies are found and are distinguished from Lewy bodies seen in Parkinson's disease by their faintly eosinophilic appearance and the absence of well-demarcated surrounding halo or their radial filamentous substructures. 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. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::lewy, WBRKeyword::body, WBRKeyword::dementia, WBRKeyword::lewy body dementia, WBRKeyword::DLB, WBRKeyword::alzheimer, WBRKeyword::alzheimer's, WBRKeyword::parkinson, WBRKeyword::parkinson's, WBRKeyword::disease, WBRKeyword::schizophrenia, WBRKeyword::falling, WBRKeyword::frequent, WBRKeyword::visual, WBRKeyword::hallucinations, WBRKeyword::neuroleptic, WBRKeyword::sensitivity, WBRKeyword::neuroleptic sensitivity
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