A 44-year-old man with a history of advanced HIV is brought to the office by his family due to progressive cognitive decline. Over the last several years he has had worsening memory deficits and difficulty carrying out simple mental tasks. The patient has had no headaches, slurred speech, muscle weakness, or changes in vision. He was diagnosed with HIV 7 years ago, but his medical follow-up and treatment compliance have been poor. The patient does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. He has difficulty with delayed recall as well as several executive function tasks. The remainder of his neurologic examination is unremarkable. Two weeks later, he dies from severe pneumonia and respiratory failure. Which of the following histopathologic findings would most likely be found on biopsy of this patient's brain?

Question

A 44-year-old man with a history of advanced HIV is brought to the office by his family due to progressive cognitive decline.  Over the last several years he has had worsening memory deficits and difficulty carrying out simple mental tasks.  The patient has had no headaches, slurred speech, muscle weakness, or changes in vision.  He was diagnosed with HIV 7 years ago, but his medical follow-up and treatment compliance have been poor.  The patient does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  He has difficulty with delayed recall as well as several executive function tasks.  The remainder of his neurologic examination is unremarkable.  Two weeks later, he dies from severe pneumonia and respiratory failure.  Which of the following histopathologic findings would most likely be found on biopsy of this patient's brain?

Quizplus · Accepted Answer

This patient with a history of long-standing HIV infection, medical noncompliance, and progressive cognitive decline likely had HIV-associated dementia. Most cases occur in those with advanced HIV who have CD4 counts <200/mm³. Patients usually develop features of subcortical dementia, including attention or working memory deficits, executive dysfunction, and slow information processing. HIV enters the central nervous system via infected monocytes and establishes a productive infection in microglial cells (resident macrophages of the central nervous system) and blood-derived perivascular macrophages. Activation of these cells occurs in response to the infection, inflammatory cytokines, and HIV-derived proteins, which leads them to cluster around small areas of necrosis (forming microglial nodules) and fuse together to form multinucleated giant cells. Because HIV does not directly infect neurons, the underlying pathology of HIV-associated dementia is thought to stem from the release of neurotoxic compounds by these activated monocytes. (Choices A and B) Cerebral amyloid angiopathy is marked by beta-amyloid deposits in the walls of cortical blood vessels. This condition is usually asymptomatic but can be associated with intracerebral hemorrhage or Alzheimer dementia. Alzheimer dementia is also associated with neuritic (senile) plaques, which are extracellular deposits of beta-amyloid surrounded by dystrophic neurites; they stain positive with Congo red and are often located in the hippocampus. Alzheimer dementia is typically seen in older adults and is characterized by slowly progressive memory impairment and higher cortical dysfunction (eg, aphasia, agnosia, apraxia). (Choice C) Patients with rabies develop eosinophilic inclusion bodies in the cytoplasm of neuronal cells (Negri bodies). Rabies is a neurotropic virus that is transmitted by the saliva of infected animals, usually via a bite wound. Patients classically develop fever, hydrophobia (fear of water), and pharyngeal spasms. (Choice E) Huntington disease is an autosomal dominant disorder that causes choreiform movement, psychiatric disturbances, and dementia. It is characterized by severe neuronal loss in the caudate nucleus. (Choice F) Lacunar infarctions cause slit-like white matter cavities with surrounding gliosis. Recurrent lacunar infarctions can result in vascular dementia, which is often characterized by sudden/stepwise cognitive decline and focal neurologic deficits. Patients with vascular dementia are typically older and usually have cardiovascular risk factors. Educational objective: HIV-associated dementia should be suspected in patients with AIDS who have progressive cognitive decline. The characteristic histopathologic finding is microglial nodules (groups of activated microglia/macrophages around small areas of necrosis) and multinucleated giant cells. __________ References: Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/10786996) Pathways to neuronal injury and apoptosis in HIV-associated dementia. (http://www.ncbi.nlm.nih.gov/pubmed/11309629)

A 44-Year-Old Man with a History of Advanced HIV Is