A 38-year-old man is brought to the emergency department after a generalized tonic-clonic seizure. He had several days of progressive headache, vomiting, and confusion prior to the episode. Temperature is 38 C (100.4 F). Physical examination shows a lethargic patient with bilateral papilledema and neck rigidity. His condition progressively worsens, and the patient dies in the hospital several days later. An autopsy is performed, and the brain histopathology is shown below. Which of the following pathogens is most likely responsible for these findings?

Question

A 38-year-old man is brought to the emergency department after a generalized tonic-clonic seizure.  He had several days of progressive headache, vomiting, and confusion prior to the episode.  Temperature is 38 C (100.4 F).  Physical examination shows a lethargic patient with bilateral papilledema and neck rigidity.  His condition progressively worsens, and the patient dies in the hospital several days later.  An autopsy is performed, and the brain histopathology is shown below.  Which of the following pathogens is most likely responsible for these findings?

Quizplus · Accepted Answer

11ec160b_387c_8acc_9249_8da85bcf8132_MD0001_00 Cryptococcus neoformans, a round/oval yeast surrounded by a thick polysaccharide capsule (clear areas on H&E tissue stain shown above), is found primarily in soil contaminated by bird droppings and is transmitted to humans via inhalation. Healthy individuals control/eliminate the infection with the cell-mediated immune response and are rarely symptomatic. However, those with compromised immunity, particularly advanced AIDS, cannot contain the infection and often develop hematologic dissemination to the brain (cryptococcal meningitis). Replication of C neoformans in the brain clogs the arachnoid villi with yeast antigens and capsular proteins, leading to obstructed cerebrospinal fluid outflow. This elevates intracranial pressure and causes slowly progressive headache, nausea and vomiting, confusion, neck rigidity, and papilledema. Seizures and brain herniation can subsequently occur. The diagnosis is typically confirmed by detection of cryptococcal antigens in cerebrospinal fluid (CSF) or visualization of encapsulated, budding yeasts in CSF using specialized stains (eg, India ink, methenamine silver); these special stains are needed as the yeasts are surrounded by clear CSF (unlike in tissue sections). Patients who develop cryptococcal meningitis often are unaware of underlying HIV infection (as is likely in this case); it is considered an AIDS-defining illness. (Choice A) Mycolic acid is the primary component of the cell wall of Mycobacterium tuberculosis. Although pulmonary infection is most common, M tuberculosis can spread to the brain and cause subacute meningitis or a focal parenchymal infection called a tuberculoma. Histopathology would show granulomas with giant cells and acid-fast bacteria. (Choice B) Prions, infectious proteins that lack nucleic acid, can cause Creutzfeldt-Jakob disease. Most cases are marked by rapidly progressive dementia and startle myoclonus. Histopathology typically reveals brain atrophy, spongiform vacuoles, and the accumulation of prions in neuronal tissue. (Choice C) Herpes simplex virus is a neurotrophic, double-stranded DNA virus that can spread through the olfactory tract to the olfactory cortex in the temporal lobe of the brain. Patients usually develop acute fever, headache, confusion, and focal neurologic issues. Histopathology typically reveals hemorrhagic inflammation with an infiltration of mononuclear cells. (Choice D) Toxoplasma gondii is a feline parasite that can cause encephalitis in patients with untreated AIDS. Manifestations include headache, confusion, fever, seizures, and focal neurologic deficits. However, histopathology would reveal T gondii cysts, not encapsulated yeasts. Educational objective: Cryptococcus neoformans is a round/oval yeast with a thick polysaccharide capsule. It is a common cause of meningoencephalitis (eg, headache, vomiting, confusion, seizure) in patients with untreated AIDS. The yeast can frequently be visualized in the cerebrospinal fluid by India ink or silver stain.

A 38-Year-Old Man Is Brought to the Emergency Department After