A 32-year-old man with HIV/AIDS (CD4 count 45 cells/μL) presents with a 2-week history of fever, headache, and progressive left-sided weakness. Contrast-enhanced MRI brain shows multiple lesions in the basal ganglia and thalamus with ring enhancement and surrounding vasogenic edema. The structure marked **A** in the diagram represents one of these ring-enhancing lesions. Which of the following is the MOST LIKELY diagnosis and the MOST APPROPRIATE initial management?

Question

Accepted Answer

B. CNS toxoplasmosis; empiric pyrimethamine + sulfadiazine + leucovorin for 6 weeks. ## Why CNS toxoplasmosis; empiric pyrimethamine + sulfadiazine + leucovorin for 6 weeks is right

CNS toxoplasmosis is the MOST COMMON cause of focal brain lesions in HIV/AIDS, occurring almost exclusively when CD4 count is <100 cells/μL. The clinical presentation (fever, headache, focal neurologic deficits over days to weeks) and imaging findings (multiple ring-enhancing lesions in basal ganglia and thalamus with vasogenic edema) are classic for toxoplasmosis. The structure marked **A** — a ring-enhancing lesion in the basal ganglia — is the pathognomonic imaging hallmark. Diagnosis is presumptive based on clinical and radiologic features in an AIDS patient with CD4 <100 and positive Toxoplasma IgG serology. Empiric treatment with pyrimethamine (200 mg loading dose, then 50–75 mg daily) + sulfadiazine (1–1.5 g QID) + leucovorin (10–25 mg daily to prevent bone marrow suppression) for 6 weeks of induction is the standard of care. Clinical/radiologic improvement is expected by 10–14 days; failure to respond should prompt stereotactic biopsy to exclude primary CNS lymphoma (Harrison's 21e; DHHS HIV OI Guidelines).

## Why each distractor is wrong

- **Primary CNS lymphoma; initiate chemotherapy with methotrexate and rituximab**: Although PCNSL is an important differential diagnosis in AIDS with focal brain lesions, it classically presents as a SINGLE periventricular lesion with homogeneous enhancement. The MULTIPLE ring-enhancing lesions in the basal ganglia and thalamus are far more typical of toxoplasmosis. PCNSL would show increased uptake on thallium-201 SPECT or 18F-FDG PET (toxoplasmosis is "cold"), and EBV DNA in CSF would be positive. Chemotherapy is not first-line for presumed toxoplasmosis.

- **Progressive multifocal leukoencephalopathy; start cidofovir and immune reconstitution**: PML typically presents with subcortical white matter lesions without enhancement or mass effect, and does not cause ring-enhancing lesions. The imaging pattern described (ring enhancement in basal ganglia with vasogenic edema) is not consistent with PML. PML is a demyelinating disease, not a mass-forming lesion.

- **Cryptococcal meningitis; initiate amphotericin B and flucytosine**: Cryptococcal meningitis presents with meningeal signs and CSF findings (elevated opening pressure, positive India ink or cryptococcal antigen). While it can occur at CD4 <100, it does not typically produce multiple ring-enhancing focal brain lesions in the basal ganglia. The imaging pattern is not consistent with cryptococcal disease.

**High-Yield:** Multiple ring-enhancing lesions in basal ganglia/thalamus at CD4 <100 = toxoplasmosis until proven otherwise; empiric therapy with pyrimethamine + sulfadiazine + leucovorin is diagnostic and therapeutic.

[cite: Harrison's Principles of Internal Medicine 21e; DHHS HIV OI Guidelines; IDSA]

Answer

A. Primary CNS lymphoma; initiate chemotherapy with methotrexate and rituximab

Answer

C. Progressive multifocal leukoencephalopathy; start cidofovir and immune reconstitution

Answer

D. Cryptococcal meningitis; initiate amphotericin B and flucytosine

Explanation

Why CNS toxoplasmosis; empiric pyrimethamine + sulfadiazine + leucovorin for 6 weeks is right

Why each distractor is wrong

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