What is the most likely infectious agent in a patient with HIV/AIDS (Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome) presenting with double vision, expressive aphasia, difficulty coordinating movements, and poor recall, with MRI findings of subcortical white matter T2 FLAIR hyperintensity?

JC Virus is the Most Likely Infectious Agent

In an HIV/AIDS patient presenting with multifocal neurological deficits (double vision, expressive aphasia, ataxia, memory impairment) and MRI showing subcortical white matter T2 FLAIR hyperintensities spanning multiple lobes, JC virus causing progressive multifocal leukoencephalopathy (PML) is the definitive diagnosis. 1

Why JC Virus is the Answer

Classic PML Presentation

• The clinical triad matches PML perfectly: cognitive dysfunction, visual loss (diplopia), and focal neurologic findings (aphasia, ataxia) occurring in a patient with AIDS 1
• The MRI findings are pathognomonic: confluent subcortical white matter hyperintensity on T2/FLAIR sequences spanning frontal, parietal, and temporal lobes is the hallmark imaging pattern of PML 1
• JC virus is a naked, double-stranded DNA polyomavirus, matching the viral description provided 2, 3

Epidemiology Confirms JC Virus

• PML occurs almost exclusively in patients with cell-mediated immunodeficiencies, particularly AIDS and hematologic malignancies 1
• Approximately 3-5% of HIV-infected individuals will develop PML, making it an AIDS-defining illness 3
• The disease specifically targets oligodendrocytes in subcortical white matter, causing demyelination 3, 4

Why the Other Options Are Incorrect

Herpes Simplex Virus (HSV)

• HSV-1 causes temporal and inferior frontal lobe involvement, not diffuse subcortical white matter disease 1
• MRI in HSV encephalitis shows temporal lobe edema with high signal on FLAIR/T2, with bilateral temporal involvement being nearly pathognomonic 1
• HSV is an enveloped DNA virus, not naked 1
• Clinical presentation typically includes fever, hemicranial headache, and behavioral abnormalities rather than the multifocal deficits seen here 1

Human Papilloma Virus (HPV)

• HPV does not cause encephalitis or CNS infections 1
• This virus causes mucocutaneous lesions and certain malignancies, not neurological disease 1

Measles Virus

• Measles virus is an enveloped RNA virus (Paramyxoviridae family), not a naked DNA virus 1
• Measles encephalitis presents with decline of consciousness, focal signs, and seizures, typically in unvaccinated individuals with recent measles exposure 1
• Subacute sclerosing panencephalitis (SSPE) has insidious onset with personality changes and myoclonic jerks, not the acute multifocal presentation described 1

Diagnostic Confirmation

CSF Testing

• CSF PCR for JC virus has 50-75% sensitivity and 98-100% specificity for PML diagnosis 1
• Quantitative PCR is available and can help monitor disease burden 1

Brain Biopsy

• Brain biopsy remains the gold standard if CSF PCR is negative but clinical suspicion remains high 1
• Histology shows demyelination with enlarged oligodendrocyte nuclei containing viral inclusions 2, 3

Critical Management Considerations

Treatment Approach

• The primary treatment is reversal or control of immunosuppression (Grade A-III recommendation) 1
• For HIV/AIDS patients, this means initiating or optimizing antiretroviral therapy immediately 5, 4
• No specific antiviral therapy exists for JC virus 1, 3, 4

IRIS Warning

• Immune reconstitution inflammatory syndrome (IRIS) may develop after starting antiretroviral therapy in HIV patients with PML 2, 4
• IRIS causes paradoxical worsening of neurological symptoms despite virologic control 4
• This requires careful monitoring and may necessitate corticosteroid therapy 4

Prognosis

• PML carries significant mortality, with median survival historically measured in months without immune reconstitution 3, 4
• Prognosis has improved with effective antiretroviral therapy in HIV patients 4

Common Pitfall to Avoid

Do not confuse PML's subcortical white matter involvement with HSV's temporal lobe predilection. The distribution pattern on MRI is the key distinguishing feature: PML shows nonenhancing, confluent subcortical white matter lesions across multiple lobes, while HSV shows temporal and inferior frontal lobe edema with enhancement 1. The clinical context of AIDS with multifocal deficits rather than fever and behavioral changes further confirms PML over HSV encephalitis 1.