Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection of the central nervous system caused by the JC virus, predominantly affecting immunosuppressed patients such as those with HIV and low CD4 counts. The clinical presentation is variable and can mimic psychiatric disorders or other neurological diseases, hindering early diagnosis.

MGA, female, 52 years old, with no known comorbidities, presented to the emergency department after a single generalized tonic-clonic seizure (< 1 minute). She had six months of apathy, social withdrawal, and lethargy – treated as depression with nortriptyline. Progressive worsening occurred, with expressive aphasia in the last two weeks and a fall one week before admission. She reported moniliasis six months earlier. On examination, she showed decreased consciousness (GCS 10), somnolence, lethargy, aphasia, and grade 2 paresis in both upper and lower limbs. Head CT revealed an intra-axial frontal expansive process with frontotemporal edema. Brain MRI with contrast showed signal alterations in the deep white matter (low T1 and high T2/FLAIR), without appreciable enhancement, predominantly in the left frontal region, extending contralaterally through the corpus callosum and posteriorly to the left temporo-insular margin – clearly asymmetric and respecting “U-fiber” limits, without significant mass effect or retraction. MR spectroscopy revealed choline and creatine peaks predominating over NAA, suggesting neuronal loss typical of high-grade infiltrative processes. HIV serology was positive, with viral load 648,000 copies/mL and CD4 count 45 cells/mm³. CSF PCR for JC virus was positive, confirming the diagnosis of Progressive Multifocal Leukoencephalopathy. Antiretroviral therapy and prophylaxis for severe immunosuppression were initiated.

This case demonstrates an atypical presentation of PML with initial depressive symptoms. Progressive neurological decline and a history of oral candidiasis were important clues to investigate immunosuppression. MRI findings and CSF PCR for JC virus were crucial for diagnosis. Early initiation of ART is essential, highlighting the importance of broad neurological evaluation in subacute neuropsychiatric cases.