HIV-associated PML MRI appearance is classically described as unifocal or multifocal areas of T2/FLAIR hyperintensity corresponding with T1 hypointensity and possibly leading edge restricted diffusion on DWI/ADC. There is no edema, mass effect, or gadolinium enhancement. There have been no reports of inflammatory MRI features in patients with HIV-associated PML who have not initiated anti-retroviral therapy.

A 61-year-old male presented to the emergency department with progressive vertigo, gait instability, nausea and vomiting, and binocular vertical diplopia. Examination demonstrated gaze-evoked nystagmus, right hypertropia, dysarthria and decreased pinprick sensation to the left face and right body. Reflexes were 3+ throughout with upgoing plantar responses bilaterally. Bilateral limb dysmetria, truncal ataxia and gait instability were also present. MRI without gadolinium showed asymmetric T2/FLAIR hyperintensities in the bilateral middle cerebellar peduncles, extending into the deep cerebellar white matter. The lesion on the right side was larger, mildly heterogeneous, and showed focal diffusion restriction and post-gadolinium enhancement. Eleven days later, repeat MRI showed interval progression of the lesions with increased T2/FLAIR signal abnormality, mass effect and post-contrast enhancement. Infectious work-up yielded HIV positivity (CD4 count of 335 cells/μL; viral load of 24913 copies/mL). A biopsy of the right cerebellar lesion was diagnostic for PML. CSF PCR of JC virus returned positive with a viral load of 8.74 x 10³ copies/ml. The patient was diagnosed with HIV-associated PML and started on anti-retroviral therapy.

HIV-associated PML should be considered despite the presence of gadolinium enhancement, edema, mass effect and punctate T2 hyperintensities with “milky way” appearance, especially if CD4 count is higher. Classically these features are seen in HIV patients started on anti-retroviral treatment presenting with PML-IRIS or multiple sclerosis patients on natalizumab presenting with PML. However, in untreated HIV patients, PML can appear inflammatory in the context of higher CD4 counts.