PML in the absence of HIV or immunosuppressive therapy (P2.319)

Objective: There are rare reports of PML affecting immunocompetent hosts. We report a case of PML in a 48 year old female with localized, indolent B-cell lymphoproliferative disorder without evidence of immunosuppression. We explore mechanistic theories regarding interactions between JCV and the immune system, and management of PML in the absence of overt immunodeficiency. Background: The patient presented to the emergency department after new-onset seizure. Over the preceding two months, she was having dizzy spells. Her partner also noted deficits in her short-term memory, deterioration of handwriting, and paraphasic errors. On examination, she had subtle right facial droop and cognitive impairment. Design/Methods: Brain MRI revealed two areas of confluent T2/FLAIR hyperintensity, involving white matter in the right temporal and left parietal regions. Brain biopsy showed oligodendrocytes and astrocytes with enlarged pale staining nuclei, and strong immunostaining with SV-40 antigen, establishing the diagnosis of PML. Repeat brain MRI showed interval development of contrast enhancement. Results: Her white blood cell count was 3,500/uL, hematocrit 31.5%, and platelets 85,000/uL. Immune work-up revealed only slightly low IgG, IgM, and IgA. EEG demonstrated right fronto-temporal slowing. CSF exam showed 1 white blood cell, 2 red blood cells, protein 21, glucose 54, and JCV DNA detected after 39.6 cycles of amplification. Mefloquine and mirtazapine were initiated, but she self-discontinued mefloquine after two weeks. She remained on levetiracetam. At six-month follow-up, she demonstrated a stable clinical course. Brain MRI showed near-resolution of the T2/FLAIR signal abnormality. Her complete blood count remained stable. She had an immune response to JCV mediated by both CD4 + and CD8 + T-cells as measured by intracellular cytokine staining. MR spectroscopy was suggestive of immune reconstitution inflammatory syndrome. Conclusions: Recovery of immune function contributed to clinical improvement. Whether treatment with mirtazapine and limited administration of mefloquine were instrumental in the clinical outcome cannot be determined, but deserve further study. Disclosure: Dr. Chu has nothing to disclose. Dr. Owusu has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Hyun has nothing to disclose. Dr. Ranpura has nothing to disclose. Dr. Baehring has nothing to disclose. Dr. Miskin has nothing to disclose. Dr. Koralnik has received personal compensation for activities with Johnson & Johnson as a scientific advisory board member. Dr. Meyer has nothing to disclose.