Atypical presentations and course of JC virus infection

There is increasing evidence that the spectrum of human polyomavirus 2 (JCV) CNS disease includes novel syndromes other than progressive multifocal leukoencephalopathy (PML), the appreciation of which is increasingly important in the context of MS therapies and immunodeficiency states. Our objective is to describe unusual presentations of JCV infection to heighten clinician awareness. We describe three case reports of various PML presentations. Firstly a 56-year-old HIV positive male with decades of viral suppression and normal immune function presented with 1 month of non-specific headache that spontaneously resolved despite an MRI showing a new area of PML and CSF being JC DNA + . He had had two similar episodes in 2013 and 2014 with MRI scans consistent with PML, CSF, JCV, and PCR positivity once and brain biopsy-positive twice. Another 61-year-old male presented with subacute binocular vision loss and was found to have newly diagnosed HIV and JCV DNA detected in CSF. MRI brain only demonstrated symmetrical chiasmo-hypothalamic enhancement. There has been some improvement with combination antiretroviral therapy and corticosteroids for immune reconstitution inflammatory syndrome (IRIS). Thirdly, a 65-year-old male presented with subacute progressive confusion and behavioural disturbance, one year post-bilateral lung transplantation. MRI brain demonstrated no evidence of PML but CSF on three occasions demonstrated a progressively increasing JCV DNA load. Despite reduction in his immunosuppression, the patient developed profound encephalopathy without localising features leading to death two months later. These cases emphasise the atypical presentations of JCV: chronic relapsing, unusual symmetrical visual pathway disease, and non-localising encephalopathy without MRI evidence of PML.