Objective:

To report a case of JC virus granule cell neuronopathy (GCN) mimicking paraneoplastic cerebellar degeneration (PCD). 

Background:

JC virus is known to cause opportunistic infections of the central nervous system in immunocompromised patients. GCN is a unique manifestation of JCV infection that often poses diagnostic challenges. 

Design/Methods:

A 78-year-old woman with a history of rheumatoid arthritis and invasive ductal carcinoma of the right breast in remission presented with two months of progressive gait impairment, dysarthria, visual disturbance, and weight loss. Home medications included azathioprine and low-dose prednisone for rheumatoid arthritis treatment. Serum testing was notable for prominent lymphopenia (absolute lymphocyte count 0.5 x 10⁹ cells/L) and negative HIV antibody screening. Brain MRI revealed moderate cerebellar atrophy, T2/FLAIR hyperintensities in the bilateral middle cerebellar peduncles without associated enhancement, and a small area of left parieto-occipital T2/FLAIR hyperintensity. Cerebrospinal fluid (CSF) analysis revealed slightly elevated protein (62 mg/dL), normal cell counts, normal glucose, and absence of oligoclonal bands. Given breast cancer history and prominent weight loss, a diagnosis of PCD was initially suspected. However, evaluations for malignancy and paraneoplastic autoantibody testing were negative. Given negative malignancy screening, atypical MRI features beyond isolated cerebellar atrophy, and known immunosuppression, the diagnosis was re-evaluated. 

Results:

CSF polymerase chain reaction testing for JC virus was positive. Given prominent cerebellar symptoms and imaging findings, a diagnosis of JC virus GCN was made with likely concomitant progressive multifocal leukoencephalopathy. Further testing revealed a CD4 lymphocyte count of 100 cells/microliter. Azathioprine and prednisone were discontinued. The patient was subsequently treated with pembrolizumab to accelerate immune reconstitution. 

Conclusions:

GCN is a rare manifestation of JC virus infection in immunocompromised patients and can mimic PCD in patients with a history of relevant malignancy. Our case illustrates the importance of including GCN in the differential diagnosis when evaluating patients with progressive cerebellar symptoms.