Heterogeneous imaging characteristics of JC virus granule cell neuronopathy (GCN): a case series and review of the literature

Abstract

Granule cell neuronopathy (GCN) is a rare JC virus (JCV)-related disease in immunocompromised patients, characterized by lytic infection of the cerebellar granule cell layer. To enable early diagnosis and intervention, we identify features of GCN and describe possible aspects of disease heterogeneity. We report on two new cases of GCN in HIV-infected patients of whom we retrospectively assessed clinical and radiologic data. In addition, we carried out a literature search and review of clinical, radiologic and histopathologic findings of all published GCN cases. Including the two new cases reported here, a total of 18 GCN cases were included in this study. HIV infection, present in 12 of the cases, was the most common underlying condition, followed by monoclonal antibody treatment which was present in three cases. Cerebellar atrophy was detected in all except two cases. In 12 patients a heterogeneous distribution pattern of white matter changes in the cerebellum and brainstem was observed. Imaging findings in GCN are remarkably heterogeneous; exhibiting cerebellar atrophy, as well as white matter pathology, particularly in the adjacent infratentorial white matter. This suggests an overlap of GCN with other JCV-related diseases, such as progressive multifocal leukoencephalopathy.

Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

“…Cerebellar white matter lesions may also be present, which suggests that GCN and PML may coexist. 50 However, in our series, all atrophic changes affected both the supratentorial and infratentorial compartments and we found no evidence of changes that could suggest the diagnosis of GCN.…”

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

“…JCV affects the neurons in the cerebellum when there is a mutation of the VP1 gene coding for the major capsid protein, which changes the viral tropism from glial cells to cerebellar granule cells. 2,4,10,14 This clinical syndrome is called granule cell neuronopathy, and the clinical manifestations include balance instability and impaired coordination with or without slurring of speech or abnormal eye movements. This atypical presentation can be diagnostically challenging, delaying testing for JCV-associated disease and the initiation of immune reconstitution.…”

“…In addition to our patients, there have been documented cases of granule cell neuronopathy in patients on long-term rituximab as well as natalizumab therapy. 2,10,14 A second diagnostic challenge was the 25% failure rate of CSF PCR testing among patients with JCV. Studies have demonstrated that the sensitivity of first-generation PCR detection for JCV DNA in CSF ranges from 75% to 95%.…”

“…[1][2][3] Normally, cellular immunity keeps the virus quiescent where it is harbored (in the urinary tract, bone marrow, lymphoid tissue, and possibly the central nervous system). 2,4,5 However, patients with abnormalities in cell-mediated immunity are vulnerable to viral reactivation, and replication occurs in glial cells (predominantly oligodendrocytes) and neurons of the cerebrum and granular cell layer of the cerebellum. This leads to demyelination and neuronal death, causing mortality within 2 to 15 months of diagnosis; however, death usually occurs within 2 months for 90% of patients who also have a hematologic malignancy.…”

HIV-Associated JC Virus-Granule-Cell Neuronopathy (JCV-GCN) with the Hot-Cross-Bun Sign

“…JCV-GCN is sometimes associated with T2-weighted/fluid-attenuated inversion recovery (FLAIR) hyperintense white matter abnormalities typical of PML but is a distinct clinical entity [1]. Only 24 cases of HIVassociated JCV-GCN, including our patient, have been reported [9][10][11][12][13][14][15][16].…”