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.
JC virus Granule cell neuronopathy HIV Magnetic resonance imaging Cerebellar atrophy Progressive multifocal leukoencephalopathy
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The authors wish to thank Dr. Alex Rovira for providing Ref.  and Phil Riley for critical reading of the manuscript.
Conflicts of interest
Mr. Wijburg, Dr. van Oosten, Dr. Murk and Dr. Karimi report no potential conflicts of interest. Dr. Killestein has accepted consulting fees from Merck-Serono, TEVA, Biogen, Genzyme and Novartis. VU Medical Center has received financial support for research activities from Bayer Schering Pharma, Biogen-Idec, GlaxoSmithKline, Merck Serono, Novartis, and Teva. Dr. Wattjes serves as a consultant for Biogen-Idec. He serves on the editorial board of European Radiology.
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