Abstract
Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients.
Highlights
Progressive multifocal leukoencephalopathy (PML) is a lytic infection of astrocytes, oligodendrocytes and neurons caused by the JC virus (JCV), leading to irreversible demyelination and neuronal damage [1]
Granule cell neuronopathy (GCN) is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions
The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort
Summary
Progressive multifocal leukoencephalopathy (PML) is a lytic infection of astrocytes, oligodendrocytes and neurons caused by the JC virus (JCV), leading to irreversible demyelination and neuronal damage [1]. PML occurs almost exclusively in immunosuppressed patients, and traditionally PML was mainly observed in human immunodeficiency virus (HIV)-infected patients and patients with hematologic malignancies. In recent years PML has emerged as a serious complication of immunosuppressive treatment. PML associated with monoclonal antibody treatment of autoimmune diseases has attracted major attention. PML has been reported especially in association with the use of natalizumab, a monoclonal antibody against the a4-integrin adhesion molecule approved for the treatment of active relapsing–remitting multiple sclerosis (MS) [2, 3]. As of June 3, 2015, 566 PML cases have been reported in more than 138,800 natalizumab-treated MS patients [4]
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