Natalizumab-associated progressive multifocal leukoencephalopathy occurring at low positive anti-JC virus antibody level

Abstract

Background: Risk of progressive multifocal leukoencephalopathy (PML), a serious adverse event of natalizumab therapy, is higher with positive anti-JC virus antibody status, greater cumulative exposure to natalizumab and prior immunosuppressant use. Plavina et al. (2014) showed that plasma or serum anti-JC virus antibody index value may allow further PML risk stratification. Among anti-JC virus antibody positive multiple sclerosis patients with no prior immunosuppressant treatment receiving natalizumab, anti-JC virus antibody index >6 months prior to PML diagnosis was significantly higher among those who developed PML with 96% consistently having an anti-JC virus antibody index >0.9. Methods: We describe a case of natalizumab-associated PML with low positive anti-JC virus index value prior to diagnosis. Results: A 53 year old man with 20 year history of relapsing remitting multiple sclerosis was diagnosed with PML following 46 infusions of natalizumab. Glatiramer acetate was his only prior immunomodulatory therapy. Routine MRI surveillance resulted in diagnosis of PML following detection of a confluent right anterior frontal T2 hyperintense lesion extending across the corpus callosum. Six months prior, routine MRI surveillance demonstrated a small right frontal T2 hyperintensity with no diffusion restriction while serum anti-JC virus antibody index was 0.69. Conclusions: Natalizumab-associated PML may develop despite low positive anti-JC virus index value.