Abstract
Natalizumab (Tysabri®) is a monoclonal antibody that prevents inflammatory cells from binding to brain endothelial cells and passing into the brain parenchyma. Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain JC virus infection that has been shown to be associated with natalizumab treatment. We describe PML in a patient with MS after 44 monthly infusions of natalizumab. With the aid of a routine Magnetic resonance imaging (MRI) scan, PML was detected before any unambiguous clinical manifestations had emerged. PML was treated with plasma exchange to accelerate removal of natalizumab. Mirtazapine and mefloquine was promptly added and approximately 1 month after plasma exchange, when an immune-reconstitution-inflammatory-syndrome appeared, steroid treatment was initiated. Steroid treatment was then continued until no virus could be detected in the cerebrospinal fluid. The outcome was favorable. We believe that this case clearly illustrates the importance of an early, presymptomatic, detection of PML, and an adequate treatment. We also propose that surveillance with MRI scans, every 3 months after 24 months of treatment, should be performed in JC virus antibody positive natalizumab-treated MS patients in order to detect PML in an early phase.
Highlights
Natalizumab (Tysabri®) was introduced for the treatment of highly active relapsing-remitting multiple sclerosis (MS) in November 2004
We describe a patient with natalizumab treatment who, based on findings on a routine Magnetic resonance imaging (MRI) scan, was diagnosed with Progressive multifocal leukoencephalopathy (PML) before any unambiguous clinical manifestations had emerged
We propose that MRI scans should be performed every 3 months after 24 months of natalizumab treatment among JC virus antibody positive MS patients
Summary
After the plasma exchange, MRI displayed a new PML lesion adjacent to the splenium in the left hemisphere, and the initial lesion in the right hemisphere had increased in size (Figure 2). MRI 2 days later still showed no gadolinium enhancement, perhaps due to the steroid treatment which had already been initiated. At this time, in the left hemisphere, the lesion adjacent to the splenium had further increased in size (Figure 2). A new CSF analysis of JC virus DNA in July, 2.5 months after plasma exchange, showed 510 copies/ml and pleocytosis (10 mono). He is still home living and needs human help for his ADL He complains of increased spasticity in his legs and left arm. An MRI scan performed in November 2012 displayed laminar necrosis in the initial PML lesion in the right parietal lobe (Figure 4)
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