Case report: nipping PML in the bud

#MSBlog: If you are natalizumab, or Tysabri, and are worried about PML this post if for you!
Epub: Lindå H, von Heijne A.Presymptomatic diagnosis with MRI and adequate treatment ameliorate the outcome after natalizumab-associated progressive multifocal leukoencephalopathy. Front Neurol. 2013;4:11. doi: 10.3389/fneur.2013.00011.

Background: Natalizumab 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. 

Case report: This is a report of PML in an MSers 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 then 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. 

Conclusion: This case clearly illustrates the importance of an early, presymptomatic, detection of PML, and an adequate treatment. The authors' 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 MSers in order to detect PML in an early phase.

"This case report illustrates that early detection and treatment of PML can result in a good prognosis for MSers on natalizumab. However, the recommendation that 3 monthly MRIs is the way to do this is premature. This strategy will need to be studied formerly in a prospective study to see if it works and is cost-effective. In the NHS, and other resource-restricted healthcare systems, MRIs are expensive and as a result restricted. Simply scanning someone every 3 months, without data to support this practice, is not feasible. At the moment we scan JCV-serpositive MSers on natalizumab annually and JCV-seronegative MSers every 2 years. Why? We do this to re-baseline them in case they develop a complication on natalizumab. A new baseline scan provides you with something to compare a new scan in the future with. Why do we do this? When MSers start natalizumab their scans usually change; i.e. some lesions regress or even disappear. In addition there is some pseudoatrophy; this refers to the phenomenon of the brain shrinking when inflammation resolves. All these factors change the way the scans look and this makes it difficult for a neuroradiologist to report new or atypical lesions that could be due PML."

"The question of whether or not we should scan JCV-positive MSers on natalizumab more frequently than annually, is an important one. if you are on natalizumab could you please answer this survey below to see what is happening to you and to see how practice varies across the world? If you know other MSers on natalizumab can you please forward them the link to this post. For this survey to be meaningful we need at least 50 respondents from your country."

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