From the Journals

MRI finds PML in some natalizumab-treated patients despite negative CSF, no symptoms


Key clinical point: Meticulous clinical and MRI follow-up in combination with repeated CSF JCV PCR testing may be warranted in natalizumab-treated MS patients with small progressive multifocal leukoencephalopathy (PML) lesions seen on MRI but with undetectable JC virus DNA in their cerebrospinal fluid.

Major finding: MS patients with smaller MRI-detected PML lesion volumes are more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML.

Study details: Retrospective cross-sectional study of 56 patients with natalizumab-associated PML.

Disclosures: The Dutch Foundation for MS Research supported the study. Individual authors reported support for the research from the Charcot Foundation, the Hertie Foundation, and the National Institutes of Health. Several of the authors reported receiving consultancy fees from pharmaceutical companies.

Source: Wijburg M et al. JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0094.

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MRI not yet ready for bigger role in PML detection

Dr. Wijburg and colleagues raise an important point in our understanding of the development of PML by showing that small brain lesions may be present at what may be the start of JCV infection when the virus is still undetectable in CSF. However, it is not yet clear how well the relationship between viral load in CSF and MRI brain lesions approximates the stages of the disease and the processes with which it affects its target brain cells.

In some cases in which CSF testing is negative, repeat testing may be worthwhile because some patients have been known to test positive only weeks after testing negative.

Suspicion for PML may be increased when MRI shows signs of PML despite negative CSF testing, but it is to early to rely on MRI alone for diagnosis.

Eugene O. Major, PhD, is with the division of neuroimmunology and neurovirology at the National Institute of Neurological Disorders and Stroke, Bethesda, Md. He reported serving on the Progressive Multifocal Leukoencephalopathy Consortium Science advisory board and has received consulting fees while serving on independent adjudication committees for Takeda/Millennium, Roche/Genentech, and GlaxoSmithKline. He also has patent rights at the National Institutes of Health as coinventor of the Ultrasensitive Quantitative Polymerase Chain Reaction Multiplex assay for the detection of JC virus DNA–distinguishing viral variants. His comments are derived from an editorial accompanying Dr. Wijburg and colleagues’ report (JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0004).



Some multiple sclerosis patients who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions seen on MRI yet have undetectable JC virus DNA in their cerebrospinal fluid, a cross-sectional, retrospective study has revealed.

The findings show that for some people with MS, PML diagnosis could be delayed if cerebrospinal fluid (CSF) sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to the authors, led by Martijn T. Wijburg, MD, of the MS Center at VU University Medical Center in Amsterdam.

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The study also described a potential correlation between PML lesion volume and John Cunningham virus (JCV) copy numbers. “To our knowledge, this is the first study that shows an association between total PML lesion volume measured by brain MRI and CSF JCV PCR [polymerase chain reaction] results in patients with [natalizumab-associated PML]. This may have considerable implications for patient care,” the research team wrote in JAMA Neurology.

PML, a lytic infection of glial and neuronal cells by the JCV, can be diagnosed when a patient exhibits clinical symptoms, JC virus DNA is detected in CSF by PCR, and specific brain lesions are seen on MRI, according to a consensus statement from the Neuroinfectious Disease section of the American Academy of Neurology.


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