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

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).