• Clemens Warnke, Gloria von Geldern, Philipp Markwerth, Thomas Dehmel, Robert Hoepner, Ralf Gold, Michael Pawlita, Tania Kümpfel, Mathias Mäurer, Martin Stangel, Florian Wegner, Reinhard Hohlfeld, Vera Straeten, Volker Limmroth, Thomas Weber, Derik Hermsen, Christoph Kleinschnitz, Hans-Peter Hartung, Mike P Wattjes, Anders Svenningson, Eugene Major, Tomas Olsson, Bernd C Kieseier, and Ortwin Adams.
• Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
• Ann. Neurol. 2014 Dec 1; 76 (6): 792-801.

ObjectiveProgressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV ) in the diagnosis of natalizumab-associated PML.MethodsAIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published.ResultsTwenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5.InterpretationDetermination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML.© 2014 American Neurological Association.

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