Fatal encephalopathy with wild-type JC virus and ruxolitinib therapy

Lauren Bowen Reoma, Christopher Julius Trindade, Maria Chiara Monaco, Jamie Solis, Marta Garcia Montojo, Phuong Vu, Kory Johnson, Erin Beck, Govind Nair, Omar I. Khan, Marta Quezado, Stephen M. Hewitt, Daniel S. Reich, Richard Childs, Avindra Nath

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24 Scopus citations

Abstract

Objective: JC virus (JCV) infection is a lytic infection of oligodendrocytes in progressive multifocal leukoencephalopathy; less common forms of central nervous system manifestations associated with JCV infection include granule cell neuronopathy, encephalopathy, and meningitis. Presented is the first case of fatal JCV encephalopathy after immunosuppressive therapy that included ruxolitinib. Methods: Postmortem analysis included next generation sequencing, Sanger sequencing, tissue immunohistochemistry, and formalin-fixed hemisphere 7T magnetic resonance imaging. Results: JCV DNA isolated from postmortem tissue samples identified a novel 12bp insertion that altered the transcription site binding pattern in an otherwise “wild-type virus,” which has long been thought to be the nonpathogenic form of JCV. Anti-VP1 staining demonstrated infection in cortical neurons, hippocampal neurons, and glial and endothelial cells. Interpretation: This expands the spectrum of identified JCV diseases associated with broad-spectrum immunosuppression, including JAK-STAT inhibitors, and sheds light on an additional neurotropic virus strain of the archetype variety. ANN NEUROL 2019;86:878–884.

Original languageEnglish
Pages (from-to)878-884
Number of pages7
JournalAnnals of Neurology
Volume86
Issue number6
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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