Abstract Details

Title The spectrum of JC-virus infection: JCV encephalopathy variant associated with cerebral edema and herniation

Topic Infectious Disease

Presentation(s) S45 - Neuroinfectious Disease: Treatments, Diagnostics, and Outcomes (1:00 PM-1:11 PM)

Poster/Presentation
Number 001

Background

The hallmark of JC virus is infection of oligodendrocytes in progressive multifocal leukoencephalopathy (PML). Atypical forms of JC virus infection include JCV meningitis, granule-cell neuronopathy, and encephalopathy, which is associated with unique mutations in the JC virus genome.

Objective

To characterize a novel case of atypical JC virus encephalopathy with global cerebral edema and herniation.

Design/Methods

This patient was followed longitudinally at the NIH. Informed consent was obtained.

Results

A 16-year-old girl underwent allogeneic stem cell transplant for refractory aplastic anemia at the NIH Clinical Center. Post-transplant, she had EBV reactivation requiring rituximab and acute skin graft versus host disease (GVHD) requiring multiple immunosuppressive therapies. Within 6 months of escalating immunosuppression, she had a sudden change in mental status with seizure-like episode in the setting of resolved RSV infection. JCV in the CSF was 445,490 copies/mL with no intracranial white matter abnormalities on imaging. Concurrently, hemophagocytic lymphohistiocytosis (HLH) was diagnosed due to elevated IL2R (3,230 pg/mL) and ferritin (59,326 mcg/L) with pancytopenia and fever. Additional immunosuppressive therapy was added for the treatment of HLH, including ruxolitinib. Over three weeks weeks, JCV in CSF was 1,779,922 copies/mL, EEG showed progressive cortical signal suppression and CT head showed global cerebral edema with herniation. JC viral load of autopsy brain was 50 million to >1 billion copies/mL tissue. Western blot confirmed VP1 protein and electron microscopy identified polyomavirus in cerebral tissue. Next-generation deep sequencing identified three predominant archetype JCV strains, and Sanger sequencing showed a novel insertion in the non-coding portion of the early mRNA transcript.

Conclusions

JC virus encephalopathy is a unique manifestation of JC virus infection that has previously been identified with agnoprotein deletion. Here we report a case with a novel insertion in non-coding RNA of archetype JC virus resulting in overwhelming CNS infection.

Authors/Disclosures
Lauren Reoma, MD, FAAN (NIH/NINDS) PRESENTER	Dr. Reoma has received research support from NIH. Dr. Reoma has a non-compensated relationship as a Vice Chair with AAN Experimental Neurotherapeutics Section that is relevant to AAN interests or activities. Dr. Reoma has a non-compensated relationship as a Federal Employee with NINDS/NIH that is relevant to AAN interests or activities. Dr. Reoma has a non-compensated relationship as a Member with ASENT Program Committee that is relevant to AAN interests or activities.
Maria Chiara Monaco	No disclosure on file
Jamie Solis, MD	Dr. Solis has nothing to disclose.
	No disclosure on file
	No disclosure on file
Omar Khan, MD, FAAN	Dr. Khan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Khan has received personal compensation in the range of $100,000-$499,999 for serving as a Director of Epilepsy Center with Veterans Affairs. An immediate family member of Dr. Khan has received personal compensation in the range of $100,000-$499,999 for serving as a Clinical Reviewer with FDA.
	No disclosure on file
Daniel Reich, MD, PhD (National Institutes of Health, Neuroimmunology Branch, NINDS)	Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Sanofi. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. Dr. Reich has received intellectual property interests from a discovery or technology relating to health care. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with PeerView. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with Integrity. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Letters and Sciences. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Academic CME. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Biohaven that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sana that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Merck KGaA EMD Serono that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Bristol-Meyers Squibb that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with ChemoCentryx that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Hyperfine that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Imaginab that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Perceptive that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Annexon that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Philips that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Siemens that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Novartis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Calico Life Sciences that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Cognito Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sudo that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Allumis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with BioCentury that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Regeneron that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Eli Lilly that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with SetPoint that is relevant to AAN interests or activities.
	No disclosure on file
Avindra Nath, MD, MBBS, FAAN (National Institutes of Health)	Dr. Nath has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Nath has received research support from National Institutes of Health. The institution of Dr. Nath has received research support from ALS Association. Dr. Nath has received intellectual property interests from a discovery or technology relating to health care.

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