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Brief Report
June 2018

Fatal Powassan Encephalitis (Deer Tick Virus, Lineage II) in a Patient With Fever and Orchitis Receiving Rituximab

Author Affiliations
  • 1Neuropathology Division, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 3Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
  • 4Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 5currently at medical student at UCSF School of Medicine, University of California, San Francisco
  • 6Weill Institute for Neurosciences, University of California, San Francisco
  • 7Department of Neurology, University of California, San Francisco
  • 8Department of Biochemistry & Biophysics, University of California, San Francisco
  • 9Chan Zuckerberg Biohub, San Francisco, California
  • 10Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Neurol. 2018;75(6):746-750. doi:10.1001/jamaneurol.2018.0132
Key Points

Question  What is the most efficient way to diagnose Powassan encephalitis in an immunocompromised patient?

Findings  In this case report of a patient with fatal Powassan encephalitis with negative serology, diagnosis was made by Powassan virus immunohistochemistry, targeted real-time polymerase chain reaction, and metagenomic next-generation sequencing.

Meaning  In immunosuppressed patients, many tools can be used to make a diagnosis when routine testing results are negative, including unbiased sequencing assays.


Importance  Powassan virus is a rare but increasingly recognized cause of severe neurological disease.

Objective  To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis.

Design, Setting, and Participants  Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center.

Exposure  Infection with Powassan virus.

Main Outcomes and Measures  Results of individual assays compared retrospectively.

Results  In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid.

Conclusions and Relevance  Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.