Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features

作者：Tory P. Johnson, H. Benjamin Larman, Myoung‐Hwa Lee, Stephen S. Whitehead, Jeffrey A. Kowalak, Camilo Toro, C. Christopher Lau, Juyun Kim, Kory Johnson, Lauren Reoma, Arline Faustin, Carlos A. Pardo, Sanjay Kottapalli, Jonathan Howard, Daniel R. Monaco, James D. Weisfeld‐Adams, Craig Blackstone, Steven Galetta, Matija Snuderl, William A. Gahl, Ilya Kister, Avindra Nath · 发表于：Annals of Neurology · 年份：2019 · DOI：10.1002/ana.25588 · 被引用次数：48 · 研究领域：Mosquito-borne diseases and control、Dementia and Cognitive Impairment Research、Biological Research and Disease Studies

OBJECTIVE: To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. METHODS: Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem. RESULTS: Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. INTERPRETATION: Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting, and chronic dengue infections have not been previously reported. Our findings suggest th...