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

Tory Johnson, Harry Larman, Myoung Hwa Lee, Stephen S. Whitehead, Jeffrey Kowalak, Camilo Toro, C. Christopher Lau, Juyun Kim, Kory R. Johnson, Lauren B. Reoma, Arline Faustin, Carlos A Pardo-Villamizar, Sanjay Kottapalli, Jonathan Howard, Daniel Monaco, James Weisfeld-Adams, Craig Blackstone, Steven Galetta, Matija Snuderl, William A. GahlIlya Kister, Avindra Nath

Research output: Contribution to journalArticle

Abstract

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 that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019.

Original languageEnglish (US)
JournalAnnals of neurology
DOIs
StateAccepted/In press - Jan 1 2019

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Dengue Virus
Dementia
Exome
Dengue
Viruses
Cerebrospinal Fluid
Central Nervous System
Infection
Viral Antibodies
Arboviruses
Polymerase Chain Reaction
Metabolome
National Institutes of Health (U.S.)
Brain
Genetic Testing
Virus Diseases
Encephalitis
Serum
Autoantibodies
Bacteriophages

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features. / Johnson, Tory; Larman, Harry; Lee, Myoung Hwa; Whitehead, Stephen S.; Kowalak, Jeffrey; Toro, Camilo; Lau, C. Christopher; Kim, Juyun; Johnson, Kory R.; Reoma, Lauren B.; Faustin, Arline; Pardo-Villamizar, Carlos A; Kottapalli, Sanjay; Howard, Jonathan; Monaco, Daniel; Weisfeld-Adams, James; Blackstone, Craig; Galetta, Steven; Snuderl, Matija; Gahl, William A.; Kister, Ilya; Nath, Avindra.

In: Annals of neurology, 01.01.2019.

Research output: Contribution to journalArticle

Johnson, T, Larman, H, Lee, MH, Whitehead, SS, Kowalak, J, Toro, C, Lau, CC, Kim, J, Johnson, KR, Reoma, LB, Faustin, A, Pardo-Villamizar, CA, Kottapalli, S, Howard, J, Monaco, D, Weisfeld-Adams, J, Blackstone, C, Galetta, S, Snuderl, M, Gahl, WA, Kister, I & Nath, A 2019, 'Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features', Annals of neurology. https://doi.org/10.1002/ana.25588
Johnson, Tory ; Larman, Harry ; Lee, Myoung Hwa ; Whitehead, Stephen S. ; Kowalak, Jeffrey ; Toro, Camilo ; Lau, C. Christopher ; Kim, Juyun ; Johnson, Kory R. ; Reoma, Lauren B. ; Faustin, Arline ; Pardo-Villamizar, Carlos A ; Kottapalli, Sanjay ; Howard, Jonathan ; Monaco, Daniel ; Weisfeld-Adams, James ; Blackstone, Craig ; Galetta, Steven ; Snuderl, Matija ; Gahl, William A. ; Kister, Ilya ; Nath, Avindra. / Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features. In: Annals of neurology. 2019.
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abstract = "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 that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019.",
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AU - Larman, Harry

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AU - Kowalak, Jeffrey

AU - Toro, Camilo

AU - Lau, C. Christopher

AU - Kim, Juyun

AU - Johnson, Kory R.

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AU - Faustin, Arline

AU - Pardo-Villamizar, Carlos A

AU - Kottapalli, Sanjay

AU - Howard, Jonathan

AU - Monaco, Daniel

AU - Weisfeld-Adams, James

AU - Blackstone, Craig

AU - Galetta, Steven

AU - Snuderl, Matija

AU - Gahl, William A.

AU - Kister, Ilya

AU - Nath, Avindra

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N2 - 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 that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019.

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