Chronic Dengue Virus Encephalitis: A Case Study and Metagenomic Analysis

Abstract

Background and objectives: Dengue virus (DENV) infection can cause acute encephalitis. Chronic encephalitis with progressive dementia is rarely reported.

Methods: We present a case of chronic encephalitis with rapidly progressive dementia, in which a potential DENV brain infection was identified with brain tissue metagenomic next-generation sequencing. Brain pathology and molecular diagnosis are also presented.

Results: A 20-year-old man from SP, Brazil, presented with rapidly progressive dementia, speech apraxia, and apathy in June 2022. By January 2023, cognitive testing showed severe global impairment (MMSE score of 18/30). MRI revealed white matter abnormalities and atrophy; CSF analysis disclosed a mild lymphocytic pleocytosis, mildly elevated protein levels, and positive CSF oligoclonal bands. Despite extensive testing ruling out common infectious and inflammatory causes, the patient's condition worsened with executive dysfunction, language impairment, tremors, and myoclonus. In August 2023, a brain biopsy and next-generation sequencing identified DENV-1 genotype V, linked to Brazilian sequences from 2000 to 2022.

Discussion: This case highlights a challenging instance of encephalitis with unknown etiology, where metagenomic analysis detected DENV-1 RNA in brain tissue, suggesting a possible cause.

Figure 1. Brain Biopsy Findings

(A) H and E staining reveals an inflammatory infiltrate in brain parenchyma, with perivascular and interstitial distribution, associated with presence of discrete white matter microglial nodules (×400x magnification); Cowdry B-like inclusions were absent. (B) Cortical regions show increased cellularity, with reactive changes in neurons and glia. Microglial nodules (blue arrow) and reactive neurons (black arrow) (×400 magnification). (C) Presence of rare perivascular B-lymphocyte aggregates (arrow). (D) CD8+ lymphocytic cells reveal a predominance of cytotoxic inflammatory cells. (E) Frequent perivascular and stromal T lymphocytes identified on immunohistochemical examination (CD3+). (F) CD138 immunoexpression demonstrates plasma cells in the inflammatory infiltrate.

Figure 2. Axial Fluid-Attenuated Inversion Recovery (FLAIR) MRI

Axial FLAIR MRI image (A) shows mild symmetric hyperintensity involving periventricular white matter (red arrows). Axial T2-weighted MRI image shows progressive atrophy evidenced in January (B) and September (C) 2023, respectively.

Figure 3. Phylogenetic Tree of Dengue Virus 1

Bootstraps higher that 70 are highlighted in circles. NC_001477 refseq and AY732483 sequences were added to tree rooting. Recovered sequence (red) clustered in a single branch (length = 0.2829) within a clade containing sequences collected from 2000 to 2022. A second clade clustered in the tree contains sequences from Brazil collected from 2022 to 2023. Tree was drawn to scale with nucleotide substitutions per site.