Dengue virus encephalitis: A systematic review and critique

Background & Objective: Neurological manifestations were reported in dengue fever. We hypothesize that the diagnosis of DEN virus (DENV) encephalitis based on current clinical diagnostic criteria has been made too liberally. We conducted a systematic review of the literature to clarify this, and to characterize DENV encephalitis better. Methods: We systematically review the literature using MEDLINE and PubMed databases papers published from 1st January 1960 to 31st March 2020. We grouped the cases into definite and probable DENV encephalitis. Definite DENV encephalitis required demonstration of DENV (live virus, viral antigens, RNA) in the central nervous system or CSF whereas probable DENV encephalitis required positive anti-DENV IgM in the CSF and evidence of virus or anti-DENV IgM in the serum. Results: Of the 230 publications obtained from literature search, 121 case reports and series appeared relevant to DENV encephalitis. After applying our inclusion criteria, only 42 cases (34.7%) were acceptable as DENV encephalitis: 30 (24.8%) definite and 12 (9.9%) probable cases. Our findings suggest that DENV encephalitis is more uncommon than previously thought. Part of the reason for non-inclusion may be because many studies relied solely on DENV serology for diagnosis. Cross-reactivities of anti-DENV with anti-JE virus immunoglobulins in serum or CSF occur and this limits their usefulness to distinguish DENV encephalitis from JE. Conclusions: The majority of DENV encephalitis cases reported in the literature did not satisfy a more stringent inclusion criteria. Further investigations including autopsy studies are warranted to better characterize and to understand the pathology and pathogenesis of DENV encephalitis.