Use of Cerebrospinal Fluid for the Diagnosis of Neuroinvasive Dengue, Zika, and Chikungunya: A 19-year systematic review

ABSTRACT

Abstract INTRODUCTION: Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections. METHODS: A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019. RESULTS: A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%). CONCLUSIONS: Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.