Aseptic Meningoencephalitis and False-Positive Result for Cryptococcus Spp. due to a Leukocyte Exclusion Artifact: A Case Report

Abstract

Introduction: Aseptic meningoencephalitis presents as a critical diagnostic emergency in immunocompetent adults. While cerebrospinal fluid (CSF) wet India ink mounting is a classic, cost-effective tool for rapid detection of Cryptococcus spp., it carries a well-documented risk of false-positive results due to leukocyte exclusion artifacts in samples with marked pleocytosis, often leading to inappropriate and potentially nephrotoxic antifungal overtreatment. Objective: To describe the diagnostic dilemma, clinical features, and molecularly guided antifungal de-escalation in an immunocompetent adult with aseptic meningoencephalitis presenting with a false-positive India ink stain on CSF. Case Presentation: A 45-year-old immunocompetent male presented with high-grade fever (40 °C), expressional aphasia, paraparesis, and positive meningeal signs following recent NSAID self-medication. Initial CSF analysis revealed marked pleocytosis (up to 20,000 cells/µL, 100% PMNs) and elevated protein levels (1,590 mg/L). A preliminary direct microscopic report indicated positive India ink staining caused by a leukocyte exclusion halo artifact, prompting the immediate empiric initiation of liposomal amphotericin B (300 mg/day) and fluconazole (1,200 mg/day). However, multiplex real-time PCR (FilmArray ME panel) returned negative for Cryptococcus neoformans/gattii and other neurotropic agents, and 7-day fungal cultures and contrast-enhanced brain MRI showed no evidence of invasive infection. Antifungals were promptly discontinued, and the patient achieved complete neurological recovery and hospital discharge under supportive anti-inflammatory therapy. Conclusions: Leukocyte exclusion artifacts in pleocytic CSF can closely mimic encapsulated Cryptococcus yeasts (pseudocryptococcosis). Rapid confirmation via multiplex PCR is essential to prevent diagnostic error, avoid unnecessary antifungal-induced nephrotoxicity, and optimize antimicrobial stewardship in acute aseptic meningoencephalitis.

Keywords: Aseptic meningitis; Meningoencephalitis; Cryptococcus; India ink; False positive; FilmArray; Polymerase chain reaction; Antimicrobial stewardship.