Cryptococcal Neuroradiological Lesions Correlate with Severity during Cryptococcal Meningoencephalitis in HIV-Positive Patients in the HAART Era

Caroline Charlier,Yves-Sébastien Cordoliani,Arnaud Fontanet,Odile Launay,Françoise Dromer,Olivier Lortholary,Loïc Chartier,Christophe Lévêque,Eleftherios Mylonakis

doi:10.1371/journal.pone.0001950

Abstract

Cryptococcal meningoencephalitis has an overall global mortality rate of 20% in AIDS patients despite antifungals. There is a need for additional means of precise assessment of disease severity. We thus studied the radiological brain images available from 62 HIV-positive patients with cryptococcocal meningoencephalitis to analyse the brain lesions associated with cryptococcosis in relationship with disease severity, and the respective diagnostic contribution of magnetic resonance (MR) versus computed tomography (CT).In this retrospective multicenter analysis, two neuroradiologists blindly reviewed the brain imaging. Prospectively acquired clinical and mycological data were available at baseline and during follow-up. Baseline images were abnormal on 92% of the MR scans contrasting with 53% of the CT scans. MR/CT cryptococcosis-related lesions included mass(es) (21%/9%), dilated perivascular spaces (46%/5%) and pseudocysts (8%/4%). The presence compared to absence of cryptococcosis-related lesions was significantly associated with high serum (78% vs. 42%, p = 0.008) and CSF (81% vs. 50%, p = 0.024) antigen titers, independently of neurological abnormalities. MR detected significantly more cryptococcosis-related lesions than CT for 17 patients who had had both investigations (76% vs. 24%, p = 0.005). In conclusion, MR appears more effective than CT for the evaluation of AIDS-associated cerebral cryptococcosis. Furthermore, brain imaging is an effective tool to assess the initial disease severity in this setting. Given this, we suggest that investigation for cryptococcosis-related lesions is merited, even in the absence of neurological abnormality, if a high fungal burden is suspected on the basis of high serum and/or CSF antigen titers.

Highlights

Cryptococcus neoformans is an encapsulated yeast responsible for severe opportunistic meningoencephalitis mostly in patients with acquired immunodeficiency syndrome (AIDS) [1,2,3]
Radiological data obtained during the post-highly active antiretroviral therapy (HAART) era is important, as all the data published so far consists of case reports or small series (n#4) of HIV-infected patients [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]
We analysed the radiological features of cerebral cryptococcosis in a large prospective cohort of HIV-infected patients in the HAART era and compared brain images with parameters assessing disease severity [3]

Summary

Introduction

Cryptococcus neoformans is an encapsulated yeast responsible for severe opportunistic meningoencephalitis mostly in patients with acquired immunodeficiency syndrome (AIDS) [1,2,3]. Retrospective radiological studies involving a limited number of HIV-infected patients with cerebral cryptococcosis have been performed in the pre-highly active antiretroviral therapy (HAART) era [4,5,6,7]. They describe the abnormal cerebral images during cryptococcal meningoencephalitis. It is possible that HAART may have had an impact on the radiological appearances of cerebral cryptococcosis This is a interesting theory when considering the demonstrated effect of protease inhibitors on some opportunistic pathogens and, the impact of indinavir or tipranavir on cryptococcal virulence [9,10]. Radiological data obtained during the post-HAART era is important, as all the data published so far consists of case reports or small series (n#4) of HIV-infected patients [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]

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