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

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.

Cryptococcus neoformansVariants Generated by Phenotypic Switching Differ in Virulence through Effects on Macrophage Activation

“…As primary effector cells of the innate immune response they kill C. neoformans, and as Ag-presenting cells they directly contribute to the cellmediated immune response (31). However, macrophages can become a safe harbor for intracellular C. neoformans and as such can promote evasion of the immune response and intracellular dissemination (1,8,12,48). Macrophages are a potential niche where C. neoformans can multiply undisturbed and then either lyse or exit from the host macrophages (2).…”

Evidence of a Role for Monocytes in Dissemination and Brain Invasion byCryptococcus neoformans

“…Brain lesions consist of early endothelial capillary damage followed by fungal proliferation, first in the perivascular spaces and then in the neuropile, with secondary seeding of the meningeal spaces (6). Local inflammation is limited (26,30), and lesions are described as dilation of the perivascular spaces and as cerebral masses (7,10,26).…”

Soap bubble appearance in brain magnetic resonance imaging: cryptococcal meningoencephalitis

“…The meningeal infection along the base of the skull may extend along the Virchow-Robin spaces, which may dilate with mucoid gelatinous material produced by the capsule of the organism. Because membranes are not formed between these spaces and the adjacent brain parenchyma, these cysts have been called gelatinous pseudocysts 2,3 .…”

“…These pseudocysts appear as multiple, small, round or oval cysts in the basal ganglia, thalami, midbrain, cerebellum and the periventricular regions with a low to intermediate T1WI signal (from mucin), a high T2WI signal and a low T2-FLAIR signal 4,[7][8][9] . Signifi cant contrast enhancements of the pseudocysts, cryptococcomas or meninges are rarely noted in immunocompromised patients due to their underlying immunosuppression and the non-immunogenic nature of the polysaccharide capsule 2,4 . Immunocompetent patients tend to present with localized neurological disease, more intense infl ammatory responses and improved clinical outcomes 4,10 .…”

“…Among patients with human immunodefi ciency virus (HIV), cryptococcal meningoencephalitis is associated with mild meningeal infl ammation and a high fungal burden 2,3 . Central nervous system (CNS) involvement can be either meningeal or parenchymal.…”