PATHOLOGY OF CRYPTOCOCCAL MENINGOENCEPHALITIS - ANALYSIS OF 27 PATIENTS WITH PATHOGENETIC IMPLICATIONS

In this autopsy series of cryptococcal meningoencephalitis (CME), the authors analyzed neuropathologic lesions in 13 human immunodeficiency virus (HIV) and 14 non-HIV-related cases. Most non-HIV patients did no t have immunosuppressive predisposing illness. Analysis of pathologica l findings revealed significant differences in the inflammatory respon se to CME in patients with and without HIV infection. None of the acqu ired immunodeficiency syndrome (AIDS) patients had granulomatous infla mmation, whereas most non-HIV-associated cases had ganulomas, supporti ng a role for cell-mediated immunity in CME. Lymphocytic infiltrate in both groups consisted of T cells (CD45RO+). In some non-HIV-associate d cases, CME was undiagnosed and untreated. In most HIV-associated cas es, CME had an encephalitic component, resulting in grossly or microsc opically visible accumulations of fungi within the brain parenchyma, w hereas in non-HIV-associated cases, CME was often confined to the suba rachnoid space and large perivascular spaces (Virchow-Robin spaces), I n non-HIV-associated cases, yeast forms were fewer and showed a more l imited distribution, In contrast, many extracellular fungi were presen t in many cases of HIV-associated CME. The principal reactive cell in CME in AIDS was brain macrophages and microglia, especially those in t he perivascular and juxtavascular locations. Reactive astrocytes were limited to large destructive lesions and subpial regions. In several p atients with HIV-associated CME, large parenchymal cryptococcomas cont ained Crytococcus neoformans (CN) with cell wall pigmentation, suggest ive of melanin. The authors suggest that in AIDS patients altered immu ne functions allow CN to accumulate within the brain, predominantly ex tracellularly, and that deficient macrophage/microglial effector funct ion may be responsible for the altered pathology. In addition, coexist ing CNS processes in HIV-associated CME may contribute to the altered pathology. The authors conclude that cryptococcal meningitis is not a disease limited to the cerebrospinal fluid (CSF) space but affects the brain more significantly than suspected. Therapeutic strategies that enhance the effector function of glial cells at the CNS-CSF barrier ma y be useful for improving the response to therapy. Copyright (C) 1996 by W.B. Saunders Company.