ABSTRACT
Case Report: Over 90% of cases of cryptococcal meningoencephalitis present in immunocompromised patients, with the majority of those being in patients with AIDS. However, this infection can also occur in patients with other immunocompromised states, such as steroid use, malignancy, rheumatologic diseases, and use of immunosuppressive medications. Delay in diagnosis can often lead to rapid neurological deterioration and mortality. Case: A young, otherwise immunocompetent patient, with a history of Chiari I malformation and recent COVID- 19 infection presented with syncope following two weeks of headaches, generalized body aches and weakness after COVID-19 diagnosis. Physical exam demonstrated an isolated CN VI palsy. Head imaging revealed new right caudate infarcts, and a cerebellar tonsillar descent compatible with history of Chiari I malformation. Initial lumbar puncture (LP) was deferred due to congenital brain herniation. Over the next few days, the patient continued to show increasing neurological deficits such as truncal ataxia and increased mood instability. The patient was transferred to the Intensive Care Unit, and LP was obtained under special neuro-critical care direction. Due to increased opening pressures and yeast on gram stain, cryptococcus was suspected and later confirmed. Although anti-fungal therapy was initiated, the patient continued to deteriorate, leading to cardiac arrest, intubation, and placement of lumbar drain. The patient unfortunately did not demonstrate neurologic recovery following arrest and progressed to brain death. Discussion(s): While cryptococcal meningoencephalitis is overwhelmingly a disease of immunocompromised patients, it can occur in immunocompetent hosts, and delay in diagnosis and treatment can lead to adverse and fatal outcomes. This patient had no known underlying conditions besides a recent mild COVID-19 infection and underlying Chiari I malformation, neither of which are known to be associated with cryptococcal meningoencephalitis. These factors may however have played a role in his disease and progression. Copyright © 2023 Southern Society for Clinical Investigation.
ABSTRACT
Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.