Central Nervous System Infections Due to Aspergillus and Other Hyaline Molds

Abstract

Central nervous system infections due to Aspergillus spp and other hyaline molds such as Fusarium and Scedosporium spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends to occur as a result of hematogenous dissemination among immunocompromised patients, and by local extension or direct inoculation secondary to trauma in immunocompetent hosts. Efforts should be directed to confirm the diagnosis by image-guided stereotactic brain biopsy when feasible. Non-culture methods could be useful to support the diagnosis, but they have not been validated to be performed in cerebral spinal fluid. Treatment of these infections is challenging given the variable susceptibility profile of these pathogens and the penetration of antifungal agents into the brain.

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

“…Direct inoculation of CNS or paraspinal tissue as a result of surgery or trauma may occur, or fungi may affect sinuses or mastoids and directly expand to the CNS (Figure 1) [14,15]. Whereas yeast are able to enter the CNS directly through the blood-brain barrier either trans-cellularly, paracellularly or inside infected phagocytes ("Trojan horse mechanism"), the exact mechanism of the blood-brain barrier penetration of molds is not well understood to date [14][15][16][17]. It was speculated that mycotoxins such as gliotoxin produced by A. fumigatus exhibit various effects which ultimately lead to intracerebral invasion of the fungus.…”

“…For example, mycotoxins are immunosuppressive and reduce the opsonization of the conidia and inhibit phagocytosis. Mycotoxins also damage microglia, which exhibits phagocytic abilities and is the major surveillance of the CNS against the fungus [14,16,18,19]. Similarly, fumonisin B1, a mycotoxin produced by Fusarium spp., damages the microglia and leads to neuronal axon demyelination [20].…”

Macrophage Proinflammatory Responses to Microorganisms and Transplanted Organs

“…Although the main target of these fungi is the lungs, some of them can also infect the brain and/or the central nervous system, causing, for example, Cryptococcal meningoencephalitis and neuroaspergillosis. Such fungal infections are especially common in the immune-suppressed HIV/AIDS patients, cancer patients receiving chemotherapy or patients after transplantation who receive anti-rejection immunosuppressive therapies [ 47 , 49 ].…”

It’s all in your head: antifungal immunity in the brain

“…As IFIs disseminate, a common target tissue is the CNS. Additionally, fungi can gain direct access to the CNS following traumatic inoculation or neurosurgical procedures [ 5 ]. Within the CNS, fungi come in contact with the brain’s specialized resident immune system, comprising barrier-associated macrophages, microglia and astrocytes [ 6 ].…”

“…Aspergillus , Mucorales, Scedosporium and Cladophialophora molds can infrequently cause CNS infections in susceptible hosts, associated with mortality rates between 50–100% [ 5 , 8 ]. These infections occur secondary to dissemination of pulmonary disease in immunocompromised patients ( Aspergillus ), direct extension from sinoorbital disease in diabetic hosts (mucormycosis) or inoculation during trauma or neurosurgical procedures, independent of the host immune status [ 5 ]. Notably, Scedosporium causes CNS infections following near-drownings [ 5 ], and Cladophialophora infects putatively immunocompetent individuals in tropical areas [ 42 ].…”