Fungal infections of the nervous system: Current perspective and controversies in management

Abstract

In the last two decades, more elaborative use of intensive care units for serious medical disorders, advancements in transplant procedures and concomitant use of immunosuppressive therapies as well as the pandemic spread of HIV, etc. have increased the incidence of systemic fungal infections, especially life threatening central nervous system (CNS) infections. The CNS fungal infections present with various clinical syndromes: meningitis; encephalitis; hydrocephalus/raised intracranial pressure (raised ICP); space occupying lesions; orbito-rhino-cerebral syndromes; acute cerebro-vascular events and spinal infections. However, the common presentations among these ones are basal meningitis, hydrocephalus, space occupying lesions (cerebral abscesses and granulomas) and stroke syndromes. Clinical picture may mimic tubercular meningitis and therefore, needs careful evaluation. The CNS mycoses carry higher risks of morbidities and mortality as compared to other infective processes and therefore promptly require precise diagnosis and appropriate medical and/or surgical management strategies to optimize the outcome. Among the antifungal drugs, the Amphotericin B had remained first line of therapy for many decades in invasive fungal infections but is not effective in many forms of mycoses. Fortunately, many useful antifungal drugs were introduced during the last two decades. Initially, the lipid based formulations of the Amphotericin B, then the new triazoles and most recently, echinocandins. These medications are used more frequently in combinations. Now evidence based data are gathering together in favor of their usefulness in the management of invasive fungal infections. But still, many questions are unanswered and controversies persist relating to their selection and use.

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

“…It is most frequently (and globally) present in domestic dishwashers [37][38][39], where internal rubber seals and plastic parts can harbour up to 10 6 colony forming units/cm 2 [39]. As people spend more time indoors and the number of immunocompromised people is rapidly increasing, the establishment of E. dermatitidis in domestic environments represents an important risk factor for human health [40,41].…”

“…After the initial infections, the fungi can spread via the haematogenous route. Fungal infections of the central nervous system occur either indirectly via lungs or paranasal sinuses, for example, after near-drowning episodes [42][43][44][45], via ocular orbits, and mastoid region of the temporal bone or retropharyngeal area, or directly as a consequence of trauma, invasive treatments, or brain surgery [41]. The potential mechanism of invasion of E. dermatitidis and other neurotropic fungi via the peripheral nervous system has not yet been described, nor have the mechanisms contributing to the spread of fungal infections to the brain.…”

“…Fungi have also been associated with other neurological diseases. Recently, an increasing number of opportunistic mycoses of the central nervous system (CNS) has been reported in healthy individuals and, in particular, in patients with sepsis, prolonged ventilation, oncological therapies, organ transplantation, overuse of antibiotics, HIV patients, and others [41,60]. Opportunistic mycoses of CNS are associated with higher morbidity and mortality [61,62] owing to pathogenic fungi such as Cryptococcus neoformans, which are able to cross the otherwise prohibitive blood-brain barrier [41,63].…”

Brain miliary enhancement

“…Candida albicans species demonstrate tropism to a variety of tissues of different organs, including the brain. During the hematologic dissemination phase, known as candidemia, the fungus travels along the bloodstream, with the potential of infecting all the perfused organs [53,54]. Clinical presentation consists of mucocutaneous candidiasis and systemic candidiasis leading to isolated organ failure or multiorgan failure such as meningitis, endocarditis, peritonitis, osteomyelitis and septic arthritis [54].…”

“…During the hematologic dissemination phase, known as candidemia, the fungus travels along the bloodstream, with the potential of infecting all the perfused organs [53,54]. Clinical presentation consists of mucocutaneous candidiasis and systemic candidiasis leading to isolated organ failure or multiorgan failure such as meningitis, endocarditis, peritonitis, osteomyelitis and septic arthritis [54]. Diagnosis can be based on CSF analysis, showing pleiocytosis, decreased glucose and increased protein concentrations and CSF cultures, with positivity estimated around 80% [53].…”