Fungal brain infections.

PURPOSE OF REVIEW: Fungal infections of the central nervous system, once a relatively rare occurrence, are increasingly common due to the expansion of immunocompromised populations at risk, and therefore are important to recognize early and manage appropriately. RECENT FINDINGS: The specific infectious risk posed by novel immune-modifying therapies can, in most cases, be predicted on the basis of the immune target and medication timing. In addition, major advances in noninvasive diagnostic tests (e.g. serum beta glucan and galactomannan assays), and the recent introduction of more effective antifungal therapies, have led to a dramatic improvement in clinical outcomes. SUMMARY: The current review provides approaches to patients with suspected central nervous system fungal infections based on host-risk factors, clinical syndromes and specific pathogens.

Epidemiology of central nervous system mycoses.

Fungal infections of the central nervous system (CNS) were considered rare until the 1970s. This is no longer true in recent years due to widespread use of corticosteroids, cytotoxic drugs and antibiotics. Immunocompromised patients with underlying malignancy organ transplantations and acquired immune deficiency syndrome are all candidates for acquiring fungal infections either in meninges or brain. A considerable number of cases of CNS fungal infections even in immunocompetent hosts have been reported. A vast array of fungi may cause infection in the CNS, but barring a few, most of them are anecdotal case reports. Cryptococcus neoformans, Candida albicans, Coccidioides immitis. Histoplasma capsulatum are common causes of fungal meningitis; Aspergillus spp, Candida spp, Zygomycetes and some of the melanized fungi are known to cause mass lesions in brain. Few fungi like C. neoformans, Cladophialophora bantiana, Exophiala dermatitidis, Ramichloridium mackenzie, Ochroconis gallopava are considered as true neurotropic fungi. Most of the fungi causing CNS infection are saprobes with worldwide distribution; a few are geographically restricted like Coccidioides immitis. The infections reach the CNS either by the hematogenous route or by direct extension from colonized sinuses or ear canal or by direct inoculation during neurosurgical procedures.

Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario.

Ubiquitously present fungi in the environment find a nidus in the human body and adopt its metabolic machinery to be in symbiosis or become pathogenic. Immunocompromised states like human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS), systemic neoplasia and organ transplantation have enhanced the frequency of fungal infections. High-risk behavior, IV drug abuse and air travel have led to the emergence of new fungal infections hitherto geographically localized. The pathology in the central nervous system (CNS) is dictated largely by the size of the fungus - the yeast forms, by virtue of their small size enter the microcirculation to cause meningitis and microabscesses, while hyphal forms invade the vasculature to manifest as large pale or hemorrhagic infarcts. The growth kinetics of fungi, the antigenic character of the capsule. the proteases secreted by the mycelial forms and the biochemical milieu in the host also determine clinical manifestations. A hospital-based analysis of the available information from India suggests that in the non-HIV patient population, hyphal forms like Aspergillosis and Zygomycosis are the most common pathogens, while yeast forms like Cryptococcus and Candida are the prime pathogens in cases of HIV/AIDS, the altered macrophage function acting in synergy with suppressed cell-mediated immunity. In Northeastern states, systemic infection by Penicillium marneffei is reported in association with HIV though CNS involvement is not recorded. Although fungal infections of the CNS are reported from various hospitals in India, studies are limited by non-availability of relevant microbiological studies and the reported prevalence data is biased by the surgical practices, availability of postmortem and microbiology and laboratory support. Detailed clinical and mycological investigations related to the interaction between the fungus and host environment is a fertile area of research to understand the basic pathogenetic mechanisms.

Imaging features of central nervous system fungal infections.

Fungal infections of the central nervous system (CNS) are rare in the general population and are invariably secondary to primary focus elsewhere, usually in the lung or intestine. Except for people with longstanding diabetes, they are most frequently encountered in immunocompromised patients such as those with acquired immunodeficiency syndrome or after organ transplantation. Due to the lack of inflammatory response, neuroradiological findings are often nonspecific and are frequently mistaken for tuberculous meningitis, pyogenic abscess or brain tumor. Intracranial fungal infections are being identified more frequently due to the increased incidence of AIDS patients, better radiological investigations, more sensitive microbiological techniques and better critical care of moribund patients. Although almost any fungus may cause encephalitis, cryptococcal meningoencephalitis is most frequently seen, followed by aspergillosis and candidiasis. The biology, epidemiology and imaging features of the common fungal infections of the CNS will be reviewed. The radiographic appearance alone is often not specific, but the combination of the appropriate clinical setting along with computed tomography or magnetic resonance may help to suggest the correct diagnosis.

Fungal infections of the CNS: treatment strategies for the immunocompromised patient.

Infections with fungi cause significant morbidity in the immunocompromised host and invasion of the CNS may lead to devastating consequences. Vulnerable individuals include those with haematological malignancies, transplant recipients, and those infected with HIV. Potential pathogens include yeasts, Aspergillus spp., other moulds of an increasing variety, and a range of dimorphic fungi, often associated with particular geographical locations. Antifungal treatments include polyenes such as amphotericin B and its lipid formulations, azoles such as fluconazole and itraconazole, and the more recent voriconazole and posaconazole. The new antifungal class of echinocandins, such as caspofungin, micafungin and anidulafungin, typically lack CNS penetration. Amphotericin B and flucytosine are used to initiate treatment for CNS yeast infections caused by Candida and Cryptococcus neoformans. Voriconazole is preferred for aspergillus, although amphotericin B, particularly in lipid formulation, is also useful. Reliable treatment data are lacking for CNS infections with most of the non-aspergillus moulds; posaconazole holds promise for the zygomycetes and perhaps some of the rarer pigmented fungi, but amphotericin B preparations are still recommended. Oral fluconazole is effective for the CNS manifestations of coccidioides, while histoplasmosis and blastomycoses typically require amphotericin B therapy. Effective treatment requires a definitive diagnosis, which is often challenging in the population at risk of CNS fungal infections.

[Central nervous system mycotic infections]. / Infecciones micóticas del sistema nervioso central.

INTRODUCTION: There has been an increased number of cases of fungal diseases of the central nervous system (CNS) during the past few years. This paper reviews current literature about these conditions, with emphasis on recent advances on diagnosis and therapy. DEVELOPMENT: While some fungi may cause disease in normal hosts, most of these microorganisms are opportunistics and affect immunocompromised hosts. With the exception of Candida albicans, that is a normal inhabitant of the intestinal tract, most fungi enter the body by inhalation or through skin abrasions. Common fungal diseases include aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, paracoccidioidomycosis, and phaeohyphomycosis. In general terms, fungal invasion of the CNS may produce one or more of the following clinical syndromes: subacute or chronic meningitis, encephalitis, parenchymal brain abscesses or granulomas, stroke, or myelopathy. Diagnosis may be difficult on clinical grounds, and data provided by neuroimaging studies or CSF examination is non-specific. Definitive diagnosis usually rest on the demonstration of the causal agent on body fluids or tissue samples. Early administration of amphotericin B, associated or not with the new azoles, is indicated to arrest the often fatal course of these conditions. CONCLUSIONS: Formerly considered rare diseases, the acquired immunodeficiency syndrome (AIDS) epidemic and the widespread use of corticosteroids and cytotoxic agents, have caused an increase in the prevalence of CNS mycosis. Development of potent antimycotic drugs have improved the prognosis of fungal diseases of the CNS. However, due to diagnostic delays or the presence of debilitating conditions, some patients still have torpid clinical courses despite proper therapy.

Infecciones micóticas del sistema nervioso central / Fungal diseases of the central nervous system

Introduction. There has been an increased number of cases of fungal diseases of the central nervous system (CNS) during the past few years. This paper reviews current literature about these conditions, with emphasis on recent advances on diagnosis and therapy. Development. While some fungi may cause disease in normal hosts, most of these microorganisms are opportunistics and affect immunocompromissed hosts. With the exception of Candida albicans, that is a normal inhabitant of the intestinal tract, most fungi enter the body by inhalation or through skin abrasions. Common fungal diseases include aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, paracoccidioidomycosis, and phaeohyphomycosis. In general terms, fungal invasion of the CNS may produce one or more of the following clinical syndromes: subacute or chronic meningitis, encephalitis, parenchymal brain abscesses or granulomas, stroke, or myelopathy. Diagnosis may be difficult on clinical grounds, and data provided by neuroimaging studies or CSF examination is non-specific. Definitive diagnosis usually rest on the demonstration of the causal agent on body fluids or tissue samples. Early administration of amphotericin B, associated or not with the new azoles, is indicated to arrest the often fatal course of these conditions. Conclusions. Formerly considered rare diseases, the acquired immunodeficiency syndrome (AIDS) epidemic and the widespread use of corticosteroids and cytotoxic agents, have caused an increase in the prevalence of CNS mycosis. Development of potent antimycotic drugs have improved the prognosis of fungal diseases of the CNS. However, due to diagnostic delays or the presence of debilitating conditions, some patients still have torpid clinical courses despite proper therapy (AU)

Introducción. En los últimos años se ha notado un aumento en el número de casos de infecciones micóticas del sistema nervioso central (SNC). En el presente trabajo revisamos la literatura acerca de estas entidades, con especial atención a los avances recientes en el diagnóstico y tratamiento. Desarrollo. Aunque algunos hongos pueden causar enfermedad en sujetos sanos, la mayoría de estos microorganismos son oportunistas y afectan sujetos con afectación del sistema inmune. Con excepción de la Candida albicans, que es un habitante del tubo digestivo, la mayoría de los hongos entran en el organismo por inhalación o a través de lesiones cutáneas. Las enfermedades micóticas más frecuentes son: aspergilosis, blastomicosis, candidia sis, coccidioidomicosis, criptococosis, istoplasmosis, mucormicosis, paracoccidiodomicosis y faeohifomicosis. En términos generales, las micosis del SNC se asocian a uno o más de los siguientes síndromes clínicos: meningitis subaguda o crónica, encefalitis, abscesos o granulomas parenquimatosos, enfermedad cerebrovascular o mielopatía. El diagnóstico suele ser difícil desde el punto de vista clínico y los datos aportados por los estudios de neuroimagen o con el estudio de LCR son inespecíficos. El diagnóstico depende de la identificación del agente causal en secreciones corporales o en muestras de tejido. La administración de anfotericina B, asociada o no con uno de los nuevos derivados azólicos, se encuentra indicada para detener el curso inexorable de estas entidades. Conclusión. Consideradas como enfermedades poco comunes, la epidemia de sida, así como el uso indiscriminado de corticosteroides y agentes citotóxicos, ha condicionado un aumento en la prevalencia de micosis del SNC. El desarrollo de potentes fármacos antimicóticos ha mejorado el pronóstico de dichas infecciones; sin embargo, debido a retrasos diagnósticos o a la presencia de enfermedades debilitantes preexistentes, algunos enfermos evolucionan desfavorablemente a pesar del tratamiento (AU)

Infections of the central nervous system in transplant recipients.

Central nervous system (CNS) infections, accounting for 4-29% of CNS lesions in transplant recipients, are a significant post-transplant complication. Focal CNS infectious lesions or brain abscesses have been documented in 0.36-1% of the transplant recipients. Mycelial fungi, particularly Aspergillus, are by far the most frequent etiologies of post-transplant brain abscesses. Bacteria, with the exception of Nocardia, are rarely associated with brain abscesses in transplant recipients. Time of onset and concurrent extraneural lesions have implications relevant towards invasive diagnostic procedures in transplant recipients with brain abscesses. Meningoencephalitis in transplant recipients is predominantly due to viruses, e.g., herpesviruses, and less frequently due to Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus. Despite a wide, and at times perplexing array of opportunistic pathogens that can cause CNS infections, the temporal association of the infection with the time elapsed since transplantation, risk factors, clinical manifestations, and neuroimaging characteristics of the lesion can allow a reasoned and rational approach towards the recognition, diagnosis, and appropriate management of CNS infections in transplant recipients.