Immunopathogenesis of central nervous system fungal infections

Fungal infections of the central nervous system (CNS) evoke humoral and cellular immune responses with the scope to enable the host to eliminate the pathogen. Immunopathogenesis of CNS fungal infections remains incompletely understood, with most of our understanding coming from studies on experimentally infected animals. However, activation of brain resident cells combined with relative expression of immunoenhancing and immunosuppressing cytokines and chemokines may play a determinant role and partially explain immunopathogenesis of CNS fungal infections.     

Treatment of fungal infections of the central nervous system

The recent development of new antifungal antimicrobials that can be administered in combination with amphotericin B or as alternatives to it has expanded the dimensions of treatment for fungal infections of the central nervous system. These disorders have acquired increasing importance as patients with malignant and other illnesses associated with immunosuppression survive longer and as renal transplantation is more widely applied. Amphotericin B has remained the most effective therapeutic preparation for most types of neurological fungal disease, although important roles for 5-fluorocytosine, miconazole, and, more recently, ketoconazole are being recognized. Bell WE: Treatment of fungal infections of the central nervous system.     

Laboratory investigation of fungal infections of the central nervous system

While fungal infections of the central nervous system (CNS) are relatively rare, fungal pathogens are increasingly being recognized as an important etiology of CNS infections, particularly amongst the growing immunocompromized population. In this paper we aim to provide a practical approach to the diagnosis of fungal infections of the CNS, review some of the diagnostic methods currently available and discuss diagnosis of certain pathogens of particular interest to the practicing neurologist.     

Immunotherapy for fungal infections with special emphasis on central nervous system infections

Opportunistic fungal infections are major causes of morbidity and mortality in the immunocompromized. Fungi have evolved complex and coordinated mechanisms to survive in the environment and the mammalian host. Fungi must adapt to "stressors" in the host, including nutrient scarcity, pH and reactive oxygen and nitrogen intermediates, in addition to evading host immunity. Knowledge of the immunopathogenesis of fungal infections has paved the way to promising strategies for immunotherapy. These include strategies that increase phagocyte number, activate innate host defense pathways in phagocytes and dendritic cells and stimulate antigen-specific immunity (e.g, vaccines). Immunotherapy must be tailored to specific immunocompromized states. Our review focuses on cryptococcosis and coccidioidomycosis because of the propensity of these diseases to involve the central nervous system (CNS). The CNS has long been considered "immunologically privileged" in the sense of being isolated from normal immune surveillance. This notion is only partially accurate. Immune-based therapies for fungal CNS disease are at an exploratory level and merit further evaluation in clinical trials.     

Epidemiology of central nervous system infections

The radiologist frequently is asked to contribute to the diagnosis of a patient with central nervous system infections, although radiologic findings usually are nonspecific. The radiologist can consider diagnostic possibilities with more accuracy if the clinician includes accurate demographic and epidemiologic information. This article organizes a broad range of central nervous system infections into demographic and epidemiologic perspective.     

Central nervous system fungal infections in tropics

Fungal infections of the central nervous system range from chronic indolent forms to acute fulminant forms causing significant morbidity and mortality. They often show atypical and variable neuroradiologic findings because of the absence of typical inflammatory response. The neuroradiologist must have high degree of suspicion in immunocompromised patients regarding the possibility of central nervous system fungal infections and keep in mind the appearances of various fungi even when immune response is intact. Next is to identify the pattern of involvement whether hematogenous or direct sinonasal and then make a well-informed speculation regarding the type of the pathogen based on the clinical features and imaging appearance.     

人类免疫缺陷病毒相关中枢神经系统机会性感染

人类免疫缺陷病毒(HIV)感染患者发生中枢神经系统机会性感染的概率极高,其发生机制与CD4+T细胞计数相关,CD4+T细胞计数越少、中枢神经系统机会性感染发生率越高。HIV相关中枢神经系统机会性感染涉及的病原体十分复杂,包括病毒、细菌、真菌和寄生虫等,不同致病菌的临床表现有相似之处,但治疗有显著差异,甄别不同病原体无疑是对临床医师的巨大挑战,及时且准确的诊断是提高患者生存率的关键。     

Fungal infections of the central nervous system: A review of fungal pathogens and treatment

Multiple factors influence the outcome of fungal infection of the central nervous system (CNS). The host and the pathogen in concert with drug delivery across the blood-brain barrier and drug activity are key factors in outcome. Drug costs can be prohibitively expensive. Drug toxicity with standard antifungal agents such as amphotericin B (infusion rate toxicity) can be reduced using simple techniques such as slower infusion and appropriate saline loading. Continuous infusion can allow relatively large doses of amphotericin B (up to 2 mg/kg/day, remaining below 0.08 mg/kg/hour) to be given with toxicity profiles comparable to expensive lipid formulations of amphotericin B. Dedicated peripherally inserted central catheters can remain in situ for weeks to months and are safe and relatively inexpensive. Correction of metabolic pathology in the case of mucormycosis and resolution of neutropenia are essential to effective treatment of filamentous fungal infections such as Mucor, Aspergillus and Scedosporium. The pharmacology and pharmacokinetics of the current major antifungal agents used to treat fungal infections of the CNS are reviewed. Tables that provide information about achievable CNS drug levels, antifungal susceptibilities and the likelihood of intrinsic drug resistance of significant fungal pathogens have been included to help the clinician with therapy. Treatment recommendations for Cryptococcal and Candida meningitis and for rhinocerebral infection with Mucor and Aspergillus have been included.     

Parasitic infections of the central nervous system

The authors give a comprehensive review of the epidemiology, clinical presentations, diagnosis and current therapy of parasitic infections with CNS manifestations in both the normal and immunocompromised host. These include toxoplasmosis, malaria, amebiasis, neurocystcersosis, hydatid disease, and trichinosis. Additional sections cover disseminated strongyloidiasis, eosinophilic meningitis, visceral and ocular larva migrans, schistosomiasis, and cerebral paragonimiasis. Emphasis is on the neurologic complications of these diseases and their presentations in populations at increased risk for acquiring or reactivating these infections.     

Fungal infections of the central nervous system

The diagnosis and treatment of central nervous system fungal infections typically pose problems for the clinician. With an increased incidence of fungal infections in immunocompromised patients, neuroradiologic imaging has become essential in determining complications and outcomes. This article provides a summary of the more common organisms encountered in fungal infections of the central nervous system and the imaging features primarily seen with CT and MR imaging.     

Amebic infections of the central nervous system

Journal of NeuroVirology - The report of death of a person from amebic meningoencephalitis, the proverbial “brain-eating ameba,” Naegleria fowleri, acquired in a state park lake in Iowa...     

Viral infections of the central nervous system

Viral infections of the central nervous system in the tropical countries of Asia and the Indian subcontinent are different from those of the Western and developed world. Many of the endemic and epidemic encephalitides that are prevalent in these regions, such as Japanese encephalitis, have characteristic findings on imaging, especially on magnetic resonance imaging, allowing a rapid diagnosis and differentiation from clinically similar syndromes. Other emerging viral infections in the region in recent years have posed new challenges. The contribution of neuroimaging to the management of these emerging infections is also discussed.     

Cerebrovascular disease in central nervous system infections

Cerebrovascular disease is a complication of a variety of infections affecting the central nervous system (CNS). Infection may cause vasculitis affecting primarily the vessels at the base of the brain in the setting of meningitis; an immune-mediated parainfectious process leading to vasospasm or thrombosis; or a hypercoagulable state in combination with endothelial dysfunction resulting from activation of inflammatory and procoagulant cascades. Although systemic signs and symptoms may be present to aid in the diagnosis, cerebral infarction secondary to infection may be indistinguishable from more typical causes of stroke. Confirmation of an infectious vasculitis may also be challenging, as brain biopsy, the gold standard for diagnosis, is rarely pursued. In many CNS infections, vascular complications portend a poor prognosis as they are often associated with devastating neurologic outcomes, including death, underscoring the importance of early recognition and appropriate therapy. In this review, we address bacterial, viral, fungal, and parasitic causes of cerebrovascular disease.