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Fungal Infections of the Central Nervous System

Panackal, Anil A. MD; Williamson, Peter R. MD, PhD

doi: 10.1212/CON.0000000000000241
Review Articles

Purpose of Review: This article summarizes current knowledge on the epidemiology, clinical presentations, diagnosis, and management of selected fungal infections of the central nervous system (CNS). Key syndromes, differential diagnoses, and therapeutic interventions according to host immune status and exposure are reviewed.

Recent Findings: Advancements in imaging of the brain and spinal cord, and molecular DNA and antigen-based laboratory diagnostics afford improved sensitivity for CNS mycoses. Newer therapeutic strategies may improve outcomes if provided early and host immunosuppression is abrogated. Adjunctive corticosteroid use for disabling neuroinflammation and cerebral edema in the setting of microbiological control may be considered. In addition, nonspecific presentations and absence of fevers in patients without human immunodeficiency virus suggest that screening for Cryptococcus meningitis be performed in all patients with subcortical dementias using a simple CSF or serum antigen test.

Summary: CNS fungal infections comprise a wide spectrum of clinical syndromes, including abscesses, meningitis/meningoencephalitis, focal masses, stroke/vasculitides, immune reconstitution inflammatory syndrome (IRIS), and spinal pathologies such as arachnoiditis. The main etiologies include Aspergillus, Cryptococcus, Candida, Mucorales, dematiaceous molds, and dimorphic endemic fungi, with the route of acquisition being respiratory or traumatic inoculation with subsequent spread hematogenously or contiguously. Proper management focuses on early effective antifungal therapy and surgery for large or compressive mass lesions. While adjunctive recombinant cytokine or growth factor use has been supported in certain hosts with refractory infections, IRIS-like reactions may occur, suggesting alternative approaches such as high-dose pulse corticosteroids followed by taper.

Address correspondence to Dr Anil A. Panackal, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N222, 9000 Rockville Pike, Bethesda, MD 20892,

Relationship Disclosure: Dr Panackal is employed by the National Institute of Allergy and Infectious Diseases (NIAID) as a staff clinician and receives research support from them as the lead associate investigator on NIAID Study Protocol #93-I-0106. Dr Panackal serves on the editorial board of the Journal of Mycology and holds an academic teaching appointment at Uniformed Services University of the Health Sciences as a civilian. Dr Williamson serves as a voting member on the Clinical and Laboratory Standards Institute Anti-fungal Subcommittee and on the editorial board of the Journal of Mycology. Dr Williamson receives research support from the National Institutes of Health and serves as principle investigator on NIAID Study Protocol #93-I-0106.

Unlabeled Use of Products/Investigational Use Disclosure: Drs Panackal and Williamson discuss the unlabeled/investigational use of steroids in the management of cerebral edema related to increased intracranial pressure from fungal paradoxical immune responses.

© 2015 American Academy of Neurology
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