Typically presents as a progressive, life-threatening, chronic or subacute meningitis.
Occurs most commonly in immunosuppressed individuals and is often accompanied by systemic involvement.
Cerebrospinal fluid (CSF) typically shows lymphocytic pleocytosis, elevated protein, and low glucose.
The most common type of fungal meningitis is caused by Cryptococcus neoformans.
A rapid aetiological diagnosis is required to guide antifungal therapy.
Complications include seizures, cerebral infarction, hydrocephalus, and elevated CSF pressure without hydrocephalus.
Meningitis is an inflammatory disease of the leptomeninges. All major fungal pathogens have the capacity to cause meningitis. The incidence of fungal meningitis is increasing worldwide due to the increasing number of patients immunosuppressed by pharmacological agents and HIV infection. Cryptococcal, histoplasmal, coccidioidal, and candidal meningitis will be discussed specifically in this topic.
History and exam
Key diagnostic factors
- presence of risk factors
- progressive headache
- severe headache
- symptoms of hydrocephalus (impaired cognitive function, confusion, coordination and gait disturbances, and urinary incontinence)
- behavioural or personality change
- reduced visual acuity and papilloedema
Other diagnostic factors
- nausea or vomiting
- reduced conscious level
- cranial nerve palsies
- weight loss
- mouth ulcers
- focal neurological signs
- lymphadenopathy, hepatosplenomegaly
- papular umbilicated skin lesions
- retinal defects
- nasal or palatal eschar
- HIV infection
- corticosteroid use
- underlying chronic disease (e.g., malignancy, organ failure, autoimmune disease, organ transplant)
- residing in or visiting northern Australia, Papua New Guinea, or Vancouver Island, Canada
- exposure to disturbed soil, chicken guano, or bat caves
- impaired cell-mediated immunity
- Filipinos and African Americans
- neutropenia or impaired phagocytic function
- infants and neonates
- central vascular catheters
- sinonasal disease
- antibacterial usage
- prior surgery
- intravenous drug use
1st investigations to order
- CT and/or MRI head scan
- fungal blood cultures (3 sets)
- serum cryptococcal antigen test
- serum + urine Histoplasma antigen
- immunodiffusion tests (IgM and IgG) and complement fixation test (IgG) for coccidioidomycosis
- cerebrospinal fluid opening pressure
- cerebrospinal fluid (CSF) WBC and differential
- cerebrospinal fluid (CSF) protein
- cerebrospinal fluid (CSF) glucose
- cerebrospinal fluid India ink stain
- cerebrospinal fluid (CSF) culture
- cerebrospinal fluid cryptococcal polysaccharide antigen test
- cerebrospinal fluid Histoplasma antigen
- cerebrospinal fluid Histoplasma antibodies
- cerebrospinal fluid coccidioidal IgG antibodies
- cerebrospinal fluid (CSF) galactomannan antigen test
Investigations to consider
- histopathology and culture of biopsies: meningeal, brain, extraneural sites of involvement
- polymerase chain reaction (PCR)
- 18F-fluorodeoxyglucose (FDG) PET/CT
- cerebrospinal fluid (CSF) (1-3)-beta-D-glucan
Abhijit Chaudhuri, DM, MD, PhD, FACP, FRCP (Glasg), FRCP (Lond)
Clinical Lead of Neuroinflammation
Department of Neurology
AC declares that he has no competing interests.
Dr Abhijit Chaudhuri would like to gratefully acknowledge Dr Thomas S. Harrison and Dr Angela Loyse, previous contributors to this topic.
TSH and AL declare that they have no competing interests.
Robert A. Larsen, MD
Associate Professor of Medicine
University of Southern California
Keck School of Medicine
RAL declares that he has no competing interests.
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