History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors include immunosuppression; exposure to disturbed soil, chicken guano, or bat caves; neutropenia; impaired phagocytic function; and neurosurgery. Infants and neonates are also at increased risk.
progressive headache
Typically presents with headache that progresses over several weeks.
severe headache
Suggests raised intracranial pressure.
Common finding of cryptococcal meningitis, where raised intracranial pressure probably occurs due to impaired reabsorption of cerebrospinal fluid at the arachnoid villi.
meningismus
Nuchal rigidity, photophobia, and headache.
symptoms of hydrocephalus (impaired cognitive function, confusion, coordination and gait disturbances, and urinary incontinence)
Classical signs of hydrocephalus.
Hydrocephalus is a common early presentation and complication of coccidioidal meningitis.
behavioural or personality change
Due to meningoencephalitis.
reduced visual acuity and papilloedema
Signs of raised intracranial pressure.
Suggestive of cryptococcal meningitis in the appropriate clinical context.
Other diagnostic factors
common
nausea or vomiting
Early feature of meningitis.
fever
Early feature of meningitis.
reduced conscious level
Common and poor prognostic marker in HIV-associated cryptococcal meningitis.[91]
cranial nerve palsies
Fungal meningitis commonly affects the basilar meninges and can injure cranial nerves.
uncommon
seizures
Inflammation of the meninges can cause seizures.
weight loss
Symptom of disseminated infection.
mouth ulcers
Symptom of disseminated infection.
focal neurological signs
Secondary to cerebral infarction. Coccidioidal infection causes arteritis of small- to mid-sized blood vessels.
lymphadenopathy, hepatosplenomegaly
Patients with histoplasmal meningitis may demonstrate these signs as a complication of disseminated progressive histoplasmosis.
dyspnoea
Cough and dyspnoea are associated with pulmonary cryptococcal involvement.
Neonates with candidal meningitis present with respiratory distress.
papular umbilicated skin lesions
Occasionally seen in cryptococcal meningitis.
retinal defects
Retinal involvement may be apparent in central nervous system candidal infection.
nasal or palatal eschar
A specific sign in the later stages of mucormycosis infection is necrotic eschar on the skin, palate, or nasal turbinates.
Risk factors
strong
HIV infection
The progressive loss of CD4+ helper cells in HIV-infected patients correlates with an increasing risk of cryptococcal meningitis. Most patients with cryptococcal meningitis have a CD4 count <100 cells/microlitre, and usually <50 cells/microlitre.[58]
corticosteroid use
The second most important risk factor for the development of cryptococcal meningitis. Solid-organ transplant recipients and patients with connective tissue diseases (e.g., sarcoid, or reticuloendothelial malignancies) who take prednisone doses of >10-20 mg/day have an increased risk of developing cryptococcal meningitis.
Cryptococcal meningitis in an immunocompetent adult after corticosteroid treatment for COVID-19 has been reported.[59]
underlying chronic disease (e.g., malignancy, organ failure, autoimmune disease, organ transplant)
In patients with non-HIV-associated cryptococcal meningitis, predisposing factors have been identified as organ transplant, chronic organ failure (liver, lung, kidney), malignancy, rheumatological disease, and sarcoidosis, irrespective of corticosteroid use.[60][61] In approximately 20% of cases of non-HIV-associated cryptococcal meningitis, no underlying cause for the development of cryptococcal meningitis is found.
exposure to disturbed soil, chicken guano, or bat caves
Histoplasmosis occurs infrequently in individuals living outside endemic areas. Risk factors for acquisition of histoplasmosis include: exposure to disturbed soil, chicken guano, or bat caves. It is important to elicit these risk factors in patients who have travelled to endemic areas.
impaired cell-mediated immunity
Patients presenting with progressive disseminated histoplasmosis and progressive disseminated coccidioidomycosis often have impaired cell-mediated immunity secondary to, for example, HIV/AIDS, transplantation, malignancy, corticosteroid use, tumour necrosis factor antagonist use, or congenital T-cell deficiencies.
Filipinos and African Americans
neutropenia or impaired phagocytic function
Neutropenia is a major risk factor for invasive candidiasis, including candidal meningitis. Defective neutrophil function (e.g., in chronic granulomatous disease) also increases the risk of invasive candidiasis. Candida meningitis may occur in patients with AIDS, but usually only when additional risk factors such as neutropenia are present.[67]
neurosurgery
Candidal meningitis is the most common fungal meningitis following central nervous system shunt or ventriculostomy placement.[68]
infants and neonates
Infants exposed to Histoplasma capsulatum are at increased risk of severe, life-threatening infection.
Candida albicans is a relatively common cause of meningitis in premature infants or infants younger than 1 month. Candidaemia in adults is less commonly associated with meningitis.
weak
residing in or visiting northern Australia, Papua New Guinea, or Vancouver Island, Canada
central vascular catheters
Patients with intravascular catheters are at increased risk for the development of candidaemia.
sinonasal disease
Chronic sinusitis or mastoiditis may be the primary source of fungal meningitis.
antibacterial usage
Prolonged therapy with broad-spectrum antimicrobials increases the risk of heavy candidal colonisation and invasive infection.
prior surgery
Surgical manipulation of a mucosal site colonised with Candida (i.e., gastrointestinal tract surgery) increases the risk of candidaemia.
hyperalimentation
Intravenous hyperalimentation increases the risk of candidaemia.
intravenous drug use
Intravenous drug users are at risk of chronic neutrophilic meningitis caused by Candida albicans.[69]
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