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Fungal meningitis

Fungal meningitis refers to meningitis caused by a fungal infection.

Incidence has increased because of an increasing number of immunosuppressed patients which includes those on immunosuppressive drugs, malignancies, AIDS and premature neonates.

Individuals with a weak immune system are most at risk, including individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, and the elderly.

May occur in the absence of immunosuppression.

Results from hematogenous spread from fungi inspired into the lungs.

Can result from direct spread from infected sinuses or following surgical or other trauma.

Because of nonspecific symptoms and subacute onset the diagnosis is often delayed weeks to months.

Symptoms of fungal meningitis are generally similar to those of other types of meningitis: fever, stiff neck, severe headache, photophobia, nausea and vomiting, and altered mental status.

Fever and headache are common but may be absent.

May be associated with a slow deterioration in mental status, confusion with dementia in the elderly.

Nuchal rigidity and photophobia seen less often than in bacterial meningitis.

May be associated with cranial nerve abnormalities.

Findings and symptoms of increased intracranial pressure may be seen, particularly in cryptococcal meningitis.

Diagnostic studies include brain imaging and analysis of the CSF.

All patients with suspected disease should undergo a lumbar puncture.

CSF evaluation includes opening pressure, cell count with differential, protein, levels glucose levels, India ink stain and or Cryptococcus antigen testing, Gram stain and cultures.

Fungal media is required to recover fungi, although Candida and Aspergillus species will grow on standard bacterial culture media.

Fungal meningitis is diagnosed by testing blood and cerebrospinal fluid for pathogens. 

Utilizing increased volumes of CSF of 5-10 mL will improve culture sensitivities.

Serologic tests for Histoplasma antigen, Coccidioides complement fixation antibody, Aspergillus antigen performed on serum or CSF can be helpful in diagnosis.

Coccidioides can cause a lethal meningitis that develops within weeks to months after and often unrecognized primary infection.

CSF analyses usually show moderate pleocytosis, low glucose levels, and mild increase in protein levels.

CSF: Measurement of opening pressure, cell count with differential, glucose and protein concentrations, Gram’s stain, India ink, and culture tests should be performed on cerebrospinal fluid when fungal meningitis is suspected.

CSF differential count typically has a predominance of mononuclear cells, but may show an increased percentage of polymorphonuclear cells.

Increased eosinophils in the CSF may be seen with coccidioidomycosis and increased neutrophils are seen with blastomycosis.

Enhanced CT or MRI of the brain may reveal meningeal enhancement or hydrocephalus and imaging must be done to rule out parenchymal changes and edema.

Fungal meningitis may be caused by the following types of fungi:

Candida – C. albicans is the most common Candida species that causes infections of the central nervous system.

Coccidioides – it is endemic to southwestern United States and Mexico. 

A third of patients presenting with disseminated coccidioidomycosis have developed meningitis.

Histoplasma – occurs in bird and bat droppings and is endemic to parts of the United States, South, and Central America. 

CNS involvement occurs in about 10-20% of cases of disseminated histoplasmosis.

Blastomyces – occurs in soil rich in decaying organic matter in the Midwest United States. 

Meningitis is an unusual manifestation of blastomycosis.

Cryptococcal meningitis is acquired through inhalation of soil contaminated with bird droppings. C. neoformans is the most common pathogen to cause fungal meningitis.

Aspergillus infections account for 5% of fungal infections involving the central nervous system.

Individuals with a weak immune system are most at risk, including individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, and the elderly.

Fungal meningitis is diagnosed by testing blood and cerebrospinal fluid for pathogens. 

Identifying the specific pathogen is necessary to determine the proper course of treatment and the prognosis.

Outcome commonly related to the underlying immune status of the patient.

More successfully treated in patients who have a reversible immunosuppressed state.

In HIV patients with cryptococcal disease, results are more successful in those with a CD4+ count greater than 100/µL.

Fungal meningitis is treated with long courses of high dose antifungal medications. 

The duration of treatment is dependent upon the causal pathogen.

Prognosis depends on the pathogen responsible for the infection and risk group: Overall mortality for Candida meningitis is 10-20%, 31% for patients with HIV, and 11% in neurosurgical cases.

Prognosis for Aspergillus and coccidioidal infections is poor.

Amphotericin B historically the mainstay of treatment, but better tolerated lipid formulations frequently substituted.

Azoles commonly used for follow-up treatment or secondary prophylaxis.

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