Histoplasma capsulatum is a dimorphic fungus that is endemic to the Ohio and Mississippi river valleys of the central United States. The fungus is acquired by inhalation. Dissemination is rare and occurs primarily in patients with defective cellular immunity, such as patients with AIDS, patients with lymphoreticular malignancies, and organ transplant recipients.  The most common presentation of CNS histoplasmosis is meningitis. The typical presentation includes fever, sweats, weight loss, headache, mental status abnormalities (including decreased level of consciousness, confusion, personality changes, and/or memory impairment), cranial nerve palsies, stroke, or seizures.  CNS histoplasmosis may also be a solitary abscess or multiple lesions, but meningitis is the much more common presentation. The majority of patients with CNS histoplasmosis have an abnormal neuroimaging study with meningeal enhancement, hydrocephalus, solitary or disseminated contrast-enhancing lesions, or various combinations of these entities. Chest radiographs should be obtained. The most common roentgenogram abnormalities in histoplasmosis are diffuse or focal pulmonary infiltrates. Histoplasma polysaccharide antigen (HPA) in urine, blood and CSF may allow for a rapid diagnosis. The presence of the HPA in CSF is a reliable indicator of CNS involvement; however, cross reactions with C. immitis, C. neoformans and Candida have been reported. Serological tests for anti-Histoplasma capsulatum antibodies may be helpful. They may also be misleading and can be negative in 10 to 25 percent of patients with disseminated histoplasmosis or falsely positive in patients with other fungal diseases or tuberculosis. Antibodies remain elevated for several years despite resolution of histoplasmosis and may lead to a misdiagnosis of patients with neurological illnesses caused by other diseases.  Examination of the CSF typically reveals a lymphocytic pleocytosis (less than or equal to 100 cells/
mm3 ), although a predominance of polymorphonuclear leukocytes may also occur. The CSF protein concentration is increased, and the CSF glucose concentration is usually decreased. It is rare to identify the fungus on CSF india ink stain. The CSF culture, however, is frequently positive, as are blood, bone marrow, and urine cultures. In general, when fungal meningitis is suspected, multiple cultures of lumbar fluid should be obtained to identify the organism. Consideration should also be given to obtaining CSF by a cisternal puncture. In cases of H. capsulatum meningitis, one CSF culture out of several is typically positive, stressing the need for repeated attempts to isolate the fungus using large volumes of centrifuged CSF.  Intravenous amphotericin B (0.75 to 1.0 mg/kg/d) remains the mainstay of treatment of CNS histoplasmosis. A total dose of 30 mg/ kg is recommended. Oral itraconazole (200 mg twice daily for several weeks) is useful in patients who relapse after a course of amphotericin B is completed and for chronic suppressive therapy in patients with AIDS. 
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