Involvement of the central nervous system (CNS) is recognized clinically in 5% to 10% of patients with progressive disseminated histoplasmosis. The risk of developing CNS histoplasmosis is increased in individuals with impaired cellular immunity, but not all patients with this condition are immunocompromised. Clinical syndromes include chronic meningitis, focal parenchymal lesions of the brain or spinal cord, stroke due to infected emboli, and diffuse encephalitis. CNS histoplasmosis should be considered in any patient with one of these syndromes who has resided in an area endemic for histoplasmosis. A high index of suspicion is necessary when extraneural signs and symptoms are absent. Culture of the causative fungus, Histoplasma capsulatum, from cerebrospinal fluid, brain tissue, or other sites is the gold standard for diagnosis. In culture-negative cases, detection of H. capsulatum antigen in cerebrospinal fluid, urine, or blood is helpful diagnostically. Aggressive and prolonged antifungal therapy is indicated in all cases of CNS histoplasmosis. There are no data from prospective comparative trials upon which to base specific recommendations for treatment. Expert opinion favors an initial course of liposomal amphotericin B, followed by at least 1 year of itraconazole.
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