Histoplasmosis of the nervous system

Elena Grebenciucova MD (

Dr. Grebenciucova of Northwestern University has received honorariums from AlphaSights, Medscape, and Trinity Partners for consulting work.

Karen L Roos MD FAAN, editor. (Dr. Roos of Indiana University School of Medicine has no relevant financial relationships to disclose.)
Originally released August 11, 2005; last updated January 23, 2019; expires January 23, 2022

This article includes discussion of histoplasmosis of the nervous system and Darling disease. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. Infection is endemic to certain areas of the United States, including the Mississippi and Ohio River Valleys, as well as parts of Central America, South America, Africa, and Southeast Asia. Organisms are spread by disturbance of ground soil contaminated by bat and avian excrement. Inhalation of spores causes infection, which primarily involves the lungs. Extrapulmonary infection can occur, though this is much less common. Immunocompromised individuals are at an increased risk for disseminated infection. In rare but serious cases, histoplasmosis affects the nervous system. Central nervous system involvement is clinically recognized in 10% to 20% of progressive, disseminated cases. CNS infection can also be isolated. Meningitis is the most common clinical manifestation of CNS histoplasmosis. Cerebral ring enhancing lesions are rarely reported. Diagnosis of histoplasmosis can be confirmed by detection of serum antigens, blood cultures, bronchoalveolar lavage, and biopsy of affected tissues. Methods for diagnosis of CNS infection are detailed below. Treatment with intravenous amphotericin B is required to penetrate the blood brain barrier, and long term use of oral itraconazole or fluconazole is necessary to prevent relapse.

Historical note and terminology

Histoplasma capsulatum was first discovered in 1905 by pathologist Samuel Darling. Accordingly, histoplasmosis was once known as “Darling's disease.” Darling described the organism as a protozoan. However, in 1912, da Rocha-Lima described the organism's resemblance to a yeast. More than 20 years later, growth on artificial medium revealed that the organism was dimorphic: a mold at room temperature and a yeast at 37°C.

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