Cryptococcal meningitis

Joseph R Berger MD (

Dr. Berger of the Perelman School of Medicine, University of Pennsylvania, received honorariums from Amgen, Biogen, Celegene, Encycle, ExcisionBio, Genentech/Roche, Inhibikase, Merck/Serono, Millennium/Takeda, Novartis, Sanofi/Genzyme, and Shire for his role as a consultant.

John E Greenlee MD, editor. (

Dr. Greenlee of the University of Utah School of Medicine received consulting fees from Sommers Schwartz for review of medical records.

Originally released November 29, 1994; last updated November 8, 2020; expires November 8, 2023


Cryptococcal meningitis is the most common form of meningitis observed in AIDS, affecting 1% to 10% of HIV-infected persons and, conversely, HIV is the greatest risk factor for cryptococcal infection. Other immunosuppressive conditions also predispose to its development, such as corticosteroid administration; however, it may also be seen in immunologically normal persons. Cryptococcal meningitis may be difficult to diagnose as its clinical features are often subtle. Headache is the most common of symptoms but it is not universally present and papilledema occurs in less than one third of persons. On occasion, cryptococcal infection of the CNS presents as mass lesion in the brain (cyst, granuloma, or abscess) or as encephalitis. The toxicity of the antifungal drugs, particularly amphotericin, may render treatment difficult. In the AIDS population, long-term prophylaxis may be required.

Key points


• Cryptococcal meningitis is the most common fungal meningitis and needs to be considered in the differential diagnosis of anyone with unexplained meningitis.


• Although meningitis is the most common neurologic manifestation of cryptococcal infection, CNS mass lesions and vascular insults may also occur.


• Cranial imaging studies either with CT scan or MRI in patients with cryptococcal meningitis may be unrevealing.


CSF cryptococcal antigen studies are typically, but not invariably, positive in cryptococcal meningitis.

Historical note and terminology

Human cryptococcal infection was first described during the last decade of the 19th century. Busse, a pathologist, and Buschke, a surgeon, separately reported the isolation of yeast from the tibia of a young woman (Busse 1894; Buschke 1895). In 1905 the yeast was identified as a CNS pathogen when von Hansemann described the first case of cryptococcal meningitis (Hansemann 1905).

Several different terms have been applied to the fungus currently referred to as Cryptococcus neoformans. Familiarity with these terms is helpful in reading the older literature. Busse employed the term “Saccharomyces hominis” because of the sarcoma-like appearance of the patient's lesions (Busse 1894). The fungus was transferred to the genus Cryptococcus by Vuillemin because of the absence of ascospores (Vuillemin 1901). Subsequently, the term “neoformans” was included to indicate “cancer or tumor-causing” in light of an association between the isolation of the organism and cancers. In 1916 Stoddard and Cutler distinguished between cryptococcus, blastomyces, and other mycoses (Stoddard and Cutler 1916). They named Cryptococcus “Torula histolytica” because of the mistaken belief that the cysts observed in tissues were the consequence of digestive actions of the organism. However, this term is no longer in use.

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