Cryptococcus neoformans is the most common fungus producing CNS infection and is an important, although not numerically frequent, etiology of meningitis. The organism is discussed in detail in Chapter 16. About 70% of cryptococcal meningitis cases are male, and the majority are of middle age. About one-half are associated with malignancy or other severe diseases or with immunodeficiency (either from underlying disease or from therapy). Meningitis due to Cryptococcus is said to produce an elevated cell count in about 95% of cases (range, 90%-97%). The count is usually less than 300/mm3 and in the majority of cases is less than 150/mm3. In one series, the CSF cell count was less than 100/mm3 in about 60% of patients. More than one half of the cells are lymphocytes. Protein levels are elevated in about 90% of cases. The CSF glucose level is decreased in 50%-75% of cases.

The LA slide test for cryptococcal antigen in CSF is the best rapid diagnostic test. It is reported to detect about 85%-90% of cases (literature range, 71%-100%). There is a slightly increased detection rate if both CSF and serum are tested. Serum testing alone detects about 50% of cases (range, 18%-71%). The LA test is discussed in detail in Chapter 16. The older procedure for detection of Cryptococcus in CSF was a wet mount using india ink or nigrosin. C. neoformans has a thick gelatinous capsule that gives the appearance of a clear zone or halo around the organism against the dark background of india ink particles. However, only about 50% (range, 40%-79%) of cases can be detected by india ink preparations, and some of these may require repeated examinations. In addition, experience is needed to avoid false positive and negative results. India ink has been replaced by the LA test.

Although LA tests for cryptococcal antigen are reasonably sensitive, culture of CSF is still considered essential. In some cases, culture may reveal organisms when the CSF cell count, protein levels, and glucose levels are all normal. Culture detects about 80% of patients on initial lumbar puncture (range, 72%-90%). Fungi require different culture media for optimum growth than the standard bacterial media, so the laboratory should be notified if fungi are suspected. In some patients, cryptococcal antigen latex studies on CSF have been positive when cultures were negative, and in a few cases, cultures were positive when the LA test result was negative.