Fungal infections of the CNS may arise without obvious predisposing cause, but they typically complicate some other disease process that suppresses immune function such as HIV, cancer chemotherapy, organ transplantation, severe burns, leukemia, lymphoma or other malignancy, diabetes, rheumatologic disease, or prolonged corticosteroid therapy. They are referred to as opportunistic. The factors operative in these clinical situations are the interference with the body’s normal flora and impaired T-cell and humoral responses. Thus, fungal infections tend to occur in patients with leukopenia, inadequate T-lymphocyte function, or insufficient antibodies. In these circumstances, other infectious agents including bacteria (Pseudomonas and other gram-negative organisms, L. monocytogenes), protozoa (Toxoplasma), and viruses (cytomegalovirus, herpes simplex, and varicella zoster) may also be opportunistic and should be considered in the aforementioned clinical situations.
Fungal meningitis develops insidiously, as a rule, over a period of several days or weeks, similar to tuberculous meningitis; the symptoms and signs are also much the same as with tuberculous infection. Involvement of several cranial nerves, arteritis with thrombosis and infarction of brain, multiple cortical and subcortical microabscesses, and hydrocephalus frequently complicate the course of fungal meningitis, just as they do in all chronic meningitides. Sometimes the patient is afebrile or has only intermittent fever.
The spinal fluid changes in fungal meningitis are also like those of tuberculous meningitis. Pressure is elevated to a varying extent, pleocytosis is moderate and lymphocytes predominate. Exceptionally, in acute cases, a pleocytosis above 1,000/mm3 and a predominant polymorphonuclear response are observed (also seen with the bacterial infections, nocardia, and actinomycosis). On the other hand, in patients with HIV or with pronounced leukopenia for other reasons, the pleocytosis may be minimal or even absent. Glucose is subnormal and protein is elevated, sometimes to very high levels.
The specific diagnosis is made from smears of the CSF sediment, from cultures and by demonstrating antigens of the organism by immunodiffusion, latex particle agglutination, or comparable antigen recognition tests. The CSF examination should also include a search for tubercle bacilli and abnormal white cells because of the not infrequent concurrence of fungal infection and tuberculosis, leukemia, or lymphoma.
Some of the special features of the more common fungal infections are indicated later.
Cryptococcosis (Torulosis, European Blastomycosis)
Cryptococcosis is one of the more frequent fungal infections of the CNS and it occurs in both normal and immunocompromised hosts. The causative organism is usually Cryptococcus neoformans but Cryptococcus gattii has also been implicated. Cryptococcus is a common soil fungus found in the roosting sites of birds, especially pigeons. Usually the respiratory tract is the portal of entry, less often the skin and mucous membranes. The pathologic changes are those of granulomatous meningitis; in addition, there may be small granulomas and cysts within the cerebral cortex, and sometimes larger granulomas and cystic nodules deep in the brain (cryptococcomas). The cortical cysts contain a gelatinous material and large numbers of organisms; the solid granulomatous nodules are composed of fibroblasts, giant cells, aggregates of organisms, and areas of necrosis.