A presumptive diagnosis can be made on a clinical basis in a patient with HIV and empiric treatment is started before confirmatory testing. If there is no improvement clinically and on imaging after a course of antibiotics, evaluation for cerebral lymphoma and other brain masses is undertaken.
Treatment Patients with a presumptive diagnosis of cerebral toxoplasmosis, are treated with oral sulfadiazine (4 g initially, then 4 to 6 g daily) and pyrimethamine (200 mg initially, then 50 to 100 mg daily) or, when cost or availability of these drugs are issues, the combination of sulfamethoxazole and trimethoprim is used. Leucovorin, 15 to 20 mg daily, should be given to counteract the antifolate action of pyrimethamine. Treatment must be continued for at least 6 weeks. In patients with HIV, treatment at lower doses is continued until the CD4 count exceeds 200 to 250/μL for 6 months or more; otherwise treatment must be lifelong to prevent relapses. Institution of treatment of HIV may precipitate a fulminant inflammatory response (immune reconstitution inflammatory syndrome, IRIS) around the parasite abscess.
This disease is caused by free-living flagellate amoebae, usually of the genus Naegleria and less frequently of the genera Acanthamoeba and Balamuthia. Naegleria is acquired by swimming in ponds or lakes where there is warm fresh water. These are rare but lethal illnesses, with several dozen instances in the last decade in the United States, where most cases have occurred in the Southeastern states.
The onset of the illness caused by Naegleria is usually abrupt, with severe headache, fever, nausea and vomiting, and stiff neck. The course is inexorably progressive—with seizures, increasing stupor and coma, and focal neurologic signs—and the outcome is practically always fatal, usually within a week of onset. The reaction in the CSF is like that in acute bacterial meningitis: increased pressure, a large number of polymorphonuclear leukocytes (not eosinophils, as in the parasitic infestations discussed further on), and increased protein and decreased glucose content. There may be a number of red blood cells in the CSF, reflecting the hemorrhagic and necrotic nature of some amebic brain lesions. The diagnosis is supported by a history of swimming in fresh warm water, particularly of swimming underwater for sustained periods, and on finding viable trophozoites in a wet preparation of unspun spinal fluid. Gram stain and ordinary cultures do not reveal the organism.
Autopsy discloses purulent meningitis and numerous small granulomatous microabscesses in the underlying cortex and white matter.
Subacute and chronic granulomatous meningoencephalitis from ameba is a rare disease in humans. Isolated instances have been reported in debilitated and immunosuppressed patients (Gonzalez et al). The organism may be difficult to culture from the CSF; most diagnoses are made from biopsy. A fatal case of ours, in a leukopenic patient who had been receiving granulocyte-stimulating factor, ran a subacute course over 1 month with headache, mild fever, stupor, and unmeasurably low CSF glucose toward the end of life (Katz et al). Initially, there were scattered, round, enhancing lesions on the MRI that disappeared with corticosteroids, much like lymphoma; later, there were more irregular confluent white matter lesions. A brain biopsy revealed amoebae that could have been easily mistaken for macrophages or cellular debris; the organism proved to be Balamuthia.