Toxoplasmosis is the generic designation applied to localized or systernic infections caused by the obligate intracellular protozoan Toxoplasma gondii. CNS involvement may assume a number of distinctive clinicomorphologic guises, this discussion focusing on a "tumefactive" variant largely confined to immunocompromised hosts and typically unassociated with clinical manifestations of extraneural parasitosis.

Once regarded as rare and encountered principally among patients treated for hematolymphoid neoplasms (Hodgkin's disease, particularly), this form of toxoplasmosis is now known to physicians the world over as a common AIDS-defining disorder and is in fact the leading cause of space-occupying intracranial lesions in the HIV-1 seropositive. Bone marrow transplant recipients have also emerged in recent years as a population prone to CNS infections of this type. Common to the afflicted is a breakdown of cell-mediated immune surveillance thought, in most cases, to permit recrudescence of the agent in dormantly parasitized neural tissues. T.gondii is noted for its silent persistence in the brain following primary infection, which is usually asymptomatic and acquired by the consumption of inadequately cooked red meats containing encysted organisms or by the inadvertent ingestion of foodstuffs, soil, or other materials contaminated by protozoal oocytes shed in the feces of domestic cats.

The clinical and neuroradiologic features of CNS toxoplasmosis are quite variable, are nonspecific, and do not suffice for definitive diagnosis. Because Toxoplasma "abscesses" favor neuron-rich gray matter structures such as the cerebral cortex, basai ganglia, and brainstem, it should come as no surprise that seizures, progressive hemipareses, and cranial nerve deficits figure prominently among their initial manifestations. Many patients, however, present without localizing complaints, evidencing instead fever, headache, lethargy, and diffuse encephalopathy, subacute in its evolution. Cranial MR imaging typically discloses multifocal, nodular lesions characterized by ring-like peripheral enhancement, surrounding edema, and mass effect, but exceptional examples are nonenhancing or diffusely so, and solitary abscesses at presentation are not rare. Studies in the HIV-1 seropositive have demonstrated that, in this population at least, cerebral toxoplasmosis only occasionally develops in patients with no serologic evidence of contact with the organism. A negative serurn anti-Toxoplasma IgG titer militates against, but does not exclude, the diagnosis in this setting. Although an etiologically specific diagnosis requires the demonstration of the protozoan in biopsy material, it has become common practice to institute antimicrobial therapy on empiric grounds in suspect cases and to reserve neurosurgical intervention for the patient who does not respond satisfactorily to such management.

Most HIV-1-seropositive individuals whose intracranial masses fail to resolve on anti-Toxoplasma chemotherapy prove to harbor primary CNS lymphomas.

The Toxoplasma "abscess"' as it is commonly called, consists of a central mass of necrotic cellular debris surrounded by edematous and inflamed brain tissue typically exhibiting conspicuous vascular abnormalities. The latter include perivascular and intramural lymphoid infiltration, endothelial swelling, thrombosis, fibrinoid necrosis, and in long-standing lesions, fibrous obliteration. It is within this perimeter zone that Toxoplasma are most numerous, the necrotic core often being devoid of identifiable organisms. Two protozoal forms are evident in active lesions. Responsible for tissue injury is the rapidly proliferating tachyzoite. This is faintly basophilic, measures approximately 2 X 6 m m, and typically exhibits a slightly crescentic or lunate profile (the Greek toxon means bow or arc). Because it is often difficult to visualize tachyzoites in routine histologic preparations and to confidently distinguish them from cellular detritus, the screening of suspect biopsy material with Toxoplasma-specific antibodies is strongly advised. More readily apparent, although present in lesser numbers, are intracellular pseudocysts and "true" (membrane-delimited) cysts that may attain diameters of up to 200 m m. These are filled with minute, PAS-positive bradyzoites (named for their slow replicative cycles); are immunologically inert; and represent the form in which Toxoplasma chronically persist in brain and other tissues. Within the CNS, bradyzoites appear to collect preferentially within neurons and perivascular macrophages.

Again, it is immune failure that is believed to somehow trigger their metamorphosis to tachyzoites and subsequent destructive invasion of neural tissues. Careful inspection of active lesions often reveals ruptured cysts that appear to be disgorging their content of protozoa into the neuropil. Like tachyzoites, bradyzoites are labeled by commercially available Toxoplasma-specific antibodies.

(Ref. Marc K. Rosemblum, Central nervous system, in Ackerman's Surgical Pathology, 8th ed.)