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.
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.
"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
K. Rosemblum, Central nervous system, in Ackerman's Surgical Pathology,