Toxoplasmosis

Definition

Caused by intracellular protozoan -Toxoplasma gondii and a leading cause of space-occupying lesion in HIV-1 positive patients.

Clinical Features

A number of distinctive clinico-morphologic guises for CNS involvement1
Solitary abscesses not rare
May be isolated involvement of spinal cord2

Tumefactive Variant

Typically no clinical manifestations of extraneural parasitosis
Usually immunocompromised:
- a common AIDS-defining disorder
  - leading cause of space-occupying intracranial lesions in HIV-1 seropositive individuals1,3
- bone marrow transplant recipients also particularly vulnerable
Presentation:
- may be:
  - seizures
  - progressive hemipareses
  - cranial nerve deficits
- often variable and nonspecific:
  - no localizing features
  - fever
  - headache
  - lethargy
  - diffuse subacutely evolving encephalopathy

Pathogenesis

Immune failure believed to trigger metamorphosis of Toxoplasma gondii bradyzoites in dormantly parasitized neural tissues to tachyzoites and subsequent destructive invasion of neural tissues
T. gondii:
- obligate intracellular protozoan
- primary infection:
  - usually asymptomatic
  - acquired by consumption of:
    - inadequately cooked red meats containing encysted organisms
    - inadvertent ingestion of materials contaminated by protozoal oocytes in feces of domestic cats
  - noted silent persistence in brain

Gross Pathology

Location of Toxoplasma ‘abscesses’:
- neuron-rich gray matter structures such as:
  - cerebral cortex
  - basal ganglia
  - brainstem

Histopathology

Toxoplasma ‘abscess’ composed of:
- central mass of necrotic cellular debris:
  - often devoid of identifiable organisms
- surrounding edematous and inflamed brain tissue:
  - typically conspicuous vascular abnormalities including:
    - perivascular and intramural lymphoid infiltration
    - endothelial swelling
    - thrombosis
    - fibrinoid necrosis
    - if longstanding, fibrous obliteration
  - Toxoplasma most numerous within this perimeter zone

Two Protozoal Forms Evident In Active Lesions

Rapidly Proliferating Tachyzoite

Responsible for tissue injury
Faintly basophilic
≈ 4–8μm in greatest dimension
Typically slightly crescentic or lunate profile:
- Greek toxon means bow or arc
Often difficult to:
- visualize in routine histologic preparations
- confidently distinguish from cellular detritus:
  - screen suspect biopsy material with Toxoplasma-specific antibodies

Intracellular Pseudocysts and ‘True’ (i.e. Membrane-delimited) Cysts

More readily apparent
In lesser numbers than tachyzoites
Diameters up to 200μm (Fig. 1
Fig. 1: Toxoplasmosis. Minute, basophilic structures representing bradyzoites fill a protozoal pseudocyst lying among infiltrating lymphocytes, plasma cells, and macrophages.
)
Filled with minute, PAS-positive bradyzoites:
- named for slow replicative cycles
- immunologically inert
- form in which Toxoplasma chronically persists in brain
- within CNS, appear to collect within neurons and perivascular macrophages
Often ruptured and appear to be disgorging their content of protozoa into neuropil

Special Stains and Immunohistochemistry

Anti-toxoplasma IgG titer:
- if negative and HIV-1 seropositive:
  - militates against, but does not exclude, diagnosis:
    - if HIV-1 seropositive only occasionally develops if no serologic evidence of contact with organism1
Tachyzoites and bradyzoites labeled by Toxoplasma-specific antibodies

Other investigations

Neuroradiology

Features:
- quite variable
- nonspecific
- do not suffice for definitive diagnosis

Cranial MRI

Typically multifocal, nodular lesions:
- with:
  - ring-like peripheral enhancement
  - surrounding edema
  - mass effect
- exceptionally:
  - nonenhancing or
  - diffusely enhancing

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Toxoplasmosis

Management

Antimicrobial therapy:
- commonly instituted empirically in suspect cases
- neurosurgery for those who do not respond:
  - if HIV-1-seropositive usually prove to harbor primary CNS lymphoma

References

1 Dukes CS, Luft BJ, Durack DT. Toxoplasmosis. Scheld WM, Whitley RJ, Durack DT editor. Infections of the central nervous system. ed. 2. Philadelphia: Lippincott-Raven; 1997.

2 Resnick DK, Comey CH, Welch WC, Martinez AJ, Hoover WW, Jacobs GB. Isolated toxoplasmosis of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome. Case report. J Neurosurg. 1995;82:493–496.

3 Navia BA, Petito CK, Gold JW, Cho ES, Jordan BD, Price RW. Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: clinical and neuropathological findings in 27 patients. Ann Neurol. 1986;19:224–238.

Last updated: 1 Jan 2007