Toxoplasma gondii is an intracellular protozoan parasite. Most human infections with T. gondii are asymptomatic, but CNS infection can potentially cause four syndromes:148,149

  • meningoencephalitis during primary infection of an immunocompetent host
  • intracerebral mass lesions or encephalitis in immunocompromised hosts
  • retinochoroiditis associated with primary infection or reactivation of an earlier infection
  • congenital toxoplasmosis, encephalitis, and retinochoroiditis as a result of transplacental fetal infection

The only definitive host for T. gondii is domestic cats.148 Transmission of T. gondii to humans occurs commonly, usually by eating undercooked meat or by inadvertent ingestion of oocysts from cat feces. Systemic parasitemia occurs after invasion of the gut lining by Toxoplasma.148

Toxoplasmosis in immunocompetent hosts

Primary infection with T. gondii in the immunocompetent host is usually asymptomatic. The most common sign is generalized lymphadenopathy, which occurs in up to 20% of patients.149 Symptomatic CNS toxoplasmosis rarely develops during primary infection in normal hosts, but unusual cases of CNS involvement in immunocompetent patients can be associated with drowsiness, confusion, seizures, and even coma.149

CSF analysis reveals mild pleocytosis, elevated protein, and normal glucose. Diagnosis is usually made on the basis of either increasing or markedly elevated serum and CSF antibody titers.148

Toxoplasmosis in immunocompromised hosts

Before AIDS, reactivation of CNS toxoplasmosis occurred most often in patients with hematologic malignancies. Because many of these patients receive immunosuppressive therapy, the relative contribution of immune dysfunction from malignancy versus immune suppression from drugs is difficult to define.148 CNS toxoplasmosis can also occur in patients receiving immunosuppressive chemotherapy after organ transplantation or for collagen vascular disorders.148–150

Toxoplasmosis is one of the most common opportunistic infections in AIDS, so cases of CNS toxoplasmosis have increased dramatically since 1981. Toxoplasmosis is responsible for over one-third of neurologic symptoms in AIDS patients.148 (In contrast, both primary CNS and metastatic lymphoma account for approximately 5% each.) More than 95% of toxoplasmic encephalitis in patients with AIDS is due to reactivation of chronic latent infection.150 For most HIV-infected patients, toxoplasmic encephalitis develops after the CD4 count falls below 100.148 In the United States, 10–40% of AIDS patients are latently infected, and 30–50% of these will develop toxoplasmic encephalitis.148

Clinical manifestations are variable, ranging from an insidious process to an acute confusional state. Reported seizure rates range from 18% to 29% and may include partial, complex partial, and generalized seizures.151,152

The differential diagnosis is wide, including:

  • cryptococcal meningitis
  • tuberculosis
  • nocardial or bacterial abscess
  • progressive multifocal leukoencephalopathy (PML)
  • malignancies, including primary CNS lymphoma

Resolving the differential diagnosis of toxoplasmosis versus primary CNS lymphoma as the etiology of an intracranial mass in the context of AIDS is a difficult clinical challenge, requiring consideration of a constellation of data.



In the immunocompetent host, acute acquired toxoplasmosis is usually established by a fourfold rise in IgG antibody titer.148Although the presence of high IgG titer suggests acute infection, such titers can persist for years after acute infection. Therefore, immunoglobulin M is used as part of the diagnostic criteria of acute-acquired toxoplasmosis.

In the immunocompromised host, serologic diagnosis of toxoplasmic encephalitis depends on the pathophysiology particular to the specific immunocompromised population. In the transplant patient, prior seronegativity or positivity can help inform the significance of serology testing after transplantation. In many immunocompromised patients, instead of rising or high titers, low or absent antitoxoplasmic antibody titers occur secondary to recrudescence of latent infection in the context of suppressed humoral immunity.148,150


MRI is the imaging modality of choice, revealing rounded, isodense or hypodense lesions with ring enhancement. In approximately 75% of cases, lesions are multiple, with a predilection for basal ganglia and brain stem. In up to 80% of cases, however, toxoplasmosis is indistinguishable from lymphoma on standard neuroimaging studies.148,150 Toxoplasmosis and CNS lymphoma both appear as single or multiple ring or nodular-enhancing mass lesions on standard CT and MRI, and both can localize to the basal ganglia and brain stem. (Lymphoma can also localize to the corpus callosum, subependymal region, or periventricular regions, so lesions in these regions are more likely to be lymphoma).153 Although there are subtle clues that can help distinguish toxoplasmosis from lymphoma, reliable differentiation by CT or MRI alone is impossible. Because they respond to different treatments, differentiation is essential.

To assist lesion identification, Thallium-201 single photon emission computerized tomography (SPECT) is used.153 Thallium-201 SPECT shows uptake in CNS lymphomas but not infections, including toxoplasmosis.153 Also, steroids that can affect appearance of lymphoma on CT and MRI do not affect SPECT results.148,150,153 The combination of serologic testing, contrast-enhanced CT or MRI, and SPECT should provide sufficient data for diagnostic differentiation. Definitive diagnosis of toxoplasmic encephalitis requires brain biopsy and subsequent histopathologic analysis.


Therapy for toxoplasmic encephalitis is the combination of pyrimethamine and sulfadiazine. Clindamycin can be used as an alternative to sulfadiazine.154 Serial neuroimaging provides the best follow-up to assess treatment progress.

Maintenance anticonvulsant therapy is usually required.

Newborns of women contracting toxoplasmosis during pregnancy should be treated with clindamycin to reduce the likelihood of developing late neurologic sequelae, including seizures.13,154

Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133. 
With permission from Elsevier (

Reviewed By: 
Steven C. Schachter, MD
Monday, March 1, 2004