Diagnostic Criteria for CNS Toxoplasmosis
A presumptive diagnosis of CNS toxoplasmosis is established by the combination of clinical symptoms, serologic evidence of prior infection, and characteristic space-occupying lesions on brain imaging. 1
Clinical Presentation
The clinical manifestations that should raise suspicion for CNS toxoplasmosis include:
- Focal neurological deficits are the most common presentation, though diffuse CNS disease can occur 2
- Fever, reduced alertness, and seizures frequently accompany the neurologic findings 1, 2
- Headache, hemiparesis, hemiplegia, or other focal neurologic symptoms 3
- The presentation can be variable and may reflect either focal or diffuse CNS involvement 1
Imaging Findings (Essential for Diagnosis)
Brain imaging is essential and demonstrates characteristic patterns:
- CT scan typically reveals multiple, bilateral, ring-enhancing lesions, particularly in the basal ganglia and cerebral corticomedullary junction 1, 2, 4
- MRI is more sensitive than CT and will confirm basal ganglia lesions in the majority of patients 1, 2, 4
- Brain abscess-like or mass-like lesions are common findings 5
- Single lesions can occur in approximately 40% of cases, though multiple lesions are more typical 3
Serologic Testing
- Serologic testing is the major method of diagnosis, though interpretation can be challenging 1, 2
- Positive Toxoplasma-specific IgG antibodies indicate prior infection and risk for reactivation 4
- Critical caveat: Cases of Toxoplasma encephalitis have been documented in persons without detectable Toxoplasma-specific IgG antibodies; therefore, negative serology does NOT exclude the diagnosis 1, 2
- IgM antibodies are typically negative in reactivation disease 3
Definitive Diagnosis
- Definitive diagnosis requires histologic or cytologic confirmation by brain biopsy, which demonstrates leptomeningeal inflammation, microglial nodules, gliosis, and Toxoplasma cysts 1
- Brain biopsy should be considered when:
- Biopsy pathology should show necrotizing inflammation with microglial nodules, gliosis, and Toxoplasma cysts or tachyzoites 4
Additional Diagnostic Methods
- Toxoplasma gondii DNA detection by PCR can be performed on CSF, peripheral blood, or other body fluids, though CSF PCR has limited sensitivity and is not standardized 1, 4
- Isolation of the parasite by mouse inoculation or tissue culture of CSF is possible but rarely performed 1
- CSF analysis may show elevated protein and pleocytosis, but these findings are nonspecific 1
Treatment Approach (Diagnostic and Therapeutic)
The preferred treatment regimen is pyrimethamine plus sulfadiazine plus leucovorin 1, 2, 4:
- Pyrimethamine: 2 mg/kg/day for 2-3 days (loading), then 1 mg/kg/day 1, 2
- Sulfadiazine: 25-50 mg/kg/dose four times daily (or 100 mg/kg/day divided twice daily for congenital cases) 1, 2
- Leucovorin (folinic acid): 10-25 mg/day must always be administered with pyrimethamine to minimize bone marrow suppression 2
Alternative regimen for sulfa-allergic patients:
- Pyrimethamine plus clindamycin with leucovorin 4, 3
- Trimethoprim-sulfamethoxazole is an alternative with similar efficacy 4
Duration and monitoring:
- Acute therapy should be continued for 6 weeks, assuming clinical and radiological improvement 2
- Clinical and radiological response should be evident within 10-14 days; lack of response warrants repeat imaging and consideration of brain biopsy 4
- Complete blood count should be performed at least weekly while on daily pyrimethamine 2
Key Clinical Pitfalls
- Never exclude CNS toxoplasmosis based on negative serology alone, as seronegative cases are well-documented 1, 2
- Single lesions do not exclude toxoplasmosis—approximately 40% of cases may present with solitary lesions 3
- In HIV-infected patients, toxoplasmosis typically occurs when CD4+ counts fall below 100-200 cells/μL, but exceptions exist 3, 6
- The diagnosis is often made presumptively based on clinical and radiographic response to empiric therapy, with biopsy reserved for non-responders 3, 6