Clinical Presentation And Differential Diagnosis

The commonest causes of cerebral mass lesions in HIV-seropositive patients are toxoplasmosis and primary cerebral lymphoma and the differential diagnosis often proves difficult. Both diagnoses occur in patients with advanced immunodeficiency (CD4 cell counts <50 X 106/L) and present with headaches and focal neurologic deficits. Clinical features that favor PCL include a more gradual onset over 2-8 weeks and the absence of a fever. CT and MRI scanning usually reveal solitary or multiple ring enhancing lesions with prominent mass effect and edema. Again, these features occur in both diagnoses, although PCL lesions are usually periventricular while toxoplasmosis more often affects the basal ganglia. Thus, the combination of clinical findings and standard radiologic investigations rarely provide a definitive diagnosis. Moreover, toxoplasma serology (IgG) is falsely negative in 10-15% of patients with cerebral toxoplasmosis. More than 85% patients with cerebral toxoplasmosis will respond clinically and radiologically to 2 weeks of anti-toxoplasma therapy, and this has become the cornerstone of the diagnostic algorithm for cerebral masses in severely immunodeficient patients.

In these patients, it has been a standard practice to commence empirical anti-toxoplasmosis treatment for 2 weeks duration, and resort to a brain biopsy if there is no clinical or radiologic improvement. This strategy avoids the routine use of brain biopsy in these patients who frequently have a very poor performance status and prognosis. Although this algorithm avoids early surgical intervention, it is relatively ineffective in diagnosing PCL early, and may compromise the outcome of therapy in these patients. In addition, there is a disinclination to treat patients with radiotherapy or chemotherapy empirically based exclusively on the failure of anti-toxoplasmosis treatment without a definitive histologic diagnosis.

The discovery that all HIV-associated PCLs are associated with EBV infection has led to the development of a PCR method that can detect EBV DNA in the CSF. This has become established as a diagnostic test with a high sensitivity (83-100%) and specificity (>90%).89-91 In addition, radionuclide imaging by 201thallium single photon emission computed tomography (201Th-SPECT) or 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is able to differentiate between PCL and cerebral toxoplasmosis. PCLs are thallium avid and demonstrate increased uptake on PET scanning; however, although both techniques have high specificity for PCL, neither are highly sensitive and thus cannot be used alone but, in combination with PCR, are emerging as a diagnostic alternative to brain biopsy. The application of PCR and 201Th-SPECT in the diagnosis of contrast-enhancing brain lesions in 27 patients was shown to result in a positive and a negative predictive value of 100% and 88%, respectively, which supports their combined value as an alternative to brain biopsy.91 Further studies are now required to compare effectiveness of PCR with 201Th-SPECT or FDG-PET.

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