In the years following the initial reports of AIDS in 1981, it was estimated that between 3% and 25% of AIDS patients in the United States would ultimately develop Toxoplasma encephalitis (1). Differences in the incidence of CNS toxoplasmosis reflected differences in the background rate of the parasitic infection among the population. The institution of primary prophylaxis, namely, the administration of antitoxoplasmosis therapy in the face of profound immunosuppression, has resulted in a significant decline in frequency of CNS toxoplasmosis. Following the introduction of highly active antiretroviral therapy (HAART), there has been a further decline in opportunistic infections associated with HIV infection; however, the data regarding the effect of HAART on CNS toxoplasmosis remain controversial. Some investigators have noted as much as a fourfold decline in the clinical recognition of the disease and a similar decline in its presence at autopsy. Others have not found a statistically significant decline in its incidence.
Similarly, with the advent of the AIDS pandemic, the incidence of primary CNS lymphomas (PCNSL) increased dramatically and, after CNS toxoplasmosis, is the second most common cause of space-occupying brain lesions in AIDS. As many as 0.6% of patients present with PCNSL concurrent with the diagnosis of AIDS, and early estimates suggested that 2% to 6% of AIDS patients would ultimately develop the disorder. Indeed, the incidence of PCNSL exceeds that of low-grade astrocytomas. Epidemiologic studies conducted since the introduction of HAART suggest a decline in the incidence of PCNSL in the AIDS population.
Usually, the patient with CNS toxoplasmosis will present with focal neurologic symptoms and signs often superimposed on a global encephalopathy. Mild hemiparesis is the most common focal finding. Headache, confusion, lethargy, brain stem and cerebellar disorders, and seizures are also observed (2, 3). These clinical features are virtually indistinguishable from those of PCNSL, which presents with confusion, lethargy, memory loss, hemiparesis, speech and language disorders, seizures, and cranial nerve palsies, in descending order of frequency. One clinical feature that is believed pathognomonic of CNS toxoplasmosis is chorea; however, it is a rare occurrence. Similarly, clinical or radiographic evidence of leptomeningeal involvement by PCNSL assists in distinguishing this disorder from toxoplasmosis.
In toxoplasmosis, neuroimaging usually reveals multiple nodular or ring-enhancing lesions with edema and mass effect. In one large study (3), only 27% of toxoplasmosis lesions were single on CT scans and only 14% on MR images. Most lesions occur in the basal ganglia (3, 4) and the frontal and parietal lobes (2, 3). The lesions of PCNSL on CT scans typically are hyperattenuated or isoattenuated, round or oval masses with homogeneous contrast enhancement and variable surrounding edema. They are often multifocal and periventricular in location. Leptomeningeal involvement may be seen. Although certain features may suggest either CNS toxoplasmosis or PCNSL, these disorders are frequently indistinguishable by neuroimaging.
Because of this diagnostic dilemma, the American Academy of Neurology published guidelines for the evaluation and management of AIDS-related intracranial mass lesions in 1998 (5). This algorithm was devised as a means to determine the need for early biopsy in the patient most likely to have PCNSL. It was predicated on the predictive values of a negative toxoplasmosis serology finding (<20% of AIDS-related CNS toxoplasmosis is associated with negative toxoplasma serology findings [3)]) and of an isolated brain lesion for the absence of CNS toxoplasmosis (5). 201Tl single photon emission CT (SPECT) and positron emission tomography were considered optional in the algorithm. 201Tl SPECT has been shown to be useful in distinguishing lymphoma from non-neoplastic lesions in AIDS, but diagnostic inaccuracy persists. Similarly, metabolic studies of these lesions employing 18F-fluoro-2-deoxyglucose PET are also helpful in distinguishing between the infectious processes and lymphoma. The sine qua non for the diagnosis of CNS toxoplasmosis remained the clinical and radiographic response to antitoxoplasmosis therapy. Fortunately, the median time to neurologic response is 5 days, with a significant improvement present in more than 90% of patients by day 14 (6).
Other diagnostic measures have been suggested as means of distinguishing between the two conditions. CSF analysis by polymerase chain reaction for Epstein Barr virus and toxoplasmosis has been proposed as a means to diagnose PCNSL and CNS toxoplasmosis, respectively. Most clinicians are properly reluctant to perform lumbar punctures in the face of brain mass lesions, and these tests are not always diagnostic. MR spectroscopy has also been suggested in this context. However, many investigators question the value of MR spectroscopy and find that PET and SPECT studies may be more helpful.
The application of diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) maps as a method to distinguish between these two entities is another contribution to our diagnostic armamentarium. Some caveats apply. Firstly, the number of patients in this study is small; there were only seven patients with CNS toxoplasmosis having a total of 13 lesions and only four with PCNSL having a total of eight lesions. Therefore, replication of the findings by a larger study is mandated. Most importantly, however, there was an overlap in ADC values between some of the toxoplasmosis lesions and some of those due to PCNSL. As a consequence, the technique is insufficient in itself to have diagnostic primacy. It does provide more data when determining whether to proceed to early biopsy for an AIDS-related mass lesion of the brain or to treat initially presumptively for toxoplasmosis. It will likely prove most useful, if validated, when incorporated with other parameters into an algorithm for the management of AIDS-related brain mass lesions.
References
- 1.Janssen RS. Epidemiology and neuroepidemiology of human immunodeficiency virus infection. In: Berger JR, Levy RM, eds. AIDS and the Nervous System. Philadelphia: Lippincott-Raven;1997. :13–37
- 2.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 [DOI] [PubMed] [Google Scholar]
- 3.Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 1992;327:1643–1648 [DOI] [PubMed] [Google Scholar]
- 4.Post MJ, Chan JC, Hensley GT, Hoffman TA, Moskowitz LB, Lippmann S. Toxoplasma encephalitis in Haitian adults with acquired immunodeficiency syndrome: a clinical-pathologic-CT correlation. AJR Am J Roentgenol 1983;140:861–868 [DOI] [PubMed] [Google Scholar]
- 5.Evaluation and management of intracranial mass lesions in AIDS. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1998;50:21–26 [DOI] [PubMed] [Google Scholar]
- 6.Luft BJ, Hafner R, Korzun AH, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team N Engl J Med 1993;329:995–1000 [DOI] [PubMed] [Google Scholar]