Utility of Brain Biopsy in Patients with Acquired Immunodeficiency Syndrome Before and After Introduction of Highly Active Antiretroviral Therapy

To the Editor:

We read with great interest the article of Rosenow and Hirschfeld (6) and would like to make some comments. First, cerebral toxoplasmosis continues to cause important morbidity and mortality in resource-limited settings, including Brazil, a country with a free and universal access program to highly active antiretroviral therapy. Second, as the authors mentioned, the goals of their proposed algorithm were to avoid unnecessary biopsies for cerebral toxoplasmosis and to diagnose cerebral lymphoma early. In most developing countries, in contrast to developed countries, cerebral lymphoma is uncommon and focal forms of central nervous system tuberculosis (especially tuberculoma and, rarely, tuberculous brain abscess) constitute the major differential diagnosis of cerebral toxoplasmosis (4, 5, 7, 8). Similarly, in our setting, a tertiary referral center in São Paulo, Brazil, cerebral toxoplasmosis and tuberculoma represent the main causes of expansive brain lesions, and both can be clinically treated. For these reasons, indications for brain biopsy are usually more conservative here when compared with settings where cerebral lymphoma is the main alternative diagnosis of cerebral toxoplasmosis.

Third, unlike Rosenow and Hirschfeld, in clinical practice we evaluate the empirical toxoplasmosis therapy at 2 weeks of treatment, considering that 93% of patients with cerebral toxoplasmosis show partial or complete radiological improvement at this point (9). In possible cases of tuberculoma, it is usually possible to introduce antituberculous treatment within these 2 weeks, after carefully evaluating the patient's history and clinical and laboratory features. Fourth, we perform early brain biopsies when an alternative diagnosis is highly probable, principally in cases of tuberculous or pyogenic abscess.

Fifth, the authors concluded that the presence of negative immunoglobulin G titers for Toxoplasma gondii is an absolute indication for biopsy. However, this recommendation is not applicable in settings with a high prevalence of toxoplasmosis in the general population. For example, in Brazil, up to 80% of the population presents a positive serology for toxoplasmosis (1). For this reason, most patients with a focal brain lesion can have immunoglobulin G titers for T. gondii. Despite this, in our center, only 2% of cerebral toxoplasmosis cases did not have immunoglobulin G titers for T. gondii (9), and the high negative predictive value of serology offers an important diagnostic clue to consider an alternative diagnosis.

Sixth, the authors reported 6 patients diagnosed with lymphoma whose lesions did not enhance with contrast medium. In our experience, 16% of cerebral toxoplasmosis cases have hypodense lesions without contrast enhancement and with an expansive effect on computed tomography (CT) (9), confirming that although certain features may suggest either cerebral toxoplasmosis or cerebral lymphoma, these disorders are frequently indistinguishable by neuroimaging (2).

Finally, as Rosenow and Hirschfeld commented, the introduction of molecular diagnosis using CSF samples is a very useful and minimally invasive approach, especially for the detection of Epstein-Barr virus and John Cunningham virus deoxyribonucleic acid. Although the detection of T. gondii deoxyribonucleic acid has not produced conclusive results in the literature, in our experience, a molecular diagnosis of cerebral toxoplasmosis using peripheral blood samples has a sensitivity of 80%, a specificity of 98%, a positive predictive value of 95%, and a negative predictive value of 91% (3). This test is especially useful in patients with expansive brain lesions who have contraindications for undergoing lumbar puncture, but the collection of blood samples needs to be performed before or during the first 3 days after the introduction of antiparasitic therapy.

The interesting results reported by Rosenow and Hirschfeld demonstrate the importance of elaborating specific algorithms based on local neuroepidemiology of focal brain lesions in patients infected with human immunodeficiency virus, the need for a continuous incorporation of alternative diagnosis tools in the management of these lesions, and the permanent contribution of brain biopsies for the definitive diagnosis of a subset of patients, despite the decline in the number of these procedures in the era of highly active antiretroviral therapy.

1.

Bahia-Oliveira LM, Jones JL, Azevedo-Silva J, Alves CC, Oréfice F, Addiss DG: Highly endemic, waterborne toxoplasmosis in north Rio de Janeiro state, Brazil. EmergInfect Dis 9:55–62, 2003.

2.

Berger JR: Mass lesions of the brain in AIDS: The dilemmas of distinguishing toxoplasmosis from primary CNS lymphoma. AJNR Am J Neuroradiol 24:554–555, 2003.

3.

Colombo FA, Vidal JE, Penalva de Oliveira AC, Hernandez AV, Bonasser-Filho F, Nogueira RS, Focaccia R, Pereira-Chioccola VL: Diagnosis of cerebral toxoplasmosis in AIDS patients in Brazil: Importance of molecular and immunological methods using peripheral blood samples. J Clin Microbiol 3:5044–5047, 2005.

4.

Lucas SB, Hounnou A, Peacock C, Beaumel A, Djomand G, N'Gbichi JM, Yeboue K, Hondé M, Diomande M, Giodano C, Doorly R, Brattegaard K, Kestens L, Smithwick R, Kadio A, Ezani N, Yapi A, De Cock KM: The mortality and pathology of HIV infection in a West African city. AIDS 7:1569–1579, 1993.

5.

Modi M, Mochan A, Modi G: Management of HIV-associated focal brain lesions in developing countries. QJM 97:413–421, 2004.

6.

Rosenow JM, Hirschfeld A: Utility of brain biopsy in patients with acquired immunodeficiency syndrome before and after introduction of highly active antiretroviral therapy. Neurosurgery 61:130–141, 2007.

7.

Shankar SK, Mahadevan A, Satishchandra P, Kumar RU, Yasha TC, Santosh V, Chandramuki A, Ravi V, Nath A: Neuropathology of HIV/AIDS with an overview of the Indian scene. Indian J Med Res 121:468–488, 2005.

8.

Trujillo JR, Jaramillo-Rangel G, Ortega-Martinez M, Penalva de Oliveira AC, Vidal JE, Bryant J, Gallo RC: International NeuroAIDS: Prospects of HIV-1 associated neurological complications. Cell Res 15:962–969, 2005.

9.

Vidal JE, Hernandez AV, de Oliveira AC, Dauar RF, Barbosa SP Jr, Focaccia R: Cerebral toxoplasmosis in HIV-positive patients in Brazil: Clinical features and predictors of treatment response in the HAART era. AIDS Patient Care STDS 19:626–634, 2005.