Opportunistic infections of the CNS in patients with AIDS: diagnosis and management

Abstract

The CNS is the second most commonly affected organ in patients with AIDS. Many opportunistic infections may involve the brain, but the four most frequent conditions are toxoplasmosis, progressive multifocal leukoencephalopathy (PML), cryptococcosis and cytomegalovirus infection. Although the incidence of these infections among patients with AIDS has decreased in the past years as a consequence of the introduction of highly active antiretroviral therapy (HAART), they remain a major cause of morbidity and mortality in this patient group. This article summarises the clinical manifestations, diagnostic procedures and management strategies for these four conditions. The clinical manifestations are nonspecific and depend on the type and location of the lesions. In clinical practice, the diagnosis of these entities is made with noninvasive methods. Imaging studies, especially magnetic resonance imaging, are very useful for the diagnosis of toxoplasmic encephalitis and PML, although their usefulness for the diagnosis of cryptococcal meningitis and cytomegalovirus infections is lower. The presence of multiple ring-enhancing lesions with surrounding oedema and mass effect is characteristic of toxoplasmosis. The response to antitoxoplasmic therapy, which is usually observed within the first 2 weeks, is also used for diagnostic purposes. Molecular methods applied to the CSF are essential for the diagnosis of PML and cytomegalovirus infections. In addition, the quantification of viral DNA of both JC virus (the causative agent of PML) and cytomegalovirus has prognostic implications and may serve to evaluate the response to therapy. Cryptococcosis may be easily diagnosed by CSF stains and cultures, as well as by the detection of the cryptococcal capsular polysaccharide antigen in the blood and, especially, the CSF. Effective treatments are available for toxoplasmosis and cryptococcosis, although adverse effects are common and some patients may not respond to therapy. In contrast, there is no specific treatment for PML, and the efficacy of anticytomegalovirus therapy is poor and the toxicity significant. HAART has improved the outcome of patients with AIDS who have infections of the CNS, and the initiation of this therapy is mandatory for all patients with such infections, particularly in those conditions for which effective therapy is not available. Lifelong secondary prophylaxis with agents for the opportunistic infections was necessary before the HAART era because the risk of recurrence was very high if only induction therapy was administered. However, today, the discontinuation of secondary prophylaxis in patients treated with HAART who have stably reached a certain immune reconstitution is possible.