The AIDS epidemic continues and, at least at the time of this writing, there is no known cure. Although it was originally thought to only affect the homosexual male and intravenous drug-abusing populations, it is now clearly found in the heterosexual community. As AIDS patients are being kept alive longer with new treatments, an increasing number are developing CNS manifestations. Magnetic resonance is clearly the imaging modality of choice to evaluate such patients, as described in this issue of Applied Imaging.­­William G. Bradley, Jr., MD, PhD, FACR

Acquired immunodeficiency syndrome (AIDS) can be found in cancer patients and those who are chronically debilitated. This article, however, will focus on patients who are infected with the human immunodeficiency virus (HIV). The theory du jour is that HIV first appeared in the human population in Africa in the late 1950s due to an inadvertent interspecies transmission of a simian immunodeficiency virus (SIV) through a bad batch of oral polio vaccine. (Monkey kidneys were used in the tissue culture to grow the oral polio vaccine.) AIDS is characterized clinically by lymphopenia with opportunistic infection by multiple nosocomial organisms as well as by characteristic malignancies, e.g., Kaposi sarcoma and lymphoma. This issue of Applied Imaging will address the appearance of AIDS in MR imaging of the brain.

Ten percent of patients with AIDS will present with central nervous system (CNS) manifestations. More than 65% of patients with AIDS will develop CNS manifestations before they die. Unfortunately, more than one disease can be present at a given time, occasionally necessitating multiple biopsies. ¹

HIV Encephalitis

Being "HIV positive" means that there are antibodies to HIV in the serum and does not necessarily mean HIV has infected the brain. Dementia is the earliest clinical manifestation of HIV infection of the brain. On MR images, prominent ventricles and sulci are noted (Figure 1), indicative of atrophy (the so-called "AIDS dementia complex"). With advancing disease, abnormal signal intensity can be found on T ₂ -weighted (T2WI) MR images in the white matter in a diffuse or focal pattern (Figure 2), the former known as "dirty white matter." These lesions tend not to enhance with gadolinium, ² although they may be detected on the basis of diffusion tensor abnormalities ³ or by proton spectroscopy. ⁴

HIV is the most common viral infection of the brain in patients with AIDS. MR spectroscopy (MRS) can be used to follow HIV encephalopathy by demonstrating progressive loss of N-acetyl-aspartate (NAA), which is a marker of viable neurons. ⁴ Cytomegalovirus (CMV) is a nosocomial viral infection occasionally affecting the brain of AIDS patients, although much less commonly than HIV. It can be recognized by linear enhancement of the ependyma in the brain and the nerve roots in the spine (Figure 3).

Toxoplasmosis

Toxoplasmosis ( Toxoplasma gondii ) is a protozoan. It is a nosocomial infection characterized by multiple ring-enhancing lesions in the brain ⁵ (Figure 4). The MR finding of such lesions generally prompts a 2- to 3-week course of treatment with pyrimethamine sulfadiazine and rescanning with MRI to gauge response. If there is no response, brain biopsy is generally performed as necrotic lymphoma can occasionally simulate toxoplasmosis. MR spectroscopy can also be used to distinguish these two entities, lymphoma demonstrating elevated choline (as do all malignancies) while toxoplasmosis demonstrates decreased choline and elevated amino acids due to the action of proteases on proteins (Figure 5).

Lymphoma

Primary CNS lymphoma ⁶ tends to be centrally located in AIDS patients (Figure 6). It is one of two lesions that can cross the corpus callosum (glioblastoma multiforme [GBM] being the other). These two entities can often be distinguished on the basis of T2WI, GBM appearing brighter than lymphoma. Both lesions tend to enhance with gadolinium, although GBM tends to not enhance centrally due to necrosis. On diffusion-weighted images, lymphoma may demonstrate mild hyperintensity due to restricted diffusion of water while GBM is usually decreased in intensity. The low signal on T2WI images and the restricted diffusion are both due to the high nuclear-cytoplasmic ratio in lymphoma.

Cryptococcosus

Cryptococcosis ( Cryptococcus neoformans ) is the most common fungal infection in AIDS. Like other fungal infections, it tends to produce a basilar meningitis. Unfortunately, cryptococcal meningitis only enhances about a third of the time with gadolinium. ⁷ It is typically recognized on the basis of enlarged perivascular ("Virchow-Robin") spaces surrounding the lenticulostriate arteries as they arise from the M1 segment of the middle cerebral artery at the base of the brain (Figure 7). These VR spaces are filled with a gelatinous pseudocyst that represents the yeast form of the fungus. These are relatively benign manifestations of the infection and do not enhance with gadolinium, i.e., they are not cryptococcomas ⁷ (which are fairly uncommon in AIDS patients).

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is an indolent viral infection that rarely enhances or causes mass effect. It is caused by a papova virus known as the "JC" virus (no relationship to Jakob Creutzfeldt).

PML most commonly affects the subcortical white matter in the high parietal region (Figure 8) and the middle cerebellar peduncle (Figure 9), however, it can occur anywhere in the brain. It is often multifocal (as the name implies), however, in one series, it was unifocal 40% of the time. Although magnetization transfer ⁸ may be able to distinguish HIV encephalitis from PML, at present PML is a diagnosis that can only be made by biopsy and, from a management standpoint, it is an important diagnosis to make. In the NYU series, the patients died an average of 4 weeks following confirmation of diagnosis. On the other hand, recent experience with highly active antiretroviral therapy is looking promising for treatment of PML. ^9,10

Conclusion

MRI (and occasionally MR spectroscopy) should be performed on all HIV-positive patients with CNS symptoms. In our institution, a routine unenhanced study of the brain (including FLAIR) is performed since gadolinium does not increase sensitivity for the detection of the disease. If abnormal signal is found, however, gadolinium is always given since it is useful to distinguish processes that generally enhance (toxoplasmosis, lymphoma, and CMV) from processes that generally do not enhance (HIV and PML). While most centers will treat enhancing lesions medically without a biopsy (presuming toxoplasmosis), we generally perform spectroscopy in such cases to distinguish toxoplasmosis from necrotic lymphoma.