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, Applications in MRI.
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
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.
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
-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,
although they may be detected on the basis of diffusion tensor
or by proton spectroscopy.
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.
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
) is a protozoan. It is a nosocomial infection characterized by
multiple ring-enhancing lesions in the brain
(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).
Primary CNS lymphoma
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.
) 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.
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
(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
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.
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