Neuroradiology Harris

S. Chrysikopoulos,

John

R. Hesselink,

#{149} Gary

MD

MD

#{149} Clayton

Encephalitis Immunodeficiency MR Imaging Clinical and

A. Press, MD A. Wiley, MD

tion,

13.203,

Brain,

MR

ter, 13.253 ma, 10.349

Radiology

Brain,

CT,

13.2054. studies,

13.2065, 13.1214

#{149} Encephalitis, #{149} Viruses,

1990;

13.1211

#{149} Brain,

13.2066, #{149} Brain,

13.253 13.2065,

MD

#{149}

by Human Virus: CT and Manifestations with Pathologic Correlation’

N

EUROLOGIC

infec-

findings

white #{149} Kaposi

travenous

occurs

may

be related

to AIDS-

associated neoplasms tic infections, a more

on opportuniscommon abnon-

mality

subconticab

is progressive

mentia, thy

termed

(1,2).

AIDS

This

is

encephalitis.

AND

METHODS

Subjects Review of neuropathologic records over a 6-year period (1982-1987) at our institution revealed 140 autopsies on patients

with

AIDS.

HIV

alone

or together

with other infectious agents or lymphoma was identified in the brains of 39 of scans,

patients. MR

Premortem

images,

for the

cranial

or both

evaluation

had

CT

been

ob-

symptoms

sarco-

tients and constitute the focus of this meport. The study population included 23 men and one woman with a mean age of 37 years (range, 27-67 years). Risk factors included homosexuality in 20 patients, in-

13.2066

175:185-191

signs

in

24 of these

patient

remaining

of a patient

with

AIDS was diagnosed to the criteria of the

Control

School

of

vember C

RSNA,

22,

Medicine,

1989; 1990

UCSD

accepted

of Radiology of Pathology Medical

January

and

the Magnetic Resonance (M.R.G., C.A.W.), University

Center,

225

9. 1990.

Address

Dickinson

reprint

St.

San

pa-

requests

Institute (H.S.C., GAP., of California, San Diego Diego,

CA

to GAP.

92103.

Received

been

the

In every

clinically Centers

wife

case,

according for Disease

(12,13).

Fourteen aminations

patients underwent and 22 underwent

MR cxCT studies.

The hospital and outpatient records, in addition to autopsy data, were available with

these

the imaging

cal Systems,

data

were

findings

All MR studies 1 .5-T superconducting

were

correlated

of the CNS.

performed with a magnet (GE Mcdi-

Milwaukee).

In all patients,

proton densityand T2-weighted images in the axial plane were acquired with the following parameters: 2,000/25, 70 (two excitations) or 3,000/30, 80 (one excitation) (repetition time [TR] msec/echo

time [TE] msec). In six patients, the initial sequence was repeated in the coronal plane and/or a Ti-weighted sequence (600/25, two excitations) was performed in the sagittal plane. Section thickness was 5 mm, with an intersection gap of 2.5 mm in all examinations. The field of view was 20 or 24 cm, with an acquisition and display matrix size of 256 X 256. In the 22 patients who underwent CT, axial, 10-mm-thick, contiguous sections from the fonamen magnum to the vertex

were

obtained

nous

administration

(150

mL

before

and after

intrave-

of contrast

of Conray-60

material

[Mallinckrodt

Mcd-

ical, St Louis]) in all patients. Three of the authors reviewed metrospectively all of the MR and CT studies

findings were divided into four categonies: (a) Atrophy-Dilatation of the yentniculan system out of proportion to the sulci and dominantly

cisterns central

enlargement

ficiency

was interpreted atrophy (there

of the

Abbreviations: From the Department J.R.H.) and the Department I

had

AIDS.

in

in one. The

without knowledge of distribution of the pathologic abnormalities. The radiologic

of neunologic

mat-

and

homosexuality

one

for all patients;

Although

many reports illustrate findings of AIDS-associated tumors and infections at computed tomography (CT) or magnetic resonance (MR) imaging (3-9), few depict the imaging manifestations of HIV encephalitis (10,1 1). In this study, we describe the cranial appearance of 24 patients with histopathologically confirmed HIV encephabitis at MR imaging and CT and correlate imaging results with clinicab and pathologic data. PATIENTS

use and

transfusion

Neuroradiology

encephabopathy

(HIV)-HIV

drug

two, and blood

de-

encephabopa-

thought to be due to infection within the central nervous system (CNS) by human immunodeficicncy virus

tamed

13.2074

dysfunction

frequently in patients with acquired immunodcficiency syndrome (AIDS). Although focal neurobogic

these terms:

R. Grafe,

Caused

To determine the computed tomographic (CT) and magnetic resonance (MR) imaging manifestations of central nervous system (CNS) infection by the human immunodeficiency virus (HIV), the authors analyzed the results of imaging of the CNS in 24 patients with HIV encephalitis confirmed at autopsy. Careful pathologic correlation demonstrated that neither CT nor MR imaging enabled detection of microglial nodules with multinucleated giant cells, the hallmark of HIV encephalitis seen in all 24 affected patients. The most common abnormality observed on images of the CNS was atrophy, demonstrated in 18 patients. Demyelination and vacuolation of white matter tracts accompanying severe HIV infection caused hypoattenuation on CT scans and hyperintensity on T2-weighted MR images. These lesions had no mass effect. MR imaging was more sensitive than CT in the detection of lesions caused by HIV or other superimposed infectious agents. Although it is often difficult to attribute any radiologic appearance to a single etiologic agent in patients with acquired immunodeficiency syndrome, the combination of atrophy and symmetric, periventricular or diffuse white matter disease suggests HIV encephalitis. Index

#{149} Marjorie

AIDS

syndrome.

= cerebrospinal munodeficiency

ed giant

cell,

PML

virus,

horns

acquired

CMV

CSF No-

temporal

as prewas no

to

immunode-

cytomegalovirus.

fluid, HIV MNGC

progressive

=

human multinucleat-

im-

multifocal

leukoencephalopathy.

185

Figure

1.

Axial,

noncontrast

CT images

from 33-year-old man with severe CNS HIV encephalitis only, obtained 3.5 months before death, demonstrate a greater degree of ventricular

dilatation

ing (arrows), phy

greater

suggest sulci

(V) than sulcal with central peripheral atrophy.

widenatro-

compatible than

hydrocephalus); exceeding

prominence

that

of

of the ventricles

was

interpreted as predominantly peripheral atrophy. The location of parenchymal volume loss (supra- and/or infratentonial) was recorded also. (b) White matter disease-Abnormal WM density or signal intensity without mass effect. (c) Gray matter disease-Abnormal gray matter density or signal intensity without mass effect. (d) Mass lesions-Lesions associated with edema, compression of adjacent structures, or both. Neuropathology Every brain was sectioned in the coronab plane at i-cm intervals. Routine regions (frontal, temporal, parietal, and occipital cortex; basal ganglia; thalamus; pineal gland; cerebellum; midbrain; and medulla), in addition to grossly abnormal regions, were sampled and paraffin em-

bedded

for histologic

several

cases,

examination.

additional

a.

b.

In

grossly

unre-

markable but radiologically abnormal mcgions were sampled for histologic study. All sections were stained with hematoxybin and eosin and examined for histopathologic features. Sections of temporal cortex cortex,

(including hippocampus), panietal basal ganglia, and thalamus were

stained for the HIV envelope glycoprotein 4i with methods described previously (14). Furthermore, sections for histopathologically abnormal regions were stained

with

(a) HIV

4i;

hematoxybin

for which a polycbonal sciences, Wamnington, (c) herpes

simplex antiserum

lycbonal

and

for

eosin

(CMV), antiserum (PobyPa) was used (15);

(b) cytomegabovirus

virus, (Dako,

for which Carpentenia,

a po-

was used; (d) Toxoplasma organisms, for which a primary cheetah antiserum was used; and (e) papovavirus (which Calif)

causes

progressive

mubtifocab

leukoence-

phalopathy

[PML]), for which in situ hybridization with a biotinylatcd probe to the JC virus was used (16). HIV encephalitis was graded mild, moderate, or severe according to the number of infected cells per focus and the

number

of foci

per

slide.

The

pres-

ence of rare HIV-positive cells (fewer than one cell per 10-power field) with or without microglial nodules was designated mild infection. The finding of occasional HIV-positive cells (more than one cell per ten 10-power fields but fewer than one cell per 10-power field) with microgliab

nodules

with

or without

multinu-

cleated giant cells (MNGCs) was graded moderate. The presence of frequent HIVpositive cells (at least one cell per 10power field) with frequent microglial nodules and with MNGCs was graded severe. 186

Radiology

#{149}

a. Figure cephalitis

b. 2.

Axial, only,

matter lucency (b) compatible

noncontrast obtained 4.5

(L) without with

CT images from 30-year-old man months prior to death, demonstrate

mass

HIV-induced

effect

within

demyelination

RESULTS Clinical

and

Laboratory

Data

The diagnosis of AIDS was establishcd from 2 months to 3 years prior to death in each patient by means of well-established clinical criteria (12,13); moreover, the serum of every patient who presented with symptoms after 1984 tested positive on the enzyme-linked immunosorbent assay and Western blot test for HIV antibodies. The most common initial manifestation of AIDS was Pneumocystis carmu pneumonia (13 patients [54%]),

the forceps seen

with severe CNS diffuse, symmetric,

minor

(a) and

corona

HIV

enwhite

madiata

at autopsy.

followed by opportunistic infections (eg, candidiasis, CNS toxoplasmosis, or disseminated infection from Mycobacterium organisms, Cryptococcus organisms, herpes simplex virus, or CMV) (seven patients [29%]), Kaposi

sarcoma

(three

lymphoma Neumobogic

(one

patients

[12%]),

patient symptoms

[4%]). and

were

the

in six

patients

(25%):

seizures

in one,

four, sis

presenting

in one.

ic dysfunction population

cranial

The

spectrum

occurring included

ncuropathics,

features

and signs

of AIDS

dementia

and

in

hcmipamcof neurobog-

in our peripheral

study and

myclitis,

ataxia, April

1990

b. Figure

3.

Images

sity-weighted out mass effect

trum

of 27-year-old

(b, c) images within the

semiovale

(arrows,

obtained pons and

(patient

1 month prior middle cerebellar

in 15 Patients Correlation Focal

Studied

1

Not done White

3 4

ease; focal (temporal lobe and pons) NFL NFL*

5

Not

6

Deep

matter

dis-

done

7

NFL

8

White

severe

CNS

to death demonstrate peduncles (arrows,

3 Months

matter

or Less

Supratentorial Atrophy

CT

2

disease, tamen)

1) with

Lesions

MR Imaging

gray

c.

14 in Table

HIV encephalitis

symmetric a), forceps

regions major,

before

Death:

CT/MR Imaging Interval

HIV Encephalitis

NFL

Severe

NA

Mild

NFL*

None

3 d

Severe

Not done NFL

Mild Mild

NA

Mild

1 mo

Moderate

NFL

Mild

NA

Moderate

Moderate

NA

Severe

Moderate

3 wk

Moderate

Moderate

5 d

Severe

Not

done

focal (puNFL*

matter

White

dis-

matter

dis-

9 10

ease; diffuse, confluent (supra- and infratentonial) Not done Not done

ease,* focal (occipital lobe, right cerebellum) Normal Normal

None None

NA NA

Severe Severe

11

NFL*

NFL

Mild

1.5 mo

Severe

12

NFL

NFL*

None

10 d

Mild

13

White matter disease*; multifocal

NFL

Mild

1 wk

Moderate

NFL*

Mild

1 mo

Severe

NFL

Moderate

NA

Mild

14

(frontal lobes) White matter disease; diffuse (su-

pra- and infraten-

15 Note-NFL * Initial

tonal)

and

matter

disease

gray

(un-

ifocal, putamen) Not done =

only.

Axial

of abnormally forceps minor,

no focal

examination

bowel

and

lesions,

NA

bladder

not applicable.

=

incontinence.

(75%) suffered encephabopathy

(somnolence, decreased attention span, slowed speech, flat affect, paired memory, disorientation, difficulty in word finding) for 175

proton

den-

months) revealed (a) normal results in 1 1 patients (seven of whom had severe HIV encephalitis), (b) a mild increase in CSF total protein levels without pleocytosis in eight patients with moderate or severe HIV encephalitis (with on without supcmimposed CMV, PML, or toxoplasmosis), and (c) a marked increase in CSF total protein levels (greater than twice the upper limit of normal in our babonatory) or pleocytosis in three patients with HIV and superimposed active CNS toxoplasmosis, cryptococcosis, or lymphoma (proved with cultures

or biopsy

performed.

Eighteen patients from a progressive

Volume

(a) and

increased signal intensity withbasal ganglia (arrows, b), and cen-

sy in most patients. However, three patients with severe HIV cnccphalitis had no dementia, and one with seveme HIV encephalitis and PML had only mild dementia. Measurements of total protein and glucose bevels as well as cellular analysis of 39 cenebrospinal fluid (CSF) samples from 22 patients (obtained 1 week to 24 months prior to death; the mean pmemontcm interval was 6

#{149} Number

1

imand 3-12

months

prior

to death.

Most

patients

in this group were unable to care for themselves for varying periods of time prior to death. Theme was good correlation between the severity of dementia and severity of HIV encephalitis at autop-

samples).

Routine

and viral (not including tunes of all specimens growth.

Pathologic and

T2-weighted

c).

Table 1 HIV-induced Lesions Radiologic-Pathologic

Patient

man

HIV) revealed

bacterial cubno

Data

The brains of our 24 study patients demonstrated diverse pathologic findings consistent with previously described

subacute

encephalitis

20). The

distinct

histopathobogic

pcarance reliable

of HIV encephalitis differentiation from Radiology

(i7-

appermits other vi#{149} 187

nab encephalitides. CNS inflammation affected predominantly the white matter and deep nuclear structunes; infiltration of the parcnchyma and penivascular spaces by bymphocytes and macnophages was seen. Reactive astrocytosis was demonstrated frequently. In severe infections, MNGCs were identified within the mononuclear infiltrate. Multiple small nodules composed of microgha, astrocytes, and occasional macrophagcs (microglial nodules) were often present, most commonly in the

cortex

and

basal

ganglia

and

infre-

quently in the white matter. Focal aneas of demyclination on diffuse white matter vacuolation were also seen occasionally. HIV encephalitis was disclosed in seven patients (29%) without other superimposed infectious on neoplastic processes. Coexisting disease was found in the remaining 17 patients (71%): CMV infection in nine (38%), CMV infection and toxoplasmosis in three (12%), PML in two (8%), lymphoma in two (8%), and CMV infection and cryptococcosis in one (4%). The severity of HIV encephalitis was graded mild in six patients (25%), moderate in five patients (21%), and severe in 13 patients (54%). The vast majority of HIV lesions detected by means of histologic cxamination were not seen at gross inspection of the brain. No focal mass lesions could be attributed to HIV infection alone.

a.

b.

d.

C.

Figure

4.

alitis,

Images

CMV

weighted

Imaging

Studies

Twenty-two patients were exammed with CT; 12 underwent multiple examinations. MR imaging studies were performed in 14 patients, four of whom underwent serial scanning. The interval between the final pncmortem MR imaging study and autopsy was less than 3 months in eight patients, 3-6 months in four patients, and 12-18 months in two patients. The interval between the final premortem CT study and autopsy was less than 3 months in 13 patients, 3-6 months in four patients, and 7-15 months in five patients. In 15 paticnts, the final premortem imaging study was performed 3 months or less before death. Their MR. CT, and pathologic findings attributable to HIV arc presented in Table 1 . Because of the relatively slow progmession of subacute HIV encephalitis, we believe that a 3-month window accommodates accurate madiobogic and pathologic correlation. A detailed description of imaging studies 188

Radiology

#{149}

from

38-year-old

encephalitis,

and

(b) images

man

(patient

toxoplasmosis.

demonstrate

Axial

toxoplasmosis

2 in

Table

1) with

T2-weighted

abscesses

severe

(a) and

with

surrounding

CNS

proton

HIV

enceph-

density-

edema

and

mass effect in both basal ganglia (arrow, a, b). Lower 12-weighted sections (c, d) show two additional lesions caused by a combination of HIV (predominantly) and CMV in the medial temporal lobe (arrow, c) and the right middle cerebellar peduncle (arrows, d). The temporal lobe lesion had a hypenmntense center, isointense rim, and surrounding hypenintense edema on 12- and proton density-weighted images. This lesion was indistinguishable from the toxoplasmosis seen also in this patient. The infratentorial lesion was smaller, poorly defined, and hyperintense; minimal effacement of the adjacent fourth ventricle is seen (d).

in all

24 patients

follows.

HIV encephalitis-Seven patients had encephalitis caused exclusively by HIV. Cerebral atrophy (moderate on severe) was seen in five patients (central atrophy greater than peniph-

cral

atrophy

in four

trab

atrophy

equivalent

atrophy in one crab, symmetric

patients

and

ccn-

to peripheral

patient) white

(Fig matter

1). Bilatdisease

was seen in three patients: diffuse white matter disease in two patients and third

pemivcntmicubam patient (Figs

had normal CT of death despite

encephalitis sions

in any

were

patient

disease in the 2, 3). Two patients

scans within 3 weeks severe, diffuse HIV

at autopsy. seen

on

CT

in this

No mass or MR

group.

be-

images

HIV and CMV encephalitis-Of nine patients with HIV and CMV encephalitis, eight had mild or modemate CNS atrophy (central atrophy predominant in five, peripheral atmophy predominant in two, and central atrophy equivalent to peripheral atmophy in one); two patients had a singbc small high-attenuation mass be-

sion

caused

by a hemorrhagic

infarc-

tion. These infanctions were attributed to CMV because pathobogic examination disclosed a focal accumubation of cytomegalic cells. Two patients had mubtifocab white matter infamcts, also attributed to CMV, and a single focus of deep gray matter disease attributed to HIV. One patient with HIV and CMV encephalitis April

1990

on gray matter disease in two patients, multiple foci of white matter disease in four patients, and diffuse white matter disease in one patient.

b. Figure 5. Images from 44-year-old man with severe HIV encephalitis and PML. Coronal T2-weighted (a) and Ti-weighted (b) images obtained 5.5 months prior to death demonstrate asymmetric white matter disease without mass effect within the region of the parietooccipital junction (arrows). At pathologic examination, these lesions were shown to have been caused by HIV and PML. Dilated occipital horns (v) are seen also.

also in this patient smaller mass lesion

Table 2 Distribution of HIV Lesions in Imaging Studies in All 24 Patients No.

White matter disease Diffuse (confluent,

supra-

bi4

Peniventricular

(lateral

ventricle)

1

Focal and/or multifocal (supra- and/or infratentonial) Deep gray matter disease Putamen Note-Only nantly due

of

and/or

infratentonial)

4

lymphoma.-There

lesions exclusively or predomito HIV are included in this table.

with

simultaneous

by HIV

alitis.-Thmcc

patients

had

this prior enceph-

simulta-

neous CNS infection with HIV, CMV, and Toxoplasma organisms. Mild or moderate atrophy was seen in two patients (greater centrally in one patient and peripherally in the other). Mass lesions attributed to toxoplasmosis (Fig 4) were seen in all. One patient had diffuse white matter disease, attributed to HIV, seen at MR imaging. In one patient, two mass lesions due to a combination of HIV and CMV were noted in the right tempoma! lobe and night middle cerebellar peduncle. The temporal lobe lesion had an isointense periphery and hypenintense center (compared with white matter on proton densityand T2-weightcd images) and induced

surrounding

high-signal-intensity

edema; this lesion abbe from Toxoplasma

Volume

175

#{149} Number

was

indistinguish-

abscesses 1

density-

coinfection (Fig HIV encephalitis

2

had a normal CT scan; however, scan was obtained 10 months death. HIV, CMV, and Toxoplasma

proton

weighted images. HIV encephalitis two patients with and PML demonstrated (moderate, central peripheral atrophy and severe atrophy dominance in the both had bilateral white matter disease

Patients

Lesions

lateral,

on both

seen

to

was phy ease lesions two

mild

and

(Fig 4). The other, was hypemintense

and

T2-

and PML.-Thc HIV encephalitis CNS atrophy atrophy equal to in one patient with central pmeother). In addition, but asymmetric in regions of

5). and primary CNS were two patients CNS involvement

lymphoma.

Lymphoma

associated with mild central atnoand unifocab white matter disin one patient and multiple mass in the other patient. In these patients, HIV encephalitis was

without

any

radiobogic

manifes-

tations. HIV, CMV, and Cryptococcus encephalitis.-Mild cortical atrophy was the only abnormality identified in the one patient with this multipleagent-induced encephalitis. Table 2 summarizes the distnibution of lesions exclusively on predominantly due to HIV and identified on CT scans, MR images, on both in all 24 patients. Comparison of MR imaging and CT.Both MR imaging and CT were performed in 12 patients. MR imaging was more sensitive for the detection of CNS abnormalities in eight pa-

tients:

MR

imaging

enabled

detection

of additional lesions caused by HIV in four patients, toxoplasmosis in three patients, and lymphoma in one patient. The additional HIV lesions detected with MR imaging appeared as solitary foci of white matter and!

MR and CT were equably sensitive in the remaining four patients: one patient with diffuse asymmetric white matter disease and three patients with atrophy only. When compared with Ti-weighted and proton density-weighted images, the T2-weighted images were superior for detecting lesions, delineating their margins, and separating a central mass from surrounding edema (Fig 4).

HIV

Encephalitis: Imaging Pathologic Correlation

and

Several abnormalities revealed by imaging of the CNS were confidently attributed to HIV infection at pathologic examination. In some patients, the abnormalities were undoubtedly accentuated by coexistent infections: Atrophy.-Supratcntonial atrophy occurred in 18 patients. In 12 patients, central atrophy revealed by CT, MR imaging, on both exceeded peripheral volume loss and conrebated well with the neuropathobogic distribution of the HIV lesions. In the autopsy material, HIV affected predominantly the deep white matten with lesser involvement of the subcortical white matter and relative sparing of the cerebral cortex. Infratentonial atrophy was seen after imaging studies in 12 patients in conjunction with atrophy of the cerebral hemispheres. Serial studies (CT, MR imaging, or both) oven an interval of V/2-ii months in 16 patients mcvealed progression of atrophy in 10 of them. White matter disease.-Extcnsivc, nearly symmetric, deep white matter disease associated with severe HIV encephalitis was seen by means of CT

on MR imaging with tonal seen

moderate atrophy. as regions

in four

of 1 1 patients

or marked supratenThese lesions were of bow attenuation

on

CT scans or as regions of high signal intensity on proton densityor T2weighted MR images relative to normal panenchyma. HIV also caused smaller (less than 1 cm) white matter or deep gray matter (basal ganglia) lesions evident only as focal regions of hypenintensity on T2-weighted images. Posterior fossa white matter disease induced by HIV (seen in two patients) was patchy on was merged with abnormally hypcnintcnsc fiber tracts descending from the cerebral cortex. Isolated infmatcntonial white Radiology

#{149} 189

matter disease was not seen. Abnormalities detected with imaging of the CNS correlated well with pathologic findings. Nevertheless, many HIV lesions seen at pathologic examination were not detected with MR imaging and CT. For example, cortical microglial nodules seen at autopsy in eight patients remained undisclosed by imaging of the CNS. In addition, although cerebral white matter and/or deep gray matter HIV lesions were present at autopsy in all 24 patients in our study, such lesions were demonstrated by imaging of the CNS in only eight patients. In only two of eight patients with brain stem or cerebellan HIV lesions at pathobog-

ic examination

did

MR

imaging

on

CT show an abnormality in the comesponding location. Even when positive, both MR imaging and CT were grossly inadequate in showing the true extent of parcnchymal disease in all instances.

DISCUSSION The neurologic AIDS arc protean cal series report

39% (21,22).

complications and common; an incidence

In a significant

of cliniof 31%-

propon-

tion (10%) of AIDS patients, ncunologic abnormalities arc the presenting complaint (22). Recently, much attention has been directed to the AIDS-dementia complex that afflicts 36%-75% of patients

during

the

course

of their

illness

(1,2,21-24). The results of extensive research suggest a direct role of HIV in the pathogenesis of this prognessive encephalitis: (a) The virus has been recovered from CSF, the brain, spinal cord, retina, and peripheral nerve of patients with HI V-related neurobogic syndromes (25-27); (b) HIV DNA and RNA sequences and HIV proteins have been identified in the CSF of such patients by antigen-capture techniques (14,2830); (c) HIV-specific immunoglobulin and antigen have also been detected in CSF (25,31); and (d) HIV within the CNS has been identified at momphobogic examination of patients with AIDS-related cncephabopathy (14,28-30,32). Studies of the neuropathologic pcct of AIDS have shown a wide

spectrum

of abnormalities

as-

in more

than 75% of autopsies; approximately 33% of the cases demonstrate cvidence of viral encephalitis. Prior to the advent of immunocytochemical and nucleic acid probes, it was impossible to define the specific viral agent responsible for the CNS in190

Radiology

#{149}

flammation.

These

techniques HIV and

new

laboratory

often demonstrate CMV in regions

cephalitis.

Microglial

both of viral en-

nodules

and

pemivascuban MNGCs accompanying gliosis of deep white and gray matter are most commonly associated with HIV infection alone or in combination with CMV. Several reports mdicate that the amount of virus (HIV or CMV) present in the CNS does not correlate with the severity and extent of the inflammatory changes (14). In our series, MR imaging and CT depicted reliably the CNS volume

loss

that

may

accompany

HIV

infec-

tion. The predominantly central vobume loss shown in most affected patients correlates well with the pmeponderance of deep white and gray matter HIV lesions seen at pathologic examination. Nevertheless, no come-

lation

was

found

between

the

degree

of volume boss and the severity of HIV infection in our series; indeed, in several patients with severe HIV

encephalitis at pathologic examination, no atrophy was demonstrated by imaging studies performed within 3 months of death. In addition, there was no correlation between the severity of dementia and the severity of atrophy or white matter disease. Both imaging techniques were insensitive for the detection of microgliab nodules induced by HIV or CMV. Cortical involvement by either virus was not seen on CT scans or MR images of any patient. Only the white matter regions most severely involved with HIV infection were detected with radiobogic studies. In our study, MR imaging enabled iden-

tification lesions

of more infratentonial than reported previously

HIV (10).

The use of a middle-field-strength (0.5-T) magnet and 10-mm-thick

the

microglial

The

long

interval

between the MR imaging

in four

of our

nodule (7-18

of our study. Imaging this group of patients

This

observation

of antigen

for

fied with methods).

each

organism

of the high polymicrobiab

sions

where

multiple

in

that

in the

it is very attnifound etiobogic extends to of CNS be-

agents,

evaluation

AIDS-rebated

particu-

mass

is more lesions

are

matter

disease,

mass lesions, involvement

MR

sensitive than CT. If detected by means of HIV infection alone presence of diffuse

imaging studies, is unlikely. The white

of suspected

encephabopathy,

imaging

in addition

to

suggests superimposed with HIV. Asymmetric

white matter disease predominating in the pamietooccipitab regions can occur with either PML alone or PML combined with HIV infection. The diagnosis of HIV encephalitis can be

suggested

by the

combination

trab atrophy and tnicubam or diffuse ease. U

rum the

symmetric white

was San

Primary

donated Diego

by

Kurt

of cen-

penivenmatter dis-

cheetah

antise-

Benirschke,

MD,

and

Zoo.

References 1.

Navia AIDS tunes.

2.

Navia

BA,

Jordan

as the

3.

BD,

BA,

Price

RW.

presenting Neuro! WM,

1987;

findings. MJD,

ma!

5.

Post Central quired spective

contrast 1985;

MJD,

fea-

acquired

immucomplex

manifestation

of

virus

infection.

44:65-69.

Brant-Zawadzki

M.

Acquired

syndrome: Radiology

neuronadio1983;

Kunsunoglu

149:485-

SJ. Hensley

Chan JC, Moskowitz Cranial CT in acquired syndrome: spectrum AJNR

The

dementia

or sole

immunodeficiency

4.

The

immunodeficiency

Arch

491. Post

RW.

I. Clinical 19:517-524.

syndrome

Kelly logic

Price

dementia complex. Ann Neurol 1986;

nodeficiency

fumthcm

the insensitivity of MR imaging and CT in the evaluation of HIV cncephabitis, especially during its early phase. Although a large number (7i%) of

of nco-

larby HIV and CMV, are found in individuab foci and even in individual cells (33). In conclusion, our data indicate

months)

of the CNS was nommab.

frequency and/on

plastic conditions in AIDS, often difficult to confidently bute radiobogic abnormalities in such patients to a single agent. The same difficulty the pathologic evaluation

human

CT on death

(identi-

immunocytochemicab

Because coexistent

is a limitation

emphasizes

the relative contribution of process to any given lesion.

Such quantitative assessment was carried out by correlating the severity of encephalitis with the amount

(10).

final prcmomtem examination and

patients

grade each

Acknowledgments: 5cc-

tions for some of the examinations in the previous study (10) may account for this discrepancy. The regions of focal on diffuse white matter abnommality detected occasionally by means of imaging studies most often reflects secondary demyclination and gliosis rather than the primary CNS

lesion,

our patients had additional infectious agents or neopbasms that were superimposed on a background of HIV encephabitis, careful pathologic assessment allowed us to separate and

GT,

LB.

Hoffman TA. immunodeficiency of diseases and opti-

enhancement

techniques.

6:743-754.

Sheldon

JJ,

Hensley

CT,

et a!.

nervous system disease in acimmunodeficiency syndrome: procorrelation using CT, MR imag-

April

1990

ing,

and

pathologic

studies.

Radiology

virus

6.

Levy

RM, Rosenbloom

Neuroradiologic

7.

8.

in AIDS: a review of 200 cases. AJNR 1986; 7:833-839. Gilleux MH, Steiner RE, Young JR. MR imaging in progressive multifocal leukoencephalopathy. AJNR 1986; 7:1033-

17.

1035.

18.

Sze

G, Brat-Zawadzki

Ramsey tions

1 1.

12.

of AIDS:

CT

MR

findings.

AJR

19.

RM, et al. HIV

encephali-

tis and meningitis. Olsen WL, Longo

AJR 1988; 151:373-380. FM, Mills CM, Norman

D.

disease

White

matter

ings at MR imaging. 169:445-448. Centers for Disease the case definition

in AIDS:

Radiology

20.

find-

for

Revision immuno-

national

MMWR

21. of

report-

1984;

34:373-

22.

syndrome.

1987; 36(suppl

1):3-l5. Wiley CA, Schrier RD. Nelson JA, Lampert PW, Oldstone MB. Cellular localization of human immunodeficiency virus the

brains

munodeficiency

n’s in AIDS

virus

and

encephalitis.

24. im-

W,

Burge

PC,

Snider

Levy

WD,

Neurol

1986;

Simpson

DM,

#{149} Number

1

de la Monte Hirsch MS. cephalomyelitis to HTLV-III 37:562-569.

27.

Pomerantz

RJ,

SM,

Infection

in

CE, Posner

JB.

RM,

Bredesen

DE,

Ann

Neurol

1988;

28.

GM,

quired

immune

29.

30.

31.

ML.

syndrome:

J Clin Pathol

virus

type I. N

Harper

infection

ME,

Hahn

BH,

in brains

et a!.

of children

with AIDS encephalopathy. 1985; 277:177-181. Gabuzda DH, Ho DD, de Ia Monte SM, Hirsch MS. Rota TA, Sobe! RA. Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol 1986; 20:289-295. Pumarola-Sune 1, Navia BA, Corolon-

C, Cho ES, Price RW.

in the brains of patients dementia complex. Ann 21:490-496. Resnick L, diManzo-Veronese synthesis tients

Intra

32.

HIV antigen

with the AIDS Neurol 1987; F, Schup-

blood-brain-barrier

of HTLV-III-specific with

neurologic

IgG symptoms

ed with AIDS or AIDS-related EngI J Med 1985; 313:1498-1504.

of

a

de La Monte retina by hu-

adults

Cardo

CD, in ac-

DR.

of the

Science

33.

Am

Shaw

and

23(suppl):527-

SL, Petito CL, Urmacher JB. Subacute encephalitis

Kuritzkes

1987; 317:1643-1647.

bach J, et a!.

533. Nielsen Posner

study.

J Med

HTLV-III

Neurologi-

Rosenblum

deficiency

et a!.

Engl

5, Gold

immune deof 50 patients.

SM, Ho DD, Schooley RI, Richardson EP. Subacute enof AIDS and its relation infection. Neurology 1987;

man immunodeficiency

19:525-535.

Nielsen

in paassociat-

complex.

N

Gyorky F, Melnick JL, Gyorky P. Human immunodeficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J Infect Dis 1987; 155:870876. Nelson JA, Reynolds-Kohler C, Oldsone

MBA, Wiley brain

cells

gy 1988;

CA. in patients

HIV and CMV coinfect with

AIDS.

Viro!o-

165:286-290.

1984;

82:678-682. 25.

Ho

DD,

lation id and

TR,

Schooley

of HTLV-III

Rota

from

neural syndromes

tissues

RI.

et a!.

cerebrospinal

of patients related

immunodeficiency syndrome. Med 1985; 313:1493-1497.

175

26.

Pro-

Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review the literature. J Neurosurg 1985; 62:475495. Price RW, Sidtis J, Rosenblum M. AIDS dementia complex: some current ques-

rologic

Volume

et a!.

leukoencephalopathy

Ann

postmortem

J Pathol

C, Nelson J. virus and JC

progressive

patients with acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 1985; 68:333-339. Petito CK, Navia BA, Cho E-S, Jordan BD, George DC, Price RW. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N EngI J Med 1985; 312:874-879. Anders KH, Guerra WF, Tomiyasu U, Vinters HV. The neuropathology of AIDS. Am J Pathol 1986; 124:537-558. Navia BA, Cho E-S, Petito CK, Price RW. The AIDS dementia complex. II. Neuro-

tions.

cytomegalovi-

Am

1988; 133:73-81. Wiley CA, Grafe M, Kennedy Human immunodeficiency

23.

of acquired

immune deficiency syndrome patients. Proc Natl Acad Sci 1986; 83:7089-7093. Wiley CA, Nelson JA. Role of human

with

cal complications of acquired ficiency syndrome: analysis Ann Neurol 1983; 14:403-418.

Control. Revision of case definition for ac-

immunodeficiency

within

P, Lang

diffuse

JWM, Metroka

ing: United States. 374. Centers for Disease

infection

Kleihues

pathology.

1988;

Control. of acquired

syndrome

MMWR

16.

D,

of 22:42-53.

CNS complica-

Post MJD, Tate LG, Quencer CT, MR and pathology in

quired

15.

GK.

and

CDC surveillance

14.

Norman

patients

leukoencephalopathy. Acta (Berl) 1988; 76:338-346.

gressive

151:449-454.

deficiency

13.

M,

The neuroradiology Roentgenol 1987;

RG, Geremia

1988;

10.

LV.

findings

Newton TH. AIDS. Semin

9.

5, Perret

in AIDS

multifocal Neuropathol

1986; 158:141-148.

flu-

with

to the

Isoneu-

acquired

N EngI

Radiology

191

#{149}