Clinical Radiology (1996) 51, 842-850

The Spectrum of MRI Findings in CNS Cryptococcosis in AIDS

K. A. MISZKIEL*, M. A. HALL-CRAGGS*, R. F. MILLERt, B. E. KENDALL*, I. D. WILKINSON*,
M. N. PALEY~ and M. J. G. HARRISON~
*MRI Unit, Imaging Department at UCL Hospitals (NHS) Trust, /'Division of Pathology and Infectious Diseases and
~Department of Neurology, UCL Medical School, The Middlesex Hospital, London UK

We retrospectively reviewed the cranial MRI appearances of 25 patients with AIDS and
microbiologically proven central nervous system (CNS) cryptococcosis. Four patients had a
normal scan. Ten patients had dilated perivascular Virchow-Robin spaces that were hyper-
intense on T2-weighted images. Nine of these patients developed progressive cryptococeomas,
eight in the basal ganglia and one in the cerebral white matter. The cryptococcomas displayed
high signal on T2-weighted and intermediate to low signal on Tl-weighted images. None
enhanced after dimeglumine gadopentetate. No abnormal dural or leptomeningeal enhance-
ment was detected in any patient. One patient developed an acquired arachnoid cyst during
treatment of CNS cryptococcosis which was thought to represent a focal collection of
organisms and mucoid material within the subarachnoid space. In addition either cerebral
atrophy and/or background white matter hyperintensity on T2-weighted images was present in
19/25 patients. In two patients the neuropathological findings at autopsy correlated well with
the imaging abnormalities. In conclusion, this spectrum of MRI appearances in CNS
cryptococcosis reflects the pathological mechanism of invasion by the fungus, but a normal
scan or one with features of CNS HIV infection such as atrophy or white matter hyperintensity
does not exclude the diagnosis. Miszkiel, K.A., Hall-Craggs, M.A., Miller, R.F., Kendall,
B.E., Wilkinson, I.D., Paley, M.N. & Harrison, M.J.G. (1996). Clinical Radiology, 51,842-
850. The Spectrum of MRI Findings in CNS Cryptococcosis in AIDS

Accepted for Publication 23 April 1996

Cryptococcus neoformans is a ubiquitous saprophytic
fungus isolated from soil contaminated by bird excreta
which may become particularly pathogenic in immuno-
compromised patients. Although most human infection
is probably secondary to inhalation, pulmonary infec-
tion with cryptococcosis is often asymptomatic or serf-
limited with the fungus having a particular predilection
for haematogenous spread to the central nervous system
(CNS).
C. neoformans is the third most common pathogen to
cause CNS infection in the acquired immune deficiency
syndrome (AIDS) after the human immunodeficiency
virus (HIV) itself and Toxoplasma gondii [1,2]. Approxi-
mately 5% of patients with AIDS will develop CNS
cryptococcosis although it rarely develops in patients
with CD4+ lymphocyte counts of greater than
200 x 106/1 [3]. Most cases of C. neoformans CNS
infection present as a subacute or chronic illness with
altered mental state, behavioural changes, headache and
fever. Focal neurological signs are unusual, occurring in
only 15% of patients [4]. In contrast to CNS cryptococ-
cosis in non-HIV immunosuppressed patientS, in AIDS
it is frequently part of disseminated infection [5]. The
diagnosis is made on the basis of a series of microbiolo-
gical investigations including cerebrospinal fluid (CSF)
culture and positive identification of the fungus with
India ink or mucicarmine staining, raised cryptococcal
antigen latex agglutination titres in CSF and blood and
positive blood cultures.
Several studies have described the magnetic resonance
imaging (MRI) findings in small cohorts of patients with
Correspondence to: Dr K. A. Miszkiel, MRI Unit, The Middlesex
Hospital, Mortimer Street, London W l N 8AA, UK.
© 1996 The Royal College of Radiologists.
CNS cryptococcosis and compared them to computed
tomography [6-8]. In this study we have reviewed the
MRI findings in a cohort of twenty-five patients with
AIDS and microbiologically confirmed CNS cryptococ-
cosis and offer a pathological explanation for the ima-
ging findings.
PATIENTS AND METHODS
We retrospectively reviewed the cranial MRI appear-
ances of twenty-five patients, twenty-three male homo-
sexuals (twenty-one Caucasians and two Afrocaribbeans)
and two female heterosexuals (of Afrocaribbean origin)
aged 24-56 years (median = 36 years), with a median
CD4+ lymphocyte count of 60 (normal range = 350-
2200 x 106/1) and with microbiologically confirmed CNS
C. neoformans infection, who were referred to a specialist
HIV/AIDS inpatient facility at UCL Hospitals between
August 1991 and October 1995. We recorded the results
of CSF culture and staining, CSF and serum crypto-
coccal antigen latex agglutination (CRAG) titres and
whether C. neoformans was cultured from blood. Two
patients had a post-mortem examination. At the time
of diagnosis MRI studies had been performed on a
1.5T scanner (Magnetom 63SP, Siemens Medical Sys-
tems, Erlangen, Germany) with a circularly polarized
transmit and receive head coil. A dual spin-echo imaging
sequence (TR = 3500ms, TE = 20/90ms, 192 x 256
acquisition matrix, FOV 230 mm, 5 mm slice thickness,
NE x 1) was acquired with 30 contiguous slices orien-
tated transversely along the plane of the temporal
lobes. In all patients Tl-weighted spin-echo sequences
 MRI 1N CNS CRYPTOCOCCOSIS I N AIDS 843

Table 1 - Results o f microbiological investigations in 25 patients with C. neoformans meningitis

Patient number CSF India ink stain C S F culture CSF CRAG titre Blood CRAG titre Blood culture

1^ + + 1:2000 1:131000 +
2A + + 1:1000 1:512 N/P
3 + + 1:2000 1:8000 -
4 + + 1:64 1:2000 N/P
5 - + - 1:2 N/P
6 + + 1:4000 1:256000 +
7 + + 1:4000 1:512 -
8 + + + * 1:8000 -
9 - - * + *** -
10 + + 1:32 1:4000 N/P
11 - + 1:4 1:16 N/P
12 + + 1:256 1:4000 +
13 + + 1:256 1:256 N/P
14 + + 1:16000 1:256000 +
15 + + 1:4000 1:128000 ÷
16 + + 1:1000 1:4000 +
17 + + 1:4000 1:4000 N/P
18 + + 1:512 1:2048 +
19 + + 1:128000 1:8000 -
20 + + 1:4000 1:4000 +
21 + + 1:512 1:4096 -
22 + + 1:512 1:16000 N/P
23 + + 1:128 1:128 +
24 - - 1:512 1:2000 +
25 - + 1:4 - -

C ~ A G = C r y p t o c o c c a l latex a g g l u t i n a t i o n titre; + = positive result, - = n e g a t i v e result, N / P = test n o t p e r f o r m e d . *Insufficient s p e c i m e n for titre;

**titre n o t d e t e r m i n e d ; ^ a u t o p s y p e r f o r m e d .

(TR = 640ms, TE = 14ms 192 x 256 acquisition matrix meningism and photophobia (n = 4), dizziness and
with 3/4 rectangular 230FOV, NE x 2) were also visual symptoms (n = 3 for both), diarrhoea and confu-
acquired coronally with 5 mm slices interspaced by a s i o n - ( n = 2 for both). Results of the neurological
1 mm gap, before and after 0.1 mmol/kg of intravenous examination at the time of presentation showed that
dimeglumine gadopentetate (Gd-DTPA, Magnevist, eight of 25 patients had new neurological signs asso-
Schering Health Care Ltd). ciated with CNS cryptococcosis including hypertonia/
The cranial M R I was reviewed as a batch, retrospec- hyperreflexia (n = 5), meningism/photophobia (n = 5),
tively and independently by two radiologists (MAHC altered mental state, extensor plantars or oculomotor
and BEK) who were experienced in the neuroradiology signs (n = 2 in each category) and hemiparesis (n = 1).
of HIV infection. Both radiologists were aware of the Four patients had a previously documented abnormality
diagnosis of CNS C. neoformans infection in the patient and 13 patients had no neurological signs. All patients
cohort. In each case consensus was achieved. In all were treated with appropriate antifungal therapy.
patients the following features were recorded: (1) abnor- Twenty-three patients survived the immediate crypto-
mal dilated Virchow-Robin (V-R) spaces which were coccal infection; one patient died from progressive CNS
defined as small punctate rounded lesions greater than C. neoformans infection and one patient died 3 months
2ram but less than 3 m m diameter [9,10], which were later; both these patients had an autopsy.
hyperintense on T2-weighted images and of low signal on
the Tl-weighted images, (2) cryptococcomas; these were
defined as lesions greater than 3 mm in size which were Microbiological Findings
hyperintense on T2-weighted images and of low or
intermediate signal on Tl-weighted images [6,11], (3) Results of the microbiological investigations are
shown in Table 1. In three patients with positive
abnormal dural or leptomeningeal enhancement, (4)
features of HIV or viral encephalopathy as indicated by blood cultures, C. neoformans was also cultured from
sputum.
cerebral atrophy and/or any patchy or diffuse background
white matter hyperintensity on the T2-weighted images
[12,13], and (5) other mass lesions or pathology. For the
purpose of this study the basal ganglia referred to include MRI Findings
the lentiform and caudate nuclei and the thalami. Cranial M R I was performed during the course of CNS
cryptococcosis in all patients. The median time interval
between lumbar puncture and initial MRI was 1 day
RESULTS (range = 0-22 days). Eighteen patients had follow-up
scans; the median number of scans performed in each
Clinical Presentation patient was 2 (range = 1-5). The median time interval at
The most common presenting symptoms in our patient which the first follow-up scan was performed was 36 days
cohort were headache (n = 23), nausea and vomiting (range = 3-510 days). Twenty-two patients were given
(n = 13) and fevers/sweats (n = 10). Less frequently intravenous Gd-DTPA, either at the time of the initial
occurring symptoms were malaise/fatigue ( n = 4 ) , scan (n = 18) or during follow-up (n = 4).
© 1996 The Royal College of Radiologists, Clinical Radiology, 51, 842 850.
844 CLINICAL RADIOLOGY

Four patients had a normal M R I at the time of were characteristically of high signal on T2-weighted and
diagnosis of CNS cryptococcosis. of intermediate to low signal on Tl-weighted sequences
The abnormalities detected in the remaining scans with a stippled appearance early on in the course of the
were as follows. illness. With disease progression the lesions became more
confluent, some better defined, with some lesions exert-
Dilated Virchow Robin Spaces/Cryptococcomas ing mild mass effect, but none had surrounding vaso-
genic oedema or haemorrhage. In three patients the basal
Multiple dilated V - R spaces were seen on the initial ganglia lesions extended superiorly to involve the corona
M R I in eight patients. These were present in the basal radiata. One patient had a different pattern of disease
ganglia (n = 8) (Fig. 1), brainstem (n = 3) (Fig. 2a and b) with multiple poorly defined high signal cryptococcomas
or the cerebral white matter (n = 3). All eight patients present on the T2-weighted images in the cerebral
with dilated V - R spaces in the basal ganglia had white matter, some in a periventricular distribution with
involvement of the lentiform nuclei, six had involvement
of the heads of the caudate nuclei and two patients had
thatamic involvement. Two patients with normal V - R
spaces on the initial M R I developed dilated V - R spaces
during the course of the illness detected on follow-up
scans; in one patient they were detected in the basal
ganglia at 8 weeks and in the other patient in the cerebral
white matter and basal ganglia at 5 weeks' follow-up.
Thus, overall ten patients developed dilated V - R spaces
as a result of CNS cryptococcosis, all with basal ganglia
involvement.
Cryptococcomas were detected in seven patients on
the initial MRI; six of these had cryptococcomas in the
basal ganglia with additional periventricular cryptococ-
comas around the lateral ventricles in three patients. The
distribution of the basal ganglia cryptococcomas was
similar to the distribution of dilated V - R spaces; six
patients had involvement of the lentiform nuclei, five
patients caudate head involvement and two patients had
cryptococcomas in the thalami. A further two patients
who did not have cryptococcomas on their initial scan
developed cryptococcomas in the basal ganglia on
follow-up scans at 17 and 60 days. The basal ganglia
cryptococcomas were bilateral in the majority of patients
(n = 7), often fairly symmetrical, and varied from several
millimetres (> 3 mm) to several centimetres in size. They (a)

(b)
Fig. 2 Axial T2-weighted images demonstrating multiple dilated V - R
Fig. 1 - Axial T2-weighted image showing multiple dilated V - R spaces spaces in the mid-brain (a) which show enlargement with disease over
in the basal ganglia region (arrow). an 18-day interval (b).

© 1996The Royal College of Radiologists, Clinical Radiology, 51,842-850.

 MRI IN CNS CRYPTOCOCCOSIS IN AIDS 845

(a)

(b) (c)
Fig. 3 - The T2-weighted axial images in this patient with co-existant cerebral atrophy demonstrate hyperintense cryptococcomas in the right side of
the pons (a), together with poorly defined cryptococcomas (arrow) in image (b) and multiple dilated V - R spaces (curved arrow) in the cerebral white
matter (e).

further lesions around the fourth ventricle and in the brain
stem (Fig. 3a, b and c) but without the characteristic basal
ganglia involvement detected in the other eight patients.
One other patient with progressive basal ganglia
© 1996 The Royal College of Radiologists, Clinical Radiology, 51, 842-850.
cryptococcomas also developed cryptococcomas
around the fourth ventricle. None of the cryptococcomas
showed enhancement after intravenous Gd-DTPA.
Two patients with basal ganglia cryptococcomas also
846 CLINICAL RADIOLOGY

(a)

(b) (c)
Fig. 4 - The T2-weighted axial image (a) is from an examination performed 8 months prior to CNS cryptococcosis. The repeat MRI at the time of
diagnosis of CNS cryptococcosis showed an acquired right fronto-temporal arachnoid cyst (white arrow) and several hyperintense well defined
cryptococcomas in the basal ganglia (b). The cryptoeoccomas are seen on the Tl-weighted coronal images as well defined intermediate low signal
lesions (e). Note the presence of peritrigonal white m~/tter hyperintensity (black arrow) on image (b) indicative of HIV/viral encephalopathy.

had arachnoid cysts. In one patient a right fronto-
temporal arachnoid cyst was thought to represent an
acquired collection of C. neoformans within the subar-
achnoid space as it had not been present on cranial MRI
performed 8 months previously (Fig. 4a, b and c). In the
other patient no previous scans were available for com-
parison, and we cannot be certain whether the right
temporal arachnoid cyst was incidental and congenital
in origin or acquired secondary to CNS cryptococcosis.
To further characterize the chronology ! i
of the
morphological changes seen on M R I during the course
of appropriate treatment, a more detailed analysis was
undertaken of the follow-up scans performed on nine of
the ten patients who had dilated V R spaces and/or
cryptococcomas. In these nine patients the median
number of follow-up scans performed per patient was 2
(range 1-5) and they were acquired between 3 and 148
days following the initial scan. Review of the first follow-
up scans performed at a median time interval of 21 days
(range = 3-94 days) from the initial M R I showed
© 1996 The Royal College of Radiolo~sts, Clinical Radiology, 51,842-850.
 MRI IN CNS CRYPTOCOCCOSIS IN AIDS 847

(b)
(a)

(c)

(a)
Fig. 5 - T2-weighted axial (a and c) and Tl-weighted coronal (b and d) images demonstrating the lag phenomenon in the radiological appearances
compared with CSF/blood parameters in CNS cryptococcosis. At the time when images (a) and (b) were acquired the blood C R A G titre was
1 : 128 000. Images (c) and (d) were acquired 32 days later by which time the blood C R A G titre had fallen to 1 : 64000 on treatment, indicating disease
response to therapy; the bilateral basal ganglia cryptococcomas increased in size during this time with marked expansion of the caudate nuclei despite
improvement in the patient's clinical condition.

progression of the dilated V - R spaces and cryptococco-
mas in all but one patient, who had a decrease in size of
the bilateral basal ganglia and periventricular lesions on
the follow-up M R I at 78 days. In the seven patients who
© 1996 The Royal College of Radiologists, Clinical Radiology, 51, 842-850.
had two or more follow-up scans performed, four
patients had progression of cryptococcomas on the
second follow-up scan despite a falling CSF (n = 3) or
blood (n -- 1) C R A G titre (Fig. 5a, b, c and d). One
848 CLINICAL RADIOLOGY
patient showed improvement on MRI (at 76 days)
despite a rising CSF CRAG, but decreasing blood
CRAG titre. Two patients showed no change in appear-
ance of the cryptococcomas from the previous scan (one
of these patients had already shown improvement on the
first follow-up scan at 78 days) despite a falling CSF
CRAG titre in one patient. Overall, when all the avail-
able follow-up scans were reviewed, in total four of the
nine patients showed eventual improvement and a
decrease in size of cryptococcomas, improvement being
first detected on MRI at a median time interval of 77
days (range 38-106 days) from the initial scan. In three
patients whose scans were judged to show overall
response to treatment, a mixed response to treatment
was seen on three follow-up scans. Not all the crypto-
coccomas responded to treatment at the same rate in
these cases; although the majority of lesions decreased in
size, others remained unchanged and one or two
increased in size.
Dural/Leptomeningeal Enhancement
These abnormalities were not detected in any patient.
Atrophy and White Matter Hyperintensity
Nineteen patients had evidence of HIV or viral ence-
phalopathy; eight of these nineteen patients had atrophy
only, two patients white matter hyperintensity only and
nine patients had both features present. The atrophy
ranged in degree from mild to moderate. Six patients
had no evidence of either atrophy or white matter
hyperintensity.
Enhancing Mass Lesions
One patient had multiple enhancing mass lesions in
the cerebral hemispheres and basal ganglia on MRI
performed 6 weeks prior to the diagnosis of CNS cryp-
tococcosis. The signal characteristics of these lesions
were those of mixed/intermediate signal on T2-weighted
images, with surrounding high signal oedema, and they
were of low signal on Tl-weighted images with foci of
high signal haemorrhage. These mass lesions showed
patchy and peripheral ring enhancement with Gd-
DTPA; follow-up scans showed response of the original
mass lesions to anti-toxoplasma drug therapy, with the
development of new superadded, well-defined, non-
enhancing cryptococcomas in the basal ganglia. These
changes were interpreted as treated toxoplasma
abscesses and concurrent C. neoformans infection. A
further three patients developed multiple enhancing
mass lesions typical of cerebral toxoplasma infection or
lymphoma on subsequent follow-up at 5 months, and at
18 months in the other two patients.
Non-specific Findings
One patient had a virtually normal scan at presenta-
tion, with minimal high signal in the heads of both
caudate nuclei on the T2-weighted images but with no
corresponding abnormality on the Tl-weighted images.
This patient did not have follow-up scans to assess the
significance of this finding but died 3 months later and
had an autopsy.
Autopsy Correlation
One patient with dilated V - R spaces in the basal
ganglia and brainstem, who developed progressive non-
enhancing basal ganglia and periventricular cryptococ-
comas on MRI over a period of 5 weeks, had a post-
mortem 2 weeks after his last MRI. Pathological
examination revealed thin and transparent lepto-
meninges and a microcystic appearance of the basal
ganglia extending to the thalamus and midbrain.
Histology confirmed cryptococcal meningo-encephalitis
and Cryptococcomas.
At post-mortem in the second patient with minimal
non-specific high signal in the caudate nuclei, macro-
scopic examination of the brain showed normal lepto-
meninges and dura, together with mild ventricular
dilatation. Histology revealed a diffuse nodular cytome-
galovirus (CMV) encephalitis in addition to cryptococcal
meningo-encephalitis.
DISCUSSION
Cryptococcal meningitis is the most common mani-
festation of CNS cryptococcosis often with a chronic
insidious course [14]. Several studies have shown that
MRI is superior to CT in identifying abnormalities in
CNS cryptococcosis, but both imaging modalities under-
estimate the number of lesions detected when compared
with pathological examination [6,15,16]. The spectrum
of imaging abnormalities detected on MRI in CNS
cryptococcosis reflects the pathological mechanism of
invasion by the fungus. In CNS cryptococcosis the
leptomeningeal involvement and associated inflamma-
tory reaction is mild and results in the production of a
mucoid material within the subarachnoid space. This
process may extend to involve the perivascular (V-R)
spaces which are extensions of the subarachnoid space
surrounding the perforating arteries into the brain
parenchyma. With cryptococcal infection these potential
spaces become dilated and filled with the mucoid
material, inflammatory cells and organisms. This is
manifest on the MRI as punctate,'hyperintense round/
oval lesions on T2-weighted images usually less than
3 mm in size with a propensity for the basal ganglia
and brainstem as we found in this study. With disease
progression these V - R increase in size, resulting in
the development of cryptococcomas, which may extend
into the brain parenchyma. Pathologically these
cryptococcomas are composed of gelatinous masses of
cryptococcal organisms interspersed by acid mucopoly-
saccharide that is produced by the organism [17].
In this study we have reviewed the cranial MRI scans
of a larger cohort of immunocompromized patients with
AIDS and CNS cryptococcosis than previously
described, many of whom underwent Gd-DTPA
enhanced serial MRI while receiving appropriate anti-
fungal treatment to characterize the chronological
changes that occur on MRI in this CNS infection.
None of the previous studies have concentrated on this
latter feature [6,7,8,18].
In our study, ten of the cohort of twenty-five patients
had features on MRI attributable to C. neoformans
meningitis; in keeping with previous studies [6,7,8,18]
we found that dilated V - R spaces and cryptococcomas
developed most commonly, but not exclusively, in the
© 1996 The Royal College of Radiologists, Clinical Radiology, 51, 842-850.
 MRI IN CNS CRYPTOCOCCOSIS IN AIDS
basal ganglia, with the lentiform nuclei most commonly
involved. The basal ganglia cryptococcomas were nearly
always bilateral. None of the cryptococcomas in our
study showed evidence of enhancement, although
enhancement of cryptococcomas in patients with AIDS
has been described, albeit infrequently. Tien et al.
reviewed the CT scans of twenty-nine immunocompro-
mized patients (twenty-eight of whom had AIDS) with
CNS cryptococcosis, 10 of whom had concomitant M RI,
four with intravenous Gd-DTPA. Enhancement of mili-
ary leptomeningeal nodules and parenchymal cryptococ-
comas on MRI was detected in two of four patients. No
histology was available in these patients so exclusion of
other concomitant pathology was not possible. Only one
patient in Tien's study had a follow-up MRI, after
antifungal treatment, which showed complete resolution
of the previously noted abnormalities, but the time
interval between the two scans was not specified [8].
Leptomeningeal nodules, or enhancement of the lep-
tomeninges or dura, was not detected in any of our
patients. Consistent leptomeningeal enhancement
caused by CNS cryptococcosis in AIDS has been demon-
strated on MRI in only one study of eight patients in
which the authors used a higher dose of Gd-DTPA
(double that conventionally used) and performed
delayed scans to amplify signal abnormalities due to
mild leptomeningeal inflammation [18]; seven of the
eight patients exhibited leptomeningeal enhancement.
In addition, one patient showed enhancement of
parenchymal cryptococcomas, while another had
enhancement of an intraventricular choroid plexus
cryptococcoma. It is not clear from this study whether
these latter findings were pathologically confirmed [18].
None of the patients.in the present study had choroid
plexus cryptococcomas and possibly the discrepancy
between the frequency of leptomeningeal enhancement
detected by us and by Andreula et al. in their study may
be accounted for by the different dose of Gd-DTPA used.
C. neoformans is surrounded by a polysaccharide
capsule which may protect it from the host inflammatory
response even in immunocompetent patients [19] but it
may also have immunosuppressive properties per se.
This, together with the profoundly immunosuppressed
state of patients with AIDS, may account for the lower
incidence of leptomeningeal or lesion enhancement
occurring in CNS cryptococcosis compared with bacter-
ial meningitis or brain abscesses [20-22]. In the study by
Mathews et al. [6], pathological examination of the brain
parenchyma adjacent to the cryptococcomas showed
no evidence of an inflammatory exudate, necrosis or
haemorrhage in any case. The meninges of the brains
examined in this study were only mildly inflammed with
mucoid material present in the subarachnoid spaces [6].
One patient in their study had evidence of abnormal
leptomeningeal enhancement on MRI, but the authors
found this to be secondary to an area of adjacent focal
cerebritis due to Nocardia [6].
To our knowledge we have described the first observa-
tion of an acquired arachnoid cyst developing during the
course of the C. neoformans meningitis in patients with
AIDS who have undergone MRI. Acquired arachnoid
cysts have been described as a consequence of meningitis
[23] and in our patient we suspect it represented a focal
collection of mucoid material Within the subarachnoid
space.
Follow-up of C. neoforrnans meningitis on MRI in
O 1996 The Royal College of Radiologists, ClinicalRadiology, 51, 842-850.
849
patients with AIDS has not been previously described in
any detail. We have studied the chronological changes
seen on MRI in this CNS infection on appropriate
antifungal treatment and shown that in general there is
poor correlation between the MRI appearances and
blood and CSF disease parameters, with a decrease in
the latter often preceding radiological improvement. In
addition cryptococcomas may show a mixed response to
treatment, with some increasing in size while others are
diminishing.
In conclusion CNS cryptococcosis produces a wide
variety of MRI appearances with dilated V - R spaces as
the earliest manifestation, with progression to intrapar-
enchymal cryptoeoccomas reflecting the distribution of
these dilated perivascular spaces. Contrast enhancement
of cryptococcomas or leptomeninges is uncommon due
to the unique characteristics of this organism and the
profoundly immunosuppressed state of this group of
patients. One or two dilated V - R spaces may be present
in normal individuals, particularly the elderly, but may
also occur in cerebral atrophy, which is common in HIV
infection [24], and in this study was a feature in seventeen
patients; thus they are not specific for CNS cryptococ-
cosis but suggest the diagnosis in the appropriate clinical
setting. In addition a normal MRI, or one showing only
evidence of HIV or viral encephalopathy, does not
exclude CNS cryptococcosis, as the typical features of
this infection occurred in only 40% of our patients. Of
those patients who had developed cryptococcomas on
follow-up MRI, initial radiological progression was seen
despite appropriate treatment and falling CSF and serum
CRAG titres. Thus it would appear that although MRI
is useful as part of the initial investigation protocol in
suspected C. neoformans meningitis serial imaging has
probably only a minimal role in monitoring response to
therapy unless the clinical scenario raises the possibility
of developing hydrocephalus or concurrent intracranial
pathology.
Acknowledgements. This work was supported by the Medical
Research Council of Great Britain under grant number: SPG8915593.
We would like to thank the pathologists Professor F. Scaravilli and
Professor S. Lucas for performing the autopsies.
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