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Journal of Medical Imaging and Radiation Oncology 55 (2011) 52–57

C O MMEN TA RY jmiro_2229 52..57

MRI findings of cerebral cryptococcosis in


immunocompetent patients
Shaoqiong Chen1, Xiaohong Chen2, Zhigang Zhang3, Li Quan1, Sichi Kuang1 and Xiao Luo1
Departments of 1Radiology and 2Neurology and 3Pathology, the Third Affiliated Hospital, Sun Yat-Sen University. Guangzhou, China

S Chen MD, PhD; X Chen MD, PhD; Z Zhang Summary


MBBS; L Quan MD; S Kuang MD; X Luo MD.
Worldwide, cerebral cryptococcal infections caused by cryptococcus neofor-
Correspondence mans are mostly found in immunocompromised patients, but less found in
Dr Shaoqiong Chen, Department of Radiology, immunocompetent patients with fewer related imaging reports in literatures.
The Third Affiliated Hospital, Sun Yat-Sen This pictorial essay describes some important MR imaging features in arriving
University, 600 Tianhe Road, Guangzhou, at diagnosis for cerebral cryptococcosis in immunocompetent patients by way
510630, China. of five illustrative cases with intact MRI data.
Email address: csq_q@yahoo.com
Key words: cerebral cryptococcosis; immunocompetent; magnetic resonance
imaging.
Conflict of interest: None.

Submitted 10 October 2010; accepted 18


October 2010.

doi:10.1111/j.1754-9485.2010.02229.x

the basal cistern5 (Fig. 1). The dilatation of subarachnoid


Introduction spaces and cerebral cisterns due to mucoid gelatinous
Cryptococcus neoformans is a ubiquitous organism that exudates or the narrow of the CSF spaces caused by
primarily infects the lungs and subsequently spreads to adherence can also be seen. This feature of meningeal
the central nervous system (CNS) through the hae- enhancement on MRI is absent or minimal in cases of
matogenous route. The CNS cryptococcal infections are AIDS-related crytococcal meningitis possibly due to
mostly found in immunocompromised hosts, and less impaired cell-mediated immunity.6 Hydrocephalus is a
found in immunocompetent patients.1 However, we have common complication of cryptococcal meningitis, which
collected 152 cases of cerebral cryptococcosis in immu- appears as dilatation of the ventricles (Fig. 1). Cerebral
nocompetent patients in our hospital during a period of infarction is also a common complication resulting from
6 years (2002–2008). As is commonly known, this the development of cerebral vasculitis with inflammation,
disease usually appears as features of meningitis, men- spasms, constriction and, eventually, thrombosis in cryp-
ingoencephalitis and cerebral vasculitis radiologically.2 tococcal meningitis patients.5 In the acute stage, diffusion
However, the development of features can have some weighted image (DWI) shows patchy lesions with hyper-
differences, depending on the host immune response.1,3,4 intense signal in the cortical areas is consistent with acute
This pictorial essay discusses the usual and unusual MRI infarction. MR angiography (MRA) may confirm the exist-
appearances of cerebral cryptococcosis in immunocom- ence of cerebral arteritis by demonstrating multiple
petent patients by way of five illustrative cases with stenoses of cerebral arteries (Fig. 1c–f).
intact MRI data, including one proven pathologically and Contrast-enhanced T1WIs (Fig. 1a,b) show diffuse
four confirmed by cerebral spinal fluid (CSF) laboratory gyriform leptomeningeal enhancement with some lep-
investigations. tomeningeal nodules (bold arrows) along the cerebral
surface, cerebral sulci and subarachnoid spaces and
basal cisterns. DWIs (Fig. 1c–e) show multiple hyperin-
Meningitis with cerebral vasculitis (Fig. 1)
tense lesions (fine arrows) in the cortical areas in both
Enhancement of the leptomeninges or sometimes dura hemispheres. Hydrocephalus is also seen (Fig. 1a–e).
and/or leptomeningeal nodules is a common MRI feature MRA (Fig. 1f) shows multiple segmental stenoses in the
of cryptococcal meningitis, which is most pronounced in left middle cerebral artery, bilateral posterior cerebral

© 2011 The Authors


52 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
MRI findings of cerebral cryptococcosis in immunocompetent patients

Fig. 1. Cerebral cryptococcal infection


mainly with meningitis and vasculitis in a
27-year-old man. Cryptococcus is identified
with CSF India ink stain.

arteries (arrowheads) and anterior cerebral arteries (Virchow-Robin (V-R) spaces) into the brain parenchyma
consistent with arteritis. along with the organisms resulting in dilatation of V-R
spaces and forming of gelatinous pseudocysts.3,7 The
dilated V-R spaces and pseudocysts are mostly found in
Encephalitis with clustered fine cysts (Fig. 2)
the basal ganglia, typically appearing as clustered linear
The leptomeningeal infection may produce voluminous or punctate cystic lesions with enhancing cystic wall
mucoid gelatinous exudates within the subarachnoid (Fig. 2a–d); and may be widely scattered over the thala-
space, which then spread through the perivascular spaces mus, midbrain (Fig. 2e), periventricular white matter and

Fig. 2. Cerebral cryptococcal infection


mainly with clustered small cysts in a 36-year-
old man. Cryptococcos is identified with CSF
India ink stain.

© 2011 The Authors


Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 53
S Chen et al.

cerebellum (Fig. 2f).3 These gelatinous pseudocysts solid nodules that often show no or minimal contrast
show higher signal intensity than the CSF on T2-fluid- enhancement and surrounding edema in immuno-
attenuated inversion recovery (T2-FLAIR) owing to their compromised patients.6 Whereas in immunocompetent
mucoid content. Enhancement of the pseudocyst wall is patients, these small parenchymal cryptococcomas often
thought to be a chronic inflammatory reaction in immu- show fine solid enhancing nodules clustered in basal
nologically intact hosts.3,4 ganglia and sparsely scattered over bilateral cerebral
Non-contrast MRIs show numerous clustered small hemispheres, cerebellums and brainstem. It is believed
lesions (fine arrows) with hypointensity on T1WI that the feature of clustered enhancing cysts or nodules
(Fig. 2a) and hyperintensity on T2WI (Fig. 2b) in bilat- found in bilateral ganglia is diagnostic for cerebral
eral basal ganglia. T2-FLAIR (Fig. 2c) shows that the cryptococcosis in immunocompetent patients.
signal intensity of these small cystic lesions is higher Contrast-enhanced T1WIs (Fig. 3a–d) show diffuse
than that of CSF with extensive surrounding hyper- gyriform leptomeningeal enhancement with some lep-
intense edema. Postcontrast images (Fig. 2d–f) show tomeningeal nodules distributed along the gyrus sulci,
typical clustered small cystic lesions (5~10 mm) with various basal cisterns and Sylvian fissures (bold arrows).
intense rim-enhancing wall in bilateral basal ganglia, Numerous linear enhancing nodules (4~12-mm long)
midbrain (bold arrow) and cerebellum (arrowhead) clustered in bilateral basal ganglia (fine arrows) and
around the fourth ventricle. sparsely scattered over bilateral cerebral hemispheres
(temporal lobes and frontal lobes), cerebellums and
brainstem are also seen. The ventricles are normal in
size but basal cisterns and Sylvian fissures are mostly
Meningoencephalitis with clustered fine narrowed.
nodules (Fig. 3)
Previous studies have indicated that gelatinous
Solitary larger arachnoid cyst (Fig. 4)
pseudocysts would develop into cryptococcomas with
disease progression. The cerebral cryptococcomas is a Intracranial cryptococcal infection can sometimes
collection of cryptococcus, gelatinous mucoid material develop a larger arachnoid cyst with only minimal
and chronic granulomatous reaction. They are usually meningeal enhancement6 (Fig. 4). This is a very unusual
several millimetres (>3 mm) to several centimetres in feature in this infection and can be mimicked as
size.4,6 On MR images, small cryptococcomas are focal the common non-infectious arachnoid cyst in the

Fig. 3. Cryptococcal infection mainly with clustered nodules in a 28-year-old Fig. 4. Intracranial cryptococcal infection with arachnoid cyst in a 22-year-old
man. Cryptococcus is identified with CSF India ink staining. woman. Cryptococcus is identified with CSF culture.

© 2011 The Authors


54 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
MRI findings of cerebral cryptococcosis in immunocompetent patients

subarachnoid spaces, especially in the cerebello-pontine


angle cistern. However, the feature of rim-enhancing
cyst with circumferential edema and accompanying
meningeal enhancement is different from the non-
infectious arachnoid cyst in imaging appearances. Pos-
sibly, the rim- enhancement is due to the patient’s ability
to induce an inflammatory response as other changes
such as pseudocysts and cryptococcomas in immuno-
competent patients.
Magnetic resonance images (Fig. 4a–c) show a
dumbbell-like arachnoid cyst (arrows) in the left cerebel-
lopontine angle which is hypointense on T1WI (Fig. 4a)
and hyperintense on T2WI (Fig. 4b) and isointense to
CSF with surrounding hyperintense edema on T2-FLAIR
(Fig. 4c). Contrast-enhanced T1WI (Fig. 4d) shows ring
enhancement of the cyst wall. Meningeal enhancement is
also seen (arrowhead).

Choroid inflammation (Fig. 5)


Choroid plexitis appearing as an enhancing enlarged
choroid with dilatation of the ventricular horn has been
described in literature.8 Our case is consistent with these
findings. However, a solitary enlargement of the occipital
horn is a very uncommon MRI feature in cerebral cryp-
Fig. 5. Intracranial cryptococcal infection with choroids inflammation in a tococcosis and other infections, which may be due to the
22-year-old woman. Cryptococcus is identified with CSF culture. (The same obstruction of cerebral spinal flow caused by crypto-
patient as that of Figure 4). coccal choroid plexitis with ependymal inflammatory
reaction and synechiae.

Fig. 6. Cryptococcal infection in a 47-year-


old man with insidious onset. The patient had
normal CSF preoperatively and underwent a
craniotomy with an initial diagnosis of brain-
stem tumour confirmed as cryptococcal
infection pathologically.

© 2011 The Authors


Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 55
S Chen et al.

Magnetic resonance images show the dilated and or nodules on MRIs, and is very easy to be misdiagnosed
trapped occipital horn of the left lateral ventricle (fine as a tumour if the laboratory study reveals normal CSF.
arrows) with periventricular extravasation of cerebrospi- Thus, it is important to make a correct diagnosis to avoid
nal fluid (Fig. 5a–c). Postcontrast image (Fig. 5c) shows improper operation in patients with insidious onset.
the intense enhancement of ependyma and the thick- Solitary cryptococcoma is a very rare lesion in lite-
ened choroid plexus (bold arrow). The dilated occipital rature reports.9 It is characterised by a localised,
horn shrinks resulting in a smaller enhancing solid lesion tumour-like mass in which the fungus has invaded the
(arrowhead) on the follow-up enhanced scan (Fig. 5d) parenchyma, producing a chronic granulomatous reac-
11 days after anti-fungal treatment. tion composed of macrophages, lymphocytes and foreign
body-type giant cells.1,4 On MRI, the cryptococcoma can
present as a rim-enhancing mass. The contrast enhance-
Solitary parenchymal mass without associated ment probably represents the patient’s ability to mount
meningitis (Figs 6,7) an immune response.2,4 In our case (Fig. 6), contrast-
When the patient’s immunocompetency is strong enough enhanced MRIs show the occupying mass in the brain-
to limit the spread of the disease, the infection may only stem to be a mixed signal mass with an enhancing rim
present as a solitary parenchymal mass without the and non-enhancing core after administration of gado-
common features of meningitis or clustered pseudocysts linium. The non-enhanced MRIs show the mass to be
isointense in wall with some hypointense areas in core on
T1WI, and hypointense in wall with some hyperintense
areas in core on T2WI, which essentially reflects the
mass is mainly composed of solid materials like granu-
lomatous and fibrous tissues with some filled fluid mate-
rials histo-pathologically. However, the shorter T1 signal
and shorter T2 signal in the mass may also reflect the
mass containing some degree of iron materials, a para-
magnetic substance that can shorten T1 & T2 relaxation
times. Besides, DWI shows hyperintense areas in the
mass seems to be an indication that the mass may
contain some collections of viscous materials. Surgical
histo-pathological specimen confirms a lot of cryptococ-
cus and mucoid gelatinous materials in the granuloma-
tous mass with prominent iron deposits on Perl stain for
iron (Fig. 7). This finding is somewhat similar to cerebral
aspergillus granuloma in previous report that the dense
population of hyphal elements and haemorrhage in
aspergillus granulomas may show T2 hypointensity due
to the paramegnatic elements such as iron, magnesium,
zinc, calcium, chromium and nickel within the hypha.10
Thus T2 hypointensity in the mass is probably a MRI
characteristic feature of some cerebral fungal infections.
The tumour-like cryptococcomas should be considered in
the differential diagnosis of rim-enhancing mass lesion in
brainstem or other unusual site.
T1WI (Fig. 6a) shows a mass of 2.6 cm ¥ 2.3 cm ¥
2.2 cm in size with surrounding hypointense edema and
posterior displacement of fourth ventricle in the pons
(more on its left side); The mass is isointense in peri-
pheral part with some hypointense areas in core and
isointense septum (fine arrow). T2WIs (Fig. 6b,c) show
the mass having a significant hypointense rim and
septum (fine arrow) and hyperintense areas in core. DWI
(Fig. 6d) shows two significant hyperintense areas
Fig. 7. The specimens with haematoxylin and eosin stain (magnification ¥200)
(a) reveals numerous small cysts containing yeasts (arrows), as well as diffuse
(bold arrow) in corresponding part of T2 hyperintense
fibroplasia and inflammatory cell infiltrates within the granulomatous tissues. area in the core. Post-contrast images (Fig. 6e,f) show
The cellular infiltrates are composed of monocytes, lymphocytes and plas- intense rim enhancement of the mass without central
mocytes. Perl stain (magnification ¥200) (b) shows blue colour staining of the enhancement (arrowheads). No feature of meningitis
iron material (arrow). is seen.

© 2011 The Authors


56 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
MRI findings of cerebral cryptococcosis in immunocompetent patients

infection in an immunocompetent patient. Am J


Conclusion Neuroradiol 2005; 26: 2522–6.
The imaging manifestations of intracranial cryptoco- 4. Gültaş li NZ, Ercan K, Orhun S, Albayrak S. MRI
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comparison of tuberculous meningitis and
ment, vasculitis, clustered enhancing small cysts or
cryptococcal meningitis. QJM 2001; 94:
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247–53.
cal appearances of the disease in immunocompetent
6. Miszkiel KA, Hall-Craggs MA, Miller RF et al. The
patients. However, the patients may also show solitary
spectrum of MRI findings in CNS cryptococcosis in
enhancing arachnoid cyst and rim-enhancing solid mass.
AIDS. Clin Radiol 1996; 51: 842–50.
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7. Chrétien F, Lortholary O, Kansau I, Neuville S, Gray
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© 2011 The Authors


Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 57