This document discusses the neuroradiology of central nervous system (CNS) fungal infections. It covers the common fungal pathogens that can cause CNS infections such as Cryptococcus neoformans and Aspergillus fumigatus. Imaging findings for various fungal infections like cryptococcosis, aspergillosis, and mucormycosis are described. Cryptococcal meningitis most commonly presents as leptomeningeal enhancement on MRI. Aspergillosis can cause hemorrhagic or infarcted lesions. Mucormycosis often involves paranasal sinus infection with intracranial extension. The document also briefly discusses spinal fungal infections and references

1. Neuroradiology of CNS Fungal
Infections
Dr. Nishtha Jain
Senior Resident
Department of Neurology
GMC, Kota.

2. • Although CNS fungal infections are uncommon, their
prevalence is rising as the number of
immunocompromised patients increases worldwide.
• CNS fungal infections are also called cerebral mycosis.
• A focal “fungus ball” is also called a mycetoma or fungal
granuloma.

3. • A number of fungal pathogens can cause CNS
infections. The common are
• Coccidioides immitis,
• Aspergillus fumigatus,
• Cryptococcus neoformans,
• Histoplasma capsulatum,
• Candida albicans, and
• Blastomyces dermatitidis.

4. • Candidiasis, mucormycosis, and cryptococcal infections
are usually opportunistic infections.
• Cryptococcal meningoencephalitis is most commonly
seen followed by aspergillosis and candidiasis.
• They occur in patients with predisposing factors such as
diabetes, hematological malignancies, and
immunosuppression.
• Coccidioidomycosis and aspergillosis affect both
immunocompetent and immunocompromised patients.

5. • Hematogenous spread from the lungs to the CNS is the
most common route of infection.
• Fungal sinonasal infections may invade the skull base
and cavernous sinus directly.
• Sinonasal disease with intracranial extension
(rhinocerebral disease) is the most common pattern of
Aspergillus and Mucor CNS infection.

6. • CNS mycoses have four basic pathologic manifestations:
• Diffuse meningeal disease (most common),
• solitary or multiple focal parenchymal lesions (common),
• disseminated nonfocal parenchymal disease (rare), and
• focal durabased masses (rarest).

7. • Immunocompetent patients have a bimodal age
distribution with fungal infections disproportionately
represented in children and older individuals.
• There is a slight male predominance.
• Immunocompromised patients of all ages and both
sexes are at risk.

8. • Findings vary with the patient's immune status.
• Well-formed fungal abscesses are seen in
immunocompetent patients.
• Imaging early in the course of a rapidly progressive
infection in an immunocompromised patient may show
diffuse cerebral edema more characteristic of
encephalitis than fungal abscess.

9. CT FINDINGS
• Findings on NECT include hypodense parenchymal
lesions caused by focal granulomas or ischemia.
• Hydrocephalus is common in patients with fungal
meningitis.
• Patients with coccidioidal meningitis may demonstrate
thickened, mildly hyperdense basal meninges.
• Multifocal parenchymal hemorrhages are common in
patients with angioinvasive fungal species.

13. MR FINDINGS
• Parenchymal lesions are typically hypointense on T1WI.
• Irregular walls with nonenhancing projections into the
cavity are typical.
• T2/FLAIR scans in patients with fungal cerebritis show
bilateral but asymmetric cortical/subcortical and basal
ganglia hyperintensity.

14. • Focal lesions (mycetomas) show high signal foci that
typically have a peripheral hypointense rim, surrounded
by vasogenic edema.
• T2* scans may show “blooming” foci caused by
hemorrhages or calcification.
• Focal paranasal sinus and parenchymal mycetomas
usually restrict on DWI.

16. • T1 C+ FS scans usually show diffuse, thick, enhancing
basilar leptomeninges.
• Angioinvasive fungi may erode the skull base, cause
plaque-like dural thickening, and occlude one or both
carotid arteries.
• Parenchymal lesions show punctate, ring-like, or
irregular enhancement.

17. • MRS shows mildly elevated Cho and decreased NAA.
• A lactate peak is seen in 90% of cases, while lipid and
amino acids are identified in approximately 50%.
• Multiple peaks resonating between 3.6 and 3.8 ppm are
common and probably represent trehalose.

24. Differential Diagnosis
• Fungal abscesses can sometimes be differentiated from
pyogenic abscesses by their more irregularly shaped
walls and internal nonenhancing projections, together
with resonance between 3.6 and 3.8 ppm on MRS.
• TB can have crenelated margins and appear similar to
fungal abscesses on standard imaging studies.
• Gross hemorrhage is more common with fungal than
either pyogenic or tubercular abscesses.
• Other mimics of fungal abscesses are primary
neoplasm (e.g., glioblastoma with central necrosis) or
metastases.

25. Aspergillosis
• Aspergillus fumigatus is the most common human
pathogen.
• Humans are infected by inhaling these spores, with the
lungs and paranasal sinuses as the primary site of
infection.
• Infection reaches the brain directly from the nasal
sinuses or is hematogenous from the lungs and
gastrointestinal tract.
• Rarely, the infection may contaminate the operative field
during a neurosurgical procedure.

26. • The pathology of CNS aspergillosis can be classified into
three forms:
• infarction,
• granulomas and
• meningitis.
• The fungal hyphae block intracerebral blood vessels,
resulting in thrombosis and subsequent infarction and
hemorrhage.
• The fungus can then spread beyond the vessel walls and
form abscesses in the altered brain tissue.

27. • Purulent lesions may be chronic and have a tendency
towards fibrosis and granuloma formation.
• Erosion of vessel wall can also form mycotic aneurysms.
• Aspergillosis is the most common cause of mycotic
aneurysm.

28. • Using computed tomography (CT) and magnetic
resonance (MR), several patterns of cerebral
aspergillosis have been reported:
• edematous lesions,
• hemorrhagic lesions,
• solid enhancing lesions referred to as aspergilloma or
tumoral form,
• abscess like ring-like enhancing lesions
• Infarction
• Mycotic aneurysms

33. • Axial T1 post-gadolinium
image shows typical
lesions of multifocal
angioinvasive
aspergillosis at the gray–
white junction
(arrowheads).

34. Cryptococcosis
• Cryptococcus neoformans is the most common mycotic
agent to affect the CNS.
• It is found in mammal and bird feces, particularly in
pigeon droppings.
• It causes disease primarily in patients with impaired
immunity, particularly in those with AIDS.
• However, up to 30% of the patients have been reported
with no predisposing condition.
• Men are more commonly infected than women by
cryptococcal infection.

35. • The infection is acquired through inhalation and spreads
hematogenously to the CNS.
• The central nervous system is the preferred site for
cryptococcal infection, because soluble anticryptococcal
factors present in serum are absent in cerebrospinal fluid
(CSF) and the polysaccharide capsule of the fungus
protects it from host inflammatory response.

36. • CNS infection can be either meningeal or parenchymal.
• Meningitis is often the primary manifestation and is most
pronounced at the base of the brain.
• Parenchymal involvement is seen as cryptococcomas,
dilated Virchow-Robin spaces or enhancing cortical
nodules.
• The commonest parenchymal sites are the midbrain and
the basal ganglia.

37. • Hydrocephalus is the most common, although
nonspecific finding.
• Pseudocysts are seen as well-circumscribed, round to
oval low-density lesions on CT and have CSF intensity
on both T1WI and T2WI, which fail to enhance.
• Demonstration of clusters of these cysts in the basal
ganglia and thalami strongly suggest cryptococcal
infection.

38. • Miliary lesions and cryptococcomas may present as
variable density masses on CT and of low intensity on
T1WIand high intensity on T2WI.
• Granulomatous lesions are located preferentially on the
ependyma of the choroid plexus and may enhance.
• However, contrast enhancement of cryptococcomas or
meninges is uncommon in immunocompromised patients
due to the underlying immunosuppression and non-
immunogenic nature of the polysaccharide capsule of
the cryptococcal organism.

39. Meningeal disease
• T1 C+ (Gd): can show leptomeningeal enhancement
Cryptococcomas
• T1: low signal
• T2 / FLAIR: high signal
• T1 C+ (Gd): variable, ranging from no enhancement to
peripheral nodular enhancement

40. Gelatinous pseudocysts
• Tend to give a "soap bubble" appearance.
• T1: low to intermediate (from mucin) signal
• T2: high signal
• FLAIR: low signal

41. • Immunocompetent patients are more likely to present
with cryptococcomas.
• Enhancement of these lesions might occur as a result of
an immunologic reaction by the host.
• Immediate and delayed imaging with a double dose of
contrast has been reported to reduce the false negative
studies by showing meningeal enhancement in
immunocompromised patients.

42. • Axial T1 post-gadolinium
image shows typical
cryptococcal meningitis
with ventricular wall
enhancement and subtle
frontal and occipital
leptomeningeal
enhancement.

47. Mucormycosis
• Mucormycosis is a life-threatening opportunistic fungal
infection.
• When spores are converted into hyphae, they become
invasive, involve blood vessels and disseminate
hematogenously or may spread through the paranasal
sinuses into the brain and orbits.

48. • Diabetics comprise at least 70% of the reported cases
and less than 5% occur in normal hosts.
• Acidosis rather than hyperglycemia appears to be the
important predisposing factor.
• Infection can also be seen in iv drug abusers, in patients
of anemia, leukemia, uremia and severe burns and in
those receiving corticosteroid or chemotherapy.

49. • The rhinocerebral form is the most common infection.
• The organism may spread directly through the cribriform
plate,or via extension into the orbit and then through the
optic canal or superior orbital fissure into the cavernous
sinus.
• Prognosis is poor even after aggressive antifungal
treatment and surgical debridement.

50. • Isolated CNS mucormycosis, a focal intracerebral infection, is
rare and is mostly seen in drug abusers.
• It presents with acute onset and rapid development of
neurological symptoms.
• The suspected source of infection is spores in the injected
substances.
• Infarcts and abscesses are found on imaging studies, most
commonly in the basal ganglia.
• Restricted diffusion may be the earliest detectable
abnormality in rhinocerebral mucormycosis.

51. • Axial T1 post-gadolinium
image shows
mucormycosis with
intracranial extension and
enhancement at the
inferior frontal lobe
following a sinus
infection.

53. Candidiasis
• Human candidiasis is most commonly caused by
Candida albicans.
• The clinical manifestations of candidiasis are primarily of
three types:
• mucocutaneous,
• cutaneous and
• systemic or disseminated.

54. • Primary candidiasis of the brain and meninges is rare;
however, CNS invasion is reported in 18-52% in
disseminated candidiasis.
• Candida causes focal necrosis around the
microcirculation mainly in the middle cerebral artery
territory producing microabscesses.
• It can also cause vasculitis, intraparenchymal
hemorrhage, aneurysms and thrombosis of small
vessels with secondary infarction.

55. • Microabcesses appear iso to hypodense on
nonenhanced CT and show multiple punctate enhancing
nodules on contrast study.
• Granuloma may appear as hyperdense nodule on CT
with nodular or ring enhancement.
• On MR, granuloma formation and brain abscess may
have hypointense signals on T2WI due to the magnetic
susceptibility effect of hemorrhage.

56. • Lesions show ring-enhancement on contrast
administration.
• MR also shows features of associated meningitis,
vasculitis and infarction.

57. • Cerebral candidiasis usually
appears as microabscesses
measuring less than 3 mm.
• Axial T1 post-gadolinium
sequences show punctate
subcortical foci of
enhancement.
• Axial DWI shows reduced
diffusion of multiple lesions,
including several not seen
on contrast-enhanced
sequence.

59. Spinal Infections
• Fungal infections of the spine are relatively uncommon.
• They have been reported with Candida, aspergillosis,
cryptococcus, coccidioidomycosis and histoplasmosis.
• Candida and Aspergillus produce disease when they
gain access to the vascular system through intravenous
lines, during implantation of prosthetic devices or during
surgery.
• For the other fungi, spinal involvement usually is the
result of hematogenous or direct spread of organisms
from an initial pulmonary source of infection.

60. • Fungal spondylitis secondary to Candida and Aspergillus
is characterized by low signal intensity on T1WI and high
signal intensity on T2WI with intervening disc
involvement.
• The bone marrow in the affected vertebral bodies may
show low signal intensity on both T1WI and T2WI due to
lack of inflammatory response in immunocompromised
patients.

61. • Skeletal coccidioidomycosis is frequently multicentric.
• The axial skeleton is the most common site.
• Spinal involvement is seen in approximately 25% of
patients with disseminated disease.
• Plain radiographs are effective in the initial evaluation of
bones and joints.

62. • CT and MR are useful in determining soft tissue
involvement and spinal abnormalities.
• The typical imaging features include disc involvement,
heterogeneous marrow signal alteration and extensive
extra-osseous involvement with lack of bony deformity.
• As the disease is multifocal, MR screening of the entire
vertebral column often reveals occult areas of
involvement.

63. • Spinal cord disease is a rare presentation of
cryptococcosis.
• Bony involvement is seen in 5% of disseminated
cryptococcosis.
• Imaging findings are not specific and simulate spinal
tuberculosis with involvement of the vertebral body along
with posterior elements and paraspinous and
perivertebral soft tissues with relative preservation of the
disc.

64. • Bone is the one of the frequent sites of disease in
patients with blastomycosis, lower thoracic or lumbar
vertebrae being most often affected.
• MR reveals destructive vertebral changes, an epidural
mass, psoas abscess and lack of involvement of the disc
spaces.
• Sparing of the disc space is due to spread of infection by
way of paravertebral structures and surrounding
potential spaces.
• Blastomycosis can rarely present as an isolated
intramedullary lesion.

67. Referrences
• Osborn's Brain Imaging
• MRI of CNS Fungal Infections: Review of Aspergillosis to
Histoplasmosis and Everything in Between. J. Starkey ·
T. Moritani · P. Kirby. Clin Neuroradiol (2014) 24:217–
230.
• Imaging features of central nervous system fungal
infections. Jain K K. Et al. Neurology India 2007 :Vol 55
Issue 3
• Unusual Presentation of Central Nervous System
Cryptococcal Infection in an Immunocompetent Patient.
Saigal G. Et al. AJNR Am J Neuroradiol 2005. 26:2522–
2526.
• Radiopedia.org.com