Neuroradiology of CNS Fungal Infections

Dr. Nishtha JainSenior Resident

Department of NeurologyGMC, Kota.

• 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.

• 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.

• 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.

• 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.

• 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).

• 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.

• 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.

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.

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.

• 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.

• 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.

• 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.

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.

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.

• 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.

• 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.

• 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

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

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.

• 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.

• 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.

• 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.

• 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.

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

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

• 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.

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

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.

• 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.

• 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.

• 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.

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

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.

• 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.

• 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.

• Lesions show ring-enhancement on contrast administration.

• MR also shows features of associated meningitis, vasculitis and infarction.

• 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.

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.

• 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.

• 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.

• 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.

• 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.

• 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.

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