CNS cryptococcosis results from infection of the central nervous system with the yeast-like fungus Cryptococcus neoformans, or less commonly, Cryptococcus gattii. It is the most common fungal infection and second most common opportunistic infection of the central nervous system.
For a general discussion of infection with this organism, please refer to the article cryptococcosis.
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Epidemiology
The disease tends to occur in immunocompromised individuals, such as those with HIV/AIDS (which account for two-thirds of cases), organ transplant recipients, patients on immunosuppressive therapy, and idiopathic cd4 lymphocytopaenia 16.
Clinical presentation
Patients with cerebral cryptococcosis can present subtly and in a subacute fashion. Signs and symptoms may not be typical of pyogenic forms of meningitis/meningoencephalitis, but can include headache (most common symptom), seizures, altered mental state, focal neurological deficits, or visual loss due to raised intracranial pressure (causing papilloedema) 12,16.
Pathology
Central nervous system involvement with cryptococcosis typically results from haematogenous spread from the lungs, which is usually the primary site. In patients with HIV/AIDS, cryptococcal infection of the CNS usually occurs when the CD4+ count drops below 100 cells/µL. The disease can have either or both of meningeal or parenchymal involvement with the former being the primary manifestation 6,16. With meningeal involvement, a greyish, mucinous exudate accumulates over the involved brain surface.
There are three dominant CNS forms to the disease depending on which part of the brain is affected:
meninges: meningitis
parenchyma: cryptococcomas
perivascular spaces: gelatinous pseudocysts
Meningitis and cryptococcomas are seen in immunocompetent hosts usually and gelatinous pseudocysts are more common in patients with HIV/AIDS.
Radiographic features
The disease can have a variety of radiographic presentations and is influenced by the degree of immunocompromise and therapy. As a result, the literature describing features has evolved considerably in parallel to marked improvements in the management of HIV and the availability of antiretroviral therapy (ART).
As a general rule, in patients who are profoundly immunocompromised (and therefore, earlier literature), cryptococcosis demonstrates little enhancement. Instead, in patients who are on more effective therapy, enhancement is more frequently encountered 13.
The range of appearances includes 1-12,14-16:
dilated perivascular spaces coalescing into gelatinous pseudocysts
leptomeningeal and pachymeningeal enhancement
cryptococcomas (or torulomas)
miliary nodules
choroid plexitis
features of CNS vasculitis (very rare)
The most common pattern, particularly in profoundly immunocompromised patients is spread along the perivascular spaces, most commonly involving the basal ganglia but also the white matter of the cerebral hemispheres, the brainstem and cerebellum 12.
CT
CT findings can be often non-specific and with normal scans seen in a significant proportion of patients (reported up to ~40% 3). Diffuse atrophy is usually the next most commonly described feature but may relate more to HIV dementia than cryptococcosis 13. Hydrocephalus and mass lesions may also each be present.
MRI
MRI is better at assessing dilated perivascular spaces, one of the most frequently described features on MRI, and basal ganglia pseudocysts. These findings are more common in immunocompromised patients. Signal characteristics can vary dependent on the form of infection.
Meningeal disease
T1 C+ (Gd): can show leptomeningeal enhancement and pachymeningeal enhancement
FLAIR C+ (Gd): high signal in subarachnoid space 12
Cryptococcomas
T1: low signal
T2/FLAIR: high signal
T1 C+ (Gd): variable, ranging from no enhancement 5 to peripheral nodular enhancement 9
DWI/ADC: variable, may have both facilitated or restricted diffusion 12,13
Dilated perivascular spaces
Dilated perivascular space can coalesce into gelatinous pseudocysts that tend to give a "soap bubble" appearance.
T1: low to intermediate (from mucin) signal 9
T2: high signal
FLAIR: variable signal ranging from full suppression to persistent high signal
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DWI/ADC
variable; may have both facilitated or restricted diffusion 12,13
maybe complicated by perforator infarct (~25%) which demonstrate restricted diffusion 16
Treatment and prognosis
Treatment is with appropriate antifungal agents (e.g. liposomal amphotericin B and flucytosine followed by fluconazole) and management of raised intracranial pressure (e.g. repeated lumbar punctures, lumbar drain, ventriculoperitoneal shunt) 16. If left untreated it is usually fatal.
Complications
From the disease:
residual neurological deficits (e.g. visual or hearing impairment, focal deficits from lacunar ischaemic stroke)
epilepsy (rare)
From therapy:
paradoxical immune reconstitution inflammatory syndrome (IRIS)
postinfectious inflammatory response syndrome (PIIRS)
specific complications relating to antifungal agents (e.g. hepatotoxicity)
Differential diagnosis
General imaging differential considerations include:
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other types of CNS infection
pyogenic abscesses
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CNS lymphoma