It is particularly important in the era of the HIV/AIDS epidemy. The encapsulated yeast-like fungus was first isolated from fruit juice by San Felice in 1894 and was shown to be present in natural sources such as milk. Various types of soil contaminated with pigeon excretia provide an environmental source of this widely prevalent organism 1).
Infection occurs through inhalation of a small diameter (<10 μm) yeast-like organism, which enters the respiratory passage but then remains dormant depending on the host reaction 2).
The mode of spread to the CNS is through haematogeneous dissemination from the lungs. Subsequently, the fungus spreads to the CSF to cause meningitis, encephalitis and ependymitis; it is this leptomeningeal spread that is responsible for the clinical manifestations, rather than choroid plexitis alone, which is often asymptomatic 3).
The CNS is the preferred site for crpytococcal infection, as the soluble anticryptococcal factors present in serum are absent from CSF. In addition, the inflammatory response evoked is minimal, as the polysaccharide capsule of the fungus hinders phagocytosis and impairs leukocyte migration 4).
see also Cryptococcal choroid plexitis.
In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered. 5).
It is a common opportunistic fungal infection in immunocompromised patients, and the imaging findings differ from those in immunocompetent patients.
The spectrum of radiological findings includes dilated perivascular spaces, gelatinous pseudocysts, intraparenchymal cryptococcomas, miliary nodules, meningeal involvement, intraventricular/choroid plexus masses and hydrocephalus 6).
Dilated Virchow Robin spaces (VR) in the basal ganglia are reported to be the most common imaging finding. As the infection spreads, mucoid gelatinous material produced by the capsule of the fungus gets enmeshed with budding cryptococci, distending and dilating the VR spaces and resulting in the formation of cysts, called gelatinous pseudocysts. These are thought to be an “unreactive” form of meningoencephalitis, preferentially located in the basal ganglia, thalamus, midbrain and dentate nuclei. Gelatinous peusdocysts are non-enhancing lesions and appear similar to CSF on all imaging sequences. Some cases appear as intermediate signal on T1 weighted images owing to the presence of mucin/mucoid material that shortens T1 relaxation time 7) 8).
The lesions extend occasionally to the parenchyma adjacent to the perivascular space, with formation of intraparenchymal cryptococcomas and miliary lesions. These lesions are microabscesses containing amorphous debris and cryptococcal organisms encased in an outer fibrous capsule, and are observed in the brain parenchyma, leptomeningeal and cisternal spaces. They are of low intensity on T1 weighted images and high intensity on T2 weighted images. Immunocompetent patients are more likely to present with cryptococcomas and, because gelatinous peusdocysts represent lesions associated with a disruption of the blood–brain barrier, they may enhance on contrast 9) 10).
Kuwahara et al 11) suggested that cerebral sulcal hyperintensity on FLAIR images is an early sign of an indolent process/recurrent inflammation, even when the CSF findings following lumbar puncture are normal. This finding implies a high protein concentration in the localised subarachnoid space.
Gelatinous pseudocysts and cryptococcomas in the choroid plexus are relatively specific for CNS cryptococcosis. A unilateral or bilateral enlargement of the choroid plexus that enhances on contrast is a relatively rare manifestation of cryptococcal infection. Choroid inflammation can progress to ependymitis, intraventricular synechiae, loculation or enlargement, and entrapment of the temporal horn owing to the obstruction of flow by cryptococci, as seen in our case. Contrast enhancement may not occur in the presence of impaired immunity 12) 13).
Therefore, diagnosis frequently depends on the identification of cryptococci in CSF through the Indian ink preparation or on the detection of cryptococcal antigen in CSF to complement the imaging findings. The former is useful when >10 colony forming units (CFU) ml−1 of yeast are present. Other than Indian ink, Alcian blue and mucicarmine are the stains used to detect the polysaccharide capsule of yeast in tissue 14).
The choice of antifungal treatment depends on the site of infection and the immune status of the patient; options include polyene-amphotericin B (Amp B), azoles (fluconazole, itraconazole) and flucytocine. Serially preformed lumbar punctures may serve to reduce headache in a patient with raised intracranial pressure. The surgical option is reserved for patients with hydrocephalus and intracranial hypertension 15).