You are in: eMedicine Specialties > Radiology > BRAIN/SPINE Cryptococcosis, CNSArticle Last Updated: Jun 21, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 7
  Author: Farhood Saremi, MD, Professor of Radiology, Director of Cardiothoracic Radiology, Department of Radiological Sciences, University of California-Irvine Farhood Saremi is a member of the following medical societies: American College of Radiology and Radiological Society of North America Coauthor(s): John L Go, MD, Assistant Professor, Department of Radiology, Section of Neuroradiology, Keck School of Medicine, University of Southern California Medical Center; Chi-Shing Zee, MD, Chief of Neuroradiology, Professor, Departments of Radiology and Neurosurgery, University of Southern California School of Medicine Editors: Lucien M Levy, MD, PhD, Director of Neuroradiology, Professor of Radiology, Department of Radiology, George Washington University Medical Center; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences Author and Editor Disclosure Synonyms and related keywords: Cryptococcus neoformans, C neoformans, cryptococcal meningitis, cryptococcal meningoencephalitis, AIDS-related cryptococcal meningitis, AIDS-related CNS cryptococcosis, cryptococcomas, gelatinous pseudocysts, Toxoplasma gondii, T gondii, inhaled yeast, CNS yeast infection INTRODUCTIONSection 2 of 7
  BackgroundCryptococcus neoformans is a yeast that most commonly infects the central nervous system (CNS). PathophysiologyMost initial cryptococcal infections occur through inhalation of the yeast from the environment. Cryptococci have large polysaccharide capsules that strongly resist phagocytosis; the inflammatory reaction to the inhaled organisms produces a primary pulmonary–lymph node complex, which usually limits spread of the yeast from this site. Most pulmonary cryptococcal infections are asymptomatic, but severely immunocompromised patients may develop diffuse interstitial pneumonitis. C neoformans spreads from the lung and intrathoracic lymph nodes to circulate in the blood, especially if the host is immunocompromised. Dissemination can occur during primary infection or during reactivation of the infection years later. The most commonly involved site is the CNS. Resistance to cryptococcosis depends primarily on cell-mediated immunity.1 Therefore, most cases of cryptococcal meningitis occur in patients with conditions that weaken this system, such as acquired immunodeficiency syndrome (AIDS), reticuloendothelial malignancies, organ transplantation, or corticosteroid therapy. The typical pathologic findings of CNS cryptococcosis include meningitis, cryptococcomas, and dilated perivascular spaces from spread of the organism. Significant differences are reported in the inflammatory response to cryptococcal meningoencephalitis among patients with and those without human immunodeficiency virus (HIV) infection. Granulomatous inflammation is not common in patients with AIDS, whereas most patients without HIV infection have granulomas; this observation suggests a role for cell-mediated immunity in cryptococcal meningoencephalitis.1 An encephalitic component is common in HIV-associated patients, resulting in macroscopically or microscopically visible accumulations of organisms within the brain parenchyma. In cases that are not associated with HIV infection, cryptococcal meningoencephalitis is often confined to the subarachnoid and perivascular Virchow-Robin spaces. In HIV-associated cases, large parenchymal cryptococcomas contain C neoformans with cell wall pigmentation that is suggestive of melanin.1 In patients with AIDS, it has been suggested that altered immune functions allow C neoformans to accumulate within the brain, predominantly extracellularly. Deficient macrophage/microglial effector function may be responsible for the altered pathology. FrequencyInternationalC neoformans is distributed worldwide. Mortality/MorbidityUntreated cryptococcal meningitis has a mortality of 100%; therefore, early recognition of the disease and treatment are essential. Clinical DetailsApproximately 5% of patients with AIDS develop CNS cryptococcosis. Following HIV and Toxoplasma gondii, C neoformans is the third most common pathogen that causes CNS infection in patients with AIDS. Most patients with C neoformans CNS infection present with subacute or chronic illness, altered mental state, behavioral changes, headache, and fever. Focal neurologic signs, however, are unusual. Preferred ExaminationThe diagnosis of CNS cryptococcosis is made on the basis of a series of microbiologic investigations, including cerebrospinal fluid (CSF) culture and positive identification of the yeast with India ink staining, elevated cryptococcal antigen latex agglutination titers in CSF and blood, and positive results with blood cultures. A diagnosis of cryptococcal meningitis in a patient with AIDS is complicated by the fact that the CSF cell count and protein and glucose results may be normal or only mildly abnormal compared with the nearly always abnormal laboratory values in HIV-negative patients with cryptococcal meningitis. The presence of fever and headache in a patient with AIDS or an individual at risk for AIDS should prompt an investigation for CNS cryptococcal disease. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are important diagnostic techniques in any patient with HIV infection or a patient with AIDS and neurologic dysfunction. Limitations of TechniquesSeveral studies have shown that MRI is superior to CT scanning in detecting abnormalities in CNS cryptococcosis,2 but both imaging modalities underestimate the number of lesions compared with pathologic examination.3 Normal MRI findings do not exclude CNS cryptococcosis because the typical features of this infection occur in only 40% of patients. DIFFERENTIALSSection 3 of 7
Brain, Abscess Brain, Lymphoma Toxoplasmosis, CNS Other Problems to Be ConsideredIntracranial mass lesions occur frequently in patients with AIDS. The most common mass lesions detected by CT scanning or MRI are abscesses from toxoplasmosis, although lymphoma and less common infectious processes, such as cryptococcomas, must also be considered. CT SCANSection 4 of 7
FindingsIn a retrospective study, CT scans of 35 patients with intracranial cryptococcal infection were reviewed.4 Findings were unremarkable in 43% of the patients. Positive findings included diffuse atrophy (34%), cryptococcomas (11%), hydrocephalus (9%), and diffuse cerebral edema (3%). Cryptococcomas are round, hypoattenuating or isoattenuating lesions that occur less commonly as gelatinous pseudocysts (rather than as granulomas or abscesses). Degree of ConfidenceCT scan findings are often nonspecific for CNS cryptococcosis. FindingsCryptococcal meningitis is the most common CNS manifestation of cryptococcosis and often has an insidious course (see Image 1). AIDS-related cryptococcal meningitis does not always produce leptomeningeal enhancement on CT scans or MRIs.3 Cryptococcal organisms spread from the basal cisterns through the Virchow-Robin spaces to the basal ganglia (see Images 1-2), internal capsule, thalamus, and brainstem.6 The production of voluminous mucoid material may enlarge the perivascular spaces. MRI is more sensitive than CT scanning in demonstrating abnormalities such as dilated perivascular spaces. These manifest on T2-weighted MRIs as punctate, hyperintense, round or oval lesions that are usually smaller than 3 mm. Enlarged perivascular spaces are not always a consequence of cryptococcosis and can be the result of age-related changes or HIV-related atrophy. Generalized atrophy is common in patients with AIDS; however, the observation of punctate hyperintensities is suggestive of cryptococcal disease, especially if other signs of diffuse atrophy (eg, ventricular and sulcal enlargement) are not present or if the patient has clinical signs or symptoms of meningitis. By definition, cryptococcomas represent a collection of organisms, inflammatory cells, and gelatinous mucoid material in the brain parenchyma. Cryptococcomas can develop when organisms have extended directly from perivascular spaces into the parenchyma (see Images 4-5) or, possibly, when they have invaded the parenchyma from other meningeal or ependymal surfaces. Cryptococcomas are hyperintense on T2-weighted images. Although contrast enhancement of cryptococcomas is uncommon in AIDS-related CNS cryptococcosis,3 it has been reported.5 The cryptococcal organism is surrounded by a polysaccharide capsule, which may protect it from the host inflammatory response even in immunocompetent patients. In immunologically intact hosts, the organisms usually induce a chronic granulomatous reaction. On MRI, the most common findings are punctate masses that demonstrate low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, without surrounding edema. Choroid plexitis of the brain is a pathologic presentation of cryptococcosis. MRI demonstrates unilateral or bilateral enlargement and dense enhancement of the choroid plexus in the lateral and fourth ventricles.7 These findings occur in association with clinical findings of leptomeningitis, and the lesion may appear as an enhancing, intraventricular mass. Unilateral cystic dilatation of the temporal horn of the lateral ventricle has also been described.7 Cho et al believed this dilatation may be due to entrapment of the temporal horn by inflamed choroid plexus, as well as extensive edema around the ipsilateral ventricle.7 Degree of ConfidenceAlthough MRI is useful as part of the initial investigation protocol in patients with suspected cryptococcal meningitis, serial imaging probably has a minimal role in monitoring response to therapy. However, magnetic resonance spectroscopy can potentially detect changes in the metabolites that are related to inflammatory activity. MULTIMEDIASection 6 of 7
REFERENCESSection 7 of 7
Article Last Updated: Jun 21, 2007 | ||||||||||||||||||||||||||||||||||||||||||
