eMedicine Specialties > Radiology > Brain/Spine

Cryptococcosis, CNS

Farhood Saremi, MD, Professor of Radiology, Director of Cardiothoracic Radiology, Department of Radiological Sciences, University of California-Irvine
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

Updated: Dec 10, 2008

Introduction

T2-weighted axial magnetic resonance image demonstrates linear and punctate hyperintensities in the basal ganglia; these represent dilated perivascular spaces caused by small cryptococcomas. Cryptococcomas vary in size from several millimeters to several centimeters.

Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.

Presentation

Demographics

• Cryptococcosis of the CNS occurs worldwide.
• If left untreated, cryptococcosis of the CNS has a mortality of 100%; therefore, early recognition and treatment of the disease are essential.

Presentation and natural history

Cryptococcus neoformans is a yeast that most commonly infects the central nervous system (CNS).¹ Most 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.^2,3,4,5

C neoformans spreads from the lung and intrathoracic lymph nodes to circulate in the blood, especially if the host is immunocompromised. Dissemination may 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.⁶ 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.^7,8,9,10

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 that cell-mediated immunity plays a role in cryptococcal meningoencephalitis.⁶ An encephalitic component is common in HIV-associated patients; encephalitis results in macroscopically or microscopically visible accumulations of organisms within the brain parenchyma. In cases of cryptococcal meningoencephalitis that are not associated with HIV infection, the infection 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.⁶ In patients with AIDS, it has been suggested that alterations in immune functions allow C neoformans to accumulate within the brain, predominantly extracellularly. Deficient macrophage/microglial effector function may be responsible for the altered pathology.

Preferred Examination

The 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; elevations in cryptococcal antigen latex agglutination titers in CSF and blood; and positive results with blood cultures.^11,12,13

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 seen in HIV-negative patients with cryptococcal meningitis. The presence of fever and headache in a patient with AIDS or in an individual at risk for AIDS should prompt an investigation for CNS cryptococcal disease.

Computed tomography (CT) 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 Techniques

Several studies have shown that MRI is superior to CT in detecting abnormalities in patients with CNS cryptococcosis,¹⁴ but with both imaging modalities, the number of lesions revealed is fewer than the number seen on pathologic examination.¹⁵ Normal MRI findings do not exclude CNS cryptococcosis because the typical features of this infection occur in only 40% of patients.

Differential Diagnoses

Brain, Abscess
Brain, Lymphoma
Toxoplasmosis, CNS

Other Problems to Be Considered

Intracranial mass lesions occur frequently in patients with AIDS. The most common mass lesions detected by CT or MRI are abscesses from toxoplasmosis, although lymphoma and less common infectious processes, such as cryptococcomas, must also be considered.

Computed Tomography

Findings

Techniques and findings

In a retrospective study, CT scans of 35 patients with intracranial cryptococcal infection were reviewed.¹⁶ 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).

In immunologically intact hosts, the cryptococci usually induce a chronic granulomatous reaction. On CT scans, cerebral cryptococcal granulomas appear as hypoattenuating or isoattenuating lesions, with or without enhancement.

Accuracy

• CT findings are often nonspecific for CNS cryptococcosis.

Imaging pearls

• Intracranial mass lesions occur frequently in patients with AIDS. The most common mass lesions detected by CT or MRI are abscesses from toxoplasmosis, although lymphoma and less common infectious processes, such as cryptococcomas, must also be considered.

Magnetic Resonance Imaging

Findings

Techniques and findings

Cryptococcal meningitis is the most common CNS manifestation of cryptococcosis; the disease often has an insidious course (see Image below and Image 1 in Multimedia Section). In cases of AIDS-related cryptococcal meningitis, leptomeningeal enhancement is not always seen on CT scans or MRIs.^13,15,17
 

Axial contrast-enhanced T1-weighted magnetic resonance image shows diffuse, gyriform leptomeningeal enhancement. Enhancing lesions in the left basal ganglia, left temporal lobe, and left occipital lobe correspond to intraparenchymal cryptococcosis.

Cryptococcal organisms spread from the basal cisterns through the Virchow-Robin spaces to the basal ganglia (see Images below and Images 1-2 in Multimedia Section), internal capsule, thalamus, and brainstem.¹⁹ The perivascular spaces may be enlarged as a result of the production of voluminous mucoid material. MRI is more sensitive than CT 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; they may be the result of age-related changes or HIV-related atrophy.

Axial contrast-enhanced T1-weighted magnetic resonance image shows diffuse, gyriform leptomeningeal enhancement. Enhancing lesions in the left basal ganglia, left temporal lobe, and left occipital lobe correspond to intraparenchymal cryptococcosis.

T1-weighted magnetic resonance image demonstrates dilated perivascular spaces in the bilateral basal ganglia.

By definition, cryptococcomas represent a collection of organisms, inflammatory cells, and gelatinous mucoid material in the brain parenchyma. Cryptococcomas may develop when organisms have extended directly from perivascular spaces into the parenchyma (see Images below and Images 3-5 in Multimedia Section) or, possibly, when they have invaded the parenchyma from other meningeal or ependymal surfaces.

T2-weighted axial magnetic resonance image demonstrates linear and punctate hyperintensities in the basal ganglia; these represent dilated perivascular spaces caused by small cryptococcomas. Cryptococcomas vary in size from several millimeters to several centimeters.

Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.

T2-weighted axial magnetic resonance image demonstrates hyperintense cryptococcomas in the midbrain.

Cryptococcomas are hyperintense on T2-weighted images. Although contrast enhancement of cryptococcomas is uncommon in cases of AIDS-related CNS cryptococcosis,¹⁵ it has been reported.¹⁸ 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.²⁰ These findings occur in association with clinical findings of leptomeningitis. The lesion may appear as an enhancing, intraventricular mass.

Unilateral cystic dilatation of the temporal horn of the lateral ventricle has also been described.²⁰ Cho et al believed this dilatation may be the result of entrapment of the temporal horn by inflamed choroid plexus, as well as extensive edema around the ipsilateral ventricle.²⁰

Accuracy

• Although MRI is useful as part of the initial investigation protocol for patients with suspected cryptococcal meningitis, serial imaging probably has a minimal role in monitoring response to therapy. However, magnetic resonance spectroscopy may detect changes in the metabolites that are related to inflammatory activity.

Multimedia

Media file 1: Axial contrast-enhanced T1-weighted magnetic resonance image shows diffuse, gyriform leptomeningeal enhancement. Enhancing lesions in the left basal ganglia, left temporal lobe, and left occipital lobe correspond to intraparenchymal cryptococcosis.

Media file 2: T1-weighted magnetic resonance image demonstrates dilated perivascular spaces in the bilateral basal ganglia.

Media file 3: T2-weighted axial magnetic resonance image demonstrates linear and punctate hyperintensities in the basal ganglia; these represent dilated perivascular spaces caused by small cryptococcomas. Cryptococcomas vary in size from several millimeters to several centimeters.

Media file 4: Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.

Media file 5: T2-weighted axial magnetic resonance image demonstrates hyperintense cryptococcomas in the midbrain.

References

1. Perfect JR, Durack DT. Fungal meningitis. In: Scheld WM, Whitely RJ, Durack DT, eds. Infections of the Central Nervous System. 2^nd ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1997:721-4.

2. Berkefeld J, Enzensberger W, Lanfermann H. Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms. Neuroradiology. Feb 1999;41(2):129-33. [Medline].

3. Eisen DP, Dean MM, O'Sullivan MV, Heatley S, Minchinton RM. Mannose-binding lectin deficiency does not appear to predispose to cryptococcosis in non-immunocompromised patients. Med Mycol. Jun 2008;46(4):371-5. [Medline].

4. Jong A, Wu CH, Zhou W, Chen HM, Huang SH. Infectomic analysis of gene expression profiles of human brain microvascular endothelial cells infected with Cryptococcus neoformans. J Biomed Biotechnol. 2008;2008:375620. [Medline].

5. Vender JR, Miller DM, Roth T, Nair S, Reboli AC. Intraventricular cryptococcal cysts. AJNR Am J Neuroradiol. Jan 1996;17(1):110-3. [Medline]. [Full Text].

6. Lee SC, Dickson DW, Casadevall A. Pathology of cryptococcal meningoencephalitis: analysis of 27 patients with pathogenetic implications. Hum Pathol. Aug 1996;27(8):839-47. [Medline].

7. Parameswaran IG, Segal BH. Immunotherapy for fungal infections with special emphasis on central nervous system infections. Neurol India. Jul-Aug 2007;55(3):260-6. [Medline].

8. Saigal G, Post MJ, Lolayekar S, Murtaza A. Unusual presentation of central nervous system cryptococcal infection in an immunocompetent patient. AJNR Am J Neuroradiol. Nov-Dec 2005;26(10):2522-6. [Medline]. [Full Text].

9. Singh N, Lortholary O, Dromer F, Alexander BD, Gupta KL, John GT, et al. Central nervous system cryptococcosis in solid organ transplant recipients: clinical relevance of abnormal neuroimaging findings. Transplantation. Sep 15 2008;86(5):647-51. [Medline].

10. Thakur R, Sarma S, Kushwaha S. Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center. Indian J Pathol Microbiol. Apr-Jun 2008;51(2):212-4. [Medline].

11. Harris DE, Enterline DS. Neuroimaging of AIDS. I. Fungal infections of the central nervous system. Neuroimaging Clin N Am. May 1997;7(2):187-98. [Medline].

12. Hospenthal DR, Bennett JE. Persistence of cryptococcomas on neuroimaging. Clin Infect Dis. Nov 2000;31(5):1303-6. [Medline].

13. Offiah CE, Turnbull IW. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients. Clin Radiol. May 2006;61(5):393-401. [Medline].

14. Patronas NJ, Makariou EV. MRI of choroidal plexus involvement in intracranial cryptococcosis. J Comput Assist Tomogr. Jul-Aug 1993;17(4):547-50. [Medline].

15. Mathews VP, Alo PL, Glass JD, Kumar AJ, McArthur JC. AIDS-related CNS cryptococcosis: radiologic-pathologic correlation. AJNR Am J Neuroradiol. Sep-Oct 1992;13(5):1477-86. [Medline].

16. Popovich MJ, Arthur RH, Helmer E. CT of intracranial cryptococcosis. AJR Am J Roentgenol. Mar 1990;154(3):603-6. [Medline]. [Full Text].

17. Kamezawa T, Shimozuru T, Niiro M, Nagata S, Kuratsu J. MRI of a cerebral cryptococcal granuloma. Neuroradiology. Jun 2000;42(6):441-3. [Medline].

18. Arnder L, Castillo M, Heinz ER, et al. Unusual pattern of enhancement in cryptococcal meningitis: in vivo findings with postmortem correlation. J Comput Assist Tomogr. Nov-Dec 1996;20(6):1023-6. [Medline].

19. Wehn SM, Heinz ER, Burger PC, Boyko OB. Dilated Virchow-Robin spaces in cryptococcal meningitis associated with AIDS: CT and MR findings. J Comput Assist Tomogr. Sep-Oct 1989;13(5):756-62. [Medline].

20. Cho IC, Chang KH, Kim YH, et al. MRI features of choroid plexitis. Neuroradiology. May 1998;40(5):303-7. [Medline].

Keywords

cryptococcosis of the central nervous system, 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

Contributor Information and Disclosures

Author

Farhood Saremi, MD, Professor of Radiology, Director of Cardiothoracic Radiology, Department of Radiological Sciences, University of California-Irvine
Farhood Saremi, MD is a member of the following medical societies: American College of Radiology and Radiological Society of North America
Disclosure: Nothing to disclose.

Coauthor(s)

John L Go, MD, Assistant Professor, Department of Radiology, Section of Neuroradiology, Keck School of Medicine, University of Southern California Medical Center
Disclosure: Nothing to disclose.

Chi-Shing Zee, MD, Chief of Neuroradiology, Professor, Departments of Radiology and Neurosurgery, University of Southern California School of Medicine
Chi-Shing Zee, MD is a member of the following medical societies: American Society of Neuroradiology
Disclosure: Nothing to disclose.

Medical Editor

Lucien M Levy, MD, PhD, Director of Neuroradiology, Professor of Radiology, Department of Radiology, George Washington University Medical Center
Lucien M Levy, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Radiology, American Heart Association, American Medical Association, American Roentgen Ray Society, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

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
James G Smirniotopoulos, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, American Society of Head and Neck Radiology, American Society of Neuroradiology, American Society of Pediatric Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

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