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Imaging in CNS Cryptococcosis

  • Author: Farhood Saremi, MD; Chief Editor: James G Smirniotopoulos, MD  more...
 
Updated: Dec 18, 2015
 

Overview

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. 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. In cases of cryptococcal meningoencephalitis that are not associated with human immunodeficiency virus (HIV) infection, the infection is often confined to the subarachnoid and perivascular Virchow-Robin spaces (see the image below).[2, 3]

Axial T2-weighted magnetic resonance image shows c 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.

Preferred Examination

Although the diagnosis of CNS cryptococcosis is made on the basis of a series of microbiologic investigations, computed tomography (CT) scanning and magnetic resonance imaging (MRI) are important diagnostic techniques in any patient with HIV infection or a patient with acquired immunodeficiency syndrome (AIDS) and neurologic dysfunction. Several studies have shown that MRI is superior to CT in detecting abnormalities in patients with CNS cryptococcosis,[4] but with both imaging modalities, the number of lesions revealed is fewer than the number seen on pathologic examination.[5] Normal MRI findings do not exclude CNS cryptococcosis, because the typical features of this infection occur in only 40% of patients.[6, 7, 8, 9, 10]

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Computed Tomography

CT scan findings are often nonspecific for CNS cryptococcosis. In a retrospective study, CT scans of 35 patients with intracranial cryptococcal infection demonstrated unremarkable findings in 43% of the patients.[11] However, positive findings included diffuse atrophy (34%), cryptococcomas (11%), hydrocephalus (9%), and diffuse cerebral edema (3%).

Cryptococcomas appear as 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, these cerebral cryptococcal granulomas appear as hypoattenuating or isoattenuating lesions, with or without enhancement.

Intracranial 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.[12]

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Magnetic Resonance Imaging

Cryptococcal meningitis is the most common CNS manifestation of cryptococcosis; the disease often has an insidious course (see the image below). In cases of AIDS-related cryptococcal meningitis, leptomeningeal enhancement is not always seen on CT scans or MRIs.[5, 13, 14, 15, 6]

Axial contrast-enhanced T1-weighted magnetic reson 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.

The cryptococcal organism is surrounded by a polysaccharide capsule, which may protect it from the host inflammatory response even in immunocompetent patients. In response to the attack on the organisms by the host's immune system, the cryptococci produce a mucoid material. In a study by Arnder et al, of 3 patients were diagnosed with cryptococcal meningitis, 2 patients demonstrated thick enhancing subarachnoid spaces on postcontrast MRIs.[16] The diagnoses were confirmed at autopsy. In the postmortem MRI and pathologic examinations of the third patient, these areas of enhancement corresponded to the abundant mucoid material secreted by the organisms.[16]

Cryptococcal organisms spread from the basal cisterns through the Virchow-Robin spaces to the basal ganglia (as shown in the images below), internal capsule, thalamus, and brainstem.[3] The perivascular spaces may be enlarged as a result of the production of voluminous mucoid material. 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; they may be the result of age-related changes or HIV-related atrophy.

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

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 may develop when organisms have extended directly from perivascular spaces into the parenchyma (see the following images) or, possibly, when they have invaded the parenchyma from other meningeal or ependymal surfaces.

T2-weighted axial magnetic resonance image demonst 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 c 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 demonst 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,[5] it has been reported.[16] 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.[17] 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.[17] 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.[17]

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.

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Contributor Information and Disclosures
Author

Farhood Saremi, MD Professor of Radiology, Department of Radiology, Keck School of Medicine of the University of Southern California

Farhood Saremi, MD is a member of the following medical societies: American College of Radiology, Society for Cardiovascular Magnetic Resonance, Society of Cardiovascular Computed Tomography, Radiological Society of North America

Disclosure: Nothing to disclose.

Coauthor(s)

Chi-Shing Zee, MD Chief of Neuroradiology, Professor, Departments of Radiology and Neurosurgery, Keck School of Medicine of the University of Southern California

Chi-Shing Zee, MD is a member of the following medical societies: American Society of Neuroradiology

Disclosure: Nothing to disclose.

John L Go, MD Assistant Professor of Clinical Radiology, Director, Spinal Imaging and Intervention, Division of Neuroradiology, University of Southern California Keck School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Chief Editor

James G Smirniotopoulos, MD Professor of Radiology, Neurology, and Biomedical Informatics, Program Director, Diagnostic Imaging Program, Center for Neuroscience and Regenerative Medicine (CNRM), 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, Association of University Radiologists, Radiological Society of North America, American Society of Pediatric Neuroradiology

Disclosure: Nothing to disclose.

Additional Contributors

Lucien M Levy, MD, PhD 

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, Radiological Society of North America

Disclosure: Nothing to disclose.

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

  3. 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. 1989 Sep-Oct. 13(5):756-62. [Medline].

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

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

  6. Dubbioso R, Pappatà S, Quarantelli M, D'Arco F, Manganelli F, Esposito M, et al. Atypical clinical and radiological presentation of cryptococcal choroid plexitis in an immunocompetent woman. J Neurol Sci. 2013 Nov 15. 334 (1-2):180-2. [Medline].

  7. Nakajima H, Takayama A, Fujiki Y, Ito T, Kitaoka H. Refractory Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient: Paradoxical Antifungal Therapy-Induced Clinical Deterioration Related to an Immune Response to Cryptococcal Organisms. Case Rep Neurol. 2015 Sep-Dec. 7 (3):204-8. [Medline].

  8. Merkler AE, Gaines N, Baradaran H, Schuetz AN, Lavi E, Simpson SA, et al. Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus neoformans in an Immunocompetent Host. Neurohospitalist. 2015 Oct. 5 (4):217-22. [Medline].

  9. Sarkis RA, Mays M, Isada C, Ahmed M. MRI findings in cryptococcal meningitis of the non-HIV population. Neurologist. 2015 Jan. 19 (2):40-5. [Medline].

  10. Loyse A, Moodley A, Rich P, Molloy SF, Bicanic T, Bishop L, et al. Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis. J Infect. 2015 Jun. 70 (6):668-75. [Medline].

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

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

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

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

  15. Starkey J, Moritani T, Kirby P. MRI of CNS fungal infections: review of aspergillosis to histoplasmosis and everything in between. Clin Neuroradiol. 2014 Sep. 24 (3):217-30. [Medline].

  16. 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. 1996 Nov-Dec. 20(6):1023-6. [Medline].

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

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

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

  20. 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. 2008 Sep 15. 86(5):647-51. [Medline].

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

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