Dr.C.Vemulapalli, Dr.A.Krishnan, Dr.R.Jain, Cryptococcus gattii meningitis in an immunocompetent patient. PRESENTATION NUMBER EE-36 Dr.C.Vemulapalli, Dr.A.Krishnan, Dr.R.Jain, Diagnostic Radiology, Oakland University William Beaumont School of Medicine, MI

DISCLAIMER The authors do not have a financial relationship with a commercial organization that may have a direct or indirect interest in the content of this presentation.

Purpose: To present intracranial imaging finding in a rare case of Cryptococcus gattii in an immunocompetent individual and briefly review literature on this emerging condition.

Case Report History: 49 year old woman presented with severe headache over a week, that was different from her usual migraine headaches. She complained of nausea and vomiting. Her other significant history included frequent travels, consistent with her occupation as a flight attendant, and history of cough with fever during her recent Puerto Rico vacation. Physical: Afebrile, normal mental status. Normal neurological examination.

CT b a Initial non contrast CT showed subcortical vasogenic edema in left superior frontal gyrus (images a and b) raising concern for possible mass lesion. This lead to further evaluation with MRI brain.

MRI c b a Subcortical T2 hyperintensity corresponding to CT finding(a). Leptomeningeal enhancement in left medial frontal region ( T1 pre and post contrast b&c).

c a b MRI brain showed additional T2 FLAIR hyperintense foci in corpus callosum, and left medial frontal region(a) with leptomeningeal enhancement in left medial frontal sulci (b) and along the right superior cerebellar peduncle (c).

Based on MRI finding of leptomeningeal enhancement and subcortical edema possible differentials of neurosarcoidosis, infective meningitis, and leptomeningeal carcinomatosis were considered. This was followed by a lumbar tap for CSF analysis.

CSF analysis showed elevated WBC (151) with lymphocytic pleocytosis (90%), mildly elevated CSF IgG, normal glucose and very minimally elevated protein (53 mg/dl). CSF cryptococcal antigen was positive and culture grew Cryptococcus gattii.

Patient was treated with 4 weeks of amphotericin and flucytosine and was placed on long term peroral fluconazole. Patient reported symptomatic improvement and significant resolution of leptomeningeal enhancement and subcortical edema on repeat MRI after 2 weeks.

a b Follow up MRI after 2 week course of antifungal treatment shows reduced subcortical edema on axial T2(a) but with residual leptomeningeal enhancement (post contrast axial T1 image b).

Discussion Cryptococcus gattii is primarily found in tropical and subtropical regions of the world unlike the more ubiquitous Cryptococcus neoformans. Cryptococcus gattii was initially recognized as causing infections in humans and animals on Vancouver Island, British Columbia. Cryptococcus gattii infections were first recognized in the United States Pacific Northwest (Oregon and Washington) in 2004 (1). To our knowledge, intracranial cryptococcosis due to Cryptococcus gattii in USA is rare and Cryptococcus gattii is now considered as an emerging disease (2)

Biology of Cryptococcus gattii

Pathogenesis: Exact incubation period for Cryptococcus gattii is variable and has been reported ranging from 2-11 months in a study by Mac Doughill et al (3). Cryptococcus gattii is typically acquired by inhalation. Initially it infects the lung with subsequent hematogenous spread to other parts particularly the central nervous system. Cryptococcus neoformans typically involves basal cisterns and spreads along perivascular spaces to involve deep brain, thalami and basal ganglia.

CNS Imaging: Most common imaging manifestation of CNS Cryptococcosis is leptomeningeal enhancement. The classic descriptions of CNS Cryptococcosis are of dilated perivascular spaces/ gelatinous cysts. These gelatinous cyst are collections of unencapsulated cryptococci from lack of immune response. CNS Cryptococcus Gattii in contrast is less likely to cause these gelatinous cystic lesions as it most commonly occurs in immuno-competent individuals Cryptococcomas which are intraparenchymal enhancing granulomatosis lesions are more likely occur in immunocompetent individuals with Cryptococcosis Gattii (4).Cryptococcus Gattii is more likely to cause large cryptococcomas / mass lesion and CNS complications than Cryptococcus Neoformans (5). Other CNS cryptococcal imaging findings include Choroid plexitis, and hydrocephalus

Conclusion: Cryptococcosis is typically seen in immunocomprised individuals but with emerging Cryptococcus gattii, Cryptococcosis can be seen in immunocompetent patients, particularly with history of travel. Leptomeningeal enhancement was the predominant imaging finding in our case of Cryptococcus gattii though there were areas of cerebral edema. While there are many causes for leptomeningeal enhancement, the relatively mild clinical symptoms of the patient (including being afebrile), contrasted against the more significant findings on imaging and led to a broad differential. It is important for neuroradiologists to consider Cryptococcus infection in immunocompetent individuals.

References CDC. Emergence of Cryptococcus gattii – Pacific Northwest, 2004-2010. MMWR. 2010 Jul 23;59(28):865-8. Harris JR, Lockhart SR, Debess E, Marsden-Haug N, Goldoft M, Wohrle R, et al. Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis. 2011 Dec;53(12):1188-95 MacDougall L, Fyfe M. Emergence of Cryptococcus gattii in a novel environment provides clues to its incubation period. J Clin Microbiol 2006; 44:1851. Mitchell DH, Sorrell TC, Allworth AM, et al .Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome. Clin Infect Dis 1995;20:611-6 . Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995; 21:28.

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