Undiagnosed cryptococcal meningoencephalitis with extensive hypoxic-ischemic brain injury mimicking grade 3 diffuse axonal injury

Czech version

Authors: Daniel Farkaš ¹; Anna Kružlíková ²; Jana Němcová ³; Vladimír Hrabovský ⁴; Silvia Farkašová Iannaccone ⁵; Alžbeta Ginelliová ¹; Lucia Fröhlichová ⁶; Marián Švajdler ³
Authors‘ workplace: Úrad pre dohľad nad zdravotnou starostlivosťou, SLaPA pracovisko, Košice ¹; Úrad verejného zdravotníctva Slovenskej republiky, Bratislava ²; Bioptická laboratoř s. r. o., Plzeň ³; Ústav lekárskej a klinickej mikrobiológie UPJŠ LF, Košice ⁴; Ústav súdneho lekárstva UPJŠ LF, Košice ⁵; Oddelenie patológie, Univerzitná nemocnica Louisa Pasteura, Košice ⁶
Published in: Čes.-slov. Patol., 57, 2021, No. 3, p. 167-173
Category: Original Articles

Overview

In this article, we report the autopsy findings of a 50-year-old immunocompetent woman, who was hospitalized with an altered state of consciousness. Examinations, including cerebrospinal fluid analysis, carried out during hospitalization failed to identify the infectious agent causing progressive loss of consciousness and quadriparesis. The patient died within 8 days of admission to the hospital. Post-mortem microscopic and culture examination revealed Cryptococcus species. Death was attributed to cryptococcal meningoencephalitis. Histologic examination revealed accumulation of cryptococcus mimicking erythrocytes and extensive hemorrhage in hematoxylin and eosin-stained sections of the brain. Multifocal obliteration of the vascular bed by yeast was accompanied by hypoxic-ischemic brain injury mimicking traumatic diffuse axonal injury.

Keywords:

cryptococcal meningoencephalitis – Cryptococcus – diffuse axonal injury – hypoxic-ischemic brain injury

Sources

1. Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am 2016; 30(1): 179-206.

2. Barnett JA. A history of research on yeasts 14: medical yeasts part 2, Cryptococcus neoformans. Yeast 2010; 27(11): 875-904.

3. Wilson JW. Cryptococcosis; Torulosis, European Blastomycosis, Busse-Buschke’s Disease J Chronic Dis 1957; 5(4): 455-459.

4. Mosberg WH Jr, Arnold JG Jr. Torulosis of the central nervous system: Review of literature and report of five cases. Ann Int Med 1950; 32: 1153-1183.

5. Fingerland A, Vortel V, Dvořák J, Zdráhal L. Generalisovaná kryptokokkosa (torulosa) Čas Lek Česk 1954; 93(30): 809-816.

6. D’Souza CA, Kronstad JW, Taylor G, et al. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. mBio 2011; 2(1): e00342-10.

7. Sharpton TJ, Neafsey DE, Galagan JE, Taylor JW. Mechanisms of intron gain and loss in Cryptococcus Genome Biol 2008; 9(1): R24.

8. Hagen F, Illnait-Zaragozí MT, Meis JF, et al. Extensive Genetic Diversity Within the Dutch Clinical Cryptococcus Neoformans Population J Clin Microbiol 2012; 50(6): 1918-1926.

9. Lin X, Heitman J. The biology of the Cryptococcus neoformans species complex. Annu Rev Microbiol 2006; 60: 69-105.

10. McFadden DC, Casadevall A. Capsule and melanin synthesis in Cryptococcus neoformans. Med Mycol 2001; 39 Suppl 1:19-30.

11. Srikanta D, Santiago-Tirado FH, Doering TL. Cryptococcus neoformans: historical curiosity to modern pathogen. Yeast 2014; 31(2): 47-60.

12. Coelho C, Bocca AL, Casadevall A. The intracellular life of Cryptococcus neoformans. Annu Rev Pathol 2014; 9: 219-238.

13. Steenbergen JN, Shuman HA, Casadevall A. Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages. Proc Natl Acad Sci U S A 2001; 98(26): 15245-15250.

14. Kwon-Chung KJ. A new genus, Filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia 1975; 67: 1197–1200.

15. Chen S, Meyer W, Sorrell TC. Cryptococcus gattii Infections Clin Microbiol Rev 2014; 27(4): 980–1024.

16. Krajcár R. Generalizovaná kryptokokóza pri chronickej glomerulonefritíde. Bratisl Lek Listy 1974; 62(3): 358-362.

17. Colombo AC, Rodrigues ML. Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis. An Acad Bras Cienc 2015; 87(2 Suppl): 1293-309.

18. Del Valle L, Piña-Oviedo S. HIV disorders of the brain: pathology and pathogenesis. Front Biosci 2006; 11: 718-732.

19. Ellis DH, Pfeiffer TJ. Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol 1990; 28(7): 1642-1644.

20. Fyfe M, MacDougall L, Romney M, et al. Cryptococcus gatti infections on Vancouver Island, British Columbia, Canada: emergence of a tropical fungus in a temperate environment. Can Commun Dis Rep 2008; 34(6): 1-12.

21. Byrnes EJ 3rd, Bildfell RJ, Frank SA, Mitchell TG, Marr KA, Heitman J. Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States. J Infect Dis 2009; 199: 1081– 1086.

22. Doering TL. How sweet it is! Cell wall biogenesis and polysaccharide capsule formation in Cryptococcus neoformans. Annu Rev Microbiol 2009; 63:223–247.

23. Nosanchuk JD, Rosas AL, Lee SC, Casadevall A. Melanisation of Cryptococcus neoformans in human brain tissue. Lancet 2000; 355(9220): 2049-2050.

24. Eisenman HC, Frases S, Nicola AM, Rodrigues ML, Casadevall A. Vesicle-associated melanization in Cryptococcus neoformans. Microbiology 2009; 155(Pt 12): 3860-3867.

25. Zhu X, Williamson PR. Role of laccase in the biology and virulence of Cryptococcus neoformans. FEMS Yeast Res 2004; 5(1): 1-10.

26. Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17(8): 873-881.

27. Leestma JE. Forensic neuropathology (2nd edn). Boca Raton London New York: CRC Pres Taylor & Francis Group; 2008: 155.

28. Graham ID, Lantos PL. Greenfield´s neuropathology (6th edn). Volume II, London: Arnold; 1997: 97-98.

29. Kozubowski L, Heitman J. Profiling a killer, the development of Cryptococcus neoformans. FEMS Microbiol Rev 2012; 36(1): 78-94.

30. Kwon-Chung KJ, Bennett JE, Theodore TS. Cryptococcus bacillisporus sp. nov.: serotype B-C of Cryptococcus neoformans. Int J Syst Bacteriol 1978; 28: 616 –620.

31. Fahey B, Degnan BM. Origin and evolution of laminin gene family diversity. Mol Biol Evol 2012; 29(7): 1823-1836.

32. Valencia Y, Cáceres DH, de Bedout C, Cano LE, Restrepo Á. Frequency of Invasive Fungal Disease in Adults: Experience of a Specialized Laboratory in Medellín, Colombia (2009- 2015). J Fungi (Basel) 2020; 6(1): 39.

33. Selby RC, Lopes NM. Torulomas (cryptococcal granulomata) of the central nervous system. J Neurosurg 1973; 38(1): 40-46.

34. Dolinak D, Matshes EW, Lew EO. Forensic Pathology. Principles and Practice. Burlington Elsevier; 2005: 284-285.

35. Armstrong D, Halliday W, Hawkins C, Takashima S. Pediatric Neuropathology A Text-Atlas. Tokyo Berlin Heidelberg New York: Springer; 2007: 392.

36. Meythaler JM, Peduzzi JD, Eleftheriou E, Novack TA. Current concepts: Diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehabil 2001; 82(10):1461–1471.

37. Lerner JT, Giza CC. Traumatic Brain Injury in Children. In: Swaiman FK, Ashwal S. eds. Swaiman´s Pediatric Neurology (6th edn). Edinburg: Elsevier; 2018: 781-785.

38. Sherriff FE, Bridges LR, Gentleman SM, Sivaloganathan S, Wilson S. Markers of axonal injury in post mortem human brain. Acta Neuropathol 1994; 88(5): 433-439.

39. Toupalík P, Bouška I, Chadová I. Rozdílnosti v imunohistochemických nálezech při úrazových a hypoxických změnách CNS. Soud Lék 2001; 46(3): 34-36

40. Dettmeyer RB. Forensic Histopathology. Fundamentals and Perspectives (2nd edn). Cham: Springer; 2018: 523.

41. Oehmichen M, Auer RN, König HC. Forensic Neuropathology and Associated Neurology. Berlin Heidelberg: Springer; 2006: 65.

42. Graham ID, Lantos PL. Greenfield´s neuropathology (6th edn). Volume I, London: Arnold; 1997: 229-231.