Prognosis of Fungal Infections Involving the Central Nervous System and Its Coverings

  • Kartik Munta
  • Jay Dip Ray Chaudhuri


Over 1.5 million fungal species have been known to be existing. There has been description of only 70,000 species reported in literature. Out of the described species, 300 have been suspected to show signs of virulence in humans. Amongst them 10–15% affect the central nervous system in human beings (Köhler et al. 2015). Fungal organisms encountered in the central nervous system can be classified into yeasts (Candida and Cryptococcus species), moniliaceous molds (Aspergillus spp., Fusarium spp.), dimorphic fungi (Blastomyces, Coccidioides, Histoplasma species), dematiaceous fungi, and Zygomycetes (Mucor spp., Rhizopus spp.).


Central nervous system Complications Fungal infections Morbidity Mortality Prognosis 



Acquired immunodeficiency syndrome


Central nervous system


Cerebrospinal fluid


Human immunodeficiency virus


  1. Antinori S, Corbellino M, Meroni L, et al. Aspergillus meningitis: a rare clinical manifestation of central nervous system aspergillosis - case report and review of 92 cases. J Infect. 2013;66(3):218–38.PubMedCrossRefGoogle Scholar
  2. Arsenault AB, Bliss JM. Neonatal candidiasis: new insights into an old problem at a unique host-pathogen interface. Curr Fungal Infect Rep. 2015;9(4):246–52.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Banerjee U, Datta K, Majumdar T, Gupta K. Cryptococcosis in India: the awakening of a giant? Med Mycol. 2001;39:51–67.5.PubMedCrossRefGoogle Scholar
  4. Brouwer AE, Rajanuwong A, Chierakul W, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet. 2004;363(9423):1764–7.PubMedCrossRefGoogle Scholar
  5. Casado JL, Quereda C, Oliva J, et al. Candidal meningitis in HIV-infected patients: analysis of 14 cases. Clin Infect Dis. 1997;25(3):673–6.PubMedCrossRefGoogle Scholar
  6. Chakrabarti A, Sharma SC. Paranasal sinus mycoses. Indian J Chest Dis Allied Sci. 2000;42:293–304.PubMedPubMedCentralGoogle Scholar
  7. Chakrabarti A, Das A, Mandal J, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 2006;44(4):335–42.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Collazos J. Opportunistic infections of the CNS in patients with AIDS: diagnosis and management. CNS Drugs. 2003;17(12):869–87.PubMedCrossRefGoogle Scholar
  9. Cooley L, Spelman D, Thursky K, et al. Infection with Scedosporium apiospermum and S. prolificans, Australia. Emerg Infect Dis. 2007;13(8):1170.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Dewsnup DH, Galgiani JN, Graybill JR, et al. Is it ever safe to stop azole therapy for Coccidioides immitis meningitis? Ann Intern Med. 1996;124(3):305–10.PubMedCrossRefGoogle Scholar
  11. Dubey A, Patwardhan RV, Sampth S, Santosh V, Kolluri S, Nanda A. Intracranial fungal granuloma: analysis of 40 patients and review of the literature. Surg Neurol. 2005;63(3):254–60.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Dupont B. Fungal infections of the central nervous system. In: Anaissie EJ, McGinnis MR, Pfaller MA, editors. Clinical mycology. 1st ed. New York: Churchill Livinstone; 2003. p. 539–53.Google Scholar
  13. Fasciano JW, Ripple MG, Suarez JI, Bhardwaj A. Central nervous system Aspergillosis: a case report and literature review. Hosp Physician. 1999;1:63–7.Google Scholar
  14. Gavito-Higuera J, Mullins CB, Ramos-Duran L, Olivas Chacon CI, Hakim N, Palacios E. Fungal infections of the central nervous system: a pictorial review. J Clin Imaging Sci. 2016;6:24.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Gopinath M, Cherian A, Baheti NN, Das A, Antonty M, Sarada C. An elusive diagnosis: Scedosporium apiospermum infection after near-drowning. Ann Indian Acad Neurol. 2010;13:213–5.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Hassan A, Poon W, Baker M, Linton C, Mühlschlegel FA. Confirmed Candida albicans endogenous fungal endophthalmitis in a patient with chronic candidiasis. Med Mycol Case Rep. 2012;1(1):42–4.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Imwidthaya P, Poungvarin N. Cryptococcosis in AIDS. Postgrad Med J. 2000;76(892):85–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Jamjoom A, al-Abedeen Jamjoom Z, al-Hedaithy S, Jamali A, Naim-Ur-Rahman MT. Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting. Br J Neurosurg. 1992;6(5):501–4.PubMedCrossRefGoogle Scholar
  19. Jarvis JN, Bicanic T, Loyse A, et al. Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: implications for improving outcomes. Clin Infect Dis. 2014;58(5):736–45.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Johnson MD, Perfect JR. Use of antifungal combination therapy: agents, order, and timing. Curr Fungal Infect Rep. 2010 May 1;4(2):87–95.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Kambugu AD, Kamya M, Mayanja-Kizza H, et al. The high mortality of HIV associated Cryptococcal meningitis despite high dose amphotericin B therapy in Uganda. 41st Annual Meeting of The Infectious Diseases Society of America. San Diego, 2003.Google Scholar
  22. Kartik M, Kanala A, Sunilnadikuda RSM, Prakasham PS. Invasive mediastinal Aspergillosis in immunocompetent male with invasion of left atrium and hilar structures. Indian J Crit Care Med. 2017;21:408–11.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Katragkou A, Pana ZD, Perlin DS, Kontoyiannis DP, Walsh TJ, Roilides E. Exserohilum infections: review of 48 cases before the 2012 United States outbreak. Med Mycol. 2014;52(4):376–86.PubMedCrossRefGoogle Scholar
  24. Köhler JR, Casadevall A, Perfect J. The spectrum of fungi that infects humans. Cold Spring Herb Perspect Med. 2015;5:a019273. Scholar
  25. Kovoor JM, Mahadevan A, Narayan JP, et al. Cryptococcal choroid plexitis as a mass lesion: MR imaging and histopathologic correlation. AJNR Am J Neuroradiol. 2002;23(2):273–6.PubMedPubMedCentralGoogle Scholar
  26. Lanternier F, Mahdaviani SA, Barbati E, et al. Inherited CARD9 deficiency in otherwise healthy children and adults with meningo-encephalitis and/or colitis caused by Candida. J Allergy Clin Immunol. 2015;135(6):1558–68.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Larone DH, Walsh TJ. Exserohilumrostratum: anatomy of a national outbreak of fungal meningitis. Clin Microbiol Newsl. 2013;35(23):185–93.CrossRefGoogle Scholar
  28. Lee BE, Cheung PY, Robinson JL, et al. Comparative study of mortality and morbidity in premature infants with candidaemia or candidal meningitis. Clin Infect Dis. 1998;27(3):559–65.PubMedCrossRefGoogle Scholar
  29. Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 1991;13:1164–9.CrossRefGoogle Scholar
  30. Lockhart SR, Iqbal N, Bolden CB, DeBess EE, Marsden-Haug N, Worhle R, Thakur R, Harris JR, Cryptococcus gattii PNW Public Health Working Group. Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro susceptibility. Diagn Microbiol Infect Dis. 2012;73:144–8.PubMedCrossRefGoogle Scholar
  31. Lu CH, Chen HL, Chang WN, et al. Assessing the chronic neuropsychologic sequelae of human immunodeficiency virus-negative cryptococcal meningitis by using diffusion tensor imaging. AJNR Am J Neuroradiol. 2011;32(7):1333–9.PubMedCrossRefGoogle Scholar
  32. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mold infections in hematopoietic stem cell transplant recipient. Clin Infect Dis. 2002;34:909–17. 4.PubMedCrossRefGoogle Scholar
  33. Mathur M, Johnson CE, Sze G. Fungal infections of the central nervous system. Neuroimaging Clin N Am. 2012;22(4):609–32.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Mattiuzzi G, Giles FJ. Management of intracranial fungal infections in patients with haematological malignancies. Br J Haematol. 2005;131:287–300.PubMedCrossRefGoogle Scholar
  35. Middleton FG, Jurgenson PF, Utz JP, Shadomy S, Shadomy J. Brain abscess caused by Cladosporium trichoides. Ann Int Med. 1976;136:444–8.CrossRefGoogle Scholar
  36. Munta K, Gopal PB, Vigg A. Invasive aspergillosis in near drowning nonneutropenic patient. Indian J Crit Care Med. 2015;19:739–42.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Newton PN, Thai LH, LH TNQ, Short JM, Chierakul W, Rajanuwong A, Pitisuttithum P, Chasombat S, Phonrat B, Maek-A-Nantawat W, Teaunadi R, Lalloo DG, White NJ. A randomized, double-blind, placebo-controlled trial of acetazolamide for the treatment of elevated intracranial pressure in cryptococcal meningitis. Clin Infect Dis. 2002;35:769–72.PubMedCrossRefGoogle Scholar
  38. Nguyen MH, Yu VL. Meningitis caused by Candida species: an emerging problem in neurosurgical patients. Clin Infect Dis. 1995;21(2):323–7.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Pagano L, Ricci P, Tonso A, et al. Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. Br J Haematol. 1997;99(2):331–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 2001;33(5):690–9.PubMedCrossRefGoogle Scholar
  41. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2010;50:291–322.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Raman Sharma R. Fungal infections of the nervous system: current perspective and controversies in management. Int J Surg. 2010;8(8):591–601.PubMedCrossRefGoogle Scholar
  43. Ribaud P, Chastang C, Latgé JP, et al. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis. 1999;28(2):322–30.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Richardson MP, Ayliffe MJ, Helbert M, Davies EG. A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test. J Immunol Methods. 1998;219(1):187–93.PubMedCrossRefGoogle Scholar
  45. Santosh V, Yasha TC, Khanna N. Fungal infections of the nervous system - a pathological study. Neurol Infect Epidemiol. 1996;1:69–79.Google Scholar
  46. Schwartz S. Cerebral aspergillus infections and meningitis. Aspergillosis: from diagnosis to prevention. Dordrecht: Springer; 2010.Google Scholar
  47. Sharma BS, Khosla VK, Kak VK, Banerjee AK, Vasishtha RK, Prasad KS, et al. Intracranial fungal granuloma. Surg Neurol. 1997a;47:48997.CrossRefGoogle Scholar
  48. Sharma BS, Prasad KSM, Banerjee AK, et al. Intracranial fungal granuloma. Surg Neurol. 1997b;47(5):489–97.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Singh N, Husain S. Infections of the central nervous system in transplant recipients. Transpl Infect Dis. 2001;2:101–11.CrossRefGoogle Scholar
  50. Singh N, Lortholary O, Alexander BD, Gupta KL, John GT, Pursell K, Munoz P, Klintmalm GB, Stosor V, del Busto R, Limaye AP, Somani J, Lyon M, Houston S, House AA, Pruett TL, Orloff S, Humar A, Dowdy L, Garcia-Diaz J, Kalil AC, Fisher RA, Husain S, Cryptococcal Collaborative Transplant Study Group. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin Infect Dis. 2005;40:1756–61.PubMedCrossRefGoogle Scholar
  51. Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis. 1995;21(1):28–36.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Thorn JL, Gilchrist KB, Sobonya RE, Gaur NK, Lipke PN, Klotz SAK. Postmortem candidemia: marker of disseminated disease. J Clin Pathol. 2010;63(4):337–40.PubMedCrossRefGoogle Scholar
  53. Venger BH, Landon G, Rose JE. Solitary Histoplasmoma of the thalamus: case report and literature review. Neurosurgery. 1987;20(5):784–7.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system, a clinical review. Medicine. 1990;69:244–60.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005;40(6):844–52.PubMedPubMedCentralCrossRefGoogle Scholar
  56. White P, Barnes R. Not over yet: fungal infections following methyl prednisolone injections smoulder on. J Clin Microbiol. 2014;52(9):3506.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kartik Munta
    • 1
  • Jay Dip Ray Chaudhuri
    • 1
  1. 1.Yashoda Superspeciality HospitalHyderabadIndia

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