Meningitis and Meningoencephalitis

  • Alexa Bodman
  • Walter A. HallEmail author


Fungal meningitis and meningoencephalitis are unusual diagnoses that are associated with significant neurological morbidity and mortality. Due to difficulty in making this diagnosis, recognition of this entity can be delayed. Common causative of fungal meningitis include Candida spp., Cryptococcus spp., Aspergillus spp., Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Mucorales. Awareness of the common fungal infections of the central nervous system (CNS) and their treatment are important for any clinician treating infections of the CNS.


Fungal meningitis Cryptococcal meningitis Aspergillosis Candida meningitis Coccidioidal meningitis 



Acquired immunodeficiency syndrome


Central nervous system


Cerebrospinal fluid


Human immunodeficiency virus


Intensive care unit


  1. Abdollahi A, Shokohi T, et al. Clinical features, diagnosis, and outcomes of rhino-orbito-cerebral mucormycosis: a retrospective analysis. Curr Med Mycol. 2016;2:15–23.PubMedPubMedCentralGoogle Scholar
  2. Adams-Chapman I, Bann CM, Das A, et al. Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. J Pediatr. 2013;163:961–967.e3.CrossRefGoogle Scholar
  3. 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;66:218–38.CrossRefGoogle Scholar
  4. Arsura EL, Johnson R, Penrose J, Stewart K, Kilgore W, Reddy CM, Bobba RK. Neuroimaging as a guide to predict outcomes for patients with coccidioidal meningitis. Clin Infect Dis. 2005;40:624–7.CrossRefGoogle Scholar
  5. Baddley JW, Andes DR, Marr KA, et al. Factors associated with mortality in transplant patients with invasive aspergillosis. Clin Infect Dis. 2010;50:1559–67.CrossRefGoogle Scholar
  6. Beardsley J, Wolbers M, Kibengo FM, et al. Adjunctive dexamethasone in HIV-associated Cryptococcal meningitis. N Engl J Med. 2016;374:542–54.CrossRefGoogle Scholar
  7. Boelaert JR, Fenves AZ, Coburn JW. Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry. Am J Kidney Dis. 1991;18:660–7.CrossRefGoogle Scholar
  8. Bongomin F, Gago S, Oladele R, Denning D. Global and multi-national prevalence of fungal diseases—estimate precision. J Fungi (Basel). 2017;3 Scholar
  9. Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, Kauffman CA. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801–12.CrossRefGoogle Scholar
  10. Chen SCA, Slavin MA, Heath CH, et al. Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. Clin Infect Dis. 2012;55:789–98.CrossRefGoogle Scholar
  11. Cherian J, Atmar RL, Gopinath SP. Shunting in cryptococcal meningitis. J Neurosurg. 2015;125(1):177–86.CrossRefGoogle Scholar
  12. Concha-Velasco F, González-Lagos E, Seas C, Bustamante B. Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis. PLoS One. 2017;12:e0174459–12.CrossRefGoogle Scholar
  13. van der Horst CM, Saag MS, Cloud GA, et al. Treatment of Cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997;337:15–21.CrossRefGoogle Scholar
  14. Dobre MC, Smoker WRK, Kirby P. A case of solitary Blastomyces dermatitidis meningitis. Clin Neurol Neurosurg. 2011;113:665–7.CrossRefGoogle Scholar
  15. Drake KW, Adam RD. Coccidioidal meningitis and brain abscesses: analysis of 71 cases at a referral center. Neurology. 2009;73:1780–6.CrossRefGoogle Scholar
  16. Franco-Paredes C, Womack T, Bohlmeyer T, Sellers B, Hays A, Patel K, Lizarazo J, Lockhart SR, Siddiqui W, Marr KA. Management of Cryptococcus gattii meningoencephalitis. Lancet Infect Dis. 2015;15:348–55.CrossRefGoogle Scholar
  17. Galgiani JN, Ampel NM, Blair JE, et al. Executive summary: 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016;63:717–22.CrossRefGoogle Scholar
  18. Gavito-Higuera. Fungal infections of the central nervous system: a pictorial review. J Clin Imaging Sci. 2016;6:24.CrossRefGoogle Scholar
  19. Hall WA, Kim P. Fungal infections of the nervous system. In: Hall WA, Kim P, editors. Neurosurgical infectious disease. New York, Stuttgart: Georg Thieme Verlag; 2013. p. 68–80.Google Scholar
  20. Hasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, Zimmer L, Ginocchio CC. Epidemiology of meningitis and encephalitis in the United States, 2011–2014. Clin Infect Dis. 2017;65:359–63.CrossRefGoogle Scholar
  21. Johnson RH, Einstein HE. Amphotericin B and coccidioidomycosis. Ann N Y Acad Sci. 2007;1111:434–41.CrossRefGoogle Scholar
  22. Kainer MA, Reagan DR, Nguyen DB, et al. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012;367:2194–203.CrossRefGoogle Scholar
  23. Kantarcioglu AS, Guarro J, De Hoog S, Apaydin H, Kiraz N. An updated comprehensive systematic review of Cladophialophora bantiana and analysis of epidemiology, clinical characteristics, and outcome of cerebral cases. Med Mycol. 2016;23:579–604.Google Scholar
  24. Kauffman CA, Malani AN. Fungal infections associated with contaminated steroid injections. In: Emerging infections 10. Washington, DC: American Society of Microbiology; 2016. p. 359–74.CrossRefGoogle Scholar
  25. Kleinschmidt-DeMasters BK. Central nervous system aspergillosis: a 20-year retrospective series. Hum Pathol. 2002;33:116–24.CrossRefGoogle Scholar
  26. Kravitz GR, Davies SF, Eckman MR, Sarosi GA. Chronic blastomycotic meningitis. Am J Med. 1981;71:501–5.CrossRefGoogle Scholar
  27. Lanternier F, Mahdaviani SA, Barbati E, et al. Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both. J Allergy Clin Immunol. 2015;135:1558–1568.e2.CrossRefGoogle Scholar
  28. Lyons JL, Thakur KT, Lee R, et al. Utility of measuring (1,3)-β-d-glucan in cerebrospinal fluid for diagnosis of fungal central nervous system infection: Table 1. J Clin Microbiol. 2014;53:319–22.CrossRefGoogle Scholar
  29. McKinnell JA, Pappas PG. Blastomycosis: new insights into diagnosis, prevention, and treatment. Clin Chest Med. 2009;30:227–39.CrossRefGoogle Scholar
  30. Melnychuk EM, Sole DP. A rare central nervous system fungal infection resulting from brown heroin use. J Emerg Med. 2017;52:314–7.CrossRefGoogle Scholar
  31. Modrzewska BD, Kurnatowska AJ, Khalid K. Drug susceptibility of fungi isolated from ICU patients. Ann Parasitol. 2017;63:189–98.PubMedGoogle Scholar
  32. Murthy JMK, Sundaram C. Fungal infections of the central nervous system. In: Neurologic aspects of systemic disease, part III, vol. 121. 1st ed. Amsterdam: Elsevier; 2014. p. 1383–401.CrossRefGoogle Scholar
  33. Mwaba P, Mwansa J, Chintu C, Pobee J, Scarborough M, Portsmouth S, Zumla A. Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions. Postgrad Med J. 2001;77:769–73.CrossRefGoogle Scholar
  34. O’Brien D, Stevens NT, Lim CH, O’Brien DF, Smyth E, Fitzpatrick F, Humphreys H. Candida infection of the central nervous system following neurosurgery: a 12-year review. Acta Neurochir. 2011;153:1347–50.CrossRefGoogle Scholar
  35. Pappas PG, Kauffman CA, Andes DR, et al. Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:409–17.CrossRefGoogle Scholar
  36. Patterson TF. Advances and challenges in management of invasive mycoses. Lancet. 2005;366:1013–25.CrossRefGoogle Scholar
  37. Pukkila-Worley R, Mylonakis E. Epidemiology and management of cryptococcal meningitis: developments and challenges. Expert Opin Pharmacother. 2008;9:551–60.CrossRefGoogle Scholar
  38. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A, Boulware DR. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17:873–81.CrossRefGoogle Scholar
  39. Riley TT, Muzny CA, Swiatlo E, Legendre DP. Breaking the mold. Ann Pharmacother. 2016;50:747–57.CrossRefGoogle Scholar
  40. Şahintürk F, Demirkaya H, Dere ÜA, Sönmez E, Altınörs N, Moray G, Haberal M. Intracranial fungal infection after solid-organ transplant. Exp Clin Transplant. 2018;16:179–82.PubMedGoogle Scholar
  41. Thompson GR III, Blair JE, Wang S, et al. Adjunctive corticosteroid therapy in the treatment of coccidioidal meningitis. Clin Infect Dis. 2017;65:338–41.CrossRefGoogle Scholar
  42. Torre-Cisneros J, Lopez OL, Kusne S, Martinez AJ, Starzl TE, Simmons RL, Martin M. CNS aspergillosis in organ transplantation: a clinicopathological study. J Neurol Neurosurg Psychiatry. 1993;56:188–93.CrossRefGoogle Scholar
  43. Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1–e38.CrossRefGoogle Scholar
  44. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807–25.CrossRefGoogle Scholar
  45. Williams PL, Johnson R, Pappagianis D, Einstein H, Slager U, Koster FT, Eron JJ, Morrison J, Aguet J, River ME. Vasculitic and encephalitic complications associated with Coccidioides immitis infection of the central nervous system in humans: report of 10 cases and review. Clin Infect Dis. 1992;14:673–82.CrossRefGoogle Scholar
  46. Zunt JR, Baldwin KJ. Chronic and subacute meningitis. Continuum (Minneap Minn). 2012;18:1290–318.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurosurgerySUNY Upstate Medical UniversitySyracuseUSA

Personalised recommendations