Central nervous system cryptococcosis in solid organ transplant recipients: clinical relevance of abnormal neuroimaging findings.

Nina Singh, Olivier Lortholary, Françoise Dromer, Barbara D Alexander, Krishan L Gupta, George T John, Ramon del Busto, Goran B Klintmalm, Jyoti Somani, G Marshall Lyon, Kenneth Pursell, Valentina Stosor, Patricia Munoz, Ajit P Limaye, Andre C Kalil, Timothy L Pruett, Julia Garcia-Diaz, Atul Humar, Sally Houston, Andrew A House, Dannah Wray, Susan Orloff, Lorraine A Dowdy, Robert A Fisher, Joseph Heitman, Marilyn M Wagener, Shahid Husain, Cryptococcal Collaborative Transplant Study Group
Author Information
  1. Nina Singh: University of Pittsburgh, Pittsburgh, PA, USA. nis5@pitt.edu

Abstract

BACKGROUND: Prognostic implications of cryptococcal antigen and outcomes associated with central nervous system (CNS) cryptococcal lesions in solid organ transplant recipients have not been fully defined.
METHODS: Patients were derived form a cohort of 122 solid organ transplant recipients with cryptococcosis in a multicenter study from 1999 to 2006.
RESULTS: Central nervous system cryptococcosis was documented in 61 patients. Serum or cerebral spinal fluid antigen titers did not correlate with mortality at 90 days or cerebral spinal fluid sterilization at 2 weeks. Central nervous system lesions were identified in 16 patients and included leptomeningeal lesions in eight, parenchymal lesions in six, and hydrocephalus in two. Overall, 13/16 CNS lesions were present at the time of diagnosis. One parenchymal and two hydrocephalus lesions, however, developed after diagnosis and fulfilled the criteria for immune reconstitution syndrome. Cerebral spinal fluid antigen titers were higher with meningeal versus parenchymal lesions, and hydrocephalus (P=0.015). Mortality was 50% (3/6) for patients with parenchymal, 12.5% (1/8) for those with leptomeningeal, and 0/3 for patients with hydrocephalus. Mortality was 31% (4/13) for patients with CNS lesions at baseline and 0/3 in those with new onset lesions.
CONCLUSIONS: Despite a higher antigen titer with meningeal lesions, outcomes tended to be worse with parenchymal compared with meningeal lesions or hydrocephalus. New onset CNS lesions may represent immune reconstitution syndrome and seemed to be associated with better outcome.

References

  1. Diagn Microbiol Infect Dis. 1997 Nov;29(3):193-8 [PMID: 9401812]
  2. J Neuroimaging. 1999 Apr;9(2):118-21 [PMID: 10208111]
  3. J Infect Dis. 2007 Mar 1;195(5):756-64 [PMID: 17262720]
  4. Neuroradiology. 1987;29(1):43-6 [PMID: 3822101]
  5. J Neurosurg. 2007 Oct;107(4 Suppl):314-7 [PMID: 17941497]
  6. Clin Infect Dis. 1995 Mar;20(3):611-6 [PMID: 7756484]
  7. Transplantation. 1996 Jan 15;61(1):146-9 [PMID: 8560554]
  8. J Antimicrob Chemother. 2000 Sep;46(3):437-42 [PMID: 10980171]
  9. J Clin Microbiol. 2005 Jun;43(6):2989-90 [PMID: 15956440]
  10. Lancet Infect Dis. 2007 Jun;7(6):395-401 [PMID: 17521592]
  11. Clin Infect Dis. 2005 Apr 1;40(7):1049-52 [PMID: 15825000]
  12. J Comput Assist Tomogr. 1980 Dec;4(6):766-9 [PMID: 7217419]
  13. PLoS One. 2008 Apr 16;3(4):e1950 [PMID: 18414656]
  14. Antimicrob Agents Chemother. 1994 Mar;38(3):460-4 [PMID: 7911289]
  15. Am J Med. 2002 Aug 1;113(2):155-7 [PMID: 12133755]
  16. Clin Infect Dis. 2000 Nov;31(5):1303-6 [PMID: 11073772]
  17. PLoS Med. 2007 Feb;4(2):e21 [PMID: 17284154]
  18. AIDS. 2005 Jul 1;19(10):1043-9 [PMID: 15958835]
  19. AJR Am J Roentgenol. 1990 Mar;154(3):603-6 [PMID: 2106227]
  20. Mycoses. 2001 Dec;44(11-12):497-501 [PMID: 11820264]
  21. Clin Infect Dis. 2002 Jan 1;34(1):7-14 [PMID: 11731939]
  22. Emerg Infect Dis. 2001 May-Jun;7(3):375-81 [PMID: 11384512]
  23. N Engl J Med. 1992 Jan 9;326(2):83-9 [PMID: 1727236]
  24. Neuropatol Pol. 1982;20(3-4):495-503 [PMID: 6763975]
  25. Clin Infect Dis. 2000 Jan;30(1):47-54 [PMID: 10619732]
  26. AIDS. 2006 Nov 14;20(17):2183-91 [PMID: 17086058]
  27. Neurology. 1985 May;35(5):731-4 [PMID: 3990973]
  28. J Infect. 2005 Aug;51(2):165-71 [PMID: 15961162]
  29. Ann Intern Med. 1974 Feb;80(2):176-81 [PMID: 4811791]
  30. Transplantation. 1994 Oct 15;58(7):855-6 [PMID: 7940723]
  31. Surg Neurol. 2005 Mar;63(3):254-60; discussion 260 [PMID: 15734518]
  32. Nat Rev Microbiol. 2003 Oct;1(1):17-24 [PMID: 15040176]
  33. Neurol India. 2007 Jul-Sep;55(3):260-6 [PMID: 17921655]
  34. Eur J Clin Microbiol Infect Dis. 2001 Oct;20(10):711-7 [PMID: 11757972]
  35. Clin Infect Dis. 1994 May;18(5):789-92 [PMID: 8075272]
  36. Radiology. 1982 Jun;143(3):703-7 [PMID: 7079496]
  37. Am J Transplant. 2007 Dec;7(12):2826-8 [PMID: 17927804]
  38. Curr Opin Immunol. 1997 Aug;9(4):484-90 [PMID: 9287178]

Grants

  1. R01 AI054719/NIAID NIH HHS
  2. R01 AI054719-03/NIAID NIH HHS

MeSH Term

Adult
Aged
Cerebrospinal Fluid
Cryptococcus
Female
Humans
Male
Meningitis, Cryptococcal
Middle Aged
Organ Transplantation
Postoperative Complications
Prognosis
Retrospective Studies

Word Cloud

Created with Highcharts 10.0.0lesionspatientsparenchymalhydrocephalusantigennervoussystemCNSsolidorgantransplantcryptococcosisCentralspinalfluidmeningealcryptococcaloutcomesassociatedrecipientscerebraltitersleptomeningealtwodiagnosisimmunereconstitutionsyndromehigherMortality0/3onsetBACKGROUND:PrognosticimplicationscentralfullydefinedMETHODS:Patientsderivedformcohort122multicenterstudy19992006RESULTS:documented61Serumcorrelatemortality90dayssterilization2weeksidentified16includedeightsixOverall13/16presenttimeOnehoweverdevelopedfulfilledcriteriaCerebralversusP=001550%3/6125%1/831%4/13baselinenewCONCLUSIONS:DespitetitertendedworsecomparedNewmayrepresentseemedbetteroutcomerecipients:clinicalrelevanceabnormalneuroimagingfindings

Similar Articles

Cited By