Summary:
Invasive aspergillosis (IA) is relatively common in allogeneic stem cell transplant (SCT) recipients. Although lungs are the most common site, central nervous system (CNS) involvement is also observed in this setting. We have retrospectively studied 14 cases of CNS aspergillosis found in a cohort of 455 allogeneic SCT recipients (incidence 3%). All patients, except one, had experienced acute graft-versus-host disease treated with high-dose methylprednisolone, and eight patients (57%) had also received ATG. The median time to the diagnosis of CNS aspergillosis was 124 days (range 49–347 days) from SCT. Pulmonary aspergillosis had been diagnosed earlier in four patients (29%). The most common initial symptoms of CNS aspergillosis were convulsions, hemiparesis, and mental alteration. Neuroradiological studies revealed single (two patients) or multiple (seven patients) focal lesions of 0.2–9 cm in diameter. Despite clinical suspicion in many patients, a confirmed diagnosis of CNS aspergillosis was made during life in only one patient. A total of 12 patients (86%) received amphotericin B. Despite therapy, all patients died 0–27 days (median seven days) after the initial CNS symptoms. CNS aspergillosis is not uncommon in allogeneic SCT recipients. Clinical manifestations are usually dramatic and progress quickly. Earlier and more effective treatment of IA is needed to prevent dissemination of infection into the CNS.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
McWhinney PHM, Kibbler CC, Hamon MD et al. Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: a 13 years' experience. Clin Infect Dis 1993; 17: 397–404.
Saugier-Veber P, Devergie A, Sulahian A et al. Epidemiology and diagnosis of invasive pulmonary aspergillosis in bone marrow transplant patients: results of a 5 year retrospective study. Bone Marrow Transplant 1993; 12: 121–124.
Jantunen E, Ruutu P, Niskanen L et al. Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. Bone Marrow Transplant 1997; 17: 801–808.
Wald A, Leisenring W, van Burik J-A, Bowden RA . Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J Infect Dis 1997; 175: 1459–1466.
Ribaud P, Chastang C, Latge JP . Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis 1999; 28: 322–330.
Jantunen E, Ruutu P, Piilonen A et al. Treatment and outcome of invasive Aspergillus infections in allogeneic BMT recipients. Bone Marrow Transplant 2000; 26: 759–762.
Denning DW . Invasive aspergillosis. Clin Infect Dis 1998; 26: 781–805.
Jantunen E, Piilonen A, Volin L et al. Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients. Bone Marrow Transplant 2000; 25: 867–871.
Beal MF, O'Carroll CP, Kleinman GM, Grossman RI . Aspergillosis of the nervous system. Neurology 1982; 32: 473–479.
Walsh TJ, Hier DB, Caplan LR . Aspergillosis of the central nervous system: clinicopathologic analysis of 17 patients. Ann Neurol 1985; 18: 574–582.
Ashdown BC, Tien RD, Felsberg GJ . Aspergillosis in brain and paranasal sinuses in immunocompromised patients: CT and MR imaging findings. Am J Roentgenol 1994; 162: 155–159.
Pagano L, Ricci P, Montillo M et al. Localization of aspergillosis to the central nervous system among patients with acute leukemia: report of 14 cases. Clin Infect Dis 1996; 23: 628–630.
deLone GR, Goldstein RA, Petermann G et al. Disseminated aspergillosis involving the brain. Am J Neuroradiol 1999; 20: 1597–1604.
Miaux Y, Ribaud P, Williams M et al. MRI of cerebral aspergillosis in patients who have had bone marrow transplantation. Am J Neuroradiol 1995; 16: 555–562.
Coley SC, Jäger HR, Szydlo RM, Goldman JM . CT and MRI manifestations of central nervous system infection following bone marrow transplantation. Clin Radiol 1999; 54: 390–397.
Maschke M, Dietrich U, Prumbaum M et al. Opportunistic CNS infection after bone marrow transplantation. Bone Marrow Transplant 1999; 23: 1167–1176.
Dietrich U, Hettman M, Maschke M et al. Cerebral aspergillosis: comparison of radiological and neuropathologic findings in patients with bone marrow transplantation. Eur Radiol 2001; 11: 1242–1249.
de Medeiros BC, de Medeiros CR, Werner B et al. Central nervous system infections following bone marrow transplantation. J Hematother Stem Cell Res 2000; 9: 535–540.
Mohrman R, Mah V, Vinters HV . Neuropathologic findings after bone marrow transplantation: an autopsy study. Hum Pathol 1990; 21: 630–639.
Graus F, Saiz A, Sierra J et al. Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukaemia: a comparative study. Neurology 1996; 46: 1004–1009.
Hagensee ME, Bauvens JE, Kjos B, Bowden RA . Brain abscess following marrow transplantation: experience at the Fred Hutchinson Cancer Research Center, 1984–1992. Clin Infect Dis 1994; 19: 402–408.
Kami M, Ogawa S, Kanda Y et al. Early diagnosis of central nervous system aspergillosis using polymerase chain reaction, latex agglutination test and enzyme-linked immunosorbent assay. Br J Haematol 1999; 106: 536–537.
Yuh WT, Nguyen HD, Gao F et al. Brain parenchymal infection in bone marrow transplant patients: CT and MRI findings. Am J Roentgenol 1994; 162: 425–430.
Bleggi-Torres LF, de Medeiros BC, Werner B et al. Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases. Bone Marrow Transplant 2000; 25: 301–307.
Denning DW . Therapeutic outcome of invasive aspergillosis. Clin Infect Dis 1996; 23: 608–615.
Patterson TF, Kirkpatrick WR, White M et al. for the I3 Aspergillus Study Group. Invasive aspergillosis. Disease spectrum, treatment practices and outcomes. Medicine 2000; 79: 250–260.
Coleman JM, Hogg GG, Rosenfeld JV, Waters KD . Invasive central nervous system aspergillosis: cure with liposomal amphotericin B, itraconazole, and radical surgery: case report and review of the literature. Neurosurgery 1995; 36: 858–863.
Schwartz S, Milatovic D, Thiel E . Successful treatment of cerebral aspergillosis with a novel triazole (voriconazole) in a patient with acute leukaemia. Br J Haematol 1997; 97: 663–665.
Baslar Z, Soysal T, Hanci M et al. Successfully treated invasive central nervous system aspergillosis in an allogeneic stem cell transplant recipient. Bone Marrow Transplant 1998; 22: 404–405.
Khoury H, Adkins D, Miller G et al.. Resolution of invasive central nervous system aspergillosis in a transplant recipient. Bone Marrow Transplant 1997; 20: 179–180.
Collette N, van der Auwera P, Pascual-Lopez A et al.. Tissue distribution and bioavailability of amphotericin B in cancer patients treated with amphotericin B deoxycholate. Antimicrob Agents Chemother 1989; 33: 363–368.
Collette N, van der Auwera P, Meunier F et al. Tissue distribution and bioavailability of amphotericin B administered in liposomes in cancer patients. J Antimicrob Chemother 1991; 27: 535–548.
Como JA, Dismukes WE . Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330: 263–272.
Herbrecht R, Denning DW, Patterson TF et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408–415.
Denning DW, Ribaud P, Milpied N et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002; 34: 563–571.
Perea S, Gonzalez G, Fothergill AW et al. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 2002; 46: 3039–3041.
Kirkpatrick WR, Perea S, Coco BJ, Patterson TF . Efficacy of caspofungin alone or in combination with voriconazole in a Guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002; 46: 2564–2568.
Acknowledgements
This study was financially supported by Blood Disease Research Foundation of Finland.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jantunen, E., Volin, L., Salonen, O. et al. Central nervous system aspergillosis in allogeneic stem cell transplant recipients. Bone Marrow Transplant 31, 191–196 (2003). https://doi.org/10.1038/sj.bmt.1703812
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703812
Keywords
This article is cited by
-
Successful treatment of multiple intracerebral aspergillosis with voriconazole alone in an Egyptian diabetic patient with autoimmune hemolytic anemia
The Egyptian Journal of Internal Medicine (2023)
-
Metagenomic next-generation sequencing for identifying pathogens in central nervous system complications after allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation (2021)
-
Fungal brain infection—no longer a death sentence
Neurosurgical Review (2021)
-
Cerebral and pulmonary aspergillosis, treatment and diagnostic challenges of mixed breakthrough invasive fungal infections: case report study
BMC Infectious Diseases (2020)
-
Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact
Bone Marrow Transplantation (2018)