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Relapsing cerebral aspergilloma associated with pregnancy
Clinical Neurology and Neurosurgery 115 (2013) 1154–1156
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Relapsing cerebral aspergilloma associated with pregnancy Anna Kruetzelmann a,∗ , Ingo Sobottka d , Jens Fiehler b , Eva Tolosa c , Christian Gerloff a , Michael Rosenkranz a a
Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany Department of Immunology, University Medical Center Hamburg-Eppendorf, Germany d LADR-Laborverbund GmbH MVZ Dr. Kramer & Kollegen, Geesthacht, Germany b c
a r t i c l e
i n f o
Article history: Received 17 April 2012 Received in revised form 17 August 2012 Accepted 15 September 2012 Available online 8 October 2012 Keywords: Fungal infection Aspergilloma Pregnancy MRI Seizures
1. Introduction Aspergilloma predominantly occur as opportunistic infections in immunocompromised patients. We report of a 31-year old white woman presented with a first-ever generalized epileptic seizure related to a cerebral aspergilloma in association with pregnancy. 2. Case report Four months after delivery of a healthy full-term infant, a 31-year-old woman presented with a first-ever epileptic seizure. She had a history of several operations on the right maxillary sinus for treatment of a not otherwise specified chronic inflammation. Besides that, the personal and family medical histories were unremarkable. Physical examination revealed visual loss (50%) on the right eye, but no further focal neurological signs. Blood tests showed moderately elevated C-reactive protein (16 mg/l, normal <5 mg/l). Cranial MR imaging (Fig. 1A) depicted a contrast enhancing mass lesion within the right maxillary sinus that propagated along the medial wall of the right orbita and penetrated through the anterior skull base, an edema of the right frontal lobe, and meningeal thickening. Cerebrospinal fluid analysis showed a
∗ Corresponding author at: Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany. Tel.: +49 40 7410 57171; fax: +49 40 7410 56721. E-mail address: [email protected] (A. Kruetzelmann). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.09.024
normal cell count and moderately elevated protein (631 mg/l, normal 140–500 mg/l). The key finding was obtained from a right frontal cortical and meningeal biopsy specimen which revealed growth of Aspergillus (A.) fumigatus in the microbiological analysis. HIV test was negative. Furthermore there is no hint of any immune deficiency in the clinical history. On the basis of the clinical findings, laboratory data and the MR images, the condition was diagnosed as chronic aspergilloma of the right maxillary sinus with secondary invasion of the right frontal lobe. The patient underwent radical operation of the right maxillary sinus, received intravenous voriconazole for 3 weeks, and oral itraconazole for another 8 weeks thereafter. Carbamazepine was administered for prevention of further seizures. Visual loss improved within only a few days, and the patient remained free of seizures. MRI three months later showed complete remission of the edema (Fig. 1B). Two years later the patient complained visual loss again and presented with a relapse of the aspergilloma one month after delivery of a healthy full-term infant. As on initial presentation, cranial MRI showed massive frontal edema and meningeal enhancement that again resolved after treatment with voriconazole. Since then the patient remained free of relapses.
3. Discussion This case provides additional evidence to two previous reports on pulmonary and disseminated aspergillosis associated with
A. Kruetzelmann et al. / Clinical Neurology and Neurosurgery 115 (2013) 1154–1156
1155
Fig. 1. MR images of the head (A) after first admission and (B) after recovery. T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences and T1-weighted sequences.
HIV-negative pregnancy [1,2]. Prior to her first pregnancy, our patient had undergone several operations of the right maxillary sinus. Former biopsies revealed an inflammatory pseudotumor. Retrospectively, this inflammation most likely had already been a chronic maxillary aspergilloma. During pregnancy this aspergilloma rapidly progressed, penetrated the skull and invaded the brain parenchyma. Antifungal therapy yielded complete remission of clinical symptoms and of visible residue on MRI, but obviously not complete elimination of A. fumigatus. It appears that a persisting fungal infection was controlled in this immunocompetent woman until she became pregnant again. There is no evidence at which timepoint after manifestation of cerebral aspergilloma seizures appear. We only know about a median interval of 8 weeks between diagnosis of a brain tumor and a first seizure. Therefore the beginning of the manifestation of the cerebral aspergilloma in our patient remained unknown, but the time coincidence with the two previous pregnancies seems convincing. In fact, pregnancy has been described as a period with changes in the immunosystem, likely to prevent fetal rejection. The multiple changes in the maternal immune system during pregnancy have already shown effects in different autoimmune diseases. It is known that during pregnancy improvement or even remission of an autoimmune disease can occur, frequently followed by a relapse after delivery. One hypothesis is, that there is an increased expression of various anti-inflammatory cytokines (e.g. IL-1R alpha or TNFR) during pregnancy, while on the other hand after delivery a
higher expression of Type 1 cytokines (e.g. TNF-alpha) is detectable. These Type 1 cytokines are associated with a post-delivery relapse of autoimmune diseases [3]. This hypothesis is well in line with opportunistic infections during pregnancy in otherwise non-immunocompromised women such as cerebral toxoplasmosis or cerebral cryptococcosis [4,5].
4. Conclusion In summary, our case suggests that pregnancy may promote severe opportunistic brain infections due to pregnancy-related immunosuppression. Therefore we conclude that the risk of fungal infections during pregnancy must be considered and that a sustainable antifungal treatment is an essential and effective therapy.
Source of funding No funding.
Conflicts of interest The authors report no conflicts of interest.
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A. Kruetzelmann et al. / Clinical Neurology and Neurosurgery 115 (2013) 1154–1156
References [1] Pagliano P, Attanasio V, Fusco U, Rossi M, Scarano F, Faella FS. Pulmonary aspergillosis with possible cerebral involvement in a previously healthy pregnant woman. Journal of Chemotherapy 2004;16: 604–7. [2] Klock C, Cerski M, Dargel A, Goldani LZ. Case report. Disseminated aspergillosis complicating pregnancy. Mycoses 2002;45:408–10.
[3] Munoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunological Reviews 2011;241:20–38. [4] Alapatt JP, Kutty RK, Jose B, Gopi P. A case of cerebral toxoplasmosis in a pregnant non-immunocompromised patient. Neurologia i Neurochirurgia Polska 2009;43:391–5. [5] Costa ML, Souza JP, Oliveira Neto AF, Pinto E, Silva JL. Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature. Revista do Instituto de Medicina Tropical de Sao Paulo 2009;51:289–94.
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Relapsing cerebral aspergilloma associated with pregnancy Anna Kruetzelmann a,∗ , Ingo Sobottka d , Jens Fiehler b , Eva Tolosa c , Christian Gerloff a , Michael Rosenkranz a a
Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany Department of Immunology, University Medical Center Hamburg-Eppendorf, Germany d LADR-Laborverbund GmbH MVZ Dr. Kramer & Kollegen, Geesthacht, Germany b c
a r t i c l e
i n f o
Article history: Received 17 April 2012 Received in revised form 17 August 2012 Accepted 15 September 2012 Available online 8 October 2012 Keywords: Fungal infection Aspergilloma Pregnancy MRI Seizures
1. Introduction Aspergilloma predominantly occur as opportunistic infections in immunocompromised patients. We report of a 31-year old white woman presented with a first-ever generalized epileptic seizure related to a cerebral aspergilloma in association with pregnancy. 2. Case report Four months after delivery of a healthy full-term infant, a 31-year-old woman presented with a first-ever epileptic seizure. She had a history of several operations on the right maxillary sinus for treatment of a not otherwise specified chronic inflammation. Besides that, the personal and family medical histories were unremarkable. Physical examination revealed visual loss (50%) on the right eye, but no further focal neurological signs. Blood tests showed moderately elevated C-reactive protein (16 mg/l, normal <5 mg/l). Cranial MR imaging (Fig. 1A) depicted a contrast enhancing mass lesion within the right maxillary sinus that propagated along the medial wall of the right orbita and penetrated through the anterior skull base, an edema of the right frontal lobe, and meningeal thickening. Cerebrospinal fluid analysis showed a
∗ Corresponding author at: Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany. Tel.: +49 40 7410 57171; fax: +49 40 7410 56721. E-mail address: [email protected] (A. Kruetzelmann). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.09.024
normal cell count and moderately elevated protein (631 mg/l, normal 140–500 mg/l). The key finding was obtained from a right frontal cortical and meningeal biopsy specimen which revealed growth of Aspergillus (A.) fumigatus in the microbiological analysis. HIV test was negative. Furthermore there is no hint of any immune deficiency in the clinical history. On the basis of the clinical findings, laboratory data and the MR images, the condition was diagnosed as chronic aspergilloma of the right maxillary sinus with secondary invasion of the right frontal lobe. The patient underwent radical operation of the right maxillary sinus, received intravenous voriconazole for 3 weeks, and oral itraconazole for another 8 weeks thereafter. Carbamazepine was administered for prevention of further seizures. Visual loss improved within only a few days, and the patient remained free of seizures. MRI three months later showed complete remission of the edema (Fig. 1B). Two years later the patient complained visual loss again and presented with a relapse of the aspergilloma one month after delivery of a healthy full-term infant. As on initial presentation, cranial MRI showed massive frontal edema and meningeal enhancement that again resolved after treatment with voriconazole. Since then the patient remained free of relapses.
3. Discussion This case provides additional evidence to two previous reports on pulmonary and disseminated aspergillosis associated with
A. Kruetzelmann et al. / Clinical Neurology and Neurosurgery 115 (2013) 1154–1156
1155
Fig. 1. MR images of the head (A) after first admission and (B) after recovery. T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences and T1-weighted sequences.
HIV-negative pregnancy [1,2]. Prior to her first pregnancy, our patient had undergone several operations of the right maxillary sinus. Former biopsies revealed an inflammatory pseudotumor. Retrospectively, this inflammation most likely had already been a chronic maxillary aspergilloma. During pregnancy this aspergilloma rapidly progressed, penetrated the skull and invaded the brain parenchyma. Antifungal therapy yielded complete remission of clinical symptoms and of visible residue on MRI, but obviously not complete elimination of A. fumigatus. It appears that a persisting fungal infection was controlled in this immunocompetent woman until she became pregnant again. There is no evidence at which timepoint after manifestation of cerebral aspergilloma seizures appear. We only know about a median interval of 8 weeks between diagnosis of a brain tumor and a first seizure. Therefore the beginning of the manifestation of the cerebral aspergilloma in our patient remained unknown, but the time coincidence with the two previous pregnancies seems convincing. In fact, pregnancy has been described as a period with changes in the immunosystem, likely to prevent fetal rejection. The multiple changes in the maternal immune system during pregnancy have already shown effects in different autoimmune diseases. It is known that during pregnancy improvement or even remission of an autoimmune disease can occur, frequently followed by a relapse after delivery. One hypothesis is, that there is an increased expression of various anti-inflammatory cytokines (e.g. IL-1R alpha or TNFR) during pregnancy, while on the other hand after delivery a
higher expression of Type 1 cytokines (e.g. TNF-alpha) is detectable. These Type 1 cytokines are associated with a post-delivery relapse of autoimmune diseases [3]. This hypothesis is well in line with opportunistic infections during pregnancy in otherwise non-immunocompromised women such as cerebral toxoplasmosis or cerebral cryptococcosis [4,5].
4. Conclusion In summary, our case suggests that pregnancy may promote severe opportunistic brain infections due to pregnancy-related immunosuppression. Therefore we conclude that the risk of fungal infections during pregnancy must be considered and that a sustainable antifungal treatment is an essential and effective therapy.
Source of funding No funding.
Conflicts of interest The authors report no conflicts of interest.
1156
A. Kruetzelmann et al. / Clinical Neurology and Neurosurgery 115 (2013) 1154–1156
References [1] Pagliano P, Attanasio V, Fusco U, Rossi M, Scarano F, Faella FS. Pulmonary aspergillosis with possible cerebral involvement in a previously healthy pregnant woman. Journal of Chemotherapy 2004;16: 604–7. [2] Klock C, Cerski M, Dargel A, Goldani LZ. Case report. Disseminated aspergillosis complicating pregnancy. Mycoses 2002;45:408–10.
[3] Munoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunological Reviews 2011;241:20–38. [4] Alapatt JP, Kutty RK, Jose B, Gopi P. A case of cerebral toxoplasmosis in a pregnant non-immunocompromised patient. Neurologia i Neurochirurgia Polska 2009;43:391–5. [5] Costa ML, Souza JP, Oliveira Neto AF, Pinto E, Silva JL. Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature. Revista do Instituto de Medicina Tropical de Sao Paulo 2009;51:289–94.