- Email: [email protected]
Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess
Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Report
Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess Benjamin L. Grannan, Vijay Yanamadala, Andrew S. Venteicher, Brian P. Walcott ⇑, John C. Barr Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit Street, WACC 745, Boston, MA 02115, USA Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 11 November 2013 Accepted 13 January 2014 Available online xxxx Keywords: Amphotericin External ventricular drain Intrathecal Mucormycosis Neurocritical care
a b s t r a c t Mucormycosis is an invasive fungal infection associated with a high mortality. Cerebral mucor abscesses can result secondary to rhinocerebral or hematogenous spread. Amphotericin B, posaconazole, and aggressive surgical resection are the hallmarks of treatment. While amphotericin is typically administered intravenously, less is known about the use of intrathecal amphotericin B. We describe a 42-year-old man who developed a cerebellar mucor abscess after undergoing hematopoietic stem cell transplant for the treatment of myelodysplastic syndrome. In the post-operative period he was admitted to the neurocritical care unit and received liposomal amphotericin B intravenously and through an external ventricular drain. This patient demonstrates that utilization of an external ventricular drain for intrathecal antifungal therapy in the post-operative period may warrant further study in patients with difficult to treat intracranial fungal abscesses. Ó 2014 Published by Elsevier Ltd.
1. Introduction The incidence of mucormycosis has been rising among bone marrow transplant recipients and patients with hematologic malignancy [1,2]. Intracranial involvement typically results from rhinocerebral or hematogenous spread, but isolated cerebral infections have been documented [3]. Early surgical resection, anti-fungal treatment, and immune system reconstitution decrease mortality [4]. We present a patient with cerebellar mucor abscess treated with surgical resection and intrathecal liposomal amphotericin B administered through an external ventricular drain (EVD). 2. Case report A 42-year-old man underwent allogeneic hematopoietic stem cell transplant for treatment of myelodysplastic syndrome. His recovery was complicated by multifocal pneumonia and Streptococcus salivarius bacteremia. His medications included tacrolimus, micafungin, famciclovir, vancomycin, and cefepime. Four weeks post-transplant he developed a right-sided occipital headache and photophobia. His neurological examination demonstrated right-sided dysmetria but was otherwise unremarkable. ⇑ Corresponding author. Tel.: +1 617 726 3303; fax: +1 617 726 2424. E-mail address: [email protected] (B.P. Walcott).
MRI revealed a 3.0 cm ring-enhancing mass in the right cerebellum with surrounding T2-hyperintensity and mild compression of the fourth ventricle. Metronidazole, ceftriaxone, and voriconazole were added to his antimicrobial regimen for broad empirical treatment. Three months post-transplant he was admitted after developing nausea and vomiting. MRI imaging showed significant fourth ventricle effacement (Fig. 1). He was admitted to the neurocritical care unit and an EVD was placed. A sub-occipital craniotomy was performed to resect the cerebellar lesion. Examination of lesion contents revealed mucormycosis (Absidia) and the patient was started on intravenous liposomal amphotericin B and posaconazole. Three 1.5 mg doses of intrathecal liposomal amphotericin B were administered through the EVD during the first post-operative week. The patient was weaned off the EVD by post-operative day 8 and discharged on post-operative day 17. Follow-up MRI demonstrated resolution of post-operative changes (Fig. 2). 3. Discussion 3.1. Management of cerebral mucormycosis Mucormycosis in patients with hematologic malignancy carries a poor prognosis, with good long-term outcome being associated with early initiation of anti-fungal therapy, neutrophil reconstitution, and surgical resection [1,5]. Liposomal amphotericin B,
http://dx.doi.org/10.1016/j.jocn.2014.01.008 0967-5868/Ó 2014 Published by Elsevier Ltd.
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008
2
Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Fig. 1. Pre-operative (A–C) and post-operative day 3 (D–F) MRI demonstrating resection of right cerebellar ring-enhancing lesion by comparing T2-weighted fluid attenuated inversion recovery (A and D), T1-weighted pre-contrast (B and E), and T1-weighted post-contrast (C and F) axial images.
Fig. 2. Ten month follow-up (A–C) MRI demonstrating resolution of post-operative changes following resection of right cerebellar lesion by comparing T2-weighted fluid attenuated inversion recovery (A), T1-weighted pre-contrast (B), and T1-weighted post-contrast (C) axial images.
posaconazole, and surgical debridement are the mainstays of treatment. A study of 70 patients with hematological malignancy and zygomycosis found that patients who started amphotericin within 6 days of diagnosis had a 48.6% 12 week mortality rate compared to 82.9% in patients who initiated therapy at a later time [5]. 3.2. Review of intrathecal amphotericin for cerebral mucormycosis We identified seven published cases of intrathecal amphotericin for treatment of mucormycosis. The first was of a 31-year-old
woman who presented with meningitis due to a frontotemporal mucor abscess. Despite surgical resection and post-operative intravenous and intrathecal amphotericin B therapy the patient died on post-operative day 5 [6]. All subsequent publications reported positive long-term outcomes, including a 31-year-old diabetic man with bilateral brain abscesses in the context of rhinocerebral mucormycosis who recovered after surgical resection and 5 weeks of intravenous and intrathecal amphotericin B via Ommaya reservoir [7], and a 26-year-old intravenous drug user with primary cerebral mucormycosis who had no long-term recurrence after
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008
Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
7 weeks of intrathecal amphotericin B via Ommaya followed by resection and 12 days of amphotericin B via EVD [8]. The remaining patients were in the pediatric population including two diabetic teenage boys (aged 14 and 16) with cerebral mucor abscesses who were successfully treated with surgery followed by intrathecal amphotericin via Ommaya reservoir [9] and intracavitary/intraventricular injections [10], respectively. A 12-year-old girl [11] with autoimmune hepatitis and rhinocerebral mucormycosis with intracranial extension and a 3-year-old immunocompetent boy [12] with seizures secondary to mucor brain abscess were also treated successfully with combined intravenous and intrathecal amphotericin B. 4. Conclusion Successful treatment of mucormycosis is dependent upon early treatment with liposomal amphotericin B and posaconazole. While there is a paucity of data confirming the efficacy of intrathecal amphotericin in patients with intracranial mucormycosis, we found that six of the seven previously published patients reported good long-term outcome, suggesting that early intrathecal therapy warrants further consideration for difficult-to-treat intracranial fungal infections. As demonstrated here and in one previous case report, EVD provide a mechanism for administering amphotericin to the intrathecal space while simultaneously treating and monitoring elevated intracranial pressure in the neurocritical care setting.
3
References [1] Bethge WA, Schmalzing M, Stuhler G, et al. Mucormycoses in patients with hematologic malignancies: an emerging fungal infection. Haematologica 2005;90:ECR22. [2] Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909–17. [3] Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53. [4] Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009;48:1743–51. [5] Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008;47:503–9. [6] Whalen MJ, Beyt BE Jr. Cryptic cerebral phycomycosis. Ann Intern Med 1979;91:655. [7] Hamill R, Oney LA, Crane LR. Successful therapy for rhinocerebral mucormycosis with associated bilateral brain abscesses. Arch Intern Med 1983;143:581–3. [8] Fong KM, Seneviratne EM, McCormack JG. Mucor cerebral abscess associated with intravenous drug abuse. Aust N Z J Med 1990;20:74–7. [9] Hamilton JF, Bartkowski HB, Rock JP. Management of CNS mucormycosis in the pediatric patient. Pediatr Neurosurg 2003;38:212–5. [10] Adler DE, Milhorat TH, Miller JI. Treatment of rhinocerebral mucormycosis with intravenous interstitial, and cerebrospinal fluid administration of amphotericin B: case report. Neurosurgery 1998;42:644–8 [discussion 648–9]. [11] Ibrahim M, Chitnis S, Fallon K, et al. Rhinocerebral mucormycosis in a 12-yearold girl. Arch Neurol 2009;66:272–3. [12] Tsung LL, Zhu XL, Chu WC, et al. Intraventricular amphotericin for absidiomycosis in an immunocompetent child. Hong Kong Med J 2010;16:137–40.
Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Report
Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess Benjamin L. Grannan, Vijay Yanamadala, Andrew S. Venteicher, Brian P. Walcott ⇑, John C. Barr Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit Street, WACC 745, Boston, MA 02115, USA Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 11 November 2013 Accepted 13 January 2014 Available online xxxx Keywords: Amphotericin External ventricular drain Intrathecal Mucormycosis Neurocritical care
a b s t r a c t Mucormycosis is an invasive fungal infection associated with a high mortality. Cerebral mucor abscesses can result secondary to rhinocerebral or hematogenous spread. Amphotericin B, posaconazole, and aggressive surgical resection are the hallmarks of treatment. While amphotericin is typically administered intravenously, less is known about the use of intrathecal amphotericin B. We describe a 42-year-old man who developed a cerebellar mucor abscess after undergoing hematopoietic stem cell transplant for the treatment of myelodysplastic syndrome. In the post-operative period he was admitted to the neurocritical care unit and received liposomal amphotericin B intravenously and through an external ventricular drain. This patient demonstrates that utilization of an external ventricular drain for intrathecal antifungal therapy in the post-operative period may warrant further study in patients with difficult to treat intracranial fungal abscesses. Ó 2014 Published by Elsevier Ltd.
1. Introduction The incidence of mucormycosis has been rising among bone marrow transplant recipients and patients with hematologic malignancy [1,2]. Intracranial involvement typically results from rhinocerebral or hematogenous spread, but isolated cerebral infections have been documented [3]. Early surgical resection, anti-fungal treatment, and immune system reconstitution decrease mortality [4]. We present a patient with cerebellar mucor abscess treated with surgical resection and intrathecal liposomal amphotericin B administered through an external ventricular drain (EVD). 2. Case report A 42-year-old man underwent allogeneic hematopoietic stem cell transplant for treatment of myelodysplastic syndrome. His recovery was complicated by multifocal pneumonia and Streptococcus salivarius bacteremia. His medications included tacrolimus, micafungin, famciclovir, vancomycin, and cefepime. Four weeks post-transplant he developed a right-sided occipital headache and photophobia. His neurological examination demonstrated right-sided dysmetria but was otherwise unremarkable. ⇑ Corresponding author. Tel.: +1 617 726 3303; fax: +1 617 726 2424. E-mail address: [email protected] (B.P. Walcott).
MRI revealed a 3.0 cm ring-enhancing mass in the right cerebellum with surrounding T2-hyperintensity and mild compression of the fourth ventricle. Metronidazole, ceftriaxone, and voriconazole were added to his antimicrobial regimen for broad empirical treatment. Three months post-transplant he was admitted after developing nausea and vomiting. MRI imaging showed significant fourth ventricle effacement (Fig. 1). He was admitted to the neurocritical care unit and an EVD was placed. A sub-occipital craniotomy was performed to resect the cerebellar lesion. Examination of lesion contents revealed mucormycosis (Absidia) and the patient was started on intravenous liposomal amphotericin B and posaconazole. Three 1.5 mg doses of intrathecal liposomal amphotericin B were administered through the EVD during the first post-operative week. The patient was weaned off the EVD by post-operative day 8 and discharged on post-operative day 17. Follow-up MRI demonstrated resolution of post-operative changes (Fig. 2). 3. Discussion 3.1. Management of cerebral mucormycosis Mucormycosis in patients with hematologic malignancy carries a poor prognosis, with good long-term outcome being associated with early initiation of anti-fungal therapy, neutrophil reconstitution, and surgical resection [1,5]. Liposomal amphotericin B,
http://dx.doi.org/10.1016/j.jocn.2014.01.008 0967-5868/Ó 2014 Published by Elsevier Ltd.
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008
2
Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Fig. 1. Pre-operative (A–C) and post-operative day 3 (D–F) MRI demonstrating resection of right cerebellar ring-enhancing lesion by comparing T2-weighted fluid attenuated inversion recovery (A and D), T1-weighted pre-contrast (B and E), and T1-weighted post-contrast (C and F) axial images.
Fig. 2. Ten month follow-up (A–C) MRI demonstrating resolution of post-operative changes following resection of right cerebellar lesion by comparing T2-weighted fluid attenuated inversion recovery (A), T1-weighted pre-contrast (B), and T1-weighted post-contrast (C) axial images.
posaconazole, and surgical debridement are the mainstays of treatment. A study of 70 patients with hematological malignancy and zygomycosis found that patients who started amphotericin within 6 days of diagnosis had a 48.6% 12 week mortality rate compared to 82.9% in patients who initiated therapy at a later time [5]. 3.2. Review of intrathecal amphotericin for cerebral mucormycosis We identified seven published cases of intrathecal amphotericin for treatment of mucormycosis. The first was of a 31-year-old
woman who presented with meningitis due to a frontotemporal mucor abscess. Despite surgical resection and post-operative intravenous and intrathecal amphotericin B therapy the patient died on post-operative day 5 [6]. All subsequent publications reported positive long-term outcomes, including a 31-year-old diabetic man with bilateral brain abscesses in the context of rhinocerebral mucormycosis who recovered after surgical resection and 5 weeks of intravenous and intrathecal amphotericin B via Ommaya reservoir [7], and a 26-year-old intravenous drug user with primary cerebral mucormycosis who had no long-term recurrence after
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008
Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
7 weeks of intrathecal amphotericin B via Ommaya followed by resection and 12 days of amphotericin B via EVD [8]. The remaining patients were in the pediatric population including two diabetic teenage boys (aged 14 and 16) with cerebral mucor abscesses who were successfully treated with surgery followed by intrathecal amphotericin via Ommaya reservoir [9] and intracavitary/intraventricular injections [10], respectively. A 12-year-old girl [11] with autoimmune hepatitis and rhinocerebral mucormycosis with intracranial extension and a 3-year-old immunocompetent boy [12] with seizures secondary to mucor brain abscess were also treated successfully with combined intravenous and intrathecal amphotericin B. 4. Conclusion Successful treatment of mucormycosis is dependent upon early treatment with liposomal amphotericin B and posaconazole. While there is a paucity of data confirming the efficacy of intrathecal amphotericin in patients with intracranial mucormycosis, we found that six of the seven previously published patients reported good long-term outcome, suggesting that early intrathecal therapy warrants further consideration for difficult-to-treat intracranial fungal infections. As demonstrated here and in one previous case report, EVD provide a mechanism for administering amphotericin to the intrathecal space while simultaneously treating and monitoring elevated intracranial pressure in the neurocritical care setting.
3
References [1] Bethge WA, Schmalzing M, Stuhler G, et al. Mucormycoses in patients with hematologic malignancies: an emerging fungal infection. Haematologica 2005;90:ECR22. [2] Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909–17. [3] Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53. [4] Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009;48:1743–51. [5] Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008;47:503–9. [6] Whalen MJ, Beyt BE Jr. Cryptic cerebral phycomycosis. Ann Intern Med 1979;91:655. [7] Hamill R, Oney LA, Crane LR. Successful therapy for rhinocerebral mucormycosis with associated bilateral brain abscesses. Arch Intern Med 1983;143:581–3. [8] Fong KM, Seneviratne EM, McCormack JG. Mucor cerebral abscess associated with intravenous drug abuse. Aust N Z J Med 1990;20:74–7. [9] Hamilton JF, Bartkowski HB, Rock JP. Management of CNS mucormycosis in the pediatric patient. Pediatr Neurosurg 2003;38:212–5. [10] Adler DE, Milhorat TH, Miller JI. Treatment of rhinocerebral mucormycosis with intravenous interstitial, and cerebrospinal fluid administration of amphotericin B: case report. Neurosurgery 1998;42:644–8 [discussion 648–9]. [11] Ibrahim M, Chitnis S, Fallon K, et al. Rhinocerebral mucormycosis in a 12-yearold girl. Arch Neurol 2009;66:272–3. [12] Tsung LL, Zhu XL, Chu WC, et al. Intraventricular amphotericin for absidiomycosis in an immunocompetent child. Hong Kong Med J 2010;16:137–40.
Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
Please cite this article in press as: Grannan BL et al. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.01.008