The Neuroradiology Journal 27: 334-338, 2014 - doi: 10.15274/NRJ-2014-10038
www.centauro.it
Histoplasmosis Brain Abscesses in an Immunocompetent Adult A Case Report and Literature Review ANA INES ANDRADE1, MAREN DONATO1, CARLOS PREVIGLIANO2, MARDJOHAN HARDJASUDARMA2 1 2
Department of Radiology, CIMED; La Plata, Buenos Aires, Argentina Department of Radiology, Louisiana State University Health Sciences Center; Shreveport, LA, USA
Key words: Histoplasma capsulatum, ring enhancing, fungal abscess, immunocompetent individual
SUMMARY – We describe the case of a 62-year-old man, who presented with a new onset of focal seizures of his right leg. There were no other clinical symptoms, and laboratory results were normal. Brain magnetic resonance imaging revealed multiple lesions, two supratentorial lesions were ring-enhancing. The brain biopsy tissue showed Histoplasma capsulatum abscesses. He improved on treatment with Amphotericin B. This case is reported since cerebral ring-enhancing lesions are rarely associated with histoplasmosis, which is also rare in an immunocompetent individual. We review the literature and discuss the radiologic and pathologic findings of this case compared with previous reports.
Introduction Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum 1. Humans are infected via inhalation of airborne microconidia, which the wind can carry for miles 2. Once in the lung, the microconidia are converted into pathogenic yeast forms that disseminate hematogenously to multiple organs, including the brain, spinal cord, and meninges 3. Histoplasmosis brain abscess is commonly seen in immunocompromised individuals 2. In addition, Histoplasma capsulatum is a neurotropic dimorphic fungus that causes self-limiting systemic mycosis in endemic regions while extra pulmonary manifestations are uncommon and typically asymptomatic 4. Central nervous system involvement is clinically recognized in 10% to 20% of cases of progressive histoplasmosis. However, in rare cases it may be an isolated finding especially in immunocompetent individuals 5. Meningitis and histoplasmoma formation are the common clinical manifestations of central nervous system histoplasmosis, whereas cerebritis and abscess are rare. To the best of our 334
knowledge, no cases of histoplasmosis brain abscesses in immunocompetent individuals have been reported. Case Report A 62-year-old man presented with a new onset of focal seizures of his right leg. This patient was not immunocompromised and serology for human immunodeficiency virus was negative. He did not have any history suggestive of deficient cellular immunity. He denied involvement with recreational activities that could have predisposed him for Histoplasma infection, or exposure to bat or bird droppings. His absolute lymphocyte count was normal. The cerebral spinal fluid culture was negative for an active infection or malignant cells. Computed tomography of the chest, abdomen and pelvis were negative for any malignancy. Magnetic resonance (MR) scan at the time showed multiple infra and supratentorial compartmental lesions, two supratentorial lesions were ring-enhancing, surrounding extensive vasogenic edema and restricted diffusion, in-
Ana Ines Andrade
A
Histoplasmosis Brain Abscesses in an Immunocompetent Adult
B
Figure 1 A,B) T1-weighted axial and coronal images after contrast administration showing the cerebellar lesions and pachymeningeal thickening.
dicating purulent content. There was also meningeal enhancement after contrast administration. Differential diagnosis like left frontal abscess coexisting with a metastatic deposit or a metastatic deposit with abscesses was included. Pathology evaluation of the brain biopsy was consistent with histoplasma capsulatum abscesses. The patient was started on oral amphotericin B. He was also started on dexamethasone as an anticerebral edema measure. The patient’s condition improved on treatment. Imaging Findings MR characteristics of the case included multiple infra and supratentorial compartmental lesions. The cerebellar lesions appeared solid in the right vermis, a second lesion was adjacent to the lateral recess of the fourth ventricle and the third in the left cerebellar hemisphere in the paravermian area (Figure 1). There were also lesions in the right hippocampus, left posterior frontal orbital gyrus, left insula, left occipital lobe, right caudate and left caudate nucleus (Figure 2). A prominent ring-enhancing lesion was seen in the left prefrontal area sur-
rounded by extensive vasogenic edema. A ringenhancing lesion in the vertex on the left side with extensive vasogenic edema was seen and also a lesion attached to the dura in the dorsal frontal pole on the left. The abscess walls of the left ring-enhancing lesions presented a hypointense signal in susceptibility-weighted imaging indicating probable hemosiderin deposits in the capsule (Figure 3). The ring-enhancing lesions had restricted diffusion and MR spectroscopy showed prominent lipid and lactate peaks with increased choline (Cho) indicating purulent content (Figure 4). Pathologic Findings Brain biopsy tissue showed Histoplasma capsulatum abscesses (Figure 5). Discussion and Literature Review Histoplasma capsulatum is an endemic fungus in certain regions of North America and Latin America, including the Ohio and Mississippi river valleys of the United States. Central nervous system involvement occurs in 5 to 20% 335
Histoplasmosis Brain Abscesses in an Immunocompetent Adult
A
B
Ana Ines Andrade
C
Figure 2 A-C) T1-weighted axial images after contrast administration showing the multiple supratentorial solid lesions. A
B
C
Figure 3 A) Susceptibility-weighted axial image showing a round lesion surrounded by extensive vasogenic edema and hypointense signal in the wall on the left prefrontal area, indicating probable hemosiderin deposits in its capsule. B,C) T1-weighted images before and after contrast administration with prominent ring-enhancing lesions. A
B
C
Figure 4 A-C) Diffusion sequences showing restricted diffusion, indicating purulent content.
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www.centauro.it
The Neuroradiology Journal 27: 334-338, 2014 - doi: 10.15274/NRJ-2014-10038
A
B
Figure 5 A) Photomicrograph shows multiple organisms in histiocytes with a pale zone suggesting a capsule (hematoxylin-eosin stain). B) Photomicrograph shows silver-stained intracytoplasmic round bodies of Histoplasma capsulatum in foamy histiocytes (Gomori methenamine silver stain).
of cases of disseminated histoplasmosis and is more common in those with underlying immunosuppressive disorders 6,7. Disseminated histoplasmosis, especially with a ring-enhancing brain lesion, is uncommon in an immunocompetent individual 8. Few patients (5%-10%) with disseminated histoplasmosis will develop central nervous system (CNS) infection, and only 25% of these will develop neurological symptoms 7. Imaging findings include hydrocephalus, histoplasmoma, vasculitis with infarctions and leptomeningeal enhancement 9. In one case series of isolated CNS histoplasmosis, 90% of patients had hydrocephalus and two patients had focal enhancement on T1 imaging 10. This case series of 11 patients included two children age three and 15 years. Recently, another child in a Histoplasma endemic region was reported to have isolated histoplasma meningoencephalitis. T1 MRI demonstrated meningeal enhancement with multiple non-enhancing lesions consistent with infarction 11. Projections into the cavity from the wall of an abscess with low apparent diffusion coefficient and no enhancement have been described as a characteristic of fungal etiology 12.
Our case had multiple lesions, two of them with ring-enhancement, restricted diffusion and thickened wall with probable hemosiderin deposits. These finding have not been reported histoplasmosis abscesses to date. Conclusion While pulmonary involvement of histoplasmosis in immunosuppressed patients is common, systemic presentation of this fungal infection in immunocompetent patients is rare and self-limiting. Isolated CNS histoplasmosis is exceedingly rare 13. To our knowledge, this is the first case in the literature of multiple histoplasmosis brain abscesses presenting with ring-enhancing lesions, irregular wall thickening and hemosiderin deposits inside. CNS fungal disease in immunocompetent hosts is unusual and requires a high index of suspicion for diagnosis. Therefore, in Histoplasma endemic regions, physicians should include CNS histoplasmosis for an early diagnosis and adequate treatment.
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Histoplasmosis Brain Abscesses in an Immunocompetent Adult
Ana Ines Andrade
References 1 Adderson E. Histoplasmosis. Pediatr Infect Dis J. 2006; 25 (1): 73-74. doi: 10.1097/01.inf.0000196922.46347.66. 2 Saccente M. Central nervous system histoplasmosis. Curr Treat Options Neurol. 2008; 10 (3): 161-167. doi: 10.1007/s11940-008-0017-x. 3 Medoff G, Kobayashi GS, Painter A, et al: Morphogenesis and pathogenicity of Histoplasma capsulatum. Infect Immun. 1987; 55 (6): 1355-1358. 4 Parihar A, Tomar V, Ojha BK, et al. Magnetic resonance imaging findings in a patient with isolated histoplasma brain abscess. Arch Neurol. 2011; 68 (4): 534-535. doi: 10.1001/archneurol.2011.59. 5 Zalduondo FM, Provenzale JM, Hulette C, et al. Meningitis, vasculitis, and cerebritis caused by CNS histoplasmosis: radiologic-pathologic correlation. Am J Roentgenol. 1996; 166 (1): 194-196. doi: 10.2214/ ajr.166.1.8571874. 6 Assi MA, Sandid MS, Baddour LM, et al. Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients. Medicine (Baltimore). 2007; 86 (3): 162-169. doi: 10.1097/md.0b013e3180679130. 7 Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore). 1990; 69 (4): 244-260. doi: 10.1097/00005792-199007000-00006. 8 Subramanian S, Abraham OC, Rupali P, et al. Disseminated histoplasmosis. J Assoc Physicians India. 2005; 53: 185-189. 9 Schuster JE1, Wushensky CA, Di Pentima MC. Chronic primary central nervous system histoplasmosis in a healthy child with intermittent neurological manifestations. Pediatr Infect Dis J. 2013; 32 (7): 794-796. doi: 10.1097/INF.0b013e31828d293e.
338
10 Schestatsky P, Chedid MF, Amaral OB, et al. Isolated central nervous system histoplasmosis in immunocompetent hosts: a series of 11 cases. Scand J Infect Dis. 2006; 38 (1): 43-48. doi: 10.1080/00365540500372895. 11 Threlkeld ZD, Broughton R, Khan GQ, et al. Isolated Histoplasma capsulatum meningoencephalitis in an immunocompetent child. J Child Neurol. 2012; 27 (4): 532535. doi: 10.1177/0883073811428780. 12 Luthra G, Parihar A, Nath K, et al. Comparative evaluation of fungal, tubercular, and pyogenic brain abscesses with conventional and diffusion MR imaging and proton MR spectroscopy. Am J Neuroradiol. 2007; 28 (7): 1332-1338. doi: 10.3174/ajnr.A0548. 13 Nguyen FN, Kar JK, Zakaria A, et al. Isolated central nervous system histoplasmosis presenting with ischemic pontine stroke and meningitis in an immunocompetent patient. JAMA Neurol. 2013; 70 (5): 638-641. doi: 10.1001/jamaneurol.2013.1043.
Ana Ines Andrade, MD Resident, Department of Radiology CIMED-La Plata 416, 5th street, La Plata Buenos Aires. Argentina Tel.: (+54) 9-221-571-7037 E-mail: [email protected]
www.centauro.it
Histoplasmosis Brain Abscesses in an Immunocompetent Adult A Case Report and Literature Review ANA INES ANDRADE1, MAREN DONATO1, CARLOS PREVIGLIANO2, MARDJOHAN HARDJASUDARMA2 1 2
Department of Radiology, CIMED; La Plata, Buenos Aires, Argentina Department of Radiology, Louisiana State University Health Sciences Center; Shreveport, LA, USA
Key words: Histoplasma capsulatum, ring enhancing, fungal abscess, immunocompetent individual
SUMMARY – We describe the case of a 62-year-old man, who presented with a new onset of focal seizures of his right leg. There were no other clinical symptoms, and laboratory results were normal. Brain magnetic resonance imaging revealed multiple lesions, two supratentorial lesions were ring-enhancing. The brain biopsy tissue showed Histoplasma capsulatum abscesses. He improved on treatment with Amphotericin B. This case is reported since cerebral ring-enhancing lesions are rarely associated with histoplasmosis, which is also rare in an immunocompetent individual. We review the literature and discuss the radiologic and pathologic findings of this case compared with previous reports.
Introduction Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum 1. Humans are infected via inhalation of airborne microconidia, which the wind can carry for miles 2. Once in the lung, the microconidia are converted into pathogenic yeast forms that disseminate hematogenously to multiple organs, including the brain, spinal cord, and meninges 3. Histoplasmosis brain abscess is commonly seen in immunocompromised individuals 2. In addition, Histoplasma capsulatum is a neurotropic dimorphic fungus that causes self-limiting systemic mycosis in endemic regions while extra pulmonary manifestations are uncommon and typically asymptomatic 4. Central nervous system involvement is clinically recognized in 10% to 20% of cases of progressive histoplasmosis. However, in rare cases it may be an isolated finding especially in immunocompetent individuals 5. Meningitis and histoplasmoma formation are the common clinical manifestations of central nervous system histoplasmosis, whereas cerebritis and abscess are rare. To the best of our 334
knowledge, no cases of histoplasmosis brain abscesses in immunocompetent individuals have been reported. Case Report A 62-year-old man presented with a new onset of focal seizures of his right leg. This patient was not immunocompromised and serology for human immunodeficiency virus was negative. He did not have any history suggestive of deficient cellular immunity. He denied involvement with recreational activities that could have predisposed him for Histoplasma infection, or exposure to bat or bird droppings. His absolute lymphocyte count was normal. The cerebral spinal fluid culture was negative for an active infection or malignant cells. Computed tomography of the chest, abdomen and pelvis were negative for any malignancy. Magnetic resonance (MR) scan at the time showed multiple infra and supratentorial compartmental lesions, two supratentorial lesions were ring-enhancing, surrounding extensive vasogenic edema and restricted diffusion, in-
Ana Ines Andrade
A
Histoplasmosis Brain Abscesses in an Immunocompetent Adult
B
Figure 1 A,B) T1-weighted axial and coronal images after contrast administration showing the cerebellar lesions and pachymeningeal thickening.
dicating purulent content. There was also meningeal enhancement after contrast administration. Differential diagnosis like left frontal abscess coexisting with a metastatic deposit or a metastatic deposit with abscesses was included. Pathology evaluation of the brain biopsy was consistent with histoplasma capsulatum abscesses. The patient was started on oral amphotericin B. He was also started on dexamethasone as an anticerebral edema measure. The patient’s condition improved on treatment. Imaging Findings MR characteristics of the case included multiple infra and supratentorial compartmental lesions. The cerebellar lesions appeared solid in the right vermis, a second lesion was adjacent to the lateral recess of the fourth ventricle and the third in the left cerebellar hemisphere in the paravermian area (Figure 1). There were also lesions in the right hippocampus, left posterior frontal orbital gyrus, left insula, left occipital lobe, right caudate and left caudate nucleus (Figure 2). A prominent ring-enhancing lesion was seen in the left prefrontal area sur-
rounded by extensive vasogenic edema. A ringenhancing lesion in the vertex on the left side with extensive vasogenic edema was seen and also a lesion attached to the dura in the dorsal frontal pole on the left. The abscess walls of the left ring-enhancing lesions presented a hypointense signal in susceptibility-weighted imaging indicating probable hemosiderin deposits in the capsule (Figure 3). The ring-enhancing lesions had restricted diffusion and MR spectroscopy showed prominent lipid and lactate peaks with increased choline (Cho) indicating purulent content (Figure 4). Pathologic Findings Brain biopsy tissue showed Histoplasma capsulatum abscesses (Figure 5). Discussion and Literature Review Histoplasma capsulatum is an endemic fungus in certain regions of North America and Latin America, including the Ohio and Mississippi river valleys of the United States. Central nervous system involvement occurs in 5 to 20% 335
Histoplasmosis Brain Abscesses in an Immunocompetent Adult
A
B
Ana Ines Andrade
C
Figure 2 A-C) T1-weighted axial images after contrast administration showing the multiple supratentorial solid lesions. A
B
C
Figure 3 A) Susceptibility-weighted axial image showing a round lesion surrounded by extensive vasogenic edema and hypointense signal in the wall on the left prefrontal area, indicating probable hemosiderin deposits in its capsule. B,C) T1-weighted images before and after contrast administration with prominent ring-enhancing lesions. A
B
C
Figure 4 A-C) Diffusion sequences showing restricted diffusion, indicating purulent content.
336
www.centauro.it
The Neuroradiology Journal 27: 334-338, 2014 - doi: 10.15274/NRJ-2014-10038
A
B
Figure 5 A) Photomicrograph shows multiple organisms in histiocytes with a pale zone suggesting a capsule (hematoxylin-eosin stain). B) Photomicrograph shows silver-stained intracytoplasmic round bodies of Histoplasma capsulatum in foamy histiocytes (Gomori methenamine silver stain).
of cases of disseminated histoplasmosis and is more common in those with underlying immunosuppressive disorders 6,7. Disseminated histoplasmosis, especially with a ring-enhancing brain lesion, is uncommon in an immunocompetent individual 8. Few patients (5%-10%) with disseminated histoplasmosis will develop central nervous system (CNS) infection, and only 25% of these will develop neurological symptoms 7. Imaging findings include hydrocephalus, histoplasmoma, vasculitis with infarctions and leptomeningeal enhancement 9. In one case series of isolated CNS histoplasmosis, 90% of patients had hydrocephalus and two patients had focal enhancement on T1 imaging 10. This case series of 11 patients included two children age three and 15 years. Recently, another child in a Histoplasma endemic region was reported to have isolated histoplasma meningoencephalitis. T1 MRI demonstrated meningeal enhancement with multiple non-enhancing lesions consistent with infarction 11. Projections into the cavity from the wall of an abscess with low apparent diffusion coefficient and no enhancement have been described as a characteristic of fungal etiology 12.
Our case had multiple lesions, two of them with ring-enhancement, restricted diffusion and thickened wall with probable hemosiderin deposits. These finding have not been reported histoplasmosis abscesses to date. Conclusion While pulmonary involvement of histoplasmosis in immunosuppressed patients is common, systemic presentation of this fungal infection in immunocompetent patients is rare and self-limiting. Isolated CNS histoplasmosis is exceedingly rare 13. To our knowledge, this is the first case in the literature of multiple histoplasmosis brain abscesses presenting with ring-enhancing lesions, irregular wall thickening and hemosiderin deposits inside. CNS fungal disease in immunocompetent hosts is unusual and requires a high index of suspicion for diagnosis. Therefore, in Histoplasma endemic regions, physicians should include CNS histoplasmosis for an early diagnosis and adequate treatment.
337
Histoplasmosis Brain Abscesses in an Immunocompetent Adult
Ana Ines Andrade
References 1 Adderson E. Histoplasmosis. Pediatr Infect Dis J. 2006; 25 (1): 73-74. doi: 10.1097/01.inf.0000196922.46347.66. 2 Saccente M. Central nervous system histoplasmosis. Curr Treat Options Neurol. 2008; 10 (3): 161-167. doi: 10.1007/s11940-008-0017-x. 3 Medoff G, Kobayashi GS, Painter A, et al: Morphogenesis and pathogenicity of Histoplasma capsulatum. Infect Immun. 1987; 55 (6): 1355-1358. 4 Parihar A, Tomar V, Ojha BK, et al. Magnetic resonance imaging findings in a patient with isolated histoplasma brain abscess. Arch Neurol. 2011; 68 (4): 534-535. doi: 10.1001/archneurol.2011.59. 5 Zalduondo FM, Provenzale JM, Hulette C, et al. Meningitis, vasculitis, and cerebritis caused by CNS histoplasmosis: radiologic-pathologic correlation. Am J Roentgenol. 1996; 166 (1): 194-196. doi: 10.2214/ ajr.166.1.8571874. 6 Assi MA, Sandid MS, Baddour LM, et al. Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients. Medicine (Baltimore). 2007; 86 (3): 162-169. doi: 10.1097/md.0b013e3180679130. 7 Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore). 1990; 69 (4): 244-260. doi: 10.1097/00005792-199007000-00006. 8 Subramanian S, Abraham OC, Rupali P, et al. Disseminated histoplasmosis. J Assoc Physicians India. 2005; 53: 185-189. 9 Schuster JE1, Wushensky CA, Di Pentima MC. Chronic primary central nervous system histoplasmosis in a healthy child with intermittent neurological manifestations. Pediatr Infect Dis J. 2013; 32 (7): 794-796. doi: 10.1097/INF.0b013e31828d293e.
338
10 Schestatsky P, Chedid MF, Amaral OB, et al. Isolated central nervous system histoplasmosis in immunocompetent hosts: a series of 11 cases. Scand J Infect Dis. 2006; 38 (1): 43-48. doi: 10.1080/00365540500372895. 11 Threlkeld ZD, Broughton R, Khan GQ, et al. Isolated Histoplasma capsulatum meningoencephalitis in an immunocompetent child. J Child Neurol. 2012; 27 (4): 532535. doi: 10.1177/0883073811428780. 12 Luthra G, Parihar A, Nath K, et al. Comparative evaluation of fungal, tubercular, and pyogenic brain abscesses with conventional and diffusion MR imaging and proton MR spectroscopy. Am J Neuroradiol. 2007; 28 (7): 1332-1338. doi: 10.3174/ajnr.A0548. 13 Nguyen FN, Kar JK, Zakaria A, et al. Isolated central nervous system histoplasmosis presenting with ischemic pontine stroke and meningitis in an immunocompetent patient. JAMA Neurol. 2013; 70 (5): 638-641. doi: 10.1001/jamaneurol.2013.1043.
Ana Ines Andrade, MD Resident, Department of Radiology CIMED-La Plata 416, 5th street, La Plata Buenos Aires. Argentina Tel.: (+54) 9-221-571-7037 E-mail: [email protected]
