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Central nervous system aspergillosis in immunocompetent patient
European Journal of Radiology Extra 63 (2007) 53–56
Central nervous system aspergillosis in immunocompetent patient Sachin Onkar Khachane ∗ , Vinay kumar, Darshana Anant Sanghvi Department of Radiology, King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College, Acharya Dhonde Marg, Parel, Mumbai 400012, Maharashtra, India Received 28 January 2007; received in revised form 10 May 2007; accepted 15 May 2007
Abstract Central nervous system aspergillosis has increased dramatically in recent years. Most patients are immunocompromised and infected from a primary site, usually the lungs or paranasal sinuses, from where the organism spreads to the central nervous system. We report the case of a 7-year-old immunocompetent girl who presented with high-grade fever with chills and developed hemiplegia with facial palsy. Imaging showed multiple, confluent, infiltrative ring enhancing lesions in the right cerebral hemisphere associated with perilesional edema and mass effect. On craniotomy, the lesion was an abscess, which was drained. Histological examination of the abscess wall showed aspergillus hyphae. The patient died 12 days after surgical drainage. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Aspergillosis; Corpus callosum; Restricted diffusion; Immunocompetent
1. Introduction Aspergilli are probably the most common group of fungi in our environment. Most aspergillus species are found in the soil. Aspergillosis occurs worldwide, with no apparent age, sex, or racial predilection. Aspergillus fumigatus, the most common pathogen, is found in the soil, but is seen most abundantly in decomposing organic materials. Invasive aspergillosis usually occurs in immune depressed individuals, such as those suffering from major burns, AIDS and immune disorders and in transplant recipients. Less commonly, it causes disease in healthy individuals. We report the case of a 7-year-old immunocompetent girl who presented with high-grade fever with chills and developed hemiplegia with facial palsy. Imaging showed multiple, confluent, infiltrative ring enhancing lesions in the right cerebral hemisphere associated with perilesional edema and mass effect. On craniotomy, the lesion was an abscess, which was ∗
Corresponding author. Tel.: +91 22 2413 6051; fax: +91 22 2414 3435. E-mail addresses: [email protected] (S.O. Khachane), vk [email protected] (V. kumar), [email protected] (D.A. Sanghvi). 1571-4675/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2007.05.005
drained. Histological examination of the abscess wall showed aspergillus hyphae.
2. Case report A 7-year-old girl presented with high-grade fever associated with chills since 2 months. She did not have any significant past medical history. The patient also complained of loss of appetite and generalized weakness. During the course of her illness, she developed left sided hemiplegia with left facial palsy. Subsequently, she developed exposure keratitis in the left eye and bedsores. Clinical examination did not reveal any infective focus in the middle ear, paranasal sinuses or oral cavity. On admission, routine hemogram revealed total leukocyte count of 4500/mm3 , hemoglobin of 5 g% and erythrocyte sedimentation rate (ESR) of 50 mm at the end of 1 h. Peripheral smear for malarial parasites was negative. Blood culture was negative for bacteria and fungus. Plain (Fig. 1a) and post contrast (Fig. 1b) CT images of the brain showed an ill-defined, non-enhancing hypodensity in the right cerebral hemisphere extending into the corpus callosum. Due to mass effect, there was compression of the ipsilateral lateral ventricle.
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S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
Fig. 1. (a) Axial unenhanced CT image of the brain shows confluent hypo density in right cerebral white matter. (b) Minimal enhancement is observed on the post contrast CT image.
The patient deteriorated with altered sensorium. Magnetic resonance imaging (MRI) of the brain was performed. MRI of the brain showed confluent, diffusely infiltrative ring enhancing lesions in the right cerebral hemisphere involving all the lobes, basal ganglia and thalamus. The lesion had infiltrated the right cerebral peduncle. It extended into the occipital horn and the body of the right lateral ventricle. The lesion also infiltrated the body and the splenium of the corpus callosum and extended to the contralateral cerebral hemisphere. Extensive perilesional edema was observed with subfalcine herniation to the left side. On post contrast images there was irregular enhancement at the periphery of the lesion (Fig. 2) whereas the necrotic centre remained non-enhancing. Low ADC values (restricted diffusion) were noted within the lesion (Fig. 3). Since there was extensive restricted diffusion in the centre of the lesion,
Fig. 2. Post contrast T1W axial image shows an irregular, infiltrative peripherally enhancing lesion involving right frontal, temporal and parietal lobes with involvement of corpus callosum.
an abscess was considered more likely. This was confirmed on surgical exploration. The abscess was surgically drained. Histopathological examination of the abscess wall revealed aspergillus hyphae (Fig. 4a and b). Postoperatively, the patient showed little improvement. She died on the 12th postoperative day due to respiratory complications.
3. Discussion Cerebral invasive aspergillosis is most commonly carried hematogenously from a pulmonary infection. Less commonly it occurs as a direct extension of sinonasal disease. Cerebral aspergillosis is seen in about 10–20% of all invasive
Fig. 3. Diffusion-weighed MRI image shows restricted diffusion in right frontotemporoparietal lobe abscess.
S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
Fig. 4. (a) Histopathological examination using haematoxylin and eosin staining shows aspergillus hyphae from the abscess wall (H&E 400×). (b) Gomori’s methinamine silver stain specific for aspergillus shows aspergillus hyphae black linear structures (GMS 400×).
aspergillosis cases [1]. Aspergillus species are second only to candidiasis as the most common cause of fungal infections of the central nervous system in immunocompromised patients. Cerebral aspergillosis has a poor prognosis in immunocompromised patients, with the mortality rate approaching 100% [2]. A. fumigatus is the most common causative organism in the genus Aspergillus, but A. flavus, A. niger and A. oxyzae are also frequently seen. Immunosuppression is the primary risk factor for disseminated CNS aspergillosis. Severe hematologic disease (such as leukemia or lymphoma) or bone marrow transplant involve much higher risk than other sources of immunosuppression, such as solid organ transplant, AIDS, diabetes, steroid use and chemotherapy [3]. The pathophysiology of aspergillus is primarily due to its angioinvasiveness. Cerebral infection will lead to acute infarcts that may or may not have hemorrhages within them. These areas of infarct can progress to infectious cerebri-
55
tis or abscess. The cerebral vasculature can be involved by mycotic aneurysms or intra-arterial thrombosis. The angioinvasive nature of the organism results in an atypical distribution of the lesions. Similar to hematogenous metastases, septic emboli, or other infections, aspergillosis may cause lesions in the corticomedullary junction. Aspergillosis tends to occlude smaller perforating arteries—so lesions may develop in the basal nuclei, thalami, corpus callosum, and brain stem. Therefore, callosal lesions may suggest the diagnosis of aspergillosis as the corpus callosum is supplied by the medial lenticulostriates and perforating branches of the pericallosal arteries. Involvement of corpus callosum was noted in our case. Pyogenic and thrombotic infarcts are uncommon in the corpus callosum [4,5]. The apparent affinity of CNS aspergillosis for perforating artery distributions is most likely due to the invasive character of aspergillus within the walls of the larger parent arteries to which it has spread hematogenously, subsequently compromising the origins of the perforating arteries. The histopathology of invasive aspergillus (IA) typically shows numerous Aspergillus hyphae intermingled with tissue necrosis, inflammatory infiltration, thrombosis, and vascular invasion by the fungus [6]. Although various diagnostic tests have been developed for IA, such as Aspergillus galactomannan and PCR assays [7,8], culture isolation of the Aspergillus organism along with clinical and radiologic correlation remains the current standard. According to the site and nature of infection, the patient may present with features of meningitis, focal neurological signs, or symptoms of raised intracranial pressure. The frequently encountered symptoms include—headache, lowgrade fever, vomiting, convulsions, cranial nerve palsy, and varying degrees of sensory and motor deficit [3]. The imaging patterns of cerebral aspergillosis vary in accordance with immune status of the patients. Multiple cortical and subcortical areas of T2 lengthening on MRI (with or without hemorrhage) and subtle ring enhancement are typical features. Ring enhancement can occur if abscesses form, but this is uncommon because lesions rarely become “walled off” in severely immunocompromised patients. However, large abscess showing subtle to moderate ring enhancement similar to our case can occur in immunocompetent and moderately immunocompromised individuals. This difference may be related to the patients’ potentially different levels of immune system compromise, as edema and enhancement have been shown to be dependent on lymphocyte and total leukocyte counts [9]. The thick irregular wall of the mass on CT and MR images indicates a competent host defense mechanism that is attempting to isolate or encapsulate the offending organisms [10]. The lesions often appear hyperintense on T2W or proton-density MR images, and exhibit restricted diffusion on diffusion-weighted MR images, indicating infarction and/or pus formation. Diffusion-weighted MR imaging can ensure the diagnosis of early infarcted areas in this form of cerebral aspergillosis, and can be beneficial in differentiating it from progressive multi-focal leukoencephalopathy and
56
S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
tumoral lesions. The subtle T1 shortening seen may represent the petechial hemorrhage often seen in the evolution of an infarct [11]. Differential diagnosis for this condition includes brain abscess due to pyogenic organisms, which sometimes may be indistinguishable from fungal abscesses. However, hemorrhage and involvement of the corpus callosum is not a frequent finding in pyogenic abscess. Metastatic lesions generally have a less fulminant clinical course and greater enhancement on post contrast imaging. Vasculitis is recognized on imaging as gray and white matter infarcts with ill-defined areas of enhancement. A ring enhancing aspergillus lesion could also resemble toxoplasmosis and tuberculosis. The prognosis for CNS aspergillosis is poor, with most reported cases being fatal. An aggressive surgical approach in nonimmunocompromised patients helps reduce the mortality from 64 to 39% in one study [12]. Complete cure has been reported with aggressive neurosurgical intervention for surgical removal of aspergillus abscesses, granulomas, and focally infarcted brain, with correction of underlying risk factors. Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. CNS aspergillosis is an infection with clinical and imaging features that vary according to the immune status of the patient. Involvement of corpus callosum and restricted diffusion on MR imaging are helpful in the early diagnosis of cerebral aspergillosis presenting with abscesses or septic infarcts [1].
References [1] Keyik B, Edguer T, Hekimoglu B. Conventional and diffusionweighted MR imaging of cerebral aspergillosis. Diagn Interv Radiol 2005;11:199–201. [2] Tempkin AD, Sobonya RE, Seeger JF, Oh ES. Conventional and diffusion-weighted MR imaging of cerebral aspergillosis. Radiographics 2006;26(4):1239–42. [3] Nadkarni T, Goel A. Aspergilloma of the brain: an overview. J Postgrad Med 2005;51(1):S37–41. [4] Osborn AG. Diagnostic neuroradiology. St. Louis: Mosby; 1994. [5] Gentry LR, Thompson B, Godersky JC. Trauma to the corpus callosum: MR features. AJNR Am J Neuroradiol 1988;9(6):1129–38. [6] Chang PK, Ehrlich KC, Linz JE, Bhatnagar D, Cleveland TE, Bennett JW. Characterization of the Aspergillus paraciticus niaD and niiA gene cluster. Curr Genet 1996;30(1):68–75. [7] Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Bougaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 2001;97:1604–10. [8] Pham AS, Tarrand JJ, May GS, Lee MS, Kontoyiannis DP, Han XY. Diagnosis of invasive mold infection by real-time quantitative PCR. Am J Clin Pathol 2003;119:38–44. [9] Yuh WT, Nguyen HD, Gao F, et al. Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings. AJR Am J Roentgenol 1994;162:425–30. [10] Phuttharak W, Hesselink JR, Wixom C. AJNR Am J Neuroradiol 2005;26:835–8. [11] Delone DR, Goldstein RA, Petermann G, et al. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol 1999;20(9):1597–604. [12] Young RF, Grade G, Grinnell V. Surgical treatment for fungal infections in the central nervous system. J Neurosurg 1985;63:371–81.
Central nervous system aspergillosis in immunocompetent patient Sachin Onkar Khachane ∗ , Vinay kumar, Darshana Anant Sanghvi Department of Radiology, King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College, Acharya Dhonde Marg, Parel, Mumbai 400012, Maharashtra, India Received 28 January 2007; received in revised form 10 May 2007; accepted 15 May 2007
Abstract Central nervous system aspergillosis has increased dramatically in recent years. Most patients are immunocompromised and infected from a primary site, usually the lungs or paranasal sinuses, from where the organism spreads to the central nervous system. We report the case of a 7-year-old immunocompetent girl who presented with high-grade fever with chills and developed hemiplegia with facial palsy. Imaging showed multiple, confluent, infiltrative ring enhancing lesions in the right cerebral hemisphere associated with perilesional edema and mass effect. On craniotomy, the lesion was an abscess, which was drained. Histological examination of the abscess wall showed aspergillus hyphae. The patient died 12 days after surgical drainage. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Aspergillosis; Corpus callosum; Restricted diffusion; Immunocompetent
1. Introduction Aspergilli are probably the most common group of fungi in our environment. Most aspergillus species are found in the soil. Aspergillosis occurs worldwide, with no apparent age, sex, or racial predilection. Aspergillus fumigatus, the most common pathogen, is found in the soil, but is seen most abundantly in decomposing organic materials. Invasive aspergillosis usually occurs in immune depressed individuals, such as those suffering from major burns, AIDS and immune disorders and in transplant recipients. Less commonly, it causes disease in healthy individuals. We report the case of a 7-year-old immunocompetent girl who presented with high-grade fever with chills and developed hemiplegia with facial palsy. Imaging showed multiple, confluent, infiltrative ring enhancing lesions in the right cerebral hemisphere associated with perilesional edema and mass effect. On craniotomy, the lesion was an abscess, which was ∗
Corresponding author. Tel.: +91 22 2413 6051; fax: +91 22 2414 3435. E-mail addresses: [email protected] (S.O. Khachane), vk [email protected] (V. kumar), [email protected] (D.A. Sanghvi). 1571-4675/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2007.05.005
drained. Histological examination of the abscess wall showed aspergillus hyphae.
2. Case report A 7-year-old girl presented with high-grade fever associated with chills since 2 months. She did not have any significant past medical history. The patient also complained of loss of appetite and generalized weakness. During the course of her illness, she developed left sided hemiplegia with left facial palsy. Subsequently, she developed exposure keratitis in the left eye and bedsores. Clinical examination did not reveal any infective focus in the middle ear, paranasal sinuses or oral cavity. On admission, routine hemogram revealed total leukocyte count of 4500/mm3 , hemoglobin of 5 g% and erythrocyte sedimentation rate (ESR) of 50 mm at the end of 1 h. Peripheral smear for malarial parasites was negative. Blood culture was negative for bacteria and fungus. Plain (Fig. 1a) and post contrast (Fig. 1b) CT images of the brain showed an ill-defined, non-enhancing hypodensity in the right cerebral hemisphere extending into the corpus callosum. Due to mass effect, there was compression of the ipsilateral lateral ventricle.
54
S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
Fig. 1. (a) Axial unenhanced CT image of the brain shows confluent hypo density in right cerebral white matter. (b) Minimal enhancement is observed on the post contrast CT image.
The patient deteriorated with altered sensorium. Magnetic resonance imaging (MRI) of the brain was performed. MRI of the brain showed confluent, diffusely infiltrative ring enhancing lesions in the right cerebral hemisphere involving all the lobes, basal ganglia and thalamus. The lesion had infiltrated the right cerebral peduncle. It extended into the occipital horn and the body of the right lateral ventricle. The lesion also infiltrated the body and the splenium of the corpus callosum and extended to the contralateral cerebral hemisphere. Extensive perilesional edema was observed with subfalcine herniation to the left side. On post contrast images there was irregular enhancement at the periphery of the lesion (Fig. 2) whereas the necrotic centre remained non-enhancing. Low ADC values (restricted diffusion) were noted within the lesion (Fig. 3). Since there was extensive restricted diffusion in the centre of the lesion,
Fig. 2. Post contrast T1W axial image shows an irregular, infiltrative peripherally enhancing lesion involving right frontal, temporal and parietal lobes with involvement of corpus callosum.
an abscess was considered more likely. This was confirmed on surgical exploration. The abscess was surgically drained. Histopathological examination of the abscess wall revealed aspergillus hyphae (Fig. 4a and b). Postoperatively, the patient showed little improvement. She died on the 12th postoperative day due to respiratory complications.
3. Discussion Cerebral invasive aspergillosis is most commonly carried hematogenously from a pulmonary infection. Less commonly it occurs as a direct extension of sinonasal disease. Cerebral aspergillosis is seen in about 10–20% of all invasive
Fig. 3. Diffusion-weighed MRI image shows restricted diffusion in right frontotemporoparietal lobe abscess.
S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
Fig. 4. (a) Histopathological examination using haematoxylin and eosin staining shows aspergillus hyphae from the abscess wall (H&E 400×). (b) Gomori’s methinamine silver stain specific for aspergillus shows aspergillus hyphae black linear structures (GMS 400×).
aspergillosis cases [1]. Aspergillus species are second only to candidiasis as the most common cause of fungal infections of the central nervous system in immunocompromised patients. Cerebral aspergillosis has a poor prognosis in immunocompromised patients, with the mortality rate approaching 100% [2]. A. fumigatus is the most common causative organism in the genus Aspergillus, but A. flavus, A. niger and A. oxyzae are also frequently seen. Immunosuppression is the primary risk factor for disseminated CNS aspergillosis. Severe hematologic disease (such as leukemia or lymphoma) or bone marrow transplant involve much higher risk than other sources of immunosuppression, such as solid organ transplant, AIDS, diabetes, steroid use and chemotherapy [3]. The pathophysiology of aspergillus is primarily due to its angioinvasiveness. Cerebral infection will lead to acute infarcts that may or may not have hemorrhages within them. These areas of infarct can progress to infectious cerebri-
55
tis or abscess. The cerebral vasculature can be involved by mycotic aneurysms or intra-arterial thrombosis. The angioinvasive nature of the organism results in an atypical distribution of the lesions. Similar to hematogenous metastases, septic emboli, or other infections, aspergillosis may cause lesions in the corticomedullary junction. Aspergillosis tends to occlude smaller perforating arteries—so lesions may develop in the basal nuclei, thalami, corpus callosum, and brain stem. Therefore, callosal lesions may suggest the diagnosis of aspergillosis as the corpus callosum is supplied by the medial lenticulostriates and perforating branches of the pericallosal arteries. Involvement of corpus callosum was noted in our case. Pyogenic and thrombotic infarcts are uncommon in the corpus callosum [4,5]. The apparent affinity of CNS aspergillosis for perforating artery distributions is most likely due to the invasive character of aspergillus within the walls of the larger parent arteries to which it has spread hematogenously, subsequently compromising the origins of the perforating arteries. The histopathology of invasive aspergillus (IA) typically shows numerous Aspergillus hyphae intermingled with tissue necrosis, inflammatory infiltration, thrombosis, and vascular invasion by the fungus [6]. Although various diagnostic tests have been developed for IA, such as Aspergillus galactomannan and PCR assays [7,8], culture isolation of the Aspergillus organism along with clinical and radiologic correlation remains the current standard. According to the site and nature of infection, the patient may present with features of meningitis, focal neurological signs, or symptoms of raised intracranial pressure. The frequently encountered symptoms include—headache, lowgrade fever, vomiting, convulsions, cranial nerve palsy, and varying degrees of sensory and motor deficit [3]. The imaging patterns of cerebral aspergillosis vary in accordance with immune status of the patients. Multiple cortical and subcortical areas of T2 lengthening on MRI (with or without hemorrhage) and subtle ring enhancement are typical features. Ring enhancement can occur if abscesses form, but this is uncommon because lesions rarely become “walled off” in severely immunocompromised patients. However, large abscess showing subtle to moderate ring enhancement similar to our case can occur in immunocompetent and moderately immunocompromised individuals. This difference may be related to the patients’ potentially different levels of immune system compromise, as edema and enhancement have been shown to be dependent on lymphocyte and total leukocyte counts [9]. The thick irregular wall of the mass on CT and MR images indicates a competent host defense mechanism that is attempting to isolate or encapsulate the offending organisms [10]. The lesions often appear hyperintense on T2W or proton-density MR images, and exhibit restricted diffusion on diffusion-weighted MR images, indicating infarction and/or pus formation. Diffusion-weighted MR imaging can ensure the diagnosis of early infarcted areas in this form of cerebral aspergillosis, and can be beneficial in differentiating it from progressive multi-focal leukoencephalopathy and
56
S.O. Khachane et al. / European Journal of Radiology Extra 63 (2007) 53–56
tumoral lesions. The subtle T1 shortening seen may represent the petechial hemorrhage often seen in the evolution of an infarct [11]. Differential diagnosis for this condition includes brain abscess due to pyogenic organisms, which sometimes may be indistinguishable from fungal abscesses. However, hemorrhage and involvement of the corpus callosum is not a frequent finding in pyogenic abscess. Metastatic lesions generally have a less fulminant clinical course and greater enhancement on post contrast imaging. Vasculitis is recognized on imaging as gray and white matter infarcts with ill-defined areas of enhancement. A ring enhancing aspergillus lesion could also resemble toxoplasmosis and tuberculosis. The prognosis for CNS aspergillosis is poor, with most reported cases being fatal. An aggressive surgical approach in nonimmunocompromised patients helps reduce the mortality from 64 to 39% in one study [12]. Complete cure has been reported with aggressive neurosurgical intervention for surgical removal of aspergillus abscesses, granulomas, and focally infarcted brain, with correction of underlying risk factors. Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. CNS aspergillosis is an infection with clinical and imaging features that vary according to the immune status of the patient. Involvement of corpus callosum and restricted diffusion on MR imaging are helpful in the early diagnosis of cerebral aspergillosis presenting with abscesses or septic infarcts [1].
References [1] Keyik B, Edguer T, Hekimoglu B. Conventional and diffusionweighted MR imaging of cerebral aspergillosis. Diagn Interv Radiol 2005;11:199–201. [2] Tempkin AD, Sobonya RE, Seeger JF, Oh ES. Conventional and diffusion-weighted MR imaging of cerebral aspergillosis. Radiographics 2006;26(4):1239–42. [3] Nadkarni T, Goel A. Aspergilloma of the brain: an overview. J Postgrad Med 2005;51(1):S37–41. [4] Osborn AG. Diagnostic neuroradiology. St. Louis: Mosby; 1994. [5] Gentry LR, Thompson B, Godersky JC. Trauma to the corpus callosum: MR features. AJNR Am J Neuroradiol 1988;9(6):1129–38. [6] Chang PK, Ehrlich KC, Linz JE, Bhatnagar D, Cleveland TE, Bennett JW. Characterization of the Aspergillus paraciticus niaD and niiA gene cluster. Curr Genet 1996;30(1):68–75. [7] Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Bougaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 2001;97:1604–10. [8] Pham AS, Tarrand JJ, May GS, Lee MS, Kontoyiannis DP, Han XY. Diagnosis of invasive mold infection by real-time quantitative PCR. Am J Clin Pathol 2003;119:38–44. [9] Yuh WT, Nguyen HD, Gao F, et al. Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings. AJR Am J Roentgenol 1994;162:425–30. [10] Phuttharak W, Hesselink JR, Wixom C. AJNR Am J Neuroradiol 2005;26:835–8. [11] Delone DR, Goldstein RA, Petermann G, et al. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol 1999;20(9):1597–604. [12] Young RF, Grade G, Grinnell V. Surgical treatment for fungal infections in the central nervous system. J Neurosurg 1985;63:371–81.