Journal of Clinical Neuroscience 22 (2015) 1191–1193
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Optic nerve aspergillosis Lisi Yuan, Richard A. Prayson ⇑ Cleveland Clinic Department of Anatomic Pathology, L25 9500 Euclid Avenue, Cleveland, OH 44122, USA
a r t i c l e
i n f o
Article history: Received 26 January 2015 Accepted 29 January 2015
Keywords: Abscess Aspergillus Aspergillosis Optic nerve
a b s t r a c t We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally eliminated in the immunocompetent host by innate immune mechanisms; however, in immunosuppressed patients, they can cause disease. The woman had a past medical history of hypertension and migraines. She presented 1 year prior to death with a new onset headache behind the left eye and later developed blurred vision and scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One month prior to the current admission, she had an MRI showing optic nerve thickening with no other findings. Because of the visual loss and a positive antinuclear antibody test, she was given a trial of high dose steroids and while it significantly improved her headache, her vision did not improve. At autopsy, the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged in diameter and there was a 1.3 cm firm nodule surrounding the left optic nerve. Histologically, an abscess surrounded and involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae were identified on Grocott’s methenamine silver stained sections, consistent with Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or infection was identified in the body. The literature on optic nerve Aspergillosis is reviewed. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Aspergillus spp. are ubiquitous in nature, commonly found growing in soil and decaying vegetation. Although inhalation of infectious conidia is a frequent event, infections caused by the fungus rarely occur in people who have a healthy immune system. People with a weakened immune system due to cancer, infection, organ transplantation, steroid use or chemotherapy are at increased risk. We report a patient with optic nerve Aspergillosis discovered at autopsy. 2. Case report A 55-year-old woman initially presented a year prior to death with new onset headaches behind the left eye. She subsequently developed blurred vision and scotoma 3 months later. A left temporal artery biopsy was done which was negative for giant cell arteritis. She received a trial treatment of indomethacin. An MRI study showed enhancement and thickening of the left optic nerve involving the distal optic nerve and optic chiasm. Because of the visual loss and a positive antinuclear antibody test, she was given a trial course of high dose steroids. Although it significantly improved her headache, her vision did not improve. Rigorous screening for infectious diseases (blood and cerebrospinal fluid studies) including fungal infections such as Aspergillus failed to demonstrate an infectious etiology. Shortly before death, she ⇑ Corresponding author. Tel.: +1 216 444 8805; fax: +1 216 445 6967. E-mail address: [email protected] (R.A. Prayson).
developed right-sided weakness and evidence of a pontine infarct on MRI studies. At autopsy, it was found that the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged, measuring 0.6 cm in diameter in comparison to 0.4 cm on the right. There was a 1.3 0.7 0.4 cm tan nodule surrounding the left optic nerve. Serial cross sections through the brainstem show multiple infarcts in the pons and cerebellum. Histologic sections taken from the left optic nerve showed an abscess (Fig. 1, 2) and evidence of angioinvasive, acute angle branching, fungal hyphae morphologically consistent with Aspergillus spp. (Fig. 3). Bacterial organisms were not seen on Gram and Ziehl Nelson stained sections. Furthermore, no gross or microscopic evidence of systemic vasculitis or infection was identified elsewhere in the body.
3. Discussion Only anecdotal cases of Aspergillus associated optic neuritis or abscess have been documented in the literature [1–3]. In most of these cases, patients were reported to be immunosuppressed, often on steroid therapy. Access of the fungus to the optic nerve and orbital region appears to occur in a number of ways, including direct extension from adjacent infected sinuses, direct extension through the bones of the orbit or via hematogenous dissemination directly from an infectious nidus elsewhere in the body (most commonly the lung) [1]. Some cases may progress to orbital apex syndrome, a condition marked by visual loss from an optic neuropathy and ophthalmoplegia due to a mass lesion near the apex of the
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Case Reports / Journal of Clinical Neuroscience 22 (2015) 1191–1193
Fig. 1. Histological sample of Aspergillosis associated optic nerve abscess with low magnification appearance showing an abscess with necrosis and neutrophils (arrows) adjacent to the left optic nerve (hematoxylin and eosin; original magnification 100).
Fig. 2. Histological sample of Aspergillosis associated optic nerve abscess. Areas of the abscess were marked by multinucleated giant cells. Fungal hyphae (arrows) can be seen intermixed with the necrosis and acute inflammation (hematoxylin and eosin; original magnification 200).
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1191–1193
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Fig. 3. Acute angle branching hyphae are highlighted on a Grocott’s methenamine silver stain invading a blood vessel wall (original magnification 200).
orbit. The etiologies are myriad and may include inflammatory conditions (such as an abscess), tumors, trauma or vascular lesions. Diagnosis of Aspergillosis is highly dependent on appropriate clinical suspicion. Central nervous system infection by Aspergillus is difficult to diagnose as the disease is so rare and cerebrospinal fluid or serum testing are not generally helpful. In our case, although no Aspergillus antigen or antibody was identified, our patient did have an increased neutrophil count suggesting possible infection. In addition, imaging findings are nonspecific, overlapping with other inflammatory processes such as vasculitis. Clinicians may choose steroids or other immunosuppressive agents as empirical treatment for a possible inflammatory process, as in the current case. More confusingly, the patient may even initially respond to such therapeutic agents as they may ameliorate the inflammation and edema caused by the angioinvasive Aspergillus, but in reality they engender the infection. Biopsy may be necessary http://dx.doi.org/10.1016/j.jocn.2015.01.012
to establish the diagnosis, however, it is an invasive procedure and is often considered as the last resort.
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. References [1] Choi MY, Bae IH, Lee JH, et al. Aspergillosis presenting as an optic neuritis. Korean J Ophthalmol 2002;16:119–23. [2] Garcia-Asensio S, Artigas JM, Barrena R. Optic nerve aspergillosis: report of a case diagnosed by fine-needle aspiration biopsy. Eur Radiol 2000;10:573–5. [3] Matsuo T, Notohara K, Yamadori I. Aspergillosis causing bilateral optic neuritis and later orbital apex syndrome. Jpn J Ophthalmol 2005;49:430–1.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Optic nerve aspergillosis Lisi Yuan, Richard A. Prayson ⇑ Cleveland Clinic Department of Anatomic Pathology, L25 9500 Euclid Avenue, Cleveland, OH 44122, USA
a r t i c l e
i n f o
Article history: Received 26 January 2015 Accepted 29 January 2015
Keywords: Abscess Aspergillus Aspergillosis Optic nerve
a b s t r a c t We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally eliminated in the immunocompetent host by innate immune mechanisms; however, in immunosuppressed patients, they can cause disease. The woman had a past medical history of hypertension and migraines. She presented 1 year prior to death with a new onset headache behind the left eye and later developed blurred vision and scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One month prior to the current admission, she had an MRI showing optic nerve thickening with no other findings. Because of the visual loss and a positive antinuclear antibody test, she was given a trial of high dose steroids and while it significantly improved her headache, her vision did not improve. At autopsy, the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged in diameter and there was a 1.3 cm firm nodule surrounding the left optic nerve. Histologically, an abscess surrounded and involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae were identified on Grocott’s methenamine silver stained sections, consistent with Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or infection was identified in the body. The literature on optic nerve Aspergillosis is reviewed. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Aspergillus spp. are ubiquitous in nature, commonly found growing in soil and decaying vegetation. Although inhalation of infectious conidia is a frequent event, infections caused by the fungus rarely occur in people who have a healthy immune system. People with a weakened immune system due to cancer, infection, organ transplantation, steroid use or chemotherapy are at increased risk. We report a patient with optic nerve Aspergillosis discovered at autopsy. 2. Case report A 55-year-old woman initially presented a year prior to death with new onset headaches behind the left eye. She subsequently developed blurred vision and scotoma 3 months later. A left temporal artery biopsy was done which was negative for giant cell arteritis. She received a trial treatment of indomethacin. An MRI study showed enhancement and thickening of the left optic nerve involving the distal optic nerve and optic chiasm. Because of the visual loss and a positive antinuclear antibody test, she was given a trial course of high dose steroids. Although it significantly improved her headache, her vision did not improve. Rigorous screening for infectious diseases (blood and cerebrospinal fluid studies) including fungal infections such as Aspergillus failed to demonstrate an infectious etiology. Shortly before death, she ⇑ Corresponding author. Tel.: +1 216 444 8805; fax: +1 216 445 6967. E-mail address: [email protected] (R.A. Prayson).
developed right-sided weakness and evidence of a pontine infarct on MRI studies. At autopsy, it was found that the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged, measuring 0.6 cm in diameter in comparison to 0.4 cm on the right. There was a 1.3 0.7 0.4 cm tan nodule surrounding the left optic nerve. Serial cross sections through the brainstem show multiple infarcts in the pons and cerebellum. Histologic sections taken from the left optic nerve showed an abscess (Fig. 1, 2) and evidence of angioinvasive, acute angle branching, fungal hyphae morphologically consistent with Aspergillus spp. (Fig. 3). Bacterial organisms were not seen on Gram and Ziehl Nelson stained sections. Furthermore, no gross or microscopic evidence of systemic vasculitis or infection was identified elsewhere in the body.
3. Discussion Only anecdotal cases of Aspergillus associated optic neuritis or abscess have been documented in the literature [1–3]. In most of these cases, patients were reported to be immunosuppressed, often on steroid therapy. Access of the fungus to the optic nerve and orbital region appears to occur in a number of ways, including direct extension from adjacent infected sinuses, direct extension through the bones of the orbit or via hematogenous dissemination directly from an infectious nidus elsewhere in the body (most commonly the lung) [1]. Some cases may progress to orbital apex syndrome, a condition marked by visual loss from an optic neuropathy and ophthalmoplegia due to a mass lesion near the apex of the
1192
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1191–1193
Fig. 1. Histological sample of Aspergillosis associated optic nerve abscess with low magnification appearance showing an abscess with necrosis and neutrophils (arrows) adjacent to the left optic nerve (hematoxylin and eosin; original magnification 100).
Fig. 2. Histological sample of Aspergillosis associated optic nerve abscess. Areas of the abscess were marked by multinucleated giant cells. Fungal hyphae (arrows) can be seen intermixed with the necrosis and acute inflammation (hematoxylin and eosin; original magnification 200).
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1191–1193
1193
Fig. 3. Acute angle branching hyphae are highlighted on a Grocott’s methenamine silver stain invading a blood vessel wall (original magnification 200).
orbit. The etiologies are myriad and may include inflammatory conditions (such as an abscess), tumors, trauma or vascular lesions. Diagnosis of Aspergillosis is highly dependent on appropriate clinical suspicion. Central nervous system infection by Aspergillus is difficult to diagnose as the disease is so rare and cerebrospinal fluid or serum testing are not generally helpful. In our case, although no Aspergillus antigen or antibody was identified, our patient did have an increased neutrophil count suggesting possible infection. In addition, imaging findings are nonspecific, overlapping with other inflammatory processes such as vasculitis. Clinicians may choose steroids or other immunosuppressive agents as empirical treatment for a possible inflammatory process, as in the current case. More confusingly, the patient may even initially respond to such therapeutic agents as they may ameliorate the inflammation and edema caused by the angioinvasive Aspergillus, but in reality they engender the infection. Biopsy may be necessary http://dx.doi.org/10.1016/j.jocn.2015.01.012
to establish the diagnosis, however, it is an invasive procedure and is often considered as the last resort.
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. References [1] Choi MY, Bae IH, Lee JH, et al. Aspergillosis presenting as an optic neuritis. Korean J Ophthalmol 2002;16:119–23. [2] Garcia-Asensio S, Artigas JM, Barrena R. Optic nerve aspergillosis: report of a case diagnosed by fine-needle aspiration biopsy. Eur Radiol 2000;10:573–5. [3] Matsuo T, Notohara K, Yamadori I. Aspergillosis causing bilateral optic neuritis and later orbital apex syndrome. Jpn J Ophthalmol 2005;49:430–1.
