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Lacunar Stroke, Cavernous Angioma, and Fusiform Aneurysm Due to Irradiation for Pilocytic Astrocytoma—A Case Report
ARTICLE IN PRESS
Case Studies
Lacunar Stroke, Cavernous Angioma, and Fusiform Aneurysm Due to Irradiation for Pilocytic Astrocytoma—A Case Report Maruyama Kunitaka, MD, Takuya Akai, MD, PhD, Naoki Akioka, MD, PhD, Takahiro Tomita, MD, PhD, Shoichi Nagai, MD, PhD, and Satoshi Kuroda, MD, PhD
Radiotherapy is a useful modality for the treatment of brain tumors, but may induce brain degeneration, tumor formation, and vasculopathy in the irradiated field. We describe a rare case of a pediatric patient who presented multiple different types of vascular events consecutively in the irradiated field including lacunar stroke because of occlusion of perforating artery, intraventricular hemorrhage from cavernoma, and subarachnoid hemorrhage because of the rupture of fusiform aneurysm, 6 years after radiotherapy against pilocytic astrocytoma. The life-threatening aneurysm was resected, and its histologic findings revealed the radiation-induced vasculopathy. We should avoid irradiation, and repeat surgical resection for the pediatric cases with pilocytic astrocytoma. Once irradiation was indicated for them, however, we should carefully follow-up not only tumor recurrence but also angiograms to predict any cerebrovascular events. Key Words: Radiation— vasculopathy—stroke—pilocytic astrocytoma—aneurysm—cavernoma. © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Case Report A 3-year-old boy was experiencing gait instability, and radiological examinations demonstrated suprasellar tumor associated with hydrocephalus. He underwent partial tumor resection with histologic diagnosis of pilocytic astrocytoma followed by chemotherapy with carboplatin and etoposide. The follow-up images showed the tumor
From the Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan. Received January 31, 2018; revision received February 20, 2018; accepted February 28, 2018. Address correspondence to Takuya Akai, MD, PhD, Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.062
regrowth, and he received conventional radiotherapy with 40 Gy for whole ventricles and 60 Gy for the tumor when he was 10 years old. He was also treated with 33.6 Gy of cyber knife radiotherapy at age of 12 years. Subsequently, he was free from tumor regrowth, but was complicated by mild mental retardation. When he was 16 years old, he suddenly developed left hemiparesis. Magnetic resonance (MR) images showed lacunar infarction in the pons (Fig 1, A) and small cavernoma in the right thalamus. MR angiography revealed multiple stenotic lesions in the intracranial arteries (Fig 1, B). He was medically treated. Two years later, however, he complained of sudden headache. Computed tomography (CT) and MR images demonstrated fresh bleeding in the lateral ventricle, third ventricle, and around the cavernoma in the thalamus (Fig 1, C, arrow), and a minor subarachnoid hemorrhage in the right Sylvian fissure (Fig 1, C, arrowhead). He was treated conservatively with hospitalization. At seventh day after admission, however, he became comatose and CT showed subarachnoid and subcortical hemorrhage in the right frontal lobe (Fig 1, D).
Journal of Stroke & Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■
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ARTICLE IN PRESS M. KUNITAKA ET AL.
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Figure 1. MR diffusion-weighted image (A) showed a fresh pontine infarction in the territory of the paramedian branch, and MR angiography (B) demonstrated multiple stenosis in the left internal carotid artery and middle cerebral artery (arrows) when he presented with the left hemiparesis 6 years after initial irradiation. Note no stenosis in the basilar artery. T2-weighted MR image (C) showed a cavernoma in the right thalamus (arrow) associated with intraventricular hemorrhage, and a minor bleeding in the right Sylvian fissure (arrowhead) 2 years later. CT image (D) and 3D-CT angiogram (E) on the seventh day after admission showed massive subcortical hematoma in the right frontal lobe and subarachnoid hemorrhage in the right Sylvian fissure. Simultaneous 3D-CT angiography showed a fusiform aneurysm in the right middle cerebral artery. The lobulated fusiform aneurysms were located on the M2-M3 bifurcation of the superior trunk. Surgical specimen (F) was obtained by trapping and resection of the fusiform aneurysm. Histology finding of the resected aneurysm (G-I) demonstrated intimal thickening with fibrosis and small inflammatory cell infiltration in the aneurysmal wall. Note that the internal elastic lamina was absent (Elastica van Gieson staining, G: ×20, H: ×100; hematoxylin and eosin staining, I: ×200).
Three-dimensional CT angiography demonstrated a fusiform aneurysm in the right middle cerebral artery (Fig 1, E). We evacuated the hematoma and resected the aneurysms with surgical trapping (Fig 1, F). He was rescued, but had persistent left hemiparesis. Histologic study of the resected aneurysm demonstrated the findings consistent with radiation-induced vasculopathy (Fig 1, G-I).
Discussion We reported a very rare case with multiple cerebrovascular events after irradiation for pilocytic astrocytoma, including lacunar stroke, the bleeding from cavernoma,
and subarachnoid or subcortical hemorrhage from the fusiform middle cerebral artery aneurysm. The multiple vasculopathy or repeated vascular events, and coexistence of meningioma and vasculopathy, have been reported.1,2 But multiple different types of vascular events in the irradiated field has not been reported. Radiotherapy is known to induce many undesirable incidents such as brain degeneration, tumor formation, and vasculopathy in the long-term survivors.1,3 These events would often be critical for them. Radiosurgery damages the endothelial cells and causes the proliferation of smooth muscle cells, leading to intimal thickening. As the degeneration progresses, this induces vessel wall hyalinization, calcification, and necrosis associated with fragmentation
ARTICLE IN PRESS RADIATION-INDUCED POLY-VASCULOPATHY
of the elastic lamina, resulting in occlusion of blood vessels in arteriovenous malformations.2,4,5 In the experimental study, endothelial cell proliferation started at 3 hours after irradiation, and the endothelial hyperplasia and vessel wall thickening continued throughout the observation period (90 days after irradiation).6 Radiation-induced histologic changes of vessels are supposed to be doserelated, and high dose radiation can induce radionecrosis.7 In our case, the radiation dose in conventional radiation at the right and the left Sylvian fissures, the third ventricle, and pons was 40, 45, 50, and 47.5 Gy by conventional radiation, respectively, and were 3.4, 26.9, 26.9, and 13.4 Gy by cyber knife, respectively. The latency between the initial irradiation and pontine infarction and cavernoma formation was 6 years. Furthermore, the formation of fusiform aneurysm required 8 years after initial irradiation. The latency and minimum radiation dose for these vascular events were reported as .26-5.7 years and 50.4 Gy in ischemic stroke,8 1.1-16.1 years and 51 Gy in cavernoma,9 and 5.7-11.2 years and 31.8 Gy in aneurysm, respectively.10 In conclusion, we reported a very rare case of a pediatric patient who repeated different types of vascular events consecutively in the irradiated field including cerebral infarction because of occlusion of perforating artery, intraventricular hemorrhage from cavernoma, and subarachnoid or subcortical hemorrhage because of the rupture of fusiform aneurysm. We should avoid irradiation, and repeat surgical resection for the pediatric cases with pilocytic astrocytoma. Once irradiation was indicated for them, however, we should carefully follow-up not only
3
tumor recurrence but also angiograms to predict any cerebrovascular events.
References 1. Campen CJ, Kranick SM, Kasner SE, et al. Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 2012;43:3035-3040. 2. Murphy ES, Xie H, Merchant TE, et al. Review of cranial radiotherapy-induced vasculopathy. J Neurooncol 2015;122:421-429. 3. Valk PE, Dillon WP. Radiation injury of the brain. AJNR Am J Neuroradiol 1991;12:45-62. 4. Shneider B, Eberhard DA, Steiner L. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 1997;87:352-357. 5. Jahan R, Solberg TD, Lee D, et al. An arteriovenous malformation model for stereotactic radiosurgery research. Neurosurgery 2007;61:152-159. 6. Yang T, Wu SL, Liang JC, et al. Time-dependent astroglial changes after gamma knife radiosurgery in the rat forebrain. Neurosurgery 2000;47:407-416. 7. Lunsford LD, Altschuler EM, Flickinger JC, et al. In vivo biological effects of stereotactic radiosurgery: a primate model. Neurosurgery 1990;27:373-382. 8. Fouladi M, Langston J, Mulhern R, et al. Silent lacunar lesions detected by magnetic resonance imaging of children with brain tumors: a late sequela of therapy. J Clin Oncol 2000;18:824-831. 9. Lew SM, Morgan JN, Psaty E, et al. Cumulative incidence of radiation-induced cavernomas in long-term survivors of medulloblastoma. J Neurosurg 2006;104:103-107. 10. Allan DNIII, El Tecle NE, El Ahmadieh TY, et al. Intracranial aneurysms in previously irradiated fields: literature review and case report. World Neurosurg 2014;81:511-519.
Case Studies
Lacunar Stroke, Cavernous Angioma, and Fusiform Aneurysm Due to Irradiation for Pilocytic Astrocytoma—A Case Report Maruyama Kunitaka, MD, Takuya Akai, MD, PhD, Naoki Akioka, MD, PhD, Takahiro Tomita, MD, PhD, Shoichi Nagai, MD, PhD, and Satoshi Kuroda, MD, PhD
Radiotherapy is a useful modality for the treatment of brain tumors, but may induce brain degeneration, tumor formation, and vasculopathy in the irradiated field. We describe a rare case of a pediatric patient who presented multiple different types of vascular events consecutively in the irradiated field including lacunar stroke because of occlusion of perforating artery, intraventricular hemorrhage from cavernoma, and subarachnoid hemorrhage because of the rupture of fusiform aneurysm, 6 years after radiotherapy against pilocytic astrocytoma. The life-threatening aneurysm was resected, and its histologic findings revealed the radiation-induced vasculopathy. We should avoid irradiation, and repeat surgical resection for the pediatric cases with pilocytic astrocytoma. Once irradiation was indicated for them, however, we should carefully follow-up not only tumor recurrence but also angiograms to predict any cerebrovascular events. Key Words: Radiation— vasculopathy—stroke—pilocytic astrocytoma—aneurysm—cavernoma. © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Case Report A 3-year-old boy was experiencing gait instability, and radiological examinations demonstrated suprasellar tumor associated with hydrocephalus. He underwent partial tumor resection with histologic diagnosis of pilocytic astrocytoma followed by chemotherapy with carboplatin and etoposide. The follow-up images showed the tumor
From the Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan. Received January 31, 2018; revision received February 20, 2018; accepted February 28, 2018. Address correspondence to Takuya Akai, MD, PhD, Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.062
regrowth, and he received conventional radiotherapy with 40 Gy for whole ventricles and 60 Gy for the tumor when he was 10 years old. He was also treated with 33.6 Gy of cyber knife radiotherapy at age of 12 years. Subsequently, he was free from tumor regrowth, but was complicated by mild mental retardation. When he was 16 years old, he suddenly developed left hemiparesis. Magnetic resonance (MR) images showed lacunar infarction in the pons (Fig 1, A) and small cavernoma in the right thalamus. MR angiography revealed multiple stenotic lesions in the intracranial arteries (Fig 1, B). He was medically treated. Two years later, however, he complained of sudden headache. Computed tomography (CT) and MR images demonstrated fresh bleeding in the lateral ventricle, third ventricle, and around the cavernoma in the thalamus (Fig 1, C, arrow), and a minor subarachnoid hemorrhage in the right Sylvian fissure (Fig 1, C, arrowhead). He was treated conservatively with hospitalization. At seventh day after admission, however, he became comatose and CT showed subarachnoid and subcortical hemorrhage in the right frontal lobe (Fig 1, D).
Journal of Stroke & Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■
1
ARTICLE IN PRESS M. KUNITAKA ET AL.
2
Figure 1. MR diffusion-weighted image (A) showed a fresh pontine infarction in the territory of the paramedian branch, and MR angiography (B) demonstrated multiple stenosis in the left internal carotid artery and middle cerebral artery (arrows) when he presented with the left hemiparesis 6 years after initial irradiation. Note no stenosis in the basilar artery. T2-weighted MR image (C) showed a cavernoma in the right thalamus (arrow) associated with intraventricular hemorrhage, and a minor bleeding in the right Sylvian fissure (arrowhead) 2 years later. CT image (D) and 3D-CT angiogram (E) on the seventh day after admission showed massive subcortical hematoma in the right frontal lobe and subarachnoid hemorrhage in the right Sylvian fissure. Simultaneous 3D-CT angiography showed a fusiform aneurysm in the right middle cerebral artery. The lobulated fusiform aneurysms were located on the M2-M3 bifurcation of the superior trunk. Surgical specimen (F) was obtained by trapping and resection of the fusiform aneurysm. Histology finding of the resected aneurysm (G-I) demonstrated intimal thickening with fibrosis and small inflammatory cell infiltration in the aneurysmal wall. Note that the internal elastic lamina was absent (Elastica van Gieson staining, G: ×20, H: ×100; hematoxylin and eosin staining, I: ×200).
Three-dimensional CT angiography demonstrated a fusiform aneurysm in the right middle cerebral artery (Fig 1, E). We evacuated the hematoma and resected the aneurysms with surgical trapping (Fig 1, F). He was rescued, but had persistent left hemiparesis. Histologic study of the resected aneurysm demonstrated the findings consistent with radiation-induced vasculopathy (Fig 1, G-I).
Discussion We reported a very rare case with multiple cerebrovascular events after irradiation for pilocytic astrocytoma, including lacunar stroke, the bleeding from cavernoma,
and subarachnoid or subcortical hemorrhage from the fusiform middle cerebral artery aneurysm. The multiple vasculopathy or repeated vascular events, and coexistence of meningioma and vasculopathy, have been reported.1,2 But multiple different types of vascular events in the irradiated field has not been reported. Radiotherapy is known to induce many undesirable incidents such as brain degeneration, tumor formation, and vasculopathy in the long-term survivors.1,3 These events would often be critical for them. Radiosurgery damages the endothelial cells and causes the proliferation of smooth muscle cells, leading to intimal thickening. As the degeneration progresses, this induces vessel wall hyalinization, calcification, and necrosis associated with fragmentation
ARTICLE IN PRESS RADIATION-INDUCED POLY-VASCULOPATHY
of the elastic lamina, resulting in occlusion of blood vessels in arteriovenous malformations.2,4,5 In the experimental study, endothelial cell proliferation started at 3 hours after irradiation, and the endothelial hyperplasia and vessel wall thickening continued throughout the observation period (90 days after irradiation).6 Radiation-induced histologic changes of vessels are supposed to be doserelated, and high dose radiation can induce radionecrosis.7 In our case, the radiation dose in conventional radiation at the right and the left Sylvian fissures, the third ventricle, and pons was 40, 45, 50, and 47.5 Gy by conventional radiation, respectively, and were 3.4, 26.9, 26.9, and 13.4 Gy by cyber knife, respectively. The latency between the initial irradiation and pontine infarction and cavernoma formation was 6 years. Furthermore, the formation of fusiform aneurysm required 8 years after initial irradiation. The latency and minimum radiation dose for these vascular events were reported as .26-5.7 years and 50.4 Gy in ischemic stroke,8 1.1-16.1 years and 51 Gy in cavernoma,9 and 5.7-11.2 years and 31.8 Gy in aneurysm, respectively.10 In conclusion, we reported a very rare case of a pediatric patient who repeated different types of vascular events consecutively in the irradiated field including cerebral infarction because of occlusion of perforating artery, intraventricular hemorrhage from cavernoma, and subarachnoid or subcortical hemorrhage because of the rupture of fusiform aneurysm. We should avoid irradiation, and repeat surgical resection for the pediatric cases with pilocytic astrocytoma. Once irradiation was indicated for them, however, we should carefully follow-up not only
3
tumor recurrence but also angiograms to predict any cerebrovascular events.
References 1. Campen CJ, Kranick SM, Kasner SE, et al. Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 2012;43:3035-3040. 2. Murphy ES, Xie H, Merchant TE, et al. Review of cranial radiotherapy-induced vasculopathy. J Neurooncol 2015;122:421-429. 3. Valk PE, Dillon WP. Radiation injury of the brain. AJNR Am J Neuroradiol 1991;12:45-62. 4. Shneider B, Eberhard DA, Steiner L. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 1997;87:352-357. 5. Jahan R, Solberg TD, Lee D, et al. An arteriovenous malformation model for stereotactic radiosurgery research. Neurosurgery 2007;61:152-159. 6. Yang T, Wu SL, Liang JC, et al. Time-dependent astroglial changes after gamma knife radiosurgery in the rat forebrain. Neurosurgery 2000;47:407-416. 7. Lunsford LD, Altschuler EM, Flickinger JC, et al. In vivo biological effects of stereotactic radiosurgery: a primate model. Neurosurgery 1990;27:373-382. 8. Fouladi M, Langston J, Mulhern R, et al. Silent lacunar lesions detected by magnetic resonance imaging of children with brain tumors: a late sequela of therapy. J Clin Oncol 2000;18:824-831. 9. Lew SM, Morgan JN, Psaty E, et al. Cumulative incidence of radiation-induced cavernomas in long-term survivors of medulloblastoma. J Neurosurg 2006;104:103-107. 10. Allan DNIII, El Tecle NE, El Ahmadieh TY, et al. Intracranial aneurysms in previously irradiated fields: literature review and case report. World Neurosurg 2014;81:511-519.