Ruptured internal carotid artery aneurysm presenting with catastrophic epistaxis after repeated stereotactic radiotherapies for anterior skull base tumor: case reports and review of the literature.

Objectives Radiation-induced aneurysm is a rare complication for head and neck tumors. Only seven cases of an aneurysm after stereotactic radiosurgery and/or stereotactic radiotherapy (SRT) have been described. We report two patients with a ruptured internal carotid artery (ICA) aneurysm presenting with catastrophic epistaxis after repeated SRT for an anterior skull base tumor. Results Two male patients received repeated SRT in various combinations following surgery for an anterior skull base tumor. They presented with significant epistaxis due to rupture of the aneurysm of the ICA 6 and 77 months after the final SRT, respectively. The aneurysms were located within the radiation field. Preoperative angiography had revealed no aneurysms. Thus the aneurysms in these cases were most likely induced by the repeated SRT. Conclusions This is a proven report of aneurysm formation following repeated SRT without conventional radiotherapy. SRT may be very effective to control malignant skull base tumors. However, the possible development of radiation-induced aneurysm of the ICA should be considered in the case of repeated SRT. The surviving patients who have received SRT should undergo sequential follow-up for possible vascular involvement.

Introduction

Radiation-induced aneurysm is a rare complication for head and neck cancer, and the pathogenesis is not fully understood.1 2 3 4 5 6 7 8 But the mechanism is likely to be similar to that of radiation-induced chronic vascular damage.9 10 11 12

Several authors have reported ∼ 30 cases of radiation-induced intracranial aneurysms with subsequent rupture.1 2 5 8 13 These aneurysms were diagnosed from 10 months to 21 years after radiation therapy. So far, only seven cases of aneurysm after stereotactic radiosurgery (SRS) and/or stereotactic radiotherapy (SRT) have been described.14 15 16 17 18 19 20 All of these patients underwent repeated radiotherapies in various combinations.

We present two cases of catastrophic epistaxis due to a ruptured internal carotid artery (ICA) aneurysm induced by repeated SRT for an anterior skull base tumor and successfully treated by endovascular surgery. This is a proven report of aneurysm formation following repeated SRT without conventional radiotherapy. SRT for skull base tumors may be very effective to control these tumors. However, these cases suggest that the development of a radiation-induced aneurysm should be considered a possible serious complication in the case of repeated SRT. Case 1 described here was reported previously in this journal.21

Case Reports

Case 1

A 29-year-old man was referred to our institution for the treatment of a large Ewing primitive neuroectodermal tumor (PNET) that occupied the right orbit and ethmoid and maxillary sinus with right progressive visual loss in four years earlier (Fig. 1A). The tumor was resected totally via the transbasal approach. Preoperative angiography revealed no abnormality. The right ICA was not injured during the surgery. Postoperatively, the patient underwent adjuvant chemotherapy and SRT with a dose ranging from 45 to 54.9 Gy in 15 fractions that produced a complete response. The right petrous ICA and surrounding structure were located within the radiation field. The recurrent tumor in the right maxillary sinus was seen 28 months after surgery. Therefore, the second SRT was performed with a dose ranging from 53.5 to 62.3 Gy in 15 fractions that resulted in the partial response. However, 42 months after surgery, tumor relapse was revealed in the right orbit that remarkably had eroded the sphenoid bone. He underwent the third SRT with a dose ranging from 52.8 to 60.0 Gy in 15 fractions. Magnetic resonance imaging (MRI) demonstrated the tumor had almost disappeared after SRT (Fig. 1B), and he was followed regularly as an outpatient.

Fig. 1

(A) Axial T1-weighted magnetic resonance image with gadolinium (MRI-Gd) before the surgery revealed the tumor in the orbit and ethmoid sinus adjacent to the right internal carotid artery (ICA). (B) Axial MRI-Gd after the third stereotactic radiotherapy demonstrated remarkable shrinkage of the tumor. (C) Computed tomography scan on emergent admission due to massive epistaxis revealed the hematoma at the middle cranial fossa and pneumocephalus. (D) Right internal carotid angiogram showed a right petrous ICA aneurysm (arrow) with slight stenosis of the adjacent ICA (arrowhead). (E) Left internal carotid angiogram after the endovascular treatment revealed the tolerable cross-flow via the anterior communicating artery.

The patient was admitted to our hospital with complaints of significant epistaxis with hypovolemic shock 6 months after the final SRT. A computed tomography scan revealed a hematoma at the middle cranial fossa and paranasal sinuses, and pneumocephalus (Fig. 1C). Cerebral angiography showed a right petrous ICA aneurysm with slight stenosis of the adjacent ICA (Fig. 1D). Because of rebleeding during the cerebral angiography, we urgently performed endovascular parent-artery occlusion without balloon test occlusion (BTO) to save his life. Cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with a tolerable cross-flow via the anterior communicating artery (ACoA) (Fig. 1E). The postoperative course was uneventful. Postoperative MRI revealed no ischemic or hemorrhagic complications. He recovered fully and was discharged 3 weeks after surgery without new neurologic deficits. But 6 months after endovascular treatment, he died from an untreatable tumor relapse.

Case 2

A 61-year-old man was admitted to our hospital for the treatment of a left large sphenocavernous meningioma in 1999 at 48 years of age. The tumor was partially resected via the orbitozygomatic approach without removal of the cavernous mass. The left ICA was not damaged during the surgery. The pathologic diagnosis was atypical meningioma. The left cavernous tumor had gradually grown 23 months after the initial surgery and was treated by SRS using gamma knife. The tumor margin was covered by the 50% isodose line, and 12 Gy were delivered to the margin. The left cavernous ICA was located within the radiation field. However, the rest of the tumor continued to grow to the infratemporal fossa (Fig. 2A). Two surgeries, using the infratemporal fossa approach and transsphenoidal approach, were required to remove the extracranial tumor without removal of the cavernous tumor 83 months after the first operation. Preoperative angiography revealed no abnormality. The left ICA was not injured during the operations. The following month, the patient underwent SRT using cyber knife with a dose ranging from 30.0 to 47.6 Gy in five fractions that produced a complete response (Fig. 2B). He was followed up on an outpatient basis.

Fig. 2

(A) Coronal T1-weighted magnetic resonance image with gadolinium (MRI-Gd) after stereotactic radiosurgery revealed tumor recurrence in the cavernous sinus and the left infratemporal fossa surrounding the left internal carotid artery (ICA). (B) MRI-Gd after stereotactic radiosurgery and stereotactic radiotherapy demonstrated an almost disappearance of the tumor. (C) Left internal carotid angiogram demonstrated a small aneurysm at the left cavernous ICA (arrow). (D) Right internal carotid angiogram after the endovascular treatment showed enough collateral flow via the anterior communicating artery.

The patient was admitted to our hospital with complaints of massive epistaxis 77 months after the last SRT. Cerebral angiography showed a small aneurysm located at the cavernous portion of the left ICA (Fig. 2C). BTO of the left ICA demonstrated the presence of collateral flow via the ACoA without a reduced regional cerebral oxygenation state on the occluded side under the monitoring of near-infrared spectroscopy. Therefore, we decided to perform endovascular internal trapping of the left ICA. Cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with enough collateral flow via the ACoA (Fig. 2D). The postoperative course was uneventful. Postoperative MRI revealed no complications. He was discharged 2 weeks after the endovascular treatment without any new neurologic deficits.

Discussion

Radiation-induced carotid artery aneurysm is a rare complication of radiation therapy for head and neck carcinoma, but it is a life-threatening situation. The pathogenesis of radiation-induced aneurysm remains speculative.1 2 3 4 5 6 7 8 However the mechanism is likely to be similar to that of radiation-induced vasculopathy, due to chronic vascular damage such as obstruction of the vasa vasorum, premature atherosclerosis, adventitial fibrosis, and necrosis of the arterial wall.9 10 11 12 Combined with high blood pressure of the great vessel, it could result in the rupture of the arterial wall and even dissection with extravasation blood.13 22 23 Therefore, even a small radiation-induced aneurysm is more prone to rupture than other common saccular aneurysms.24

The clinical characteristics of radiation-induced aneurysms differ from other saccular aneurysms.13 Radiation-induced aneurysms originate directly from the arterial wall, which is less likely to be influenced by the direction of the blood flow, in contrast to other saccular aneurysms. Therefore, the formation of an aneurysm after irradiation might occur at any location on the vessel included within the radiation fields. In our cases, these aneurysms were not located at a branching site and were included within the radiation field. The angiography before the initial surgery revealed no aneurysm formation. In addition, the carotid arteries were not injured during the surgery. These findings suggest that the SRT was responsible for the formation of the carotid artery aneurysm.

Several authors have reported ∼ 30 cases of radiation-induced intracranial aneurysms with subsequent rupture.1 2 5 8 13 These aneurysms were diagnosed from 10 months to 21 years after radiation therapy. However, our literature review yielded only seven cases of aneurysm induced by SRS and/or SRT.14 15 16 17 18 19 20

Among them, four cases were presented as anterior inferior cerebellar artery aneurysm induced by SRS (gamma knife) for vestibular schwannoma.14 18 19 20 The remaining three cases were reported as ICA aneurysms15 16 17 (Table 1). With the inclusion of our cases, these patients were three men and two women (mean age: 52.2 years; range: 29–62 years). There were two cases of nasopharyngeal carcinoma, and one each of pituitary adenoma, atypical meningioma, and Ewing PNET. Three patients underwent operations without ICA injury before the final radiotherapy. All patients received repeated radiotherapies in various combinations. In addition, only our cases received repeated SRS or SRT without conventional radiotherapy. Although the interval between the latest radiotherapy and the diagnosis of the aneurysm varied from 3 months to 13 years (mean: 49.8 months), three cases developed within a year. These results indicated that repeated SRT causes an aneurysm to occur earlier than conventional radiotherapy or single SRT.

Table 1

Reported cases of internal carotid artery aneurysm after stereotactic radiotherapy

Study	Auyeung et al15	Cheng et al16	Endo et al17	Case 1(the present report) Tamura et al21	Case 2(the present report)
Age, y/Sex	52/F	57/M	62/F	29/M	61/M
Diagnosis	Nasopharyngeal carcinoma	Nasopharyngeal carcinoma	Pituitary adenoma	Ewing PNET	Atypical meningioma
Surgical resection of the tumor/ICA injury	None	None	Two transsphenoidal/No ICA injury	Transbasal/No ICA injury	Three times (orbitozygomatic, infratemporal fossa, transsphenoidal)/No ICA injury
Aneurysm rupture after the final surgery, mo	–	–	156	48	78
RT course and dose, Gy	1. Conventional RT (not described)2. SRS (not described)	1. Conventional RT (70.4)2. 3DCRT (40) + brachytherapy (18)	1. SRS (25–35)2. Conventional RT (55.2)	1. SRT (45.0–54.9)2. SRT (53.5–62.3)3. SRT (52.8–60.0)	1. SRS (12.0–25.0)2. SRT (30.0–47.6)
Aneurysm rupture after the final RT, mo	3	7	156	6	77
Aneurysm location	Petrous	Petrous	Petrous	Petrous	Cavernous
Presentation	Epistaxis	Epistaxis	Epistaxis	SAH, epistaxis	Epistaxis
Treatment	Stent	None (self-thrombosis)	EC-IC bypass; coil	Coil	Coil
Outcome	Good (follow-up for 3 mo)	Good (follow-up for 18 mo)	Good (follow-up for 2 mo)	Died 6 mo afterward due to tumor relapse	Good (follow-up for 24 mo)

Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; EC-IC bypass, external carotid-internal carotid artery bypass; ICA, internal carotid artery; PNET, primitive neuroectodermal tumor; RT, radiotherapy; SAH, subarachnoid hemorrhage; SRS, stereotactic radiosurgery; SRT, stereotactic radiotherapy.

SRT makes it possible to deliver efficacious therapeutic doses accurately to the targeted lesion with secure preservation of adjacent normal anatomical structures. However, if these structures are located within the targeted lesion, they must be involved in the radiation field. Excessive doses into them by repeated SRT can lead to critical complications. Therefore the surviving patients who have received SRT should undergo sequential follow-up for possible vascular involvement.

Treatment for radiation-induced aneurysms includes clipping,2 3 5 24 25 26 trapping,11 27 and wrapping the aneurysm and parent artery.2 5 28 29 In addition, parent artery occlusion using an endovascular technique is effective.19 28 30 Because of the high risk of mortality, if the radiation-induced aneurysm ruptures, aggressive surgical intervention or endovascular treatment should be considered for the aneurysm. Sacrifice of the carotid artery would lead to severe cerebrovascular events, and therefore a BTO should be performed. If a BTO is successful, trapping or parent artery occlusion becomes an option. If the patient cannot tolerate the test, an extracranial-to-intracranial bypass surgery should be considered. In case 1 of our series, the patient was semicomatose and in a state of hypovolemic shock due to repeated massive epistaxis. Therefore, an immediate salvage procedure was needed to save his life without performing BTO. In case 2, the patient could tolerate the test adequately. Hence ICA was sacrificed for parent artery occlusion.

We have presented two cases of a ruptured ICA aneurysm induced by repeated SRT for anterior skull base tumor. It was definitely difficult to clarify accurately the timing of aneurysm formation in our cases. In addition, although the primary factor was presumed the high dose delivered to the ICA by the repeated SRT, an unrecognized carotid injury at the former surgical intervention to the tumor or direct damage to the vessel wall by the tumor could also have been the probable causes. There are some reports on iatrogenic intracranial traumatic aneurysms after the resection of skull base tumors.31 32 33 It was suggested that most traumatic intracranial aneurysms have a symptomatic onset within 4 weeks after injury of the vessel wall.32 In our cases, however, the hemorrhagic presentation appeared 48 and 78 months after the final surgery, respectively. Therefore, we are convinced that the aneurysms in our cases were most likely induced by the repeated SRT and indicated a low probability of traumatic origin. Histologic analysis, if possible, might contribute to an understanding of the entity of these lesions.

Conclusions

We present two cases of catastrophic epistaxis due to ICA aneurysm that were most likely induced by repeated SRT for anterior skull base tumors. The SRT may be very effective to control the residual tumor as well as tumor relapse. However, the possible development of radiation-induced aneurysm of the carotid artery should be considered in the case of repeated SRT for malignant skull base tumors.