Case Report
Embolic stroke secondary to spontaneous thrombosis of unruptured intracranial aneurysm: Report of three cases
Interventional Neuroradiology 0(00) 1–5 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1591019915618169 ine.sagepub.com
Antonio Arauz1, Herna´n M Patin˜o-Rodrı´guez1, Mo´nica Chavarrı´a-Medina1, Mayra Becerril1, Jose´ G Merino2 and Marco Zenteno1
Abstract Intracranial aneurysms uncommonly present with ischemic stroke. Parent artery occlusion due to local extension of the luminal thrombus, aneurysms ejecting emboli to distal arteries, or increased mass effect have been described as possible pathogenic mechanisms. Guidelines for the management of these patients are absent. We present the clinical outcome and radiological characteristics of three patients with spontaneous thrombosis of intracranial aneurysms as a cause of ischemic stroke. This information is relevant given the possible benign history in terms of stroke recurrence and risk of bleeding.
Keywords Ischemic stroke, unruptured aneurysm, thrombosis Received 30 September 2015; accepted 24 October 2015
Introduction Unruptured intracranial aneurysms (UIA) may be found incidentally or may produce symptoms secondary to mass effect. In addition, slow blood flow within large or giant aneurysms can occasionally lead to thrombosis, distal embolization, and stroke.1 Among patients with UIA, the reported prevalence of ischemic stroke or transient ischemic attack is low (3–6.3%),2 and as a result, knowledge of the clinical and radiological features of stroke due to thrombosed UIA is limited. In this paper, we report the clinical and radiological characteristics of three patients who presented with ischemic stroke and thrombosed UIAs in a location corresponding to the clinical symptoms of stroke.
Case 1 A 59-year-old man arrived to the emergency department (ED) with a six-hour history of sudden dizziness, gait ataxia, and left-sided weakness. He had a history of a hypertensive intracranial hemorrhage two years prior, and his baseline modified Rankin score (mRS) was 2. He was taking an angiotensin converting enzyme inhibitor (ACEI) for hypertension. On arrival to the ED, he was stuporous, did not have a vertical oculocephalic response, and only feebly withdrew his limbs to painful stimulation. Soon after the initial evaluation, he was intubated for airway protection. Magnetic resonance imaging (MRI) revealed multiple acute infarcts in
the territory of the basilar artery—bilateral cerebellar, bulbar, pontine and mesencephalic—suggesting embolism as a cause of the stroke. In addition, he had an enlarged basilar artery seen as a hypointense rounded mass adjacent to the pons with internal hyperintensity suggestive of a large thrombosed aneurysm. Digital subtraction angiography (DSA) confirmed the presence of a trilobulated vertebral aneurysm extending into the basilar artery with late filling suggestive of partial thrombosis (Figure 1). He was started on aspirin, atorvastatin, and, for deep venous thrombosis (DVT) prophylaxis, enoxaparin. No other sources of embolism were found on transthoracic echocardiogram and Holter monitoring. DSA ruled out carotid and vertebral atherosclerotic disease. Interventional or surgical procedures for treatment of the aneurysm were not considered due to the severity of the symptoms and the burden of the infarcts. At the six-month follow-up visit, he had not had a subarachnoid hemorrhage or
1
Instituto Nacional de Neurologia y Neurocirugı´a Manuel Velasco Suarez, Mexico 2 Johns Hopkins Community Physicians, USA Corresponding author: Herna´n M Patin˜o-Rodrı´guez, Instituto Nacional de Neurologia y Neurocirugı´a Manuel Velasco Suarez, Av insurgentes Sur, 3877 Col La Fama, Mexico City, 14269, Mexico. Email: [email protected]
2
Interventional Neuroradiology 0(00)
Figure 1. (a) and (b) MRI T2 sequence shows multiple hyperintense lesions in the posterior circulation territory and a BA aneurysm. (c) and (d) DSA confirms the presence of a partially thrombosed trilobulated BA aneurysm. MRI, magnetic resonance imaging; BA, basilar artery; DSA, digital subtraction angiography.
recurrent stroke but his mRS was 5. The thrombosed aneurysm was unchanged on MRI.
Case 2 A 38-year-old woman was brought to the ED with a 12-hour history of headache, dizziness, and blindness. Her past medical history was unremarkable. On admission, she was somnolent, with cortical blindness, bilateral exotropia, and right hemiparesis. Brain MRI showed bilateral occipital-temporal and right thalamic infarcts with hemorrhagic transformation on the left suggesting a top of the basilar artery occlusion. Additionally, she had two large areas of vascular flow void suggestive of aneurysms: one was in the basilar artery and had areas of internal hyperintensity consistent with aneurysmal thrombosis, and the other was in the first portion of the left middle cerebral artery (MCA). DSA confirmed these findings (Figure 2) and ruled out either extra- or intracranial carotid or vertebral atherosclerotic disease. Work-up did not reveal a source of cardiac embolism. She was started on aspirin, atorvastatin, and enoxaparin (for DVT prophylaxis). She did not have any procedures to treat the aneurysms
due to her clinical condition. At the six-month followup visit, she remained free of recurrent stroke, and the aneurysms remained unchanged on MRI, but her mRS was 4. Because of her clinical deficits, she did not want to have surgical or interventional treatment of either aneurysm.
Case 3 A 60-year-old woman was admitted to the ED with sudden aphasia and right hemiparesis. She had a history of hypertension treated with ACEI. On MRI, she had a left anterior circulation infarct and a large aneurysm at the origin of the left MCA that had an area of internal hyperintensity on T2 and enhanced after gadolinium administration. This pattern is compatible with a partially thrombosed supraclinoid aneurysm. DSA confirmed a saccular aneurysm of the choroidal segment (Figure 3) and ruled out carotid atherosclerotic disease. Acute medical management included aspirin, atorvastatin, and DVT prophylaxis. She did not have a source of cardiac embolus. One month later, the aneurysm was clipped. Two years later, she had not had recurrent stroke, but her mRS was still 4.
Arauz et al.
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Figure 2. (a) MRI gradient echo images show the bilateral occipital ischemic stroke with hemorrhagic transformation on the left and a partially thrombosed aneurysm of the basilar artery. (b) T2 shows right thalamic and bilateral occipitotemporal infarcts and a sacular aneurysm of the left M1 segment of the MCA. (c) and (d) DSA confirms the presence of a partially thrombosed top-of-the-basilar aneurysm.
Discussion Almost 50% of intracranial giant aneurysms can present with spontaneous thrombosis. Factors associated with UIA thrombosis include the ratio between aneurysmal volume and aneurysmal neck size, the age of the aneurysm, and intrasaccular hemodynamic changes that involve endothelial damage.3 This phenomenon has also been reported in children and in patients with small saccular aneurysms.1,4–6 Cerebral infarcts can be the first manifestation of spontaneous thrombosis of large or giant UIAs. Parent artery occlusion due to local extension of the luminal thrombus, distal embolization, and increased mass effect have been implicated as possible pathogenic mechanisms.1,7 This paper presents three patients with spontaneous thrombosis of an UIA and embolic ischemic stroke. In all three cases, the imaging features of the infarcts were suggestive of embolism, alternative etiologies were ruled out, and the presence of aneurysmal thrombus was confirmed. These features suggest a causal relationship between the aneurysm and the infarct. All patients had large aneurysms. Black and German found that the larger the volume of the aneurysmal sac in relation to
the cross-sectional area of the neck, the more sluggish the flow within the fundus, which increased the possibility of thrombosis.8 At this point, there is no consensus about the best way to approach patients with UIA and ischemic stroke. Antiplatelets may inhibit platelet aggregation and activation within the aneurysmal sac and reduce the risk of ischemic events (4). The risk of subarachnoid hemorrhage while on antiplatelet medication is unknown. Spontaneous recanalization of a previously thrombosed aneurysm can also occur.9 Our patients received a low dose of aspirin, and we did not observe hemorrhagic complications. None of our three patients had recurrent ischemic stroke at the time of follow-up, and none had recanalization. In one patient, the aneurysm was clipped, and in two treatments was only medical because their clinical conditions were poor. While the reported incidence of recurrent ischemic events in patients with thrombosed UIA is low, surgical treatment of the aneurysm may provide protection. Qureshi et al. found a recurrence of ischemic stroke or TIA in 4/21 patients treated with conservative management compared with
4
Interventional Neuroradiology 0(00)
Figure 3. (a) MRI T2 with ischemic changes in the left MCA territory and a partially thrombosed aneurysm. (b) Gadolinium enhanced MRI showing the supraclinoid saccular aneurysm. (c) and (d) DSA confirmed a PTA of the choroidal segment of the left ICA with intrasaccular retention of the contrast. (e) and (f) DSA one day after clipping proved total exclusion of the aneurysm. MCA, middle cerebral artery; ICA, internal carotid artery; PTA, partial thrombosed aneurysm.
1/20 patients treated with a surgical approach (2). The role of surgery or endovascular interventions in patients with UIA and ischemic stroke, however, is not clear. Aneurysm clipping may be beneficial because it decreases the risk of subsequent embolization and of subarachnoid hemorrhage. However, given the risk of intraoperative thromboembolic events, it is possible that the risk of surgery in these patients is higher than in patients with asymptomatic UIA. Elective coiling of UIA is another therapeutic
alternative, and the use of aspirin or clopidogrel may reduce the risk of associated thromboembolic complications.10,11 Since studies have excluded (or not reported) patients with previous spontaneous thrombosis, the evidence base to guide therapeutic choices in these patients is limited. In our opinion, manipulation of the intrasaccular thrombus during coiling can lead to further embolization, and further studies are needed before this option can be widely implemented.
Arauz et al. While the prognosis of patients with UIA with stroke is good,1 in our series, regardless of whether the patient was treated medically or surgically, all cases had a bad outcome (mRS > 3). Nanda et al.12 compared the outcome of patients with unruptured cerebral aneurysms presenting with ischemic episodes to that of a group who presented with Hunt– Hess grades of 0 and 1 without ischemic symptoms. The group with ischemic symptoms had poor prognoses.
Conclusion Ischemic stroke is a rare but serious complication of UIA. In this series, three patients with confirmed spontaneous aneurysm thrombosis presented with large, disabling, cerebral infarcts. During follow-up, no ischemic recurrences or subarachnoid hemorrhage were observed. This information is relevant given the possible benign history in terms of stroke recurrence and risk of bleeding.
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Funding The authors received no financial support for the research, authorship, and/or publication of this article. 10.
Declaration of conflicting interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
11.
References 1. McLaughlin N and Bojanowski MW. Unruptured cerebral aneurysms presenting with ischemic events. Can J Neurol Sci 2008; 35: 588–592. 2. Qureshi AI, Mohammad Y, Yahia AM, et al. Ischemic events associated with unruptured intracranial aneurysms: multicenter clinical study and review of the
12.
literature. Neurosurgery 2000; 46: 282–289; discussion 9–90. Whittle IR, Dorsch NW and Besser M. Spontaneous thrombosis in giant intracranial aneurysms. J Neurol Neurosurg Psychiatry 1982; 45: 1040–1047. Mokin M, Darkhabani Z, Binning MJ, et al. Small unruptured partially thrombosed aneurysms and stroke: report of three cases and review of the literature. J Neurointerv Surg 2012; 4: e6. Gonc¸alves VM, Cristino N, Cunha E, et al. Spontaneous thrombosis in giant aneurysm of the anterior communicating artery complex in pediatric age: five-year followup. Case Rep Vasc Med 2014; 2014: 236041. Smrcka M, Ogilvy CS and Koroshetz W. Small aneurysms as a cause of thromboembolic stroke. Bratisl Lek Listy 2002; 103: 250–253. Cohen JE, Itshayek E, Yitshayek E, et al. Spontaneous thrombosis of cerebral aneurysms presenting with ischemic stroke. J Neurol Sci 2007; 254: 95–98. Black SP and German WJ. Observations on the relationship between the volume and the size of the orifice of experimental aneurysms. J Neurosurg 1960; 17: 984–990. Kooshkabadi A, Jankowitz B, Choi PA, et al. Thrombosis and spontaneous recanalization of a giant intracranial aneurysm: diagnostic and management pearls in a pediatric patient. J Neurosurg Pediatr 2015; 15: 78–81. Yamada NK, Cross DT, Pilgram TK, et al. Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 2007; 28: 1778–1782. Kang HS, Han MH, Kwon BJ, et al. Is clopidogrel premedication useful to reduce thromboembolic events during coil embolization for unruptured intracranial aneurysms? Neurosurgery 2010; 67: 1371–1376; discussion 6. Nanda A and Vannemreddy PS. Cerebral ischemia as a presenting feature of intracranial aneurysms: a negative prognostic indicator in the management of aneurysms. Neurosurgery 2006; 58: discussion, 831–837.
Embolic stroke secondary to spontaneous thrombosis of unruptured intracranial aneurysm: Report of three cases
Interventional Neuroradiology 0(00) 1–5 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1591019915618169 ine.sagepub.com
Antonio Arauz1, Herna´n M Patin˜o-Rodrı´guez1, Mo´nica Chavarrı´a-Medina1, Mayra Becerril1, Jose´ G Merino2 and Marco Zenteno1
Abstract Intracranial aneurysms uncommonly present with ischemic stroke. Parent artery occlusion due to local extension of the luminal thrombus, aneurysms ejecting emboli to distal arteries, or increased mass effect have been described as possible pathogenic mechanisms. Guidelines for the management of these patients are absent. We present the clinical outcome and radiological characteristics of three patients with spontaneous thrombosis of intracranial aneurysms as a cause of ischemic stroke. This information is relevant given the possible benign history in terms of stroke recurrence and risk of bleeding.
Keywords Ischemic stroke, unruptured aneurysm, thrombosis Received 30 September 2015; accepted 24 October 2015
Introduction Unruptured intracranial aneurysms (UIA) may be found incidentally or may produce symptoms secondary to mass effect. In addition, slow blood flow within large or giant aneurysms can occasionally lead to thrombosis, distal embolization, and stroke.1 Among patients with UIA, the reported prevalence of ischemic stroke or transient ischemic attack is low (3–6.3%),2 and as a result, knowledge of the clinical and radiological features of stroke due to thrombosed UIA is limited. In this paper, we report the clinical and radiological characteristics of three patients who presented with ischemic stroke and thrombosed UIAs in a location corresponding to the clinical symptoms of stroke.
Case 1 A 59-year-old man arrived to the emergency department (ED) with a six-hour history of sudden dizziness, gait ataxia, and left-sided weakness. He had a history of a hypertensive intracranial hemorrhage two years prior, and his baseline modified Rankin score (mRS) was 2. He was taking an angiotensin converting enzyme inhibitor (ACEI) for hypertension. On arrival to the ED, he was stuporous, did not have a vertical oculocephalic response, and only feebly withdrew his limbs to painful stimulation. Soon after the initial evaluation, he was intubated for airway protection. Magnetic resonance imaging (MRI) revealed multiple acute infarcts in
the territory of the basilar artery—bilateral cerebellar, bulbar, pontine and mesencephalic—suggesting embolism as a cause of the stroke. In addition, he had an enlarged basilar artery seen as a hypointense rounded mass adjacent to the pons with internal hyperintensity suggestive of a large thrombosed aneurysm. Digital subtraction angiography (DSA) confirmed the presence of a trilobulated vertebral aneurysm extending into the basilar artery with late filling suggestive of partial thrombosis (Figure 1). He was started on aspirin, atorvastatin, and, for deep venous thrombosis (DVT) prophylaxis, enoxaparin. No other sources of embolism were found on transthoracic echocardiogram and Holter monitoring. DSA ruled out carotid and vertebral atherosclerotic disease. Interventional or surgical procedures for treatment of the aneurysm were not considered due to the severity of the symptoms and the burden of the infarcts. At the six-month follow-up visit, he had not had a subarachnoid hemorrhage or
1
Instituto Nacional de Neurologia y Neurocirugı´a Manuel Velasco Suarez, Mexico 2 Johns Hopkins Community Physicians, USA Corresponding author: Herna´n M Patin˜o-Rodrı´guez, Instituto Nacional de Neurologia y Neurocirugı´a Manuel Velasco Suarez, Av insurgentes Sur, 3877 Col La Fama, Mexico City, 14269, Mexico. Email: [email protected]
2
Interventional Neuroradiology 0(00)
Figure 1. (a) and (b) MRI T2 sequence shows multiple hyperintense lesions in the posterior circulation territory and a BA aneurysm. (c) and (d) DSA confirms the presence of a partially thrombosed trilobulated BA aneurysm. MRI, magnetic resonance imaging; BA, basilar artery; DSA, digital subtraction angiography.
recurrent stroke but his mRS was 5. The thrombosed aneurysm was unchanged on MRI.
Case 2 A 38-year-old woman was brought to the ED with a 12-hour history of headache, dizziness, and blindness. Her past medical history was unremarkable. On admission, she was somnolent, with cortical blindness, bilateral exotropia, and right hemiparesis. Brain MRI showed bilateral occipital-temporal and right thalamic infarcts with hemorrhagic transformation on the left suggesting a top of the basilar artery occlusion. Additionally, she had two large areas of vascular flow void suggestive of aneurysms: one was in the basilar artery and had areas of internal hyperintensity consistent with aneurysmal thrombosis, and the other was in the first portion of the left middle cerebral artery (MCA). DSA confirmed these findings (Figure 2) and ruled out either extra- or intracranial carotid or vertebral atherosclerotic disease. Work-up did not reveal a source of cardiac embolism. She was started on aspirin, atorvastatin, and enoxaparin (for DVT prophylaxis). She did not have any procedures to treat the aneurysms
due to her clinical condition. At the six-month followup visit, she remained free of recurrent stroke, and the aneurysms remained unchanged on MRI, but her mRS was 4. Because of her clinical deficits, she did not want to have surgical or interventional treatment of either aneurysm.
Case 3 A 60-year-old woman was admitted to the ED with sudden aphasia and right hemiparesis. She had a history of hypertension treated with ACEI. On MRI, she had a left anterior circulation infarct and a large aneurysm at the origin of the left MCA that had an area of internal hyperintensity on T2 and enhanced after gadolinium administration. This pattern is compatible with a partially thrombosed supraclinoid aneurysm. DSA confirmed a saccular aneurysm of the choroidal segment (Figure 3) and ruled out carotid atherosclerotic disease. Acute medical management included aspirin, atorvastatin, and DVT prophylaxis. She did not have a source of cardiac embolus. One month later, the aneurysm was clipped. Two years later, she had not had recurrent stroke, but her mRS was still 4.
Arauz et al.
3
Figure 2. (a) MRI gradient echo images show the bilateral occipital ischemic stroke with hemorrhagic transformation on the left and a partially thrombosed aneurysm of the basilar artery. (b) T2 shows right thalamic and bilateral occipitotemporal infarcts and a sacular aneurysm of the left M1 segment of the MCA. (c) and (d) DSA confirms the presence of a partially thrombosed top-of-the-basilar aneurysm.
Discussion Almost 50% of intracranial giant aneurysms can present with spontaneous thrombosis. Factors associated with UIA thrombosis include the ratio between aneurysmal volume and aneurysmal neck size, the age of the aneurysm, and intrasaccular hemodynamic changes that involve endothelial damage.3 This phenomenon has also been reported in children and in patients with small saccular aneurysms.1,4–6 Cerebral infarcts can be the first manifestation of spontaneous thrombosis of large or giant UIAs. Parent artery occlusion due to local extension of the luminal thrombus, distal embolization, and increased mass effect have been implicated as possible pathogenic mechanisms.1,7 This paper presents three patients with spontaneous thrombosis of an UIA and embolic ischemic stroke. In all three cases, the imaging features of the infarcts were suggestive of embolism, alternative etiologies were ruled out, and the presence of aneurysmal thrombus was confirmed. These features suggest a causal relationship between the aneurysm and the infarct. All patients had large aneurysms. Black and German found that the larger the volume of the aneurysmal sac in relation to
the cross-sectional area of the neck, the more sluggish the flow within the fundus, which increased the possibility of thrombosis.8 At this point, there is no consensus about the best way to approach patients with UIA and ischemic stroke. Antiplatelets may inhibit platelet aggregation and activation within the aneurysmal sac and reduce the risk of ischemic events (4). The risk of subarachnoid hemorrhage while on antiplatelet medication is unknown. Spontaneous recanalization of a previously thrombosed aneurysm can also occur.9 Our patients received a low dose of aspirin, and we did not observe hemorrhagic complications. None of our three patients had recurrent ischemic stroke at the time of follow-up, and none had recanalization. In one patient, the aneurysm was clipped, and in two treatments was only medical because their clinical conditions were poor. While the reported incidence of recurrent ischemic events in patients with thrombosed UIA is low, surgical treatment of the aneurysm may provide protection. Qureshi et al. found a recurrence of ischemic stroke or TIA in 4/21 patients treated with conservative management compared with
4
Interventional Neuroradiology 0(00)
Figure 3. (a) MRI T2 with ischemic changes in the left MCA territory and a partially thrombosed aneurysm. (b) Gadolinium enhanced MRI showing the supraclinoid saccular aneurysm. (c) and (d) DSA confirmed a PTA of the choroidal segment of the left ICA with intrasaccular retention of the contrast. (e) and (f) DSA one day after clipping proved total exclusion of the aneurysm. MCA, middle cerebral artery; ICA, internal carotid artery; PTA, partial thrombosed aneurysm.
1/20 patients treated with a surgical approach (2). The role of surgery or endovascular interventions in patients with UIA and ischemic stroke, however, is not clear. Aneurysm clipping may be beneficial because it decreases the risk of subsequent embolization and of subarachnoid hemorrhage. However, given the risk of intraoperative thromboembolic events, it is possible that the risk of surgery in these patients is higher than in patients with asymptomatic UIA. Elective coiling of UIA is another therapeutic
alternative, and the use of aspirin or clopidogrel may reduce the risk of associated thromboembolic complications.10,11 Since studies have excluded (or not reported) patients with previous spontaneous thrombosis, the evidence base to guide therapeutic choices in these patients is limited. In our opinion, manipulation of the intrasaccular thrombus during coiling can lead to further embolization, and further studies are needed before this option can be widely implemented.
Arauz et al. While the prognosis of patients with UIA with stroke is good,1 in our series, regardless of whether the patient was treated medically or surgically, all cases had a bad outcome (mRS > 3). Nanda et al.12 compared the outcome of patients with unruptured cerebral aneurysms presenting with ischemic episodes to that of a group who presented with Hunt– Hess grades of 0 and 1 without ischemic symptoms. The group with ischemic symptoms had poor prognoses.
Conclusion Ischemic stroke is a rare but serious complication of UIA. In this series, three patients with confirmed spontaneous aneurysm thrombosis presented with large, disabling, cerebral infarcts. During follow-up, no ischemic recurrences or subarachnoid hemorrhage were observed. This information is relevant given the possible benign history in terms of stroke recurrence and risk of bleeding.
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3.
4.
5.
6.
7.
8.
9.
Funding The authors received no financial support for the research, authorship, and/or publication of this article. 10.
Declaration of conflicting interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
11.
References 1. McLaughlin N and Bojanowski MW. Unruptured cerebral aneurysms presenting with ischemic events. Can J Neurol Sci 2008; 35: 588–592. 2. Qureshi AI, Mohammad Y, Yahia AM, et al. Ischemic events associated with unruptured intracranial aneurysms: multicenter clinical study and review of the
12.
literature. Neurosurgery 2000; 46: 282–289; discussion 9–90. Whittle IR, Dorsch NW and Besser M. Spontaneous thrombosis in giant intracranial aneurysms. J Neurol Neurosurg Psychiatry 1982; 45: 1040–1047. Mokin M, Darkhabani Z, Binning MJ, et al. Small unruptured partially thrombosed aneurysms and stroke: report of three cases and review of the literature. J Neurointerv Surg 2012; 4: e6. Gonc¸alves VM, Cristino N, Cunha E, et al. Spontaneous thrombosis in giant aneurysm of the anterior communicating artery complex in pediatric age: five-year followup. Case Rep Vasc Med 2014; 2014: 236041. Smrcka M, Ogilvy CS and Koroshetz W. Small aneurysms as a cause of thromboembolic stroke. Bratisl Lek Listy 2002; 103: 250–253. Cohen JE, Itshayek E, Yitshayek E, et al. Spontaneous thrombosis of cerebral aneurysms presenting with ischemic stroke. J Neurol Sci 2007; 254: 95–98. Black SP and German WJ. Observations on the relationship between the volume and the size of the orifice of experimental aneurysms. J Neurosurg 1960; 17: 984–990. Kooshkabadi A, Jankowitz B, Choi PA, et al. Thrombosis and spontaneous recanalization of a giant intracranial aneurysm: diagnostic and management pearls in a pediatric patient. J Neurosurg Pediatr 2015; 15: 78–81. Yamada NK, Cross DT, Pilgram TK, et al. Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 2007; 28: 1778–1782. Kang HS, Han MH, Kwon BJ, et al. Is clopidogrel premedication useful to reduce thromboembolic events during coil embolization for unruptured intracranial aneurysms? Neurosurgery 2010; 67: 1371–1376; discussion 6. Nanda A and Vannemreddy PS. Cerebral ischemia as a presenting feature of intracranial aneurysms: a negative prognostic indicator in the management of aneurysms. Neurosurgery 2006; 58: discussion, 831–837.
