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Small unruptured partially thrombosed aneurysms and stroke: report of three cases and review of the literature
  1. Maxim Mokin1,
  2. Ziad Darkhabani1,
  3. Mandy J Binning2,3,
  4. Elad I Levy3,4,
  5. Adnan H Siddiqui3,4
  1. 1Department of Neurology, University at Buffalo, State University of New York, Buffalo, New York, USA
  2. 2Stroke and Cerebrovascular Center of New Jersey, Hamilton, New Jersey, USA
  3. 3Department of Neurosurgery, University at Buffalo, State University of New York, Buffalo, New York
  4. 4Department of Radiology, University at Buffalo, State University of New York, Buffalo, New York, USA
  1. Correspondence to Dr Adnan H Siddiqui, Department of Neurosurgery and Radiology, University at Buffalo, State University of New York, Buffalo, New York 14209, USA; asiddiqui{at}ubns.com

Abstract

Several case reports and studies suggest that partially thrombosed large and giant aneurysms are potential sources of distal embolic events. However, there are limited data on small thrombosed aneurysms as a possible cause of ischemic events. Three patients are reported who presented with acute ischemic stroke and in whom the initial imaging studies showed a small (<10 mm), unruptured, partially thrombosed aneurysm. In each case, the aneurysm location was confirmed by a conventional angiogram. In all cases, the aneurysms were found on the proximal middle cerebral artery, in the territory corresponding to the clinical symptoms of the stroke. The mechanism of middle cerebral artery embolic event was thought to be related to the thrombus within the aneurysm, causing subsequent embolization into distal related vascular territory. Two of these patients had craniotomy for aneurysm clipping; one was managed conservatively with medical therapy alone. Thrombosis of small, unruptured intracranial aneurysms should be considered as a possible cause of acute-onset stroke symptoms in patients with acute ischemic stroke. It is under-recognized in the current literature, and no guidelines currently exist for medical or surgical treatment of such aneurysms. Medical management is often decided on an individual basis. Surgical treatment mostly involves aneurysmal clipping rather than coiling.

  • Acute ischemic stroke
  • intracranial aneurysm
  • small
  • unruptured
  • thrombosed aneurysm
  • brain
  • tumor
  • spine
  • thrombectomy
  • catheter
  • balloon
  • thrombolysis
  • stroke
  • stent
  • stenosis
  • malformation
  • intervention
  • device
  • coil
  • atherosclerosis
  • angioplasty
  • angiography
  • aneurysm

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Introduction

Increasing reported evidence suggests a link between unruptured intracranial aneurysms and transient or permanent ischemic events.1–3 These studies include mostly patients who present with either large or giant aneurysms. Frequency, location, and characteristics of smaller aneurysms and their association with clinical symptoms have been less studied and are poorly understood. Especially rare are cases of spontaneous thrombosis of small aneurysms, and there are currently no recommendations for the management of patients harboring aneurysms who present with clinical symptoms secondary to ischemic events. Here, we describe three similar patients in whom the diagnostic investigation revealed a small partially thrombosed aneurysm in a location corresponding to the clinical symptoms. We also review the current literature in an attempt to summarize findings relative to this topic.

Case reports

Case 1

A patient in their early 50s with an unremarkable medical history presented to the emergency room at our institution with left-sided hemiparesis. A diagnostic imaging investigation was performed. A CT perfusion study showed a perfusion deficit suggesting an acute ischemic infarction in the territory of the right middle cerebral artery (MCA) (figure 1A). Brain MRI showed an area of acute ischemia in the same vascular territory. A small round area (7.1 mm in diameter) of hyperdense signal was observed in the proximal sylvian fissure on a non-contrast CT scan, which led to suspicion of a thrombosed aneurysm (figure 1B). CT angiography demonstrated an embolus occluding the distal right M1 segment with further occlusion of the superior M2 division of the right MCA; however, no definite aneurysm was noted (figure 1C). Conventional catheter-based diagnostic cerebral angiography confirmed the presence of a small, partially thrombosed aneurysm measuring 8.6×5.2 mm, just proximal to the right MCA bifurcation, as well as a filling defect in the frontal branches of the right MCA (figure 1D).

Figure 1

Case 1. (A) CT perfusion study shows increased time to peak suggesting acute ischemic infarct of the right middle cerebral artery (MCA) territory. (B) Axial non-contrast cranial CT scan demonstrating a small hyperdense signal (arrow) leading to suspicion of a thrombosed aneurysm. The area of hyperdensity measures 7.1 mm in diameter. (C) CT angiogram shows occlusion of the superior M2 division of the right MCA (arrow). (D) 3-D reconstruction of conventional digital subtraction angiogram shows an 8.6×5.2 mm, partially thrombosed aneurysm (arrow) of the right MCA bifurcation and partial filling of the distal branches. (E) Repeat conventional digital subtraction angiogram performed 2 months later demonstrates an 8.4×6.3 mm aneurysm (arrow) with complete recanalization and no intraluminal thrombus observed.

Treatment was started with a daily regimen of aspirin (325 mg) and atorvastatin (80 mg). Transesophageal echocardiography showed a small patent foramen ovale, but no right-to-left shunting was detected during a color-flow Doppler study. There was also no evidence of mural thrombus, valvular or intracardiac vegetations, or atrial fibrillation. The patient was discharged to home on the aforementioned medical regimen and was scheduled for delayed cerebral angiography. Repeat angiography 2 months later demonstrated the presence of an aneurysm, which measured 8.4×6.3 mm, at the anterior temporal branch of the right MCA. No intraluminal thrombus was observed at that time (figure 1E). The angiogram also demonstrated complete recanalization of the previously occluded MCA branches. An MRI study obtained around that time also failed to show thrombus within the aneurysm. On the basis of size, symptomatic nature, and after deliberation of the results of the International Study of Unruptured Intracranial Aneurysms (ISUIA 2),4 treatment was recommended. Given that the aneurysm was broad-based and appeared to incorporate the anterior temporal branch, it was felt to be unsuitable for coil embolization; and 4 months after the stroke, the patient underwent craniotomy for aneurysm clipping, which at that time showed the aneurysm, measuring approximately 1.5 cm in size.

Case 2

A patient in their mid-50s presented to the emergency room with left-sided hemiparesis and a left facial droop. The patient described experiencing a similar episode (albeit a transient one) of weakness 4 days earlier. Brain MRI revealed restricted diffusion in the right frontal lobe and right insula (figure 2A). MR angiography showed a right MCA aneurysm that was suggestive of an acute thrombus adjacent to or within the fundus of the aneurysm. A conventional angiogram was obtained to evaluate for acute thrombus related to this stroke distribution and confirmed the presence of a 4.5 mm, broad-based, right MCA aneurysm at the level of the MCA trifurcation (figure 2B). A cardiac investigation showed a normal left ventricular ejection fraction and no evidence of atrial septal defect, patent foramen ovale, or thrombus within the heart chambers. However, the patient was found to have an antithrombin III deficiency, which was treated with warfarin anticoagulation. The patient's aneurysm is being followed up non-invasively with CT angiography.

Figure 2

Case 2. (A) Acute ischemic stroke in the right middle cerebral artery (MCA) territory is seen on diffusion-weighted MRI. (B) Digital subtraction angiogram shows a broad-based aneurysm measuring 4.5 mm in diameter (arrow), at the level of the M1 trifurcation of the right MCA.

Case 3

A patient in their mid-50s presented with mild left-sided hemiparesis, dysarthria and facial droop. The initial imaging studies showed a right MCA perfusion deficit with increased time-to-peak (figure 3A) and a small 5 mm right MCA aneurysm with possible occlusion of the superior trunk. An infarct was seen in the right frontal operculum on MRI. Conventional angiography confirmed a 3.5×4.4 mm right MCA bifurcation aneurysm with a thrombus inside that was further extending into, and occluding, the superior trunk of the MCA (figure 3B). An evaluation to determine the cause of the patient's stroke symptoms, including echocardiography, cardiac monitoring, and investigation for hypercoagulability, was negative; and the cause was thought to be related to thrombus within the aneurysm (on the basis of the angiography results). The patient was managed with daily aspirin (325 mg) and discharged to home. The patient returned 2 weeks later for an uneventful right pterional craniotomy for aneurysm clipping as the aneurysm was not considered amenable to endovascular coiling and was subsequently discharged home, without complication.

Figure 3

Case 3. (A) Right middle cerebral artery (MCA) perfusion deficit with increased time to peak is seen on the initial CT perfusion study. (B) A small 3.5×4.4 mm right MCA bifurcation aneurysm with occlusion of the superior trunk (arrow) of the MCA is demonstrated on the subsequent angiographic study.

Discussion

There is no systematic review of the literature specifically describing small thrombosed aneurysms as a cause of acute ischemic stroke, and no recommendations currently exist for management of such aneurysms. Previous studies have attempted to determine the frequency and clinical characteristics of ischemic events associated with unruptured intracranial aneurysms which were mostly large and giant.3 5 However, these studies did not consider whether the presence of intraluminal thrombosis was associated with corresponding ischemic symptoms. The overall incidence of unruptured aneurysms in patients presenting with ischemic symptoms ranges from 3% to 6%.3 Giant aneurysms are known to undergo spontaneous thrombosis more frequently, possibly owing to more stagnant flow within the fundus of the aneurysm.6–8 Aneurysm thrombosis after subarachnoid hemorrhage has been reported with hypotension, vasospasm and local damage to the arterial wall, all described as potential risk factors.9

Friedman et al2 studied the characteristics of symptoms associated with unruptured intracranial aneurysms smaller than 10 mm in size. Partial or complete deficit of the third cranial nerve was the most common symptom in patients with incidentally found unruptured aneurysms, followed by cerebral ischemia and vision loss. Surgical treatment by aneurysm clipping was reported to be successful in preventing further ischemic episodes. However, patients with partially thrombosed aneurysms were excluded from this study. Another retrospective study of 463 patients with unruptured cerebral aneurysms found, on the basis of MRI data, 11 patients with acute ischemic changes in the corresponding symptomatic vascular territory.10 Partial thrombosis was present in five cases; interestingly, none of the aneurysms smaller than 10 mm in size showed evidence of intraluminal thrombosis. Therefore, although smaller aneurysms can be associated with ischemic events, direct neuroimaging evidence confirming the presence of intraluminal thrombus as a potential source of distal embolization is insufficient. A review of the English literature reveals a very limited number of cases showing small partially thrombosed aneurysms associated with clinical ischemic events.3 11 Such aneurysms range in size from 5 to 8 mm and are found at proximal MCA segments or intracranial internal carotid artery segments. These are the locations where large unruptured aneurysms associated with ischemic changes are found. Less common locations for unruptured large aneurysms include the superior cerebellar artery, the basilar artery and the paraophthalmic region. One report also describes a thrombosed lateral lenticulostriate aneurysm as a cause of stroke-related hemiparesis in a child.12

Unruptured cerebral aneurysms have also been linked to episodes of transient ischemic attack.1 13 14 The most common symptoms include homonymous hemianopia, weakness, numbness and dysarthria. Similarly, the proposed mechanism for such transient clinical transient events is thrombosis of the aneurysmal sac with subsequent embolization. The patient from our second case also initially experienced a transient ischemic event (left arm and leg weakness) that later was followed by a permanent left hemiparesis and right MCA stroke. This case suggests that small aneurysms can also present with transient symptoms and may serve as a source of emboli.

Different imaging modalities have varying degrees of sensitivity in their ability to detect a thrombus within the aneurysm lumen. Although in most cases intraluminal clots are well visualized by conventional angiography, occasionally the clot is not evident on a CT scan or a conventional angiogram and can only be detected with MRI.15 Specifically, new approaches such as gadolinium-enhanced high-resolution MRI and flow-suppressed MRI might prove to be more sensitive for detection of such cases, as these techniques have been shown to be more reliable and accurate in detection of extracranial carotid plaque disease and intraluminal thrombi.16 17 Therefore, all imaging studies should be carefully reviewed for evidence of intraluminal thrombus when unruptured aneurysms are discovered.

Medical and surgical management of aneurysms causing transient ischemic symptoms or stroke is mostly decided on an individual basis, taking into account the corresponding clinical symptoms, size of the ischemic core infarct volume and—most importantly—the results of a complete stroke investigation including cardiac and hypercoagulability evaluations, as well as investigation of possible intracranial and extracranial arterial stenoses. To reduce the risk of future ischemic events in such patients, antiplatelet therapy is the most commonly used medical treatment; it is thought to prevent the process of platelet aggregation inside the aneurysmal sac. Treatment with aspirin has led to a low incidence of recurrent ischemic events.3 After the initiation of antiplatelet therapy, one of our patients (case 1) had complete recanalization of distal vessels and disappearance of the intraluminal thrombus 2 months after the ischemic event, possibly suggesting the benefit of this therapy. In addition, treatment with a high-dose statin might have provided a further advantage in the achievement of complete recanalization. In a recent study of patients undergoing endovascular procedures for acute ischemic stroke, the group receiving statins had higher recanalization rates than the group who were not receiving such treatment.18 Warfarin anticoagulation therapy was chosen in our second patient, because a hypercoagulable state was thought to have contributed to the stroke. The third patient was treated with aspirin and craniotomy because the stroke investigation was negative and the aneurysm was located at the bifurcation of the occluded vessel, raising concern that the partially thrombosed aneurysm might be responsible.

Surgical treatment mostly involves aneurysmal clipping rather than coiling, because the parent vessel is intimately associated with the aneurysm in these cases and is in danger of inadvertent sacrifice or occlusion during the coiling procedure. The decision to perform microsurgical clipping was based primarily on anatomic features of the aneurysm and parent vessels. In addition, endovascular manipulation can cause further embolism by disturbing pre-existing thrombus inside the aneurysm sac—although this is not an absolute contraindication to coil embolization. In general, for partially thrombosed small aneurysms we use the same anatomic criteria to determine appropriate treatment as we would use for non-thrombosed aneurysms. However, we acknowledge that the cases we present were retrospective and included only two patients in whom a surgical clipping approach was chosen. Administration of clopidogrel and/or aspirin significantly lowers the risk of thromboembolic complications associated with coil embolization of unruptured intracranial aneurysms.19 20 Use of antiplatelet therapy might prove beneficial in endovascular treatment of small, partially thrombosed aneurysms.

A prospective study comparing surgical clipping with endovascular coiling would be the most accurate way to evaluate the two approaches and their limitations; unfortunately, given that cases of thrombosed aneurysms are rare, such a study might be difficult to carry out.

References

Footnotes

  • Competing interests MJB, ZD and MM have no financial conflicts of interest. EIL receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS), other research support (devices) and an honorarium from Boston Scientific and research support from Codman & Shurtleff, Inc and ev3/Covidien Vascular Therapies; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman & Shurtleff, Inc; serves as a consultant per project and/or per hour for Codman & Shurtleff, Inc, ev3/Covidien Vascular Therapies and TheraSyn Sensors, Inc; and receives fees for carotid stent training from Abbott Vascular and ev3/Covidien Vascular Therapies. EIL has no consulting salary agreements. All consulting is per project and/or per hour. AHS has received research grants from the National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1, Hemodynamic induction of pathologic remodeling leading to intracranial aneurysms) and the University at Buffalo (Research Development Award); holds financial interests in Hotspur, Intratech Medical, StimSox and Valor Medical; serves as a consultant to Codman & Shurtleff, Inc, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting and Penumbra; belongs to the speakers' bureaus of Codman & Shurtleff, Inc and Genentech; serves on an advisory board for Codman & Shurtleff; and has received honoraria from the American Association of Neurological Surgeons' courses, an Emergency Medicine Conference, Genentech, Neocure Group LLC and from Abbott Vascular and Codman &Shurtleff, Inc for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms. He has no consulting salary agreements. All consulting is per project and/or per hour.

  • Ethics approval Health Sciences Institutional Review Board, University at Buffalo, State University of New York.

  • Provenance and peer review Not commissioned; externally peer reviewed.