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Abstract
Background Cavernous carotid artery aneurysms (CCAs) represent a unique subset of intracranial aneurysms due to their distinct natural history and the anatomy of the cavernous sinus. Enlarging CCAs can cause elastic compression of the parent internal carotid artery (ICA). We suggest defining aneurysms that cause luminal stenosis of their parent vessels as ‘matricidal aneurysms.’
Though many patients are asymptomatic, presenting symptoms of CCAs include ophthalmoplegia with resulting diplopia, vision changes, pain, ptosis, facial numbness, and cavernous-carotid fistula. Less commonly, patients with CCAs can present with epistaxis, subarachnoid hemorrhage, and—in cases of matricidal aneurysms—ischemia due to stenosis. The proper management of stenosis caused by a matricidal CCA is not well established and may not be intuitive.
Methods We present a multicenter retrospective case series of patients with matricidal CCAs.
Results Forty patients with matricidal aneurysms presented with both asymptomatic and symptomatic stenosis. These patients were either treated with conservative medical management, coiling, flow diversion, or endovascular sacrifice of the parent artery. Planned treatment modalities were not executed in 11 cases (28% treatment failure rate). Presenting symptoms, patient outcomes, and follow-up data are presented for all cases.
Conclusion Matricidal aneurysms require careful consideration and planning. The restricted anatomy of the cavernous sinus can make successful execution of endovascular interventions more difficult. Direct elastic compression of the parent artery does not respond to angioplasty and stenting in the same way atherosclerotic stenosis does. Because of this, planning for the possibility of parent vessel sacrifice is important.
- aneurysm
- coil
- flow diverter
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Introduction
Cavernous carotid artery aneurysms (CCAs) represent 2%–13% of intracranial aneurysms but differ from other intracranial aneurysms in both their clinical presentation and natural history.1–4 CCAs are unique among intracranial aneurysms in that the location portends a more favorable natural history than those in subarachnoid locations. Patients with asymptomatic cavernous carotid aneurysms found incidentally will remain asymptomatic in 67% of cases at 4-year follow-up.5 CCA rupture risk increases with increasing aneurysm size: the 5-year rupture risk of asymptomatic CCAs 13mm–24 mm in size is 3%, and increases to 6.4% in asymptomatic CCAs>25 mm.1 6 Left untreated, the mortality rate for CCAs is less than that of subarachnoid aneurysms, but morbidity is variable.4 5 As such, CCAs have historically been left untreated until they manifest symptoms, such as cranial neuropathy or ischemic stroke due to acute thrombosis, mass effect, or bone erosion: outcomes after treatment are variable based on treatment modality.2 4 5 7
With the advent of flow diversion, it appears that treatment of CCAs is more common. CCAs often have a wide neck, making flow diversion a good treatment option.8 They are anatomically difficult to clip and surgery carries a high risk of morbidity.7 Flow diversion has the benefit of maintaining patency of the internal carotid artery (ICA), as does primary coiling or stent-assisted coiling.9 If flow diversion or coil embolization are not feasible, balloon test occlusion (BTO) of the ICA with cerebral monitoring can be performed to determine if parent artery sacrifice will be tolerated.7 Parent vessel sacrifice can be performed with or without bypass, depending on the results of the BTO.
It is possible for the growth of a CCA within the confines of the cavernous sinus to cause direct compression and stenosis of the parent artery. We define ‘matricidal’ aneurysms as aneurysms that cause stenosis of the ICA. Matricidal CCAs exert direct compression on the parent ICA that can result in ischemia—a less-often described symptom of this subclass of aneurysms. A study by Kupersmith et al demonstrated that this risk of ischemia (0.37% per patient year) is greater than the risk of subarachnoid hemorrhage in patients with CCAs.3 Matricidal aneurysms represent a small subset of CCAs and the proper treatment of these aneurysms is not clear. We explore the clinical presentation of patients with cavernous carotid aneurysms as it pertains to degree of carotid stenosis and symptoms on presentation. This relationship has not been previously well described. Following review of the treatments and outcomes of this group of patients, we will discuss the treatment options for patients with matricidal CCAs and identify special considerations that may be necessary.
Methods
We identified 40 patients with both symptomatic and asymptomatic matricidal cavernous carotid aneuryisms who presented to seven different institutions from 2005 to 2016. Patient identification and collection of follow-up data were performed retrospectively. The degree of carotid stenosis at presentation and treatment methodology for each patient were noted in all cases. Stenosis was defined by WASID criteria: stenosis >70%= severe; stenosis 50%–70%=moderate; and stenosis <50%= mild.10 As this was a retrospective study, there was no treatment protocol. Each case was managed as decided by the treating team at each respective institution. Stroke, cranial neuropathies of the cavernous sinus at presentation, and modified Rankin Scale (mRS) scores at follow-up were noted. Patient descriptive statistics and outcome data were analyzed.
Results
All patients’ presenting symptoms, treatment, follow-up, and outcomes are presented in table 1. The average age at presentation was 58 years' old; 85% of the patients were women; and one patient had bilateral CCAs. Stenosis of the cavernous segment of the ICA was measured in each patient and ranged from 8% to greater than 95% stenosis with an average of 45% stenosis. Five patients (12.5%) had severe stenosis, 12 (30%) had moderate stenosis, and 23 (57.5%) had mild stenosis at presentation.
All patients’ presenting, treatment, and follow-up data
Symptoms at presentation were recorded and are outlined in table 2. Within our population of patients with matricidal cavernous aneurysms, 75% had either ophthalmoplegia or diplopia on initial presentation. Headache or other pain was the second most common symptom occurring in 43% of patients. Less common were vision changes (18%), ptosis (13%), facial numbness (5%), and seizures (2.7%). Two patients presented with ischemic symptoms (5%) and two patients presented with aneurysmal rupture (5%). Three patients (7.5%) were initially asymptomatic with aneurysms discovered after motor vehicle accident (Case 8), screening MRI/magnetic resonance angiography (MRA) for family history of aneurysm (Case 15), and imaging ordered for an unrelated complaint of hearing loss (Case 6). Thirty-seven patients presented with mRS ≤2; two patients presented with mRS=3; and one patient presented with mRS >3.
Presenting symptoms and demographics by degree of stenosis
Thirty-nine of 40 patients had follow-up visits, and the average follow-up time was 19 months (range,<1–81 months). Three patients (7.5%) died; two other patients (5.4%) had worsening of mRS score; and eight patients (20%) had clinical signs of a stroke after their procedure, three of whom had confirmed stroke on post-procedural MRI. Thirty-five patients either maintained (n=19) or improved (n=17) pre-procedural mRS. Nine of these patients were completely asymptomatic (mRS=0) at the time of last follow-up. The patient with >95% stenosis (Case 1) presented with mild left-sided hemiparesis secondary to right brain ischemia, as well as diplopia. This was the only patient with a poor functional outcome related to the natural history of the aneurysm and resultant cavernous carotid stenosis.
Only one patient was managed medically at presentation by intention (Case 2). This patient had 85% stenosis and was on chronic anticoagulation for pulmonary embolus (PE). They were monitored for almost 2 years before being treated with flow diversion.
The remaining 39 patients received treatment at time of presentation with various combinations of flow diversion, coiling (unassisted, stent-assisted, or balloon-assisted), or sacrifice of the ICA (with or without bypass). Several illustrative cases are elaborated below, and the treatment details are summarized in table 3. Flow diversion was the most commonly attempted primary treatment (n=20) but failed six times (30%) with four of these patients receiving carotid sacrifice instead (Cases 10, 12, 32, and 33);.The fifth patient was managed conservatively (Case 26), and the sixth patient underwent successful flow diversion during a second attempt at a later date (Case 2). Of the 20 flow diversion cases, three were done with Surpass (Stryker, Kalamazoo, USA), one was a pseudo flow diversion with two overlapping Enterprise (Codman, Raynham, USA) stents, and the other 16 were Pipeline (Medtronic, Minneapolis, USA). Vessel sacrifice was chosen 12 times as the primary treatment, four of these with intended concomitant bypass. One of the 12 patients had a failed attempted bypass and was then treated with stent-coiling (Case 31). Another patient had a declining neurologic exam and never went to surgery (Case 1). Unassisted or balloon/stent-assisted coiling was the intended treatment seven times but failed twice, both resulting in parent vessel sacrifice (Cases 18 and 36) and representing a failure rate of 29%.
Intended treatments and outcomes
Five cases with severe stenosis
In total, five patients were identified with severe carotid stenosis from their matricidal aneurysms. Only one presented with ischemic symptoms. The others were also symptomatic on presentation with cranial neuropathies or subarachnoid hemorrhage. Three of the five patients maintained their presenting mRS following treatment and one died. These five cases are detailed below.
Case 1
This patient presented to the emergency department with left-sided weakness and double-vision from right ophthalmoparesis. The patient was found to have a partially thrombosed right-sided CCA causing >95% stenosis of the ICA on angiogram. After failing the nuclear medicine portion of a BTO, plans were made for parent vessel sacrifice with bypass. Before surgery could be performed, ischemic symptoms progressed rapidly to left hemiplegia with left-sided neglect from critical stenosis of the ICA. The patient was then managed conservatively with antiplatelet therapy (325 mg aspirin daily). The mRS score on presentation was 2 and was 4 at discharge because of the larger stroke burden. Symptoms persisted at last follow-up 44 months' ater. In this case it is thought that the presentation of symptomatic severe stenosis required more urgent treatment.
Case 2
This patient presented with ophthalmoparesis due to a partially thrombosed left CCA causing 85% stenosis of the ICA. The patient was on chronic anticoagulation at presentation due to a history of pulmonary emboli. They were continued on anticoagulation after aneurysm discovery and managed conservatively with close follow-up for 20 months. At that point, an MRI/MRA showed recanalization of the aneurysm and decreased stenosis from 85% to 60%, which was confirmed by angiogram. The patient then underwent flow diversion with a Pipeline stent, which was uncomplicated. In this case the patient had no ischemic symptoms. The aneurysm eventually partially recanalized with treatment for PEs and there was sufficient reduction in luminal stenosis to allow for safe treatment with flow diversion.
Case 3
This patient presented with a partial left sixth nerve palsy and double- vision and was found to have a left CCA causing 80% luminal stenosis of the parent ICA. They were treated with parent vessel sacrifice using coils, and symptoms remained stable after the procedure with no stroke related to the intervention. This patient was lost to long-term follow-up, but vessel sacrifice was noted to be successful during the peri-procedural observation period.
Case 4
This patient presented with right-sided ptosis and partial ophthalmoplegia and was found to have 80% ICA stenosis on angiogram due to a large right CCA. Flow diversion was chosen as treatment due to the lack of ischemic symptoms. The patient underwent flow diversion and required angioplasty of the flow diverter. They developed postoperative right hemisphere transient ischemia that resolved when blood pressure was increased. On post-op day 3, the patient developed anterior cerebral artery (ACA) ischemia and angiogram showed flow limitation with poor filling of that territory. This was treated with repeat angioplasty, resulting in improved filling of the ACA and continued significant (50%) residual stenosis of the ICA. The patient originally presented with an mRS score of 1, which was stable at 6-month follow-up, but symptom severity was improved with stable 50% stenosis of the parent vessel seen on imaging.
Case 5
This patient presented with a subarachnoid hemorrhage and mRS score of 5. The patient was found to have 75% stenosis of the right parent ICA from a matricidal aneurysm. The patient received the planned treatment of flow diversion using a Pipeline device and coils. The patient suffered a postoperative stroke and died 6 days following the procedure. We believe that the stenotic nature of the parent vessel contributed to the poor patient outcome.
Additional case of cerebral ischemia
Case 11
This patient presented with a disconjugate gaze due to partial third and sixth nerve palsies on the right side, mild right ptosis, and left facial droop. Angiogram revealed a right CCA aneurysm with 60% luminal stenosis. The patient was treated with two Surpass Flow Diverters and balloon angioplasty used to improve stent apposition. The patient remained stable at 1 month follow-up with mild symptoms and mRS score of 1.
Patients with increased disability after intervention
Five patients had worsening disability or died during the course of their follow-up (Cases 1, 5, 26, 29, and 32). Eight patients suffered clinical strokes or transient ischemic attack after their procedure, three of whom showed MRI evidence of stroke after treatment (Cases 1, 29, and 32), and two had clinical decline in mRS (Cases 1 and 32). The first patient with a decline in functional status (Case 1) was described previously and was the only patient with severe stenosis and symptomatic ischemia at presentation. The remaining three patients with neurologic decline are presented below. Case 5 was also mentioned above: this patient presented due to aneurysmal rupture with an mRS score of 5 and died within a week of the flow-diverting procedure.
Case 26
This patient presented with diplopia due to a large left CCA that caused 35% luminal stenosis of the ICA per angiogram. The patient had mRS score of 2 at presentation. A Pipeline flow diverter was attempted, but not successfully deployed, and repeat angiogram showed stable post-operative stenosis. The patient had no strokes seen on MRI after treatment but went on to develop a subdural hematoma and died (mRS=6) on post-operative day 20.
Case 29
This patient presented with left ophthalmoplegia due to a left CCA with an mRS score of 2. Angiography demonstrated 34% luminal stenosis of the parent ICA. The patient was treated with flow diversion and postoperative luminal stenosis was measured as 36%. Hemorrhagic stroke developed that occurred 12 hours' post-procedure. The patient died (mRS=6) 1 year later from complications of disability caused by the stroke.
Case 32
This patient presented with left ophthalmoplegia due to a large left CCA causing 22% parent artery stenosis. Imaging also revealed an asymptomatic right-sided CCA, as well as a MCA aneurysm. The patient underwent and passed balloon test occlusion with nuclear medicine assessment of perfusion with plans to treat the left CCA by Pipeline embolization. Pipeline was attempted but was unsuccessful and carotid sacrifice was performed instead. The patient developed a clinical stroke after the treatment due to a left middle cerebral artery occlusion. The stroke was caught acutely but could not be managed endovascularly in the setting of the carotid sacrifice. The patient was taken to the operating room for an open surgical MCA thrombectomy. The patient did have a stroke after treatment and had increased disability at 6-month follow-up with an mRS score of 4, which had worsened from an mRS score of 2 exhibited at presentation.
Discussion
Matricidal CCAs cause external compression on, and stenosis of, the ICA as they grow within the confines of the cavernous sinus (figure 1). Stenosis can be worsened with thrombosis of the aneurysm and, as Case 3 illustrates, may improve if the aneurysm recanalizes. The usual treatment options are available: coil embolization, stent-coiling, flow diversion, and vessel sacrifice/trapping with or without bypass. Of course, patients may also be managed conservatively. Whatever treatment is undertaken, it should be understood that the cavernous ICA stenosis seen in these patients is caused by the aneurysm via an external compression mechanism. It should therefore be expected to behave differently than more common atherosclerotic stenotic lesions typically seen in other locations in the neck and head.
This large cavernous carotid aneuryism is an example of a matricidal aneurysm. The size of the aneurysm itself, within the cavernous sinus, compresses the carotid artery externally and can potentially cause severe stenosis or occlusion. This external compression may not respond to intervention by flow diversion and angioplasty in the same way that we would expect from other types of stenosis.
Neurologic disability at presentation was generally mild: one patient presented with an mRS score of 5, two patients presented with an mRS score of 3, two patients presented with aneurysmal rupture, and all remaining patients presented with an mRS ≤2. Pain and diplopia can be disabling, but their disability is relatively mild compared with the potential disability caused by stroke and is an argument at least to consider conservative therapy for lesions that have not yet caused flow limitation. Neurologic decline was most commonly related to treatment with four treated patients having an mRS score at last follow-up of 4 or greater. One patient declined clinically after non-surgical management illustrating a natural history of flow limitation and ischemia.
Although flow diversion was the most commonly attempted single treatment (20 of 40 patients), it also failed six times, resulting in a failure rate of 30%. Similarly, coil embolization with or without stent assistance had a failure rate of 29%: five of the seven patients with treatment failures eventually underwent carotid sacrifice, emphasizing the importance of a balloon test occlusion prior to treatment. These are higher failure rates than are seen for the treatment of other intracranial aneurysms, representing yet another reason for caution in planning treatment for a matricidal cavernous aneurysm.11
The three patient mortalities all occurred after attempted Pipeline treatments. In one case we attribute the failure to the pathology—that is, the Pipeline was aborted, and the patient developed a subdural hematoma and died 20 days' later (Case 26). In the other two cases, the Pipeline treatment was technically successful, but the patients suffered strokes and died later due to complications of their disabilities—one patient died 6 days' later (Case 5) and the other patient within 1 year of treatment (Case 29). The preoperative stenosis was severe (75%) in the patient who died within a week and was mild (only 35% and 32%) in the two other patients, so it is difficult to say whether the matricidal nature of the aneurysm contributed directly to the outcome.
Of note, the three Surpass cases were technically successful as was the pseudo-flow diversion case with overlapping enterprise stents. Two of these Surpass cases were done in patients with moderate stenosis (Cases 11 and 15). The third had mild stenosis (Case 27) and at 2-year follow-up had worsened, but asymptomatic stenosis at the distal end of the stent with persistent (but reduced) aneurysm filling.
Several noteworthy points can be demonstrated from this case series. First, it is important to note that cavernous aneurysms can grow to cause direct elastic compression of the parent vessel. This is a rare cause of intracranial stenosis and has not been previously well described. Although external compression of the parent artery by an aneurysm can occur at any location, we have found this process to be most common in the cavernous carotid artery segment due to the tight confines of the cavernous sinus. Since the advent of flow diversion, it appears cavernous carotid aneurysms are being treated more frequently.
Most intracranial arterial stenosis is responsive to angioplasty and stenting, but direct aneurysmal compression is elastic and does not respond well to these maneuvers. Recognition of this elastic stenosis by the treating physician is critical in order to plan the appropriate treatment and to minimize potential morbidity and mortality. If the cause of stenosis is not recognized, there can be increased risks with treatment by flow diversion: further stenosis is likely caused by the added volume and collapse of the malleable flow diverting stent under the elastic recoil of the aneurysmal wall. In the setting of severe stenosis, particularly in patients presenting with ischemic symptoms, the implantation of a stent or flow diverter may not adequately address the pathology.
On the contrary, in some cases of severe stenosis, particularly in patients presenting with ischemic symptoms, the implantation of a stent or flow diverter may worsen the pathology by adding metal to the stenotic segment without relieving the flow restriction. It is important for treating physicians to note that patient outcomes after treatment are significantly worse in patients with severe stenosis. For this reason, we recommend balloon-test occlusion of any severe stenosis (>70%) prior to treatment. Parent vessel sacrifice is a reasonable treatment option and can still be employed to good effect in some cases.
There are several limitations to this study. The retrospective nature of the study means that treatment decisions are inherently biased. Only two patients were managed conservatively for any period of time, and only one of these two patients was conservative by intention-to-treat. Therefore, very little can be concluded about the natural history of this disease if left untreated. What we can conclude about the natural history of this disease must be gleaned from the presenting symptoms of this patient group. To our knowledge this is the first description of an uncommon pathology with a small number of patients. A larger patient population would be required for any statistical analysis and conclusions regarding superiority of a treatment option. This study is simply meant to illustrate trends seen in early analysis of the treatment of this pathology.
Conclusions
Matricidal aneurysms are rare among CCAs, which themselves occur infrequently. By definition, these aneurysms present with narrowing of the ICA, but it is uncommon that they present with ischemic symptoms. In our patient population, significant neurologic decline was more often secondary to treatment than to the natural history of the aneurysm with the caveat that natural history was not examined well in this study. Only one patient was followed without treatment, although treatment was initially planned (Case 1).
As incidental aneurysms are now found at increased rates with advanced neuroimaging, it becomes important to consider conservative management in patients with matricidal CCAs in comparison with subarachnoid aneurysms. For symptomatic patients, if treatment is undertaken, more consideration should be given to older techniques, such as vessel sacrifice with or without bypass. Treatment with flow diversion in these patients is problematic due to external compression of the carotid by the aneurysm. Pipeline embolization of these aneurysms may only improve the stenosis as the aneurysm remodels, and rates of flow diversion failure and significant thromboembolic complications appear to be higher in this population of aneurysms than in other intracranial aneurysms. Further study will be required in order to make conclusions on the best way to manage these aneurysms and to expand our understanding of the natural history.
Acknowledgments
The authors acknowledge assistance from the Endovascular Neurosurgery Research Group members. The authors also wish to thank Andrew J. Gienapp (Neuroscience Institute, Le Bonheur Children’s Hospital and Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN) for copy editing, preparation of the manuscript for publishing, and publication assistance.
References
Footnotes
Contributors All authors of this work met ICMJE criteria for authorship and made substantial contributions to the conception and design, acquisition of data, analysis and interpretation of data, drafting, critical revising, and final approval of this manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests CN is a consultant for Leica and has received research support from Microvention. BGW is a consultant for Stryker Neurovascular, serves as a proctor for Medtronic, and receives royalties from Peter Lazic, Inc. AJR is a consultant for Microvention. LJK serves as a consultant for Medtronic, receives grant support from the National Institutes of Health and the National Institute of Neurological Disorders and Stroke, and is a shareholder of Spi Surgical, Inc. MRL serves as a consultant for Medtronic and Minnetronix, Inc., receives unrestricted educational grants from Medtronic and Stryker, and is a shareholder of eLoupes, Inc. PK is a consultant for Medtronic and Stryker. ASA is a consultant for Leica, Medtronic, Microvention, Penumbra, Siemens, and Stryker; received research support from Microvention, Penumbra, and Siemens; received personal fees from Sequent; and is a shareholder in Cerebrotech and Synchron.
Ethics approval The University of Tennessee Health Science Center IRB, Memphis, TN # 18-05813-XM.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No other data are available for sharing.
Collaborators Adam Arthur, Bernard Bendock, Mandy Jo Binning, Alan S. Boulos, Richard Fessler, Lee Guterman, Ricardo Hanel, Daniel Hoit, L.Nelson Hopkins, III, Jay Howington, Robert James, Peter Kan, Alex A Khalessi, Louis Kim, David Langer, Giuseppe Lanzino, Elad Levy, Demetrius Lopes, William Mack, Robert Mericle, J Mocco, Aditya Pandey, Robert Replogle, Howard Riina, Andrew J Ringer, Rafael Rodriguez, Eric Saugaveau, Clemens Schirmer, Adnan Siddiqui, Rabih Tawk, Raymond Turner, Erol Veznedaroglu, Babu Welch, Jonathan White.
Patient consent for publication Not required.