Endovascular management of giant aneurysms: An introspection
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.156278
Source of Support: None, Conflict of Interest: None
Aims: To evaluate the outcome of giant intra-dural aneurysms managed with endovascular techniques.
Keywords: Endovascular treatment; follow-up; giant aneurysms; untreated
Giant aneurysms have a diameter that exceeds 2.5 cm. , Their natural history, when left untreated, is quite dismal. , In a prospective study, Drake et al.  reported that 15 of the 18 patients with untreated giant aneurysms died or experienced severe morbidity as a direct result of complications caused by the aneurysm. Until recently, very few large series had focused on comparing the outcome in patients who were treated for their giant intra-dural aneurysms versus those in whom the aneurysm was left untreated , The goal of the present study is to investigate the risk factors and outcome of giant intra-dural aneurysms who were either treated with endovascular techniques or left untreated.
A total of 39 consecutive patients with a giant intra-dural aneurysm were enrolled between January 2006 and March 2012 at our center. All patients underwent a cerebral digital subtraction angiography with balloon occlusion test (BOT). Tolerance to test occlusion was assessed by a detailed neurologic examination consisting of evaluation of cranial nerve function, muscle strength and language ability every 5 min or when a deficit was perceived. If the patient tolerated 20 min of normal tension, the balloon was deflated for 10 min and then the test was repeated under hypotension for another 20 min. Hypotension was induced by the infusion of sodium nitroprusside (2.5-7.5 mg/kg body weight/min). After the mean arterial pressure was reduced to two-thirds of the baseline, hypotension was maintained for 20 min provided that the mean arterial blood pressure was not less than 55 mmHg. If the patient tolerated BOT under hypotension, he/she was considered clinically able to tolerate parent vessel occlusion (PVO). The test was terminated immediately if any neurologic deficit developed during test occlusion under normotensive or hypotensive conditions. Patients who could tolerate the BOT were treated by PVO, and those who could not tolerate the BOT were treated using a stent/coil.
When the use of a stent was planned, the patients were pre-medicated with anti-platelet therapy consisting of aspirin 100 mg and clopidogrel 75 mg for 3 days before the procedure. After the procedure, clopidogrel (75 mg/day) was recommended for an additional 30 days and aspirin (100 mg/day) was recommended for 6 months. After the PVO, the patients were treated with hypervolemia.
Results and outcome evaluation
The degree of the aneurysmal occlusion was classified as complete obliteration, neck remnant or incomplete occlusion. The length of the angiographic follow-up period was 9.3 ± 10.5 months (range, 3-39 months). The clinical follow-up (6-71 months, 28.2 ± 18.1 months) was assessed by the Modified Rankin Scale (mRS) scores at the last follow up visit or by a telephone call.
Logistic regression analysis was performed to evaluate the association between sex, age (younger than 60 years vs. 60 years and older), clinical presentation, aneurysmal size (<35 mm vs. ≥35 mm), and the treatment given. The significance level was set at 0.05.
There were 15 women (38.5%) and 24 men (61.5%), with a mean age of 44.7 years (range: 9-68 years). Six (15.4%) patients presented with subarachnoid hemorrhage (SAH), and 21 (53.8%) with headache or neurologic deficits due to the mass effect of the aneurysm, 11 (28.2%) presented with ischemia and in one (2.6%) patient, the aneurysm was detected incidentally. The size of the aneurysm ranged from 25 to 50 mm (mean 30.1 ± 6.6 mm). Thirteen aneurysms involved the paraclinoid segment of the internal carotid artery (ICA), three involved the middle cerebral artery (MCA) and 23 involved the vertebrobasilar circulation. Nine patients refused endovascular or surgical treatment [Table 1].
Thirty aneurysms were treated with endovascular methods. Eleven aneurysms were treated by PVO (eight with coils, two with balloons, one with balloon and coils), 11 aneurysms by stent-assisted coiling, 1 aneurysm with coils, six aneurysms with stent only, and one aneurysm with coils and onyx [Table 2].
Among the 30 patients with a giant intradural aneurysm treated using the endovascular technique, the initial post-procedural angiogram revealed complete occlusion, aneurysmal neck remnant and, incomplete occlusion in 15 (50.0%), 3 (10.0%) and 12 (40.0%) patients, respectively. In the 12 patients with an anterior circulation aneurysm, an immediate angiogram demonstrated complete aneurysmal occlusion, aneurysmal neck remnant and incomplete occlusion in 50.0% (n = 6), 16.7% (n = 2) and 33.3% (n = 4) patients, respectively; among the 18 patients treated for posterior circulation aneurysms, the angiography demonstrated complete aneurysmal occlusion, aneurysmal neck remnant and incomplete occlusion in 50.0% (n = 9), 5.5% (n = 1) and 44.4% (n = 8) patients, respectively [Figure 1] and [Figure 2]. The post-procedural aneurysmal hemorrhage occurred in eight patients. This included four anterior and four posterior circulation aneurysms, resulting in a 30-day mortality of 23.3% (n = 7) and morbidity of 3.3% (n = 1). Six of them occurred in patients who had an incomplete (5 with an incomplete aneurysmal occlusion and one with a neck remnant) aneurysmal occlusion, who were on anti-platelet medication after they had undergone a stent-assisted treatment. Two giant vertebral artery aneurysms with presumed complete occlusion by PVO eventually experienced a SAH. Seventy-five percent of the post-procedural aneurysmal hemorrhage (four posterior and two anterior circulation) occurred within 2 weeks following the procedure.
Ten patients refused to get a check angiogram repeated at follow-up visits; seven patients died of post-procedural hemorrhage in the subsequent two weeks following the procedure. An angiographic follow-up was available in 13 (43.3%) patients who had undergone endovascular management. The follow-up angiogram (DSA) revealed recanalization in five (38.5%) patients within 9.3 ± 10.5 months after treatment. Four of these aneurysms were retreated.
Of those nine untreated giant intra-dural aneurysms, four patients died (44.4%). Two of them had SAH and two others, ischemic complications associated with vertebral and basilar artery aneurysms. The symptoms worsened in two patients (22.2%) and remained unchanged in 3 (33.3%; mean 30.2 ± 26.2 months). The follow-up (mean 28.2 ± 18.1 months) examination of the 12 anterior circulation aneurysms managed with endovascular techniques revealed that the symptoms resolved in five (41.7%), improved in three (25.0%) and worsened in one (8.3%) patient, and three (25.0%) patients died [aneurysmal hemorrhage due to incomplete aneurysm occlusion occurred in four patients and resulted in a mortality in 25% (n = 3) and morbidity in 8.3% (n = 1)]. A good clinical outcome (mRS 0-1) was observed in eight (66.7%) patients. Among the 18 posterior circulation aneurysms who underwent endovascular treatment, the symptoms resolved in six (33.3%) patients, improved in seven (38.9%) patients, and worsened because of mass effect in one (5.6%) patient. Four patients died of post-procedural hemorrhage (22.2%). A good clinical outcome (mRS 0-1) was observed in nine (50.0%) patients. The overall mortality and morbidity figures of the 30 patients in the endovascular group were 23.3% (n = 7) and 6.7% (n = 2), respectively.
The patient's sex, presentation, size (≥25 mm vs. ≥35 mm) and age did not significantly correlate with worsening symptoms. The patients who were not treated with an endovascular procedure had a significantly poorer outcome than those who were treated (P = 0.045). There was no significant difference in the final outcome between anterior and posterior circulation aneurysms (P = 0.746) or, whether or not the parent vessels was occluded (P = 0.271) with endovascular treatment.
In this study, we found an overall mortality of 44.4% and morbidity of 22.2% in the group of untreated giant intra-dural aneurysms; and, a mortality of 23.3% and a morbidity of 6.7% in patients undergoing endovascular treatment. Babak et al.  have found that endovascular treatment of giant aneurysms carries an overall mortality of 29% and a morbidity of 26%, for a cumulative morbidity and mortality of 55% over 24.8 months of clinical follow-up (the series included seven cavernous segment aneurysms). The reason for the greater morbidity and mortality in their series as compared to ours was perhaps due to the greater number of ruptured aneurysms (10 of their 39 cases) when compared to our treated patients (only three ruptured aneurysms). It is well established that patients with unruptured aneurysms usually have a better outcome and lower mortality. Ha  treated nine cases of giant intra-cranial aneurysms with endovascular methods; six (67%) of the nine patients had a near-complete occlusion as evidenced on the post-operative angiogram (at a mean duration of 13.5 months after the procedure). They believed that endovascular treatment could be an alternative option for managing giant aneurysms and may also serve as an adjuvant to surgical intervention. Our patients had comparable results with 60% of our patients achieving 95% or higher occlusion rates. In the study by Dumont et al.  there were eight mortalities among 26 patients of giant aneurysms treated with endovascular techniques (31%). Their mortality and morbidity statistics were comparable to our results. Chalouhi et al.  coiled 334 large or giant aneurysms with only one mortality and 10.5% morbidity. Contrary to our results, they concluded that stent-assisted coiling has a a lower recurrence rate, lesser requirement for retreatment and lesser re-hemorrhage rates with no additional morbidity when compared with the conventional coiling technique [Table 3].
PVO is a curative modality for patients who can tolerate it. ,,, For giant aneurysms close to the circle of Willis, a careful evaluation of the cross flow and a pre-procedural BOT are important steps that need to be undertaken in order to detect and prevent hypoperfusion by PVO. ,, The complications of PVO include early or late stroke and "de novo" aneurysm formation at a distant site because of hemodynamic changes in the circle of Willis. ,, Occasionally, patients with sufficient collateral circulation from the anterior circulation via the posterior communicating artery can tolerate PVO of the bilateral vertebral arteries or the basilar artery.  In the present study, two giant dissecting aneurysms of MCA, at a distance from the circle of Willis, were treated by PVO. The aneurysms were completely obliterated without any complication due to the presence of a good collateral circulation. Two of the 11 patients treated by PVO had a bad outcome. Among the 19 patients in whom the aneurysm was coiled or underwent a stent assisted coiling with parent vessel preservation, seven of the patients had a bad outcome. There were also 12 patients in whom the endovascular treatment failed to completely occlude the aneurysm. It is likely that the morbidity rate will rise with further follow-up as the aneurysm is still "active." PVO, in a patient who has tolerated a proper BOT, is a safe and effective way of curing these lesions.
In our patient group, of the 18 patients with 95% or greater occluded aneurysms, three developed a SAH. Our data suggests that there is a 16.7% risk of SAH for even those aneurysms that may have been occluded to 95% or greater degree. This may be due to the perfusion of blood within the thin walled aneurysmal sac even when the aneurysm appears completely occluded and the initial or follow-up angiography shows almost complete occlusion. , No fresh ischemic stroke or the development of new aneurysms were detected in any of our patients.
Recently, flow diversion and endoluminal reconstruction with devices like pipeline and silk stent have been used to exclude the aneurysm from the circulation. ,,, Although the initial published results indicate a generally favorable risk-benefit profile for flow diverters, early and delayed complications such as ipsilateral intra-parenchymal hemorrhage and in-stent thrombosis have often been reported. ,, The major complications associated with flow diverters are perforator artery stroke, aneurysm re-rupture and in-stent stenosis and thrombosis. ,
Using silk flow diverters, complete occlusion of the aneurysm was observed in 81.8% aneurysms, and ischemic complications and parent artery occlusion occurred in 10% of patients, respectively. The aneurysmal rupture rate was 3.5% and the cumulative mortality was 4.9%.  For the pipeline embolization device, the aneurysm occlusion rate was 79.7%, the cumulative mortality rate was 2.3%, the stroke rate was 1.9%, the transient ischemic attack rate was 2.0% and the rate of intra-cranial hemorrhage was 2.3%.  The long-term outcome still needs to be evaluated.
Surgical options should also be considered for these aneurysms. A high flow extra-cranial-intra-cranial bypass with trapping is a good option in selected patients. Yashar et al.  describe a consecutive series of 54 patients with 56 aneurysms requiring cerebral revascularization. Forty-five patients (81.8%) had a good outcome (Glasgow Outcome Scale 4 or 5) and there were seven cases of mortality (12.7%) and an additional nine cases of morbidity (15.8%).
Tim et al.  retrospectively identified 184 aneurysms measuring 20 mm or larger (85 very large, 99 giant) treated with surgical and endovascular therapy, and their results suggest that patients with a poor functional status, giant aneurysms and aneurysms in the posterior circulation had a significantly higher proportion of poor outcome at follow-up.
Giant intra-dural aneurysms may often have a poor clinical outcome. Endovascular treatment of these lesions have relatively better results than the results obtained following their conservative management. However, the treatment is associated with high complication rates and a low chance of cure. Hopefully, better endovascular technologies combined with surgical strategies will provide better outcomes.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]