Clinical and Angiographic Follow-up of Ruptured Intracranial Aneurysms Treated with Endovascular Embolization

Materials and Methods

The Toronto Western Hospital maintains a prospective data base where clinical, radiologic, and therapeutic information on intracranial aneurysms are collected. A retrospective review was performed to obtain clinical and angiographic data on all consecutive patients who presented to our institution with subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm and were successfully treated by coiling between May 1994 and April 2008. All patients with aneurysmal SAH in whom endovascular treatment was completed were included. Data base records were checked for accuracy in electronic and/or paper charts. Follow-up information was obtained from chart notes dictated at our multidisciplinary clinic.

This study encompasses 3 different populations of coiled aneurysms, reflecting changes in our practice with time. Initially, endovascular treatment was performed if surgery was considered too dangerous. Then, during the ISAT trial, case patients were randomly assigned to coiling or clipping, and patients not participating in the trial were treated after a multidisciplinary conference involving the cerebrovascular neurosurgeon and the endovascular therapist. After the ISAT results, endovascular treatment became our first choice for suitable aneurysms. Failed coiling attempts (no coil placed in the aneurysmal sac) and planned parent vessel occlusions were excluded. The influence of age, sex, aneurysm size (< 5 mm, 5–15 mm, 15–25 mm, > 25 mm) and location, and initial angiographic result (complete, neck remnant, and body remnant) with intraprocedural complications, aneurysmal recanalization, need to re-treat, and rebleeding were analyzed with use of the χ² test, the t test, and the Fisher Exact test (significance defined as a P value < .05). The SAS System version 9.1.3 (SAS Institute, Cary, NC) was used for all analyses. A similar analysis was performed in a subgroup of patients (n = 153) with more than 11 months of follow-up to evaluate the long-term results.

Results

For the analysis, we divided our cohort into 2 equal groups, each containing a similar number of patients. The first half of our cohort was treated between May 1994 and June 2004 and the second half, between June 2004 and April 2008. In this study, we refer to group 1 as the group of patients treated before June 2004 and group 2 as those treated after June 2004. From 1994 to 2008, endovascular treatment was attempted in 411 patients (453 aneurysms) who presented with ruptured intracranial aneurysms. Twelve patients had 2 aneurysms coiled at the time of rupture, and 1 patient had 3 aneurysms coiled. Treatment was not possible in 34 cases (8.3%) that were excluded from this analysis. Twenty-five failed attempts occurred before June 2004 (12.1%), and 9 (4.4%) occurred after June 2004. A total of 391 aneurysms were treated in 377 patients early after the rupture. Patient characteristics are shown in Table 1 and aneurysm locations in Table 2.

Outcome at discharge of 377 patients is shown in Table 3. Good outcome (GOS, 5) was achieved in 278 patients (74%). Sixty-six patients (18%) had moderate disability or a poor clinical outcome, and 33 patients (8.8%) died. In good-grade patients (Hunt-Hess I–III), 247 (83%) had a GOS of 5 and 16 (5.3%) died, whereas in poor-grade patients (Hunt-Hess IV and V), good outcome or moderate disability (GOS 4 and 5) was achieved in only 44 (56%) and 17 (22%) died.

There were 53 significant procedural complications in 45 patients (12%; Table 4) that resulted in a poor outcome or death in 11 patients (2.9%). Four of these 11 patients had aneurysm perforations, and 5 had a parent-vessel occlusion or distal emboli. An internal carotid dissection occurred in 1 patient, and mass effect from the coil mass causing a permanent third cranial nerve palsy occurred in another. One patient had a rupture of the basilar artery during a balloon-assisted coiling procedure. In the entire cohort, aneurysm perforation occurred in 23 patients (6.1%). There were 16 aneurysm perforations (8.5%) in group 1 and 7 (3.7%) in group 2. Aneurysm perforation resulted in transient morbidity or no deficit in 19 (82.6%) of 23 patients, permanent morbidity in 1 patient, and death in 3 patients (4 poor outcomes of 23 [17.3%]). Parent-vessel occlusions and/or distal emboli occurred in 22 (5.8%) of all patients: 16 patients (8.5%) in group 1, and 6 patients (3.2%) in group 2. Thromboembolic complications resulted in transient morbidity or no deficit in 17 (77.3%) of 22 patients, permanent morbidity in 4 (18.2%), and death in 1 (4.5%). This patient who died had an associated aneurysm perforation.

Abciximab (ReoPro; Eli Lilly, Indianapolis, Ind) was used in 27 patients for thrombus formation at or near the parent vessel/coil interface. Since August 2002, abciximab has been used in 27 (11%) of 237 patients. The drug was either given intravenously as a bolus (25 μg/kg) or intra-arterially at a lower dose (4–12 mg titrated to response) through a microcatheter near the intraluminal clot. Our current protocol is to use the full, single intravenous dose, and in only a few cases did we give the 12-hour intravenous infusion following the initial intravenous or intra-arterial bolus. Most patients (25/27) had no neurologic deficits related to thromboembolic complications. One patient experienced permanent neurologic sequelae from the distal emboli, and another had a second hemorrhage from the aneurysm the following day and was re-treated with surgical clipping. Technical complications without clinical significance occurred in 8 patients: coil herniation into the parent vessel in 4 patients, coil stretching in 2 patients, stent inadvertently deployed proximal to the aneurysm in 1 patient, and traumatic catheterization of the urethra in 1 patient.

Complete follow-up was achieved in 292 (85% of surviving) patients. GOS at last follow-up is shown in Table 5. The average interval between treatment and the last follow-up was 22.3 months (range, 20 days to 119.8 months). Additional treatment was required in 31 patients (11%). Eleven (3.7%) were re-treated with surgical clipping and 21 (7.1%) underwent additional embolization, with 5 requiring a third embolization. One patient was initially re-treated with coils and subsequent clipping. At their last clinical examination, 245 patients (84%) had no clinical deficits. Rehemorrhage after coiling occurred in 8 patients (2.1%). Six patients had an early rehemorrhage, defined as less than 30 days’ postcoiling (5 within 48 hours of treatment). Outcomes of rehemorrhages were poor (Table 6). Four of the patients who had rebleeding were in group 1, and 3 patients who had rebleeding were in group 2. Complete occlusion at the time of coiling was achieved in 2 of the 6 aneurysms that re-bled early. One patient treated with a combination of Matrix and bare platinum coils had rebleeding at 5.5 months. The rebleeding rate with Matrix (2.8%) was similar to the overall results. There was no rebleeding in patients treated with HydroCoil or a combination of HydroCoil and bare platinum.

A total of 166 subjects had follow-up durations longer than 11 months. Information on 153 patients was used to analyze which factors were associated with aneurysm recanalization and the need for re-treatment (13 patients were excluded because of unavailable information regarding aneurysm recanalization). The presence of a body remnant after coiling was significantly related to aneurysm recanalization (P < .0001) and with the need for re-treatment (P = .0433). The very small number of rebleedings (2 in this subgroup) did not allow for any statistical correlation.

Discussion

The primary goal of treatment of a ruptured aneurysm is to prevent rehemorrhage. However, rehemorrhage after treatment is still an issue. The ISAT trial demonstrated an overall rehemorrhage rate of 4.9%, with an incidence of rebleeding after surgical clipping of 1.2%.¹ Rebleeding risk after surgical clipping has been reported to be low, varying from 1.9% to 3.2%, higher with incomplete sac occlusion.^22–25 Recanalization is a known issue with endovascular treatment, but its impact on rebleeding rates is not completely clarified. Despite recanalization rates as high as 38%, reports on the incidence of rebleeding after coiling vary.^26–30 In our study, the overall incidence of rehemorrhage was 2.1%, with time until rebleeding ranging from 0 days to 118.6 months (almost 10 years). Six of the 8 patients had a subsequent hemorrhage within 30 days of treatment, 5 within 48 hours. We found a risk for rebleeding of 1.6% during the first 30 days after coiling, decreasing to 0.7% after that. There were 2 episodes of late rebleeding, 1 almost 10 years after treatment, the longest interval between treatment and rebleeding after endovascular embolization reported so far.^4,9,11 The second rebleed occurred less than 6 months from treatment. This latter rebleed led to changes in our practice regarding follow-up imaging. Ruptured aneurysms treated with coiling are now imaged with MRA before discharge, at 2 to 3 months and then 6 months after treatment for assessment of early recanalization. Follow-up imaging is then performed yearly or every other year, depending on the presence of a remnant.

Outcome after rehemorrhage was poor, with a 62.5% mortality rate, concurrent with another series reporting high mortality rates after early rerupture.^4,8 It is interesting to note that rebleeding rates were not different in completely occluded aneurysms compared with aneurysms with neck or body remnant (χ², 1.135; P = .28), a result supported by others. Rebleeding occurred after complete occlusion in 2 patients, a neck remnant in 4, and a body remnant in 2. Sluzewski et al²⁸ also found no significant difference in the risk for rehemorrhage between complete and incomplete occlusion, with 4 of 6 early (< 30 days) reruptures occurring after complete occlusion of the aneurysm. Different results were shown by investigators in the Cerebral Aneurysm Rerupture After Treatment study on predictors of rehemorrhage after treatment of ruptured intracranial aneurysms, who found the degree of aneurysm occlusion to be highly predictive of the risk for rerupture, which increased progressively as the packing attenuation decreased.²⁷ Accordingly, there was no difference in the re-treatment rates of aneurysms with neck remnant (9.4%) compared with completely occluded (6.7%) aneurysms (χ², 0.776; P = .38). As expected, aneurysms with a body remnant at the end of the coiling were re-treated more often (24% re-treatment rate) than lesions completely occluded or left with a neck remnant (χ², 5.959; P = .0146). In ruptured aneurysms, we no longer strive for complete occlusion in every case because those with a neck remnant have a similar natural history as those that are completely occluded. We do not struggle for a perfect angiographic result because the complication rate may increase with attempts to achieve the ideal picture.

Periprocedural complications occurred in 12% of our patients, with permanent morbidity or mortality rate related to the procedure in 2.9%, a complication rate similar to other studies. Our permanent morbidity and mortality rates were lower than other single-center studies on ruptured aneurysms.^3,18,30–33 This may reflect our conservative strategy regarding the immediate angiographic result. The most common procedural complication was intraprocedural rupture (6.1%). This rate is similar to that of reports in the literature.^11,18,32,34 In our cohort, a small size (defined as an aneurysm sac smaller than 5 mm) had no influence in the rate of intraprocedural rupture. The risk for intraprocedural perforation was 7.6% for aneurysms less than 5 mm and 5.0% for aneurysms more than 5 mm (χ², 0.715; P = .3979). Other authors have demonstrated an increased risk for perforation in small aneurysms. Nguyen et al³⁵ recently demonstrated that the risk for rupture increases from 2.3% for aneurysms more than 3 mm to 11.7% for those less than 3 mm. Our size categorization was arbitrary, and the cutoff value for small aneurysms was at 5 mm. The results may have been different if very small lesions (< 3 mm in size) were analyzed separately.

Thromboembolic complications occurred in 5.8% of all patients and were more frequent in the first half of our experience (8.5% of patients in group 1 and 3.2% of patients in group 2 [χ², 3.859; P = .0495]). A major difference between the 2 groups is the introduction of abciximab (ReoPro) during endovascular procedures after 2004. Abciximab, a monoclonal antibody glycoprotein IIa/IIIb inhibitor, has shown to be very effective in the treatment of acute thromboembolic complications during endovascular procedures.³⁶ We used abciximab (intravenously or intra-arterially) in 27 patients when thrombus was evident during the procedure, and there were no symptomatic thromboembolic events in 93% of these patients. One patient had an ischemic stroke in the motor cortex, and another had a subsequent hemorrhage from the treated aneurysm the following day and underwent craniotomy and clipping. Intracerebral hemorrhages have been described with abciximab use.³⁷

Imaging follow-up (MRA and/or conventional angiography) was achieved in 70.5% of the treated aneurysms, and similar to other studies, our recanalization rate was 20.2%.^4,5,7,11,18 Recanalization occurred regardless of the initial angiographic result, but as expected, the risk was higher if a body remnant was left (χ², 11.791; P = .0006). Grunwald et al⁷ demonstrated that only 12.7% of completely occluded aneurysms recanalized compared with 40% of those with initial 80% to 95% occlusion, and Raymond et al¹¹ demonstrated recanalization rates of 20.0% in completely occluded aneurysms vs 40.1% recanalization of aneurysms with neck remnants and 51.1% recanalization of aneurysms with body remnants. This difference, however, was significant only in the short term. In our study, the interval between treatment and recanalization was similar for patients with initial neck and body remnants (average, 6.6 months) but slightly longer for completely occluded aneurysms (average, 9.6 months), suggesting that recanalization occurs after complete occlusion, but at a slower pace. Recanalization of a completely occluded aneurysm was detected up to 46 months after treatment.

The overall incidence of complications, including failed attempts and recanalization (Table 7), decreased from 14.8% in group 1 compared with 6.9% in group 2 (χ², 4.825; P = .0280). This may be attributed to the learning curve of the endovascular therapists, higher volumes of patients in group 2, technical advances, and the use of abciximab. The number of patients is the same in both groups, though group 1 encompasses 10 years and group 2, only 4 years. This finding is in agreement with that of other studies demonstrating the benefit of surgical treatment of intracranial aneurysms in high-volume centers.³⁸ Multisection CTA with 3D reconstructions; rotational angiography with high-quality images; and availability of better microcatheters, coils, stents, and balloons are likely to have had a positive influence in our results.

Conclusions

Long-term clinical and angiographic follow-up after coiling of ruptured aneurysms confirms its efficacy as a primary treatment technique. Rebleeding rates after treatment are low, but recanalization remains an issue, even in aneurysms that are initially completely occluded. Long-term imaging follow-up is advised. Initial angiographic appearance is not a good predictor of rehemorrhage, recanalization, and long-term outcome.