Endovascular Therapy of 500 Small Asymptomatic Unruptured Intracranial Aneurysms

Natural Course of Small Asymptomatic UIAs

The ISUIA study group investigators¹ reported the results of a large retrospective multicenter study regarding the natural history of UIAs in 1449 patients with 1937 UIAs. They suggested that the rupture rates of aneurysms measuring <10 mm, 10–25 mm, and ≥25 mm in patients with no history of SAH were 0.05%, approximately 1%, and 6%, respectively; they concluded that small asymptomatic UIAs with no history of SAH have a benign natural course and a low risk of bleeding when left untreated. Furthermore, the ISUIA investigators² reported that 5-year cumulative rupture rates of aneurysms measuring <7 mm were 0% in the ICA, AcomA, ACA, or MCA and 2.5% in the posterior circulation or the PcomA. However, the limitations of the study included its retrospective nature, the short follow-up period, and a registration bias.

There are 2 articles in the literature on the rupture risk of UIAs in the Japanese population. Ishibashi et al¹¹ reported the rupture risk in 419 patients with 529 UIAs with a mean follow-up duration of 905.3 days. The aneurysm size, history of SAH, and location in the posterior circulation were significant risk factors. The aneurysmal rupture rates according to aneurysm size were 0.8% in small (<4.9 mm), 1.2% in medium (<9.9 mm), 7.1% in large (>10 mm), and 43.1% in giant (>25 mm) aneurysms. Sonobe et al³ reported the aneurysmal rupture rate of small (<5 mm) asymptomatic UIAs. In their report, 448 aneurysms in 374 patients were prospectively analyzed with the mean follow-up period of 41.0 months. The average aneurysmal rupture rates were 0.54% overall, 0.34% for single aneurysms, and 0.95% for multiple aneurysms.

Comparison between Surgical Clipping and Endovascular Therapy

An aggregate analysis of the literature by Lee et al¹² in 2005 showed that the cumulative adverse outcome rates for endovascular therapy and surgical clipping of UIAs were 8.8% and 17.8%, respectively. Alshekhlee et al¹³ studied the difference of hospital mortality rates between surgical clipping and endovascular therapy of UIAs from the National Inpatient Sample data base for the years 2000 thorough 2006 in US hospitals. They found that endovascular therapy was associated with low hospital mortality rates (0.57%) compared with surgical clipping (1.6%). According to the literature, the morbidity and mortality of endovascular therapy seem to be lower than those of surgical clipping. However, a true comparison between the risks of endovascular therapy and surgical clipping is difficult because of the differences in the characteristics of patients and aneurysms. Furthermore, the various physicians' technical skills and the degree of development of endovascular devices could not be evaluated objectively. To our knowledge, there are no reports directly comparing surgical clipping and endovascular therapy of small asymptomatic UIAs.

Technical Complications

Im et al⁴ reported results of endovascular therapy in 435 small asymptomatic UIAs. There were a total of 44 procedure-related complications (10.1%): 24 thromboembolisms, 11 coil protrusions or herniations into the parent vessel, 4 intraprocedural aneurysmal ruptures, 3 device-related complications, and 2 femoral-access complications. In the ATENA study¹⁴ of a large volume of patients with 739 UIAs and 700 procedures conducted at 27 Canadian and French neurointerventional centers, the rates of thromboembolic events and intraprocedural aneurysmal rupture were 7.1% and 2.6%, respectively. Standhardt et al¹⁵ reported 10.9% of thromboembolic events in 173 patients with UIAs treated by endovascular therapy. Five patients (3%) in their study had strokes, including major and minor deficits (0.5% and 2.5%, respectively).

Although the risk of thromboembolic events was low in the small UIAs (1–6 mm) in the ATENA study,¹⁴ the occurrence of thromboembolic complications was not significant regarding location, aneurysm size, or embolization technique. In our series, thromboembolic complications detected by CT as the main technique occurred in 3.8%. Only the D/N ratio of <1.5 was a significant risk factor of thromboembolic complications.

In the ATENA study,¹⁴ intraprocedural aneurysmal rupture was observed in 18 patients (2.6%). Among those 18 patients, 5 manifested a permanent clinical aggravation, and 3 patients died. Gonzalez et al¹⁶ reported 3 intraprocedural aneurysmal ruptures (1.4%) in 247 UIAs, and 1 patient died. In our series, intraprocedural aneurysmal rupture occurred in 7 aneurysms (1.4%). All of the patients who had an intraprocedural aneurysmal rupture were discharged without any neurologic deficits. There have been a few reports that endovascular therapy of very small intracranial aneurysms (≤3 mm) has a high risk of intraprocedural aneurysmal rupture.^4,17,18 In our series, the risk of intraprocedural aneurysmal rupture of very small aneurysms (≤3 mm) was not significantly high. On the other hand, the failure rate was significantly high in the very small aneurysms. We speculate that physicians did not hesitate to abort the procedure to prevent an intraprocedural aneurysmal rupture if an abnormal delivery wire tension or unstable microcatheter position or both were recognized.

Endovascular Therapy Feasibility

Failure of the endovascular therapy of UIAs was reported in 5.0%–9.5%.^{10,19⇓⇓–22} In our series, failure occurred in 3.8% (19/500), which is lower compared with that in previous reports. An unfavorable D/N ratio of <1.5 is considered the most responsible factor.

Morbidity and Mortality

In the Wiebers et al² ISUIA study, the mortality and morbidity rates at 30 days (defined as an mRS of 3–5 and impaired cognitive status) of 451 patients treated with endovascular therapy were 1.7% and 7.3%, respectively. Lanterna et al²³ reported a systematic review of the literature of 30 studies comprising 1379 patients with UIAs treated by endovascular therapy. They found that the overall permanent morbidity and mortality rates were 7% and 0.6%, respectively. In the ATENA study,¹⁴ the 1-month morbidity and mortality rates were 1.7% and 1.4%, respectively. Im et al⁴ reported that the procedure-related permanent morbidity rate of 358 small asymptomatic UIAs was 0.27% and the mortality was zero.

We strictly defined the “morbidity” as a change of mRS > 0 and the “mortality” as all deaths during the perioperative period. Nevertheless, our morbidity and morality rates (0.8% and 0.2%, respectively) were comparable with those of previous reports. However, the morbidity and mortality in our series might be underestimated because the patients did not undergo an independent neurologic examination by a board-certified neurologist before and after the endovascular therapy. Therefore, subtle neurologic deficits might have been missed. Furthermore, the cognitive status of the patients was not evaluated as it was in the ISUIA study.

Anatomic Follow-Ups and Retreatments

Im et al⁴ reported the anatomic follow-up results of 358 small asymptomatic UIAs by plain radiography and/or MR angiography and/or conventional angiography ≥6 months after endovascular therapy. Stable aneurysm occlusion was achieved for 94.1%, and recurrence occurred in 5.87%. Only 1.7% of coiled aneurysms required retreatment.⁴ In our study, the recurrence rate was 16.9%, and 2.9% of coiled aneurysms received retreatment. Particularly, aneurysms measuring <5 mm and/or with a D/N ratio of ≥1.5 had a low recurrence rate in the short-to-midterm period. These results suggest that with endovascular therapy of small asymptomatic UIAs, there is a low risk of recurrence and little need of retreatment. However, prospective studies with longer follow-up periods are warranted to definitively assess the true anatomic outcome.

Effectiveness in Preventing Aneurysmal SAH

Recurrence is a well-known drawback of endovascular therapy of intracranial aneurysms. Therefore, patients treated with endovascular therapy have to undergo long-term clinical and radiologic follow-up. Currently, it is unclear whether endovascular therapy actually reduces the bleeding risk of UIAs. Im et al⁴ reported that only 1 of 306 patients (0.3%) with small coiled asymptomatic UIAs had aneurysmal SAH. Even though complete occlusion was achieved, a 5-mm MCA bifurcation aneurysm bled for 18 months after endovascular therapy. The patient was lost to clinical follow-up after initial treatment. Gallas et al¹⁹ did not experience posttreatment aneurysmal SAH in the 278 UIAs making up 77% of the aneurysms of <10 mm endovascularly treated, with a mean follow-up period of 38 months. In our series, there were no patients who had aneurysmal SAH after endovascular therapy, with a mean follow-up of 34.7 months. These results suggest that endovascular therapy of UIAs, particularly that of small asymptomatic UIAs, provides sufficient protection from aneurysmal SAH in short-to-midterm periods. However, longer clinical and neuroimaging follow-up periods are mandatory to determine the accurate effectiveness of endovascular therapy in preventing aneurysmal SAH.

Learning Curve

Murayama et al²⁴ reported their 11 years' experience of GDC embolization of cerebral aneurysms. They divided the subjects into 2 groups: group A included their initial 5 years' experience, and group B included the later 6 years' experience. Immediate angiographic outcome showed an increase in the rate of CO and a decrease in the occurrence of RN in group B. There were no significant differences in the rate of failure between groups A and B. They also found that group B was associated with an overall lower rate of technical complications than group A (7.3% compared with 11.3%, respectively). Pierot et al²⁵ compared the safety of endovascular therapy of UIAs between hospitals with a large volume of cases (>20) and those with a small volume of cases (≤20). They found that there were no significant differences regarding the clinical or anatomic outcomes between the 2.

In our series, there was a high rate of failure in the first 100 aneurysms. Despite the fact that aneurysms with anatomic characteristics that presented a therapeutic challenge for endovascular therapy were treated among the later cases, the reasons for decreased failure seem to be related to the practitioners' technical advances and the development of the right devices.

Limitations

Because our study included retrospective data acquisition, a prospective study with a more rigorous technical and follow-up strategy is warranted. Because the anatomic and clinical outcomes and procedure-related complications were assessed by the authors, the results could be biased. We could not determine the safety or efficacy of the biologically modified coils because we mainly used bare platinum coils. The stent-assisted technique was not assessed because intracranial stents had not been approved commercially in Japan during the study period. The patients in our series were not representative of the whole population of patients with small asymptomatic UIAs because surgically treated or untreated UIAs were not included in this study. Decisions regarding treatment indications may induce an inclusion bias.