A systematic review of pipeline embolization device for giant intracranial aneurysms
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.198200
Source of Support: None, Conflict of Interest: None
The experience with respect to the treatment of giant intracranial aneurysms with flow-diversion devices is limited. The aim of the present systematic review was to evaluate the effect of the pipeline embolization device (PED) on giant intracranial aneurysms. Eligible related articles were identified by searching the PubMed, Web of Science, Springer, ScienceDirect, and OVID databases using “giant aneurysm” and “pipeline” as the search items. The date of the last search was November 20, 2015. This systematic review adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In a total of 9 eligible studies with 200 patients and 215 aneurysms, 40 (18.6%) giant (aneurysm diameter >25mm) intracranial aneurysms treated with PED were analyzed. During a 6 to 34 month follow-up, complete occlusion was achieved in 23 (57.5%) cases. Seven patients (17.5%) developed intracranial hemorrhage, 5 developed ischemic attack (12.5%), and 13 (32.5%) developed a mass effect after PED treatment. The complication rate was 77.8% in PED for giant vertebrobasilar artery aneurysms. The cumulative mortality rate for giant paraclinoid carotid artery and middle cerebral artery aneurysms was 13.3% and increased up to 50% for giant vertebrobasilar artery aneurysms. The complete obliteration rate of PED for giant intracranial aneurysms was approximately 60%. Mass effect is the most mechanism of complications. Complication and mortality rates associated with PED for giant vertebrobasilar artery aneurysms are still extremely high.
Keywords: Aneurysms, embolization device, giant, intracranial, pipeline
Giant intracranial aneurysms are classified according to their size (greater than 2.5 cm in diameter) and have high morbidity and mortality. They are relatively infrequent, comprising approximately 5% of all aneurysms in most series. The mortality rates for untreated giant intradural aneurysms is as high as 65% after 2–5 years of follow-up, with a rupture rate for conservatively treated intradural giant aneurysms of approximately 8–10% per year. Morphologically, giant aneurysms are divided into saccular and fusiform types, with fusiform aneurysms arising more commonly in the vertebrobasilar and middle cerebral territories. The pipeline embolization device (PED; ev3 Endovascular, Plymouth, MN, USA) was initially approved for large/giant internal carotid artery (ICA) aneurysms by the US Food and Drug Administration in 2011. However, data regarding giant aneurysms treated with PED remains meagre and most of the studies have a relatively short follow-up duration. In view of these considerations, we conducted a systematic review to evaluate the effect of PED on patients with giant intracranial aneurysms.
This systematic review adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible related articles were identified by searching PubMed, Web of Science, Springer, ScienceDirect, and OVID databases. The combination of search strings that was used in all database searches included the terms “giant aneurysm” and “pipeline,” The last literature search was conducted on November 20, 2015. All retrieved studies were scanned independently by two reviewers (LV and GE) to include only patients with giant aneurysm treated by PED that had reported their clinical outcomes. We excluded the following articles from the final analysis: (a) Review studies, (b) studies with less than 5 patients, (c) case reports, and (d) articles without clinical outcomes of giant aneurysms. Data on giant aneurysms treated by PED in all subgroups were extracted independently by the 2 authors who performed the literature search (LV and Jiang). Individual-level data available in the studies were collected and analyzed.
All statistical analyses were conducted using SPSS 16.0. We subsequently conducted subgroup analyses according to the saccular and fusiform morphologies, aneurysm locations (internal carotid artery [ICA], middle cerebral artery [MCA], and vertebrobasilar artery), the use of adjunct coils, as well as treatment without coils. Chi-square test was used to determine the factors associated with the acute (<30 days) and delayed (>30 days) complications (neurological deficits caused by ischemic or hemorrhagic episodes, as well as mass effect), morbidity (modified Rankin score 2), and mortality, complete aneurysmal occlusion and a preferable clinical outcome (modified Rankin score 0–1). P< 0.05 was statistically significant.
Systematic searches of the PubMed, Web of Science, Springer, ScienceDirect, and OVID databases yielded 66, 18, 80, 72, and 10 results, respectively. After removing duplicate studies, the titles and abstracts from the remaining 218 studies were screened and 28 potentially eligible studies for the systematic review were retained. After retrieving the full-text versions of the aforementioned 4 studies, 19 full-text articles were excluded because the clinical outcomes of giant aneurysms were not reported [Figure 1]. The final 9 search results comprised 42 giant aneurysms in 42 patients [Table 1].,,,,,,,, Two patients whose details were not available were also excluded, and 40 patients [4 (10%) with ruptured and 36 (90% ) with unruptured aneurysms] were analyzed [Table 2].
Acute and delayed complications
During a 6-34 month follow-up, complete exclusion of the aneurysm from circulation was achieved in 23 (57.5%) cases. The cumulative morbidity was 15% and mortality rate was 27.5%. Twelve patients (30%) developed intracranial hemorrhage, 10 developed an ischemic attack (25%), and 8 (20%) developed a mass effect after PED treatment. The complication rate of PED for giant vertebrobasilar artery aneurysms was 94.4%. The cumulative mortality rate for giant internal carotid artery and middle cerebral artery aneurysms was 9.1%, while the mortality for giant vertebrobasilar artery aneurysms treated with PED was 50%.
Overall analysis and subgroup analyses
The complication and mortality rates were lower in patients with ICA and MCA aneurysms as compared to vertebrobasilar aneurysms (OR 11.769, 95% CI: 1.319–105.008; P = 0.011 and OR 10.000, 95% CI: 1.786–55.976; P = 0.005). Correspondingly, a good clinical outcome (mRS 0–1) was higher in patients with giant ICA and MCA aneurysms (OR 5.343, 95% CI: 1.350–21.144; P = 0.016). A higher complete obliteration rate was identified for giant saccular aneurysms as compared to giant fusiform aneurysms (OR 4.667, 95% CI: 0.990–22.008; P = 0.049). There were no differences between angiographic and clinical outcomes between patients who underwent adjunct coiling and those who did not.
Given the fact that giant aneurysms are often difficult to coil and obliterate completely, thus leading to residual or recurrent aneurysms, multiple retreatments, occasional hemorrhage, and neurological deterioration from progressive aneurysmal enlargement,, flow diversion has recently emerged as an attractive measure for these aneurysms. Flow diversion treatment of giant aneurysms appears to offer many promising early results. However, there are reports of some apparently successful treatments being complicated by mass effect and aneurysmal hemorrhage. The findings from the current systematic review indicate that the incidence of complications and mortality after PED treatment of giant aneurysm is high. Giant aneurysms, therefore, represent a high-risk disease that requires a high-risk treatment with there being no dramatic change in the treatment outcomes in the PED era.
Dumont et al., published a series of patients with giant intracranial aneurysms treated with endovascular techniques between December 2001 and July 2007 with a follow-up of more than 2 years, and reported a 29% long-term mortality after endovascular treatment of giant aneurysms. Between August 2007 and December 2012, their single-institution experience demonstrated 8 (31%) mortalities among 26 treated patients, with 12 patients associated with perioperative complications and 12 patients with permanent neurological morbidity or death (46%) at the last follow-up (9.4 ± 18 months). Our current endovascular techniques (coil embolization with or without stent assistance or liquid embolic agents) for the treatment of 30 giant cerebral aneurysms between January 2006 and March 2012 resulted in a 30% morbidity and mortality, and approximately 50% mortality in the untreated 9 cases during a follow-up of up to 6 years.
The treatment of almost all the aneurysms located at the vertebrobasilar artery resulted in a permanent neurological morbidity or death. Complications were more common in patients presenting with mass effect, which has been our experience as well.,,, In this review, among the giant aneurysms treated with PED devices, hemorrhagic, ischemic, and mass effect complications occurred after treatment in 75% patients, while morbidity and mortality occurred in more than 40% patients. A review of the literature performed by Nanda et al., showed a favorable 10% (2 deaths among 21 reported cases) morbidity and mortality among patients with giant aneurysms treated with flow diversion; however, the rate of complete obliteration of these giant aneurysms was only 54% among the 13 cases with follow-up. However, this review had a smaller number of patients, less vertebrobasilar artery aneurysms, and a limited follow-up duration.
With the availability of PED devices, we are more likely to treat a cavernous or paraclinoid giant aneurysm with an endovascular approach, which we feel offers superior treatment with a lower risk than that offered by a craniotomy and clip ligation. This review shows that PED devices are ideally suited to treat giant ICA aneurysms. In our own experience, no new deficits developed among giant ICA giant aneurysms treated with PED.
Limitations of the study
Certain limitations of this report need to be acknowledged. A major limitation of this study is the small number of patients because of the general lack of quality data and the low number of patients. There was a marked heterogeneity in the follow-up between studies. The follow-up data was not reported in 3 studies, and 2 cases (4.8% of this review) in a study by Kan et al., had to be excluded because their outcome was not reported. This creates an issue for interpreting the long-term outcomes and assessing the rate of rebleeding after treatment. Four studies were small series (comprised <15 patients). Moreover, there is a possibility of a publication bias. We excluded case reports and smaller studies, and chose series that included small aneurysms as well as giant aneurysms to reduce the publication bias and exclude the learning curve effect. We did not analyze vertebrobasilar aneurysms by subtype or etiology such as fusiform or dolichoectatic lesions, and midbasilar saccular lesions. Moreover, factors related to the patient's age, sex, and dual antiplatelet regimen were not analyzed because such information could not be extracted from the articles, and doses of dual antiplatelet regimen were not reported in 5 studies.
The complete obliteration rate of PED for giant intracranial aneurysms was approximately 60%. The mortality of patients treated with PED for giant anterior circulation aneurysms was approximately 10%. Complication and mortality rates associated with PED for giant vertebrobasilar artery aneurysms were extremely high.
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Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2]