Basilar apex aneurysm : case series, systematic review and meta-analysis

Basilar apex aneurysm : case series, systematic review and meta-analysis

Journal Pre-proof Basilar apex aneurysm : case series, systematic review and meta-analysis Charlotte Dandurand, MD, Swetha Prakash, BSc, Amir A. Sepeh...

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Journal Pre-proof Basilar apex aneurysm : case series, systematic review and meta-analysis Charlotte Dandurand, MD, Swetha Prakash, BSc, Amir A. Sepehry, BA, MSc, PhD, Katherine Tourigny, BSc, Charles S. Haw, MD MSc FRCSC, Peter Gooderham, MD FRCSC, Justin Moore, MD, PhD, MPH, FRACS, Gary Redekop, BSc MD MSc FRCSC PII:

S1878-8750(20)30339-9

DOI:

https://doi.org/10.1016/j.wneu.2020.02.064

Reference:

WNEU 14339

To appear in:

World Neurosurgery

Received Date: 17 November 2019 Revised Date:

8 February 2020

Accepted Date: 10 February 2020

Please cite this article as: Dandurand C, Prakash S, Sepehry AA, Tourigny K, Haw CS, Gooderham P, Moore J, Redekop G, Basilar apex aneurysm : case series, systematic review and meta-analysis, World Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2020.02.064. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.

Word count: 2,247 Word count (abstract): 232/250 Number of Figures: 2 Number of Tables: 5 Number of e-figure: 0

Basilar apex aneurysm : case series, systematic review and meta-analysis Dandurand, Charlotte, MD*1; Prakash, Swetha, BSc1; Sepehry, Amir A, BA, MSc, PhD 2

; Tourigny, Katherine, BSc1; Haw, Charles S, MD MSc FRCSC1; Gooderham, Peter,

MD FRCSC1; Moore, Justin, MD, PhD, MPH, FRACS3; Redekop, Gary, BSc MD MSc FRCSC1 1.

UBC, Faculty of Medicine, Division of Neurosurgery, Vancouver, Canada

2.

Faculty of Medicine, Division of Neurology, The University of British Columbia,

Vancouver, British Columbia, Canada; 3.

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston,

Massachusetts, United States

*Corresponding Author: Charlotte Dandurand, MD

Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, Canada 11115- 2775 Laurel Street, Vancouver, BC, V5Z 1M9 Email: [email protected] Phone: 514-926-2890 The study protocol is published on PROSPERO (CRD42018089370) Cover title: Basilar apex aneurysm Key words: intracranial aneurysm, basilar artery aneurysm, basilar apex, basilar bifurcation, endovascular procedures, microsurgery Source of funding: None Conflicts of interest or disclosure: The authors have no conflicts of interest to disclose nor do they have any financial or industry relationships to disclose.

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Cover title : Basilar apex aneurysm meta-analysis

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Key words: intracranial aneurysm, basilar artery aneurysm, basilar apex, basilar bifurcation,

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endovascular procedures, microsurgery

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ABSTRACT

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BACKGROUND: A lower rate of aneurysmal recanalization in stent assisted coiling vs coiling

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alone has been observed in aneurysms overall.

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OBJECTIVE: This study aims to primarily stratify and compare degree of occlusion per

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treatment modality in basilar apex aneurysms. Secondary outcomes were retreatment, post

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treatment hemorrhage and procedure-related complications.

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METHODS: Medical literature including MEDLINE and EMBASE database was searched. We

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performed meta-regressions, bias analysis and fail-safe N. We controlled for the quality of the

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studies.

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RESULTS: Data from eligible studies (N=12) and study center patients (n=117) were pooled for

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a total of 396 nonduplicated patients. Stent-assisted coiling had a lower rate of retreatment (17%

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vs 24%) and higher rate of post treatment haemorrhage (5% vs 3%) compared to coiling. Stent-

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assisted coiling had a higher rate of complete occlusion (55% vs 45%) and a lower rate of

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residual aneurysm (15% vs 23%) compared to coiling. Comparative analyses were performed.

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Microsurgical technique remained the most morbid treatment modality with the best rate of

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complete occlusion (93%) and lowest rates of rehemorrhage (2%) and retreatment (5%).

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CONLUSION: This is the first and largest meta-analysis focused on patients treated for basilar

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apex aneurysm. We report higher rehemorrhage rates with stent-assisted coiling. This study

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provides benchmark data to guide clinicians in future treatment decision-making and encourages

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future research to stratify outcomes.

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Introduction

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Basilar apex aneurysms account for approximately 5% of all intracranial aneurysms and

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are the most common aneurysms of the posterior circulation1, 2. Basilar apex aneurysms are

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widely recognized as challenging for microsurgical repair.

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replaced microsurgical clipping globally to lower morbidity and mortality1. However,

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endovascular treatment usually achieves lower rates of long-term occlusions compared to

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clipping3. Furthermore, the retreatment rate for basilar aneurysms appears higher than aneurysms

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at other locations1, 2, 4, 5. Microsurgical clipping has been associated with high rates of cranial

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nerve palsies, thalamoperforator injuries and difficulty with proximal control1, 3. Nevertheless,

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microsurgical clipping may be appropriate for aneurysms with complex morphology in young

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patients3. Patients with initial incomplete occlusion require frequent angiographic follow-ups and

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Endovascular therapy has largely

often retreatment. This chronic state is associated with reductions in patients’ quality of life.4-9.

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Individual studies have found that stent assisted coiling has been associated with better

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occlusion rates compared to coiling alone 10-12. However, basilar aneurysms are unique and have

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different postoperative outcomes than aneurysm at other locations13. Currently, it is unclear

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which techniques are optimal in treating patients with basilar aneurysms. Thus, utilizing large

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pooled numbers of patients can provide clinicians with more accurate estimates of the outcomes

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and risks for varying treatment strategies specifically for basilar aneurysms.

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Using a large case series combined with a systematic review and meta-analysis of the

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literature, this study aims to compare occlusion rates between treatment modalities and

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secondarily, the risks of the techniques and the risk of retreatment.

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Methods

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The data used for this study is available from the corresponding author upon request. The Institutional Review Ethics Board approved this study.

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Study center series

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All patients with basilar apex aneurysm treated at the study institution from 2001 to 2017

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were retrospectively reviewed using a prospectively maintained database. Inclusion criteria were:

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1) microsurgical or endovascular treatment of basilar apex aneurysm; 2) recorded treatment

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modality; 3) at least one radiological and clinical follow-up with the degree of occlusion noted 6

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months after treatment. The exclusion criteria was: 1) hypothermic circulatory arrest used during

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treatment. Information collected including patient demographics, radiological and clinical

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characteristics, treatment techniques, and clinical and radiological outcomes. Treatment

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decisions were made at the time of initial evaluation by the treating surgeon. The degree of

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occlusion was classified as: 1) complete occlusion; 2) residual neck; or 3) residual aneurysm as

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described by the Raymond-Roy angiographic classification scheme for grading the occlusion of

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treated aneurysm14, 15.

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Literature review

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Search strategy

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Preferred Reporting of Items for Systematic Reviews and Meta-Analyses protocols

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(PRISMA-P)16,

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coiling an intracranial aneurysm was in 1997 by Higashida et al18. The first self-expandable

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intracranial stent was introduced and approved in 200119. Therefore, we systematically reviewed

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the literature (MEDLINE and EMBASE) from January 1st, 2001 to November 30th 2017. Key

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words and Medical Subject Headings (MeSH) terms used in alone or in combination included:

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“basilar tip”, “basilar apex”, “basilar bifurcation”, “intracranial aneurysm”. The search was

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limited to humans. The reference lists of all retrieved articles were reviewed for further

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identification of potentially relevant studies.

was used. The first reported use of a balloon-expandable coronary stent for

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Study selection

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Two authors (CD, KT) reviewed titles and abstracts for selection criteria. Inclusion

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criteria were: 1) microsurgical or endovascular treatment of basilar apex aneurysm; 2) recorded

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treatment modality; 3) at least one radiological and clinical follow-up with degree of occlusion

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minimum 6 months after treatment stratified by treatment modality. Exclusion criteria were: 1)

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aneurysm at other location or inability to stratify outcomes by aneurysm location; 2) radiological

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and clinical follow-up of less than 6 months; 3) case series/ case reports of less than 5 patients; 4)

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hypothermic circulatory arrest used during treatment; 5) technical notes, reviews, letters to the

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editors, commentaries and articles without an abstract; 6) articles in languages other than English

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or French. When institutions published duplicate studies with accumulating numbers of patients

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or increased lengths of follow-up, only the most complete report was included for quantitative

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assessment at each time interval. Any disagreement during article selection was resolved by a

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discussion with a senior author (GR).

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Data extraction and quality evaluation

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Data was extracted from article texts, tables and figures. Data extraction included: year of

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publication, geographic origin, study design, demographics, clinical presentation, admission

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radiological characteristics, treatment modality, radiological and clinical outcomes, follow-up

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period and mortality. Radiological outcomes were classified as 1) complete occlusion; 2)

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residual neck; or 3) residual aneurysm. This was based on Raymond-Roy angiographic

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classification scheme for grading the occlusion of treated aneurysm14,

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radiological outcomes were separated into 4 treatment groups: coiling alone, stent-assisted

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coiling, stent only and microsurgical clipping. Treatment groups to be included in analysis had

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to include patients from more than one study to reduce bias. Quality of evidence was assessed

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using National Heart, Lung, and Blood Institute study quality assessment tools for case series

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and cohort studies.

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. Clinical and

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Outcomes Primary outcome was defined as degree of occlusion. Secondary outcomes were

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retreatment, post treatment hemorrhage and procedure-related complications.

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Data analysis

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Data was analysed as either continuous or categorical to calculate an aggregate

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prevalence rate or effect-size estimate (OR: Odd ratio), using comprehensive meta-analysis

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software (Ver. 2.0). A random effects model was used. Sensitivity analysis was carried out on

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post treatment hemorrhage and retreatment rates, then followed by the assessment of Fail-safe N

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and publication bias assessment. Publication bias was assessed using funnel plots, Begg and

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Mazumdar rank correlation and Egger’s regression intercepts (with a cut-off alpha level was set

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to 0.05 a priori). Subsequently, a Duval and Tweedie’s trim and fill analysis was performed.

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Results

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Case series

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This case series included 117 patients treated for a basilar apex aneurysm (Table 1). 104

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patients (89%) were treated via endovascular modalities and 13 patients (11%) were treated via

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microsurgical clipping. 68 patients (65%) were treated with unassisted coiling and 36 patients

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(35%) were treated with stent-assisted coiling.

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Search results

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The literature review delivered 464 articles. After duplicate removal, 371 articles were

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available for review (Figure 1). 15 articles were additionally found by reviewing references and

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articles published during the reviewing process. The rate of agreement between authors (C.D.

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and K.T.) for inclusion in the study was 85%. 12 studies met the inclusion criteria20-31 (Table 2). 7

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All studies had a retrospective design. The quality of the studies was assessed using the National

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Institutes of Health Study Quality Assessment Tools and a quality score which ranged from 56-

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89%. The geographic distribution of studies was as follows: Asia 42%, North America 46%, and

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Europe 13%. Only one study contributed to the stent only treatment group with 4 patients20.

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This group was not included in results to limit bias.

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Clinical Characteristics

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396 non-duplicated patients were included in this analysis. Overall, 76 % were female.

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The mean age was 55.4 years (Table 2). Patients were almost equally distributed between

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ruptured and unruptured (49% and 51%, respectively). Mean aneurysmal size was 9.7 mm. The

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mean angiographic follow-up was 36.8 months. The Y-stent technique was most commonly

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used. However, the stent insertion technique was inconsistently reported and outcomes were not

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stratified per stent insertion technique among studies preventing comparative analysis.

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Radiological outcomes

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The microsurgical group had a complete occlusion rate of 93% (Table 3). The stent-

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assisted coiling group had a complete occlusion rate of 55%. The unassisted coiling group had a

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complete occlusion rate of 45%. The coiling only group had the highest rate of residual neck

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(31%) and residual aneurysm (23%). Coiling had the highest rate of retreatment at 24% (95 %CI:

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17-33%, p=0.00), followed by stent-assisted coiling at 17% (95%CI: 11-24%, p=<0.01 and

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microsurgical clipping at 5% (95%CI: 1-24%, p=0.00). Stent-assisted coiling had the highest rate

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of post treatment hemorrhage at 5% (95%CI: 2-12%, p=0.00), followed by coiling only at 3%

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(95%CI: 1-8%, p=0.00) and microsurgical at 2% (95%CI: 0-9%, p=0.00). The effect of study

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quality on the post treatment hemorrhage and retreatment rates was appraised via sensitive

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analysis, and was non-significant (P= 0.81).

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Microsurgical clipping had higher odds ratio of complete occlusion compared to stent-

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assisted coiling (OR: 10,38, 95% CI:4.26-25.29, p=0.00) and coiling (OR:15.31, 95% CI:6.30-

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37.19, p=0.00) (Table 4, Figure 2). Stent-assisted coiling had a higher odds ratio of complete

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occlusion compared to coiling only but did not reach statistical significance (OR:1.47, 95%

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CI:0.94-2.31, p=0.09). Microsurgical clipping had significantly lower odds of resulting in a

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residual neck than stent-assisted coiling or coiling and clipping had significantly lower odds of

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residual aneurysm than coiling. Age and sex did not have an effect on degree of occlusion

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outcomes with meta-regressions analysis. A sensitivity analysis based on the affect of study

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quality on complete occlusion, residual neck and residual aneurysm was non-significant

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(P=0.16}.

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Clinical outcomes

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One study did not report clinical outcomes and was excluded from analysis31. The

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microsurgical group had the highest rate of permanent and temporary postoperative neurological

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complications (17% and 78%, respectively) (Table 5). The vast majority of temporary

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postoperative adverse neurological events consisted of oculomotor nerve palsies. The

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microsurgical group also had the highest rate of hemorrhagic events (p-intraoperative rupture)

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and perforator injury. Coiling had a trend towards higher rates of postoperative adverse events

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compared to stent-assisted coiling, but this was not statistical significant. Non-neurological

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adverse events consisted primarily of access-related complications such as groin or

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retroperitoneal hematomas, wound infection and cerebrospinal fluid leak. The inclusion and

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exclusion criteria prevent analysis of procedure-related mortality or early rerupture-related

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mortality, as these patients had less than 6 months follow-up.

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Sensitivity analysis

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The overall aggregate event rate (point estimate) of post treatment hemorrhage was 4%

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(95%CI: 2-7%, N=14, 6/362 individuals). Modality specific post treatment hemorrhage rate

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were; 3% for coiling (95%CI: 1- 8%, N=3, 4/159 individuals); 2% for microsurgical (95%CI: 0-

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9%, N=3, 0/82 individuals); 5% for stent-assisted coiling (95%CI: 2-12%, N=8, 2/121

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individuals). Based on Begg and Mazumdar rank correlation, we found the possibility of

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publication bias. Further examination utilizing Duval and Tweedie’s trim and fill method found

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that no study affected the point estimate. The fail-safe N showed that with observed Z-value of -

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10.168, alpha level of 0.05 (2-tailed) and 12 included studies, we would need 363 studies with

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equal characteristics to significantly change the effect size estimate.

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The overall aggregate rate (point estimate) of retreatment was 19% (95%CI: 14-24%,

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N=14, 51/336 individuals). Specifically, retreatment rate for coiling was 24% (95%CI: 17-33%,

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N=2, 29/50 individuals), 5% for microsurgical (95%IC: 1-24%, N=3, 2/82 individuals), and 17%

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for stent-assisted coiling (95%CI: 11-24%, N=9, 20/134 individuals). Both Begg and Mazumdar

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rank correlation suggested the possibility of publication bias in the studies included. However,

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after examining with Duval and Tweetie’s trim and fill, we found that no study significantly

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affected the results. The classical fail-safe N showed that with observed Z-value of -9.272, we

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would need 300 studies with equal characteristics to significantly change the effect size estimate.

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Discussion

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This is the first systematic review and largest pooled comparative analysis on basilar

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apex aneurysms treatment outcomes. The main findings of this study is that microsurgery

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provides higher rates of complete aneurysm occlusion, lower rates of retreatment and post

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treatment hemorrhage, but was associated with a higher rate of complications. Additionally,

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stent-assisted coiling provides a lower rate of retreatment and a higher rate of complete occlusion

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compared to coils alone but was associated with higher rates of post-treatment hemorrhage.

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While several studies have identified better rates of occlusion with stent assisted

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compared to coiling alone, to our knowledge, this is the first study to report higher post treatment

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hemorrhage rates with stent-assisted coiling11, 12, 32-34. One possible explanation might be the

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necessary use of dual antiplatelets when inserting stents. Phan et al. reported an increased

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mortality in stent-assisted coiling, which may be explained by our findings10. This finding may

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be unique to the basilar apex aneurysms. These lesions generally have less favourable anatomy

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with wider necks, larger domes and incorporation into other branches. These features create a

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challenge for achieving complete occlusion and increase the risk of rebleeding7.

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The risk of post treatment hemorrhage is strongly associated with the aneurysms degree

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of occlusion8, 35. In this study, the stent-assisted coiling group had higher rates of post treatment

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hemorrhage, despite having similar or better rates of occlusion compared to coiling. The CARAT

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group reported that the degree of occlusion was a strong predictor of the risk of subsequent

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rupture, which supports efforts of complete occlusion at initial aneurysm treatment35. The

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International Subarachnoid Aneurysm Trial (ISAT) determined that incomplete occlusion was a

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risk factor for retreatment36. The degree of occlusion also affects patient monitoring.

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Incompletely occluded aneurysm require more frequent follow-ups, which adds to the cost of

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treatment and can negatively impact patients6.

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This data is consistent with previous work comparing stent assisted coiling and coiling

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only, suggesting that there may be a trade-off between higher rates of occlusion and post

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procedure hemorrhage. 33.

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More recently, posterior circulation aneurysms, including basilar bifurcation aneurysms,

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have been selectively treated with flow diverters37. The comparison between flow-diverters and

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other well established treatment modalities should be made in future studies when the literature

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provides a larger number of patients.

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Limitations

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This study is limited by the inability to extract and stratify baseline aneurysm

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characteristics such as size, configuration and rupture status from the literature. Future research

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reporting different treatment modalities results should stratify not only outcomes, but also

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baseline characteristics of the disease such as aneurysm characteristics and rupture status. Future

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studies should consistently report the stent insertion technique. This would allow readers to

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better understand treatment decision-making and better interpret the reported outcomes.

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Furthermore, this case series was retrospective and thus had all the limitations inherent to this

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study design.

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Conclusion

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This is the first systematic review on basilar apex aneurysms. Based on this study, stent-

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assisted coiling provides a lower rate of retreatment compared to coiling, but higher rates of post

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treatment hemorrhage. Microsurgical treatment remains the most morbid procedure. This study

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provides benchmark numbers for clinicians to guide treatment decision-making and encourages

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future research to stratify outcomes by treatment modalities.

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351 352 353 354 355 356

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vertebrobasilar artery aneurysms for reducing recanalization: Mid-term results. Acta Neurochirurgica. 2013;155:2009-2017 Blackburn SL, Kadkhodayan Y, Shekhtman E, Derdeyn CP, Cross DT, 3rd, Moran CJ. Treatment of basilar tip aneurysms with horizontal pca to pca stent-assisted coiling: Case series. J Neurointerv Surg. 2013;5:212-216 Spiotta AM, Gupta R, Fiorella D, Gonugunta V, Lobo B, Rasmussen PA, et al. Mid-term results of endovascular coiling of wide-necked aneurysms using double stents in a y configuration. Neurosurgery. 2011;69:421-429 Lozen A, Manjila S, Rhiew R, Fessler R. Y-stent-assisted coil embolization for the management of unruptured cerebral aneurysms: Report of six cases. Acta Neurochirurgica. 2009;151:1663-1672 Krisht AF, Krayenbuhl N, Sercl D, Bikmaz K, Kadri PA. Results of microsurgical clipping of 50 high complexity basilar apex aneurysms. Neurosurgery. 2007;60:242-250; discussion 250-242 Thorell WE, Chow MM, Woo HH, Masaryk TJ, Rasmussen PA. Y-configured dual intracranial stent-assisted coil embolization for the treatment of wide-necked basilar tip aneurysms. Neurosurgery. 2005;56:1035-1040; discussion 1035-1040 Lusseveld E, Brilstra EH, Nijssen PC, van Rooij WJ, Sluzewski M, Tulleken CA, et al. Endovascular coiling versus neurosurgical clipping in patients with a ruptured basilar tip aneurysm. Journal of Neurology, Neurosurgery & Psychiatry. 2002;73:591-593 Liu Y, Wang F, Wang M, Zhang G. Comparison of stent-assisted coil placement and coiling-only for the treatment of ruptured intracranial aneurysms. Med Sci Monit. 2017;23:5697-5704 Yang H, Sun Y, Jiang Y, Lv X, Zhao Y, Li Y, et al. Comparison of stent-assisted coiling vs coiling alone in 563 intracranial aneurysms: Safety and efficacy at a high-volume center. Neurosurgery. 2015;77:241-247; discussion 247 Chalouhi N, Starke RM, Koltz MT, Jabbour PM, Tjoumakaris SI, Dumont AS, et al. Stent-assisted coiling versus balloon remodeling of wide-neck aneurysms: Comparison of angiographic outcomes. AJNR Am J Neuroradiol. 2013;34:1987-1992 Johnston SC, Dowd CF, Higashida RT, Lawton MT, Duckwiler GR, Gress DR, et al. Predictors of rehemorrhage after treatment of ruptured intracranial aneurysms: The cerebral aneurysm rerupture after treatment (carat) study. Stroke. 2008;39:120-125 Campi A, Ramzi N, Molyneux AJ, Summers PE, Kerr RS, Sneade M, et al. Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the international subarachnoid aneurysm trial (isat). Stroke. 2007;38:1538-1544 Bender MT, Colby GP, Jiang B, Lin LM, Campos JK, Xu R, et al. Flow diversion of posterior circulation cerebral aneurysms: A single-institution series of 59 cases. Neurosurgery. 2019;84:206-216

357 358 359 360 361 362 363 364 365 366 367

Figure 1. Flow diagram

368 369 370 371 372 373 374 375 376 377 378 379 380

16

381 382 383 384 385 386 387 388 389 390 391 392

Figure 2. Forest plot for treatment modality comparison per degree of occlusion outcome

393 394 395 396 397 398 399 400 401 402 403 404

17

405

18

Table 1. Degree of occlusion and clinical outcomes for the present case series. Variable Degree of Occlusion Complete

Total n =117

Microsurgical n =13 (11%)

Coiling Only n = 68 (58%)

Stent-assisted Coiling n = 36 (31%)

51 (44%)

8 (61%)

27 (40%)

16 (45%)

Residual neck

45 (38%)

1 (8%)

27 (40%)

17 (47%)

Residual aneurysm

21 (18%)

4 (31%)

14 (20%)

3 (8%)

4 (3%)

0

3 (4%)

1 (3%)

Permanent

16 (14%)

7 (54%)

7 (10%)

2 (6%)

Temporary

12 (10%)

3 (23%)

8 (12%)

1 (3%)

Clinical Events Non-Neurological Neurological

Asymptomatic

6 (5%)

0

4 (6%)

2 (6%)

Thromboembolic Events

18 (15%)

3 (23%)

11 (16%)

4 (11%)

Hemorrhagic Events

5 (4%)

3 (23%)

1 (1%)

1 (6%)

Cranial Nerve Palsies

11 (9%)

5 (38%)

6 (9%)

0

0

0

0

0

26 (22%)

2 (15%)

17 (25%)

7 (19%)

5 (4%)

0

3 (4%)

2 (6%)

Perforator Injury Retreatment Post-treatment hemorrhage

0 0 0 Mortality1 1 Patients deceased less than 6 months following treatment were excluded as per pre-established criteria

0

Table 2. Meta-analysis summary of patient demographics and treatment modality per study Number of Patients per Treatment Modality Number of Patients

Mean Age (years)

% Female

Aneurysm Size (mm)

Angiographic follow-up (months)

Microsurgical

Coiling only

Stent-assisted coiling

Stent only

117

56

72

8.6

66.8

13 (11%)

68 (58%)

36 (31%)

0

Dmytriw et al. (2018)20

9

59

56

17.7

24.9

0

0

5 (56%)

4 (44%)

Tjahjadi et al. (2017)21

98

N/R

N/R

N/R

43.5

0

52 (53%)

46 (47%)

0

Matsukawa et al. (2015)22

23

61

100

5.2

12.3

23 (100%)

0

0

0

Chen et al. (2015)23

5

47

60

11.2

17.6

0

0

5 (100%)

0

Jeon et al. (2014)24

21

57

76

11.4

16.1

0

0

21 (100%)

0

Rho et al. (2013)25

8

53

75

8.8

15.9

0

0

8 (100%)

0

Blackburn et al. (2013)26

6

50

N/R

10.9

21.7

0

0

6 (100%)

0

Spiotta et al. (2011)27

13

55

69

10.4

20.6

0

0

13 (100%)

0

Lozen et al. (2009)28

5

N/R

100

12.6

41.4

0

0

5 (100%)

0

Krisht et al. (2007)

46

52

78

N/R

12.0

46 (100%)

0

0

0

Thorell et al. (2005)30

6

N/R

N/R

N/R

7.0

0

0

6 (100%)

0

Lusseveld et al. (2002)31

39

N/R

N/R

N/R

6.0

0

39 (100%)

0

0

Meta-analysis

396

55.4

76

9.7

36.8

82

159

151

4

Author (year) Present Series (2018)

29

Table 3. Degree of occlusion and clinical outcomes Stent Assisted Coiling Total

Microsurgical

Coiling Only

Stent Only N=10 n=151 (38%)

N=14 n=396

N=3 n=82 (21%)

N=3 n=159 (40%)

51 (13%)

2 (5%)

29 (24%)1

20 (17%)

6 (2%)

0 (0%)

4 (3%)

2 (5%)

Complete

232 (59%)

76 (93%)

72 (45%)

83 (55%)

1 (25%)

Residual neck

99 (25%)

1 (1%)

50 (31%)

46 (30%)

2 (50%)

Residual aneurysm

65 (16%)

5 (6%)

37 (23%)

22 (15%)

1 (25%)

Variable Retreatment Post treatment hemorrhage

2

3

N=1 n=4 (1%) 0

0

Degree of Occlusion

1

n=50; 2n=134; 3n=121

Table 4. Radiological outcomes: Treatment modalities comparison per degree of occlusion Odds Ratio

Lower Limit

Upper Limit

p-Value

Sample size (event/total)

Microsurgical vs coiling

15.31

6.30

37.19

0.00

76/82 vs. 72/159

Stent-assisted coiling vs coiling

1.47

0.94

2.31

0.09

83/151 vs. 72/159

Microsurgical vs stent-assisted coiling

10.38

4.26

25.29

0.00

76/82 vs. 83/151

Microsurgical vs coiling

0.03

0.00

0.20

0.00

1/82 vs. 50/159

Stent-assisted coiling vs coiling

0.96

0.59

1.55

0.85

46/151 vs. 50/159

Microsurgical vs stent-assisted coiling

0.03

0.00

0.21

0.00

1/82 vs. 46/151

Microsurgical vs coiling

0.21

0.08

0.57

0.00

5/82 vs. 37/159

Stent-assisted coiling vs coiling

0.56

0.31

1.01

0.05

22/151 vs. 37/159

Microsurgical vs stent-assisted coiling

0.38

0.14

1.05

0.06

5/82 vs. 22/151

Variable Complete

Residual Neck

Residual Aneurysm

Table 5. Clinical outcomes per treatment modality Neurological

Variable

Total Number of Clinical Events

NonNeurological

Permanent

83

3 (4%)

N=3 n=82

Thrombo embolic Events

Hemorrha gic Events

Cranial Nerve Palsies

Perforator Injury

0

10 (28%)

4 (5%)

67 (82%)

7 (9%)

N=3 n=82

N=3 n=82

N=2 n=36

N=3 n=82

N=3 n=82

N=3 n=82

8 (12%)

4 (6%)

0

11 (16%)

1 (1%)

6 (9%)

0

N=1 n=68

N=1 n=68

N=3 n=82

N=1 n=68

N=1 n=68

N=1 n=68

N=1 n=68

N=1 n=68

1 (1%)

7 (7%)

7 (7%)

6 (6%)

0

13 (12%)

2 (3%)

2 (3%)

0

N=9 n=105

N=9 n=105

N=9 n=105

N=9 n=105

N=9 n=105

N=6 n=65

N=9 n=105

N=7 n=71

N=6 n=66

N=5 n=60

0

0

0

0

0

0

0

0

0

0

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

N=1 n=4

Mortality

Temporary

Asymptoma tic

14 (17%)

64 (78%)

2 (2%)

N=3 n=82

N=3 n=82

N=3 n=82

22

3 (4%)

7 (10%)

N=1 n=68

N=1 n=68

21

1

Microsurgical

Coiling only

Stent-assisted coiling

Stent only

N=number of studies; n=number of patients 1

Patients deceased less than 6 months following treatment were excluded as per pre-established criteria

1

CD: Charlotte Dandurand CI: Confidence interval GR: Gary Redekop ISAT: International Subarachnoid Aneurysm Trial KT: Katherine Tourigny MeSH: Medical subject headings OR: Odd ratio PRISMA-P: Preferred Reporting of Items for Systematic Reviews and Meta-Analyses protocols

Credit author statement Ms. Ref. No.: WNS-19-5960

Title: Basilar apex aneurysm : case series, systematic review and meta-analysis

Dandurand, Charlotte : conceptualization, methodology, data curation, writing original draft, writing review and editing, visualization, supervision, project administration Prakash, Swetha: data curation, writing original draft, writing review and editing Sepehry, Amir A: methodology, formal analysis, writing original draft Tourigny, Katherine : data curation, writing original draft Haw, Charles S : writing review and editing Gooderham, Peter : writing review and editing Moore, Justin : writing review and editing Redekop, Gary : conceptualization, writing review and editing

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: