REVIEW

Coiling Versus Microsurgical Clipping in the

Treatment of Unruptured Middle Cerebral Artery
Aneurysms: A Meta-Analysis
Meshal Alreshidi, MSc‡∗
David J. Cote, BS§∗
Hormuzdiyar H. Dasenbrock,
MD, MPH§
Michael Acosta, MSc§
Anil Can, MD§
Joanne Doucette, MS, MSLIS‡
Thomas Simjian, PharmD‡
M. Maher Hulou, MD§
Lee A. Wheeler, MD, PhD§
Kevin Huang, MD§
Hasan A. Zaidi, MD§
Rose Du, MD, PhD§
M. Ali Aziz-Sultan, MD§
Rania A. Mekary, MSc, PhD‡ §∗
Timothy R. Smith, MD, PhD,
MPH§∗
‡
Massachusetts College of Pharmacy
and Health Sciences (MCPHS), Boston,
Massachusetts; § Cushing Neurosurgical
Outcomes Center, Department of
Neurosurgery, Brigham and Women’s
Hospital, Harvard Medical School, Boston,
Massachusetts
BACKGROUND: Open microsurgical clipping of unruptured intracranial aneurysms has
long been the gold standard, yet advancements in endovascular coiling techniques have
begun to challenge the status quo.
OBJECTIVE: To compare endovascular coiling with microsurgical clipping among adults
with unruptured middle cerebral artery aneurysms (MCAA) by conducting a meta-analysis.
METHODS: A systematic search was conducted from January 2011 to October 2015 to
update a previous meta-analysis. All studies that reported unruptured MCAA in adults
treated by microsurgical clipping or endovascular coiling were included and cumulatively
analyzed.
RESULTS: Thirty-seven studies including 3352 patients were included. Using the random-
effects model, pooled analysis of 11 studies of microsurgical clipping (626 aneurysms)
revealed complete aneurysmal obliteration in 94.2% of cases (95% confidence interval [CI]
87.6%-97.4%). The analysis of 18 studies of endovascular coiling (759 aneurysms) revealed
complete obliteration in 53.2% of cases (95% CI: 45.0%-61.1%). Among clipping studies,
22 assessed neurological outcomes (2404 aneurysms), with favorable outcomes in 97.9%
(95% CI: 96.8%-98.6%). Among coiling studies, 22 examined neurological outcomes (826
aneurysms), with favorable outcomes in 95.1% (95% CI: 93.1%-96.5%). Results using the
fixed-effect models were not materially different.
CONCLUSION: This updated meta-analysis demonstrates that surgical clipping for unrup-
tured MCAA remains highly safe and efficacious. Endovascular treatment for unruptured
MCAAs continues to improve in efficacy and safety; yet, it results in lower rates of occlusion.
KEY WORDS: Aneurysm, Clipping, Coiling, Middle cerebral artery, Neurosurgery
Neurosurgery 0:1–11, 2017 DOI:10.1093/neuros/nyx623 www.neurosurgery-online.com
logical deficits or death.2-4 Patients are frequently

T
he widespread use of detailed neurovas-
∗
These authors contributed equally to cular imaging has led to an increase in presented with the dilemma of either watchful
this work. the detection of unruptured intracranial waiting for an unsecured aneurysm or surgical
aneurysms.1,2 Although the lifetime risk of intervention for these lesions with the risk
Correspondence:
Timothy R. Smith, MD, PhD, MPH, aneurysmal rupture in many cases is relatively of iatrogenic complications. Often, patients
Brigham and Women’s Hospital, small, with many authors reporting rates of may desire surgical management of unruptured
15 Francis Street, approximately 1% per year, rupture can be aneurysms to prevent later rupture.1,2,5
Boston, MA 02115.
E-mail: trsmith@partners.org
devastating and can result in permanent neuro- For the last century, the gold standard for
treating intracranial aneurysms has been micro-
Received, May 9, 2017. surgical clipping.6-13 In the last 2 decades,
Accepted, December 12, 2017. incremental improvements and popularization
ABBREVIATIONS: CI, confidence interval; FE, fixed
effects, GOS, Glasgow Outcomes Scale; MCAA, of endovascular coiling techniques has led
Copyright 
C 2018 by the

Congress of Neurological Surgeons
middle cerebral artery aneurysms; mRS, Modified
Rankin Scale; NOS, Newcastle Ottawa scale; RE,
random effects.
Supplemental digital content is available for this article at
www.neurosurgery-online.com.
to significant controversy regarding the ideal
management strategy for unruptured intracranial
aneurysms of the cerebral vessels.1-3,5,14
Endovascular coiling is advantageous because
it avoids a large incision and a craniotomy,

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 ALRESHIDI ET AL
which shortens recovery time and lowers the risk of a variety
of perioperative complications.1,2,5 On long-term follow-up,
however, coiling often results in the recanalization of aneurysms
due to coil compaction, necessitating frequent angiographic
follow-up while exposing the patient to risk of aneurysmal
rupture in the interim.1,2 Although neurosurgical clipping is
more invasive, many studies demonstrate its long-term durability
in aneurysmal obliteration.1-3 The decision to treat using
coiling and clipping techniques depends on both patient and
aneurysm characteristics as well as institutional and surgeon
experience.1-3,5,12,15-17
We analyzed the neurovascular literature to provide an
objective comparison of both endovascular coiling and micro-
surgical clipping with regard to the safety and efficacy of
the treatment of unruptured middle cerebral artery aneurysms
(MCAA). The field of endovascular neurosurgery is rapidly
evolving, with frequent improvements in technique, technology,
and outcomes.5,7,12,15-23 Because of these rapid changes, we
updated a previously conducted meta-analysis that included
studies through December 2010.1
METHODS
Literature Search
A systematic search was conducted using the PubMed, EMBASE,
and Cochrane databases from January 2011 (ending search date of the
previous meta-analysis) through October 2015 for studies evaluating the
efficacy and safety of microsurgical clipping or endovascular coiling in
patients with unruptured MCAAs. The search strategy combined search
terms for clipping, coiling, and MCAA by using multiple versions of
medical terms and text words (Table A in Appendix, Supplemental
Digital Content). Additional articles were identified by hand search.
Study Selection
Studies were included if they: (1) reported clipping or coiling
treatment outcomes for adult patients (or a subgroup) with unrup-
tured MCAAs; (2) reported occlusion rates, neurological morbidity, or
both; (3) measured efficacy by complete occlusion of the aneurysm
demonstrated by digital subtraction angiography (primary outcome), or
measured safety by a combination of either the Modified Rankin Scale
(mRS; 0-3) or the Glasgow Outcomes Scale (GOS; 4-5) (secondary
outcome); and (4) were published between 2011 and 2015. Exclusion
criteria included non-English studies, animal studies, and articles that
reported both procedures in a single patient, reported ruptured MCAAs,
included assistive devices such as stents, balloons, or specially treated
coils, included <2 patients, or were systematic reviews, review articles, or
meta-analyses. Titles and abstracts were screened and potentially relevant
articles were selected for full-text evaluation, which was performed
independently by 4 investigators. Discrepancies were resolved by the
senior authors. Study quality was evaluated using the modified Newcastle
Ottawa scale (NOS).24
Data Extraction
Extracted data included study characteristics (publication year;
country of origin; sample size; study design; number of aneurysms; study
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duration; NOS score), intervention characteristics (surgery type), efficacy
results (number of complete occlusion for coling or clipping; time of
occlusion assessment), and safety outcome (mRS and GOS, assessment
time of mRS or GOS). Data extraction was conducted independently by
3 investigators. Discrepancies were resolved by the senior authors.
Data Analysis
Data analysis was performed using Comprehensive Meta-Analysis
Version 3 (Biostat, Inc, Englewood, New Jersey). The random-effects
(RE) model according to the method of DerSimonian and Laird25 that
accounted for variation between and within studies was used to obtain
the overall summary effect (aneurysmal occlusion rate or favorable neuro-
logical outcome rate) and their 95% confidence intervals (CI) to assess
treatment efficacy and safety in patients with MCAA and to conduct
subgroup analyses, meta-regression, and cumulative meta-analyses. The
fixed-effects (FE) model using the inverse variance method was evaluated
for comparison. The effect estimates in each group of studies (clipping
vs coiling) were assumed to follow a binomial distribution.
Forest plots were used to visualize the individual and summary
estimates. Heterogeneity was evaluated among studies by Cochran’s Q
test (P < .10) and I2 to measure the proportion of total variation
due to that heterogeneity. An I2 value > 50% was considered to be
high.26 Potential sources of heterogeneity were explored using subgroup
analyses by the following categorical covariates: continent of study origin;
study design; study quality; and journal impact factor. A metaregression
for each of the four outcomes was used to explore sources of hetero-
geneity on the continuous covariate (study duration in years). Additional
cumulative meta-analyses by publication year were performed to assess
for any changes over time for the 2 modalities, and subgroup analyses
were also performed comparing the studies included in the prior analysis
with those included in this updated meta-analysis. Potential publication
bias was assessed by using funnel plots, Egger’s linear regression test, and
Begg’s correlation test. If publication bias was indicated, the trim-and-fill
method was used to recalculate the pooled effect estimate. A P-value <
.05 was considered significant except where otherwise specified.
RESULTS
We identified 3003 articles from PubMed, 5942 articles
from Embase, and 312 articles from the Cochrane Library
(Figure 1). After removing duplicates, screening titles and
abstracts, and full text review, 8 articles met our inclusion
criteria.4,10,12,13,16,23,27,28 Three relevant studies11,17,29 were
added based on hand search. These 11 studies,4,10-13,16,17,23,27-29
in addition to the 26 studies retrieved from the previous
meta-analysis,6,9,15,19,20,30-45 resulted in 37 studies for final
analysis (3352 aneurysms, 2162 clipping, 1190 coiling; Table).
Overall, there were 22 studies examining clipping and 23 studies
examining coiling (Tables B and C in Appendix, Supplemental
Digital Content).
Outcomes
Aneurysmal occlusion was examined in 11 studies assessing
clipping and 18 studies assessing coiling. Studies examining
aneurysmal occlusion were performed postoperatively using
digital subtraction catheter-based angiography, except for 1
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 CLIP VS. COIL: A META-ANALYSIS

FIGURE 1. Study selection flowchart.

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TABLE. All Studies (n = 37) Included in the Meta-Analysis (14 Clip Studies; 15 Coil Studies; 8 Clip and Coil Studies)

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Number of Number of North Study Newcastle-
ALRESHIDI ET AL

patients with patients with American (N), includes data Ottawa

Type of Intervention unruptured unruptured Enrollment Europe (E), on coil and quality scale
Author, year country case series (clip or coil) MCA and coil MCA and clip period or Asia (A) clip patients (# of stars)

Studies included from the previous meta-analysis by Smith et al, 20151 (n = 26 studies)
Aghakhani, 2008 Belgium9 Retro Clip – 117 1996-2006 E N 8

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Bracard, 2010 France36 Retro Coil 79 – 1992-2001 E N 6
Brinjiki, 2011 USA37 Retro Coil 26 – 2002-2009 N N 4
Deruty, 1996 France6 Retro Clip – 29 1990-1995 E N 5
Doerfler, 2006 Germany30 Retro Coil 16 – 2000-2004 E N 8
Gerlach, 2007 Germany31 Prosp Clip – 35 1999-2005 E N 4
Guglielmi, 2008 USA32 Retro Coil 61 – Unknown N N 5
Guresir, 2011 Germany33 Prosp Coil and Clip 21 108 1999-2009 E Y 5
Horowitz, 2006 USA34 Retro Coil 10 – 1999-2005 N N 6
Iijima, 2005 France19 Retro Coil 77 – 1998-2002 E N 6
Im, 2009 Korea35 Retro Coil 46 – 2002-2006 A N 4
Kim, 2010 Korea39 Retro Coil and clip 85 360 2006 A Y 4
Kim, 2011 Korea38 Retro Coil 70 – 2000-2009 A N 7
Lubicz, 2006 Belgium15 Retro Coil 19 – 2004-2005 E N 4
Morgan, 2010 Australia40 Prosp Clip – 263 1989-2009 E NN 8
Moroi, 2005 Japan41 Retro Clip – 201 1993-2000 A N 7
Nanda, 2002 USA42 Retro Clip – 18 1995-2001 N N 8
Niskanen, 2005 Finland43 Retro Coil and clip 12 82 1997-2000 E Y 6
Nusbaum 2006 USA44 Retro Clip – 169 1997-2005 N N 5
Oishi, 2009 Japan20 Retro Coil 45 – 2001-2007 A N 6
Quadros, 2007 France45 Retro Coil and clip 22 4 2001-2006 E Y 6
Raftapolous, 2003 Belgium8 Prosp Coil 12 – 1996-2001 E N 4
Regli, 1999 Switzerland7 Prosp Coil and clip 13 32 1993-1997 E Y 3
Regli, 2002 Switzerland18 Prosp Clip – 36 997-2000 E N 4
Suzuki, 2009 USA21 Retro Coil 67 – 1990-1997 N N 3
Vendrell, 2009 France22 Retro Coil 72 – 1999-2006 E N 3
Studies included from the current meta-analysis (n = 11 studies)
Aboukais, 2014 France16 Retro Clip – 24 2009 E N 6

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Diaz, 2014 USA13 RRetro Coil and clip 40 25 2005-2010 N Y 6
Jung, 2011 Korea28 Retro Clip – 19 1999-2010 A N 5
Rodriguez-Hernandez, 2013 USA12 Retro Clip 261 – 1997-2010 AN N 5
Jang, 2015 Korea4 Retro Coil and clip 25 286 1999-2013 A Y 5
Jin, 2013 Korea27 Retro Coil 42 – 2003-2008 A N 6
Mori, 2011 Japan10 Retro Clip – 100 Unknown A N 5
Mortimer, 2014 UK23 Retro Coil 53 – 1996-2012 E N 6
Dammann, 2014 Germany17 Retro Coil and clip 16 87 2006-2010 E Y 6
Seule, 2012 Switzerland29 Retro Clip N 24 1999-2009 E N 5
Choi, 2012 Korea11 Retro Clip N 143 2007-2010 A N 6

MCA, middle cerebral artery; Retro, retrospective; Prosp, prospective.

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 CLIP VS. COIL: A META-ANALYSIS

FIGURE 2. Forest plot showing occlusion prevalence after clipping (95% CI) in adult patients with MCAA (n = 626
aneurysms in 11 studies). For all figures, horizontal lines denote 95% CIs; solid squares represent the point estimate
of each study and the diamond represents the pooled estimate of the intervention effect. The size of the solid squares
is proportional to the weight of the study. Further details about each study are provided in Table A in Appendix,
Supplemental Digital Content.

study17 in which occlusion was evaluated at 6 mo. Postoper-
ative neurological function was evaluated in all of the 22 clipping
studies and in 22 of the 23 coiling studies.
Clip Aneurysmal Occlusion
Pooled analysis of 11 studies of clipped cases (626 aneurysms)
revealed complete occlusion in 94.2% of cases (95% CI, 87.6%-
97.4%) with the RE model and 88.8% (95% CI, 85.1%-
91.7%) with the FE model (I2 = 75.3%; P-heterogeneity < .01;
Figure 2).
Using the RE model, no significant subgroup effect was found
when stratifying by the following trial-level covariates: continent
(P = .55); study type (P = .35); study duration (P = .95);
study quality (P = .19); and impact factor (P = .68; Table D
in Appendix, Supplemental Digital Content). Metaregression
by study duration was not significant (P = .67).
When using the FE model, there was a significant subgroup
effect with the following trial-level covariates: study design (P-
interaction = .03): prospective studies had a higher occlusion
rate (96.4%; I2 = 0%; 3 studies) than the retrospective studies
(87.7%; I2 = 79.7%; 8 studies); continent (P-interaction < .01):
studies conducted in Asia had a higher occlusion rate (95.9%; I2
= 0%; 3 studies) than studies in Europe (83.9%, I2 = 74.3%,
6 studies) or North America (80.1%; I2 = 62.4%; 2 studies);
and study quality (P-interaction < .01): higher study quality
reported a lower occlusion rate (85.1%; I2 = 80.5%; 6 studies)
than lower quality studies (96.2%; I2 = 0%; 5 studies; Table D in
Appendix, Supplemental Digital Content). Metaregression by
study duration did not explain the differences in results between
the included studies (P = .46).
Cumulative meta-analysis by publication year did not reveal
improvement in clip efficacy with time, starting with an occlusion
rate of 98% in 1999 and gradually decreasing to 94% in 2014.
The pooled occlusion rate in the new studies added in this
updated meta-analysis (90.4%; I2 = 85.1%, 5 studies; RE)
showed a slightly lower occlusion rate than the data from the prior
meta-analysis1 (97.4%; I2 = 0%, 6 studies; FE; P-interaction =
.09, RE and P-interaction < .01, FE; Table D in Appendix,
Supplemental Digital Content).
Coil Aneurysmal Occlusion
Pooled analysis of 18 studies of coiled cases (759 aneurysms)
revealed complete occlusion in 53.2% of cases (95% CI, 45.0%
to 61.1%) with the RE model and in 53.6% (95% CI, 49.8%-
57.3%) with the FE model (I2 = 76.0%; P-heterogeneity <.01;
Figure 3).
Using the RE model, no significant subgroup effect was found
when stratifying by continent (P = .43); study design (P = .08);
study quality (P = .34); and impact factor (P = .10; Table D in
Appendix, Supplemental Digital Content). Meta-regression by
study duration was not significant (P = .30).
When using the FE model, there was a significant subgroup
effect with the following trial-level covariates: study design (P-
interaction = .03): retrospective studies had a higher occlusion
rate (54.2%; I2 = 76.6%; 16 studies) than prospective studies
(30.2%; I2 = 50.1%; 2 studies); continent (P-interaction = .03):

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 ALRESHIDI ET AL
FIGURE 3. Forest plot showing occlusion prevalence after coiling (95% CI) in adult patients with MCAA (n = 759 aneurysms).
Further details about each study are provided in Table B in Appendix, Supplemental Digital Content.
studies conducted in Asia had a higher occlusion rate (61.0%; I2
= 0%; 3 studies) than studies in Europe (53.9%, I2 = 79.5%,
10 studies) or North America (47.0%; I2 = 70.6%; 5 studies;
Table D in Appendix, Supplemental Digital Content). Meta-
regression by study duration revealed that studies with a longer
duration had a lower occlusion rate than studies with a shorter
duration (slope = −0.07; P < .01).
Cumulative meta-analysis by publication year revealed a
gradual improvement in coil efficacy with time starting with an
occlusion rate of 15% in 1999, reaching a cumulative peak of
59% in 2006 and then gradually decreasing again to 53% in 2014.
The pooled occlusion rate in the new studies added in this meta-
analysis (48.4%; I2 = 63.5%, 5 studies; RE) was not statistically
significantly different from the data from the prior meta-analysis1
(55.1%; I2 = 79.5%, 13 studies; RE; P-interaction = .48, RE and
P-interaction = .28, FE; Table D in Appendix, Supplemental
Digital Content).
Clip Neurological Outcomes
Pooled analysis of 22 studies of clipped cases (2404 aneurysms)
revealed favorable neurological outcomes in 97.9% of cases (95%
CI, 96.8%-98.6%) with the RE model and in 97.3% (95% CI,
96.4%-98.0%) with the FE model (I2 = 30.4%; P-heterogeneity
= .09; Figure 4).
Using the RE model, subgroup analysis revealed a signif-
icant difference only among continents (P < .01; Table D in
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Appendix, Supplemental Digital Content). Reported favorable
neurological outcomes were highest in studies conducted in
Asia (98.9%; I2 = 0%; 6 studies), followed by European
and Australian studies (97.3%; I2 = 0%; 12 studies), and
North American studies (95.6%; I2 = 42.6%; 4 studies). Meta-
regression by study duration did not reveal a change in favorable
neurological outcomes rates with longer study duration (P = .77).
Results from the FE model were similar (Table D in Appendix,
Supplemental Digital Content).
Cumulative meta-analysis by publication year revealed consis-
tently favorable neurological outcomes over time starting with
97% in 1996 and ending with 98% in 2015. The pooled reported
favorable neurological outcomes in the new studies added in this
meta-analysis (97.5%; I2 = 36.6%, 10 studies; RE) were not
statistically significantly different from the data from the prior
meta-analysis1 (98.2%; I2 = 8.47%, 12 studies; RE; P-interaction
= .47, RE and P-interaction = .047, FE; Table D in Appendix,
Supplemental Digital Content)
Coil Neurological Outcomes
Pooled analysis of 22 studies of coiled cases (826 aneurysms)
revealed favorable outcomes in 95.1% of cases (95% CI, 93.1%-
96.5%) with the RE and FE models (I2 = 0%; P-heterogeneity
= .56; Figure 5). There were no significant differences upon
subgroup analyses using both RE and FE models (all P >
.05; Table D in Appendix, Supplemental Digital Content).
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FIGURE 4. Forest plot showing the prevalence of favorable neurological outcomes after clipping (95% CI) in adult patients
with MCAA (n = 2404 aneurysms). Further details about each study are provided in Table A in Appendix, Supplemental
Digital Content.
Meta-regression on study duration did not reveal a change in
favorable neurological outcomes rates with longer study duration
(P = .22, RE and FE).
Cumulative meta-analysis by publication year revealed a consis-
tently reported favorable neurological outcome with time starting
with 96% in 1999 and cumulating to 95% in 2015. The pooled
reported favorable neurological outcomes in the new studies
added in this meta-analysis (94.4%; I2 = 0%, 8 studies; FE) were
not statistically significantly different from the data from the prior
meta-analysis1 (95.5%; I2 = 0%, 14 studies; FE; P-interaction =
.56, RE and FE; Table D in Appendix, Supplemental Digital
Content).
Occlusion Rates and Neurological Outcomes in Clip vs.
Coil
When clip and coil were directly compared using the RE
model, the P-interaction comparing the occlusion rates outcome
was <.01 (clip occlusion rate = 94.2%, 95% CI, 87.6%-
97.4% vs coil occlusion rate = 53.2%, 95% CI, 45.0%-61.1%).
Similarly, the P-interaction comparing the neurological outcomes
was <0.01 (clip favorable neurological outcome rate = 97.9%,
95% CI, 96.8%-98.6% vs coil favorable neurological outcome
rate = 95.1%, 95% CI, 93.1%-96.5%). Results were not
materially different using the FE model.
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CLIP VS. COIL: A META-ANALYSIS
Publication Bias
Publication bias was assessed for each outcome. No publication
bias was indicated for coil aneurysmal occlusion, but there was
mild publication bias for the remaining 3 outcomes. In each case,
Begg’s rank correlation test indicated no publication bias, while
Egger’s linear regression test did. A trim-and-fill method was then
performed on each of the outcomes and indicated an imputed
effect size that was not materially different from the original
effect size (Table E and Figures A-D in Appendix, Supplemental
Digital Content).
DISCUSSION
Appropriate management of unruptured intracranial
aneurysms remains one of the major dilemmas of modern neuro-
surgical practice.2,6,9,12,16,42,43 Surgical options for MCAA
currently include open clipping and endovascular coiling, each
of which provide significant advantages and disadvantages. As
endovascular technology and technique continue to advance,
outcomes for aneurysm coiling procedures—including both
efficacy and safety outcomes—continue to improve, making
optimal management of unruptured MCAA a situation of near
clinical equipoise.1,2
To evaluate and compare outcomes for endovascular
coiling versus microsurgical clipping of MCAA, Smith et al1
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FIGURE 5. Forest plot showing the prevalence of favorable neurological outcomes after coiling (95% CI) in adult patients with MCAA
(n = 826 aneurysms). Further details about each study are provided in Table B in Appendix, Supplemental Digital Content.
previously undertook a systematic review and meta-analysis using
data published 5 or more years ago.1 That meta-analysis demon-
strated that aneurysmal obliteration rates in clipped cases were
44.7% higher than the coiled cases, and that favorable outcome
rates of clipped cases were comparable to coiled cases. The results
of the updated meta-analysis presented here largely support
these findings, but may demonstrate interval improvement in
outcomes after endovascular surgery.
At least 2 major decisions must be made when an unruptured
intracranial aneurysm is identified: first, the care team and patient
must decide whether the aneurysm should be treated. Watchful
waiting is a reasonable option for some intracranial aneurysms at
low risk of rupture. If the decision to treat is made, the care team
and patient must then decide between endovascular coiling and
microsurgical clipping. The goal of treatment is 2-fold: first, the
treatment method must ultimately attain radiographic evidence
of aneurysmal obliteration in order to protect the patient from
risk of future rupture. Secondly, the risk of intervention must be
lower than the natural history of the risk of rupture.
In most published series, microsurgical-clipping results in
higher rates of aneurysmal occlusion postoperatively, and lower
rates of long-term recanalization.1,5,6,11 Recanalization of coiled
aneurysms necessitates increased angiographic follow-up, which
can increase healthcare costs, increase radiation exposure risk to
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the patient, and increase risk of aneurysmal rupture in the interim.
Despite these disadvantages, endovascular coiling has the benefit
of being less invasive.
The controversy surrounding the Barrow Ruptured Aneurysm
Trial characterizes this treatment dilemma well.46-50 Although
patients included in that trial had ruptured aneurysms, the
results reported mirrored those shown here—endovascular treat-
ments were relatively comparable in safety, but often resulted
in lower rates of aneurysmal obliteration and higher rates of
retreatment.46,48 Further complicating the matter are the many
differences in technology used and the operative experience of
the treating surgeon. To control for these differences, some
studies have recently been undertaken using nationally represen-
tative datasets to evaluate outcomes for aneurysms.51 Although
adequately stratifying aneurysms by type, size, risk, and other
important factors may be difficult with national databases, these
studies can nevertheless provide new and interesting data on the
treatment of these lesions.
In light of these controversies and the relative dearth of
high-quality evidence in this area, this meta-analysis provides
important information for neurosurgeons treating MCAA. First,
the results demonstrate comparable safety between coiling and
clipping, specifically with regard to neurological outcome. Rates
of favorable outcomes did not differ significantly between
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clipping and coiling among the studies reported here, and the
absolute difference was less than 5%, with both treatment modal-
ities having favorable outcomes in more than 95% of cases. In
these cases, however, patients were selected a priori for either
coiling or clipping based upon numerous patient and aneurysmal
factors. It is possible that if this selection bias were eliminated,
the absolute difference in favorable outcomes could change. It is
interesting to note, however, that this difference has decreased in
size from the previously published meta-analysis, possibly demon-
strating that the safety of endovascular treatment is improving
with patient selection, technology or experience.1 While safety
was comparable, these studies, when pooled, demonstrated signif-
icantly higher surgical success—as measured by aneurysmal
obliteration—in clipped cases.
Strengths of this study include the specific nature of the
pathology studied. Because of the many variations in treatment
strategies for intracranial aneurysms, the location and type often
dictate optimum management. This study was also able to control
for heterogeneity across studies by using study-level covariates,
such as study design, study duration, and study quality. Publi-
cation bias, which can be a major issue in the study or surgical
outcomes, was assessed using 2 different methods. This study
included all relevant contemporary studies on the treatment of
MCAA, making it the most up-to-date compilation of the liter-
ature and data on a controversial and frequently shifting topic.
Limitations
Limitations of this study are largely dictated by the nature
of the included studies. There is a high degree of selection
bias by treatment modality among the included studies, because
the studies included in the meta-analysis were not restricted
to randomized controlled trials. Among the presented results,
the direct statistical comparison between clipping and coiling
should be regarded with particular caution, as this calculation
was made between separate case series and not studies designed to
compare the 2 modalities. In addition, some modern studies were
excluded on the basis of treatment modality, particularly with
regard to novel endovascular treatments like balloon assistance
and stents, which may result in an underestimation of the efficacy
of coiling. Therefore, the findings of this study cannot necessarily
be generalized to endovascular treatments in general, given that
these novel adjuncts have been excluded. Lastly, this study was
restricted only to outcomes for patients with unruptured MCAA.
Intracranial aneurysms often present to neurosurgical care after
rupture, and can be located along any of the cerebral vessels.
The findings of this study cannot necessarily be generalized to
treatment outcomes for all intracranial aneurysms; further study
is needed for evaluation of clipping and coiling in these diverse
contexts.
CONCLUSION
This updated meta-analysis demonstrates that surgical clipping
for unruptured MCAA remains highly safe and efficacious.
NEUROSURGERY
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CLIP VS. COIL: A META-ANALYSIS
Endovascular treatment for unruptured MCAAs continues to
improve in efficacy and safety; yet, it results in lower rates of
occlusion.
Disclosure
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
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Supplemental digital content is available for this article at www.neurosurgery-
online.com.
COMMENTS
W ithin this meta-analysis, the authors present an updated
assessment of the efficacy and safety of microsurgical clipping
compared to endovascular coiling of unruptured middle cerebral artery
(MCA) aneurysms. The group previously analyzed this relationship in
a 2015 meta-analysis,1 and this current study includes new data from
January 2011 to October 2015. As they note, until the last several
years, craniotomy and clipping for MCA aneurysms has been the de
facto standard of care. Indeed, the present analysis suggests that surgical
clipping leads to higher rates of long-term radiographic obliteration,
compared to endovascular coiling, whereas procedural morbidity remains
constant between treatment groups. Interestingly, in comparison to the
authors’ 2015 meta-analysis, the rates of aneurysm obliteration following
endovascular coiling improved, a likely result of advances in endovascular
technologies and improved operator technique.
While this analysis provides valuable conclusions about the current
management of unruptured MCA aneurysms, it lacks data on emerging
endovascular techniques for aneurysm obliteration, such as flow-
diversion,2 stent- and balloon-assisted coiling,3,4 and parent vessel
occlusion,3 which have been shown to improve aneurysm occlusion rates
compared to standard coiling.5 As the authors note, this may lead to
underestimation of endovascular aneurysm occlusion rates.
Overall, the authors’ conclusions serve to reinforce the distinctions
between coiling and clipping for unruptured MCA aneurysms. How a
differing occlusion rate affects long-term patient survival and neurologic
outcome remains to be determined. Ultimately, it is at the discretion of
the treating neurosurgeon or interventionalist which modality to employ,
a decision that is influenced by personal and institutional experience.
Kurt Yaeger
J Mocco
New York, New York
www.neurosurgery-online.com

1. Smith TR, Cote DJ, Dasenbrock HH, et al. Comparison of the Efficacy
and Safety of Endovascular Coiling Versus Microsurgical Clipping for Unrup-
tured Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-Analysis.
World Neurosurg. 2015;84(4):942-953. doi:10.1016/j.wneu.2015.05.073.
2. Bhogal P, AlMatter M, Bäzner H, Ganslandt O, Henkes H, Aguilar Pérez M.
Flow Diversion for the Treatment of MCA Bifurcation Aneurysms-A Single Centre
Experience. Front Neurol. 2017;8:20. doi:10.3389/fneur.2017.00020.
3. Huang L, Cao W, Ge L, et al. Endovascular management of giant middle cerebral
artery aneurysms. Int J Clin Exp Med. 2015;8(5):7517-7525. http://www.ncbi.
nlm.nih.gov/pubmed/26221295. Accessed June 1, 2017.
4. Feng Z, Li Q, Zhao R, et al. Endovascular Treatment of Middle Cerebral Artery
Aneurysm with the LVIS Junior Stent. J Stroke Cerebrovasc Dis. 2015;24(6):1357-
1362. doi:10.1016/j.jstrokecerebrovasdis.2015.02.016.
5. Chalouhi N, Daou B, Barros G, et al. Matched Comparison of Flow Diversion
and Coiling in Small, Noncomplex Intracranial Aneurysms. Neurosurgery. April
2017. doi:10.1093/neuros/nyw070.
T he authors present a meta-analysis on treatment of unruptured MCA
aneurysms by endovascular coiling versus surgical clipping. They
provide an in-depth statistical analysis of published data to outline the
safety and efficacy of endovascular coiling vs microsurgical clipping.
NEUROSURGERY
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CLIP VS. COIL: A META-ANALYSIS
The neurological outcomes and overall safety profiles were similar
between the 2 treatment modalities but the rate of occlusion of MCA
aneurysms was significantly lower with endovascular coiling. As noted
by the authors, the analysis can certainly help guiding the decision on
the treatment modality based on specific parameters (ie morbidity of
treatment, occlusion rate, functional outcome, etc). However, in our
modern era, the main question lies as to which factors are crucial for
a specific patient when treated by a specific physician with a specific set
of skills at a specific center? While these factors muddle the standard of
care for unruptured aneurysms, the healthcare costs should not be under-
estimated when centers able of treating aneurysms are multiplying at an
alarming speed with specialists from multiple disciplines! On a global
level, while we witness a decreased number of aneurysms treated by our
discipline together with a rapid evolution in the endovascular field, we
wonder how practice trends will affect these results should this topic be
reassessed in the future!
Neil Haranhalli
Rabih G. Tawk
Jacksonville, Florida
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